Antidepressant-like effect of magnolol on BDNF up-regulation and serotonergic system activity in unpredictable chronic mild stress treated rats.

PubMed

Li, Lu-Fan; Lu, Jie; Li, Xiu-Min; Xu, Chang-Liang; Deng, Ji-Min; Qu, Rong; Ma, Shi-Ping

2012-08-01

Magnolol is the main constituent identified in the barks of Magnolia officinalis, which has been used for the treatment of mental disorders including depression in China. In this study, we investigated the antidepressant-like effect of magnolol, and its possible mechanisms in rats subjected to unpredictable chronic mild stress (UCMS). High performance liquid chromatography with electrochemical detection (HPLC-ECD) and immunohistochemical staining analysis were applied to explore the mechanisms underlying the antidepressant-like effect of magnolol. Magnolol (20, 40 mg/kg) significantly reversed UCMS-induced reduction in sucrose consumption and deficiency in locomotor activity. In addition, it was observed that administration of magnolol (20, 40 mg/kg) restored brain-derived neurotrophic factor (BDNF) expression, and normalized the serotonergic system changes in the UCMS-treated rats. These results confirmed the antidepressant-like effect of magnolol, which might be based primarily on its ability to increase the BDNF expression and enhance the activity of the serotonergic system in rat brains. Copyright © 2012 John Wiley & Sons, Ltd.

Unpredictable chronic mild stress differentially impairs social and contextual discrimination learning in two inbred mouse strains

PubMed Central

van Boxelaere, Michiel; Clements, Jason; Callaerts, Patrick; D’Hooge, Rudi

2017-01-01

Alterations in the social and cognitive domain are considered important indicators for increased disability in many stress-related disorders. Similar impairments have been observed in rodents chronically exposed to stress, mimicking potential endophenotypes of stress-related psychopathologies such as major depression disorder (MDD), anxiety, conduct disorder, and posttraumatic stress disorder (PTSD). Data from numerous studies suggest that deficient plasticity mechanisms in hippocampus (HC) and prefrontal cortex (PFC) might underlie these social and cognitive deficits. Specifically, stress-induced deficiencies in neural plasticity have been associated with a hypodopaminergic state and reduced neural plasticity persistence. Here we assessed the effects of unpredictable chronic mild stress (UCMS) on exploratory, social and cognitive behavior of females of two inbred mouse strains (C57BL/6J and DBA/2J) that differ in their dopaminergic profile. Exposure to chronic stress resulted in impaired circadian rhythmicity, sociability and social cognition in both inbred strains, but differentially affected activity patterns and contextual discrimination performance. These stress-induced behavioral impairments were accompanied by reduced expression levels of brain derived neurotrophic factor (BDNF) in the prefrontal cortex. The strain-specific cognitive impairment was coexistent with enhanced plasma corticosterone levels and reduced expression of genes related to dopamine signaling in hippocampus. These results underline the importance of assessing different strains with multiple test batteries to elucidate the neural and genetic basis of social and cognitive impairments related to chronic stress. PMID:29166674

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

PubMed

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.

3,5,6,7,8,3′,4′-Heptamethoxyflavone Ameliorates Depressive-Like Behavior and Hippocampal Neurochemical Changes in Chronic Unpredictable Mild Stressed Mice by Regulating the Brain-Derived Neurotrophic Factor: Requirement for ERK Activation

PubMed Central

Sawamoto, Atsushi; Okuyama, Satoshi; Amakura, Yoshiaki; Yoshimura, Morio; Yamada, Takashi; Yokogoshi, Hidehiko; Nakajima, Mitsunari

2017-01-01

We previously reported that the subcutaneous administration of 3,5,6,7,8,3′,4′-heptamethoxyflavone (HMF), a citrus polymethoxyflavone, attenuated depressive-like behavior and increased the expression of brain-derived neurotrophic factor (BDNF) in the hippocampus of a corticosterone-induced depression-like mouse model. We herein demonstrated that (1) HMF was detectable in the brain 10 and 30 min after its oral administration, (2) orally administered HMF improved chronic unpredictable mild stress (CUMS)-induced pathological conditions, including body weight loss and depressive-like behavior, and CUMS-induced neurochemical changes, such as reduction in BDNF expression, decrease in neurogenesis, and decreased level of phosphorylated calcium-calmodulin-dependent protein kinase II in the hippocampus, and (3) these effects of HMF were inhibited by the pre-administration of U0126, a mitogen-activated protein (MAP) kinase inhibitor. These results suggest that orally administered HMF is beneficial for the upregulation of BDNF in the hippocampus via the extracellular signal-regulated kinase1/2 (ERK1/2)/MAP system, which may account for its antidepression effects. PMID:29023414

Ghrelin alleviates anxiety- and depression-like behaviors induced by chronic unpredictable mild stress in rodents.

PubMed

Huang, Hui-Jie; Zhu, Xiao-Cang; Han, Qiu-Qin; Wang, Ya-Lin; Yue, Na; Wang, Jing; Yu, Rui; Li, Bing; Wu, Gen-Cheng; Liu, Qiong; Yu, Jin

2017-05-30

As a regulator of food intake, ghrelin also plays a key role in mood disorders. Previous studies reported that acute ghrelin administration defends against depressive symptoms of chronic stress. However, the effects of long-term ghrelin on rodents under chronic stress hasn't been revealed. In this study, we found chronic peripheral administration of ghrelin (5nmol/kg/day for 2 weeks, i.p.) could alleviate anxiety- and depression-like behaviors induced by chronic unpredictable mild stress (CUMS). The depression-like behaviors were assessed by the forced swimming test (FST), and anxiety-like behaviors were assessed by the open field test (OFT) and the elevated plus maze test (EPM). Meanwhile, we observed that peripheral acylated ghrelin, together with gastral and hippocampal ghrelin prepropeptide mRNA level, were significantly up-regulated in CUMS mice. Besides, the increased protein level of growth hormone secretagogue receptor (GHSR) in hippocampus were also detected. These results suggested that the endogenous ghrelin/GHSR pathway activated by CUMS plays a role in homeostasis. Further results showed that central treatment of ghrelin (10μg/rat/day for 2 weeks, i.c.v.) or GHRP-6 (the agonist of GHSR, 10μg/rat/day for 2 weeks, i.c.v.) significantly alleviated the depression-like behaviors induced by CUMS in FST and sucrose preference test (SPT). Based on these results, we concluded that central GHSR is involved in the antidepressant-like effect of exogenous ghrelin treatment, and ghrelin/GHSR may have the inherent neuromodulatory properties against depressive symptoms. Copyright © 2017 Elsevier B.V. All rights reserved.

Magnolol treatment reversed the glial pathology in an unpredictable chronic mild stress-induced rat model of depression.

PubMed

Li, Lu-Fan; Yang, Jie; Ma, Shi-Ping; Qu, Rong

2013-07-05

Growing evidence indicates that glia atrophy contributes to the pathophysiology and the pathogenesis of major depressive disorder. Magnolol is the main constituent identified in the bark of Magnolia officinalis, which has been used for the treatment of mental disorders, including depression, in Asian countries. In this study, we investigated the antidepressant-like effect and the possible mechanisms of magnolol in rats subjected to unpredictable chronic mild stress (UCMS). The ameliorative effect of magnolol on depression symptoms was investigated through behavior tests, including sucrose preference test, open-field test and forced-swimming test. In addition, the levels of glial fibrillary acidic protein (GFAP), an astrocyte marker, in the hippocampus and prefrontal cortex were determined by immunohistochemistry, Western blot, and reverse transcription-polymerase chain reaction (RT-PCR). Exposure to UCMS resulted in a decrease of behavioral activity, whereas magnolol (20, 40 mg/kg) and fluoxetine (20mg/kg) administration significantly reversed the depressive-like behaviors (P<0.05).Moreover, treatment with magnolol effectively increased GFAP mRNA and protein levels in UCMS rats. These results confirmed the antidepressant-like effect of magnolol, which maybe primarily mediated by reversing the glial atrophy in the UCMS rat brain. Copyright © 2013 Elsevier B.V. All rights reserved.

Ferulic acid inhibits neuro-inflammation in mice exposed to chronic unpredictable mild stress.

PubMed

Liu, Ya-Min; Shen, Ji-Duo; Xu, Li-Ping; Li, Han-Bing; Li, Yu-Cheng; Yi, Li-Tao

2017-04-01

Ferulic acid is a hydroxycinnamic acid that widely presents in plant cell wall components. It has been demonstrated that ferulic acid can attenuate depressive-like behaviors in both forced swimming test and tail suspension test. Considering that depression is an inflammatory related mental disease, our present study was aimed to investigate the role of ferulic acid in the regulation of microglia activation, pro-inflammatory cytokines, nuclear factor kappa B (NF-κB) and nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome in mice exposed to chronic unpredictable mild stress (CUMS). Our results firstly showed that decreased sucrose preference and increased immobility time were completely reversed by administration with ferulic acid and fluoxetine for four weeks. Then, we found that CUMS significantly caused interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) up-regulation, microglia, NF-κB signaling and NLRP3 inflammasome activation in the prefrontal cortex. On the contrary, these activated inflammatory response induced by CUMS were reversed by ferulic acid and fluoxetine as well, suggesting that anti-inflammatory related mechanism was involved in the antidepressant-like effects of ferulic acid in stressed mice. Copyright © 2017 Elsevier B.V. All rights reserved.

Geraniol produces antidepressant-like effects in a chronic unpredictable mild stress mice model.

PubMed

Deng, Xue-Yang; Xue, Jin-Song; Li, Hong-Yan; Ma, Zhan-Qiang; Fu, Qiang; Qu, Rong; Ma, Shi-Ping

2015-12-01

Geraniol (GE), which has neuroprotection and anti-inflammation activities, is mostly abundant in the essential oils of rose, ginger, lemon, orange, lavender etc. However, its antidepressant-like effect has not been reported before. The present study was designed to investigate whether GE confers an antidepressant effect in mice exposed to a chronic unpredictable mild stress (CUMS) model of depression and to explore its possible mechanisms. The results showed that GE treatments for 3 weeks significantly alleviated the depression-related behaviors of CUMS-exposed mice, as indicated by restored decreased sucrose preference and shortened immobile time in both the forced swimming tests (FST) and tail suspension tests (TST). And these ameliorative effects of GE treatment were involved with regulating CUMS-induced pro-inflammatory cytokine interleukin-1 beta (IL-1β) related neuro-inflammation. We further found that GE treatment reversed CUMS-induced IL-1β elevation, possibly by inhibiting nuclear factor kappa B (NF-κB) pathway activation and regulating nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome expression. Taken together, our findings suggested that GE exerted a potential antidepressant-like effect in CUMS mice model of depression, which may provide an insight into the potential of GE in therapeutic implications for depression. Copyright © 2015 Elsevier Inc. All rights reserved.

The Antidepressant Agomelatine Improves Memory Deterioration and Upregulates CREB and BDNF Gene Expression Levels in Unpredictable Chronic Mild Stress (UCMS)-Exposed Mice

PubMed Central

Gumuslu, Esen; Mutlu, Oguz; Sunnetci, Deniz; Ulak, Guner; Celikyurt, Ipek K.; Cine, Naci; Akar, Furuzan; Savlı, Hakan; Erden, Faruk

2014-01-01

Agomelatine, a novel antidepressant with established clinical efficacy, acts as an agonist of melatonergic MT1 and MT2 receptors and as an antagonist of 5-HT2C receptors. The present study was undertaken to investigate whether chronic treatment with agomelatine would block unpredictable chronic mild stress (UCMS)-induced cognitive deterioration in mice in passive avoidance (PA), modified elevated plus maze (mEPM), novel object recognition (NOR), and Morris water maze (MWM) tests. Moreover, the effects of stress and agomelatine on brain-derived neurotrophic factor (BDNF) and cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) messenger ribonucleic acid (mRNA) levels in the hippocampus was also determined using quantitative real-time polymerase chain reaction (RT-PCR). Male inbred BALB/c mice were treated with agomelatine (10 mg/kg, i.p.), melatonin (10 mg/kg), or vehicle daily for five weeks. The results of this study revealed that UCMS-exposed animals exhibited memory deterioration in the PA, mEPM, NOR, and MWM tests. The chronic administration of melatonin had a positive effect in the PA and +mEPM tests, whereas agomelatine had a partial effect. Both agomelatine and melatonin blocked stress-induced impairment in visual memory in the NOR test and reversed spatial learning and memory impairment in the stressed group in the MWM test. Quantitative RT-PCR revealed that CREB and BDNF gene expression levels were downregulated in UCMS-exposed mice, and these alterations were reversed by chronic agomelatine or melatonin treatment. Thus, agomelatine plays an important role in blocking stress-induced hippocampal memory deterioration and activates molecular mechanisms of memory storage in response to a learning experience. PMID:24634580

Decreased hedonic responsiveness following chronic mild stress is not secondary to loss of body weight.

PubMed

Willner, P; Moreau, J L; Nielsen, C K; Papp, M; Sluzewska, A

1996-07-01

Chronic exposure to mild unpredictable stress (CMS) has previously been found to decrease hedonic responsiveness, as measured by the consumption of palatable sweet solutions or sensitivity to brain stimulation reward. These effects are reversed by chronic treatment with antidepressant drugs, and the CMS procedure has been proposed as a relatively valid animal model of depression. It has recently been suggested that the behavioural effects of CMS may be secondary to loss of body weight. This article collates data from five laboratories using the CMS procedure. Data are presented from seven studies using five different rat strains, as well as CD1 mice. Three-week exposure to CMS significantly decreased sucrose consumption by Lister hooded, PVG hooded, Wistar, and Wistar WU rats, and by CD1 mice, and sensitivity to brain stimulation reward in Ibm:Ro Ro rats. Weight loss in different experiments varied between 0 and 10%. Hedonic sensitivity relative to body weight (e.g., mg sucrose/g body weight) decreased significantly in all experiments. Animals maintained on a restricted feeding regime lost weight but did not show decreases in sucrose intake. It is concluded that decreased hedonic sensitivity following chronic mild stress cannot be attributed to loss of body weight.

Agmatine attenuates chronic unpredictable mild stress-induced anxiety, depression-like behaviours and cognitive impairment by modulating nitrergic signalling pathway.

PubMed

Gawali, Nitin B; Bulani, Vipin D; Gursahani, Malvika S; Deshpande, Padmini S; Kothavade, Pankaj S; Juvekar, Archana R

2017-05-15

Agmatine, a neurotransmitter/neuromodulator, has shown to exert numerous effects on the CNS. Chronic stress is a risk factor for development of depression, anxiety and deterioration of cognitive performance. Compelling evidences indicate an involvement of nitric oxide (NO) pathway in these disorders. Hence, investigation of the beneficial effects of agmatine on chronic unpredictable mild stress (CUMS)-induced depression, anxiety and cognitive performance with the involvement of nitrergic pathway was undertaken. Mice were subjected to a battery of stressors for 28days. Agmatine (20 and 40mg/kg, i.p.) alone and in combination with NO modulators like L-NAME (15mg/kg, i.p.) and l-arginine (400mg/kg i.p.) were administered daily. The results showed that 4-weeks CUMS produces significant depression and anxiety-like behaviour. Stressed mice have also shown a significant high serum corticosterone (CORT) and low BDNF level. Chronic treatment with agmatine produced significant antidepressant-like behaviour in forced swim test (FST) and sucrose preference test, whereas, anxiolytic-like behaviour in elevated plus maze (EPM) and open field test (OFT) with improved cognitive impairment in Morris water maze (MWM). Furthermore, agmatine administration reduced the levels of acetylcholinesterase and oxidative stress markers. In addition, agmatine treatment significantly increased the BDNF level and inhibited serum CORT level in stressed mice. Treatment with L-NAME (15mg/kg) potentiated the effect of agmatine whereas l-arginine abolished the anxiolytic, antidepressant and neuroprotective effects of agmatine. Agmatine showed marked effect on depression and anxiety-like behaviour in mice through nitrergic pathway, which may be related to modulation of oxidative-nitrergic stress, CORT and BDNF levels. Copyright © 2017 Elsevier B.V. All rights reserved.

Xiao-Yao-San, a Chinese Medicine Formula, Ameliorates Chronic Unpredictable Mild Stress Induced Polycystic Ovary in Rat

PubMed Central

Sun, Hao-Yu; Li, Quan; Liu, Yu-Ying; Wei, Xiao-Hong; Pan, Chun-Shui; Fan, Jing-Yu; Han, Jing-Yan

2017-01-01

Chronic stress induces endocrine disturbance, which contributes to the development of polycystic ovary syndrome (PCOS), a condition that remains a challenge for clinicians to cope with. The present study investigated the effect of Xiao-Yao-San (XYS), a traditional Chinese medicine formula used for treatment of gynecological disease, on the chronic stress-induced polycystic ovary and its underlying mechanism. Female Sprague-Dwaley rats underwent a 3 weeks chronic unpredictable mild stress (CUMS) procedure to establish the PCOS model, followed by 4 weeks treatment with XYS (0.505 g/kg or 1.01 g/kg) by gavage. Granulosa cells were exposed to noradrenaline (1 mM) in vitro for 24 h, followed by incubation with or without XYS-treated rat serum for 24 h. Post-treatment with XYS ameliorated CUMS-induced irregular estrous cycles and follicles development abnormalities, decrease of estradiol and progesterone level as well as increase of luteinizing hormone in serum, reduced cystic follicles formation and the apoptosis and autophagy of granulosa cells, attenuated the increase in dopamine beta hydroxylase and c-fos level in locus coeruleus, the noradrenaline level in serum and ovarian tissue, and the expression of beta 2 adrenergic receptor in ovarian tissue. Besides, XYS alleviated the reduction of phosphorylation of ribosomal protein S6 kinase polypeptide I and protein kinase B, as well as the increase of microtubule-associated protein light chain 3-I to microtubule-associated protein light chain 3-II conversion both in vivo and in vitro. This study demonstrated XYS as a potential strategy for CUMS induced polycystic ovary, and suggested that the beneficial role of XYS was correlated with the regulation of the sympathetic nerve activity. PMID:29018356

Antidepressant-Like Behavioral, Anatomical, and Biochemical Effects of Petroleum Ether Extract from Maca (Lepidium meyenii) in Mice Exposed to Chronic Unpredictable Mild Stress

PubMed Central

Ai, Zhong; Cheng, Ai-Fang; Yu, Yuan-Tao; Yu, Long-Jiang

2014-01-01

Abstract Maca has been consumed as a medical food in Peru for thousands of years, and exerts anxiolytic and antidepressant effects. Our present study aimed to evaluate the behavior and anatomical and biochemical effects of petroleum ether extract from maca (ME) in the chronic unpredictable mild stress (CUMS) model of depression in mice. Three different doses of maca extract (125, 250, and 500 mg/kg) were orally administrated in the six-week CUMS procedure. Fluoxetine (10 mg/kg) was used as a positive control drug. Maca extract (250 and 500 mg/kg) significantly decreased the duration of immobility time in the tail suspension test. After treatment with maca extract (250 and 500 mg/kg), the granule cell layer in the dentate gyrus appeared thicker. Maca extract (250 and 500 mg/kg) also induced a significant reduction in corticosterone levels in mouse serum. In mouse brain tissue, after six weeks of treatment, noradrenaline and dopamine levels were increased by maca extract, and the activity of reactive oxygen species was significantly inhibited. Serotonin levels were not significantly altered. These results demonstrated that maca extract (250 and 500 mg/kg) showed antidepressant-like effects and was related to the activation of both noradrenergic and dopaminergic systems, as well as attenuation of oxidative stress in mouse brain. PMID:24730393

Antidepressant-like behavioral, anatomical, and biochemical effects of petroleum ether extract from maca (Lepidium meyenii) in mice exposed to chronic unpredictable mild stress.

PubMed

Ai, Zhong; Cheng, Ai-Fang; Yu, Yuan-Tao; Yu, Long-Jiang; Jin, Wenwen

2014-05-01

Maca has been consumed as a medical food in Peru for thousands of years, and exerts anxiolytic and antidepressant effects. Our present study aimed to evaluate the behavior and anatomical and biochemical effects of petroleum ether extract from maca (ME) in the chronic unpredictable mild stress (CUMS) model of depression in mice. Three different doses of maca extract (125, 250, and 500 mg/kg) were orally administrated in the six-week CUMS procedure. Fluoxetine (10 mg/kg) was used as a positive control drug. Maca extract (250 and 500 mg/kg) significantly decreased the duration of immobility time in the tail suspension test. After treatment with maca extract (250 and 500 mg/kg), the granule cell layer in the dentate gyrus appeared thicker. Maca extract (250 and 500 mg/kg) also induced a significant reduction in corticosterone levels in mouse serum. In mouse brain tissue, after six weeks of treatment, noradrenaline and dopamine levels were increased by maca extract, and the activity of reactive oxygen species was significantly inhibited. Serotonin levels were not significantly altered. These results demonstrated that maca extract (250 and 500 mg/kg) showed antidepressant-like effects and was related to the activation of both noradrenergic and dopaminergic systems, as well as attenuation of oxidative stress in mouse brain.

Impact of chronic unpredicted mild stress-induced depression on repaglinide fate via glucocorticoid signaling pathway.

PubMed

Wei, Hongyan; Zhou, Ting; Tan, Boyu; Zhang, Lei; Li, Mingming; Xiao, Zhijun; Xu, Feng

2017-07-04

Chronic unpredicted mild stress (CUMS)-induced depression could alter the pharmacokinetics of many drugs in rats, however, the underlying mechanism is not clear. In this work we studied the pharmacokinetics of repaglinide, and explored the role of glucocorticoid and adrenergic signaling pathway in regulating drug metabolizing enzymes (DMEs) in GK rats and BRL 3A cells. The plasma cortisol and epinephrine levels were increased, meanwhile the pharmacokinetics of repaglinide were altered significantly in depression model rats. Forty-nine genes in liver of model rats displayed significant difference comparing to control rats. The differentially expressed genes enriched in the drug metabolism and steroid hormone biosynthesis pathway significantly, and Nr1i3 matched 335 connectivity genes. CAR and Ugt1a1 protein expression were enhanced significantly in liver of model rats. The mRNA expression of Ugt1a1 and Nr1i2 were increased 2 and 4 times respectively with dexamethasone (DEX) and 8-Br-cAMP co-treatment in BRL 3A cells. The protein expression of PXR was up-regulated, too. However, RU486 reversed the up-regulated effect. The adrenergic receptor agonists had little impact on the DMEs in BRL 3A. Our data suggested that CUMS-induced depression might up-regulate DMEs expression via glucocorticoid signaling pathway, and accelerate the fate of the repaglinide in spontaneous diabetes rats.

Impact of chronic unpredicted mild stress-induced depression on repaglinide fate via glucocorticoid signaling pathway

PubMed Central

Tan, Boyu; Zhang, Lei; Li, Mingming; Xiao, Zhijun; Xu, Feng

2017-01-01

Chronic unpredicted mild stress (CUMS)-induced depression could alter the pharmacokinetics of many drugs in rats, however, the underlying mechanism is not clear. In this work we studied the pharmacokinetics of repaglinide, and explored the role of glucocorticoid and adrenergic signaling pathway in regulating drug metabolizing enzymes (DMEs) in GK rats and BRL 3A cells. The plasma cortisol and epinephrine levels were increased, meanwhile the pharmacokinetics of repaglinide were altered significantly in depression model rats. Forty-nine genes in liver of model rats displayed significant difference comparing to control rats. The differentially expressed genes enriched in the drug metabolism and steroid hormone biosynthesis pathway significantly, and Nr1i3 matched 335 connectivity genes. CAR and Ugt1a1 protein expression were enhanced significantly in liver of model rats. The mRNA expression of Ugt1a1 and Nr1i2 were increased 2 and 4 times respectively with dexamethasone (DEX) and 8-Br-cAMP co-treatment in BRL 3A cells. The protein expression of PXR was up-regulated, too. However, RU486 reversed the up-regulated effect. The adrenergic receptor agonists had little impact on the DMEs in BRL 3A. Our data suggested that CUMS-induced depression might up-regulate DMEs expression via glucocorticoid signaling pathway, and accelerate the fate of the repaglinide in spontaneous diabetes rats. PMID:28574832

Unpredictable chronic mild stress induces anxiety and depression-like behaviors and inactivates AMP-activated protein kinase in mice.

PubMed

Zhu, Shenghua; Wang, Junhui; Zhang, Yanbo; Li, Victor; Kong, Jiming; He, Jue; Li, Xin-Min

2014-08-12

The unpredictable chronic mild stress (UCMS) model was developed based upon the stress-diathesis hypothesis of depression. Most effects of UCMS can be reversed by antidepressants, demonstrating a strong predictive validity of this model for depression. However, the mechanisms underlying the effects induced by UCMS remain incompletely understood. Increasing evidence has shown that AMP-activated protein kinase (AMPK) regulates intracellular energy metabolism and is especially important for neurons because neurons are known to have small energy reserves. Abnormalities in the AMPK pathway disturb normal brain functions and synaptic integrity. In the present study, we first investigated the effects of UCMS on a battery of different tests measuring anxiety and depression-like behaviors in female C57BL/6N mice after 4 weeks of UCMS exposure. Stressed mice showed suppressed body weight gain, heightened anxiety, and increased immobility in the forced swim and tail suspension tests. These results are representative of some of the core symptoms of depression. Simultaneously, we observed decrease of synaptic proteins in the cortex of mice subjected to UCMS, which is associated with decreased levels of phosphorylated AMP-activated protein kinase α (AMPKα) and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase). Our findings suggest that AMPKα inactivation might be a mechanism by which UCMS causes anxiety/depression-like behaviors in mice. Copyright © 2014 Elsevier B.V. All rights reserved.

Can Ocimum basilicum relieve chronic unpredictable mild stress-induced depression in mice?

PubMed

Ayuob, Nasra Naeim; Firgany, Alaa El-Din L; El-Mansy, Ahmed A; Ali, Soad

2017-10-01

Depression is one of the important world-wide health problems. This study aimed to assess the ameliorative effect of Ocimum basilicum (OB) essential oil on the behavioral, biochemical and histopathological changes resulted from exposure to chronic unpredictable mild stress (CUMS). It also aimed to investigate the underlying mechanism in an animal model of depression. Forty male Swiss albino mice were divided into four groups (n=10): control, CUMS (exposed to CUMS for 4weeks), CUMS plus fluoxetine, and CUMS plus OB. At the end of the experiment, behavioral changes, serum corticosterone level, protein and gene expressions of brain derived neurotropic factor (BDNF) and glucocorticoid receptors (GR) in the hippocampus was all assessed. Immunoexpression of surface makers of glial fibrillary acidic protein (GFAP), Ki67, Caspase-3, BDNF and GR in the hippocampus were estimated. Data were analyzed by using the statistical package for the social sciences (SPSS). OB alleviated both behavioral and biochemical changes recorded in mice after exposure to CUMS. It also reduced neuronal atrophy observed in the hippocampal region III cornu ammonis (CA3) and dentate gyrus and restored back astrocyte number. OB decreased apoptosis in both neurons and glial cells and increased neurogenesis in the dentate gyrus in a pattern comparable to that of fluoxetine. Increased BDNF and GR gene and protein expressions seems to be behind the antidepressant-like effect of OB. Ocimum basilicum ameliorates the changes induced after exposure to the chronic stress. Assessing Ocimum basilicum efficacy on human as antidepressant is recommended in further studies. Copyright © 2017. Published by Elsevier Inc.

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

PubMed

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.

Antidepressant-like effect of flaxseed secoisolariciresinol diglycoside in ovariectomized mice subjected to unpredictable chronic stress.

PubMed

Ma, Xing; Wang, Rui; Zhao, Xin; Zhang, Chong; Sun, Jiao; Li, Jianxin; Zhang, Lu; Shao, Tuo; Ruan, Lina; Chen, Liang; Xu, Ying; Pan, Jianchun

2013-03-01

Secoisolariciresinol diglycoside (SDG), a predominant lignan in flaxseed, has antioxidant activity as a dietary supplement. The purpose of the present study was to investigate the antidepressant-like effect and the possible mechanism of flaxseed SDG when the ovariectomized mice were exposed to the unpredictable chronic mild stress procedure. Chronic stress induced the increases in immobility time in mouse model of despair tests, but administration with SDG (80 and 160 mg/kg, p.o.) for 21 days inhibited these behavioral changes caused by stress in both forced swimming and tail suspension tests. These doses that affected the immobile response did not affect locomotor activity. Moreover, the changes in the serum corticosterone and adrenocorticotropic hormone (ACTH) levels were also measured to explore the SDG-associated regulation of hypothalamus-pituitary-adrenals (HPA) axis. The results indicated that the chronic stress-induced increases in the serum corticosterone and ACTH were reversed by treatment with high doses of SDG. Chronic treatment with SDG also affected the body weight of mice and IL-6, IL1β levels in the frontal cortex. In addition, chronic stress procedure induced a decrease in brain-derived neurotrophic factor (BDNF) expression in the frontal cortex of mice; while treatment with SDG reversed this reduction of BDNF. All these results provide compelling evidence that the behavioral effects of flaxseed SDG in the ovariectomized mice might be related to their modulating effects on the neuroendocrine-immune network and neurotrophin factor expression.

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

PubMed

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 inflammation, which allows the study of physio-pathological stress aspects over prolonged time periods of at least 60days. Copyright © 2016 Elsevier Inc. All rights reserved.

Effect of (4a) a novel 5-HT3 receptor antagonist on chronic unpredictable mild stress induced depressive-like behavior in mice: an approach using behavioral tests battery.

PubMed

Kurhe, Yeshwant; Mahesh, Radhakrishnan; Gupta, Deepali; Thangaraj, Devadoss

2015-01-01

The inconsistent therapeutic outcome necessitates designing and identifying novel therapeutic interventions for depression. Hence, the present study deals with the investigation of antidepressant-like effects of a novel 5-HT3 receptor antagonist (4-phenylpiperazin-1-yl) (quinoxalin-2-yl) methanone (4a) on chronic unpredictable mild stress (CUMS) induced behavioral and biochemical alterations. Animals were subjected to different stressors for a period of 28 days. On day 15 after the subsequent stress procedure, mice were administered with (4a) (2 and 4 mg/kg p.o.), escitalopram (10 mg/kg p.o.), or vehicle (10 mL/kg p.o.) until day 28 along with the CUMS. Thereafter, behavioral battery tests like locomotor score, sucrose preference test, forced swim test (FST), tail suspension test (TST), and elevated plus maze (EPM) were performed. Biochemical assays like lipid peroxidation, nitrite levels, reduced glutathione (GSH), catalase, and superoxide dismutase (SOD) were estimated in the mice brain homogenate. (4a) Dose dependently attenuated the behavioral alterations by increasing the sucrose consumption, reducing the immobility time in FST and TST, increasing the open arm number of entries and time in EPM. Furthermore, biochemical alterations were reversed by (4a) as examined by reduced lipid peroxidation and nitrite levels and elevated antioxidant enzyme levels like GSH, catalase and SOD. (4a) exhibits antidepressant potential by reversing the CUMS induced behavioral and biochemical changes in mice.

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

PubMed Central

Deep, Satayanarayan; Prasad, Dipti; Singh, Shashi Bala; Khan, Nilofar

2016-01-01

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. PMID:26901349

Saikosaponin D relieves unpredictable chronic mild stress induced depressive-like behavior in rats: involvement of HPA axis and hippocampal neurogenesis.

PubMed

Li, Hong-Yan; Zhao, Ying-Hua; Zeng, Min-Jie; Fang, Fang; Li, Min; Qin, Ting-Ting; Ye, Lu-Yu; Li, Hong-Wei; Qu, Rong; Ma, Shi-Ping

2017-11-01

Saikosaponin D (SSD), a major bioactive component isolated from Radix Bupleuri, has been reported to exert neuroprotective properties. The present study was designed to investigate the anti-depressant-like effects and the potential mechanisms of SSD. Behavioural tests including sucrose preference test (SPT), open field test (OFT) and forced swim test (FST) were performed to study the antidepressant-like effects of SSD. In addition, we examined corticosterone and glucocorticoid receptor (GR) levels to evaluate hypothalamic-pituitary-adrenal (HPA) axis function. Furthermore, hippocampal neurogenesis was assessed by testing doublecortin (DCX) levels, and neurotrophic molecule levels were also investigated in the hippocampus of rats. We found that unpredictable chronic mild stress (UCMS) rats displayed lost body weight, decreased sucrose consumption in SPT, reduced locomotive activity in OFT, and increased immobility time in FST. Chronic treatment with SSD (0.75, 1.50 mg/kg) remarkably ameliorated the behavioral deficiency induced by UCMS procedure. SSD administration downregulated elevated serum corticosterone levels, as well as alleviated the suppression of GR expression and nuclear translocation caused by UCMS, suggesting that SSD is able to remit the dysfunction of HPA axis. In addition, Western blot and immunohistochemistry analysis showed that SSD treatment significantly increased the generation of neurons in the hippocampus of UCMS rats indicated by elevated DCX levels. Moreover, hippocampal neurotrophic molecule levels of UCMS rats such as phosphorylated cAMP response element binding protein (p-CREB) and brain-derived neurotrophic factor (BDNF) were raised after SSD treatment. Together, Our results suggest that SSD opposed UCMS-induced depressive behaviors in rats, which was mediated, partially, by the enhancement of HPA axis function and consolidation of hippocampal neurogenesis.

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

PubMed

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. Copyright © 2016 Elsevier B.V. All rights reserved.

Increasing adult hippocampal neurogenesis in mice after exposure to unpredictable chronic mild stress may counteract some of the effects of stress.

PubMed

Culig, Luka; Surget, Alexandre; Bourdey, Marlene; Khemissi, Wahid; Le Guisquet, Anne-Marie; Vogel, Elise; Sahay, Amar; Hen, René; Belzung, Catherine

2017-11-01

Major depression is hypothesized to be associated with dysregulations of the hypothalamic-pituitary-adrenal (HPA) axis and impairments in adult hippocampal neurogenesis. Adult-born hippocampal neurons are required for several effects of antidepressants and increasing the rate of adult hippocampal neurogenesis (AHN) before exposure to chronic corticosterone is sufficient to protect against its harmful effects on behavior. However, it is an open question if increasing AHN after the onset of chronic stress exposure would be able to rescue behavioral deficits and which mechanisms might be involved in recovery. We investigated this question by using a 10-week unpredictable chronic mild stress (UCMS) model on a transgenic mouse line (iBax mice), in which the pro-apoptotic gene Bax can be inducibly ablated in neural stem cells following Tamoxifen injection, therefore enhancing the survival of newborn neurons in the adult brain. We did not observe any effect of our treatment in non-stress conditions, but we did find that increasing AHN after 2 weeks of UCMS is sufficient to counteract the effects of UCMS on certain behaviors (splash test and changes in coat state) and endocrine levels and thus to display some antidepressant-like effects. We observed that increasing AHN lowered the elevated basal corticosterone levels in mice exposed to UCMS. This was accompanied by a tamoxifen-induced reversal of the lack of stress-induced decrease in neuronal activation in the anteromedial division of the bed nucleus of the stria terminalis (BSTMA) after intrahippocampal dexamethasone infusion, pointing to a possible mechanism through which adult-born neurons might have exerted their effects. Our results contribute to the neurogenesis hypothesis of depression by suggesting that increasing AHN may be beneficial not just before, but also after exposure to stress by counteracting several of its effects, in part through regulating the HPA axis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Differential regulation of catecholamine synthesis and transport in rat adrenal medulla by fluoxetine treatment.

PubMed

Spasojevic, Natasa; Jovanovic, Predrag; Dronjak, Sladjana

2015-03-01

We have recently shown that chronic fluoxetine treatment acted significantly increasing plasma norepinephrine and epinephrine concentrations both in control and chronically stressed adult male rats. However, possible effects of fluoxetine on catecholamine synthesis and re-uptake in adrenal medulla have been largely unknown. In the present study the effects of chronic fluoxetine treatment on tyrosine hydroxylase, a rate-limiting enzyme in catecholamine synthesis, as well as a norepinephrine transporter and vesicular monoamine transporter 2 gene expressions in adrenal medulla of animals exposed to chronic unpredictable mild stress (CUMS) for 4 weeks, were investigated. Gene expression analyses were performed using a real-time quantitative reverse transcription-PCR. Chronically stressed animals had increased tyrosine hydroxylase mRNA levels and decreased expression of both transporters. Fluoxetine increased tyrosine hydroxylase and decreased norepinephrine transporter gene expression in both unstressed and CUMS rats. These findings suggest that chronic fluoxetine treatment increased plasma catecholamine levels by affecting opposing changes in catecholamine synthesis and uptake.

Metabolite identification in fecal microbiota transplantation mouse livers and combined proteomics with chronic unpredictive mild stress mouse livers.

PubMed

Li, Bo; Guo, Kenan; Zeng, Li; Zeng, Benhua; Huo, Ran; Luo, Yuanyuan; Wang, Haiyang; Dong, Meixue; Zheng, Peng; Zhou, Chanjuan; Chen, Jianjun; Liu, Yiyun; Liu, Zhao; Fang, Liang; Wei, Hong; Xie, Peng

2018-01-31

Major depressive disorder (MDD) is a common mood disorder. Gut microbiota may be involved in the pathogenesis of depression via the microbe-gut-brain axis. Liver is vulnerable to exposure of bacterial products translocated from the gut via the portal vein and may be involved in the axis. In this study, germ-free mice underwent fecal microbiota transplantation from MDD patients and healthy controls. Behavioral tests verified the depression model. Metabolomics using gas chromatography-mass spectrometry, nuclear magnetic resonance, and liquid chromatography-mass spectrometry determined the influence of microbes on liver metabolism. With multivariate statistical analysis, 191 metabolites were distinguishable in MDD mice from control (CON) mice. Compared with CON mice, MDD mice showed lower levels for 106 metabolites and higher levels for 85 metabolites. These metabolites are associated with lipid and energy metabolism and oxidative stress. Combined analyses of significantly changed proteins in livers from another depression model induced by chronic unpredictive mild stress returned a high score for the Lipid Metabolism, Free Radical Scavenging, and Molecule Transports network, and canonical pathways were involved in energy metabolism and tryptophan degradation. The two mouse models of depression suggest that changes in liver metabolism might be involved in the pathogenesis of MDD. Conjoint analyses of fecal, serum, liver, and hippocampal metabolites from fecal microbiota transplantation mice suggested that aminoacyl-tRNA biosynthesis significantly changed and fecal metabolites showed a close relationship with the liver. These findings may help determine the biological mechanisms of depression and provide evidence about "depression microbes" impacting on liver metabolism.

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

PubMed Central

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

Ondansetron attenuates depression co-morbid with obesity in obese mice subjected to chronic unpredictable mild stress; an approach using behavioral battery tests.

PubMed

Kurhe, Yeshwant; Radhakrishnan, Mahesh; Gupta, Deepali

2014-09-01

The aim of the present work was to investigate the role of ondansetron on the high fat diet (HFD) induced obese mice for behavioral and biochemical alterations using chronic unpredictable mild stress (CUMS) model of depression. Animals were fed with high fat diet for 14 weeks and subjected to different stress procedures for 4 weeks. Treatment with ondansetron was started on day 15. After day 28 behavioral assays and biochemical estimations were performed. Behavioral paradigms viz. sucrose preference test, locomotor score, forced swim test (FST) and elevated plus maze (EPM), whereas biochemical parameters like plasma glucose, total cholesterol, triglycerides and total proteins were estimated. Results examines that in behavioral assays, ondansetron significantly (P < 0.05) increased sucrose consumption, reduced immobility time in FST, increased the percent entries and time in open arm in EPM. In biochemical assessments elevated plasma glucose, total cholesterol, triglycerides and total proteins were significantly (P < 0.05) reversed by ondansetron treatment in HFD obese animals subjected to CUMS. The study indicates that the obese mice subjected to CUMS exhibited severe depressive-like symptoms and ondansetron significantly reversed the behavioral and biochemical alterations. In the present study the plasma glucose level indicates that, it could be "altered glucose level" playing an important role in depression co-morbid with obesity. Ondansetron through allosteric modulation of serotonergic system elevates the serotonin level and thereby regulates the insulin secretion and hence, reversing the "altered glucose level", could be the possible antidepressive-like mechanism against depression co-morbid with obesity.

Antidepressant-like effects of oleoylethanolamide in a mouse model of chronic unpredictable mild stress.

PubMed

Jin, Peng; Yu, Hai-Ling; Tian-Lan; Zhang, Feng; Quan, Zhe-Shan

2015-06-01

Oleoylethanolamide (OEA) is an endocannabinoid analog that belongs to a family of endogenous acylethanolamides. Increasing evidence suggests that OEA may act as an endogenous neuroprotective factor and participate in the control of mental disorder-related behaviors. In this study, we examined whether OEA is effective against depression and investigated the role of circulating endogenous acylethanolamides during stress. Mice were subjected to 28days of chronic unpredictable mild stress (CUMS), and during the last 21days, treated with oral OEA (1.5-6mg/kg) or 6mg/kg fluoxetine. Sucrose preference and open field test activity were used to evaluate depression-like behaviors during CUMS and after OEA treatment. Weights of the prefrontal cortex and hippocampus were determined, and the adrenal index was measured. Furthermore, changes in serum adrenocorticotropic hormone (ACTH), corticosterone (CORT) and total antioxidant capacity (T-AOC), brain-derived neurotrophic factor (BDNF), and lipid peroxidation product malondialdehyde (MDA) levels, and superoxide dismutase (SOD) activities in the hippocampus and prefrontal cortex were detected. Our findings indicate that OEA normalized sucrose preferences, locomotion distances, rearing frequencies, prefrontal cortex and hippocampal atrophy, and adrenal indices. In addition, OEA reversed the abnormalities of BDNF and MDA levels and SOD activities in the hippocampus and prefrontal cortex, as well as changes in serum levels of ACTH, CORT, and T-AOC. The antidepressant effects of OEA may be related to the regulation of BDNF levels in the hippocampus and prefrontal cortex, antioxidant defenses, and normalizing hyperactivity in the hypothalamic-pituitary-adrenal axis (HPA). Copyright © 2015 Elsevier Inc. All rights reserved.

Ethanol extract of Rehmannia glutinosa exerts antidepressant-like effects on a rat chronic unpredictable mild stress model by involving monoamines and BDNF.

PubMed

Wang, Jun-Ming; Pei, Li-Xin; Zhang, Yue-Yue; Cheng, Yong-Xian; Niu, Chun-Ling; Cui, Ying; Feng, Wei-Sheng; Wang, Gui-Fang

2018-06-01

The dried roots of Rehmannia glutinosa Libosch. (Scrophulariaceae) are of both medicinal and nutritional importance. Our previous study has found that the 80% ethanol extract of R. glutinosa (RGEE) produced antidepressant-like activities in mouse behavioral despair depression models. However, its mechanisms are still unclear. The present study aimed to observe the antidepressant-like mechanisms of RGEE on a rat chronic unpredictable mild stress (CUMS) model by involving monoaminergic neurotransmitters and brain-derived neurotrophic factor (BDNF). CUMS-stressed rats were orally given RGEE daily (150, 300, and 600 mg/kg) or fluoxetine hydrochloride (FH) for 3 weeks after starting the CUMS procedure. Sucrose preference test was carried out to observe depression-like behavior, and serum and brain tissues were used for neurochemical and fluorescent quantitative reverse transcription PCR analysis. Results demonstrated that CUMS induced depression-like behavior, whereas RGEE and FH administration inhibited this symptom. Furthermore, CUMS caused excessively elevated levels of serum corticosterone (CORT), an index of hypothalamic-pituitary-adrenal (HPA) axis hyperactivity, in a manner attenuated by RGEE and FH administration. RGEE administration also further elevated monoamine neurotransmitters and BDNF levels, up-regulated the mRNA expression of BDNF and tropomyosin-related kinase B (TrkB) in hippocampus of rats suffering CUMS. Together, our findings suggest that RGEE can improve CUMS-evoked depression-like behavior, and indicate its mechanisms may partially be associated with restoring HPA axis dysfunctions, enhancing monoamineergic nervous systems, and up-regulating BDNF and TrkB expression.

Ocimum basilicum improve chronic stress-induced neurodegenerative changes in mice hippocampus.

PubMed

Ayuob, Nasra Naeim; El Wahab, Manal Galal Abd; Ali, Soad Shaker; Abdel-Tawab, Hanem Saad

2018-06-01

Alzheimer's disease (AD), one of the progressive neurodegenerative diseases might be associated with exposure to stress and altered living conditions. This study aimed to evaluate the effectiveness of Ocimum basilicum (OB) essential oils in improving the neurodegenerative-like changes induced in mice after exposed to chronic unpredictable mild stress (CUMS). Forty male Swiss albino mice divided into four groups (n = 10); the control, CUMS, CUMS + Fluoxetine, CUMS + OB were used. Behavioral tests, serum corticosterone level, hippocampus protein level of the glucocorticoid receptors (GRs) and brain-dreived neurotropic factor (BDNF) were determined after exposure to CUMS. Hippocampus was histopathologically examined. Data were analyzed using statistical package for the social sciences (SPSS) and P value of less than 0.05 was considered significant. OB diminished the depression manifestation as well as impaired short term memory observed in the mice after exposure to the CUMS as evidenced by the forced swimming and elevated plus maze test. OB also up-regulated the serum corticosterone level, hippocampal protein level of the glucocorticoid receptor and the brain-derived neurotropic factor and reduced the neurodegenerative and atrophic changes induced in the hippocampus after exposure to CUMS. Essential oils of OB alleviated the memory impairment and hippocampal neurodegenerative changes induced by exposure to the chronic unpredictable stress indicating that it is the time to test its effectiveness on patients suffering from Alzheimer disease.

The Role of Musk in Relieving the Neurodegenerative Changes Induced After Exposure to Chronic Stress.

PubMed

Abd El Wahab, Manal Galal; Ali, Soad Shaker; Ayuob, Nasra Naeim

2018-06-01

This study aimed to evaluate the effect induced by musk on Alzheimer's disease-such as neurodegenerative changes in mice exposed to chronic unpredictable mild stress (CUMS). Forty male Swiss albino mice were divided into 4 groups (n = 10); control, CUMS, CUMS + fluoxetine, CUMS + musk. At the end of the experiment, behavior of the mice was assessed. Serum corticosterone level, hippocampal protein level of the glucocorticoid receptors, and brain-derived neurotropic factor were also assessed. Hippocampus was histopathologically examined. Musk improved depressive status induced after exposure to CUMS as evidenced by the forced swimming and open field tests and improved the short-term memory as evidenced by the elevated plus maze test. Musk reduced both corticosterone levels and the hippocampal neurodegenerative changes observed after exposure to CUMS. These improvements were comparable to those induced by fluoxetine. Musk alleviated the memory impairment and neurodegenerative changes induced after exposure to the chronic stress.

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

NASA Astrophysics Data System (ADS)

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.

Effect of tribulus terrestris saponins on behavior and neuroendocrine in chronic mild stress depression rats.

PubMed

Wang, Zhe; Zhang, Dongdong; Hui, Shan; Zhang, Yingjin; Hu, Suiyu

2013-04-01

To observe the effect of tribulus terrestris saponins (TTS) on behavior and neuroendocrine of chronic mild stress (CMS) depression rats. Thirty male Sprague-Dawley rats were randomly allocated to six groups: vehicle group, CMS group, CMS + fluoxetine group and CMS + TTS of low-dosage (0.375 g/kg), medium-dosage (0.75 g/kg) and high-dosage (2.25 g/kg) groups. All rats except the vehicle group singly housed and exposed an unpredicted sequence of mild stressors. The behavior of rats was detected by open-field test (OFT) and sucrose preference test (SPT). The concentration of corticotropin-releasing factor (CRF) and adrenocorticotropic hormone (ACTH) in serum of the rats were detected by radioimmunoassay. The concentration of cortisol (CORT) in serum was detected by enzyme immunoassay. CMS procedure not only significantly decreased the scores of crossing, rears and grooming in OFT and the sucrose preference in SPT (all P < 0.01), but also markedly increased serum CRH and CORT levels (both P < 0.05). Treatment with TTS (0.75 and 2.25 g/kg) could significantly prevent all of these abnormalities induced by CMS (P < 0.05, P < 0.01). CMS can affect rat behavior and neuroendocrine and cause depression. TTS has the antagonism on CMS and produce antidepressive effects.

Antidepressant-like Effect of Bacopaside I in Mice Exposed to Chronic Unpredictable Mild Stress by Modulating the Hypothalamic-Pituitary-Adrenal Axis Function and Activating BDNF Signaling Pathway.

PubMed

Zu, Xianpeng; Zhang, Mingjian; Li, Wencai; Xie, Haisheng; Lin, Zhang; Yang, Niao; Liu, Xinru; Zhang, Weidong

2017-11-01

Preliminary studies conducted in our laboratory have confirmed that Bacopaside I (BS-I), a saponin compound isolated from Bacopa monnieri, displayed antidepressant-like activity in the mouse behavioral despair model. The present investigation aimed to verify the antidepressant-like action of BS-I using a mouse model of behavioral deficits induced by chronic unpredictable mild stress (CUMS) and further probe its underlying mechanism of action. Mice were exposed to CUMS for a period of 5 consecutive weeks to induce depression-like behavior. Then, oral gavage administrations with vehicle (model group), fluoxetine (12 mg/kg, positive group) or BS-I (5, 15, 45 mg/kg, treated group) once daily were started during the last two weeks of CUMS procedure. The results showed that BS-I significantly ameliorated CUMS-induced depression-like behaviors in mice, as characterized by an elevated sucrose consumption in the sucrose preference test and reduced immobility time without affecting spontaneous locomotor activity in the forced swimming test, tail suspension test and open field test. It was also found that BS-I treatment reversed the increased level of plasma corticosterone and decreased mRNA and protein expressions of glucocorticoid receptor induced by CUMS exposure, indicating that hypothalamic-pituitary-adrenal (HPA) axis hyperactivity of CUMS-exposed mice was restored by BS-I treatment. Furthermore, chronic administration of BS-I elevated expression levels of brain-derived neurotrophic factor (BDNF) (mRNA and protein) and activated the phosphorylation of extracellular signal-regulated kinase and cAMP response element-binding protein in the hippocampus and prefrontal cortex in mice subjected to CUMS procedure. Taken together, these results indicated that BS-I exhibited an obvious antidepressant-like effect in mouse model of CUMS-induced depression that was mediated, at least in part, by modulating HPA hyperactivity and activating BDNF signaling pathway.

Decreased Prostaglandin D2 Levels in Major Depressive Disorder Are Associated with Depression-Like Behaviors.

PubMed

Chu, Cuilin; Wei, Hui; Zhu, Wanwan; Shen, Yan; Xu, Qi

2017-09-01

Prostaglandin (PG) D2 is the most abundant prostaglandin in the mammalian brain. The physiological and pharmacological actions of PGD2 in the central nervous system seem to be associated with some of the symptoms exhibited by patients with major depressive disorder. Previous studies have found that PGD2 synthase was decreased in the cerebrospinal fluid of major depressive disorder patients. We speculated that there may be a dysregulation of PGD2 levels in major depressive disorder. Ultra-performance liquid chromatography-tandem mass spectrometry coupled with a stable isotopic-labeled internal standard was used to determine PGD2 levels in the plasma of major depressive disorder patients and in the brains of depressive mice. A total of 32 drug-free major depressive disorder patients and 30 healthy controls were recruited. An animal model of depression was constructed by exposing mice to 5 weeks of chronic unpredictable mild stress. To explore the role of PGD2 in major depressive disorder, selenium tetrachloride was administered to simulate the change in PGD2 levels in mice. Mice exposed to chronic unpredictable mild stress exhibited depression-like behaviors, as indicated by reduced sucrose preference and increased immobility time in the forced swimming test. PGD2 levels in the plasma of major depressive disorder patients and in the brains of depressive mice were both decreased compared with their corresponding controls. Further inhibiting PGD2 production in mice resulted in an increased immobility time in the forced swimming test that could be reversed by imipramine. Decreased PGD2 levels in major depressive disorder are associated with depression-like behaviors. © The Author 2017. Published by Oxford University Press on behalf of CINP.

Resveratrol prevents cognitive deficits induced by chronic unpredictable mild stress: Sirt1/miR-134 signalling pathway regulates CREB/BDNF expression in hippocampus in vivo and in vitro.

PubMed

Shen, Jun; Xu, Linling; Qu, Chujie; Sun, Huimin; Zhang, Junjian

2018-04-30

Chronic unpredictable mild stress (CUMS) leads to neuropsychiatric disorders, such as depression, anxiety and cognitive impairment. Resveratrol is a natural polyphenol existed in polygonum cuspidatum and has been demonstrated to be a potent activator of Sirtuin 1 (Sirt1). Previous studies reported that resveratrol treatment ameliorated CUMS-induced depressive-like behavior and cognitive deficits through upregulating cAMP response element-binding protein (CREB) and brain derived neurotrophic factor (BDNF) expression. However, the upstream signalling pathway mediating CREB/BDNF expression and then exerting a protective role on cognitive function remains unclear. The present study aims to investigate the possible mechanism of resveratrol on CUMS-induced cognitive deficits. Male Sprague Dawley rats were adminstrated resveratrol (40 and 80 mg/kg) every day for 4 consecutive weeks before exposure to CUMS procedure. Morris Water Maze test was used to appraise spatial learing and memory of rats. Sirt1/miR-134 signalling pathway and CREB/BDNF expression in hippocampus of rats were measured. We also explored Sirt1/miR-134 signalling pathway and CREB/BDNF expression in primary cultured hippocampus neurons with resveratrol (25, 50 and 100 μmol/L) treatment. We found that resveratrol treatment prevented spatial learing and memory impairment induced by CUMS. Meanwhile the potential mechanism of resveratrol was associated with increased levels of Sirt1, CREB phosphorylation (p-CREB), CREB, BDNF and decreased levels of miR-134 in vivo and in vitro. In conclusion, our study showed that the neuroprotective effect of resveratrol on CUMS-induced cognitive impairment may rely on activating Sirt1/miR-134 pathway and then upregulating its downstream CREB/BDNF expression in hippocampus. Copyright © 2018 Elsevier B.V. All rights reserved.

Essential oil of Syzygium aromaticum reverses the deficits of stress-induced behaviors and hippocampal p-ERK/p-CREB/brain-derived neurotrophic factor expression.

PubMed

Liu, Bin-Bin; Luo, Liu; Liu, Xiao-Long; Geng, Di; Li, Cheng-Fu; Chen, Shao-Mei; Chen, Xue-Mei; Yi, Li-Tao; Liu, Qing

2015-02-01

Syzygium aromaticum has been widely used in traditional medicine. Our study investigated the safety and antidepressant-like effects of the essential oil of S. aromaticum after acute or long-term treatment. Using GC-MS, a total of eight volatile constituents were identified in the essential oil of S. aromaticum. The single LD50 was approximately 4500 mg/kg based on a 24-h acute oral toxicity study. In a long-term repeated toxicity study of this essential oil (100, 200, and 400 mg/kg, p. o.), only 400 mg/kg induced a significant decrease in body weight. In addition, no significant changes in relative organ weights and histopathological analysis were observed in all doses of essential oil-treated mice compared with the control group. Furthermore, acute S. aromaticum essential oil administration by gavage exerted antidepressant-like effects in the forced swimming test (200 mg/kg, p < 0.05) and tail suspension test (100 and 200 mg/kg, p < 0.05). Long-term S. aromaticum essential oil treatment via gavage significantly increased sucrose preference (50 mg/kg, p < 0.05; 100 and 200 mg/kg, p < 0.01) as well as elevated the protein levels of hippocampal p-ERK, p-CREB, and brain-derived neurotrophic factor in mice exposed to chronic unpredictable mild stress. These results confirmed the safety of the essential oil of S. aromaticum and suggested that its potent antidepressant-like property might be attributed to the improvement in the hippocampal pERK1/2-pCREB-BDNF pathway in rats exposed to chronic unpredictable mild stress. Georg Thieme Verlag KG Stuttgart · New York.

Decreased Prostaglandin D2 Levels in Major Depressive Disorder Are Associated with Depression-Like Behaviors

PubMed Central

Chu, Cuilin; Wei, Hui; Zhu, Wanwan; Shen, Yan

2017-01-01

Abstract Background Prostaglandin (PG) D2 is the most abundant prostaglandin in the mammalian brain. The physiological and pharmacological actions of PGD2 in the central nervous system seem to be associated with some of the symptoms exhibited by patients with major depressive disorder. Previous studies have found that PGD2 synthase was decreased in the cerebrospinal fluid of major depressive disorder patients. We speculated that there may be a dysregulation of PGD2 levels in major depressive disorder. Methods Ultra-performance liquid chromatography-tandem mass spectrometry coupled with a stable isotopic-labeled internal standard was used to determine PGD2 levels in the plasma of major depressive disorder patients and in the brains of depressive mice. A total of 32 drug-free major depressive disorder patients and 30 healthy controls were recruited. An animal model of depression was constructed by exposing mice to 5 weeks of chronic unpredictable mild stress. To explore the role of PGD2 in major depressive disorder, selenium tetrachloride was administered to simulate the change in PGD2 levels in mice. Results Mice exposed to chronic unpredictable mild stress exhibited depression-like behaviors, as indicated by reduced sucrose preference and increased immobility time in the forced swimming test. PGD2 levels in the plasma of major depressive disorder patients and in the brains of depressive mice were both decreased compared with their corresponding controls. Further inhibiting PGD2 production in mice resulted in an increased immobility time in the forced swimming test that could be reversed by imipramine. Conclusion Decreased PGD2 levels in major depressive disorder are associated with depression-like behaviors. PMID:28582515

Antidepressant-like effect of the water extract of the fixed combination of Gardenia jasminoides, Citrus aurantium and Magnolia officinalis in a rat model of chronic unpredictable mild stress.

PubMed

Xing, Hang; Zhang, Kuo; Zhang, Ruowen; Shi, Huiyan; Bi, Kaishun; Chen, Xiaohui

2015-12-01

Water extract of the fixed combination of Gardenia jasminoides Ellis fruit, Citrus aurantium L. fruit and Magnolia officinalis Rehd. et Wils. bark, traditional name - Zhi-Zi-Hou-Po (ZZHPD) is used for treatment of depressive-like symptoms in traditional Chinese medicine for centuries. The present study aimed to explore antidepressant-like effects and potential mechanisms of ZZHPD in a rat model of chronic unpredictable mild stress (CUMS). Antidepressant-like effects of ZZHPD were investigated through behavioral tests, and potential mechanism was assessed by neuroendocrine system, neurotrophin and hippocampal neurogenesis. Antidepressant-like effects of ZZHPD (3.66, 7.32 and 14.64 g/kg/day) were estimated through coat state test, sucrose preference test, forced swimming test and open-field test. Effects of ZZHPD on hypothalamic-pituitary-adrenal (HPA) axis were evaluated by hormones measurement and dexamethasone suppression test. In addition, the expression of brain-derived neurotrophic factor (BDNF) in hippocampus was measured, as well as hippocampal neurogenesis was investigated by doublecortin (DCX) and 5-bromo-2-deoxyuridine/neuronal nuclei (BrdU/NeuN). The results demonstrated that ZZHPD significantly reversed the depressive-like behaviors, normalized the levels of adrenocorticotropic hormone (ACTH) and corticosterone (CORT), restored the negative feedback loop of HPA axis and improved the levels of BDNF, DCX and BrdU/NeuN compared with those in CUMS-induced rats. The above results revealed that ZZHPD exerted antidepressant-like effects possibly by normalizing HPA axis function, increasing expression of BDNF in hippocampus and promoting hippocampal neurogenesis. Copyright © 2015 Elsevier GmbH. All rights reserved.

BDNF and COX-2 participate in anti-depressive mechanisms of catalpol in rats undergoing chronic unpredictable mild stress.

PubMed

Wang, Jun-Ming; Yang, Lian-He; Zhang, Yue-Yue; Niu, Chun-Ling; Cui, Ying; Feng, Wei-Sheng; Wang, Gui-Fang

2015-11-01

Catalpol, a major compound in Rehmannia glutinosa with both medicinal and nutritional values, has been previously confirmed to shorten the duration of immobility in mice exposed to tail suspension and forced swimming tests. This study attempted to examine the anti-depressive mechanisms of catalpol in rats undergoing chronic unpredictable mild stress (CUMS) by involving brain-derived neurotrophic factor (BDNF) and cyclooxygenase-2 (COX-2). CUMS-exposed rats were given catalpol daily (5, 10, and 20mg/kg, ig) or a reference drug, fluoxetine hydrochloride (FH, 10mg/kg, ig), at 5 weeks after starting the CUMS procedure. Sucrose preference test was performed to observe depression-like behavior, and serum and brain tissues were used for neurochemical and fluorescent quantitative reverse transcription PCR analysis. CUMS induced depression-like behavior, whereas catalpol and FH administration attenuated this symptom. Moreover, CUMS caused excessively elevated levels of serum corticosterone, an index of hypothalamic-pituitary-adrenal (HPA) axis hyperactivation, in a manner attenuated by catalpol and FH administration. Catalpol administration also further decreased BDNF activities, downregulated the mRNA expression of BDNF and tropomyosin-related kinase B (TrkB), and reversed the excessive elevation in the activities and mRNA expression levels of COX-2 and prostaglandin E2 (PGE2) in the hippocampus and frontal cortex of rats undergoing CUMS. Results indicate that catalpol can ameliorate CUMS-induced depression-like behavior, and suggest its mechanisms may partially be ascribed to restoring HPA axis dysfunctions, upregulating BDNF expression and its cognate receptor TrkB, and downregulating COX-2 expression, thereby reducing PGE2 levels in the brain. Copyright © 2015 Elsevier Inc. All rights reserved.

Branch retinal vein thrombosis and visual loss probably associated with pegylated interferon therapy of chronic hepatitis C

PubMed Central

Gonçalves, Luciana Lofego; Farias, Alberto Queiroz; Gonçalves, Patrícia Lofego; D’Amico, Elbio Antonio; Carrilho, Flair José

2006-01-01

Ophthalmological complications with interferon therapy are usually mild and reversible, not requiring the withdrawal of the treatment. We report a case of a patient who had visual loss probably associated with interferon therapy. Chronic hepatitis C virus infection (genotype 1a) was diagnosed in a 33-year old asymptomatic man. His past medical history was unremarkable and previous routine ophthalmologic check-up was normal. Pegylated interferon alpha and ribavirin were started. Three weeks later he reported painless reduction of vision. Ophthalmologic examination showed extensive intraretinal hemorrhages and cotton-wool spots, associated with inferior branch retinal vein thrombosis. Antiviral therapy was immediately discontinued, but one year later he persists with severely decreased visual acuity. This case illustrates the possibility of unpredictable and severe complications during pegylated interferon therapy. PMID:16874884

Dendritic Spines in Depression: What We Learned from Animal Models

PubMed Central

Qiao, Hui; Li, Ming-Xing; Xu, Chang; Chen, Hui-Bin; An, Shu-Cheng; Ma, Xin-Ming

2016-01-01

Depression, a severe psychiatric disorder, has been studied for decades, but the underlying mechanisms still remain largely unknown. Depression is closely associated with alterations in dendritic spine morphology and spine density. Therefore, understanding dendritic spines is vital for uncovering the mechanisms underlying depression. Several chronic stress models, including chronic restraint stress (CRS), chronic unpredictable mild stress (CUMS), and chronic social defeat stress (CSDS), have been used to recapitulate depression-like behaviors in rodents and study the underlying mechanisms. In comparison with CRS, CUMS overcomes the stress habituation and has been widely used to model depression-like behaviors. CSDS is one of the most frequently used models for depression, but it is limited to the study of male mice. Generally, chronic stress causes dendritic atrophy and spine loss in the neurons of the hippocampus and prefrontal cortex. Meanwhile, neurons of the amygdala and nucleus accumbens exhibit an increase in spine density. These alterations induced by chronic stress are often accompanied by depression-like behaviors. However, the underlying mechanisms are poorly understood. This review summarizes our current understanding of the chronic stress-induced remodeling of dendritic spines in the hippocampus, prefrontal cortex, orbitofrontal cortex, amygdala, and nucleus accumbens and also discusses the putative underlying mechanisms. PMID:26881133

Antidepressant Effect and Recognition Memory Improvement of Two Novel Plant Extract Combinations - Antistress I and Anti-stress II on Rats Subjected to a Model of Mild Chronic Stress.

PubMed

Kandilarov, Ilin K; Zlatanova, Hristina I; Georgieva-Kotetarova, Maria T; Kostadinova, Ivanka I; Katsarova, Mariana N; Dimitrova, Stela Z; Lukanov, Ludmil K; Sadakov, Ferit

2018-03-01

Chronic stress is one of the main factors which lead to depression - a psychiatric disorder affecting millions of people and predicted to be the second ranked cause of premature death in 2020. Depression is often associated with cognitive disturbances and memory deficit. Plant based therapy could be effective in the treatment of mild to moderate depression due to its low level of adverse reaction, its good tolerability and compliance. 72 male Wistar rats, divided in 9 groups were given orally for 8 weeks two combinations of dry plant extracts - Antistress I and Antistress II and five individual dry extracts obtained from Serratula coronata, Hypericum perforatum, Valeriana officinalis, Crataegus monogyna and Melissa officinalis. The animals were exposed to a chronic unpredictable mild stress for 8 weeks. The depression-like symptoms were evaluated with Forced swim test while the assessment of the memory deficit was performed with Novel object recognition test. Antistress II demonstrates antidepressant effect while Antistress I doesn't improve the depressive-like symptoms. The individual extracts of Hypericum perforatum and Valeriana officinalis also possess antidepressant properties. Antistress II improves the cognition as well as the individual extracts of Hypericum perforatum, Valeriana officinalis and especially Serratula coronata. Dry extract from Serratula tend to have the best effect regarding the recognition memory. The effect of Antistress I on memory deficit is negligible. Antistress II possesses antidepressant effect and improves the recognition memory while Antistress I doesn't demonstrate any of the above-described effects.

HCN2 channels in the ventral tegmental area regulate behavioral responses to chronic stress

PubMed Central

Zhong, Peng; Vickstrom, Casey R; Liu, Xiaojie; Hu, Ying; Yu, Laikang; Yu, Han-Gang

2018-01-01

Dopamine neurons in the ventral tegmental area (VTA) are powerful regulators of depression-related behavior. Dopamine neuron activity is altered in chronic stress-based models of depression, but the underlying mechanisms remain incompletely understood. Here, we show that mice subject to chronic mild unpredictable stress (CMS) exhibit anxiety- and depressive-like behavior, which was associated with decreased VTA dopamine neuron firing in vivo and ex vivo. Dopamine neuron firing is governed by voltage-gated ion channels, in particular hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. Following CMS, HCN-mediated currents were decreased in nucleus accumbens-projecting VTA dopamine neurons. Furthermore, shRNA-mediated HCN2 knockdown in the VTA was sufficient to recapitulate CMS-induced depressive- and anxiety-like behavior in stress-naïve mice, whereas VTA HCN2 overexpression largely prevented CMS-induced behavioral deficits. Together, these results reveal a critical role for HCN2 in regulating VTA dopamine neuronal activity and depressive-related behaviors. PMID:29256865

Z-Guggulsterone Produces Antidepressant-Like Effects in Mice through Activation of the BDNF Signaling Pathway

PubMed Central

Liu, Feng-Guo; Hu, Wen-Feng; Wang, Ji-Li; Wang, Peng; Gong, Yu; Tong, Li-Juan; Jiang, Bo; Zhang, Wei; Qin, Yi-Bin; Chen, Zhuo

2017-01-01

Abstract Background: Z-guggulsterone, an active compound extracted from the gum resin of the tree Commiphora mukul, has been shown to improve animal memory deficits via activating the brain-derived neurotrophic factor signaling pathway. Here, we investigated the antidepressant-like effect of Z-guggulsterone in a chronic unpredictable stress mouse model of depression. Methods: The effects of Z-guggulsterone were assessed in mice with the tail suspension test and forced swimming test. Z-guggulsterone was also investigated in the chronic unpredictable stress model of depression with fluoxetine as the positive control. Changes in hippocampal neurogenesis as well as the brain-derived neurotrophic factor signaling pathway after chronic unpredictable stress/Z-guggulsterone treatment were investigated. The tryptophan hydroxylase inhibitor and the tyrosine kinase B inhibitor were also used to explore the antidepressant-like mechanisms of Z-guggulsterone. Results: Z-guggulsterone (10, 30 mg/kg) administration protected the mice against the chronic unpredictable stress-induced increases in the immobile time in the tail suspension test and forced swimming test and also reversed the reduction in sucrose intake in sucrose preference experiment. Z-guggulsterone (10, 30 mg/kg) administration prevented the reductions in brain-derived neurotrophic factor protein expression levels as well as the phosphorylation levels of cAMP response element binding protein, extracellular signal-regulated kinase 1/2, and protein kinase B in the hippocampus and cortex induced by chronic unpredictable stress. Z-guggulsterone (10, 30 mg/kg) treatment also improved hippocampal neurogenesis in chronic unpredictable stress-treated mice. Blockade of the brain-derived neurotrophic factor signal, but not the monoaminergic system, attenuated the antidepressant-like effects of Z-guggulsterone. Conclusions: Z-guggulsterone exhibits antidepressant activity via activation of the brain-derived neurotrophic factor signaling pathway and upregulation of hippocampal neurogenesis. PMID:28339691

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

PubMed

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. Copyright © 2014 Elsevier Ltd. All rights reserved.

Elevation of synaptic protein is associated with the antidepressant-like effects of ferulic acid in a chronic model of depression.

PubMed

Liu, Ya-Min; Hu, Chun-Yue; Shen, Ji-Duo; Wu, Su-Hui; Li, Yu-Cheng; Yi, Li-Tao

2017-02-01

Ferulic acid is a hydroxycinnamic acid that widely presents in plant cell wall components. It has been demonstrated that ferulic acid can reverse depressive-like behaviors in both forced swimming test and tail suspension test. However, it is unclear whether chronic ferulic acid treatment can ameliorate the depressive-like behaviors in chronic unpredictable mild stress (CUMS). Because of the putative relationship between neurotrophic system and antidepressant-like activity, we also investigated the effects of chronic ferulic acid on the brain-derived neurotrophic factor (BDNF), postsynaptic protein PSD95, presynaptic protein synapsin I in both prefrontal cortex and hippocampus. The results showed that ferulic acid significantly alleviated CUMS-induced depressive-like behaviors in sucrose preference test and forced swimming test. In addition, ferulic acid significantly up-regulated the levels of BDNF, PSD95 and synapsin I in the prefrontal cortex and hippocampus. The present data indicated that ferulic acid exerted the antidepressant-like effects on behaviors by increasing neurotrophin-related synaptic protein levels in CUMS mice. Copyright © 2016. Published by Elsevier Inc.

Lack of vasopressin does not prevent the behavioural and endocrine changes induced by chronic unpredictable stress.

PubMed

Varga, János; Domokos, Agnes; Barna, István; Jankord, Ryan; Bagdy, György; Zelena, Dóra

2011-01-15

Vasopressin (VP) plays an important role in hypothalamo-pituitary-adrenal (HPA) axis regulation and in stress-related disorders. Our previous studies confirmed the role of VP in acute situations, where VP-deficient Brattleboro rats had less depression-like behaviour compared to animals that express VP. In this study, we test the hypothesis that VP-deficient rats are more resistant to the development of chronic HPA axis hyperactivity and depression-like symptoms after chronic unpredictable stress (CUS). Male VP-deficient Brattleboro rats were compared to their heterozygous littermates (controls). CUS consisted of different mild stimuli for 5 weeks. Elevated plus maze and forced swim test were used for behavioural characterization, while organs and blood for HPA axis parameters were collected at the end of the experiment. In controls, CUS resulted in the development of chronic stress state characterized by typical somatic (body weight reduction, thymus involution) and endocrine changes (resting plasma ACTH and corticosterone elevation and POMC mRNA elevation in anterior lobe of the pituitary). Floating time in the forced swim test was enhanced together with reduced open arm entries on elevated plus maze and a reduction in daily food intake. Unexpectedly, the lack of VP did not alter the effect of CUS on the somatic and behavioural measures, but only prevented CUS-induced corticosterone changes. In conclusion, lifelong VP-deficiency has a positive effect on corticosterone elevation following CUS but does not affect the behavioural consequences of CUS. It is likely that the interplay of several related factors, rather than an alteration in a single neuropeptide, modulates behaviour and disease pathogenesis. Copyright © 2010 Elsevier Inc. All rights reserved.

Depression and substance use comorbidity: What we have learned from animal studies.

PubMed

Ng, Enoch; Browne, Caleb J; Samsom, James N; Wong, Albert H C

2017-07-01

Depression and substance use disorders are often comorbid, but the reasons for this are unclear. In human studies, it is difficult to determine how one disorder may affect predisposition to the other and what the underlying mechanisms might be. Instead, animal studies allow experimental induction of behaviors relevant to depression and drug-taking, and permit direct interrogation of changes to neural circuits and molecular pathways. While this field is still new, here we review animal studies that investigate whether depression-like states increase vulnerability to drug-taking behaviors. Since chronic psychosocial stress can precipitate or predispose to depression in humans, we review studies that use psychosocial stressors to produce depression-like phenotypes in animals. Specifically, we describe how postweaning isolation stress, repeated social defeat stress, and chronic mild (or unpredictable) stress affect behaviors relevant to substance abuse, especially operant self-administration. Potential brain changes mediating these effects are also discussed where available, with an emphasis on mesocorticolimbic dopamine circuits. Postweaning isolation stress and repeated social defeat generally increase acquisition or maintenance of drug self-administration, and alter dopamine sensitivity in various brain regions. However, the effects of chronic mild stress on drug-taking have been much less studied. Future studies should consider standardizing stress-induction protocols, including female subjects, and using multi-hit models (e.g. genetic vulnerabilities and environmental stress).

[Open-field behavioral study in rat hyperlipidemia combined with chronic unpredictable mild stress model].

PubMed

Hu, Hua; Zhang, Yingchun; Xu, Yeqing; Liu, Chunfeng; Wang, Liwei

2015-06-16

To investigate behavioral changes in a rat hyperlipidemia model induced by high lipid feed combined with depression by Chronic Unpredictable Mild Stress (CUMS). 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. (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). 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.

Modulation of GSK-3β/β-Catenin Signaling Contributes to Learning and Memory Impairment in a Rat Model of Depression.

PubMed

Hui, Jiaojie; Zhang, Jianping; Pu, Mengjia; Zhou, Xingliang; Dong, Liang; Mao, Xuqiang; Shi, Guofeng; Zou, Jian; Wu, Jingjing; Jiang, Dongmei; Xi, Guangjun

2018-04-23

It is widely accepted that cognitive processes, such as learning and memory, are affected in depression, but the molecular mechanisms underlying the interactions of these 2 disorders are not clearly understood. Recently, glycogen synthase kinase-3 beta (GSK-3β)/β-catenin signaling was shown to play an important role in the regulation of learning and memory. The present study used a rat model of depression, chronic unpredictable stress, to determine whether hippocampal GSK-3β/β-catenin signaling was involved in learning and memory alterations. Our results demonstrated that chronic unpredictable stress had a dramatic influence on spatial cognitive performance in the Morris water maze task and reduced the phosphorylation of Ser9 of GSK-3β as well as the total and nuclear levels of β-catenin in the hippocampus. Inhibition of GSK3β by SB216763 significantly ameliorated the cognitive deficits induced by chronic unpredictable stress, while overexpression of GSK3β by AAV-mediated gene transfer significantly decreased cognitive performance in adult rats. In addition, chronic unpredictable stress exposure increased the expression of the canonical Wnt antagonist Dkk-1. Furthermore, chronic administration of corticosterone significantly increased Dkk-1 expression, decreased the phosphorylation of Ser9 of GSK-3β, and resulted in the impairment of hippocampal learning and memory. Our results indicate that impairment of learning and memory in response to chronic unpredictable stress may be attributed to the dysfunction of GSK-3β/β-catenin signaling mediated by increased glucocorticoid signaling via Dkk-1.

Therapeutic potential of silymarin in chronic unpredictable mild stress induced depressive-like behavior in mice.

PubMed

Thakare, Vishnu N; Patil, Rajesh R; Oswal, Rajesh J; Dhakane, Valmik D; Aswar, Manoj K; Patel, Bhoomika M

2018-02-01

Silymarin, a plant-derived polyphenolic flavonoid of Silybum marianum, elicited significant antidepressant-like activity in an acute restraint stress model of depression. It improved monoamines, mainly 5-hydroxytryptamine (5-HT) levels in the cortex, dopamine (DA) and norepinephrine (NE) in the cerebellum in mice. The present study was undertaken to explore the antidepressant potential of silymarin in chronic unpredictable mild stress (CUMS) induced depressive-like behavior in mice, and to find out its probable mechanism(s) of action, mainly neurogenesis, neuroinflammation, and/or oxidative stress. The mice were subjected to CUMS for 28 days (4 weeks) and administered with silymarin (100 mg/kg and 200 mg/kg), or fluoxetine or vehicle from days 8 to 28 (3 weeks simultaneously). Animals were evaluated for behavioral changes, such as anhedonia by sucrose preference test, behavioral despair by forced swim test, and exploratory behaviors by an open field test. In addition, neurobiochemical alterations, mainly monoamines, 5-HT, NE, DA, neurotrophic factor BDNF, and cytokines, IL-6, TNF-α, oxidant-antioxidant parameters by determining the malondialdehyde formation (an index of lipid peroxidation process), superoxide dismutase (SOD) and catalase (CAT) activity in hippocampus and cerebral cortex along with serum corticosterone were investigated. Our findings reveal that mice subjected to CUMS exhibited lower sucrose preference, increase immobility time without affecting general locomotion of the animals, and reduce BDNF, 5-HT, NE, and DA level, increased serum corticosterone, IL-6 and TNF-α along with an oxidant-antioxidant imbalance in the hippocampus and cerebral cortex. Silymarin significantly reversed the CUMS-induced changes in the hippocampus and cerebral cortex in mice. Thus, the possible mechanism involved in the antidepressant-like activity of silymarin is correlated to the alleviation of monoaminergic, neurogenesis (enhancing 5-HT, NE, and BDNF levels), and attenuation of inflammatory cytokines system and oxidative stress by modulation of corticosterone response, restoration of antioxidant defense system in cerebral cortex and hippocampus.

Anti-depressant-like effects of Jieyu chufan capsules in a mouse model of unpredictable chronic mild stress

PubMed Central

Zhao, Hui; Liang, Bingyu; Yu, Linjie; Xu, Yun

2017-01-01

Jieyu chufan (JYCF) is a well-known Chinese traditional medicine used for depression; however, the molecular mechanism underlying its anti-depressant action has remained elusive. In the present study, the anti-depressant effects of JYCF and the potential mechanisms were investigated in a mouse model. Five groups of 12 C57BL/6 mice each were used in the study, including a normal control group (NC group), a model control group (MC group) and three groups, which received different doses of JYCF (1.25, 2.5 and 5 g/kg) orally for 21 days (JYCF groups). The MC group and the three JYCF groups were subjected to 3 weeks of unpredictable chronic mild stress (UCMS) to induce depression-like behavior. All groups were subjected to a sucrose consumption test along with a forced swimming test to confirm depression-like behavior, an open-field test and an elevated plus maze test to confirm anxiety-like behavior, and a Morris water maze test to evaluate spatial learning and memory. In addition, synaptic density in the hippocampus was evaluated and western blot and immunostaining were used to analyze hippocampal expression of postsynaptic density protein-95 (PSD95), synaptophysin (Syn), cyclic adenosine monophosphate response element binding protein (CREB), brain-derived neurotrophic factor (BDNF), Akt and glycogen synthase kinase (GSK)-3β as well as their phosphorylated (p) versions. The results showed that JYCF (2.5 and 5 g/kg) alleviated depressive-like behaviors and increased synaptic density in UCMS mice. Moreover, JYCF upregulated the expression of PSD95, Syn and BDNF and increased phosphorylated Akt, CREB and GSK-3β in the hippocampus. These results suggested that JYCF exerts an anti-depressant-like activity in UCMS-induced mice, which is likely to be mediated by reversing the stress-induced disruption of BDNF and GSK-3β activity. PMID:28810562

Validation of the long-term assessment of hypothalamic-pituitary-adrenal activity in rats using hair corticosterone as a biomarker.

PubMed

Scorrano, Fabrizio; Carrasco, Javier; Pastor-Ciurana, Jordi; Belda, Xavier; Rami-Bastante, Alicia; Bacci, Maria Laura; Armario, Antonio

2015-03-01

The evaluation of chronic activity of the hypothalamic-pituitary-adrenal (HPA) axis is critical for determining the impact of chronic stressful situations. However, current methods have important limitations. The potential use of hair glucocorticoids as a noninvasive retrospective biomarker of long-term HPA activity is gaining acceptance in humans and wild animals. However, there is no study examining hair corticosterone (HC) in laboratory animals. The present study validates a method for measuring HC in rats and demonstrates that it properly reflects chronic HPA activity. The HC concentration was similar in male and female rats, despite higher total plasma corticosterone levels in females, tentatively suggesting that it reflects free rather than total plasma corticosterone. Exposure of male rats to 2 different chronic stress protocols (chronic immobilization and chronic unpredictable stress) resulted in similarly higher HC levels compared to controls (1.8-fold). HC also increased after a mild chronic stressor (30 min daily restraint). Chronic administration of 2 different doses of a long-acting ACTH preparation dramatically increased HC (3.1- and 21.5-fold, respectively), demonstrating that a ceiling effect in HC accumulation is unlikely under other more natural conditions. Finally, adrenalectomy significantly reduced HC. In conclusion, HC measurement in rats appears appropriate to evaluate integrated chronic changes in circulating corticosterone. © FASEB.

Protective effects of chronic mild stress during adolescence in the low-novelty responder rat.

PubMed

Rana, Samir; Nam, Hyungwoo; Glover, Matthew E; Akil, Huda; Watson, Stanley J; Clinton, Sarah M; Kerman, Ilan A

2016-01-01

Stress-elicited behavioral and physiologic responses vary widely across individuals and depend on a combination of environmental and genetic factors. Adolescence is an important developmental period when neural circuits that guide emotional behavior and stress reactivity are still maturing. A critical question is whether stress exposure elicits contrasting effects when it occurs during adolescence versus adulthood. We previously found that Sprague-Dawley rats selectively bred for low-behavioral response to novelty (bred Low Responders; bLRs) are particularly sensitive to chronic unpredictable mild stress (CMS) exposure in adulthood, which exacerbates their typically high levels of spontaneous depressive- and anxiety-like behavior. Given developmental processes known to occur during adolescence, we sought to determine whether the impact of CMS on bLR rats is equivalent when they are exposed to it during adolescence as compared with adulthood. Young bLR rats were either exposed to CMS or control condition from postnatal days 35-60. As adults, we found that CMS-exposed bLRs maintained high levels of sucrose preference and exhibited increased social exploration along with decreased immobility on the forced swim test compared with bLR controls. These data indicate a protective effect of CMS exposure during adolescence in bLR rats.

Blockade of AT1 type receptors for angiotensin II prevents cardiac microvascular fibrosis induced by chronic stress in Sprague-Dawley rats.

PubMed

Firoozmand, Lília Taddeo; Sanches, Andrea; Damaceno-Rodrigues, Nilsa Regina; Perez, Juliana Dinéia; Aragão, Danielle Sanches; Rosa, Rodolfo Mattar; Marcondes, Fernanda Klein; Casarini, Dulce Elena; Caldini, Elia Garcia; Cunha, Tatiana Sousa

2018-04-20

To test the effects of chronic-stress on the cardiovascular system, the model of chronic mild unpredictable stress (CMS) has been widely used. The CMS protocol consists of the random, intermittent, and unpredictable exposure of laboratory animals to a variety of stressors, during 3 consecutive weeks. In this study, we tested the hypothesis that exposure to the CMS protocol leads to left ventricle microcirculatory remodeling that can be attenuated by angiotensin II receptor blockade. Male Sprague-Dawley rats were randomly assigned into four groups: Control, Stress, Control + losartan, and Stress + losartan (N = 6, each group, losartan: 20 mg/kg/day). The rats were euthanized 15 days after CMS exposure, and blood samples and left ventricle were collected. Rats submitted to CMS presented increased glycemia, corticosterone, noradrenaline and adrenaline concentration, and losartan reduced the concentration of the circulating amines. Cardiac angiotensin II, measured by high-performance liquid chromatography (HPLC), was significantly increased in the CMS group, and losartan treatment reduced it, while angiotensin 1-7 was significantly higher in the CMS losartan-treated group as compared with CMS. Histological analysis, verified by transmission electron microscopy, showed that rats exposed to CMS presented increased perivascular collagen and losartan effectively prevented the development of this process. Hence, CMS induced a state of microvascular disease, with increased perivascular collagen deposition, that may be the trigger for further development of cardiovascular disease. In this case, CMS fibrosis is associated with increased production of catecholamines and with a disruption of renin-angiotensin system balance, which can be prevented by angiotensin II receptor blockade.

Adaptogenic activity of Siotone, a polyherbal formulation of Ayurvedic rasayanas.

PubMed

Bhattacharya, S K; Bhattacharya, A; Chakrabarti, A

2000-02-01

Siotone (ST) is a herbal formulation comprising of Withania somnifera, Ocimum sanctum, Asparagus racemosus, Tribulus terristris and shilajit, all of which are classified in Ayurveda as rasayanas which are reputed to promote physical and mental health, improve defence mechanisms of the body and enhance longevity. These attributes are similar to the modern concept of adaptogenic agents, which are, known to afford protection of the human physiological system against diverse stressors. The present study was undertaken to investigate the adaptogenic activity of ST against chronic unpredictable, but mild, footshock stress induced perturbations in behaviour (depression), glucose metabolism, suppressed male sexual behaviour, immunosuppression and cognitive dysfunction in CF strain albino rats. Gastric ulceration, adrenal gland and spleen weights, ascorbic acid and corticosterone concentrations of adrenal cortex, and plasma corticosterone levels, were used as the stress indices. Panax ginseng (PG) was used as the standard adaptogenic agent for comparison. Additionally, rat brain levels of tribulin, an endogenous endocoid postulated to be involved in stress, were also assessed in terms of endogenous monoamine oxidase (MAO) A and MAOB inhibitory activity. Chronic unpredictable footshock induced marked gastric ulceration, significant increase in adrenal gland weight and plasma corticosterone levels, with concomitant decreases in spleen weight, and concentrations of adrenal gland ascorbic acid and corticosterone. These effects were attenuated by ST (50 and 100 mg/kg, p.o.) and PG (100 mg/kg, p.o.), administered once daily over a period of 14 days, the period of stress induction. Chronic stress also induced glucose intolerance, suppressed male sexual behaviour, induced behavioural depression (Porsolt's swim despair test and learned helplessness test) and cognitive dysfunction (attenuated retention of learning in active and passive avoidance tests), and immunosuppression (leucocyte migration inhibition and sheep RBC challenged increase in paw oedema in sensitized rats). All these chronic stress-induced perturbations were attenuated, dose-dependently by ST (50 and 100 mg/kg, p.o.) and PG (100 mg/kg, p.o.). Chronic stress-induced increase in rat brain tribulin activity was also reversed by these doses of ST and by PG. The results indicate that ST has significant adaptogenic activity, qualitatively comparable to PG, against a variety of behavioural, biochemical and physiological perturbations induced by unpredictable stress, which has been proposed to be a better indicator of clinical stress than acute stress parameters. The likely contribution of the individual constituents of ST in the observed adaptogenic action of the polyherbal formulation, have been discussed.

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

PubMed

Chaby, Lauren E; Cavigelli, Sonia A; White, Amanda; Wang, Kayllie; Braithwaite, Victoria A

2013-01-01

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 [F (1, 12) = 5.000, P < 0.05], altered coping response [T (1, 14) = 2.216, P = 0.04], and accelerated decision-making [T (1, 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 [T (1, 14) = 2.240, P = 0.04; T (1, 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.

Etazolate rescues behavioral deficits in chronic unpredictable mild stress model: modulation of hypothalamic-pituitary-adrenal axis activity and brain-derived neurotrophic factor level.

PubMed

Jindal, Ankur; Mahesh, Radhakrishnan; Bhatt, Shvetank

2013-11-01

Preliminary study in our laboratory showed that etazolate produced antidepressant- and anxiolytic-like effects in rodent models, however, the ability of etazolate to produce antidepressant- and anxiolytic-like effects and underlying mechanism(s) in chronic unpredictable mild stress (CUMS) model have not been adequately addressed. This study was aimed to investigate the beneficial effects of etazolate on CUMS-induced behavioral deficits (depression- and anxiety-like behaviors). In addition, the possible underlying mechanism(s) of etazolate in CUMS model was also investigated by measuring serum corticosterone (CORT) and brain-derived neurotrophic factor (BDNF) levels. Mice were subjected to a battery of stressors for 28 days. Etazolate (0.5 and 1 mg/kg, p.o.) and fluoxetine (20mg/kg, p.o.) were administered during the last 21 days (8-28th) of the CUMS paradigm. The results showed that 4-weeks CUMS produces significant depression-like behavior in tail suspension test (TST) and partial anxiety-like behavior in elevated plus maze (EPM) and open field test (OFT). Stressed mice have also shown a significant high serum CORT and low BDNF level. Chronic treatment with etazolate (0.5 and 1mg/kg., p.o.) and fluoxetine (20mg/kg., p.o.) produced significant antidepressant-like behavior in TST (decreased duration of immobility), whereas, partial anxiolytic-like behavior in EPM (increased percentage of open arm entries) and OFT (increased % central ambulation score, total ambulation score and time spent in center zone). In addition, etazolate and fluoxetine treatment significantly (p<0.05) increased the BDNF level and inhibited the hypothalamic-pituitary-adrenocortical (HPA) axis hyperactivity, as evidenced by low serum CORT level in stressed mice. In addition, etazolate and fluoxetine also showed significant antidepressant- and anxiolytic-like effects in normal control mice. In this study no significant changes were observed in locomotor activity in actophotometer test. Moreover, we did not find any effect of etazolate and fluoxetine on CORT and BDNF levels in normal control mice. In conclusion, the results of the present study suggested compelling evidences that etazolate has more marked effect on depression-like behavior in mice, which is atleast in part may be related to their modulating effects on the HPA axis and BDNF level. Copyright © 2013 Elsevier Ltd. All rights reserved.

Antidepressants recruit new neurons to improve stress response regulation

PubMed Central

Surget, A; Tanti, A; Leonardo, E D; Laugeray, A; Rainer, Q; Touma, C; Palme, R; Griebel, G; Ibarguen-Vargas, Y; Hen, R; Belzung, C

2011-01-01

Recent research suggests an involvement of hippocampal neurogenesis in behavioral effects of antidepressants. However, the precise mechanisms through which newborn granule neurons might influence the antidepressant response remain elusive. Here, we demonstrate that unpredictable chronic mild stress in mice not only reduces hippocampal neurogenesis, but also dampens the relationship between hippocampus and the main stress hormone system, the hypothalamo-pituitary-adrenal (HPA) axis. Moreover, this relationship is restored by treatment with the antidepressant fluoxetine, in a neurogenesis-dependent manner. Specifically, chronic stress severely impairs HPA axis activity, the ability of hippocampus to modulate downstream brain areas involved in the stress response, the sensitivity of the hippocampal granule cell network to novelty/glucocorticoid effects and the hippocampus-dependent negative feedback of the HPA axis. Remarkably, we revealed that, although ablation of hippocampal neurogenesis alone does not impair HPA axis activity, the ability of fluoxetine to restore hippocampal regulation of the HPA axis under chronic stress conditions, occurs only in the presence of an intact neurogenic niche. These findings provide a mechanistic framework for understanding how adult-generated new neurons influence the response to antidepressants. We suggest that newly generated neurons may facilitate stress integration and that, during chronic stress or depression, enhancing neurogenesis enables a dysfunctional hippocampus to restore the central control on stress response systems, then allowing recovery. PMID:21537331

Fluoxetine regulates mTOR signalling in a region-dependent manner in depression-like mice.

PubMed

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

2015-11-02

Previous studies have demonstrated that the mammalian target of rapamycin (mTOR) signaling pathway has an important role in ketamine-induced, rapid antidepressant effects despite the acute administration of fluoxetine not affecting mTOR phosphorylation in the brain. However, the effects of long-term fluoxetine treatment on mTOR modulation have not been assessed to date. In the present study, we examined whether fluoxetine, a type of commonly used antidepressant agent, alters mTOR signaling following chronic administration in different brain regions, including the frontal cortex, hippocampus, amygdala and hypothalamus. We also investigated whether fluoxetine enhanced synaptic protein levels in these regions via the activation of the mTOR signaling pathway and its downstream regulators, p70S6K and 4E-BP-1. The results indicated that chronic fluoxetine treatment attenuated the chronic, unpredictable, mild stress (CUMS)-induced mTOR phosphorylation reduction in the hippocampus and amygdala of mice but not in the frontal cortex or the hypothalamus. Moreover, the CUMS-decreased PSD-95 and synapsin I levels were reversed by fluoxetine, and these effects were blocked by rapamycin only in the hippocampus. In conclusion, our findings suggest that chronic treatment with fluoxetine can induce synaptic protein expression by activating the mTOR signaling pathway in a region-dependent manner and mainly in the hippocampus.

Antidepressant Effects of the Ginsenoside Metabolite Compound K, Assessed by Behavioral Despair Test and Chronic Unpredictable Mild Stress Model.

PubMed

Song, Wu; Guo, Yan; Jiang, Shuang; Wei, Lin; Liu, Zhi; Wang, Xiaoyan; Su, Ying

2018-05-22

Depression is a major social and health problem worldwide. Compound K (CK), an intestinal metabolite of panaxadiol ginsenosides, has been demonstrated to possess significant pharmacological effects on the central nervous system (CNS). Here, we set up this study to investigate the antidepressant effect of CK, and to explore the potential mechanisms underlying this activity. The behavioral despair model and chronic unpredictable mild stress (CUMS) model were established in mice or rats, respectively. Forced swimming test (FST), tail suspension test (TST) and locomotor activity were performed in mice, while the open-field test, food consumption and sucrose preference were assessed in rats. To investigate the underlying mechanism, the levels of endogenous noradrenaline, dopamine (DA), 5-hydroxytryptamine (5-HT) and their metabolites in the prefrontal cortex (PFC) and hippocampus were detected by HPLC coupled with electron detector. The dopamine degradation enzyme (COMT and MAO) expression was measured by western blot. The BDNF and NGF expression were investigated by immunohistochemical staining analysis. The results showed CK (10, 30 mg/kg) intragastric administration for 14 days significantly shorten the immobility time in FST and TST, which could be partially reversed by a D1 receptor antagonist Sch23390. For CUMS rats, CK alleviated the depressant-like behaviors, including decreased food consumption, spontaneous locomotor activity and lower sucrose preference, while WAY-100635, a 5-HT 1A receptor antagonist, could attenuate this effect. In addition, CK increased the levels of 5-HT, DA and their metabolites in the PFC and hippocampus of CUMS rats, and could reverse overexpression of MAO B in PFC and hippocampus. CK also increased the GSH and GPx activity in the hippocampus and PFC. The IHC results revealed the BDNF and NGF expression were increased in CK-treated rats. The obtained results indicate that CK exhibits antidepressant effects in rodents, which may be due to the regulation of monoamine neurotransmitter concentration, enhancement of antioxidant capacity, as well as increase of neurotrophin expression in the CNS.

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

PubMed Central

Jia, Hong-mei; Feng, Yu-fei; Liu, Yue-tao; Chang, Xing; Chen, Lin; Zhang, Hong-wu; Ding, Gang; Zou, Zhong-mei

2013-01-01

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 the comprehensive potential depression-related biomarkers and helpful in further understanding the underlying molecular mechanisms of depression through the disturbance of metabolic pathways. PMID:23696839

Antidepressant-like effect of essential oil of Perilla frutescens in a chronic, unpredictable, mild stress-induced depression model mice.

PubMed

Ji, Wei-Wei; Li, Rui-Peng; Li, Meng; Wang, Shu-Yuan; Zhang, Xian; Niu, Xing-Xing; Li, Wei; Yan, Lu; Wang, Yang; Fu, Qiang; Ma, Shi-Ping

2014-10-01

Perilla frutescens (Perilla leaf), a garnishing vegetable in East Asian countries, as well as a plant-based medicine, has been used for centuries to treat various conditions, including depression. Several studies have demonstrated that the essential oil of P. frutescens (EOPF) attenuated the depressive-like behavior in mice. The present study was designed to test the anti-depressant effects of EOPF and the possible mechanisms in an chronic, unpredictable, mild stress (CUMS)-induced mouse model. With the exposure to stressor once daily for five consecutive weeks, EOPF (3, 6, and 9 mg·kg(-1)) and a positive control drug fluoxetine (20 mg·kg(-1)) were administered through gastric intubation to mice once daily for three consecutive weeks from the 3(rd) week. Open-field test, sucrose consumption test, tail suspension test (TST), and forced swimming test (FST) were used to evaluate the behavioral activity. The contents of 5-hydroxytryptamine (5-HT) and its metabolite, 5-hydroxyindoleacetic acid (5-HIAA), in mouse hippocampus were determined by HPLC-ECD. Serum interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)-α levels were evaluated by enzyme-linked immunosorbent assay (ELISA). The results showed that CUMS significantly decreased the levels of 5-HT and 5-HIAA in the hippocampus, with an increase in plasma IL-6, IL-1β, and TNF-α levels. CUMS also reduced open-field activity, sucrose consumption, as well as increased immobility duration in FST and TST. EOPF administration could effectively reverse the alterations in the concentrations of 5-HT and 5-HIAA; reduce the IL-6, IL-1β, and TNF-α levels. Moreover, EOPF could effectively reverse alterations in immobility duration, sucrose consumption, and open-field activity. However, the effect was not dose-dependent. In conclusion, EOPF administration exhibited significant antidepressant-like effects in mice with CUMS-induced depression. The antidepressant activity of EOPF might be related to the relation between alteration of serotonergic responses and anti-inflammatory effects. Copyright © 2014 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Chronic unpredictable mild stress decreases BDNF and NGF levels and Na(+),K(+)-ATPase activity in the hippocampus and prefrontal cortex of mice: antidepressant effect of chrysin.

PubMed

Filho, C B; Jesse, C R; Donato, F; Giacomeli, R; Del Fabbro, L; da Silva Antunes, M; de Gomes, M G; Goes, A T R; Boeira, S P; Prigol, M; Souza, L C

2015-03-19

Our working hypothesis is that brain neurotrophins and brain Na(+),K(+)-ATPase may be strongly associated with the occurrence of depression in animals subjected to chronic unpredictable mild stress (CUMS). Still, we believe that chrysin, a natural and bioactive flavonoid found in honey and some plants, can provide satisfactory effects on antidepressant therapy. Thus, we aimed to evaluate the effect of CUMS on brain-derived neurotropic factor (BDNF) and nerve growth factor (NGF) levels as well as the Na(+),K(+)-ATPase activity in the hippocampus and prefrontal cortex of female mice. We also aimed to examine the effect of a 28-day oral treatment with chrysin (5 or 20mg/kg) in female mice subjected to CUMS, comparing to the effect of fluoxetine. Results showed that CUMS applied for 28days induced a decrease in BDNF and NGF levels as well as in the Na(+),K(+)-ATPase activity. CUMS also promoted a depressive status in the swimming forced test (FST), in the sucrose preference test, and in corticosterone levels. Chrysin (20mg/kg) and fluoxetine also occasioned the up-regulation of BDNF and NGF levels in non-stressed mice and in mice subjected to CUMS. CUMS decreased non-protein thiol (NPSH) levels and increased reactive oxygen species (ROS) levels. In response to these changes, the glutathione reductase (GR), glutathione peroxidase (GPx) and catalase (CAT) activities were increased in mice exposed to CUMS. Chrysin and fluoxetine treatments protected against all these alterations, suggesting the involvement of the antioxidant function in the antidepressant effect of chrysin and fluoxetine. In conclusion, CUMS decreased BDNF and NGF levels as well as the Na(+),K(+)-ATPase activity in mice. Chrysin presented antidepressant effect in mice on behavioral, neurotrophic and biochemistry parameters equivalent to fluoxetine. Furthermore, we suggest that the up-regulation of BDNF and NGF levels is a mechanism possibly involved in the antidepressant effect of chrysin in mice. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Resveratrol ameliorates chronic unpredictable mild stress-induced depression-like behavior: involvement of the HPA axis, inflammatory markers, BDNF, and Wnt/β-catenin pathway in rats.

PubMed

Yang, Xin-Hua; Song, Su-Qi; Xu, Yun

2017-01-01

Classic antidepressant drugs are modestly effective across the population and most are associated with intolerable side effects. Recently, numerous lines of evidence suggest that resveratrol (RES), a natural polyphenol, possesses beneficial therapeutic activity for depression. The aim of the present study was to explore whether RES exhibits an antidepressant-like effect in a depression model and to explore the possible mechanism. A depression model was established via chronic unpredictable mild stress (CUMS), after which the model rats in the RES and fluoxetine groups received a daily injection of RES or fluoxetine, respectively. The sucrose preference test, open field test, and forced swimming test were used to explore the antidepressant-like effects of RES. The activity of the hypothalamic-pituitary-adrenal (HPA) axis was evaluated by detecting the plasma corticosterone concentration and hypothalamic mRNA expression of corticotrophin-releasing hormone. The plasma interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor-α (TNF-α) concentrations were measured by enzyme-linked immunosorbent assay. Hippocampal protein expression of brain-derived neurotrophic factor (BDNF) and the Wnt/β-catenin pathway were analyzed by western blot. The results showed that RES relieved depression-like behavior of CUMS rats, as indicated by the increased sucrose preference and the decreased immobile time. Rats that received RES treatment exhibited reduced plasma corticosterone levels and corticotrophin-releasing hormone mRNA expression in the hypothalamus, suggesting that the hyperactivity of the HPA axis in CUMS rats was reversed by RES. Moreover, after RES treatment, the rats exhibited increased plasma IL-6, CRP, and TNF-α concentrations. Furthermore, RES treatment upregulated the hippocampal protein levels of BDNF and the relative ratio of p-β-catenin/β-catenin while downregulating the relative ratio of p-GSK-3β/GSK-3β. Our findings suggest that RES improved depressive behavior in CUMS rats by downregulating HPA axis hyperactivity, increasing BDNF expression and plasma IL-6, CRP, and TNF-α concentrations, and regulating the hippocampal Wnt/β-catenin pathway.

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

PubMed

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. Copyright © 2014 Elsevier B.V. All rights reserved.

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

PubMed Central

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

2015-01-01

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 two days and given one retention trial on the third day, with brains removed 30 minutes 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. PMID:25591480

[Role of stress in depression insomnia and sleep characteristics of commonly used animal stress models].

PubMed

Li, Yi-Ying; Hu, Zhen-Zhen; Huang, Zhi-Li; Yang, Su-Rong

2012-01-01

Depression and insomnia are intimately related. Depressed patients usually manifest sleep discontinuity and early awakening, reduced or no slow wave sleep (SWS) and shortened latency of rapid eye movement (REM) sleep. These sleep abnormalities are very similar to those caused by over activated hypothalamic-pituitary-adrenal (HPA) axis with stress. Therefore, the animal models developed by post-traumatic stress disorder or chronic unpredictable mild stress could be used to evaluate drugs which have effects of both anti-depression and improvement of sleep quality, and to provide a more reliable platform for further studis on the mechanisms of depression and accompanied insomnia. This review mainly focuses on the typical features of sleep disturbance of depression, possible pathophysiological mechanisms, establishment of animal stress models and analysis of their abnormal sleep characteristics.

Hereditary chronic pancreatitis

PubMed Central

Rosendahl, Jonas; Bödeker, Hans; Mössner, Joachim; Teich, Niels

2007-01-01

Hereditary chronic pancreatitis (HCP) is a very rare form of early onset chronic pancreatitis. With the exception of the young age at diagnosis and a slower progression, the clinical course, morphological features and laboratory findings of HCP do not differ from those of patients with alcoholic chronic pancreatitis. As well, diagnostic criteria and treatment of HCP resemble that of chronic pancreatitis of other causes. The clinical presentation is highly variable and includes chronic abdominal pain, impairment of endocrine and exocrine pancreatic function, nausea and vomiting, maldigestion, diabetes, pseudocysts, bile duct and duodenal obstruction, and rarely pancreatic cancer. Fortunately, most patients have a mild disease. Mutations in the PRSS1 gene, encoding cationic trypsinogen, play a causative role in chronic pancreatitis. It has been shown that the PRSS1 mutations increase autocatalytic conversion of trypsinogen to active trypsin, and thus probably cause premature, intrapancreatic trypsinogen activation disturbing the intrapancreatic balance of proteases and their inhibitors. Other genes, such as the anionic trypsinogen (PRSS2), the serine protease inhibitor, Kazal type 1 (SPINK1) and the cystic fibrosis transmembrane conductance regulator (CFTR) have been found to be associated with chronic pancreatitis (idiopathic and hereditary) as well. Genetic testing should only be performed in carefully selected patients by direct DNA sequencing and antenatal diagnosis should not be encouraged. Treatment focuses on enzyme and nutritional supplementation, pain management, pancreatic diabetes, and local organ complications, such as pseudocysts, bile duct or duodenal obstruction. The disease course and prognosis of patients with HCP is unpredictable. Pancreatic cancer risk is elevated. Therefore, HCP patients should strongly avoid environmental risk factors for pancreatic cancer. PMID:17204147

Integration of animal behaviors under stresses with different time courses

PubMed Central

Zheng, Lun; Zheng, Xigeng

2014-01-01

We used animal models of “forced swim stress” and “chronic unpredictable stress”, and tried to reveal whether a passive coping style of high flotation behavior in forced swim stress predicts anhedonia behavior after chronic unpredictable stress, and whether the dopamine system regulates floating and anhedonia behaviors. Our results confirmed that depression-prone rats use “floating behavior” as a coping strategy in forced swim stress and more readily suffer from anhedonia during chronic unpredictable stress. Intraperitoneal injection or nucleus accumbens microinjection of the dopamine 2/3 receptor subtype agonist ropinirole reduced floating behaviors in depression-prone animals, but increased sucrose preference in rats showing anhedonia. These data indicate that floating behavior is a defensive mode that is preferred by susceptible individuals under conditions of acute stress. Simultaneously, these animals more readily experienced anhedonia under long-term stress; that is, they were more readily affected by depression. Our results suggest that dopamine 2/3 receptor subtypes in the nucleus accumbens play an important role in floating behaviors and anhedonia. PMID:25317159

Nicotine Significantly Improves Chronic Stress-Induced Impairments of Cognition and Synaptic Plasticity in Mice.

PubMed

Shang, Xueliang; Shang, Yingchun; Fu, Jingxuan; Zhang, Tao

2017-08-01

The aim of this study was to examine if nicotine was able to improve cognition deficits in a mouse model of chronic mild stress. Twenty-four male C57BL/6 mice were divided into three groups: control, stress, and stress with nicotine treatment. The animal model was established by combining chronic unpredictable mild stress (CUMS) and isolated feeding. Mice were exposed to CUMS continued for 28 days, while nicotine (0.2 mg/kg) was also administrated for 28 days. Weight and sucrose consumption were measured during model establishing period. The anxiety and behavioral despair were analyzed using the forced swim test (FST) and open-field test (OFT). Spatial cognition was evaluated using Morris water maze (MWM) test. Following behavioral assessment, both long-term potentiation (LTP) and depotentiation (DEP) were recorded in the hippocampal dentate gyrus (DG) region. Both synaptic and Notch1 proteins were measured by Western. Nicotine increased stressed mouse's sucrose consumption. The MWM test showed that spatial learning and reversal learning in stressed animals were remarkably affected relative to controls, whereas nicotine partially rescued cognitive functions. Additionally, nicotine considerably alleviated the level of anxiety and the degree of behavioral despair in stressed mice. It effectively mitigated the depression-induced impairment of hippocampal synaptic plasticity, in which both the LTP and DEP were significantly inhibited in stressed mice. Moreover, nicotine enhanced the expression of synaptic and Notch1 proteins in stressed animals. The results suggest that nicotine ameliorates the depression-like symptoms and improves the hippocampal synaptic plasticity closely associated with activating transmembrane ion channel receptors and Notch signaling components. Graphical Abstract ᅟ.

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

PubMed

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. Copyright © 2015. Published by Elsevier B.V.

How does early maternal separation and chronic stress in adult rats affect the immunoreactivity of serotonergic neurons within the dorsal raphe nucleus?

PubMed

Pollano, Antonella; Trujillo, Verónica; Suárez, Marta M

2018-01-01

Vulnerability to emotional disorders like depression derives from interactions between early and late environments, including stressful conditions. The serotonin (5HT) system is strongly affected by stress and chronic unpredictable stress can alter the 5HT system. We evaluated the distribution of active serotonergic neurons in the dorsal raphe nucleus (DR) through immunohistochemistry in maternally separated and chronically stressed rats treated with an antidepressant, tianeptine, whose mechanism of action is still under review. Male Wistar rats were subjected to daily maternal separation (MS) for 4.5 h between postnatal days (PND) 1-21, or to animal facility rearing (AFR). Between (PND) days 50-74, rats were exposed to chronic unpredictable stress and were treated daily with tianeptine (10 mg/kg) or vehicle. We found an interaction between the effects of MS and chronic unpredictable stress on Fos-5HT immunoreactive cells at mid-caudal level of the DR. MS-chronically stressed rats showed an increase of Fos-5HT immunoreactive cells compared with AFR-chronically stressed rats. The ventrolateral (DRL/VLPAG) and dorsal (DRD) subdivisions of the DR were significantly more active than the ventral part (DRV). At the rostral level of the DR, tianeptine decreased the number of Fos-5HT cells in DR in the AFR groups, both unstressed and stressed. Overall, our results support the idea of a match in phenotype exhibited when the early and the adult environment correspond.

Fluoxetine regulates mTOR signalling in a region-dependent manner in depression-like mice

PubMed Central

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

2015-01-01

Previous studies have demonstrated that the mammalian target of rapamycin (mTOR) signaling pathway has an important role in ketamine-induced, rapid antidepressant effects despite the acute administration of fluoxetine not affecting mTOR phosphorylation in the brain. However, the effects of long-term fluoxetine treatment on mTOR modulation have not been assessed to date. In the present study, we examined whether fluoxetine, a type of commonly used antidepressant agent, alters mTOR signaling following chronic administration in different brain regions, including the frontal cortex, hippocampus, amygdala and hypothalamus. We also investigated whether fluoxetine enhanced synaptic protein levels in these regions via the activation of the mTOR signaling pathway and its downstream regulators, p70S6K and 4E-BP-1. The results indicated that chronic fluoxetine treatment attenuated the chronic, unpredictable, mild stress (CUMS)-induced mTOR phosphorylation reduction in the hippocampus and amygdala of mice but not in the frontal cortex or the hypothalamus. Moreover, the CUMS-decreased PSD-95 and synapsin I levels were reversed by fluoxetine, and these effects were blocked by rapamycin only in the hippocampus. In conclusion, our findings suggest that chronic treatment with fluoxetine can induce synaptic protein expression by activating the mTOR signaling pathway in a region-dependent manner and mainly in the hippocampus. PMID:26522512

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

PubMed

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. Copyright © 2010 Elsevier B.V. All rights reserved.

The antidepressant effect of an antiulcer pentadecapeptide BPC 157 in Porsolt's test and chronic unpredictable stress in rats. A comparison with antidepressants.

PubMed

Sikiric, P; Separovic, J; Buljat, G; Anic, T; Stancic-Rokotov, D; Mikus, D; Marovic, A; Prkacin, I; Duplancic, B; Zoricic, I; Aralica, G; Lovric-Bencic, M; Ziger, T; Perovic, D; Rotkvic, I; Mise, S; Hanzevacki, M; Hahn, V; Seiwerth, S; Turkovic, B; Grabarevic, Z; Petek, M; Rucman, R

2000-01-01

Various antidepressants have antiulcer activity. Likewise, the models currently used in ulcers and depression disorders research have a considerable degree of similarity. Therefore, the possibility that depression disorders could be effectively influenced by a primary antiulcer agent with a cyto/organoprotective activity, such as the novel stomach pentadecapeptide BPC 157, was investigated in two rat depression assays. First, a forced swimming test (a Porsolt's procedure) was used. As a more severe procedure, chronic unpredictable stress (after 5 d of unpredictable stress protocol, once daily drug application during stress procedure, open field-immobility test assessment at fourth or sixth day of medication) was used. In a forced swimming test, a reduction of the immobility time in BPC 157 (10 microg, 10 ng x kg(-1) i.p.) treated rats corresponds to the activity of the 15 mg or 40 mg (i.p.) of conventional antidepressants, imipramine or nialamide, respectively, given according to the original Porsolt's protocol. In chronic unpredictable stress procedure, particular aggravation of experimental conditions markedly affected the conventional antidepressant activity, whereas BPC 157 effectiveness was continuously present. The effect of daily imipramine (30 mg) medication could be seen only after a more prolonged period, but not after a shorter period (i.e., 4-d protocol). In these conditions, no delay in the effectiveness was noted in BPC 157 medication and a reduction of the immobility of chronically stressed rats was noted after both 4 and 6 d of BPC 157 (10 microg, 10 ng) medication.

Prenatal exposure to escitalopram and/or stress in rats: a prenatal stress model of maternal depression and its treatment

PubMed Central

Bourke, Chase H.; Capello, Catherine F.; Rogers, Swati M.; Yu, Megan L.; Boss-Williams, Katherine A.; Weiss, Jay M.; Stowe, Zachary N.; Owens, Michael J.

2014-01-01

Rationale A rigorously investigated model of stress and antidepressant administration during pregnancy is needed to evaluate possible effects on the mother. Objective The objective of this study was to develop a model of clinically relevant prenatal exposure to an antidepressant and stress during pregnancy to evaluate the effects on maternal care behavior. Results Female rats implanted with 28 day osmotic minipumps delivering the SSRI escitalopram throughout pregnancy had serum escitalopram concentrations in a clinically observed range (17-65 ng/mL). A separate cohort of pregnant females exposed to a chronic unpredictable mild stress paradigm on gestational days 10-20 showed elevated baseline (305 ng/mL), and acute stress-induced (463 ng/mL), plasma corticosterone concentrations compared to unstressed controls (109 ng/mL). A final cohort of pregnant dams were exposed to saline (control), escitalopram, stress, or stress and escitalopram to determine the effects on maternal care. Maternal behavior was continuously monitored over the first 10 days post parturition. A reduction of 35% in maternal contact and 11% in nursing behavior was observed due to stress during the light cycle. Licking and grooming behavior was unaffected by stress or drug exposure in either the light or dark cycle. Conclusions These data indicate that: 1) clinically relevant antidepressant treatment during human pregnancy can be modeled in rats using escitalopram; 2) chronic mild stress can be delivered in a manner that does not compromise fetal viability; and 3) neither of these prenatal treatments substantially altered maternal care post parturition. PMID:23436130

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

ERIC Educational Resources Information Center

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…

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

PubMed

Sai, Jin-Kan; Suyama, Masafumi; Kubokawa, Yoshihiro; Watanabe, Sumio

2008-02-28

To investigate the usefulness of secretin injection-MRCP for the diagnosis of mild chronic pancreatitis. 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. 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 agreement (kappa statistics) concerning the diagnosis of an abnormal branch pancreatic duct and of mild chronic pancreatitis was good to excellent. Secretin injection-MRCP might be useful for the diagnosis of mild chronic pancreatitis.

Tianeptine, olanzapine and fluoxetine show similar restoring effects on stress induced molecular changes in mice brain: An FT-IR study

NASA Astrophysics Data System (ADS)

Türker-Kaya, Sevgi; Mutlu, Oğuz; Çelikyurt, İpek K.; Akar, Furuzan; Ulak, Güner

2016-05-01

Chronic stress which can cause a variety of disorders and illness ranging from metabolic and cardiovascular to mental leads to alterations in content, structure and dynamics of biomolecules in brain. The determination of stress-induced changes along with the effects of antidepressant treatment on these parameters might bring about more effective therapeutic strategies. In the present study, we investigated unpredictable chronic mild stress (UCMS)-induced changes in biomolecules in mouse brain and the restoring effects of tianeptine (TIA), olanzapine (OLZ) and fluoxetine (FLX) on these variations, by Fourier transform infrared (FT-IR) spectroscopy. The results revealed that chronic stress causes different membrane packing and an increase in lipid peroxidation, membrane fluidity. A significant increment for lipid/protein, Cdbnd O/lipid, CH3/lipid, CH2/lipid, PO-2/lipid, COO-/lipid and RNA/protein ratios but a significant decrease for lipid/protein ratios were also obtained. Additionally, altered protein secondary structure components were estimated, such as increment in random coils and beta structures. The administration of TIA, OLZ and FLX drugs restored these stress-induced variations except for alterations in protein structure and RNA/protein ratio. This may suggest that these drugs have similar restoring effects on the consequences of stress activity in brain, in spite of the differences in their action mechanisms. All findings might have importance in understanding molecular mechanisms underlying chronic stress and contribute to studies aimed for drug development.

Chronic unpredictable stress regulates visceral adipocyte‐mediated glucose metabolism and inflammatory circuits in male rats

PubMed Central

Karagiannides, Iordanes; Golovatscka, Viktoriya; Bakirtzi, Kyriaki; Sideri, Aristea; Salas, Martha; Stavrakis, Dimitris; Polytarchou, Christos; Iliopoulos, Dimitrios; Pothoulakis, Charalabos; Bradesi, Sylvie

2014-01-01

Abstract Chronic psychological stress is a prominent risk factor involved in the pathogenesis of many complex diseases, including major depression, obesity, and type II diabetes. Visceral adipose tissue is a key endocrine organ involved in the regulation of insulin action and an important component in the development of insulin resistance. Here, we examined for the first time the changes on visceral adipose tissue physiology and on adipocyte‐associated insulin sensitivity and function after chronic unpredictable stress in rats. Male rats were subjected to chronic unpredictable stress for 35 days. Total body and visceral fat was measured. Cytokines and activated intracellular kinase levels were determined using high‐throughput multiplex assays. Adipocyte function was assessed via tritiated glucose uptake assay. Stressed rats showed no weight gain, and their fat/lean mass ratio increased dramatically compared to control animals. Stressed rats had significantly higher mesenteric fat content and epididymal fat pad weight and demonstrated reduced serum glucose clearing capacity following glucose challenge. Alterations in fat depot size were mainly due to changes in adipocyte numbers and not size. High‐throughput molecular screening in adipocytes isolated from stressed rats revealed activation of intracellular inflammatory, glucose metabolism, and MAPK networks compared to controls, as well as significantly reduced glucose uptake capacity in response to insulin stimulation. Our study identifies the adipocyte as a key regulator of the effects of chronic stress on insulin resistance, and glucose metabolism, with important ramifications in the pathophysiology of several stress‐related disease states. PMID:24819750

5,7-Dimethoxycoumarin prevents chronic mild stress induced depression in rats through increase in the expression of heat shock protein-70 and inhibition of monoamine oxidase-A levels.

PubMed

Yang, Wei; Wang, Huanlin

2018-02-01

The current study was aimed to investigate the role of 5,7-dimethoxycoumarin in the prevention of chronic mild stress induced depression in rats. The chronic mild stress rat model was prepared using the known protocols. The results from open-field test showed that rats in the chronic mild stress group scored very low in terms of crossings and rearings than those of the normal rats. However, pre-treatment of the rats with 10 mg/kg doses of 5,7-dimethoxycoumarin prevented decline in the locomotor activity by chronic mild stress. The level of monoamine oxidase-A in the chronic mild stress rat hippocampus was markedly higher. Chronic mild stress induced increase in the monoamine oxidase-A level was inhibited by pre-treatment with 10 mg/kg doses of 5,7-dimethoxycoumarin in the rats. Chronic mild stress caused a marked increase in the level of caspase-3 mRNA and proteins in rat hippocampus tissues. The increased level of caspase-3 mRNA and protein level was inhibited by treatment of rats with 5,7-dimethoxycoumarin (10 mg/kg). 5,7-Dimethoxycoumarin administration into the rats caused a marked increase in the levels of heat shock protein-70 mRNA and protein. The levels of heat shock protein-70 were markedly lower both in normal and chronic mild stress groups of rats compared to the 5,7-dimethoxycoumarin treated groups. Thus 5,7-dimethoxycoumarin prevented the chronic mild stress induced depression in rats through an increase in the expression of heat shock protein-70 and inhibition of monoamine oxidase-A levels.

Relationships among attention networks and physiological responding to threat.

PubMed

Sarapas, Casey; Weinberg, Anna; Langenecker, Scott A; Shankman, Stewart A

2017-02-01

Although researchers have long hypothesized a relationship between attention and anxiety, theoretical and empirical accounts of this relationship have conflicted. We attempted to resolve these conflicts by examining relationships of attentional abilities with responding to predictable and unpredictable threat - related but distinct motivational process implicated in a number of anxiety disorders. Eighty-one individuals completed a behavioral task assessing efficiency of three components of attention - alerting, orienting, and executive control (Attention Network Test - Revised). We also assessed startle responding during anticipation of both predictable, imminent threat (of mild electric shock) and unpredictable contextual threat. Faster alerting and slower disengaging from non-emotional attention cues were related to heightened responding to unpredictable threat, whereas poorer executive control of attention was related to heightened responding to predictable threat. This double dissociation helps to integrate models of attention and anxiety and may be informative for treatment development. Copyright © 2016 Elsevier Inc. All rights reserved.

Relationships Among Attention Networks and Physiological Responding to Threat

PubMed Central

Sarapas, Casey; Weinberg, Anna; Langenecker, Scott A.

2016-01-01

Although researchers have long hypothesized a relationship between attention and anxiety, theoretical and empirical accounts of this relationship have conflicted. We attempted to resolve these conflicts by examining relationships of attentional abilities with responding to predictable and unpredictable threat, related but distinct motivational process implicated in a number of anxiety disorders. Eighty-one individuals completed a behavioral task assessing efficiency of three components of attention – alerting, orienting, and executive control (Attention Network Test - Revised). We also assessed startle responding during anticipation of both predictable, imminent threat (of mild electric shock) and unpredictable contextual threat. Faster alerting and slower disengaging from non-emotional attention cues were related to heightened responding to unpredictable threat, whereas poorer executive control of attention was related to heightened responding to predictable threat. This double dissociation helps to integrate models of attention and anxiety and may be informative for treatment development. PMID:27816781

ProBDNF Signaling Regulates Depression-Like Behaviors in Rodents under Chronic Stress.

PubMed

Bai, Yin-Yin; Ruan, Chun-Sheng; Yang, Chun-Rui; Li, Jia-Yi; Kang, Zhi-Long; Zhou, Li; Liu, Dennis; Zeng, Yue-Qing; Wang, Ting-Hua; Tian, Chang-Fu; Liao, Hong; Bobrovskaya, Larisa; Zhou, Xin-Fu

2016-11-01

Chronic exposure to stressful environment is a key risk factor contributing to the development of depression. However, the mechanisms involved in this process are still unclear. Brain-derived neurotropic factor (BDNF) has long been investigated for its positive role in regulation of mood, although the role of its precursor, proBDNF, in regulation of mood is not known. In this study, using an unpredictable chronic mild stress (UCMS) paradigm we found that the protein levels of proBDNF were increased in the neocortex and hippocampus of stressed mice and this UCMS-induced upregulation of proBDNF was abolished by chronic administration of fluoxetine. We then established a rat model of UCMS and found that the expression of proBDNF/p75 NTR /sortilin was upregulated, whereas the expression of mature BDNF and TrkB was downregulated in both neocortex and hippocampus of chronically stressed rats. Finally, we found that the injection of anti-proBDNF antibody via intracerebroventricular (i.c.v.) and intraperitoneal (i.p.) approaches into the UCMS rats significantly reversed the stress-induced depression-like behavior and restored the exploratory activity and spine growth. Although intramuscular injection of AAV-proBDNF did not exacerbate the UCMS-elicited rat mood-related behavioral or pathological abnormalities, i.c.v. injection of AAV-proBDNF increased the depression-like behavior in naive rats. Our findings suggest that proBDNF plays a role in the development of chronic stress-induced mood disturbances in rodents. Central (i.c.v.) or peripheral (i.p.) inhibition of proBDNF by injecting specific anti-proBDNF antibodies may provide a novel therapeutic approach for the treatment of stress-related mood disorders.

Effects of berberine on a rat model of chronic stress and depression via gastrointestinal tract pathology and gastrointestinal flora profile assays.

PubMed

Zhu, Xiaohui; Sun, Yangdong; Zhang, Chenggang; Liu, Haifeng

2017-05-01

Chronic stress and depression are challenging conditions to treat, owing to their complexity and lack of clinically available and effective therapeutic agents. The aim of the present study was to investigate the mechanism by which berberine acts, by examining alterations to gastrointestinal tract histopathology and flora profile in a rat model, following the induction of stress. Research associating gastrointestinal flora and depression has increased, thus, the present study hypothesized that stress induces depression and changes in the gastrointestinal system. The chronic mild stress rat model was previously established based on a set of 10 chronic unpredictable stress methods. In the present study, the measurements of body weight, behavior, gastrointestinal tract histopathology and gastrointestinal flora profile were collected in order to elucidate understanding of chronic stress and depression in this region. In the present study, induced stress and the resulting depression was demonstrated to significantly decrease the body weight and sucrose preference of rats, as well as significantly increasing traverse time, vertical movement time, grooming time and motionless time in an open‑field test. Following modeling and subsequent treatment with low or high doses of berberine, the measurements were significantly different when compared with unstressed rats. Berberine appears to reverse the physical damage brought about by stress within the gastric mucosa and intestinal microvilli of the stomach, ileum, cecum and colon. Using enterobacterial repetitive intergenic consensus sequence‑based polymerase chain reaction analysis, several distinctive bands disappeared following modeling; however, novel distinctive bands appeared in response to the graded berberine treatment. In conclusion, the present study identified that high concentrations of berberine markedly protects rats from various symptoms of chronic stress and depression, with the potential of facilitating treatment within clinical practice.

An efficient chronic unpredictable stress protocol to induce stress-related responses in C57BL/6 mice.

PubMed

Monteiro, Susana; Roque, Susana; de Sá-Calçada, Daniela; Sousa, Nuno; Correia-Neves, Margarida; Cerqueira, João José

2015-01-01

Exposure to chronic stress can have broad effects on health ranging from increased predisposition for neuropsychiatric disorders to deregulation of immune responses. The chronic unpredictable stress (CUS) protocol has been widely used to study the impact of stress exposure in several animal models and consists in the random, intermittent, and unpredictable exposure to a variety of stressors during several weeks. CUS has consistently been shown to induce behavioral and immunological alterations typical of the chronic stress-response. Unfortunately C57BL/6 mice, one of the most widely used mouse strains, due to the great variety of genetically modified lines, seem to be resistant to the commonly used 4-week-long CUS protocol. The definition of an alternative CUS protocol allowing the use of C57BL/6 mice in chronic stress experiments is a need. Here, we show that by extending the CUS protocol to 8 weeks is possible to induce a chronic stress-response in C57BL/6 mice, as revealed by abrogated body weight gain, increased adrenals weight, and an overactive hypothalamic-pituitary-adrenal axis with increased levels of serum corticosterone. Moreover, we also observed stress-associated behavioral alterations, including the potentiation of anxious-like and depressive-like behaviors and a reduction of exploratory behavior, as well as subtle stress-related changes in the cell population of the thymus and of the spleen. The present protocol for C57BL/6 mice consistently triggers the spectrum of CUS-induced changes observed in rats and, thus, will be highly useful to researchers that need to use this particular mouse strain as an animal model of neuropsychiatric disorders and/or immune deregulation related to CUS.

Hippocampal FXR plays a role in the pathogenesis of depression: A preliminary study based on lentiviral gene modulation.

PubMed

Chen, Wei-Guan; Zheng, Jia-Xuan; Xu, Xi; Hu, Yu-Ming; Ma, Yu-Min

2018-06-01

As a well-known bile acid receptor, the role of Farnesoid X receptor (FXR) in the digestive system and cardiovascular system has been widely explored. However, there are very few studies involving FXR in the central nervous system. In this study, we explored the role of FXR in the pathogenesis of depression, a serious and worldwide neuropsychiatric disease. It was found that chronic unpredictable mild stress (CUMS) fully enhanced the protein and mRNA expressions of FXR in hippocampus, but not medial prefrontal cortex (mPFC). Overexpression of hippocampal FXR induced notable depressive-like behaviors and decreased expression of brain-derived neurotrophic factor (BDNF) in naïve rats, while knockdown of hippocampal FXR fully prevented the effects of CUMS on rat behaviors and hippocampal BDNF expression. Taken together, our research extends the knowledge of FXR's role in the central nervous system, and may provide a potential and novel therapeutic target for treating depression. Copyright © 2018 Elsevier B.V. All rights reserved.

The effect of chronic mild stress on tumor-bearing rats' behavior and its mechanism.

PubMed

Xiu, Li-Juan; Lin, Hui-Ming; Wei, Pin-Kang

2010-03-31

Much evidence has demonstrated that stress and tumor interact, but the mechanisms are poorly understood. The purpose of this study is to discuss the effect of unpredictable chronic mild stress (CMS) upon the behavior of Walker 256 tumor-bearing rats and its mechanism. Observe the effects of CMS on the sucrose consumption, activities, body weight and levels of serums TNF-alpha and IL-6 of both tumor-bearing rats and non-tumor-bearing rats, and on the levels of Bcl-2 and the phosphor-ERK1/2 in their hippocampus. CMS can reduce the average sucrose consumption, behavioral scores, body weight gain, expression of Bcl-2 and p-ERK1/2 protein in hippocampus, and increase serums TNF-alpha and IL-6 of both tumor-bearing rats and non-tumor-bearing rats. The stressed tumor-bearing rats had less sucrose consumption, body weight gain and lower behavioral scores, but higher level of serum TNF-alpha than stressed non-tumor-bearing rats. A negative correlation was found between the levels of serum TNF-alpha and sucrose consumption, while a positive correlation between the expression of Bcl-2 protein in hippocampus proper and sucrose consumption. CMS can reduce the protein levels of Bcl-2 and p-ERK1/2 in the rats' hippocampus, which contributes to the changes in the rats' behavior caused by CMS. Tumor-bearing rats are prone to behave depressively after the exposure to CMS. Our findings have suggested that the tumor, by increasing the inflammatory reaction, can be taken as a stressor, affecting the hippocampus and consequently causing depression by decreasing the expression of Bcl-2 and p-ERK1/2 in hippocampus. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

Chronic mild stress in submissive mice: Marked polydipsia and social avoidance without hedonic deficit in the sucrose preference test.

PubMed

Gross, Moshe; Pinhasov, Albert

2016-02-01

In the Chronic Mild Stress (CMS) protocol, rodents are exposed to unpredictable stressors to induce anxiety-like behavior and hedonic deficit in the Sucrose Preference test (SPT). Since CMS-induced anxiety- and anhedonic-like behavior may depend upon individual vulnerability to stress, we hypothesized that selectively bred Submissive (Sub) mice would exhibit heightened anxiety- and anhedonic-like behavior, in response to CMS exposure. We anticipated that the testing of Sub mice alongside their Wt counterparts in a battery of behavioral assays would identify parameters most sensitive to CMS effects. To test these assumptions, Sub mice and their outbred Sabra (Wt) counterparts underwent a five-week CMS-SPT regimen. CMS exposure led to reduced preference for sucrose (sucrose-sweetened water as percent of total intake) among both mouse strains (p<0.01 Wt; p<0.05 Sub). However, this effect was attributed to CMS-induced polydipsia, indicated by mice's increased water consumption, (p<0.01 Wt and Sub), without changes in sucrose intake. Furthermore, CMS-exposed Sub mice, but not Wt, demonstrated impaired social exploration in the Three Chamber test (p<0.05) and anxiety-like effects in the Elevated Plus Maze (p<0.05). Moreover, in a separate experiment, social isolation alone was sufficient to induce polydipsia in Sub mice, without affecting Wt mice's drinking behavior. The present findings suggest that the EPM and Three Chamber tests may be valuable complementary measures of CMS effects, alongside the Sucrose Preference test, and introduce the Sub mouse strain for use in study of susceptibility to stress. Copyright © 2015 Elsevier B.V. All rights reserved.

Prenatal stress increases the obesogenic effects of a high-fat-sucrose diet in adult rats in a sex-specific manner.

PubMed

Paternain, L; de la Garza, A L; Batlle, M A; Milagro, F I; Martínez, J A; Campión, J

2013-03-01

Stress during pregnancy can induce metabolic disorders in adult offspring. To analyze the possible differential response to a high-fat-sucrose (HFS) diet in offspring affected by prenatal stress (PNS) or not, pregnant Wistar rats (n = 11) were exposed to a chronic mild stress during the third week of gestation. The aim of this study was to model a chronic depressive-like state that develops over time in response to exposure of rats to a series of mild and unpredictable stressors. Control dams (n = 11) remained undisturbed. Adult offspring were fed chow or HFS diet (20% protein, 35% carbohydrate, 45% fat) for 10 weeks. Changes in adiposity, biochemical profile, and retroperitoneal adipose tissue gene expression by real-time polymerase chain reaction were analyzed. An interaction was observed between HFS and PNS concerning visceral adiposity, with higher fat mass in HFS-fed stressed rats, statistically significant only in females. HFS modified lipid profile and increased insulin resistance biomarkers, while PNS reduced insulin concentrations and the homeostasis model assessment index. HFS diet increased gene (mRNA) expression for leptin and apelin and decreased cyclin-dependent kinase inhibitor 1A and fatty acid synthase (Fasn), whereas PNS increased Fasn and stearoyl-CoA desaturase1. An interaction between diet and PNS was observed for adiponutrin (Adpn) and peroxisome proliferator-activated receptor-γ coactivator1-α (Ppargc1a) gene expression: Adpn was increased by the PNS only in HFS-fed rats, whereas Ppargc1a was increased by the PNS only in chow-fed rats. From these results, it can be concluded that experience of maternal stress during intrauterine development can enhance predisposition to obesity induced by a HFS diet intake.

Morphological and genetic perspectives of peach fruit responses to spring frost

USDA-ARS?s Scientific Manuscript database

Spring frost is one of the most unpredictable cropping factors in many peach production areas. A severe spring frost can wipe out an entire peach crop whereas a mild spring frost may naturally help thinning as is common practice in commercial peach production. The extent of frost damage depends on t...

BDNF-GSK-3β-β-Catenin Pathway in the mPFC Is Involved in Antidepressant-Like Effects of Morinda officinalis Oligosaccharides in Rats.

PubMed

Xu, Ling-Zhi; Xu, De-Feng; Han, Ying; Liu, Li-Jing; Sun, Cheng-Yu; Deng, Jia-Hui; Zhang, Ruo-Xi; Yuan, Ming; Zhang, Su-Zhen; Li, Zhi-Meng; Xu, Yi; Li, Jin-Sheng; Xie, Su-Hua; Li, Su-Xia; Zhang, Hong-Yan; Lu, Lin

2017-01-01

Morinda officinalis oligosaccharides have been reported to exert neuroprotective and antidepressant-like effects in the forced swim test in mice. However, the mechanisms that underlie the antidepressant-like effects of Morinda officinalis oligosaccharides are unclear. Chronic unpredictable stress and forced swim test were used to explore the antidepressant-like effects of Morinda officinalis oligosaccharides and resilience to stress in rats. The phosphoinositide-3 kinase inhibitor LY294002 was microinjected in the medial prefrontal cortex to explore the role of glycogen synthase kinase-3β in the antidepressant-like effects of Morinda officinalis oligosaccharides. The expression of brain-derived neurotrophic factor, phosphorylated-Ser9-glycogen synthase kinase 3β, β-catenin, and synaptic proteins was determined in the medial prefrontal cortex and the orbitofrontal cortex by western blot. We found that Morinda officinalis oligosaccharides effectively ameliorated chronic unpredictable stress-induced depression-like behaviors in the sucrose preference test and forced swim test. The Morinda officinalis oligosaccharides also significantly rescued chronic unpredictable stress-induced abnormalities in the brain-derived neurotrophic factor-glycogen synthase kinase-3β-β-catenin pathway and synaptic protein deficits in the medial prefrontal cortex but not orbitofrontal cortex. The activation of glycogen synthase kinase-3β by the phosphoinositide-3 kinase inhibitor LY294002 abolished the antidepressant-like effects of Morinda officinalis oligosaccharides in the forced swim test. Naïve rats that were treated with Morinda officinalis oligosaccharides exhibited resilience to chronic unpredictable stress, accompanied by increases in the expression of brain-derived neurotrophic factor, phosphorylated-Ser9-glycogen synthase kinase-3β, and β-catenin in the medial prefrontal cortex. Our findings indicate that the brain-derived neurotrophic factor-glycogen synthase kinase-3β-β-catenin pathway in the medial prefrontal cortex may underlie the antidepressant-like effect of Morinda officinalis oligosaccharides and resilience to stress. © The Author 2016. Published by Oxford University Press on behalf of CINP.

Gemfibrozil has antidepressant effects in mice: Involvement of the hippocampal brain-derived neurotrophic factor system.

PubMed

Ni, Yu-Fei; Wang, Hao; Gu, Qiu-Yan; Wang, Fei-Ying; Wang, Ying-Jie; Wang, Jin-Liang; Jiang, Bo

2018-04-01

Major depressive disorder has become one of the most serious neuropsychiatric disorders worldwide. However, currently available antidepressants used in clinical practice are ineffective for a substantial proportion of patients and always have side effects. Besides being a lipid-regulating agent, gemfibrozil is an agonist of peroxisome proliferator-activated receptor-α (PPAR-α). We investigated the antidepressant effects of gemfibrozil on C57BL/6J mice using the forced swim test (FST) and tail suspension test (TST), as well as the chronic unpredictable mild stress (CUMS) model of depression. The changes in brain-derived neurotrophic factor (BDNF) signaling cascade in the brain after CUMS and gemfibrozil treatment were further assessed. Pharmacological inhibitors and lentivirus-expressed short hairpin RNA (shRNA) were also used to clarify the antidepressant mechanisms of gemfibrozil. Gemfibrozil exhibited significant antidepressant actions in the FST and TST without affecting the locomotor activity of mice. Chronic gemfibrozil administration fully reversed CUMS-induced depressive-like behaviors in the FST, TST and sucrose preference test. Gemfibrozil treatment also restored CUMS-induced inhibition of the hippocampal BDNF signaling pathway. Blocking PPAR-α and BDNF but not the serotonergic system abolished the antidepressant effects of gemfibrozil on mice. Gemfibrozil produced antidepressant effects in mice by promoting the hippocampal BDNF system.

Sex differences in stress-induced visceral hypersensitivity following early life adversity: a two hit model.

PubMed

Prusator, D K; Greenwood-Van Meerveld, B

2016-12-01

Early life adversity (ELA) has been indicated as a risk factor for the development of stress axis dysfunction in adulthood, specifically in females. We previously showed that unpredictable ELA induces visceral hyperalgesia in adult female rats. It remains to be determined whether ELA alters visceral nociceptive responses to stress in adulthood. The current study tested the hypothesis that following ELA, exposure to an adulthood stressor, or second hit, serves as a risk factor for exaggerated stress-induced visceral hypersensitivity that is sex-specific. Following ELA, adult stress was induced via a single exposure (acute) or repetitive daily exposure, 1 h/day for 7 days (chronic), to water avoidance stress (WAS). Acute WAS increased pain behaviors in all adult female rats, however, females that experienced unpredictable ELA exhibited significantly more pain behaviors compared to those exposed to predictable ELA or controls. Following chronic WAS, all adult females exhibited increased pain responses, however, an exaggerated response was observed in rats exposed to unpredictable or predictable ELA compared to controls. Similarly, in adult male rats exposure to acute or chronic WAS increased pain behaviors, however, there were no differences in pain behaviors between ELA groups. This study highlights a novel consequence of ELA on stress-induced visceral nociception in adulthood that is sex-specific. More importantly, our study suggests that ELA not only serves as a risk factor for development of chronic pain in adulthood, but also serves as a predisposition for worsening of visceral pain following adult stress in female rats. © 2016 John Wiley & Sons Ltd.

A feasibility study of predictable and unpredictable surf-like sounds for tinnitus therapy using personal music players.

PubMed

Durai, Mithila; Kobayashi, Kei; Searchfield, Grant D

2018-05-28

To evaluate the feasibility of predictable or unpredictable amplitude-modulated sounds for tinnitus therapy. The study consisted of two parts. (1) An adaptation experiment. Loudness level matches and rating scales (10-point) for loudness and distress were obtained at a silent baseline and at the end of three counterbalanced 30-min exposures (silence, predictable and unpredictable). (2) A qualitative 2-week sound therapy feasibility trial. Participants took home a personal music player (PMP). Part 1: 23 individuals with chronic tinnitus and part 2: seven individuals randomly selected from Part 1. Self-reported tinnitus loudness and annoyance were significantly lower than baseline ratings after acute unpredictable sound exposure. Tinnitus annoyance ratings were also significantly lower than the baseline but the effect was small. The feasibility trial identified that participant preferences for sounds varied. Three participants did not obtain any benefit from either sound. Three participants preferred unpredictable compared to predictable sounds. Some participants had difficulty using the PMP, the average self-report hours of use were low (less <1 h/day). Unpredictable surf-like sounds played using a PMP is a feasible tinnitus treatment. Further work is required to improve the acceptance of the sound and ease of PMP use.

Effects of maternal stress during pregnancy on learning and memory via hippocampal BDNF, Arc (Arg3.1) expression in offspring.

PubMed

Guan, Su-Zhen; Ning, Li; Tao, Ning; Lian, Yu-Long; Liu, Ji-Wen; Ng, Tzi Bun

2016-09-01

The intrauterine environment has a significant long-term impact on individual's life, this study was designed to investigate the effect of stress during pregnancy on offspring's learning and memory abilities and analyze its mechanisms from the expression of BDNF and Arc in the hippocampus of the offspring. A rat model of maternal chronic stress during pregnancy was mating from 3rd day during been subjecting to chronic unpredictable mild stress (CUMS). The body weights and behavioral changes were recorded, and plasma corticosterone levels were determined by radioimmunoassay. The learning and memory abilities of the offspring were measured by Morris water maze testing from PND 42. The expression of hippocampal BDNF and Arc mRNA and protein were respectively measured using RT-PCR and Western blotting. Results indicated that an elevation was observed in the plasma corticosterone level of rat model of maternal chronic stress during pregnancy, a reduction in the crossing and rearing movement times and the preference for sucrose. The body weight of maternal stress's offspring was lower than the control group, and the plasma corticosterone level was increased. Chronic stress during pregnancy had a significant impact on the spatial learning and memory of the offspring. The expression of BDNF mRNA and protein, Arc protein in offspring of maternal stress during pregnancy was attenuated and some relationships existed between these parameters. Collectively, these findings disclose that long-time maternal stress during pregnancy could destroy spatial learning and memory abilities of the offspring, the mechanism of which is related to been improving maternal plasma corticosterone and reduced hippocampal BDNF, Arc of offspring rats. Copyright © 2016. Published by Elsevier B.V.

Cathepsin C Aggravates Neuroinflammation Involved in Disturbances of Behaviour and Neurochemistry in Acute and Chronic Stress-Induced Murine Model of Depression.

PubMed

Zhang, Yanli; Fan, Kai; Liu, Yanna; Liu, Gang; Yang, Xiaohan; Ma, Jianmei

2018-01-01

Major depression has been interpreted as an inflammatory disease characterized by cell-mediated immune activation, which is generally triggered by various stresses. Microglia has been thought to be the cellular link between inflammation and depression-like behavioural alterations. The expression of cathepsin C (Cat C), a lysosomal proteinase, is predominantly induced in microglia in neuroinflammation. However, little is known about the role of Cat C in pathophysiology of depression. In the present study, Cat C transgenic mice and wild type mice were subjected to an intraperitoneal injection of LPS (0.5 mg/kg) and 6-week unpredictable chronic mild stress (UCMS) exposure to establish acute and chronic stress-induced depression model. We examined and compared the behavioural and proinflammatory cytokine alterations in serum and depression-targeted brain areas of Cat C differentially expressed mice in stress, as well as indoleamine 2,3-dioxygenase (IDO) and 5-hydroxytryptamine (5HT) levels in brain. The results showed that Cat C overexpression (Cat C OE) promoted peripheral and central inflammatory response with significantly increased TNFα, IL-1β and IL-6 in serum, hippocampus and prefrontal cortex, and resultant upregulation of IDO and downregulation of 5HT expression in brain, and thereby aggravated depression-like behaviours accessed by open field test, forced swim test and tail suspension test. In contrast, Cat C knockdown (Cat C KD) partially prevented inflammation, which may help alleviate the symptoms of depression in mice. To the best of our knowledge, we are the first to demonstrate that Cat C aggravates neuroinflammation involved in disturbances of behaviour and neurochemistry in acute and chronic stress-induced murine model of depression.

Sex-Dependent Anti-Stress Effect of an α5 Subunit Containing GABAA Receptor Positive Allosteric Modulator

PubMed Central

Piantadosi, Sean C.; French, Beverly J.; Poe, Michael M.; Timić, Tamara; Marković, Bojan D.; Pabba, Mohan; Seney, Marianne L.; Oh, Hyunjung; Orser, Beverley A.; Savić, Miroslav M.; Cook, James M.; Sibille, Etienne

2016-01-01

Rationale: Current first-line treatments for stress-related disorders such as major depressive disorder (MDD) act on monoaminergic systems and take weeks to achieve a therapeutic effect with poor response and low remission rates. Recent research has implicated the GABAergic system in the pathophysiology of depression, including deficits in interneurons targeting the dendritic compartment of cortical pyramidal cells. Objectives: The present study evaluates whether SH-053-2’F-R-CH3 (denoted “α5-PAM”), a positive allosteric modulator selective for α5-subunit containing GABAA receptors found predominantly on cortical pyramidal cell dendrites, has anti-stress effects. Methods: Female and male C57BL6/J mice were exposed to unpredictable chronic mild stress (UCMS) and treated with α5-PAM acutely (30 min prior to assessing behavior) or chronically before being assessed behaviorally. Results: Acute and chronic α5-PAM treatments produce a pattern of decreased stress-induced behaviors (denoted as “behavioral emotionality”) across various tests in female, but not in male mice. Behavioral Z-scores calculated across a panel of tests designed to best model the range and heterogeneity of human symptomatology confirmed that acute and chronic α5-PAM treatments consistently produce significant decreases in behavioral emotionality in several independent cohorts of females. The behavioral responses to α5-PAM could not be completely accounted for by differences in drug brain disposition between female and male mice. In mice exposed to UCMS, expression of the Gabra5 gene was increased in the frontal cortex after acute treatment and in the hippocampus after chronic treatment with α5-PAM in females only, and these expression changes correlated with behavioral emotionality. Conclusion: We showed that acute and chronic positive modulation of α5 subunit-containing GABAA receptors elicit anti-stress effects in a sex-dependent manner, suggesting novel therapeutic modalities. PMID:27920723

Antidepressant-like Effects of LPM580153, A Novel Potent Triple Reuptake Inhibitor.

PubMed

Zhang, Fangxi; Shao, Jing; Tian, Jingwei; Zhong, Yan; Ye, Liang; Meng, Xiangjing; Liu, Qiaofeng; Wang, Hongbo

2016-04-07

The purpose of this study was to characterize a novel compound, 4-[2-(dimethylamino)-1-(1-hydroxycyclohexyl) ethyl] phenyl 3-nitrophenyl ether, designated LPM580153. We used several well-validated animal models of depression to assess the antidepressant-like activity of LPM580153, followed by a neurotransmitter uptake assay and a corticosterone-induced cell injury model to explore its mechanism of action. In mice, LPM580153 reduced immobility time in the tail suspension test, and in rats subjected to chronic unpredictable mild stress it reversed reductions in body weight gain and ameliorated anhedonia. The neurotransmitter uptake assay results demonstrated that LPM580153 inhibited the uptake of serotonin, norepinephrine and dopamine. Furthermore, LPM580153 protected the SH-SY5Y cells against the cytotoxic activity of corticosterone, an action that might be related to the role of LPM580153 in increasing the protein levels of BDNF, p-ERK1/2, p-AKT, p-CREB and p-mTOR. Together, these findings indicate that LPM580153 is a novel triple reuptake inhibitor with robust antidepressant-like effects.

The rapid antidepressant effect of ketamine in rats is associated with down-regulation of pro-inflammatory cytokines in the hippocampus

PubMed Central

Wang, Nan; Yu, Hai-Ying; Shen, Xiao-Feng; Gao, Zhi-Qin; Yang, Chun; Yang, Jian-Jun

2015-01-01

Objectives. Active inflammatory responses play an important role in the pathogenesis of depression. We hypothesized that the rapid antidepressant effect of ketamine is associated with the down-regulation of pro-inflammatory mediators. Methods. Forty-eight rats were equally randomized into six groups (a control and five chronic unpredictable mild stress (CUMS) groups) and given either saline or 10 mg/kg ketamine, respectively. The forced swimming test was performed, and the hippocampus was subsequently harvested for the determination of levels of interleukin (IL)-1β, IL-6, tumour necrosis factor-α (TNF-α), indoleamine 2,3-dioxygenase (IDO), kynurenine (KYN), and tryptophan (TRP). Results. CUMS induced depression-like behaviours and up-regulated the hippocampal levels of IL-1β, IL-6, TNF-α, IDO, and the KYN/TRP ratio, which were attenuated by a sub-anaesthetic dose of ketamine. Conclusion. CUMS-induced depression-like behaviours are associated with a reduction in hippocampal inflammatory mediators, whereas ketamine’s antidepressant effect is associated with a down-regulation of pro-inflammatory cytokines in the rat hippocampus. PMID:26220286

A representative prescription for emotional disease, Ding-Zhi-Xiao-Wan restores 5-HT system deficit through interfering the synthesis and transshipment in chronic mild stress-induced depressive rats.

PubMed

Dong, Xian-Zhe; Li, Zhao-Liang; Zheng, Xiao-Li; Mu, Li-Hua; Zhang, Gang-qiang; Liu, Ping

2013-12-12

Ding-Zhi-Xiao-Wan (DZ, also known as Kai-Xin-San) is a famous traditional Chinese medicine used for the treatment of emotional disease. Previously, we have found that in a variety of animal models of depression (such as tail suspension model, model of chronic fatigue and forced swimming model) DZ demonstrated significant antidepressant behavior and promoted the production of 5-hydroxytryptamine (5-HT). However, the mechanisms of 5-HT regulation are still unclear. Therefore, the current study is designed to further investigate the antidepressant effect of DZ by observing its influence on 5-HT synthesis, metabolism, transport and other key links, so as to clarify the molecular mechanism of its 5-HT regulation. Solitary rising combined with the chronic unpredictable mild stress (CMS) was used to establish the rat model of depression. The rats were given DZ for 3 weeks, the behavior change and the following items in hippocampus and prefrontal cortex were detected simultaneously: 5-HT, 5-hydroxyindoleacetic acid (5-HIAA), tryptophan hydroxylase (TPH), aromatic amino acid decarboxylase (AADC), monoamine oxidase (MAO) and 5-HT transporter (5-HTT) were observed. Our results showed that treatment with the DZ significantly improved the behavior and simultaneously increased the 5-HT level in the hippocampus, prefrontal cortex tissues and hippocampus extracellular of depressive rats. In future studies revealed that DZ could significantly increase the protein and mRNA expression of the key enzymes TPH during the 5-HT synthesis process in the hippocampus and prefrontal cortex of the depressed rats, and suppress the expression of 5-HTT protein and mRNA at the same time. But it had no effects on MAO-A and MAO-B activities. We believe that antidepressant effect of DZ is caused by the increase of 5-HT synthesis and reduction of 5-HT re-uptake, and eventually increase the content of 5-HT in the brain and the synaptic gaps. © 2013 Published by Elsevier Ireland Ltd.

Antidepressant-like effect of Butea superba in mice exposed to chronic mild stress and its possible mechanism of action.

PubMed

Mizuki, Daishu; Matsumoto, Kinzo; Tanaka, Ken; Thi Le, Xoan; Fujiwara, Hironori; Ishikawa, Tsutomu; Higuchi, Yoshihiro

2014-10-28

Butea superba (BS) is a Thai medicinal plant that has been used as a folk medicine to improve physical and mental conditions and to prevent impaired sexual performance in middle-aged or elderly males. We have previously reported that this plant extract could improve cognitive deficits and depression-like behavior in olfactory bulbectomized mice, an animal model of dementia and depression. In this study we examined the effect of BS on depression-like behavior in mice subjected to unpredictable chronic mild stress (UCMS) to clarify the antidepressant-like activity of BS and the molecular mechanism underlying this effect. UCMS mice were administered BS daily (300 mg of dried herb weight/kg, p.o.) or a reference drug, imipramine (IMP, 10 mg/kg, i.p.), 1 week after starting the UCMS procedure. We employed the sucrose preference test and the tail suspension test to analyze anhedonia and depression-like behavior of mice, respectively. Serum and brain tissues of mice were used for neurochemical and immunohistochemical studies. The UCMS procedure induced anhedonia and depression-like behavior, and BS treatment, as well as IMP treatment, attenuated these symptoms. UCMS caused an elevation of serum corticosterone level, an index of hyper-activation of the hypothalamic-pituitary-adrenal (HPA) axis, in a manner attenuated by BS and IMP treatment. BS treatment also attenuated UCMS-induced decrease in the expression levels of brain-derived neurotrophic factor (BDNF) mRNA, cyclic AMP-responsive element binding protein (CREB) and a phosphorylated form of N-methyl-d-aspartate receptor subunit NR1, synaptic plasticity-related signaling proteins. Moreover, the UCMS procedure reduced doublecortin-positive cells in the dentate gyrus region of the hippocampus. BS administration reversed these UCMS-induced neurochemical and histological abnormalities. These results suggest that BS can ameliorate chronic stress-induced depression-like symptoms and that the effects of BS are mediated by restoring dysfunctions of the HPA axis and synaptic plasticity-related signaling systems and neurogenesis in the hippocampus. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Berberine attenuates depressive-like behaviors by suppressing neuro-inflammation in stressed mice.

PubMed

Liu, Ya-Min; Niu, Le; Wang, Lin-Lin; Bai, Li; Fang, Xiao-Yan; Li, Yu-Cheng; Yi, Li-Tao

2017-09-01

Berberine, the major constituent alkaloid originally from the famous Chinese herb Huanglian (Coptis chinensis), has been shown to exert antidepressant-like effects in rodents. However, it is still not clear the involvement of neuro-inflammation suppression in the effects of berberine. The purpose of this study was to determine whether berberine affects the neuro-inflammation system in mice induced by chronic unpredictable mild stress (CUMS). Berberine was orally administrated in normal or CUMS mice for successive four weeks. Behavioral evaluation showed that berberine prevented the depressive deficits both in sucrose preference test and novelty-suppressed feeding test. The elevation of hippocampal pro-inflammatory cytokines such as interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), as well as the activation of microglia were decreased by berberine. In addition, chronic berberine treatment inhibited nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway as the phosphorylated proteins of NF-κB, IκB kinase (IKK)α and IKKβ in the hippocampus were suppressed after berberine administration. Furthermore, inducible nitric oxide synthase (iNOS), one downstream target of NF-κB signaling pathway was also inhibited by berberine. In conclusion, these findings suggest that administration of berberine could prevent depressive-like behaviors in CUMS mice by suppressing neuro-inflammation in the hippocampus. Copyright © 2017 Elsevier Inc. All rights reserved.

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

PubMed

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

2014-05-01

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

Sex differences in the stress response in SD rats.

PubMed

Lu, Jing; Wu, Xue-Yan; Zhu, Qiong-Bin; Li, Jia; Shi, Li-Gen; Wu, Juan-Li; Zhang, Qi-Jun; Huang, Man-Li; Bao, Ai-Min

2015-05-01

Sex differences play an important role in depression, the basis of which is an excessive stress response. We aimed at revealing the neurobiological sex differences in the same study in acute- and chronically-stressed rats. Female Sprague-Dawley (SD) rats were randomly divided into 6 groups: chronic unpredictable mild stress (CUMS), acute foot shock (FS) and controls, animals in all 3 groups were sacrificed in proestrus or diestrus. Male SD rats were randomly divided into 3 groups: CUMS, FS and controls. Comparisons were made of behavioral changes in CUMS and control rats, plasma levels of corticosterone (CORT), testosterone (T) and estradiol (E2), and of the hypothalamic mRNA-expression of stress-related molecules, i.e. estrogen receptor α and β, androgen receptor, aromatase, mineralocorticoid receptor, glucocorticoid receptor, corticotropin-releasing hormone, arginine vasopressin and oxytocin. CUMS resulted in disordered estrus cycles, more behavioral and hypothalamic stress-related molecules changes and a stronger CORT response in female rats compared with male rats. Female rats also showed decreased E2 and T levels after FS and CUMS, while male FS rats showed increased E2 and male CUMS rats showed decreased T levels. Stress affects the behavioral, endocrine and the molecular response of the stress systems in the hypothalamus of SD rats in a clear sexual dimorphic way, which has parallels in human data on stress and depression. Copyright © 2015 Elsevier B.V. All rights reserved.

Quercetin prevents chronic unpredictable stress induced behavioral dysfunction in mice by alleviating hippocampal oxidative and inflammatory stress.

PubMed

Mehta, Vineet; Parashar, Arun; Udayabanu, Malairaman

2017-03-15

It is now evident that chronic stress is associated with anxiety, depression and cognitive dysfunction and very few studies have focused on identifying possible methods to prevent these stress-induced disorders. Previously, we identified abundance of quercetin in Urtica dioica extract, which efficiently attenuated stress related complications. Therefore, current study was designed to investigate the effect of quercetin on chronic unpredicted stress (CUS) induced behavioral dysfunction, oxidative stress and neuroinflammation in the mouse hippocampus. Animals were subjected to unpredicted stress for 21days, during which 30mg/kg quercetin was orally administered to them. Effect of CUS and quercetin treatment on animal behavior was assessed between day 22-26. Afterward, the hippocampus was processed to evaluate neuronal damage, oxidative and inflammatory stress. Results revealed that stressed animals were highly anxious (Elevated Plus Maze and Open Field), showed depressive-like behavior (sucrose preference task), performed poorly in short-term and long-term associative memory task (passive avoidance step-through task) and displayed reduced locomotion (open field). Quercetin alleviated behavioral dysfunction in chronically stressed animals. Compared to CUS, quercetin treatment significantly reduced anxiety, attenuated depression, improved cognitive dysfunction and normalized locomotor activity. Further, CUS elevated the levels of oxidative stress markers (TBARS, nitric oxide), lowered antioxidants (total thiol, catalase), enhanced expression of pro-inflammatory cytokines (IL-6, TNF-α, IL-1β and COX-2) in the hippocampus and damaged hippocampal neurons. Quercetin treatment significantly lowered oxidative and inflammatory stress and prevented neural damage. In conclusion, quercetin can efficiently prevent stress induced neurological complications by rescuing brain from oxidative and inflammatory stress. Copyright © 2017 Elsevier Inc. All rights reserved.

Chronic Unpredictable Stress (CUS)-Induced Anxiety and Related Mood Disorders in a Zebrafish Model: Altered Brain Proteome Profile Implicates Mitochondrial Dysfunction

PubMed Central

Chakravarty, Sumana; Reddy, Bommana R.; Sudhakar, Sreesha R.; Saxena, Sandeep; Das, Tapatee; Meghah, Vuppalapaty; Brahmendra Swamy, Cherukuvada V.; Kumar, Arvind; Idris, Mohammed M.

2013-01-01

Anxiety and depression are major chronic mood disorders, and the etiopathology for each appears to be repeated exposure to diverse unpredictable stress factors. Most of the studies on anxiety and related mood disorders are performed in rodents, and a good model is chronic unpredictable stress (CUS). In this study, we have attempted to understand the molecular basis of the neuroglial and behavioral changes underlying CUS-induced mood disorders in the simplest vertebrate model, the zebrafish, Danio rerio. Zebrafish were subjected to a CUS paradigm in which two different stressors were used daily for 15 days, and thorough behavioral analyses were performed to assess anxiety and related mood disorder phenotypes using the novel tank test, shoal cohesion and scototaxis. Fifteen days of exposure to chronic stressors appears to induce an anxiety and related mood disorder phenotype. Decreased neurogenesis, another hallmark of anxiety and related disorders in rodents, was also observed in this zebrafish model. The common molecular markers of rodent anxiety and related disorders, corticotropin-releasing factor (CRF), calcineurin (ppp3r1a) and phospho cyclic AMP response element binding protein (pCREB), were also replicated in the fish model. Finally, using 2DE FTMS/ITMSMS proteomics analyses, 18 proteins were found to be deregulated in zebrafish anxiety and related disorders. The most affected process was mitochondrial function, 4 of the 18 differentially regulated proteins were mitochondrial proteins: PHB2, SLC25A5, VDAC3 and IDH2, as reported in rodent and clinical samples. Thus, the zebrafish CUS model and proteomics can facilitate not only uncovering new molecular targets of anxiety and related mood disorders but also the routine screening of compounds for drug development. PMID:23691016

Chronic Vortioxetine Treatment Reduces Exaggerated Expression of Conditioned Fear Memory and Restores Active Coping Behavior in Chronically Stressed Rats.

PubMed

Hatherall, Lauren; Sánchez, Connie; Morilak, David A

2017-04-01

Stress is a risk factor for depression and anxiety disorders, disrupting neuronal processes leading to exaggerated fear and compromised coping behaviors. Current antidepressants are only partially effective. Vortioxetine, a novel multimodal antidepressant, is a serotonin transporter inhibitor; 5-HT3, 5-HT7, and 5-HT1D receptor antagonist; 5-HT1B partial agonist; and 5-HT1A agonist. We have shown that chronic dietary vortioxetine administration reversed stress-induced deficits in cognitive flexibility. In the present studies, we investigated the generality of vortioxetine's effects on other stress-related behavioral changes after different types of chronic stress. In experiment 1, rats were fear-conditioned by pairing a tone with footshock, then exposed to chronic plus acute prolonged stress. In experiment 2, rats were exposed to chronic unpredictable stress. In both experiments, beginning on day 4 of chronic stress, vortioxetine was given in the diet (24 mg/kg/d). In experiment 1, effects of vortioxetine were tested on stress-induced changes in retention and extinction of cue-conditioned fear, and in experiment 2, on coping behavior on the shock probe defensive burying test after chronic stress. Chronic stress exaggerated the expression of conditioned fear memory. Vortioxetine restored fear memory to control levels and rendered extinction in stressed rats comparable with that in controls. In experiment 2, chronic unpredictable stress caused a shift from active to passive coping behavior, and vortioxetine restored active coping. Vortioxetine reduced exaggerated expression of conditioned fear and restored adaptive coping behavior following 2 different types of chronic stress, adding to the evidence of its therapeutic potential in the management of depression and anxiety disorders. © The Author 2016. Published by Oxford University Press on behalf of CINP.

Complex interactions between the subject factors of biological sex and prior histories of binge-drinking and unpredictable stress influence behavioral sensitivity to alcohol and alcohol intake.

PubMed

Quadir, Sema G; Guzelian, Eugenie; Palmer, Mason A; Martin, Douglas L; Kim, Jennifer; Szumlinski, Karen K

2017-08-10

Alcohol use disorders, affective disorders and their comorbidity are sexually dimorphic in humans. However, it is difficult to disentangle the interactions between subject factors influencing alcohol sensitivity in studies of humans. Herein, we combined murine models of unpredictable, chronic, mild stress (UCMS) and voluntary binge-drinking to examine for sex differences in the interactions between prior histories of excessive ethanol-drinking and stress upon ethanol-induced changes in motor behavior and subsequent drinking. In Experiment 1, female mice were insensitive to the UCMS-induced increase in ethanol-induced locomotion and ethanol intake under continuous alcohol-access. Experiment 2 revealed interactions between ethanol dose and sex (females>males), binge-drinking history (water>ethanol), and UCMS history (UCMS>controls), with no additive effect of a sequential prior history of both binge drinking and UCMS observed. We also observed an interaction between UCMS history and sex for righting recovery. UCMS history potentiated subsequent binge-drinking in water controls of both sexes and in male binge-drinking mice. Conversely, a prior binge-drinking history increased subsequent ethanol intake in females only, irrespective of prior UCMS history. In Experiment 3, a concurrent history of binge-drinking and UCMS did not alter ethanol intake, nor did it influence the ethanol dose-locomotor response function, but it did augment alcohol-induced sedation and reduced subsequent alcohol intake over that produced by binge-drinking alone. Thus, the subject factors of biological sex, prior stressor history and prior binge-drinking history interact in complex ways in mice to impact sensitivity to alcohol's motor-stimulating, -incoordinating and intoxicating effects, as well as to influence subsequent heavy drinking. Copyright © 2017 Elsevier Inc. All rights reserved.

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

PubMed

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.

Impacts of cannabinoid receptor ligands on nicotine- and chronic mild stress-induced cognitive and depression-like effects in mice.

PubMed

Pekala, Karolina; Michalak, Agnieszka; Kruk-Slomka, Marta; Budzynska, Barbara; Biala, Grazyna

2018-07-16

Taking into account the rather frequent concomitance of nicotine abuse and stress, we aimed to research memory- and depression-related effects of nicotine administration in combination with chronic mild unpredictable stress (CMUS) in mice and an involvement of the endocannabinoid system through CB1 and CB2 receptors. Mice were submitted to the CMUS for 4 weeks. Effects on depression-like behaviors and cognition, exerted by a combined administration of CB1, i.e., Oleamide (2.5, 5.0 mg/kg), AM 251 (0.1, 0.25 mg/kg) and CB2, i.e., JWH 133 (0.5, 2.0 mg/kg), AM 630 (0.25, 2.0 mg/kg) receptor ligands and nicotine (0.05, 0.1, 0.2 and 0.5 mg/kg), were then studied in stressed and unstressed mice by the forced swimming test and the passive avoidance paradigm, respectively. The results revealed that the CMUS-exposed mice exhibited depression-like behaviors and memory disturbances, while both effects were alleviated by nicotine. CB1 receptor ligands decreased antidepressive and cognitive (the latter for CB1 receptor antagonist only) effects of subchronic nicotine administration in stressed mice. CB1 and CB2 receptor antagonists exerted themselves some procognitive effects in those mice. Regarding the unstressed mice, CB1 and CB2 receptor ligands reversed the antidepressive effects of subchronic nicotine administration, while nicotine, in an ineffective dose, co-administered with CB2 receptor ligands, improved cognition. We confirmed the role of the two main subtypes of cannabinoid receptors, termed CB1 and CB2, on stress- and nicotine-related behavioral changes in mice. Our study has contributed to the understanding of the mechanisms involved in stress- and nicotine-induced disorders, such as anhedonia and memory disturbances. Copyright © 2018 Elsevier B.V. All rights reserved.

Chronic sorrow in caregivers of school age children with sickle cell disease: a grounded theory approach.

PubMed

Northington, L

2000-01-01

Chronic illness affects over 1 million children in the United States annually. One such illness prominent in the African-American population is sickle cell disease (SCD), which affects approximately 1 in 375 African Americans in the United States. This potentially life-threatening disease requires caregivers to carefully monitor and supervise children with SCD. Monitoring and caring for children with SCD places heavy burdens, demands, and responsibilities on these caregivers. The psychological stressors and unpredictable nature of the disease could cause caregivers to experience a variety of emotions, with one being chronic sorrow. The purposes of this study were to examine the process of chronic sorrow in caregivers of school age children with SCD, identify the characteristics of chronic sorrow, and generate a substantive theory of chronic sorrow. The methodology used was grounded theory, and data were generated through two interview sessions, a demographic questionnaire, field notes, and memos. Data analyses were performed following the principles of grounded theory. Data suggested these caregivers move through three overlapping stages: learning about and incorporating SCD into their daily lives; experiencing the sorrow; and doing what one has to do and moving on. The diagnosis was the initial trigger to evoke feelings, including sorrow. As time progressed, other internal and external triggers began to evoke feelings of sorrow that eventually became chronic. A process of repatterning began as caregivers learned to live with the unpredictable consequences of SCD, which produced the feelings of chronic sorrow. Repatterning behaviors enabled caregivers to "do what you have to do and move on."

The Spectrum of Disease in Chronic Traumatic Encephalopathy

ERIC Educational Resources Information Center

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…

Disease Knowledge, Illness Perceptions, and Quality of Life in Adolescents With Sickle Cell Disease: Is There a Link?

PubMed Central

Asnani, Monika Rani; Barton-Gooden, Antoinette; Grindley, Marlyn; Knight-Madden, Jennifer

2017-01-01

Disease knowledge, illness perceptions, and quality of life (QOL) were examined in 150 adolescents (mean age = 16.1 years, SD = 1.9; 49.3% males) with sickle cell disease (SCD). Females had higher knowledge (P = .004), lower QOL (P = .02), and perceived their illness to be more unpredictable (P = .03). Those with more severe disease perceived their illness to be unpredictable with worse outcomes. Those with higher knowledge scores perceived their illness to be chronic, made more sense of their illness, and perceived greater personal and treatment control. Final hierarchical regression model showed that secondary education as compared to primary education level (P < .001) was positively correlated whereas disease severity (P < .001), perceived unpredictability (P = .024), and negative emotions (P < .001) were negatively correlated with QOL. Health practitioners should assess adolescents’ illness perceptions and encouraging continuing schooling and addressing emotional/psychological problems could improve their QOL. PMID:29152543

Hyperbaric Oxygen Therapy in the Treatment of Chronic Mild-Moderate Blast-Induced Traumatic Brain Injury Post-Concussion Syndrome (PCS) and Post Traumatic Stress Disorder (PTSD)

DTIC Science & Technology

2016-10-01

Award Number: W81XWH-10-1-0962 TITLE: Hyperbaric Oxygen Therapy in the Treatment of Chronic Mild-Moderate Blast-Induced Traumatic Brain Injury...164. TITLE AND SUBTITLE 5a. CONTRACT NUMBER W81XWH-10-1-0962 Hyperbaric Oxygen Therapy in the Treatment of Chronic Mild-Moderate Blast-Induced...month follow-up period post-hyperbaric oxygen treatment. 1 additional subject is scheduled to be screened in October 2016 and 3 are awaiting first

Chronic psychological stress induces vascular inflammation in rabbits.

PubMed

Lu, Xiao Ting; Liu, Yun Fang; Zhao, Li; Li, Wen Jing; Yang, Rui Xue; Yan, Fang Fang; Zhao, Yu Xia; Jiang, Fan

2013-01-01

Psychological stress is associated with a systemic inflammatory response. It is unclear, however, whether psychological stress contributes to vascular inflammation. Here, we examined the effects of unpredictable chronic mild stress (UCMS) on vascular inflammation in rabbits. One hundred rabbits were randomly divided into control and stress groups. UCMS was induced by a set of defined adverse conditions applied in a shuffled order for 4, 8, 12, or 16 weeks, and rabbits were killed 24 h after the end of the UCMS protocol. Expression of different inflammatory molecules was analyzed by real-time polymerase chain reaction, immunohistochemistry, or enzyme-linked immunosorbent assay. UCMS resulted in depression-like behaviors, decreased body weight gain, and hypertension with no significant effects on serum lipids. Aortic mRNA and protein expression for tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), monocyte chemoattractant protein-1 (MCP-1), macrophage migration inhibitory factor, and expression of intercellular adhesion molecule-1 (ICAM-1) protein were increased. UCMS increased circulating concentrations of corticosterone, TNF-α, and CRP throughout. Moreover, stress downregulated the expression of endothelial nitric oxide synthase. At 16 weeks of UCMS, macrophage infiltration and lipid accumulation in the subendothelial space were detected in the aorta. In cultured murine vascular smooth muscle cells, treatment with serum from stressed rabbits significantly increased phosphorylation of p38 and c-Jun N-terminal kinase (JNK), and upregulated expression of MCP-1 and ICAM-1 mRNAs, in which the effect was blunted by a TNF-α neutralizing antibody or p38 and JNK inhibitors. Our results indicate that chronic psychological stress induces vascular inflammation via TNF-α and p38/JNK pathways, which may contribute to the development of atherosclerosis.

microRNA and mRNA profiles in ventral tegmental area relevant to stress-induced depression and resilience.

PubMed

Sun, Xiaoyan; Song, Zhenhua; Si, Yawei; Wang, Jin-Hui

2018-06-01

Chronic stress with lack of reward presumably may impair brain reward circuit, leading to major depressive disorder (MDD). Most individuals experiencing chronic stress do not suffer from MDD, i.e., resilience, implying the presence of endogenous anti-depression in the brain. Molecular mechanisms underlying stress-induced depression versus resilience were investigated. Mice were treated by chronic unpredictable mild stress (CUMS) for four weeks. Their mood state was assessed by behavioral tasks, such as sucrose preference, Y-maze and forced swimming testes. To reveal comprehensive molecular profiles of major depression versus resilience, mRNA and microRNA profiles were analyzed by high-throughput sequencing in the ventral tegmental area (VTA) harvested from control, CUMS-susceptible and CUMS-resilience mice. In data analyses of control versus CUMS-susceptible mice as well as control versus CUMS-resilience mice, 1.5 fold ratio in reads per kilo-base per million reads was set as the threshold to judge the involvement of mRNAs and microRNAs in the CUMS, depression or resilience. The downregulation of synaptic vesicle cycle, neurotrophin, GABAergic synapse and morphine addiction as well as the upregulation of transmitter release, calcium signal and cAMP-dependent response element binding are associated to CUMS-susceptibility. The downregulation of tyrosine metabolism and protein process in endoplasmic reticulum as well as the upregulation of amino acid biosynthesis, neuroactive ligand-receptor interaction and dopaminergic synapse are associated to CUMS-resilience. Therefore, the impairment of neurons and GABA/dopaminergic synapses in the VTA is associated with major depression. The upregulation of these entities is associated with resilience. Consistent results obtained from analyzing mRNAs and microRNAs as well as using different approaches strengthen our finding and conclusion. Copyright © 2018. Published by Elsevier Inc.

Dysregulation of the hypothalamus-pituitary-adrenal axis predicts some aspects of the behavioral response to chronic fluoxetine: association with hippocampal cell proliferation

PubMed Central

Khemissi, Wahid; Farooq, Rai Khalid; Le Guisquet, Anne-Marie; Sakly, Mohsen; Belzung, Catherine

2014-01-01

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 5th week 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 labeling. 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. PMID:25324748

Exercise and multiple sclerosis.

PubMed

White, Lesley J; Dressendorfer, Rudolph H

2004-01-01

The pathophysiology of multiple sclerosis (MS) is characterised by fatigue, motor weakness, spasticity, poor balance, heat sensitivity and mental depression. Also, MS symptoms may lead to physical inactivity associated with the development of secondary diseases. Persons with MS are thus challenged by their disability when attempting to pursue an active lifestyle compatible with health-related fitness. Although exercise prescription is gaining favour as a therapeutic strategy to minimise the loss of functional capacity in chronic diseases, it remains under-utilised as an intervention strategy in the MS population. However, a growing number of studies indicate that exercise in patients with mild-to-moderate MS provides similar fitness and psychological benefits as it does in healthy controls. We reviewed numerous studies describing the responses of selected MS patients to acute and chronic exercise compared with healthy controls. All training studies reported positive outcomes that outweighed potential adverse effects of the exercise intervention. Based on our review, this article highlights the role of exercise prescription in the multidisciplinary approach to MS disease management for improving and maintaining functional capacity. Despite the often unpredictable clinical course of MS, exercise programmes designed to increase cardiorespiratory fitness, muscle strength and mobility provide benefits that enhance lifestyle activity and quality of life while reducing risk of secondary disorders. Recommendations for the evaluation of cardiorespiratory fitness, muscle performance and flexibility are presented as well as basic guidelines for individualised exercise testing and training in MS. Special considerations for exercise, including medical management concerns, programme modifications and supervision, in the MS population are discussed.

Spirituality, Illness Unpredictability, and Math Anxiety Effects on Negative Affect and Affect-Management Coping for Individuals Diagnosed with Alpha-1 Antitrypsin Deficiency.

PubMed

Worthington, Amber K; Parrott, Roxanne L; Smith, Rachel A

2018-04-01

A growing number of genetic tests are included in diagnostic protocols associated with many common conditions. A positive diagnosis associated with the presence of some gene versions in many instances predicts a range of possible outcomes, and the uncertainty linked to such results contributes to the need to understand varied responses and plan strategic communication. Uncertainty in illness theory (UIT; Mishel, 1988, 1990) guided the investigation of efforts to feel in control and hopeful regarding genetic testing and diagnosis for alpha-1 antitrypsin deficiency (AATD). Participants included 137 individuals with AATD recruited from the Alpha-1 Research Registry who were surveyed about their subjective numeracy, anxiety about math, spirituality, perceptions of illness unpredictability, negative affect regarding genetic testing, and coping strategies about a diagnosis. Results revealed that experiencing more fear and worry contributed both directly and indirectly to affect-management coping strategies, operating through individual perceptions of illness unpredictability. The inability to predict the symptoms and course of events related to a genetic illness and anxiety regarding math heightened fear and worry. Spirituality lessened both illness unpredictability and negative affective responses to a diagnosis. Results affirm the importance of clinician and counselor efforts to incorporate attention to patient spirituality. They also illustrate the complexity associated with strategic efforts to plan communication about the different versions of a gene's effects on well-being, when some versions align with mild health effects and others with severe effects.

PhenoWorld: a new paradigm to screen rodent behavior

PubMed Central

Castelhano-Carlos, M; Costa, P S; Russig, H; Sousa, N

2014-01-01

Modeling depression in animals has inherent complexities that are augmented by intrinsic difficulties to measure the characteristic features of the disorder. Herein, we describe the PhenoWorld (PhW), a new setting in which groups of six rats lived in an ethological enriched environment, and have their feeding, locomotor activity, sleeping and social behavior automatically monitored. A battery of emotional and cognitive tests was used to characterize the behavioral phenotype of animals living in the PhW and in standard conditions (in groups of six and two rats), after exposure to an unpredictable chronic mild stress paradigm (uCMS) and antidepressants. Data reveal that animals living in the PhW displayed similar, but more striking, behavioral differences when exposed to uCMS, such as increased behavioral despair shown in the forced swimming test, resting/sleep behavior disturbances and reduced social interactions. Moreover, several PhW-cage behaviors, such as spontaneous will to go for food or exercise in running wheels, proved to be sensitive indicators of depressive-like behavior. In summary, this new ethological enriched paradigm adds significant discriminative power to screen depressive-like behavior, in particularly rodent's hedonic behavior. PMID:26126181

Probing for Neuroadaptations to Unpredictable Stressors in Addiction: Translational Methods and Emerging Evidence

PubMed Central

Kaye, Jesse T.; Bradford, Daniel E.; Magruder, Katherine P.; Curtin, John J.

2017-01-01

Stressors clearly contribute to addiction etiology and relapse in humans, but our understanding of specific mechanisms remains limited. Rodent models of addiction offer the power, flexibility, and precision necessary to delineate the causal role and specific mechanisms through which stressors influence alcohol and other drug use. This review describes a program of research using startle potentiation to unpredictable stressors that is well positioned to translate between animal models and clinical research with humans on stress neuroadaptations in addiction. This research rests on a solid foundation provided by three separate pillars of evidence from (a) rodent behavioral neuroscience on stress neuroadaptations in addiction, (b) rodent affective neuroscience on startle potentiation, and (c) human addiction and affective science with startle potentiation. Rodent stress neuroadaptation models implicate adaptations in corticotropin-releasing factor and norepinephrine circuits within the central extended amygdala following chronic alcohol and other drug use that mediate anxious behaviors and stress-induced reinstatement among drug-dependent rodents. Basic affective neuroscience indicates that these same neural mechanisms are involved in startle potentiation to unpredictable stressors in particular (vs. predictable stressors). We believe that synthesis of these evidence bases should focus us on the role of unpredictable stressors in addiction etiology and relapse. Startle potentiation in unpredictable stressor tasks is proposed to provide an attractive and flexible test bed to encourage tight translation and reverse translation between animal models and human clinical research on stress neuroadaptations. Experimental therapeutics approaches focused on unpredictable stressors hold high promise to identify, repurpose, or refine pharmacological and psychosocial interventions for addiction. PMID:28499100

Probing for Neuroadaptations to Unpredictable Stressors in Addiction: Translational Methods and Emerging Evidence.

PubMed

Kaye, Jesse T; Bradford, Daniel E; Magruder, Katherine P; Curtin, John J

2017-05-01

Stressors clearly contribute to addiction etiology and relapse in humans, but our understanding of specific mechanisms remains limited. Rodent models of addiction offer the power, flexibility, and precision necessary to delineate the causal role and specific mechanisms through which stressors influence alcohol and other drug use. This review describes a program of research using startle potentiation to unpredictable stressors that is well positioned to translate between animal models and clinical research with humans on stress neuroadaptations in addiction. This research rests on a solid foundation provided by three separate pillars of evidence from (a) rodent behavioral neuroscience on stress neuroadaptations in addiction, (b) rodent affective neuroscience on startle potentiation, and (c) human addiction and affective science with startle potentiation. Rodent stress neuroadaptation models implicate adaptations in corticotropin-releasing factor and norepinephrine circuits within the central extended amygdala following chronic alcohol and other drug use that mediate anxious behaviors and stress-induced reinstatement among drug-dependent rodents. Basic affective neuroscience indicates that these same neural mechanisms are involved in startle potentiation to unpredictable stressors in particular (vs. predictable stressors). We believe that synthesis of these evidence bases should focus us on the role of unpredictable stressors in addiction etiology and relapse. Startle potentiation in unpredictable stressor tasks is proposed to provide an attractive and flexible test bed to encourage tight translation and reverse translation between animal models and human clinical research on stress neuroadaptations. Experimental therapeutics approaches focused on unpredictable stressors hold high promise to identify, repurpose, or refine pharmacological and psychosocial interventions for addiction.

Modeling consequences of prolonged strong unpredictable stress in zebrafish: Complex effects on behavior and physiology.

PubMed

Song, Cai; Liu, Bai-Ping; Zhang, Yong-Ping; Peng, Zhilan; Wang, JiaJia; Collier, Adam D; Echevarria, David J; Savelieva, Katerina V; Lawrence, Robert F; Rex, Christopher S; Meshalkina, Darya A; Kalueff, Allan V

2018-02-02

Chronic stress is the major pathogenetic factor of human anxiety and depression. Zebrafish (Danio rerio) have become a novel popular model species for neuroscience research and CNS drug discovery. The utility of zebrafish for mimicking human affective disorders is also rapidly growing. Here, we present a new zebrafish model of clinically relevant, prolonged unpredictable strong chronic stress (PUCS). The 5-week PUCS induced overt anxiety-like and motor retardation-like behaviors in adult zebrafish, also elevating whole-body cortisol and proinflammatory cytokines - interleukins IL-1β and IL-6. PUCS also elevated whole-body levels of the anti-inflammatory cytokine IL-10 and increased the density of dendritic spines in zebrafish telencephalic neurons. Chronic treatment of fish with an antidepressant fluoxetine (0.1mg/L for 8days) normalized their behavioral and endocrine phenotypes, as well as corrected stress-elevated IL-1β and IL-6 levels, similar to clinical and rodent data. The CNS expression of the bdnf gene, the two genes of its receptors (trkB, p75), and the gfap gene of glia biomarker, the glial fibrillary acidic protein, was unaltered in all three groups. However, PUCS elevated whole-body BDNF levels and the telencephalic dendritic spine density (which were corrected by fluoxetine), thereby somewhat differing from the effects of chronic stress in rodents. Together, these findings support zebrafish as a useful in-vivo model of chronic stress, also calling for further cross-species studies of both shared/overlapping and distinct neurobiological responses to chronic stress. Copyright © 2017 Elsevier Inc. All rights reserved.

Sex hormones affect acute and chronic stress responses in sexually dimorphic patterns: Consequences for depression models.

PubMed

Guo, Lei; Chen, Yi-Xi; Hu, Yu-Ting; Wu, Xue-Yan; He, Yang; Wu, Juan-Li; Huang, Man-Li; Mason, Matthew; Bao, Ai-Min

2018-05-21

Alterations in peripheral sex hormones may play an important role in sex differences in terms of stress responses and mood disorders. It is not yet known whether and how stress-related brain systems and brain sex steroid levels fluctuate in relation to changes in peripheral sex hormone levels, or whether the different sexes show different patterns. We aimed to investigate systematically, in male and female rats, the effect of decreased circulating sex hormone levels following gonadectomy on acute and chronic stress responses, manifested as changes in plasma and hypothalamic sex steroids and hypothalamic stress-related molecules. Experiment (Exp)-1: Rats (14 males, 14 females) were gonadectomized or sham-operated (intact); Exp-2: gonadectomized and intact rats (28 males, 28 females) were exposed to acute foot shock or no stressor; and Exp-3: gonadectomized and intact rats (32 males, 32 females) were exposed to chronic unpredictable mild stress (CUMS) or no stressor. For all rats, plasma and hypothalamic testosterone (T), estradiol (E2), and the expression of stress-related molecules were determined, including corticotropin-releasing hormone, vasopressin, oxytocin, aromatase, and the receptors for estrogens, androgens, glucocorticoids, and mineralocorticoids. Surprisingly, no significant correlation was observed in terms of plasma sex hormones, brain sex steroids, and hypothalamic stress-related molecule mRNAs (p > 0.113) in intact or gonadectomized, male or female, rats. Male and female rats, either intact or gonadectomized and exposed to acute or chronic stress, showed different patterns of stress-related molecule changes. Diminished peripheral sex hormone levels lead to different peripheral and central patterns of change in the stress response systems in male and female rats. This has implications for the choice of models for the study of the different types of mood disorders which also show sex differences. Copyright © 2018 Elsevier Ltd. All rights reserved.

Development of a Vaccine Targeting Triple-Negative Breast Cancer

DTIC Science & Technology

2013-11-01

node Mild hyperplasia and moderate granulomatous perinodal cellulitis mild hyperplasia mild hyperplasia and granulomatous lymphadenitis with...free lipid NSL Mild hyperplasia and moderate granulomatous perinodal cellulitis and steatosis, chronic. Salivary glands NSL NSL NSL NSL NSL

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

PubMed

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.

Regulation of the kynurenine metabolism pathway by Xiaoyao San and the underlying effect in the hippocampus of the depressed rat.

PubMed

Wang, Jiajia; Li, Xiaofang; He, Shugui; Hu, Lijun; Guo, Jiewen; Huang, Xiangning; Hu, Jinqing; Qi, Yaoqun; Chen, Bin; Shang, Dewei; Wen, Yuguan

2018-03-25

Xiaoyao San (XYS) is a classic Chinese herbal formula for treatment of depression. The present study aimed to investigate the antidepressant effects of XYS in a rat model of chronic unpredictable mild stress (CUMS) and the underlying mechanisms. A CUMS rat model of depression was established via 4 weeks of unpredictable stimulation. Then the rats were orally administered paroxetine and XYS for 2 weeks with continued stress. Behavioral assessments, including an open field test (OFT), sucrose preference test (SPT) and forced swim test (FST), were conducted to evaluate the antidepressant effects of XYS. The concentrations in rat plasma of tryptophan (Trp) and its metabolic products, including kynurenine (Kyn) and quinolinic acid (QUIN), were determined using high performance liquid chromatography tandem mass spectrometry with electrochemical detection (HPLC-MS/MS). The mRNA and protein levels in rat hippocampus of depression-related brain derived neurotrophic factor (BDNF), cyclic AMP response element binding protein (CREB) and nerve cell adhesion molecule (NCAM) were determined by real-time qPCR and Western blot, respectively. Enzyme Linked Immunosorbent Assay (ELISA) was used to detect the activities of indoleamine 2,3-dioxygenase (IDO) and kynurenine-3-monooxygenase (KMO) in rat plasma. The results showed that a successful CUMS rat model was established through 4 weeks of continuous unpredictable stimulation, as indicated by the significant decrease in locomotor activity and increase in immobility time in the OFT, reduction in body weight and food intake etc. Compared with the normal group, the concentrations of Kyn and QUIN had significantly (p < 0.05) decreased at day 28 in the control group, but then improved after drug treatment with paroxetine and XYS. There were no obvious changes in the activities of IDO and KMO. Compared with the normal group, the mRNA of NCAM, CREB and BDNF were significantly down-regulated (p < 0.001) in the control group, BDNF gene was up-regulated by paroxetine or XYS treatment, NCAM and CREB gene did not change in XYS group, protein expressions of BDNF and CREB were significantly increased, and NCAM was significantly reduced (p < 0.05). XYS reversed the abnormalities of the tryptophan-kynurenine metabolic pathways in depressed rats and achieved an excellent antidepressant effect. Its direct impact may be observed as changes in biological indicators in rat hippocampus tissue. Copyright © 2017 Elsevier B.V. All rights reserved.

Windsurfing Injuries: Added Awareness for Diagnosis, Treatment, and Prevention.

ERIC Educational Resources Information Center

Rosenbaum, Daryl A.; Dietz, Thomas E.

2002-01-01

With proper training and safety precautions, windsurfing is relatively safe, but its unique equipment and unpredictable environmental conditions can produce serious injuries. Clinicians may see fall-related ankle injuries, tarsometatarsal injuries, or anterior shoulder dislocations; chronic low-back pain from torso stress; skin lacerations; and…

Vicarious social defeat stress: Bridging the gap between physical and emotional stress.

PubMed

Sial, Omar K; Warren, Brandon L; Alcantara, Lyonna F; Parise, Eric M; Bolaños-Guzmán, Carlos A

2016-01-30

Animal models capable of differentiating the neurobiological intricacies between physical and emotional stress are scarce. Current models rely primarily on physical stressors (e.g., chronic unpredictable or mild stress, social defeat, learned helplessness), and neglect the impact of psychological stress alone. This is surprising given extensive evidence that a traumatic event needs not be directly experienced to produce enduring perturbations on an individual's health and psychological well-being. Post-traumatic stress disorder (PTSD), a highly debilitating neuropsychiatric disorder characterized by intense fear of trauma-related stimuli, often occurs in individuals that have only witnessed a traumatic event. By modifying the chronic social defeat stress (CSDS) paradigm to include a witness component (witnessing the social defeat of another mouse), we demonstrate a novel behavioral paradigm capable of inducing a robust behavioral syndrome reminiscent of PTSD in emotionally stressed adult mice. We describe the vicarious social defeat stress (VSDS) model that is capable of inducing a host of behavioral deficits that include social avoidance and other depressive- and anxiety-like phenotypes in adult male mice. VSDS exposure induces weight loss and spike in serum corticosterone (CORT) levels. A month after stress, these mice retain the social avoidant phenotype and have an increased CORT response when exposed to subsequent stress. The VSDS is a novel paradigm capable of inducing emotional stress by isolating physical stress/confrontation in mice. The VSDS model can be used to study the short- and long-term neurobiological consequences of exposure to emotional stress in mice. Copyright © 2015 Elsevier B.V. All rights reserved.

Interaction of brain 5-HT synthesis deficiency, chronic stress and sex differentially impact emotional behavior in Tph2 knockout mice.

PubMed

Gutknecht, Lise; Popp, Sandy; Waider, Jonas; Sommerlandt, Frank M J; Göppner, Corinna; Post, Antonia; Reif, Andreas; van den Hove, Daniel; Strekalova, Tatyana; Schmitt, Angelika; Colaςo, Maria B N; Sommer, Claudia; Palme, Rupert; Lesch, Klaus-Peter

2015-07-01

While brain serotonin (5-HT) function is implicated in gene-by-environment interaction (GxE) impacting the vulnerability-resilience continuum in neuropsychiatric disorders, it remains elusive how the interplay of altered 5-HT synthesis and environmental stressors is linked to failure in emotion regulation. Here, we investigated the effect of constitutively impaired 5-HT synthesis on behavioral and neuroendocrine responses to unpredictable chronic mild stress (CMS) using a mouse model of brain 5-HT deficiency resulting from targeted inactivation of the tryptophan hydroxylase-2 (Tph2) gene. Locomotor activity and anxiety- and depression-like behavior as well as conditioned fear responses were differentially affected by Tph2 genotype, sex, and CMS. Tph2 null mutants (Tph2(-/-)) displayed increased general metabolism, marginally reduced anxiety- and depression-like behavior but strikingly increased conditioned fear responses. Behavioral modifications were associated with sex-specific hypothalamic-pituitary-adrenocortical (HPA) system alterations as indicated by plasma corticosterone and fecal corticosterone metabolite concentrations. Tph2(-/-) males displayed increased impulsivity and high aggressiveness. Tph2(-/-) females displayed greater emotional reactivity to aversive conditions as reflected by changes in behaviors at baseline including increased freezing and decreased locomotion in novel environments. However, both Tph2(-/-) male and female mice were resilient to CMS-induced hyperlocomotion, while CMS intensified conditioned fear responses in a GxE-dependent manner. Our results indicate that 5-HT mediates behavioral responses to environmental adversity by facilitating the encoding of stress effects leading to increased vulnerability for negative emotionality.

Chronic stress induces brain region specific alterations of molecular rhythms in mice that correlate with depression-like behavior

PubMed Central

Logan, Ryan W.; Edgar, Nicole; Gillman, Andrea G.; Hoffman, Daniel; Zhu, Xiyu; McClung, Colleen A.

2015-01-01

Background Emerging evidence implicates circadian abnormalities as a component of the pathophysiology of major depressive disorder (MDD). The suprachiasmatic nucleus (SCN) of the hypothalamus coordinates rhythms throughout the brain and body. On a cellular level, rhythms are generated by transcriptional, translational, and post-translational feedback loops of core circadian genes and proteins. In patients with MDD, recent evidence suggests reduced amplitude of molecular rhythms in extra-SCN brain regions. We investigated whether unpredictable chronic mild stress (UCMS), an animal model that induces a depression-like physiological and behavioral phenotype, induces circadian disruptions similar to those seen with MDD. Methods Activity and temperature rhythms were recorded in C57BL/6J mice before, during, and after exposure to UCMS, and brain tissue explants were collected from Period2 luciferase (Per2::luc) mice following UCMS to assess cellular rhythmicity. Results UCMS significantly decreased circadian amplitude of activity and body temperature in mice, similar to findings in MDD patients and these changes directly correlate with depression-related behavior. While amplitude of molecular rhythms in the SCN was decreased following UCMS, surprisingly, rhythms in the nucleus accumbens were amplified with no changes seen in the prefrontal cortex or amygdala. These molecular rhythm changes in the SCN and the nucleus accumbens (NAc) also directly correlated with mood-related behavior. Conclusions These studies find that circadian rhythm abnormalities directly correlate with depression-related behavior following UCMS and suggest a desynchronization of rhythms in the brain with an independent enhancement of rhythms in the NAc. PMID:25771506

UROLOGIC CHRONIC PELVIC PAIN SYNDROME FLARES AND THEIR IMPACT: QUALITATIVE ANALYSIS IN THE MAPP NETWORK

PubMed Central

Sutcliffe, Siobhan; Bradley, Catherine S.; Clemens, J. Quentin; James, Aimee S.; Konkle, Katy S.; Kreder, Karl J.; Lai, H. Henry; Mackey, Sean C.; Ashe-McNalley, Cody P.; Rodriguez, Larissa V.; Barrell, Edward; Hou, Xiaoling; Robinson, Nancy A.; Mullins, Chris; Berry, Sandra H.

2015-01-01

Introduction Although in-depth qualitative information is critical for understanding patients’ symptom experiences and for developing patient-centered outcome measures, only one previous qualitative study has assessed urologic chronic pelvic pain syndrome (UCPPS) symptom exacerbations (“flares”). Methods We conducted eight focus groups of female UCPPS (interstitial cystitis/bladder pain syndrome) patients at four sites of the MAPP Research Network (n=57, mean=7/group) to explore the full spectrum of flares and their impact on patients’ lives. Results Flare experiences were common and varied widely in terms of UCPPS symptoms involved, concurrent non-pelvic symptoms (e.g., diarrhea), symptom intensity (mild to severe), duration (minutes to years), and frequency (daily to

The protective role of Bax Inhibitor-1 against chronic mild stress through the inhibition of monoamine oxidase A

PubMed Central

Lee, Hwa-Young; Lee, Geum-Hwa; Marahatta, Anu; Lin, Shun-Mei; Lee, Mi-Rin; Jang, Kyu Yun; Kim, Kyung Min; Lee, Hee Jae; Lee, Jae-Won; Bagalkot, Tarique Rajasaheb; Chung, Young-Chul; Lee, Yong-Chul; Kim, Hyung-Ryong; Chae, Han-Jung

2013-01-01

The anti-apoptotic protein Bax inhibitor-1 (BI-1) is a regulator of apoptosis linked to endoplasmic reticulum (ER) stress. It has been hypothesized that BI-1 protects against neuron degenerative diseases. In this study, BI-1−/− mice showed increased vulnerability to chronic mild stress accompanied by alterations in the size and morphology of the hippocampi, enhanced ROS accumulation and an ER stress response compared with BI-1+/+ mice. BI-1−/− mice exposed to chronic mild stress showed significant activation of monoamine oxidase A (MAO-A), but not MAO-B, compared with BI-1+/+ mice. To examine the involvement of BI-1 in the Ca2+-sensitive MAO activity, thapsigargin-induced Ca2+ release and MAO activity were analyzed in neuronal cells overexpressing BI-1. The in vitro study showed that BI-1 regulates Ca2+ release and related MAO-A activity. This study indicates an endogenous protective role of BI-1 under conditions of chronic mild stress that is primarily mediated through Ca2+-associated MAO-A regulation. PMID:24292328

The protective effects of social bonding on behavioral and pituitary-adrenal axis reactivity to chronic mild stress in prairie voles.

PubMed

McNeal, Neal; Appleton, Katherine M; Johnson, Alan Kim; Scotti, Melissa-Ann L; Wardwell, Joshua; Murphy, Rachel; Bishop, Christina; Knecht, Alison; Grippo, Angela J

2017-03-01

Positive social interactions may protect against stress. This study investigated the beneficial effects of pairing with a social partner on behaviors and neuroendocrine function in response to chronic mild stress (CMS) in 13 prairie vole pairs. Following 5 days of social bonding, male and female prairie voles were exposed to 10 days of CMS (mild, unpredictable stressors of varying durations, for instance, strobe light, white noise, and damp bedding), housed with either the social partner (paired group) or individually (isolated group). Active and passive behavioral responses to the forced swim test (FST) and tail-suspension test (TST), and plasma concentrations of adrenocorticotropic hormone (ACTH) and corticosterone, were measured in all prairie voles following the CMS period. Both female and male prairie voles housed with a social partner displayed lower durations of passive behavioral responses (immobility, a maladaptive behavioral response) in the FST (mean ± SEM; females: 17.3 ± 5.4 s; males: 9.3 ± 4.6 s) and TST (females: 56.8 ± 16.4 s; males: 40.2 ± 11.3 s), versus both sexes housed individually (females, FST: 98.6 ± 12.9 s; females, TST: 155.1 ± 19.3 s; males, FST: 92.4 ± 14.1 s; males, TST: 158.9 ± 22.0 s). Female (but not male) prairie voles displayed attenuated plasma stress hormones when housed with a male partner (ACTH: 945 ± 24.7 pg/ml; corticosterone: 624 ± 139.5 ng/ml), versus females housed individually (ACTH: 1100 ± 23.2 pg/ml; corticosterone: 1064 ± 121.7 ng/ml). These results may inform understanding of the benefits of social interactions on stress resilience. Lay Summary: Social stress can lead to depression. The study of social bonding and stress using an animal model will inform understanding of the protective effects of social bonds. This study showed that social bonding in a rodent model can protect against behavioral responses to stress, and may also be protective against the elevation of stress hormones. This study provides evidence that bonding and social support are valuable for protecting against stress in humans.

Experimental studies on possible regulatory role of nitric oxide on the differential effects of chronic predictable and unpredictable stress on adaptive immune responses.

PubMed

Thakur, Tarun; Gulati, Kavita; Rai, Nishant; Ray, Arunabha

2017-09-01

The present study was designed to investigate the effects of chronic predictable stress (CPS) and chronic unpredictable stress (CUS) on immunological responses in KLH-sensitized rats and involvement of NOergic signaling pathways mediating such responses. Male Wistar rats (200-250g) were exposed to either CPS or CUS for 14days and IgG antibody levels and delayed type hypersensitivity (DTH) response was determined to assess changes in adaptive immunity. To evaluate the role of nitric oxide during such immunomodulation, biochemical estimation of stable metabolite of nitric oxide (NOx) and 3-nitrotyrosine (3-NT, a marker of peroxynitrite formation) were done in both blood and brain. Chronic stress exposure resulted in suppression of IgG and DTH response and elevated NOx and 3-NT levels, with a difference in magnitude of response in CPS vs CUS. Pretreatment with aminoguanidine (iNOS inhibitor) caused further reduction of adaptive immune responses and attenuated the increased NOx and 3-NT levels in CPS or CUS exposed rats. On the other hand 7-NI (nNOS inhibitor) did not significantly affect these estimated parameters. The results suggest involvement of iNOS and lesser/no role of nNOS during modulation of adaptive immunity to stress. Thus, the result showed that predictability of stressors results in differential degree of modulation of immune responses and complex NO-mediated signaling mechanisms may be involved during responses. Copyright © 2017. Published by Elsevier B.V.

3 CFR 8615 - Proclamation 8615 of December 7, 2010. National Influenza Vaccination Week, 2010

Code of Federal Regulations, 2011 CFR

2011-01-01

... people living with HIV, chronic lung disease, diabetes, heart disease, neurologic conditions, and certain... influenza virus, we were reminded of the severity and unpredictability of this serious disease. Thousands of... this disease. Together, we can prepare as individuals and as a Nation for this year's flu season and...

The Small College Guide to Financial Health: Beating the Odds.

ERIC Educational Resources Information Center

Townsley, Michael K.

This book analyzes the latest data and economic models to explore whether an unpredictable economy, changes in student preference, tuition that outpaced inflation, and new forms of competition will plunge small colleges into chronic financial distress. It then suggests ways small colleges can position themselves to avoid economic disaster by…

Multiple Sclerosis and Employment: A Research Review Based on the International Classification of Function

ERIC Educational Resources Information Center

Frain, Michael P.; Bishop, Malachy; Rumrill, Phillip D., Jr.; Chan, Fong; Tansey, Timothy N.; Strauser, David; Chiu, Chung-Yi

2015-01-01

Multiple sclerosis (MS) is an unpredictable, sometimes progressive chronic illness affecting people in the prime of their working lives. This article reviews the effects of MS on employment based on the World Health Organization's International Classification of Functioning, Disability and Health model. Correlations between employment and…

Neurochemical, hormonal, and behavioral effects of chronic unpredictable stress in the rat

PubMed Central

Cox, Brittney M.; Alsawah, Fares; McNeill, Peter C.; Galloway, Matthew P.; Perrine, Shane A.

2011-01-01

The high comorbidity of anxiety and depression suggests a potential degree of commonality in their etiologies. The chronic unpredictable stress (CUS) model effectively replicates depressive-like phenotypes; however, the ability of CUS to produce anxiety-like behaviors has not been adequately addressed. Using the CUS paradigm (2 stressors per day for 10 days) in adult Sprague Dawley rats we identified behavioral, hormonal, and neurochemical changes one day after the cessation of treatment. Stress attenuated weight gain throughout the study and increased locomotor activity one day after treatment, but had no effect on anxiety-behavior as measured by the elevated plus maze. In addition, plasma corticosterone levels were positively correlated with hypothalamic serotonin (5-HT) activity one day after stress treatment as determined by the ratio of the metabolite 5-hydroxyindoleacetic acid (5-HIAA) to the parent compound (5-HIAA/5-HT ratio). These data suggest behavioral phenotypes associated with depression, but not comorbid anxiety, emerge in the immediate period after cessation of stress and that stress related physiology is related to 5-HT activity in the hypothalamus. PMID:21277333

Antidepressant-like effects of mild hypoxia preconditioning in the learned helplessness model in rats.

PubMed

Rybnikova, Elena; Mironova, Vera; Pivina, Svetlana; Tulkova, Ekaterina; Ordyan, Natalia; Vataeva, Ludmila; Vershinina, Elena; Abritalin, Eugeny; Kolchev, Alexandr; Nalivaeva, Natalia; Turner, Anthony J; Samoilov, Michail

2007-05-07

The effects of preconditioning using mild repetitive hypobaric hypoxia (360 Torr for 2 h each of 3 days) have been studied in the learned helplessness model of depression in rats. Male Wistar rats displayed persistent depressive symptoms (depressive-like behaviour in open field, increased anxiety levels in elevated plus maze, ahedonia, elevated plasma glucocorticoids and impaired dexamethasone test) following the exposure to unpredictable and inescapable footshock in the learned helplessness paradigm. Antidepressant treatment (ludiomil, 5 mg/kg i.p.) augmented the development of the depressive state. The hypoxic preconditioning had a clear antidepressive action returning the behavioural and hormonal parameters to the control values and was equally effective in terms of our study as the antidepressant. The findings suggest hypoxic preconditioning as an effective tool for the prophylaxis of post-stress affective pathologies in humans.

The neuropathology of traumatic brain injury.

PubMed

Mckee, Ann C; Daneshvar, Daniel H

2015-01-01

Traumatic brain injury, a leading cause of mortality and morbidity, is divided into three grades of severity: mild, moderate, and severe, based on the Glasgow Coma Scale, the loss of consciousness, and the development of post-traumatic amnesia. Although mild traumatic brain injury, including concussion and subconcussion, is by far the most common, it is also the most difficult to diagnose and the least well understood. Proper recognition, management, and treatment of acute concussion and mild traumatic brain injury are the fundamentals of an emerging clinical discipline. It is also becoming increasingly clear that some mild traumatic brain injuries have persistent, and sometimes progressive, long-term debilitating effects. Evidence indicates that a single traumatic brain injury can precipitate or accelerate multiple age-related neurodegenerations, increase the risk of developing Alzheimer's disease, Parkinson's disease, and motor neuron disease, and that repetitive mild traumatic brain injuries can provoke the development of a tauopathy, chronic traumatic encephalopathy. Clinically, chronic traumatic encephalopathy is associated with behavioral changes, executive dysfunction, memory loss, and cognitive impairments that begin insidiously and progress slowly over decades. Pathologically, chronic traumatic encephalopathy produces atrophy of the frontal and temporal lobes, thalamus, and hypothalamus, septal abnormalities, and abnormal deposits of hyperphosphorylated tau (τ) as neurofibrillary tangles and disordered neurites throughout the brain. The incidence and prevalence of chronic traumatic encephalopathy and the genetic risk factors critical to its development are currently unknown. Chronic traumatic encephalopathy frequently occurs as a sole diagnosis, but may be associated with other neurodegenerative disorders, including Alzheimer's disease, Lewy body disease, and motor neuron disease. Currently, chronic traumatic encephalopathy can be diagnosed only at autopsy; however, promising efforts to develop imaging, spinal fluid, and peripheral blood biomarkers are underway to diagnose and monitor the course of disease in living subjects. © 2015 Elsevier B.V. All rights reserved.

Magnetic resonance imaging detection of multiple ischemic injury produced in an adult rat model of minor stroke followed by mild transient cerebral ischemia.

PubMed

Tuor, Ursula I; Qiao, Min

2017-04-01

To determine whether cumulative brain damage produced adjacent to a minor stroke that is followed by a mild transient ischemia is detectable with MRI and histology, and whether acute or chronic recovery between insults influences this damage. A minor photothrombotic (PT) stroke was followed acutely (1-2 days) or chronically (7 days) by a mild transient middle cerebral artery occlusion (tMCAO). MRI was performed after each insult, followed by final histology. The initial PT produced small hyperintense T 2 and DW infarct lesions and peri-lesion regions of scattered necrosis and modestly increased T 2 . Following tMCAO, in a slice and a region adjacent to the PT, a region of T 2 augmentation was observed when recovery between insults was acute but not chronic. Within the PT slice, a modest region of exacerbated T 2 change proximate to the PT was also observed in the chronic group. Corresponding histological changes within regions of augmented T 2 included increased vacuolation and cell death. Within regions adjacent to an experimental minor stroke, a recurrence of a mild transient cerebral ischemia augmented T 2 above increases produced by tMCAO alone, reflecting increased damage in this region. Exacerbation appeared broader with acute versus chronic recovery between insults.

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

ERIC Educational Resources Information Center

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…

Differential SPECT activation patterns associated with PASAT performance may indicate frontocerebellar functional dissociation in chronic mild traumatic brain injury.

PubMed

Hattori, Naoya; Swan, Megan; Stobbe, Gary A; Uomoto, Jay M; Minoshima, Satoshi; Djang, David; Krishnananthan, Ruben; Lewis, David H

2009-07-01

Patients with mild traumatic brain injury (TBI) often complain of cognitive fatigue during the chronic recovery phase. The Paced Auditory Serial Addition Test (PASAT) is a complex psychologic measure that may demonstrate subtle deficiencies in higher cognitive functions. The purpose of this study was to investigate the brain activation of regional cerebral blood flow (rCBF) with PASAT in patients with mild TBI to explore mechanisms for the cognitive fatigue. Two groups consisting of 15 patients with mild TBI and 15 healthy control subjects underwent (99m)Tc-ethylene cysteine dimer SPECT at rest and during PASAT on a separate day. Cortical rCBF was extracted using a 3-dimensional stereotactic surface projection and statistically analyzed to identify areas of activation, which were compared with PASAT performance scores. Image analysis demonstrated a difference in the pattern of activation between patients with mild TBI and healthy control subjects. Healthy control subjects activated the superior temporal cortex (Brodmann area [BA] 22) bilaterally, the precentral gyrus (BA 9) on the left, and the precentral gyrus (BA 6) and cerebellum bilaterally. Patients with mild TBI demonstrated a larger area of supratentorial activation (BAs 9, 10, 13, and 46) but a smaller area of activation in the cerebellum, indicating frontocerebellar dissociation. Patients with mild TBI and cognitive fatigue demonstrated a different pattern of activation during PASAT. Frontocerebellar dissociation may explain cognitive impairment and cognitive fatigue in the chronic recovery phase of mild traumatic brain injury.

Investigation on the antidepressant effect of sea buckthorn seed oil through the GC-MS-based metabolomics approach coupled with multivariate analysis.

PubMed

Tian, Jun-sheng; Liu, Cai-chun; Xiang, Huan; Zheng, Xiao-fen; Peng, Guo-jiang; Zhang, Xiang; Du, Guan-hua; Qin, Xue-mei

2015-11-01

Depression is one of the prevalent and serious mental disorders and the number of depressed patients has been on the rise globally during the recent decades. Sea buckthorn seed oil from traditional Chinese medicine (TCM) is edible and has been widely used for treatment of different diseases for a long time. However, there are few published reports on the antidepressant effect of sea buckthorn seed oil. With the objective of finding potential biomarkers of the therapeutic response of sea buckthorn seed oil in chronic unpredictable mild stress (CUMS) rats, urine metabolomics based on gas chromatography-mass spectrometry (GC-MS) coupled with multivariate analysis was applied. In this study, we discovered a higher level of pimelic acid as well as palmitic acid and a lower level of suberic acid, citrate, phthalic acid, cinnamic acid and Sumiki's acid in urine of rats exposed to CUMS procedures after sea buckthorn seed oil was administered. These changes of metabolites are involved in energy metabolism, fatty acid metabolism and other metabolic pathways as well as in the synthesis of neurotransmitters and it is helpful to facilitate the efficacy evaluation and mechanism elucidating the effect of sea buckthorn seed oil for depression management.

Chronic mild stress influences nerve growth factor through a matrix metalloproteinase-dependent mechanism.

PubMed

Kucharczyk, Mateusz; Kurek, Anna; Detka, Jan; Slusarczyk, Joanna; Papp, Mariusz; Tota, Katarzyna; Basta-Kaim, Agnieszka; Kubera, Marta; Lason, Wladyslaw; Budziszewska, Bogusława

2016-04-01

Stress is generally a beneficial experience that motivates an organism to action to overcome the stressful challenge. In particular situations, when stress becomes chronic might be harmful and devastating. The hypothalamus is a critical coordinator of stress and the metabolic response; therefore, disruptions in this structure may be a significant cause of the hormonal and metabolic disturbances observed in depression. Chronic stress induces adverse changes in the morphology of neural cells that are often associated with a deficiency of neurotrophic factors (NTFs); additionally, many studies indicate that insufficient NTF synthesis may participate in the pathogenesis of depression. The aim of the present study was to determine the expression of the nerve growth factor (NGF) in the hypothalamus of male rats subjected to chronic mild stress (CMS) or to prenatal stress (PS) and to PS in combination with an acute stress event (AS). It has been found that chronic mild stress, but not prenatal stress, acute stress or a combination of PS with AS, decreased the concentration of the mature form of NGF (m-NGF) in the rat hypothalamus. A discrepancy between an increase in the Ngf mRNA and a decrease in the m-NGF levels suggested that chronic mild stress inhibited NGF maturation or enhanced the degradation of this factor. We have shown that NGF degradation in the hypothalamus of rats subjected to chronic mild stress is matrix metalloproteinase-dependent and related to an increase in the active forms of some metalloproteinases (MMP), including MMP2, MMP3, MMP9 and MMP13, while the NGF maturation process does not seem to be changed. We suggested that activated MMP2 and MMP9 potently cleave the mature but not the pro- form of NGF into biologically inactive products, which is the reason for m-NGF decomposition. In turn, the enhanced expression of Ngf in the hypothalamus of these rats is an attempt to overcome the reduced levels of m-NGF. Additionally, the decreased level of m-NGF together with the increased level of pro-NGF can decrease TrkA-mediated neuronal survival signalling and enhance the action of pro-NGF on the p75(NTR) receptor, respectively, to evoke pro-apoptotic signalling. This hypothesis is supported by elevated levels of the caspase-3 mRNA in the hypothalamus of rats subjected to chronic mild stress. Copyright © 2015 Elsevier Ltd. All rights reserved.

The contribution of rib fractures to chronic pain and disability.

PubMed

Gordy, Stephanie; Fabricant, Loic; Ham, Bruce; Mullins, Richard; Mayberry, John

2014-05-01

The contribution of rib fractures to chronic pain and disability is not well described. Two hundred three patients with rib fractures were followed for 6 months. Chronic pain was assessed using the McGill Pain Questionnaire Pain Rating Index and Present Pain Intensity (PPI) scales. Disability was defined as a decrease in work or functional status. The prevalence of chronic pain was 22% and disability was 53%. Acute PPI predicted chronic pain. Associated injuries, bilateral rib fractures, injury severity score, and number of rib fractures were not predictive of chronic pain. No acute injury characteristics were predictive of disability. Among 89 patients with isolated rib fractures, the prevalence of chronic pain was 28% and of disability was 40%. No injury characteristics predicted chronic pain. Bilateral rib fractures and acute PPI predicted disability. The contribution of rib fractures to chronic pain and disability is significant but unpredictable with conventional injury descriptors. Copyright © 2014 Elsevier Inc. All rights reserved.

Probiotics and Antibiotic-Associated Diarrhea and Clostridium difficile Infection

NASA Astrophysics Data System (ADS)

Surawicz, Christina M.

Diarrhea is a common side effect of antibiotics. Antibiotics can cause diarrhea in 5-25% of individuals who take them but its occurrence is unpredictable. Diarrhea due to antibiotics is called antibiotic-associated diarrhea (AAD). Diarrhea may be mild and resolve when antibiotics are discontinued, or it may be more severe. The most severe form of AAD is caused by overgrowth of Clostridium difficile which can cause severe diarrhea, colitis, pseudomembranous colitis, or even fatal toxic megacolon. Rates of diarrhea vary with the specific antibiotic as well as with the individual susceptibility.

Chronic Stress and Fatigue-Related Quality of Life after Mild-to-Moderate Traumatic Brain Injury (TBI)

PubMed Central

Bay, Esther; de-Leon, Marita B.

2010-01-01

Objective To determine relationships between chronic stress, fatigue-related quality of life (QOL-F) and related covariates after mild-to-moderate traumatic brain injury (TBI). Design Observational and cross-sectional Participants A total of 84 community-dwelling individuals with mild-to-moderate TBI recruited from multiple out-patient rehabilitation clinics assessed on average 15 months after injury. Method Data were collected with self-report surveys and chart abstraction. Measures Neurofunctional Behavioral Inventory, Perceived Stress Scale-14, Impact of Events Scale, McGill Pain Short-form Scale, and modified version of the Fatigue Impact Scale. Results Fatigue-related quality of life was associated with somatic symptoms, perceived situational stress, but not with event-related stress (PTSD symptoms) related to index TBI, pre-injury demographic, or post-injury characteristics. Somatic symptoms and chronic situational stress accounted for 42% of the variance in QOL (F). Conclusions QOL (F) in community-dwelling individuals with mild-to- moderate TBI is associated with chronic situational stress and somatic symptoms. Symptom management strategies may need to include general stress management to reduce fatigue burden and improve quality of life. PMID:21169862

Characterization of GABAergic marker expression in the chronic unpredictable stress model of depression

PubMed Central

Banasr, Mounira; Lepack, Ashley; Fee, Corey; Duric, Vanja; Maldonado-Aviles, Jaime; DiLeone, Ralph; Sibille, Etienne; Duman, Ronald S.; Sanacora, Gerard

2017-01-01

Evidence continues to build suggesting that the GABAergic neurotransmitter system is altered in brains of patients with major depressive disorder. However, there is little information available related to the extent of these changes or the potential mechanisms associated with these alterations. As stress is a well-established precipitant to depressive episodes, we sought to explore the impact of chronic stress on GABAergic interneurons. Using western blot analyses and quantitative real-time PCR (qPCR) we assessed the effects of five-weeks of chronic unpredictable stress (CUS) exposure on the expression of GABA-synthesizing enzymes (GAD65 and GAD67), calcium-binding proteins (calbindin (CB), parvalbumin (PV) and calretinin (CR)), and neuropeptides co-expressed in GABAergic neurons (somatostatin (SST), neuropeptide Y (NPY), vasoactive intestinal peptide (VIP) and cholecystokinin (CCK)) in the prefrontal cortex (PFC) and hippocampus (HPC) of rats. We also investigated the effects of corticosterone (CORT) and dexamethasone (DEX) exposure on these markers in vitro in primary cortical and hippocampal cultures. We found that CUS induced significant reductions of GAD67 protein levels in both the PFC and HPC of CUS-exposed rats, but did not detect changes in GAD65 protein expression. Similar protein expression changes were found in vitro in cortical neurons. In addition, our results provide clear evidence of reduced markers of interneuron population(s), namely SST and NPY, in the PFC, suggesting these cell types may be selectively vulnerable to chronic stress. Together, this work highlights that chronic stress induces regional and cell type-selective effects on GABAergic interneurons in rats. These findings provide additional supporting evidence that stress-induced GABA neuron dysfunction and cell vulnerability play critical roles in the pathophysiology of stress-related illnesses, including major depressive disorder. PMID:28835932

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

ERIC Educational Resources Information Center

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…

3xTgAD mice exhibit altered behavior and elevated Aβ after chronic mild social stress

PubMed Central

Rothman, Sarah M.; Herdener, Nathan; Camandola, Simonetta; Texel, Sarah J.; Mughal, Mohamed R.; Cong, Wei-Na; Martin, Bronwen; Mattson, Mark P

2014-01-01

Chronic stress may be a risk factor for developing Alzheimer’s disease (AD), but most studies of the effects of stress in models of AD utilize acute adverse stressors of questionable clinical relevance. The goal of this work was to determine how chronic psychosocial stress affects behavioral and pathological outcomes in an animal model of AD, and to elucidate underlying mechanisms. A triple-transgenic mouse model of AD (3xTgAD mice) and nontransgenic control mice were used to test for an affect of chronic mild social stress on blood glucose, plasma glucocorticoids, plasma insulin, anxiety and hippocampal Aβ, ptau and BDNF levels. Despite the fact that both control and 3xTgAD mice experienced rises in corticosterone during episodes of mild social stress, at the end of the 6 week stress period 3xTgAD mice displayed increased anxiety, elevated levels of Aβ oligomers and intraneuronal Aβ, and decreased BDNF levels, whereas control mice did not. Findings suggest 3xTgAD mice are more vulnerable than control mice to chronic psychosocial stress, and that such chronic stress exacerbates Aβ accumulation and impairs neurotrophic signaling. PMID:21855175

Prevalence of Cerebral Microhemorrhage following Chronic Blast-Related Mild Traumatic Brain Injury in Military Service Members Using Susceptibility-Weighted MRI.

PubMed

Lotan, E; Morley, C; Newman, J; Qian, M; Abu-Amara, D; Marmar, C; Lui, Y W

2018-05-24

Cerebral microhemorrhages are a known marker of mild traumatic brain injury. Blast-related mild traumatic brain injury relates to a propagating pressure wave, and there is evidence that the mechanism of injury in blast-related mild traumatic brain injury may be different from that in blunt head trauma. Two recent reports in mixed cohorts of blunt and blast-related traumatic brain injury in military personnel suggest that the prevalence of cerebral microhemorrhages is lower than in civilian head injury. In this study, we aimed to characterize the prevalence of cerebral microhemorrhages in military service members specifically with chronic blast-related mild traumatic brain injury. Participants were prospectively recruited and underwent 3T MR imaging. Susceptibility-weighted images were assessed by 2 neuroradiologists independently for the presence of cerebral microhemorrhages. Our cohort included 146 veterans (132 men) who experienced remote blast-related mild traumatic brain injury (mean, 9.4 years; median, 9 years after injury). Twenty-one (14.4%) reported loss of consciousness for <30 minutes. Seventy-seven subjects (52.7%) had 1 episode of blast-related mild traumatic brain injury; 41 (28.1%) had 2 episodes; and 28 (19.2%) had >2 episodes. No cerebral microhemorrhages were identified in any subject, as opposed to the frequency of SWI-detectable cerebral microhemorrhages following blunt-related mild traumatic brain injury in the civilian population, which has been reported to be as high as 28% in the acute and subacute stages. Our results may reflect differences in pathophysiology and the mechanism of injury between blast- and blunt-related mild traumatic brain injury. Additionally, the chronicity of injury may play a role in the detection of cerebral microhemorrhages. © 2018 by American Journal of Neuroradiology.

Prior exposure to repeated immobilization or chronic unpredictable stress protects from some negative sequels of an acute immobilization.

PubMed

Pastor-Ciurana, Jordi; Rabasa, Cristina; Ortega-Sánchez, Juan A; Sanchís-Ollè, Maria; Gabriel-Salazar, Marina; Ginesta, Marta; Belda, Xavier; Daviu, Núria; Nadal, Roser; Armario, Antonio

2014-05-15

Exposure to chronic unpredictable stress (CUS) is gaining acceptance as a putative animal model of depression. However, there is evidence that chronic exposure to stress can offer non-specific stress protection from some effects of acute superimposed stressors. We then compared in adult male rats the protection afforded by prior exposure to CUS with the one offered by repeated immobilization on boards (IMO) regarding some of the negative consequences of an acute exposure to IMO. Repeated exposure to IMO protected from the negative consequences of an acute IMO on activity in an open-field, saccharin intake and body weight gain. Active coping during IMO (struggling) was markedly reduced by repeated exposure to the same stressor, but it was not affected by a prior history of CUS, suggesting that our CUS protocol does not appear to impair active coping responses. CUS exposure itself caused a strong reduction of activity in the open-field but appeared to protect from the hypo-activity induced by acute IMO. Moreover, prior CUS offered partial protection from acute IMO-induced reduction of saccharin intake and body weight gain. It can be concluded that a prior history of CUS protects from some of the negative consequences of exposure to a novel severe stressor, suggesting the development of partial cross-adaptation whose precise mechanisms remain to be studied. Copyright © 2014 Elsevier B.V. All rights reserved.

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.

PubMed

Li, Ying; Ji, Yong-juan; Jiang, Hong; Liu, De-xiang; Zhang, Qian; Fan, Shu-jian; Pan, Fang

2009-07-05

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. 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. 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 in both age groups (P < 0.05), a reduction that was still present at the eighth day after stress (P < 0.05). Stress and age were the main factors affecting the expression of BDNF (F = 9.408, P < 0.05; F = 106.303, P < 0.05). The aged stress group showed lower BDNF expression compared to the young stressed group at every testing time point. Stress has age-dependent effects on behavioral responses and hippocampal BDNF expression in rats.

Unpredictable Variable Prenatal Stress Programs Expression of Genes Involved in Appetite Control and Energy Expenditure

NASA Technical Reports Server (NTRS)

Moyer, E. L.; Al-Shayeb, B.; Baer, L. A.; Ronca, A. E.

2016-01-01

Exposure to stress in the womb shapes neurobiological and physiological outcomes of offspring in later life, including body weight regulation and metabolic profiles. Our previous work utilizing a centrifugation-induced hyper-gravity demonstrated significantly increased (8-15%) body mass in male, but not female, rats exposed throughout gestation to chronic 2-g from conception to birth. We reported a similar outcome in adult offspring exposed throughout gestation to Unpredictable Variable Prenatal Stress (UVPS). Here we examine gene expression changes and the plasma of animals treated with our UVPS model to identify a potential role for prenatal stress in this hypergravity programming effect. Specifically we focused on appetite control and energy expenditure pathways in prenatally stressed adult (90-day-old) male Sprague-Dawley rats.

Antidepressant effects of abscisic acid mediated by the downregulation of corticotrophin-releasing hormone gene expression in rats.

PubMed

Qi, Cong-Cong; Zhang, Zhi; Fang, Hui; Liu, Ji; Zhou, Nan; Ge, Jin-Fang; Chen, Fang-Han; Xiang, Cheng-Bin; Zhou, Jiang-Ning

2014-10-31

Corticotrophin-releasing hormone (CRH) is considered to be the central driving force of the hypothalamic-pituitary-adrenal axis, which plays a key role in the stress response and depression. Clinical reports have suggested that excess retinoic acid (RA) is associated with depression. Abscisic acid (ABA) and RA are direct derivatives of carotenoids and share a similar molecular structure. Here, we proposed that ABA also plays a role in the regulation of CRH activity sharing with the RA signaling pathway. [3H]-ABA radioimmunoassay demonstrated that the hypothalamus of rats shows the highest concentration of ABA compared with the cortex and the hippocampus under basal conditions. Under acute stress, ABA concentrations increased in the serum, but decreased in the hypothalamus and were accompanied by increased corticosterone in the serum and c-fos expression in the hypothalamus. Moreover, chronic ABA administration increased sucrose intake and decreased the mRNA expression of CRH and retinoic acid receptor alpha (RARα) in the hypothalamus of rats. Furthermore, ABA improved the symptom of chronic unpredictable mild stress in model rats, as indicated by increased sucrose intake, increased swimming in the forced swim test, and reduced mRNA expression of CRH and RARα in the rat hypothalamus. In vitro, CRH expression decreased after ABA treatment across different neural cells. In BE(2)-C cells, ABA inhibited a series of retinoid receptor expression, including RARα, a receptor that could facilitate CRH expression directly. These results suggest that ABA may play a role in the pathogenesis of depression by downregulating CRH mRNA expression shared with the RA signaling pathway. © The Author 2014. Published by Oxford University Press on behalf of CINP.

Antidepressant effects of magnolol in a mouse model of depression induced by chronic corticosterone injection.

PubMed

Bai, Yongtao; Song, Lihua; Dai, Guoliang; Xu, Meijuan; Zhu, Lijing; Zhang, Weidong; Jing, Wen; Ju, Wenzheng

2018-07-01

Evidence showed that the stress hormone corticosterone (CORT) injection resulted in dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis implicated in major depressive disorder. Magnolol, main constituent identified in the barks of Magnolia officinalis, exerted antidepressant effects in a rat model of depression induced by chronic unpredictable mild stress in previous studies. However, its antidepressant-like effects and mechanisms have never been studied in depression model induced by CORT administration in rodents. This study aimed to investigate the antidepressant-like effects and possible mechanisms of magnolol in CORT-treated mice by utilizing a combination of behavioral and biochemical analysis. The depressive model was developed by subcutaneous injection of CORT for 21 days at a dose of 20 mg/kg. CORT administration formed depressive-like behaviors in mice, as indicated by increased immobility time in the forced swim test (FST) and tail suspension test (TST), as well as decreased sucrose intake in sucrose preference test (SPT). Moreover, we also found that CORT levels in serum were significantly increased, along with the decrease of brain-derived neurotrophic factor (BDNF) mRNA, BDNF protein, 5-hydroxytryptamine (5-HT) and norepinephrine (NE) levels in the hippocampus. Treatment with magnolol alleviated depressive-like behaviors, reduced the levels of CORT, and improved the levels of BDNF protein, 5-HT, and NE compared with those in CORT-treated mice. These findings indicated that magnolol possessed antidepressant effects in mice exposed to CORT, which might be partially related to modulate HPA axis, up-regulate BDNF expression and increase neurotransmitters levels in the hippocampus. Copyright © 2018 Elsevier Inc. All rights reserved.

Enhanced aggressive behaviour in a mouse model of depression.

PubMed

Yang, C R; Bai, Y Y; Ruan, C S; Zhou, H F; Liu, D; Wang, X F; Shen, L J; Zheng, H Y; Zhou, X F

2015-02-01

Depression is one of the most common chronic mental disorders, which is a leading cause of morbidity and mortality in patients. Depression often leads to offensive and defensive behaviours but the underlying mechanisms are not known. We propose that the aggressive behaviours in depression can be modelled in animal experiments. In this study, we successfully established a mouse model of depression using the chronic unpredictable mild stress (CUMS) paradigm and detected aggressive and social dominance behaviours in rodents by resident/intruder test and social dominance tube test (SDTT), respectively. The CUMS-exposed mice showed increased defensive, offensive and aggressive behaviours in the resident-intruder test. In the SDTT, these mice showed enhanced social dominance. These alterations were associated with reduced MAP-2 expression in the hippocampus while no difference in β-tubulin expression was detected. In addition, the treatment of anti-depressant fluoxetine reversed the aggressive behaviours without reducing the social dominance behaviour induced by CUMS. However, fluoxetine did effectively reverted the changes in MAP-2 expression in the hippocampus. In addition, the nonspecific tricyclic antipsychotic drug, clozapine, reversed all symptoms of CUMS-exposed mice including aggressive tendencies, impulsive violence, social dominance behaviour and MAP-2 expression in the hippocampus. The results suggests that social maladjustment such as competition and social dominance are likely related to the dopaminergic system rather than the serotonergic system and the hippocampal dendritic structure protein MAP-2. Thus, dominance can be separated from aggression. This study shows that aggression/hostility and social hierarchy/dominance are increased in the CUMS-exposed mice and thus provide an excellent model for further study in the diagnosis and the treatment of depression-associated aggression.

[Effects of Betel shisanwei ingredients pill on AC-cAMP-PKA signal transduction pathways in hippocampus and prefrontal cortex of depressive rats].

PubMed

Tong, Hai-Ying; Wu, Jisiguleng; Bai, Liang-Feng; Bao, Wu-Ye; Hu, Rilebagen; Li, Jing; Zhang, Yue

2014-05-01

To observe the effects of Mongolian pharmaceutical Betel shisanwei ingredients pill on AC-cAMP-PKA signal transduction pathways in hippocampus and prefrontal cortex of depressive rats. Sixty male Wistar rats were randomly divided into six groups according to the sugar consumption test (10 rats in each group), normal control group,model group,fluoxetine group (3.3 mg x kg(-1)) and low dose, medium dose and high dose group (0.25, 0.5, 1 g x kg(-1)) of Betel shisanwei ingredients pill. Except the normal control,the other groups were treated with the chronic unpredictable mild stress stimulation combined with lonely raising for 28 days. 10 mL x kg(-1) of drugs were given to each rat once daily,continuously for 28 days. The AC activity of the hippocampus and prefrontal cortex were determined by radiation immunity analysis (RIA), while cAMP and PKA quantity were determinated by Enzyme-linked immunosorbent (ELISA). The AC activity, cAMP and PKA quantity of hippocampus and prefrontal of mouse model of Chronic stress depression decreased significantly than those of control group (P < 0.05 or P < 0.01). However, the AC activity, cAMP and PKA quantity of rat hippocampus and prefrontal cortex in the fluoxetine group and the Mongolian pharmaceutical Betel shisanwei ingredients pill group indecreased significantly than those of model group (P < 0.01 or P < 0.05). Especially for the high dose group of Mongolian pharmaceutical Betel shisanwei ingredients pill. The AC-cAMP-PKA signal transduction pathways in hippocampus and prefrontal cortex of depression model of rats is down-regulated, whereas Mongolian pharmaceutical Betel shisanwei ingredients pill could up-regulated it to resist depression.

Sensitivity of the prefrontal GABAergic system to chronic stress in male and female mice: Relevance for sex differences in stress-related disorders.

PubMed

Shepard, Ryan; Page, Chloe E; Coutellier, Laurence

2016-09-22

Stress-induced modifications of the prefrontal cortex (PFC) are believed to contribute to the onset of mood disorders, such as depression and anxiety, which are more prevalent in women. In depression, the PFC is hypoactive; however the origin of this hypoactivity remains unclear. Possibly, stress could impact the prefrontal GABAergic inhibitory system that, as a result, impairs the functioning of downstream limbic structures controlling emotions. Preclinical evidence indicates that the female PFC is more sensitive to the effects of stress. These findings suggest that exposure to stress could lead to sex-specific alterations in prefrontal GABAergic signaling, which contribute to sex-specific abnormal functioning of limbic regions. These limbic changes could promote the onset of depressive and anxiety behaviors in a sex-specific manner, providing a possible mechanism mediating sex differences in the clinical presentation of stress-related mood disorders. We addressed this hypothesis using a mouse model of stress-induced depressive-like behaviors: the unpredictable chronic mild stress (UCMS) paradigm. We observed changes in prefrontal GABAergic signaling after exposure to UCMS most predominantly in females. Increased parvalbumin (PV) expression and decreased prefrontal neuronal activity were correlated in females with severe emotionality deficit following UCMS, and with altered activity of the amygdala. In males, small changes in emotionality following UCMS were associated with minor changes in prefrontal PV expression, and with hypoactivity of the nucleus accumbens. Our data suggest that prefrontal hypoactivity observed in stress-related mood disorders could result from stress-induced increases in PV expression, particularly in females. This increased vulnerability of the female prefrontal PV system to stress could underlie sex differences in the prevalence and symptomatology of stress-related mood disorders. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Fighting for control in an unpredictable life – a qualitative study of older persons’ experiences of living with chronic dizziness

PubMed Central

2014-01-01

Background Dizziness in older people is associated with disability and reduced quality of life. Few studies have investigated how daily life is affected from the older person’s perspective. Identifying barriers and resources in daily life could guide health care in how to direct efficient interventions. The aim of this study was to explore older persons’ experiences of living with chronic dizziness. Methods In this qualitative study seven women aged 74–84 years and six men aged 73–87 years with chronic dizziness (≥3 months) recruited from a primary health care centre in 2012 participated in semi-structured interviews. The interviews were analysed by content analysis. Results Interpretation of the interviews resulted in the overall theme “Fighting for control in an unpredictable life” with two themes. The first theme “Striving towards normality” revealed a struggle in daily life in searching for a cure or improvement and finding a way to maintain ordinary life. This process could result in feelings of resignation or adaption to daily life, and factors that supported living with chronic dizziness were described. The second theme “Having a precarious existence” revealed that daily life included being exposed to threats such as a fear of recurrent attacks or of falling, which resulted in an insecure and inflexible way of life. A feeling that symptoms were not taken seriously was described. Conclusions The present study showed that older persons with chronic dizziness have needs that are not met by health care. Despite the fact that frequent contact with health care was described, the respondents described barriers in daily life that led to a restricted, inflexible and insecure daily life. Health care should therefore be individually tailored with focus on aspects of daily life, especially safety aspects. Support should also be continued until the older persons with chronic dizziness have developed coping strategies to gain control of their daily life. PMID:25175932

Corticosteroid-treated chronic active hepatitis in remission: uncertain prognosis of chronic persistent hepatitis.

PubMed

Czaja, A J; Ludwig, J; Baggenstoss, A H; Wolf, A

1981-01-01

To assess the prognosis of patients with severe chronic hepatitis after histologic examination had shown an improvement to chronic persistent hepatitis, we followed 52 such patients regularly for 54 +/- 4 months after the cessation of corticosteroid therapy. In 24 patients, the condition deteriorated 7 +/- 1 months after therapy and required further treatment with prednisone. Histologic features of chronic active hepatitis, including bridging and multilobular necrosis, were documented in all 14 patients in whom biopsies were performed. In 20 of 24 patients, the disease responded to retreatment, but 13 again had relapses, and cirrhosis developed in two. Of 28 patients who remained asymptomatic for 48 +/- 6 months, 17 retained features of chronic persistent hepatitis, and nine had improvement to normal histologic features. Cirrhosis developed in two patients without clinical manifestations of active inflammation. Findings before and after treatment did not predict outcome. We conclude that severe chronic active hepatitis that has been treated with prednisone and converted to chronic persistent hepatitis will often and unpredictably deteriorate after treatment has been stopped. Cirrhosis develops rarely but may occur with or without clinically overt chronic active hepatitis.

Diffusion MRI and MR spectroscopy reveal microstructural and metabolic brain alterations in chronic mild stress exposed rats: A CMS recovery study.

PubMed

Khan, Ahmad Raza; Hansen, Brian; Wiborg, Ove; Kroenke, Christopher D; Jespersen, Sune Nørhøj

2018-02-15

Chronic mild stress (CMS) induced depression elicits several debilitating symptoms and causes a significant economic burden on society. High variability in the symptomatology of depression poses substantial impediment to accurate diagnosis and therapy outcome. CMS exposure induces significant metabolic and microstructural alterations in the hippocampus (HP), prefrontal cortex (PFC), caudate-putamen (CP) and amygdala (AM), however, recovery from these maladaptive changes are limited and this may provide negative effects on the therapeutic treatment and management of depression. The present study utilized anhedonic rats from the unpredictable CMS model of depression to study metabolic recovery in the ventral hippocampus (vHP) and microstructural recovery in the HP, AM, CP, and PFC. The study employed 1 H MR spectroscopy ( 1 H MRS) and in-vivo diffusion MRI (d-MRI) at the age of week 18 (week 1 post CMS exposure) week 20 (week 3 post CMS) and week 25 (week 8 post CMS exposure) in the anhedonic group, and at the age of week 18 and week 22 in the control group. The d-MRI data have provided an array of diffusion tensor metrics (FA, MD, AD, and RD), and fast kurtosis metrics (MKT, W L and W T ). CMS exposure induced a significant metabolic alteration in vHP, and significant microstructural alterations were observed in the HP, AM, and PFC in comparison to the age match control and within the anhedonic group. A significantly high level of N-acetylaspartate (NAA) was observed in vHP at the age of week 18 in comparison to age match control and week 20 and week 25 of the anhedonic group. HP and AM showed significant microstructural alterations up to the age of week 22 in the anhedonic group. PFC showed significant microstructural alterations only at the age of week 18, however, most of the metrics showed significantly higher value at the age of week 20 in the anhedonic group. The significantly increased NAA concentration may indicate impaired catabolism due to astrogliosis or oxidative stress. The significantly increased W L in the AM and HP may indicate hypertrophy of AM and reduced volume of HP. Such metabolic and microstructural alterations could be useful in disease diagnosis and follow-up treatment intervention in depression and similar disorders. Copyright © 2017 Elsevier Inc. All rights reserved.

N-Acetylcysteine Reverses Anxiety and Oxidative Damage Induced by Unpredictable Chronic Stress in Zebrafish.

PubMed

Mocelin, Ricieri; Marcon, Matheus; D'ambros, Simone; Mattos, Juliane; Sachett, Adrieli; Siebel, Anna M; Herrmann, Ana P; Piato, Angelo

2018-06-06

There is accumulating evidence on the use of N-acetylcysteine (NAC) in the treatment of patients with neuropsychiatric disorders. As a multi-target drug and a glutathione precursor, NAC is a promising molecule in the management of stress-related disorders, for which there is an expanding field of research investigating novel therapies targeting oxidative pathways. The deleterious effects of chronic stress in the central nervous system are a result of glutamatergic hyperactivation, glutathione (GSH) depletion, oxidative stress, and increased inflammatory response, among others. The aim of this study was to investigate the effects of NAC in zebrafish submitted to unpredictable chronic stress (UCS). Animals were initially stressed or not for 7 days, followed by treatment with NAC (1 mg/L, 10 min) or vehicle for 7 days. UCS decreased the number of entries and time spent in the top area in the novel tank test, which indicate increased anxiety levels. It also increased reactive oxygen species (ROS) levels and lipid peroxidation (TBARS) while decreased non-protein thiols (NPSH) and superoxide dismutase (SOD) activity. NAC reversed the anxiety-like behavior and oxidative damage observed in stressed animals. Additional studies are needed to investigate the effects of this agent on glutamatergic modulation and inflammatory markers related to stress. Nevertheless, our study adds to the existing body of evidence supporting the clinical evaluation of NAC in mood disorders, anxiety, post-traumatic stress disorder, and other conditions associated with stress.

Effect of chronic unpredictable stress on short term dietary restriction and its modulation by multivitamin-mineral supplementation.

PubMed

Hasan, Shirin; Fatima, Naureen; Bilal, Nayeem; Suhail, Nida; Fatima, Sabiha; Morgan, Enas N; Aldebasy, Yousef; Alzohairy, Mohammad A; Banu, Naheed

2013-06-01

Dietary restriction (DR) lowers steady-state levels of oxidative stress and alters behavioral, physiological and biochemical responses in mammals. However, various factors effect its application in humans like socio-cultural, appetite and the daily life stress. Physiological and psychological stress owing to fast-paced lifestyles, translates into oxidative stress. In this work, the role of chronic unpredictable stress (CUS) on the effects of short term DR in mice in terms of biochemical and oxidative stress parameters was investigated. Further, the modulatory role of multivitamin-mineral supplement (MVM) on CUS and DR induced biochemical changes was studied to delineate the role of micronutrient supplementation. DR treatment increased the antioxidant status in the circulation and liver of mice but in the presence of chronic stressors there was a significant shift towards the pro-oxidant state. A decrease was found in the activities of antioxidant enzymes superoxide dismutase, catalase, and glutathione-S-transferase and glutathione reductase in the rats exposed to CUS with DR (CUS+DR), with an increased malondialdehyde and a decreased glutathione (GSH) levels as compared to the controls. Liver function enzymes-glutamate oxaloacetate transaminase and glutamate pyruvate transaminase were increased and a significant DNA damage was observed. Oral MVM supplement significantly improved this oxidative deterioration. Hence, MVM supplementation appears to potentially offer an effective intervention in the DR regimen to combat daily life physical and mental stress. Copyright © 2013 Elsevier Ltd. All rights reserved.

[Chronic pancreatitis: which is the role of 320-row CT for the staging?].

PubMed

Stabile Ianora, Amato Antonio; Rubini, Giuseppe; Lorusso, Filomenamila; Ambriola, Angela; Rella, Leonarda; Di Crescenzo, Vincenzo; Moschetta, Marco

2013-01-01

The purpose of this study was to evaluate the diagnostic potential of multi-planar and volumetric reconstructions obtained from isotropic data by using 16-slice computed tomography (CT) in the diagnosis and staging of chronic pancreatitis. In a group of 42 patients CT images were evaluated searching for alterations in morphology and structure of the pancreas, alterations of the Wirsung duct, dilatation of the bile ducts, fluid collections, and vascular involvement of the digestive tract. The disease was then staged in mild, moderate and severe and correlated with the clinical staging. CT allowed the recognition of chronic pancreatitis in all cases. The staging was correct in 25/42 patients, with an accuracy rate of 59.5%. In the staging of moderate and severe forms, CT correlation with clinical and laboratory data was valid, but in mild forms it appeared less significant. Multi-detector CT is accurate in the recognition of moderate, advanced forms of chronic pancreatitis and in the identification of its complications, while it is poorly correlated with the clinical staging in mild forms of the disease.

Sub-anesthetic doses of ketamine exert antidepressant-like effects and upregulate the expression of glutamate transporters in the hippocampus of rats.

PubMed

Zhu, Xianlin; Ye, Gang; Wang, Zaiping; Luo, Jie; Hao, Xuechao

2017-02-03

Clinical studies on the role of the glutamatergic system in the pathogenesis of depression found that ketamine induces an antidepressant response, but the molecular mechanisms remain unclear. The present study investigated the effects of sub-anesthetic doses of ketamine on the glutamate reuptake function in the rat hippocampus. Chronic unpredictable mild stress (CUMS) was applied to construct animal models of depression. Sixty adult male Sprague-Dawley rats were randomly assigned to 5 groups and received a different regimen of CUMS and ketamine (10, 25, and 50mg/kg) treatment. The sucrose preference test and open-field test were used to assess behavioral changes. The expression levels of excitatory amino acid transporters (EAATs) were measured by western blot. Microdialysis and high-performance liquid chromatography (HPLC) were used to detect hippocampal glutamate concentrations. We found that the expression of EAAT2 and EAAT3 were obviously downregulated, and extracellular concentrations of glutamate were significantly increased in the hippocampi of depressive-like rats. Ketamine (10, 25, and 50mg/kg) upregulated the expression of EAAT2 and EAAT3, decreased the hippocampal concentration of extracellular glutamate, and alleviated the rats' depressive-like behavior. The antidepressant effect of ketamine may be linked to the regulation of EAAT expression and the enhancement of glutamate uptake in the hippocampus of depressive-like rats. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

An investigation of the antidepressant action of xiaoyaosan in rats using ultra performance liquid chromatography-mass spectrometry combined with metabonomics.

PubMed

Gao, Xiao-Xia; Cui, Jie; Zheng, Xing-Yu; Li, Zhen-Yu; Choi, Young-Hae; Zhou, Yu-Zhi; Tian, Jun-Sheng; Xing, Jie; Tan, Xiao-Jie; Du, Guan-Hua; Qin, Xue-Mei

2013-07-01

A rapid, highly sensitive, and selective method was applied in a non-invasive way to investigate the antidepressant action of Xiaoyaosan (XYS) using ultra performance liquid chromatography-mass spectrometry (UPLC-MS) and chemometrics. Many significantly altered metabolites were used to explain the mechanism. Venlafaxine HCl and fluoxetine HCl were used as chemical positive control drugs with a relatively clear mechanism of action to evaluate the efficiency and to predict the mechanism of action of XYS. Urine obtained from rats subjected to chronic unpredictable mild stress (CUMS) was analyzed by UPLC-MS. Distinct changes in the pattern of metabolites in the rat urine after CUMS production and drug intervention were observed using partial least squares-discriminant analysis. The results of behavioral tests and multivariate analysis showed that CUMS was successfully reproduced, and a moderate-dose XYS produced significant therapeutic effects in the rodent model, equivalent to those of the positive control drugs, venlafaxine HCl and fluoxetine HCl. Metabolites with significant changes induced by CUMS were identified, and 17 biomarker candidates for stress and drug intervention were identified. The therapeutic effect of XYS on depression may involve regulation of the dysfunctions of energy metabolism, amino acid metabolism, and gut microflora changes. Metabonomic methods are valuable tools for measuring efficacy and mechanisms of action in the study of traditional Chinese medicines. Copyright © 2012 John Wiley & Sons, Ltd.

The antidepressant-like effect of Ocimum basilicum in an animal model of depression.

PubMed

Ali, S S; Abd El Wahab, M G; Ayuob, N N; Suliaman, M

2017-01-01

We investigated the efficacy of Ocimum basilicum (OB) essential oils for treating depression related behavioral, biochemical and histopathological changes caused by exposure to chronic unpredictable mild stress (CUMS) in mice and to explore the mechanism underlying the pathology. Male albino mice were divided into four groups: controls; CUMS; CUMS plus fluoxetine, the antidepressant administered for pharmacological validation of OB; and CUMS plus OB. Behavioral tests included the forced swim test (FST), elevated plus-maze (EPM) and the open field test (OFT); these tests were performed at the end of the experiment. We assessed serum corticosterone level, protein, gene and immunoexpression of brain-derived neurotropic factor (BDNF) and glucocorticoid receptors (GRs) as well as immunoexpression of glial fibrillary acidic protein (GFAP), Ki67, caspase-3 in the hippocampus. CUMS caused depression in the mice as evidenced by prolonged immobility in the FST, prolonged time spent in the open arms during the EPM test and reduction of open field activity in the OFT. OB ameliorated the CUMS induced depressive status. OB significantly reduced the corticosterone level and up-regulated protein and gene expressions of BDNF and GR. OB reduced CUMS induced hippocampal neuron atrophy and apoptosis, and increased the number of the astrocytes and new nerve cells. OB significantly increased GFAP-positive cells as well as BDNF and GR immunoexpression in the hippocampus.

Impact of repeated asenapine treatment on FosB/ΔFosB expression in neurons of the rat central nucleus of the amygdala: colocalization with corticoliberine (CRH) and effect of an unpredictable mild stress preconditioning.

PubMed

Majercikova, Z; Kiss, A

2015-04-01

FosB/ΔFosB expression in the central amygdalar nucleus (CeA) in response to repeated asenapine (ASE) treatment (an atypical antipsychotic used for the treatment of schizophrenia) was studied in normal rats and rats preconditioned with chronic unpredictable variable mild stress (CMS). The goal of this study was to reveal whether repeated ASE treatment for 14 days may: 1) induce FosB/ΔFosB expression in the amygdala, 2) activate CRH-synthesizing neurons in the CeA, and 3) interfere with 21 days lasting concomitant CMS preconditioning. Four groups of animals were studied: controls and ASE-, CMS-, and CMS+ASE-treated ones. CMS consisted of the restrain, social isolation, crowding, swimming, and cold and lasted 21 days. The ASE and CMS+ASE groups were from the 7th day of the experiment treated with ASE (0.3 mg/kg, subcutaneously - s.c.) twice a day, i.e. together for 14 days. Controls and CMS groups were treated with saline (300 µl/rat, s.c.) twice a day for 14 days. All the animals were sacrificed on the 22nd day, i.e. 16-18 hours after the last treatments. Single FosB/ΔFosB, FosB/ΔFosB colocalizations with CRH, and CRH immunolabeled perikarya were investigated in the CeA using a combined light and fluorescent immunohistochemistry. The distribution aspect of the black FosB/ΔFosB profiles was homogeneous over the whole CeA and no significant differences in the number of FosB/ΔFosB profiles between the individual groups of the rats really occurred. The level of colocalization pattern of FosB/ΔFosB in CRH perikarya was also very similar between the individual groups and in each case it reached approximately 10% of double-labeling. No differences were also seen in the number of CRH immunolabeled perikarya. The density of CRH nerve projections within the CeA was very alike in the individual groups of animals investigated. The study provides a new anatomical/functional finding about the lack of the stimulatory effect of the repeated ASE treatment on the expression of FosB/ΔFosB, FosB/ΔFosB/CRH colocalizations, and CRH immunolabeled perikarya number in the CeA. In addition, CMS preconditioning itself neither stimulated nor inhibited FosB/ΔFosB expression, nor altered the impact of ASE on the activity of CRH neurons in the CeA.

Electrophysiological Biomarkers of Chemotherapy-related Cognitive Impairment and Recovery

ClinicalTrials.gov

2017-05-01

Myelodysplastic Syndrome; Effects of Chemotherapy; Mild Cognitive Impairment; Multiple Myeloma; Non-hodgkin Lymphoma; Chronic Lymphocytic Leukemia; Acute Lymphoid Leukemia; Chronic Myeloid Leukemia; Acute Myeloid Leukemia

Developmental Exposure to Mild Variable Stress: Adult ...

EPA Pesticide Factsheets

In utero exposure to mild variable stress has been reported to influence learning and memory formation in offspring. Our research aims to examine whether nonchemical environmental stressors will exacerbate effects to chemical exposure. This study utilized a varying stress paradigm to simulate human psychosocial stress incurred during and after pregnancy to identify phenotypic learning changes in adult offspring that are potential stress markers. We additionally wanted to compare these behavioral outcomes to rat performance induced by perinatal exposure to manganese (Mn), a neurotoxic environmental element, at 2 or 5 g/l in drinking water throughout gestation and lactation. Pregnant Long Evans rats were exposed to an unpredictable series of mild stressful events which had previously been shown to increase maternal corticosterone levels. Nonchemical stressors were presented from GD 13 through GD 21 and included varying noise, light, housing, and confinement during both sleep and wake cycles. A subgroup of offspring was also exposed to periods of maternal separation. Starting at PND 97 offspring were trained with a trace fear conditioning protocol whereby rats were exposed to a compound cue (light and tone) followed by 30 seconds (trace period) and a mild foot shock (1mA, 0.5 seconds). Five paired training sessions occurred on the first day. The following day, context and cue learning were assessed by measuring motor activity. Preliminary data suggests adu

Effectiveness of a partnership-based self-management programme for patients with mild and moderate chronic obstructive pulmonary disease: a pragmatic randomized controlled trial.

PubMed

Jonsdottir, Helga; Amundadottir, Olof R; Gudmundsson, Gunnar; Halldorsdottir, Bryndis S; Hrafnkelsson, Birgir; Ingadottir, Thorbjorg Soley; Jonsdottir, Rosa; Jonsson, Jon Steinar; Sigurjonsdottir, Ellen D; Stefansdottir, Ingibjorg K

2015-11-01

To evaluate the effectiveness of a 6-month, partnership-based self-management programme for patients with mild and moderate chronic obstructive pulmonary disease. Self-management is a widely valued concept used to address contemporary issues of chronic health problems. Findings of self-management programmes for people with chronic obstructive pulmonary disease are inconclusive. Pragmatic randomized control trial. Patients, 45-65 years old, with mild and moderate chronic obstructive pulmonary disease were invited with a family member. Experimental group (n = 48) participated in a 6-month, partnership-based self-management programme consisting of: (a) three to four conversations between nurse and patient-family member; (b) 6 months of smoking cessation; and (c) interdisciplinary team-patient-family member group meeting. Control group (n = 52) received usual care. Data were collected at months zero, six and 12. The trial lasted from June 2009-March 2013. Patients with mild and moderate chronic obstructive pulmonary disease who participated in the partnership-based self-management programme perceived less intrusiveness of the disease and its treatment than patients in the control group. Patients in the experimental group did not have better health-related quality of life, less anxiety or depression, increased physical activity, fewer exacerbations or better smoking status than patients in the control group. Patients in both groups found participation in the research useful and important. The partnership-based self-management programme had benefits concerning perception of the intrusiveness of chronic obstructive pulmonary disease and its treatment on lifestyles, activities and interests for young patients with the disease in its early stages. High satisfaction in control group, low family attendance and the relatively short treatment period may explain the less than expected benefits of the programme. © 2015 John Wiley & Sons Ltd.

Salivary Levels of IL-6 and IL-17 Could Be an Indicator of Disease Severity in Patients with Calculus Associated Chronic Periodontitis

PubMed Central

Batool, Husniah; Nadeem, Ahmed; Tahir, Romeeza

2018-01-01

Background/Purpose. Chronic periodontitis is an inflammatory disease of gums that causes loss of supporting structures of teeth, that is, gingiva, periodontal ligament, cementum, and alveolar bone. Levels of various cytokines in the serum, gingival tissues, and gingival crevicular fluid in patients with chronic periodontitis have been studied, but limited data are available on the level of cytokines in saliva. Therefore, a study was designed to determine levels of salivary IL-6 and IL-17 in patients with calculus associated chronic periodontitis. Materials and Methods. It was a comparative, cross-sectional study that is comprised of 41 healthy controls and 41 calculus associated chronic periodontitis patients (CP patients). According to the degree of attachment loss, CP patients were subcategorized as mild (CAL 1-2 mm), moderate (CAL 3-4 mm), and severe (CAL > 5 mm) forms of periodontitis. Salivary levels of IL-6 and IL-17 were determined using enzyme-linked immunosorbent assay (ELISA) technique. Data was analyzed using SPSS 20.0. Results. Between healthy controls and CP patients (moderate and severe disease), a statistically significant difference was observed in the concentrations of IL-6 and IL-17. In CP patients, the highest mean ± SD of salivary IL-6 and IL-17 was observed in severe CP, followed by moderate and mild CP. Regarding level of IL-6, a statistically significant difference was observed between mild and severe disease and between moderate and severe subcategories of CP patients. Similarly, statistically significant difference was observed in the level of IL-17 between mild and moderate, mild and severe disease, and moderate and severe disease. Conclusion. The levels of salivary IL-6 and IL-17 were increased significantly in calculus associated CP patients as compared to healthy controls and these levels increased with the progression of CP. Clinical Significance. Salivary levels of IL-6 and IL-17 may help in the subcategorization of CP. PMID:29670909

Chronic Lung Allograft Dysfunction: A Systematic Review of Mechanisms.

PubMed

Royer, Pierre-Joseph; Olivera-Botello, Gustavo; Koutsokera, Angela; Aubert, John-David; Bernasconi, Eric; Tissot, Adrien; Pison, Christophe; Nicod, Laurent; Boissel, Jean-Pierre; Magnan, Antoine

2016-09-01

Chronic lung allograft dysfunction (CLAD) is the major limitation of long-term survival after lung transplantation. Chronic lung allograft dysfunction manifests as bronchiolitis obliterans syndrome or the recently described restrictive allograft syndrome. Although numerous risk factors have been identified so far, the physiopathological mechanisms of CLAD remain poorly understood. We investigate here the immune mechanisms involved in the development of CLAD after lung transplantation. We explore the innate or adaptive immune reactions induced by the allograft itself or by the environment and how they lead to allograft dysfunction. Because current literature suggests bronchiolitis obliterans syndrome and restrictive allograft syndrome as 2 distinct entities, we focus on the specific factors behind one or the other syndromes. Chronic lung allograft dysfunction is a multifactorial disease that remains irreversible and unpredictable so far. We thus finally discuss the potential of systems-biology approach to predict its occurrence and to better understand its underlying mechanisms.

Sports-related brain injuries: connecting pathology to diagnosis.

PubMed

Pan, James; Connolly, Ian D; Dangelmajer, Sean; Kintzing, James; Ho, Allen L; Grant, Gerald

2016-04-01

Brain injuries are becoming increasingly common in athletes and represent an important diagnostic challenge. Early detection and management of brain injuries in sports are of utmost importance in preventing chronic neurological and psychiatric decline. These types of injuries incurred during sports are referred to as mild traumatic brain injuries, which represent a heterogeneous spectrum of disease. The most dramatic manifestation of chronic mild traumatic brain injuries is termed chronic traumatic encephalopathy, which is associated with profound neuropsychiatric deficits. Because chronic traumatic encephalopathy can only be diagnosed by postmortem examination, new diagnostic methodologies are needed for early detection and amelioration of disease burden. This review examines the pathology driving changes in athletes participating in high-impact sports and how this understanding can lead to innovations in neuroimaging and biomarker discovery.

Timing matters: the interval between acute stressors within chronic mild stress modifies behavioral and physiologic stress responses in male rats.

PubMed

Cavigelli, Sonia A; Bao, Alexander D; Bourne, Rebecca A; Caruso, Michael J; Caulfield, Jasmine I; Chen, Mary; Smyth, Joshua M

2018-04-12

Chronic mild stress can lead to negative health outcomes. Frequency, duration, and intensity of acute stressors can affect health-related processes. We tested whether the temporal pattern of daily acute stressors (clustered or dispersed across the day) affects depression-related physiology. We used a rodent model to keep stressor frequency, duration, and intensity constant, and experimentally manipulated the temporal pattern of acute stressors delivered during the active phase of the day. Adult male Sprague-Dawley rats were exposed to one of three chronic mild stress groups: Clustered: stressors that occurred within 1 hour of each other (n = 21), Dispersed: stressors that were spread out across the active phase (n = 21), and Control: no stressors presented (n = 21). Acute mild stressors included noise, strobe lights, novel cage, cage tilt, wet bedding, and water immersion. Depression-related outcomes included: sucrose preference, body weight, circulating glucocorticoid (corticosterone) concentration after a novel acute stressor and during basal morning and evening times, and endotoxin-induced circulating interleukin-6 concentrations. Compared to control rats, those in the Clustered group gained less weight, consumed less sucrose, had a blunted acute corticosterone response, and an accentuated acute interleukin-6 response. Rats in the Dispersed group had an attenuated corticosterone decline during the active period and after an acute stressor compared to the Control group. During a chronic mild stress experience, the temporal distribution of daily acute stressors affected health-related physiologic processes. Regular exposure to daily stressors in rapid succession may predict more depression-related symptoms, whereas exposure to stressors dispersed throughout the day may predict diminished glucocorticoid negative feedback.

Prevalence of pulmonary artery hypertension in patients of chronic obstructive pulmonary disease and its correlation with stages of chronic obstructive pulmonary disease, exercising capacity, and quality of life.

PubMed

Gupta, Kamlesh Kumar; Roy, Bidyut; Chaudhary, Shyam Chand; Mishra, Arvind; Patel, M L; Singh, Jitendra; Kumar, Vivek

2018-01-01

Pulmonary arterial hypertension (PAH) is a complication of chronic obstructive pulmonary disease (COPD) in advance stages, and its presence indicates poor prognosis. The present study was design to know the prevalence of PAH in patients with COPD and its correlation with stages of COPD, exercising capacity, and quality of life. It is a cross-sectional prevalence study over a period of 1 year from August 2015 to July 2016. The study included 109 COPD patients, diagnosed by spirometry, and severity was determined according Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification criteria. Screening two-dimensional echocardiography was done to determine pulmonary arterial hypertension and exercising capacity assessed by 6 min walk test (6MWT) while the quality of life was assessed by St George respiratory Questionnaire for COPD (SGRQ-C) Questionnaires. Out of 109 patients, PAH was present in 68 (62.4%) cases consisting of mild grade 41 (37.6%), moderate grade 11 (10.1%), and severe grade 16 (14.7%). In GOLD A stage, there were 20 cases of mild PAH and Stage B included 18 cases of mild and 3 cases of moderate PAH. Stage C had 3 cases of mild and 8 cases of moderate PAH while Stage D had 16 cases of severe PAH. In 6MWT, patients with severe grade PAH fail to perform the test while patients with mild to moderate PAH walked short distance. In SGRQ-C Questionnaires symptom, activity, impact, and total score were high with the severity of PAH. The prevalence of PAH in COPD was significant. Therefore, every COPD patient should be evaluated for PAH.

Prevalence of pulmonary artery hypertension in patients of chronic obstructive pulmonary disease and its correlation with stages of chronic obstructive pulmonary disease, exercising capacity, and quality of life

PubMed Central

Gupta, Kamlesh Kumar; Roy, Bidyut; Chaudhary, Shyam Chand; Mishra, Arvind; Patel, M. L.; Singh, Jitendra; Kumar, Vivek

2018-01-01

Background: Pulmonary arterial hypertension (PAH) is a complication of chronic obstructive pulmonary disease (COPD) in advance stages, and its presence indicates poor prognosis. Aims and Objective: The present study was design to know the prevalence of PAH in patients with COPD and its correlation with stages of COPD, exercising capacity, and quality of life. Materials and Methods: It is a cross-sectional prevalence study over a period of 1 year from August 2015 to July 2016. The study included 109 COPD patients, diagnosed by spirometry, and severity was determined according Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification criteria. Screening two-dimensional echocardiography was done to determine pulmonary arterial hypertension and exercising capacity assessed by 6 min walk test (6MWT) while the quality of life was assessed by St George respiratory Questionnaire for COPD (SGRQ-C) Questionnaires. Results: Out of 109 patients, PAH was present in 68 (62.4%) cases consisting of mild grade 41 (37.6%), moderate grade 11 (10.1%), and severe grade 16 (14.7%). In GOLD A stage, there were 20 cases of mild PAH and Stage B included 18 cases of mild and 3 cases of moderate PAH. Stage C had 3 cases of mild and 8 cases of moderate PAH while Stage D had 16 cases of severe PAH. In 6MWT, patients with severe grade PAH fail to perform the test while patients with mild to moderate PAH walked short distance. In SGRQ-C Questionnaires symptom, activity, impact, and total score were high with the severity of PAH. Conclusion: The prevalence of PAH in COPD was significant. Therefore, every COPD patient should be evaluated for PAH. PMID:29915733

[Correlation of matrix metalloproteinase-9 polymorphisms with chronic periodontitis in Uygur adults].

PubMed

Ma, T; Li, D D; Huang, P; Zhao, J

2017-06-09

Objective: To investigate the association between matrix metalloproteinase-9 (MMP-9) polymorphisms and chronic periodontitis in Uygur adults. Methods: A total of 196 patients with chronic periodontitis and 97 healthy controls were selected from 2 500 Uygur people. Buccal swab samples were taken, the genomic DNA was extracted and the genotype distribution and allele frequency of MMP-9 were determined by PCR-restriction fragment length polymorphism (PCR-RFLP). The distribution of genotypes, allele frequencies and risk factors were analyzed by chi-square test and multiple logistic regression. Results: Significant difference was found between healthy controls and the mild periodontitis and moderate to severe periodontitis in the MMP-9 1562C/T CC genotype expression (χ(2)=9.901, P= 0.002; χ(2)=13.397, P< 0.001), and detectable rate of MMP-9 1562C/T CC genotype in the three groups was 31.3%(30/96), 53.5% (53/99), 27.8%(27/97), respectively. The detectable rate of CT genotype expression in the three groups were 65.6% (63/96), 45.5% (45/99), 69.1% (67/97) respectively and there was significant difference between healthy controls and mild periodontitis and between the mild periodontitis and moderate to severe periodontitis (χ(2)=8.025, P= 0.005; χ(2)=11.159, P< 0.001). There was also significant difference in allele frequency between healthy controls and mild periodontitis and between mild periodontitis and moderate to severe periodontitis (χ(2)=6.270, P= 0.012; χ(2)=8.184, P= 0.004). Logistic analysis showed that age under 35 years old was the protective factor of chronic periodontitis ( OR= 0.061, 95% CI =0.035-0.108, P< 0.001) while the male and CT genotype were the risk factors of chronic periodontitis ( OR= 2.392, 95% CI =1.496-3.819, P< 0.001; OR= 1.280, 95% CI =0.794-2.067, P= 0.031). Conclusions: The susceptibility to chronic periodontitis in Uygur adults in Moyu county of Xinjiang is related to the age and gender and polymorphism of MMP-9. The age over 35 years old, male and CT genotype may be the risk factors of chronic periodontitis in Uygur adults.

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

PubMed

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.

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

PubMed Central

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. PMID:26580066

Chronic Stress and Posttraumatic Stress Disorders.

ERIC Educational Resources Information Center

Davidson, Laura M.; Baum, Andrew

1986-01-01

Examined the relationship between chronic stress and symptoms of posttraumatic stress syndrome in people living within five miles of the Three Mile Island (TMI) nuclear power station. Results provided evidence of substantive links between chronic stress and development of mild symptoms of posttraumatic stress disorder. (Author/BL)

Muscle magnetic resonance imaging sensitivity does not decrease in chronic, mild, or proximal lower limb neuropathies.

PubMed

Deroide, Nicolas; Bousson, Valérie; Daguet, Edouard; Dumurgier, Julien; Tin, Sophie Ng Wing; Hannouche, Didier; Richette, Pascal; Beaudreuil, Johann; Lioté, Frédéric; Lévy, Bernard; Vicaut, Eric; Laredo, Jean Denis; Kubis, Nathalie

2012-05-01

Muscle magnetic resonance imaging (MRI) is an innovative tool for exploring focal neuropathies. However, its usefulness in mild, proximal, or chronic lesions, when electromyography (EMG), the current "gold standard" sensitivity is inadequate, has yet to be studied. Clinical, MRI, and EMG examinations were performed in 113 muscles of 17 consecutive patients with clinically diagnosed lower limb focal neuropathies. The sensitivity and specificity of MRI and EMG were evaluated in relation to disease duration, severity, and anatomical location. Muscle MRI was highly sensitive for the detection of denervated muscle, and, unlike EMG, its sensitivity did not decrease regardless of the anatomical location, duration, or severity of the neuropathy. Five MRI false positives were noted, including three in the thigh muscles. Muscle MRI is an alternative tool to EMG in proximal, mild, or chronic clinical diagnoses of lower limb focal neuropathies. However, it also seems prone to false-positive results, particularly in proximal muscles. Copyright © 2012 Wiley Periodicals, Inc.

Chiropractic chronic low back pain sufferers and self-report assessment methods. Part II. A reliability study of the Middlesex Hospital Questionnaire and the VAS Disability Scales Questionnaire.

PubMed

Leboeuf, C; Love, A; Crisp, T C

1989-04-01

The subjective complaints of 41 chronic low back pain sufferers attending a chiropractic clinic were assessed twice prior to therapy with a widely used psychological self-report assessment tool, the Middlesex Hospital Questionnaire (MHQ) and a newly developed VAS Disability Scales Questionnaire (DISQ), both of which investigate various aspects of certain basic positions and activities. Reliability was generally acceptable with these two questionnaires. Subjects participating in the study were commonly found to score within the normal range on the MHQ, indicating that psychological disturbance was not a major feature of their presentation. However, mild mood disturbance was commonly reported, and a more sensitive tool may need to be developed for this type of mildly affected chronic low back pain sufferers. The DISQ generally indicated subjects were mildly to moderately affected by their low back trouble and that sitting and leisure activities were the most pain provoking. Recommendations for further development of the disability scale are made.

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

PubMed

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.

Modulation of the tissue reninangiotensin-aldosterone system in dogs with chronic mild regurgitation through the mitral valve.

PubMed

Fujii, Yoko; Orito, Kensuke; Muto, Makoto; Wakao, Yoshito

2007-10-01

To investigate whether the tissue and plasma renin-angiotensin-aldosterone system (RAAS) is activated in dogs with mild regurgitation through the mitral valve and determine the contribution of chymase and angiotensin-converting enzyme (ACE) to the activation of the RAAS and potential production of angiotensin II during the chronic stage of mild mitral valve regurgitation. 5 Beagles with experimentally induced mild mitral valve regurgitation and 6 clinically normal (control) Beagles. Tissue ACE and chymase-like activities and plasma RAAS were measured and the RAAS evaluated approximately 1,000 days after experimental induction of mitral valve regurgitation in the 5 dogs. Dogs with experimentally induced mitral valve regurgitation did not have clinical signs of the condition, although echocardiography revealed substantial eccentric hyper- trophy. On the basis of these findings, dogs with mitral valve regurgitation were classified as International Small Animal Cardiac Health Council class Ib. Plasma activity of renin and plasma concentrations of angiotensin I, angiotensin II, and aldosterone were not significantly different between dogs with mitral valve regurgitation and clinically normal dogs. Tissue ACE activity was significantly increased and chymase-like activity significantly decreased in dogs with mitral valve regurgitation, compared with values in clinically normal dogs. The tissue RAAS was modulated without changes in the plasma RAAS in dogs with mild mitral valve regurgitation during the chronic stage of the condition. An ACE-dependent pathway may be a major route for production of angiotensin II during this stage of the condition.

Women in chronic pain: sense of control and encounters with health professionals.

PubMed

Skuladottir, Hafdis; Halldorsdottir, Sigridur

2008-07-01

An evolving theory on "women's sense of control while in chronic pain and the results of the quality of their encounters with health professionals" is introduced in this article. According to the theory, the main challenge of women in chronic pain is to maintain a sense of control of self and the pain to avoid demoralization, which is seen as a potential threat for all women in chronic pain. To retain a sense of control, women are challenged to learn to live with the pain and cope with the unpredictability and incurability of the pain. They are challenged to find meaning in their suffering, to create personal space, and to be self-protective as well as to keep a positive self-image and self-esteem while trying to live a "normal" life in dignity in spite of the pain and warding off isolation and demoralization. Health professionals are seen as potentially powerful people in the lives of women in chronic pain. Empowerment or disempowerment from them greatly influences whether women in chronic pain are demoralized or not.

Mild Traumatic Brain Injury Chronically Impairs Sleep- and Wake-Dependent Emotional Processing.

PubMed

Mantua, Janna; Henry, Owen S; Garskovas, Nolan F; Spencer, Rebecca M C

2017-06-01

A single traumatic brain injury (TBI), even when mild (ie, concussion), can cause lasting consequences. Individuals with a history of chronic (>1-year prior) mild TBI have an increased risk of mood disturbances (eg, depression, suicide). This population also has lingering sleep alterations, including poor sleep quality and changes in sleep stage proportions. Given these sleep deficits, we aimed to test whether sleep-dependent emotional memory consolidation is reduced in this population. We utilized a mild TBI group (3.7 ± 2.9 years post injury) and an uninjured (non-TBI) population. Participants viewed negative and neutral images both before and after a 12-hour period containing sleep ("Sleep" group) or an equivalent period of time spent awake ("Wake" group). Participants rated images for valence/arousal at both sessions, and memory recognition was tested at session two. The TBI group had less rapid eye movement (REM), longer REM latency, and more sleep complaints. Sleep-dependent memory consolidation of nonemotional images was present in all participants. However, consolidation of negative images was only present in the non-TBI group. A lack of differentiation between the TBI Sleep and Wake groups was due to poor performance in the sleep group and, unexpectedly, enhanced performance in the wake group. Additionally, although the non-TBI participants habituated to negative images over a waking period, the TBI participants did not. We propose disrupted sleep- and wake-dependent emotional processing contributes to poor emotional outcomes following chronic, mild TBI. This work has broad implications, as roughly one-third of the US population will sustain a mild TBI during their lifetime. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

Mild Traumatic Brain Injury Chronically Impairs Sleep- and Wake-Dependent Emotional Processing

PubMed Central

Mantua, Janna; Henry, Owen S.; Garskovas, Nolan F.

2017-01-01

Abstract Study Objectives: A single traumatic brain injury (TBI), even when mild (ie, concussion), can cause lasting consequences. Individuals with a history of chronic (>1-year prior) mild TBI have an increased risk of mood disturbances (eg, depression, suicide). This population also has lingering sleep alterations, including poor sleep quality and changes in sleep stage proportions. Given these sleep deficits, we aimed to test whether sleep-dependent emotional memory consolidation is reduced in this population. We utilized a mild TBI group (3.7 ± 2.9 years post injury) and an uninjured (non-TBI) population. Methods: Participants viewed negative and neutral images both before and after a 12-hour period containing sleep (“Sleep” group) or an equivalent period of time spent awake (“Wake” group). Participants rated images for valence/arousal at both sessions, and memory recognition was tested at session two. Results: The TBI group had less rapid eye movement (REM), longer REM latency, and more sleep complaints. Sleep-dependent memory consolidation of nonemotional images was present in all participants. However, consolidation of negative images was only present in the non-TBI group. A lack of differentiation between the TBI Sleep and Wake groups was due to poor performance in the sleep group and, unexpectedly, enhanced performance in the wake group. Additionally, although the non-TBI participants habituated to negative images over a waking period, the TBI participants did not. Conclusions: We propose disrupted sleep- and wake-dependent emotional processing contributes to poor emotional outcomes following chronic, mild TBI. This work has broad implications, as roughly one-third of the US population will sustain a mild TBI during their lifetime. PMID:28460124

5-HT1A/1B Receptors as Targets for Optimizing Pigmentary Responses in C57BL/6 Mouse Skin to Stress

PubMed Central

Wu, Hua-Li; Pang, Si-Lin; Liu, Qiong-Zhen; Wang, Qian; Cai, Min-Xuan; Shang, Jing

2014-01-01

Stress has been reported to induce alterations of skin pigmentary response. Acute stress is associated with increased turnover of serotonin (5-hydroxytryptamine; 5-HT) whereas chronic stress causes a decrease. 5-HT receptors have been detected in pigment cells, indicating their role in skin pigmentation. To ascertain the precise role of 5-HT in stress-induced pigmentary responses, C57BL/6 mice were subjected to chronic restraint stress and chronic unpredictable mild stress (CRS and CUMS, two models of chronic stress) for 21 days, finally resulting in abnormal pigmentary responses. Subsequently, stressed mice were characterized by the absence of a black pigment in dorsal coat. The down-regulation of tyrosinase (TYR) and tyrosinase-related proteins (TRP1 and TRP2) expression in stressed skin was accompanied by reduced levels of 5-HT and decreased expression of 5-HT receptor (5-HTR) system. In both murine B16F10 melanoma cells and normal human melanocytes (NHMCs), 5-HT had a stimulatory effect on melanin production, dendricity and migration. When treated with 5-HT in cultured hair follicles (HFs), the increased expression of melanogenesis-related genes and the activation of 5-HT1A, 1B and 7 receptors also occurred. The serum obtained from stressed mice showed significantly decreased tyrosinase activity in NHMCs compared to that from nonstressed mice. The decrease in tyrosinase activity was further augmented in the presence of 5-HTR1A, 1B and 7 antagonists, WAY100635, SB216641 and SB269970. In vivo, stressed mice received 5-HT precursor 5-hydroxy-l-tryptophan (5-HTP), a member of the class of selective serotonin reuptake inhibitors (fluoxetine; FX) and 5-HTR1A/1B agonists (8-OH-DPAT/CP94253), finally contributing to the normalization of pigmentary responses. Taken together, these data strongly suggest that the serotoninergic system plays an important role in the regulation of stress-induced depigmentation, which can be mediated by 5-HT1A/1B receptors. 5-HT and 5-HTR1A/1B may constitute novel targets for therapy of skin hypopigmentation disorders, especially those worsened with stress. PMID:24586946

Self-esteem of young adults with chronic health conditions: appraising the effects of perceived impact.

PubMed

Ireys, H T; Gross, S S; Werthamer-Larsson, L A; Kolodner, K B

1994-12-01

The relationships between selected condition characteristics and self-esteem were investigated in a randomly drawn, community-based sample of 286 young adults with chronic illnesses and disabilities. Whether appraisals of the impact of the condition mediated relationships between condition characteristics and self-esteem, as measured by the Rosenberg Self-Esteem Scale, was also measured. As a group, the youth in this sample reported positive self-esteem. When sociodemographic and condition-related variables were considered simultaneously, maternal education, unpredictability of symptoms, prognosis, sensory impairment, and the presence of a co-occurring learning disability were found to have direct effects on esteem. Perceived impact mediated the relationship between condition characteristics and self-esteem. The results are discussed in relation to the role of impact appraisal in determining the emotional well-being of young adults with chronic illnesses.

Effects of Mild Chronic Intermittent Cold Exposure on Rat Organs

PubMed Central

Wang, Xiaohui; Che, Honglei; Zhang, Wenbin; Wang, Jiye; Ke, Tao; Cao, Rui; Meng, Shanshan; Li, Dan; Weiming, Ouyang; Chen, Jingyuan; Luo, Wenjing

2015-01-01

Cold adaptation is a body's protective response to cold stress. Mild chronic intermittent cold (CIC) exposure has been used to generate animal models for cold adaptation studies. However, the effects of mild CIC exposure on vital organs are not completely characterized. In the present study, we exposed rats to mild CIC for two weeks, and then measured the body weights, the weights of brown adipose tissue (BAT), the levels of ATP and reactive oxygen species (ROS) in the brains, livers, hearts, muscles and BATs. Rats formed cold adaptation after exposure to CIC for two weeks. Compared to rats of the control group that were hosted under ambient temperature, rats exposed to mild CIC showed a lower average body weight, but a higher weight of brown adipose tissue (BAT). Rats exposed to CIC for two weeks also exhibited higher levels of ATP and ROS in all examined organs as compared to those of the control group. In addition, we determined the expression levels of cold-inducible RNA binding protein (Cirbp) and thioredoxin (TRX) in rat tissues after 2 weeks of CIC exposure. Both Cirbp and TRX were increased, suggesting a role of these two proteins for establishment of cold adaptation. Together, this study reveals the effects of mild CIC exposure on vital organs of rats during CIC exposure. PMID:26327811

Clinical correlates to assist with chronic traumatic encephalopathy diagnosis: Insights from a novel rodent repeat concussion model.

PubMed

Thomsen, Gretchen M; Ko, Ara; Harada, Megan Y; Ma, Annie; Wyss, Livia; Haro, Patricia; Vit, Jean-Philippe; Avalos, Pablo; Dhillon, Navpreet K; Cho, Noell; Shelest, Oksana; Ley, Eric J

2017-06-01

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease linked to repetitive head injuries. Chronic traumatic encephalopathy symptoms include changes in mood, behavior, cognition, and motor function; however, CTE is currently diagnosed only postmortem. Using a rat model of recurrent traumatic brain injury (TBI), we demonstrate rodent deficits that predict the severity of CTE-like brain pathology. Bilateral, closed-skull, mild TBI was administered once per week to 35 wild-type rats; eight rats received two injuries (2×TBI), 27 rats received five injuries (5×TBI), and 13 rats were sham controls. To determine clinical correlates for CTE diagnosis, TBI rats were separated based on the severity of rotarod deficits and classified as "mild" or "severe" and further separated into "acute," "short," and "long" based on age at euthanasia (90, 144, and 235 days, respectively). Brain atrophy, phosphorylated tau, and inflammation were assessed. All eight 2×TBI cases had mild rotarod deficiency, 11 5×TBI cases had mild deficiency, and 16 cases had severe deficiency. In one cohort of rats, tested at approximately 235 days of age, balance, rearing, and grip strength were significantly worse in the severe group relative to both sham and mild groups. At the acute time period, cortical thinning, phosphorylated tau, and inflammation were not observed in either TBI group, whereas corpus callosum thinning was observed in both TBI groups. At later time points, atrophy, tau pathology, and inflammation were increased in mild and severe TBI groups in the cortex and corpus callosum, relative to sham controls. These injury effects were exacerbated over time in the severe TBI group in the corpus callosum. Our model of repeat mild TBI suggests that permanent deficits in specific motor function tests correlate with CTE-like brain pathology. Assessing balance and motor coordination over time may predict CTE diagnosis.

Cerebral glucose uptake in patients with chronic mental and cognitive sequelae following a single blunt mild TBI without visible brain lesions.

PubMed

Komura, Akifumi; Kawasaki, Tomohiro; Yamada, Yuichi; Uzuyama, Shiho; Asano, Yoshitaka; Shinoda, Jun

2018-06-19

The aim of this study is to investigate glucose uptake on FDG-PET in patients with chronic mental and cognitive symptoms following a single blunt mild traumatic brain injury (TBI) and without visible brain lesions on CT/MRI. Eighty-nine consecutive patients (mean age 43.8±10.75) who had a single blunt mild TBI from a traffic accident and suffering from chronic mental and cognitive symptoms without visible brain lesions on CT/MRI were enrolled in the study. Patients underwent FDG-PET imaging, and the mean interval between the TBI and FDG-PET was 50.0 months. The Wechsler Adult Intelligence Scale version III testing was performed within one month of the FDG-PET. A control group consisting of 93 healthy adult volunteers (mean age 42.2±14.3 years) also underwent FDG-PET. The glucose uptake pattern from FDG-PET in the patient group was compared to that from normal controls using statistical parametric mapping. Glucose uptake was significantly decreased in the bilateral prefrontal area and significantly increased around the limbic system in the patient group compared to normal controls. This topographical pattern of glucose uptake is different from that reported previously in patients with diffuse axonal injury (DAI), but may be similar to that seen in patients with major depression disorder. These results suggest that the pathological mechanism causing chronic mental and cognitive symptoms in patients with a single blunt mild TBI and without visible brain lesions might be different from that due to primary axonopathy in patients with DAI.

Antidepressant-Like Effects of Acupuncture-Insights From DNA Methylation and Histone Modifications of Brain-Derived Neurotrophic Factor.

PubMed

Jiang, Huili; Zhang, Xuhui; Lu, Jun; Meng, Hong; Sun, Yang; Yang, Xinjing; Zhao, Bingcong; Bao, Tuya

2018-01-01

Sensitive and stable biomarkers that facilitate depression detection and monitor the antidepressant efficiency are currently unavailable. Thus, the objective is to investigate the potential of DNA methylation and histone modifications of brain-derived neurotrophic factor (BDNF) in monitoring severity and antidepressive effects of acupuncture. The depression rat model was imitated by social isolation and chronic unpredicted mild stress (CUMS). The expression of serum BDNF was detected by enzyme-linked immunosorbent assay (ELISA), the hippocampal BDNF, acetylation levels in histone H3 lysine 9 (acH3K9), and HDAC2 by Western blot, the hippocampal mRNA of BDNF by RT-polymerase chain reaction (PCR). The DNA methylation patterns of the promoter I of BDNF was detected by MS-PCR. We investigated that the expression of BDNF in serum and hippocampus were significantly downregulated compared with controls. The same trend was found in mRNA of BDNF. Notably, acupuncture reversed the downregulation of BDNF in serum and hippocampus and mRNA of BDNF compared with model group. Acupuncture reversed the CUMS-induced downregulation of hippocampal acH3K9. On the contrary, the CUMS-induced upregulation of hippocampal HDAC2 in model group was significantly reversed by acupuncture. Collectively, the antidepressant effect of acupuncture might be mediated by regulating the DNA methylation and histone modifications of BDNF, which may represent novel biomaker for detection of depression and monitoring severity and antidepressive effects.

Qualitative and quantitative changes in phospholipids and proteins investigated by spectroscopic techniques in animal depression model.

PubMed

Depciuch, J; Sowa-Kucma, M; Nowak, G; Papp, M; Gruca, P; Misztak, P; Parlinska-Wojtan, M

2017-04-05

Depression becomes nowadays a high mortality civilization disease with one of the major causes being chronic stress. Raman, Fourier Transform Infra Red (FTIR) and Ultraviolet-Visible (UV-vis) spectroscopies were used to determine the changes in the quantity and structure of phospholipids and proteins in the blood serum of rats subjected to chronic mild stress, which is a common animal depression model. Moreover, the efficiency of the imipramine treatment was evaluated. It was found that chronic mild stress not only damages the structure of the phospholipids and proteins, but also decreases their level in the blood serum. A 5weeks imipramine treatment did increase slightly the quantity of proteins, leaving the damaged phospholipids unchanged. Structural information from phospholipids and proteins was obtained by UV-vis spectroscopy combined with the second derivative of the FTIR spectra. Indeed, the structure of proteins in blood serum of stressed rats was normalized after imipramine therapy, while the impaired structure of phospholipids remained unaffected. These findings strongly suggest that the depression factor, which is chronic mild stress, may induce permanent (irreversible) damages into the phospholipid structure identified as shortened carbon chains. This study shows a possible new application of spectroscopic techniques in the diagnosis and therapy monitoring of depression. Copyright © 2016 Elsevier B.V. All rights reserved.

Qualitative and quantitative changes in phospholipids and proteins investigated by spectroscopic techniques in animal depression model

NASA Astrophysics Data System (ADS)

Depciuch, J.; Sowa-Kucma, M.; Nowak, G.; Papp, M.; Gruca, P.; Misztak, P.; Parlinska-Wojtan, M.

2017-04-01

Depression becomes nowadays a high mortality civilization disease with one of the major causes being chronic stress. Raman, Fourier Transform Infra Red (FTIR) and Ultraviolet-Visible (UV-vis) spectroscopies were used to determine the changes in the quantity and structure of phospholipids and proteins in the blood serum of rats subjected to chronic mild stress, which is a common animal depression model. Moreover, the efficiency of the imipramine treatment was evaluated. It was found that chronic mild stress not only damages the structure of the phospholipids and proteins, but also decreases their level in the blood serum. A 5 weeks imipramine treatment did increase slightly the quantity of proteins, leaving the damaged phospholipids unchanged. Structural information from phospholipids and proteins was obtained by UV-vis spectroscopy combined with the second derivative of the FTIR spectra. Indeed, the structure of proteins in blood serum of stressed rats was normalized after imipramine therapy, while the impaired structure of phospholipids remained unaffected. These findings strongly suggest that the depression factor, which is chronic mild stress, may induce permanent (irreversible) damages into the phospholipid structure identified as shortened carbon chains. This study shows a possible new application of spectroscopic techniques in the diagnosis and therapy monitoring of depression.

Chronic variable stress improves glucose tolerance in rats with sucrose-induced prediabetes

PubMed Central

Packard, Amy E. B.; Ghosal, Sriparna; Herman, James P.; Woods, Stephen C.; Ulrich-Lai, Yvonne M.

2014-01-01

The incidence of type-2 diabetes (T2D) and the burden it places on individuals, as well as society as a whole, compels research into the causes, factors and progression of this disease. Epidemiological studies suggest that chronic stress exposure may contribute to the development and progression of T2D in human patients. To address the interaction between chronic stress and the progression of T2D, we developed a dietary model of the prediabetic state in rats utilizing unlimited access to 30% sucrose solution (in addition to unlimited access to normal chow and water), which led to impaired glucose tolerance despite elevated insulin levels. We then investigated the effects of a chronic variable stress paradigm (CVS; twice daily exposure to an unpredictable stressor for 2 weeks) on metabolic outcomes in this prediabetic model. Chronic stress improved glucose tolerance in prediabetic rats following a glucose challenge. Importantly, pair-fed control groups revealed that the beneficial effect of chronic stress did not result from the decreased food intake or body weight gain that occurred during chronic stress. The present work suggests that chronic stress in rodents can ameliorate the progression of diet-induced prediabetic disease independent of chronic stress-induced decreases in food intake and body weight. PMID:25001967

Chronic Diarrhea: A Concern After Gallbladder Removal?

MedlinePlus

Chronic diarrhea: A concern after gallbladder removal? I had my gallbladder removed six months ago, and I'm still having diarrhea. Is this ... mild diarrhea after cholecystectomy is not cause for concern, but speak to your doctor if you are ...

Cost-effectiveness of eplerenone in patients with systolic heart failure and mild symptoms.

PubMed

Lee, Dawn; Wilson, Koo; Akehurst, Ron; Cowie, Martin R; Zannad, Faiez; Krum, Henry; van Veldhuisen, Dirk J; Vincent, John; Pitt, Bertram; McMurray, John J V

2014-11-01

In the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF), aldosterone blockade with eplerenone decreased mortality and hospitalisation in patients with mild symptoms (New York Heart Association class II) and chronic systolic heart failure (HF). The present study evaluated the cost-effectiveness of eplerenone in the treatment of these patients in the UK and Spain. Results from the EMPHASIS-HF trial were used to develop a discrete-event simulation model estimating lifetime direct costs and effects (life years and quality-adjusted life years (QALYs) gained) of the addition of eplerenone to standard care among patients with chronic systolic HF and mild symptoms. Eplerenone plus standard care compared with standard care alone increased lifetime direct costs per patient by £4284 for the UK and €7358 for Spain, with additional quality-adjusted life expectancy of 1.22 QALYs for the UK and 1.33 QALYs for Spain. Mean lifetime costs were £3520 per QALY in the UK and €5532 per QALY in Spain. Probabilistic sensitivity analysis suggested a 100% likelihood of eplerenone being regarded as cost-effective at a willingness-to-pay threshold of £20 000 per QALY (UK) or €30 000 per QALY (Spain). By currently accepted standards of value for money, the addition of eplerenone to optimal medical therapy for patients with chronic systolic HF and mild symptoms is likely to be cost-effective. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

The Relation Between Injury of the Spinothalamocortical Tract and Central Pain in Chronic Patients With Mild Traumatic Brain Injury.

PubMed

Kim, Jin Hyun; Ahn, Sang Ho; Cho, Yoon Woo; Kim, Seong Ho; Jang, Sung Ho

2015-01-01

Little is known about the pathogenetic etiology of central pain in patients with traumatic brain injury (TBI). We investigated the relation between injury of the spinothalamocortical tract (STT) and chronic central pain in patients with mild TBI. Retrospective survey. We recruited 40 consecutive chronic patients with mild TBI and 21 normal control subjects: 8 patients were excluded by the inclusion criteria and the remaining 32 patients were finally recruited. The patients were classified according to 2 groups based on the presence of central pain: the pain group (22 patients) and the nonpain group (10 patients). Diffusion tensor tractography for the STT was performed using the Functional Magnetic Resonance Imaging of the Brain Software Library. Values of fractional anisotropy (FA), mean diffusivity (MD), and tract volume of each STT were measured. Lower FA value and tract volume were observed in the pain group than in the nonpain group and the control group (P < .05). By contrast, higher MD value was observed in the pain group than in the nonpain group and the control group (P < .05). However, no significant differences in all diffusion tensor imaging parameters were observed between the nonpain group and the control group (P > .05). Decreased FA and tract volume and increased MD of the STTs in the pain group appeared to indicate injury of the STT. As a result, we found that injury of the STT is related to the occurrence of central pain in patients with mild TBI. We believe that injury of the STT is a pathogenetic etiology of central pain following mild TBI.

Quercetin ameliorates chronic unpredicted stress-induced behavioral dysfunction in male Swiss albino mice by modulating hippocampal insulin signaling pathway.

PubMed

Mehta, Vineet; Singh, Tiratha Raj; Udayabanu, Malairaman

2017-12-01

Chronic stress is associated with impaired neurogenesis, neurodegeneration and behavioral dysfunction, whereas the mechanism underlying stress-mediated neurological complications is still not clear. In the present study, we aimed to investigate whether chronic unpredicted stress (CUS) mediated neurological alterations are associated with impaired hippocampal insulin signaling or not, and studied the effect of quercetin in this scenario. Male Swiss albino mice were subjected to 21day CUS, during which 30mg/kg quercetin treatment was given orally. After 21days, behavioral functions were evaluated in terms of locomotor activity (Actophotometer), muscle coordination (Rota-rod), depression (Tail Suspension Test (TST), Forced Swim Test (FST)) and memory performance (Passive-avoidance step-down task (PASD)). Further, hippocampal insulin signaling was evaluated in terms of protein expression of insulin, insulin receptor (IR) and glucose transporter 4 (GLUT-4) and neurogenesis was evaluated in terms of doublecortin (DCX) expression. 21day CUS significantly impaired locomotion and had no effect on muscle coordination. Stressed animals were depressed and showed markedly impaired memory functions. Quercetin treatment significantly improvement stress-mediated behavior dysfunction as indicated by improved locomotion, lesser immobility time and greater frequency of upward turning in TST and FST and increased transfer latency on the day 2 (short-term memory) and day 5 (long-term memory) in PASD test. We observed significantly higher IR expression and significantly lower GLUT-4 expression in the hippocampus of stressed animals, despite of nonsignificant difference in insulin levels. Further, chronic stress impaired hippocampal neurogenesis, as indicated by the significantly reduced levels of hippocampal DCX expression. Quercetin treatment significantly lowered insulin and IR expression and significantly enhanced GLUT-4 and DCX expression in the hippocampus, when compared to CUS. In conclusion, quercetin treatment efficiently alleviated stress mediated behavioral dysfunction by modulating hippocampal insulin signaling and neurogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

Contextualising renal patient routines: Everyday space-time contexts, health service access, and wellbeing.

PubMed

McQuoid, Julia; Jowsey, Tanisha; Talaulikar, Girish

2017-06-01

Stable routines are key to successful illness self-management for the growing number of people living with chronic illness around the world. Yet, the influence of chronically ill individuals' everyday contexts in supporting routines is poorly understood. This paper takes a space-time geographical approach to explore the everyday space-time contexts and routines of individuals with chronic kidney disease (CKD). We ask: what is the relationship between renal patients' space-time contexts and their ability to establish and maintain stable routines, and, what role does health service access play in this regard? We draw from a qualitative case study of 26 individuals with CKD in Australia. Data comprised self-reported two day participant diaries and semi-structured interviews. Thematic analysis of interview transcripts was guided by an inductive-deductive approach. We examined the embeddedness of routines within the space-time contexts of participants' everyday lives. We found that participants' everyday space-time contexts were highly complex, especially for those receiving dialysis and/or employed, making routines difficult to establish and vulnerable to disruption. Health service access helped shape participants' everyday space-time contexts, meaning that incidences of unpredictability in accessing health services set-off 'ripple effects' within participants' space-time contexts, disrupting routines and making everyday life negotiation more difficult. The ability to absorb ripple effects from unpredictable health services without disrupting routines varied by space-time context. Implications of these findings for the deployment of the concept of routine in health research, the framing of patient success in self-managing illness, and health services design are discussed. In conclusion, efforts to understand and support individuals in establishing and maintaining routines that support health and wellbeing can benefit from approaches that contextualise and de-centre everyday human behaviour. Opportunities to support renal patients in managing illness and experiencing wellbeing outside the clinical setting lie in a space-time re-design of chronic care services. Copyright © 2017 Elsevier Ltd. All rights reserved.

Circuit and synaptic mechanisms of repeated stress: Perspectives from differing contexts, duration, and development.

PubMed

Bath, Kevin G; Russo, Scott J; Pleil, Kristen E; Wohleb, Eric S; Duman, Ronald S; Radley, Jason J

2017-12-01

The current review is meant to synthesize research presented as part of a symposium at the 2016 Neurobiology of Stress workshop in Irvine California. The focus of the symposium was "Stress and the Synapse: New Concepts and Methods" and featured the work of several junior investigators. The presentations focused on the impact of various forms of stress (altered maternal care, binge alcohol drinking, chronic social defeat, and chronic unpredictable stress) on synaptic function, neurodevelopment, and behavioral outcomes. One of the goals of the symposium was to highlight the mechanisms accounting for how the nervous system responds to stress and their impact on outcome measures with converging effects on the development of pathological behavior. Dr. Kevin Bath's presentation focused on the impact of disruptions in early maternal care and its impact on the timing of hippocampus maturation in mice, finding that this form of stress drove accelerated synaptic and behavioral maturation, and contributed to the later emergence of risk for cognitive and emotional disturbance. Dr. Scott Russo highlighted the impact of chronic social defeat stress in adolescent mice on the development and plasticity of reward circuity, with a focus on glutamatergic development in the nucleus accumbens and mesolimbic dopamine system, and the implications of these changes for disruptions in social and hedonic response, key processes disturbed in depressive pathology. Dr. Kristen Pleil described synaptic changes in the bed nuclei of the stria terminalis that underlie the behavioral consequences of allostatic load produced by repeated cycles of alcohol binge drinking and withdrawal. Dr. Eric Wohleb and Dr. Ron Duman provided new data associating decreased mammalian target of rapamycin (mTOR) signaling and neurobiological changes in the synapses in response to chronic unpredictable stress, and highlighted the potential for the novel antidepressant ketamine to rescue synaptic and behavioral effects. In aggregate, these presentations showcased how divergent perspectives provide new insights into the ways in which stress impacts circuit development and function, with implications for understanding emergence of affective pathology.

Contextualising renal patient routines: Everyday space-time contexts, health service access, and wellbeing

PubMed Central

McQuoid, Julia; Jowsey, Tanisha; Talaulikar, Girish

2017-01-01

Stable routines are key to successful illness self-management for the growing number of people living with chronic illness around the world. Yet, the influence of chronically ill individuals’ everyday contexts in supporting routines is poorly understood. This paper takes a space-time geographical approach to explore the everyday space-time contexts and routines of individuals with chronic kidney disease (CKD). We ask: what is the relationship between renal patients’ space-time contexts and their ability to establish and maintain stable routines, and, what role does health service access play in this regard? We draw from a qualitative case study of 26 individuals with CKD in Australia. Data comprised self-reported two day participant diaries and semi-structured interviews. Thematic analysis of interview transcripts was guided by an inductive-deductive approach. We examined the embeddedness of routines within the space-time contexts of participants’ everyday lives. We found that participants’ everyday space-time contexts were highly complex, especially for those receiving dialysis and/or employed, making routines difficult to establish and vulnerable to disruption. Health service access helped shape participants’ everyday space-time contexts, meaning that incidences of unpredictability in accessing health services set-off ‘ripple effects’ within participants’ space-time contexts, disrupting routines and making everyday life negotiation more difficult. The ability to absorb ripple effects from unpredictable health services without disrupting routines varied by space-time context. Implications of these findings for the deployment of the concept of routine in health research, the framing of patient success in self-managing illness, and health services design are discussed. In conclusion, efforts to understand and support individuals in establishing and maintaining routines that support health and wellbeing can benefit from approaches that contextualise and de-centre everyday human behaviour. Opportunities to support renal patients in managing illness and experiencing wellbeing outside the clinical setting lie in a space-time re-design of chronic care services. PMID:28482275

Pharmacological Characterization of H05, a Novel Serotonin and Noradrenaline Reuptake Inhibitor with Moderate 5-HT2A Antagonist Activity for the Treatment of Depression.

PubMed

Xu, Xiangqing; Wei, Yaqin; Guo, Qiang; Zhao, Song; Liu, Zhiqiang; Xiao, Ting; Liu, Yani; Qiu, Yinli; Hou, Yuanyuan; Zhang, Guisen; Wang, KeWei

2018-06-01

Multitarget antidepressants selectively inhibiting monoaminergic transporters and 5-hydroxytryptamine (5-HT) 2A receptor have demonstrated higher efficacy and fewer side effects than selective serotonin reuptake inhibitors. In the present study, we synthesized a series of novel 3-(benzo[d][1,3]dioxol-4-yloxy)-3-arylpropyl amine derivatives, among which compound H05 was identified as a lead, exhibiting potent inhibitory effects on both serotonin ( K i = 4.81 nM) and norepinephrine (NE) ( K i = 6.72 nM) transporters and moderate 5-HT 2A antagonist activity (IC 50 = 60.37 nM). H05 was able to dose-dependently reduce the immobility duration in mouse forced swimming test and tail suspension test, with the minimal effective doses lower than those of duloxetine, and showed no stimulatory effect on locomotor activity. The administration of H05 (5, 10, and 20 mg/kg, by mouth) significantly shortened the immobility time of adrenocorticotropin-treated rats that serve as a model of treatment-resistant depression, whereas imipramine (30 mg/kg, by mouth) and duloxetine (30 mg/kg, by mouth) showed no obvious effects. Chronic treatment with H05 reversed the depressive-like behaviors in a rat model of chronic unpredictable mild stress and a mouse model of corticosterone-induced depression. Microdialysis analysis revealed that the administration of H05 at either 10 or 20 mg/kg increased the release of 5-HT and NE from the frontal cortex. The pharmacokinetic (PK) and brain penetration analyses suggest that H05 has favorable PK properties with good blood-brain penetration ability. Therefore, it can be concluded that H05, a novel serotonin and NE reuptake inhibitor with 5-HT 2A antagonist activity, possesses efficacious activity in the preclinical models of depression and treatment-resistant depression, and it may warrant further evaluation for clinical development. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

Resilient emotionality and molecular compensation in mice lacking the oligodendrocyte-specific gene Cnp1

PubMed Central

Edgar, N M; Touma, C; Palme, R; Sibille, E

2011-01-01

Altered oligodendrocyte structure and function is implicated in major psychiatric illnesses, including low cell number and reduced oligodendrocyte-specific gene expression in major depressive disorder (MDD). These features are also observed in the unpredictable chronic mild stress (UCMS) rodent model of the illness, suggesting that they are consequential to environmental precipitants; however, whether oligodendrocyte changes contribute causally to low emotionality is unknown. Focusing on 2′-3′-cyclic nucleotide 3′-phosphodiesterase (Cnp1), a crucial component of axoglial communication dysregulated in the amygdala of MDD subjects and UCMS-exposed mice, we show that altered oligodendrocyte integrity can have an unexpected functional role in affect regulation. Mice lacking Cnp1 (knockout, KO) displayed decreased anxiety- and depressive-like symptoms (i.e., low emotionality) compared with wild-type animals, a phenotypic difference that increased with age (3–9 months). This phenotype was accompanied by increased motor activity, but was evident before neurodegenerative-associated motor coordination deficits (⩽9–12 months). Notably, Cnp1KO mice were less vulnerable to developing a depressive-like syndrome after either UCMS or chronic corticosterone exposure. Cnp1KO mice also displayed reduced fear expression during extinction, despite normal amygdala c-Fos induction after acute stress, together implicating dysfunction of an amygdala-related neural network, and consistent with proposed mechanisms for stress resiliency. However, the Cnp1KO behavioral phenotype was also accompanied by massive upregulation of oligodendrocyte- and immune-related genes in the basolateral amygdala, suggesting an attempt at functional compensation. Together, we demonstrate that the lack of oligodendrocyte-specific Cnp1 leads to resilient emotionality. However, combined with substantial molecular changes and late-onset neurodegeneration, these results suggest the low Cnp1 seen in MDD may cause unsustainable and maladaptive molecular compensations contributing to the disease pathophysiology. PMID:22832658

Therapeutic equivalence of two formulations of calcipotriol-betamethasone ointment: a multi-centre, randomized, double-blind study in adult patients with chronic plaque psoriasis.

PubMed

Habjanic, N; Koytchev, R; Yankova, R; Kerec-Kos, M; Grabnar-Peklar, D

2018-06-26

Topical agents are the first-line therapy for psoriasis and treatment of choice for mild to moderate chronic plaque psoriasis. Patients with severe psoriasis often use topical therapies at least for selected body areas. 1,2 Corticosteroids and vitamin D analogues are effective, commonly used topical therapies for mild to moderate plaque psoriasis and are often used in combination due to their complementary pharmacodynamic activities. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

'It just has to click': Internists' views of: what constitutes productive interactions with chronically ill patients.

PubMed

Kromme, N M H; Ahaus, C T B; Gans, R O B; van de Wiel, H B M

2016-05-27

According to the Chronic Care Model, productive interactions are crucial to patient outcomes. Despite productive interactions being at the heart of the Model, however, it is unclear what constitutes such an interaction. The aim of this study was to gain a better understanding of physician views of productive interactions with the chronically ill. We conducted a qualitative study and interviewed 20 internists working in an academic hospital. The data were analyzed using a constructivist approach of grounded theory. To categorize the data, a coding process within which a code list was developed and tested with two other coders was conducted. The participants engaged in goal-directed reasoning when reflecting on productive interactions. This resulted in the identification of four goal orientations: (a) health outcome; (b) satisfaction; (c) medical process; and (d) collaboration. Collaboration appeared to be conditional for reaching medical process goals and ultimately health outcome and satisfaction goals. Achieving rapport with the patient ('clicking,' in the term of the participants) was found to be a key condition that catalyzed collaboration goals. Clicking appeared to be seen as a somewhat unpredictable phenomenon that might or might not emerge, which one had to accept and work with. Goal orientations were found to be related to the specific medical context (i.e., a participant's subspecialty and the nature of a patient's complaint). The participants viewed a productive interaction as essentially goal-directed, catalyzed by the two parties clicking, and dependent on the nature of a patient's complaint. Using the findings, we developed a conceptual process model with the four goal orientations as wheels and with clicking in the center as a flywheel. Because clicking was viewed as important, but somewhat unpredictable, teaching physicians how to click, while taking account of the medical context, may warrant greater attention.

Emotional Stress and Cardiovascular Complications in Animal Models: A Review of the Influence of Stress Type

PubMed Central

Crestani, Carlos C.

2016-01-01

Emotional stress has been recognized as a modifiable risk factor for cardiovascular diseases. The impact of stress on physiological and psychological processes is determined by characteristics of the stress stimulus. For example, distinct responses are induced by acute vs. chronic aversive stimuli. Additionally, the magnitude of stress responses has been reported to be inversely related to the degree of predictability of the aversive stimulus. Therefore, the purpose of the present review was to discuss experimental research in animal models describing the influence of stressor stimulus characteristics, such as chronicity and predictability, in cardiovascular dysfunctions induced by emotional stress. Regarding chronicity, the importance of cardiovascular and autonomic adjustments during acute stress sessions and cardiovascular consequences of frequent stress response activation during repeated exposure to aversive threats (i.e., chronic stress) is discussed. Evidence of the cardiovascular and autonomic changes induced by chronic stressors involving daily exposure to the same stressor (predictable) vs. different stressors (unpredictable) is reviewed and discussed in terms of the impact of predictability in cardiovascular dysfunctions induced by stress. PMID:27445843

Eff ect of a single asenapine treatment on Fos expression in the brain catecholamine-synthesizing neurons: impact of a chronic mild stress preconditioning.

PubMed

Osacka, J; Horvathova, L; Majercikova, Z; Kiss, Alexander

2017-04-25

Fos protein expression in catecholamine-synthesizing neurons of the substantia nigra (SN) pars compacta (SNC, A8), pars reticulata (SNR, A9), and pars lateralis (SNL), the ventral tegmental area (VTA, A10), the locus coeruleus (LC, A6) and subcoeruleus (sLC), the ventrolateral pons (PON-A5), the nucleus of the solitary tract (NTS-A2), the area postrema (AP), and the ventrolateral medulla (VLM-A1) was quantitatively evaluated aft er a single administration of asenapine (ASE) (designated for schizophrenia treatment) in male Wistar rats preconditioned with a chronic unpredictable variable mild stress (CMS) for 21 days. Th e aim of the present study was to reveal whether a single ASE treatment may 1) activate Fos expression in the brain areas selected; 2) activate tyrosine hydroxylase (TH)-synthesizing cells displaying Fos presence; and 3) be modulated by CMS preconditioning. Control (CON), ASE, CMS, and CMS+ASE groups were used. CMS included restraint, social isolation, crowding, swimming, and cold. Th e ASE and CMS+ASE groups received a single dose of ASE (0.3 mg/kg, s.c.) and CON and CMS saline (300 μl/rat, s.c.). The animals were sacrificed 90 min aft er the treatments. Fos protein and TH-labeled immunoreactive perikarya were analyzed on double labeled histological sections and enumerated on captured pictures using combined light and fluorescence microscope illumination. Saline or CMS alone did not promote Fos expression in any of the structures investigated. ASE alone or in combination with CMS elicited Fos expression in two parts of the SN (SNC, SNR) and the VTA. Aside from some cells in the central gray tegmental nuclei adjacent to LC, where a small number of Fos profiles occurred, none or negligible Fos occurrence was detected in the other structures investigated including the LC and sLC, PON-A5, NTS-A2, AP, and VLM-A1. CMS preconditioning did not infl uence the level of Fos induction in the SN and VTA elicited by ASE administration. Similarly, the ratio between the amount of free Fos and Fos colocalized with TH was not aff ected by stress preconditioning in the SNC, SNR, and the VTA. Th e present study provides an anatomical/functional knowledge about the nature of the acute ASE treatment on the catecholamine-synthesizing neurons activity in certain brain structures and their missing interplay with the CMS preconditioning.

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

PubMed Central

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

2016-01-01

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. PMID:27869181

Diagnosis of hyperthyroidism in cats with mild chronic kidney disease.

PubMed

Wakeling, J; Moore, K; Elliott, J; Syme, H

2008-06-01

In cats with concurrent hyperthyroidism and non-thyroidal illnesses such as chronic kidney disease, total thyroxine concentrations are often within the laboratory reference range (19 to 55 nmol/l). The objective of the study was to determine total thyroxine, free thyroxine and/or thyroid-stimulating hormone concentrations in cats with mild chronic kidney disease. Total thyroxine, free thyroxine and thyroid-stimulating hormone were measured in three groups. The hyperthyroidism-chronic kidney disease group (n=16) had chronic kidney disease and clinical signs compatible with hyperthyroidism but a plasma total thyroxine concentration within the reference range. These cats were subsequently confirmed to be hyperthyroid at a later date. The chronic kidney disease-only group (n=20) had chronic kidney disease but no signs of hyperthyroidism. The normal group (n=20) comprised clinically healthy senior (>8 years) cats. In 4 of 20 euthyroid chronic kidney disease cats, free thyroxine concentrations were borderline or high (> or =40 pmol/l). In the hyperthyroidism-chronic kidney disease group, free thyroxine was high in 15 of 16 cats, while thyroid-stimulating hormone was low in 16 of 16 cats. Most hyperthyroidism-chronic kidney disease cats (14 of 16) had total thyroxine greater than 30 nmol/l, whereas all the chronic kidney disease-only cats had total thyroxine less than 30 nmol/l. The combined measurement of free thyroxine with total thyroxine or thyroid-stimulating hormone may be of merit in the diagnosis of hyperthyroidism in cats with chronic kidney disease.

[Disease management programs from a health insurer's point of view].

PubMed

Szymkowiak, Christof; Walkenhorst, Karen; Straub, Christoph

2003-06-01

Disease Management Programmes represent a great challenge to the German statutory health insurance system. According to politicians, disease management programmes are an appropriate tool for increasing the level of care for chronically ill patients significantly, while at the same time they can slow down the cost explosion in health care. The statutory health insurers' point of view yields a more refined picture of the chances and risks involved. The chances are that a medical guideline-based, evidence-based, co-operative care of the chronically ill could be established. But also, there are the risks of misuse of disease management programmes and of misallocation of funds due to the ill-advised linkage with the so-called risk compensation scheme (RSA) balancing the sickness funds' structural deficits through redistribution. The nation-wide introduction of disease management programmes appears to be a gigantic experiment whose aim is to change the care of chronically ill patients and whose outcome is unpredictable.

Chronic Obstructive Pulmonary Disease, Cognitive Impairment, and Development of Disability: The Health and Retirement Study

PubMed Central

Richardson, Caroline R.; Han, MeiLan K.; Cigolle, Christine T.

2014-01-01

Rationale: The relationship between chronic obstructive pulmonary disease (COPD) and cognitive impairment in leading to disability has not been characterized. Objectives: We aimed to investigate the prevalence and cumulative incidence of disability among adults with and without COPD and the association of COPD and cognitive impairment with disability. Methods: We analyzed 2006–2008 waves of the Health and Retirement Study, a nationally representative longitudinal health survey. COPD was self-reported. Prevalent disability was defined as baseline dependency in one or more activities of daily living (ADLs) and incident disability as one or more additional ADL dependencies. We used a validated performance-based measure of cognition to identify dementia and mild cognitive impairment. Covariates included seven chronic diseases, four geriatric syndromes, and sociodemographics. We used logistic regression to test associations between COPD, cognitive status, and prevalent/incident disability. Measurements and Main Results: Of 17,535 participants at least 53 years of age in wave 2006 (representing 77.7 million Americans), 9.5% reported COPD and 13.5% mild cognitive impairment; 17.5% of those with COPD had mild cognitive impairment. Prevalent disability for COPD was 12.8% (5.2% for no-COPD, P < 0.001). An additional 9.2% with COPD developed incident disability at 2 years (4.0% for no-COPD, P < 0.001). In adjusted models, COPD was associated with baseline (odds ratio, 2.0) and incident disability (odds ratio, 2.1; adjusted for baseline disability). Cognitive impairment had an additive effect to COPD. The COPD–disability association, prevalent/incident, was of similar or greater magnitude than that of other chronic diseases (e.g., stroke, diabetes). The associations were maintained in sensitivity analyses using alternative definitions of disability (dependency in two or more ADLs, dependency in instrumental ADLs), and in analysis excluding respondents with dementia. Conclusions: Both COPD and mild cognitive impairment increase the risk of disability. The risk conferred by COPD is significant and similar or higher than other chronic diseases. PMID:25285360

Shifting of attentional set is inadequate in severe burnout: Evidence from an event-related potential study.

PubMed

Sokka, Laura; Leinikka, Marianne; Korpela, Jussi; Henelius, Andreas; Lukander, Jani; Pakarinen, Satu; Alho, Kimmo; Huotilainen, Minna

2017-02-01

Individuals with prolonged occupational stress often report difficulties in concentration. Work tasks often require the ability to switch back and forth between different contexts. Here, we studied the association between job burnout and task switching by recording event-related potentials (ERPs) time-locked to stimulus onset during a task with simultaneous cue-target presentation and unpredictable switches in the task. Participants were currently working people with severe, mild, or no burnout symptoms. In all groups, task performance was substantially slower immediately after task switch than during task repetition. However, the error rates were higher in the severe burnout group than in the mild burnout and control groups. Electrophysiological data revealed an increased parietal P3 response for the switch trials relative to repetition trials. Notably, the response was smaller in amplitude in the severe burnout group than in the other groups. The results suggest that severe burnout is associated with inadequate processing when rapid shifting of attention between tasks is required resulting in less accurate performance. Copyright © 2016 Elsevier B.V. All rights reserved.

Are there gender differences in cognitive function, chronic stress, and neurobehavioral symptoms after mild-to-moderate traumatic brain injury?

PubMed

Covassin, Tracey; Bay, Esther

2012-06-01

Research is inconclusive on whether gender differences exist in cognitive function in persons who sustain a mild-to-moderate traumatic brain injury (TBI). Furthermore, it is also unclear whether there is a relationship between chronic stress and cognitive function in these persons. The purpose of this integrative review is to determine whether gender differences exist in cognitive function, neurobehavioral symptoms, and chronic stress levels after a mild-to-moderate TBI. Participants (n = 72) were recruited from eight outpatient rehabilitation centers. Participants completed the demographic questions, the Immediate Postconcussion Assessment Cognitive Testing neurocognitive test battery, the Perceived Stress Scale-14, and the Neurobehavioral Functioning Inventory (NFI). Gender differences were present on verbal memory composite scores (p = .033), with women performing worse than men. There were no other between-gender differences on cognitive tasks, neurobehavioral symptoms, or chronic stress. Higher chronic stress levels result in a decrease in verbal memory (p = .015) and motor processing speed (p = .006) and slower reaction time (p = .007) for women. As male NFI cognition scores increased, motor processing speed scores decreased (p = .012) and reaction time got slower (p = .019), whereas women exhibited decreased verbal memory (p = .017) and slower reaction time (p = .034). As NFI motor symptoms increased, men exhibited decreased verbal memory (p = .005), visual memory (p = .002), and motor processing speed (p = .002) and slower reaction time (p = .002). Overall, this study only found gender differences on verbal memory composite scores, whereas the remaining cognitive tasks, neurobehavioral symptoms, and chronic stress did not indicate gender differences. Correlations between chronic stress, neurobehavioral symptoms, and cognitive function differed in both men and women with TBI. Persons in the chronic phase of recovery from a TBI may benefit from training in compensatory strategies for verbal memory deficits and stress management.

Effect of high-frequency repetitive transcranial magnetic stimulation on chronic central pain after mild traumatic brain injury: A pilot study.

PubMed

Choi, Gyu-Sik; Kwak, Sang Gyu; Lee, Han Do; Chang, Min Cheol

2018-02-28

Central pain can occur following traumatic brain injury, leading to poor functional recovery, limitation of activities of daily living, and decreased quality of life. The aim of this study was to determine whether high-frequency (10 Hz) repetitive transcranial magnetic stimulation, applied over the primary motor cortex of the affected hemisphere, can be used to manage chronic central pain after mild traumatic brain injury. Prospective randomized feasibility study. Twelve patients with mild traumatic brain injury and chronic central pain were randomly assigned to transcranial magnetic stimulation (high-frequency stimulation, 10 sessions) or sham groups. Diffuse tensor tractography revealed partially injured spinothalamocortical tracts in all recruited patients. A numerical rating scale (NRS) was used to evaluate pain intensity during pre-treatment and immediately after the 5th transcranial magnetic stimulation session (post1), 10th transcranial magnetic stimulation session (post2), and 1 (post3), 2 (post4), and 4 weeks (post 5) after finishing treatment. Physical and mental health status were evaluated using the Short Form 36 Health Survey (SF-36), including physical and mental component scores (PCS, MCS). The NRS score of the repetitive transcranial magnetic stimulation group was significantly lower than the sham group score at all clinical evaluation time-points during and after transcranial magnetic stimulation sessions. The transcranial magnetic stimulation group's SF-36 PCS score was significantly higher at post2, post3, post4, and post5 compared with the sham group. High-frequency transcranial magnetic stimulation may be used to manage chronic central pain and improve quality of life in patients with mild traumatic brain injury. However, this is a pilot study and further research is needed.

Clinical comparison of 99mTc exametazime and 123I Ioflupane SPECT in patients with chronic mild traumatic brain injury.

PubMed

Newberg, Andrew B; Serruya, Mijail; Gepty, Andrew; Intenzo, Charles; Lewis, Todd; Amen, Daniel; Russell, David S; Wintering, Nancy

2014-01-01

This study evaluated the clinical interpretations of single photon emission computed tomography (SPECT) using a cerebral blood flow and a dopamine transporter tracer in patients with chronic mild traumatic brain injury (TBI). The goal was to determine how these two different scan might be used and compared to each other in this patient population. Twenty-five patients with persistent symptoms after a mild TBI underwent SPECT with both (99m)Tc exametazime to measure cerebral blood flow (CBF) and (123)I ioflupane to measure dopamine transporter (DAT) binding. The scans were interpreted by two expert readers blinded to any case information and were assessed for abnormal findings in comparison to 10 controls for each type of scan. Qualitative CBF scores for each cortical and subcortical region along with DAT binding scores for the striatum were compared to each other across subjects and to controls. In addition, symptoms were compared to brain scan findings. TBI patients had an average of 6 brain regions with abnormal perfusion compared to controls who had an average of 2 abnormal regions (p<0.001). Patient with headaches had lower CBF in the right frontal lobe, and higher CBF in the left parietal lobe compared to patients without headaches. Lower CBF in the right temporal lobe correlated with poorer reported physical health. Higher DAT binding was associated with more depressive symptoms and overall poorer reported mental health. There was no clear association between CBF and DAT binding in these patients. Overall, both scans detected abnormalities in brain function, but appear to reflect different types of physiological processes associated with chronic mild TBI symptoms. Both types of scans might have distinct uses in the evaluation of chronic TBI patients depending on the clinical scenario.

Old worries and new anxieties: behavioral symptoms and mild cognitive impairment in a population study.

PubMed

Andreescu, Carmen; Teverovsky, Esther; Fu, Bo; Hughes, Tiffany F; Chang, Chung-Chou H; Ganguli, Mary

2014-03-01

To disentangle the complex associations of depression and anxiety with mild cognitive impairment (MCI) at the population level. We examined subgroups of anxiety symptoms and depression symptom profiles in relation to MCI, which we defined using both cognitive and functional approaches. We used an epidemiologic, cross-sectional study with an age-stratified, random, population-based sample of 1,982 individuals aged 65 years and over. Three definitions of MCI were used: 1) a purely cognitive classification into amnestic and nonamnestic MCI, 2) a combined cognitive-functional definition by International Working Group (IWG) criteria, and 3) a purely functional definition by the Clinical Dementia Rating (CDR) of 0.5. Three depression profiles were identified by factor analysis of the modified Center for Epidemiological Studies-Depression Scale: core mood, self-esteem/interpersonal, and apathy/neurovegetative profiles. Three anxiety groups, chronic mild worry, chronic severe anxiety, and recent-onset anxiety, were based on screening questions. Recent-onset anxiety was associated with MCI by nonamnestic and IWG criteria, chronic severe anxiety was associated with MCI by all definitions, and chronic mild worry was associated with none. Of the depression profiles, the core mood profile was associated with CDR-defined MCI, the apathy/neurovegetative profile was associated with MCI by amnestic, IWG, and CDR definitions, and the self-esteem/interpersonal profile was associated with none. In this population-based sample, subgroups with different anxiety and depression profiles had different relationships with cognitive and functional definitions of MCI. Anxiety, depression, and MCI are all multidimensional entities, interacting in complex ways that may shed light on underlying neural mechanisms. Copyright © 2014 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Remedying Social Skills Deficits in a Chronic Schizophrenic-Retarded Person.

ERIC Educational Resources Information Center

Jackson, Henry J.; Martin, Rose

1983-01-01

An adult chronic schizophrenic, residual type, with an additional diagnosis of mild-moderate retardation, received social skills training (SST). Videotaped role-play assessments showed change occurred following SST, while a multiple-baseline design demonstrated functional control over the behaviors. (Author/CL)

Pervasive Developmental Disorder Behavior in Adolescents with Intellectual Disability and Co-Occurring Somatic Chronic Diseases

ERIC Educational Resources Information Center

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…

Pulmonary Microvascular Blood Flow in Mild Chronic Obstructive Pulmonary Disease and Emphysema. The MESA COPD Study

PubMed Central

Hueper, Katja; Vogel-Claussen, Jens; Parikh, Megha A.; Austin, John H. M.; Bluemke, David A.; Carr, James; Choi, Jiwoong; Goldstein, Thomas A.; Gomes, Antoinette S.; Hoffman, Eric A.; Kawut, Steven M.; Lima, Joao; Michos, Erin D.; Post, Wendy S.; Po, Ming Jack; Prince, Martin R.; Liu, Kiang; Rabinowitz, Dan; Skrok, Jan; Smith, Ben M.; Watson, Karol; Yin, Youbing; Zambeli-Ljepovic, Alan M.

2015-01-01

Rationale: Smoking-related microvascular loss causes end-organ damage in the kidneys, heart, and brain. Basic research suggests a similar process in the lungs, but no large studies have assessed pulmonary microvascular blood flow (PMBF) in early chronic lung disease. Objectives: To investigate whether PMBF is reduced in mild as well as more severe chronic obstructive pulmonary disease (COPD) and emphysema. Methods: PMBF was measured using gadolinium-enhanced magnetic resonance imaging (MRI) among smokers with COPD and control subjects age 50 to 79 years without clinical cardiovascular disease. COPD severity was defined by standard criteria. Emphysema on computed tomography (CT) was defined by the percentage of lung regions below −950 Hounsfield units (−950 HU) and by radiologists using a standard protocol. We adjusted for potential confounders, including smoking, oxygenation, and left ventricular cardiac output. Measurements and Main Results: Among 144 participants, PMBF was reduced by 30% in mild COPD, by 29% in moderate COPD, and by 52% in severe COPD (all P < 0.01 vs. control subjects). PMBF was reduced with greater percentage emphysema−950HU and radiologist-defined emphysema, particularly panlobular and centrilobular emphysema (all P ≤ 0.01). Registration of MRI and CT images revealed that PMBF was reduced in mild COPD in both nonemphysematous and emphysematous lung regions. Associations for PMBF were independent of measures of small airways disease on CT and gas trapping largely because emphysema and small airways disease occurred in different smokers. Conclusions: PMBF was reduced in mild COPD, including in regions of lung without frank emphysema, and may represent a distinct pathological process from small airways disease. PMBF may provide an imaging biomarker for therapeutic strategies targeting the pulmonary microvasculature. PMID:26067761

Pulmonary Microvascular Blood Flow in Mild Chronic Obstructive Pulmonary Disease and Emphysema. The MESA COPD Study.

PubMed

Hueper, Katja; Vogel-Claussen, Jens; Parikh, Megha A; Austin, John H M; Bluemke, David A; Carr, James; Choi, Jiwoong; Goldstein, Thomas A; Gomes, Antoinette S; Hoffman, Eric A; Kawut, Steven M; Lima, Joao; Michos, Erin D; Post, Wendy S; Po, Ming Jack; Prince, Martin R; Liu, Kiang; Rabinowitz, Dan; Skrok, Jan; Smith, Ben M; Watson, Karol; Yin, Youbing; Zambeli-Ljepovic, Alan M; Barr, R Graham

2015-09-01

Smoking-related microvascular loss causes end-organ damage in the kidneys, heart, and brain. Basic research suggests a similar process in the lungs, but no large studies have assessed pulmonary microvascular blood flow (PMBF) in early chronic lung disease. To investigate whether PMBF is reduced in mild as well as more severe chronic obstructive pulmonary disease (COPD) and emphysema. PMBF was measured using gadolinium-enhanced magnetic resonance imaging (MRI) among smokers with COPD and control subjects age 50 to 79 years without clinical cardiovascular disease. COPD severity was defined by standard criteria. Emphysema on computed tomography (CT) was defined by the percentage of lung regions below -950 Hounsfield units (-950 HU) and by radiologists using a standard protocol. We adjusted for potential confounders, including smoking, oxygenation, and left ventricular cardiac output. Among 144 participants, PMBF was reduced by 30% in mild COPD, by 29% in moderate COPD, and by 52% in severe COPD (all P < 0.01 vs. control subjects). PMBF was reduced with greater percentage emphysema-950HU and radiologist-defined emphysema, particularly panlobular and centrilobular emphysema (all P ≤ 0.01). Registration of MRI and CT images revealed that PMBF was reduced in mild COPD in both nonemphysematous and emphysematous lung regions. Associations for PMBF were independent of measures of small airways disease on CT and gas trapping largely because emphysema and small airways disease occurred in different smokers. PMBF was reduced in mild COPD, including in regions of lung without frank emphysema, and may represent a distinct pathological process from small airways disease. PMBF may provide an imaging biomarker for therapeutic strategies targeting the pulmonary microvasculature.

Can long-term corticosteriods lead to blindness? A case series of central serous chorioretinopathy induced by corticosteroids.

PubMed

Loo, Jing-Liang; Lee, Shu-Yen; Ang, Chong-Lye

2006-07-01

Long-term, high-dose corticosteroid therapy is well-known to cause systemic and ocular complications. A lesser known complication is chronic central serous chorioretinopathy (CSCR). Although idiopathic central serous chorioretinopathy (CSCR) is known to be mild with spontaneous recovery and minimal effects on the final visual acuity, chronic CSCR as a complication of long- term steroid therapy behaves differently, and may cause irreversible visual impairment. Three cases of chronic, recurrent CSCR were precipitated by longterm corticosteroids prescribed for post-renal transplant immunosuppressive therapy, postpituitary surgery and pemphigus vulgaris. Two cases resolved with tapering of corticosteroids while one case was treated by focal laser photocoagulation. Two eyes had severe impairment of vision as a result of subretinal scar formation while the other 4 eyes had mild reduction of visual acuity from retinal epithelium pigment atrophy. Long-term corticosteroid therapy can be complicated by severe, chronic and recurrent CSCR and occasionally peripheral exudative retinal detachment. This may result in subretinal fibrosis and permanent loss of vision.

Study of gastro-oesophageal reflux disease in patients with mild-to-moderate chronic obstructive pulmonary disease in India.

PubMed

Kamble, Nitish L; Khan, Naushad A; Kumar, Naresh; Nayak, Hemanta K; Daga, Mradul K

2013-04-01

To study the incidence and pattern of gastro-oesophageal reflux disease (GORD) in patients with mild-to-moderate chronic obstructive pulmonary disease (COPD) using dual-probe 24-h oesophageal pH recording. This was a prospective study of 50 patients with mild-to-moderate stage COPD based on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines. A detailed history of illness along with spirometry was done in all patients. In the study group, reflux symptoms were measured using a validated scoring system. All the patients underwent oesophageal manometry and dual-probe 24-h oesophageal pH recording. Symptoms of gastro-oesophageal reflux were present in 38 patients. Twenty-four-hour oesophageal pH monitoring revealed pathological reflux in 31 out of 38 symptomatic and 8 out of 12 asymptomatic patients. The overall rate of GORD was 78% in our study. Only distal GORD was observed in 11 (28.9%), and both distal and proximal GORD was observed in 20 (52.6%) out of the 38 symptomatic subjects. In the remaining 12 asymptomatic patients, eight had GORD. Distal GORD was present in six (50%) patients, and two (16.6%) had both distal and proximal GORD in this group. Isolated proximal GORD was not observed in any patient. There is an increased occurrence of GORD in patients with even mild-to-moderate COPD. © 2013 The Authors. Respirology © 2013 Asian Pacific Society of Respirology.

Molecular and Genetic Investigation of Tau in Chronic Traumatic Encephalopathy (Log No. 13267017)

DTIC Science & Technology

2017-10-01

AWARD NUMBER: W81XWH-14-1-0399 TITLE: Molecular & Genetic Investigation of Tau in Chronic Traumatic Encephalopathy (Log No. 13267017) PRINCIPAL...neuropathological findings we are currently characterizing in individuals with CTE reflect molecular and genetic differences that will enable the...INTRODUCTION: Repetitive mild traumatic brain injury leads to neurological symptoms and chronic traumatic encephalopathy (CTE). The molecular changes

Junctional bradycardia with verapamil in renal failure--care required even with mild hyperkalaemia.

PubMed

Hegazi, M O; Aldabie, G; Al-Mutairi, S; El Sayed, A

2012-12-01

Treatment for hypertension with verapamil has a favourable renoprotective effect and is generally considered safe in patients with mild to moderate renal failure. In this report, we highlight the vulnerability of patients with mild to moderate renal failure to verapamil side effects especially in the presence of hyperkalaemia. We report two cases of junctional bradycardia with slow release (SR) verapamil therapy in the presence of mild hyperkalaemia in patients with mild to moderate chronic renal failure. Verapamil and hyperkalaemia may synergistically increase the vulnerability to atrioventricular conduction delay. Renal failure patients with baseline mild hyperkalaemia are particularly liable to bradyarrhythmias with SR verapamil. In such cases, we would recommend verapamil dose reduction and avoidance of SR formulation. In cases of verapamil toxicity, actively treating any level of hyperkalaemia is recommended. © 2012 Blackwell Publishing Ltd.

Scale of Unpredictability Beliefs: Reliability and Validity.

PubMed

Ross, Lisa Thomson; Short, Stephen D; Garofano, Marina

2016-11-16

Experiencing unpredictability in the environment has a variety of negative outcomes. However, these are difficult to ascertain due to the lack of a psychometrically sound measure of unpredictability beliefs. This article summarizes the development of the Scale of Unpredictability Beliefs (SUB), which assesses perceptions about unpredictability in one's life, in other people, and in the world. In Study I, college students (N = 305) responded to 68 potential items as well as other scales. Exploratory factor analysis yielded three internally consistent subscales (Self, People, and World; 16 items total). Higher SUB scores correlated with more childhood family unpredictability, greater likelihood of parental alcohol abuse, stronger causal uncertainty, and lower self-efficacy. In Study II, a confirmatory factor analysis supported the three-factor solution (N = 186 college students). SUB scores correlated with personality, childhood family unpredictability, and control beliefs. In most instances the SUB predicted family unpredictability and control beliefs beyond existing unpredictability measures. Study III confirmed the factor structure and replicated family unpredictability associations in an adult sample (N = 483). This article provides preliminary support for this new multi-dimensional, self-report assessment of unpredictability beliefs, and ideas for future research are discussed.

The combined effect of clothianidin and environmental stress on the behavioral and reproductive function in male mice

PubMed Central

HIRANO, Tetsushi; YANAI, Shogo; OMOTEHARA, Takuya; HASHIMOTO, Rie; UMEMURA, Yuria; KUBOTA, Naoto; MINAMI, Kiichi; NAGAHARA, Daichi; MATSUO, Eiko; AIHARA, Yoshiko; SHINOHARA, Ryota; FURUYASHIKI, Tomoyuki; MANTANI, Youhei; YOKOYAMA, Toshifumi; KITAGAWA, Hiroshi; HOSHI, Nobuhiko

2015-01-01

Neonicotinoids, some of the most widely used pesticides in the world, act as agonists to the nicotinic acetylcholine receptors (nAChRs) of insects, resulting in death from abnormal excitability. Neonicotinoids unexpectedly became a major topic as a compelling cause of honeybee colony collapse disorder, which is damaging crop production that requires pollination worldwide. Mammal nAChRs appear to have a certain affinity for neonicotinoids with lower levels than those of insects; there is thus rising concern about unpredictable adverse effects of neonicotinoids on vertebrates. We hypothesized that the effects of neonicotinoids would be enhanced under a chronic stressed condition, which is known to alter the expression of targets of neonicotinoids, i.e., neuronal nAChRs. We performed immunohistochemical and behavioral analyses in male mice actively administered a neonicotinoid, clothianidin (CTD; 0, 10, 50 and 250 mg/kg/day), for 4 weeks under an unpredictable chronic stress procedure. Vacuolated seminiferous epithelia and a decrease in the immunoreactivity of the antioxidant enzyme glutathione peroxidase 4 were observed in the testes of the CTD+stress mice. In an open field test, although the locomotor activities were not affected, the anxiety-like behaviors of the mice were elevated by both CTD and stress. The present study demonstrates that the behavioral and reproductive effects of CTD become more serious in combination with environmental stress, which may reflect our actual situation of multiple exposure. PMID:25960033

Chronic 'speech catatonia' with constant logorrhea, verbigeration and echolalia successfully treated with lorazepam: a case report.

PubMed

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.

[Correlation between interleukin-10 polymorphisms and susceptibility to chronic periodontitis among Uygur adults in the Moyu area].

PubMed

Yuhui, Zhang; Ping, Huang; Jing, Lin; Jin, Zhao

2017-10-01

This study aims to investigate the association between interleukin (IL)-10-597 (C/A) single-nucleotide polymorphisms and chronic periodontitis of Moyu Uygur population in Xinjiang Uygur Autonomous Region of China. In accordance with the inclusion and exclusion criteria, the buccal swabs of 300 subjects were randomly selected from the epidemiological investigation of Uygur adults in Moyu county on April and May 2013. The study was conducted on a healthy control group, a mild chronic periodontitis group, and a moderate-to-severe chronic periodontitis group, with each comprising 100 samples. The IL-10-597(C/A) site in the promoter sequences was analyzed using the tetra-primer amplification refractory mutation system-polymerase chain reaction method to test the genotype and allele distributions. Statistical analysis was performed using Chi-squared test and ordinal classification Logistic regression analysis. The genotype and allele frequencies of the IL-10-597(C/A) site in the healthy control group, mild chronic periodontitis group, and moderate-to-severe chronic periodontitis group exhibited no significant difference (P>0.05). The age of all the samples was associated with chronic periodontitis. The risk of chronic periodontitis in the people of 55-65 years old was 25 times in the people under the age of 35 (OR=25.56, P<0.001). The IL-10-597 (C/A) single-nucleotide polymorphisms in the gene promoter are not associated with chronic periodontitis in Uygur adult population.

Effectiveness of Behavioral Therapy for Chronic Low Back Pain: A Component Analysis.

ERIC Educational Resources Information Center

Turner, Judith A.; And Others

1990-01-01

Evaluated effects of group behavioral therapy including aerobic exercise, behavioral therapy alone, and aerobic exercise alone on pain and physical and psychological disability among mildly disabled chronic low-back-pain patients (n=96). The combined behavioral therapy and exercise group improved significantly more pretreatment to posttreatment…

Chronic stress disrupts neural coherence between cortico-limbic structures.

PubMed

Oliveira, João Filipe; Dias, Nuno Sérgio; Correia, Mariana; Gama-Pereira, Filipa; Sardinha, Vanessa Morais; Lima, Ana; Oliveira, Ana Filipa; Jacinto, Luís Ricardo; Ferreira, Daniela Silva; Silva, Ana Maria; Reis, Joana Santos; Cerqueira, João José; Sousa, Nuno

2013-01-01

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 stress (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.

Bilateral chronic sacral neuromodulation for treatment of lower urinary tract dysfunction.

PubMed

Hohenfellner, M; Schultz-Lampel, D; Dahms, S; Matzel, K; Thüroff, J W

1998-09-01

Chronic sacral neuromodulation aims at functional restoration of selected forms of nonneurogenic and neurogenic bladder dysfunction. The original technique, as described by Tanagho and Schmidt, provides unilateral sacral nerve stimulation via an implanted stimulator powering an electrode inserted into a sacral foramen. Its drawback was that the implant failed unpredictably in some patients despite previous successful percutaneous test stimulation. Therefore, we modified the stimulation technique to improve the efficacy of chronic sacral neuromodulation. Guarded bipolar electrodes powered by an implantable neurostimulator were attached bilaterally directly to the S3 nerves through a sacral laminectomy in 9 women and 2 men (mean age 43.4 years). Of the patients 5 had urinary incontinence due to detrusor hyperactivity and 6 had urinary retention from detrusor hypocontractility. Mean followup with repeated urodynamics was 13 months (range 9 to 28). Four significant complications were encountered in 4 patients. In 10 patients the urological sequelae of the neurological disorder were alleviated significantly (50% or more), including 5 who experienced complete relief of symptoms. The efficacy of chronic sacral neuromodulation can be improved by bilateral attachment of electrodes directly to the sacral nerves.

Long-term moderate elevation of corticosterone facilitates avian food-caching behaviour and enhances spatial memory.

PubMed

Pravosudov, Vladimir V

2003-12-22

It is widely assumed that chronic stress and corresponding chronic elevations of glucocorticoid levels have deleterious effects on animals' brain functions such as learning and memory. Some animals, however, appear to maintain moderately elevated levels of glucocorticoids over long periods of time under natural energetically demanding conditions, and it is not clear whether such chronic but moderate elevations may be adaptive. I implanted wild-caught food-caching mountain chickadees (Poecile gambeli), which rely at least in part on spatial memory to find their caches, with 90-day continuous time-release corticosterone pellets designed to approximately double the baseline corticosterone levels. Corticosterone-implanted birds cached and consumed significantly more food and showed more efficient cache recovery and superior spatial memory performance compared with placebo-implanted birds. Thus, contrary to prevailing assumptions, long-term moderate elevations of corticosterone appear to enhance spatial memory in food-caching mountain chickadees. These results suggest that moderate chronic elevation of corticosterone may serve as an adaptation to unpredictable environments by facilitating feeding and food-caching behaviour and by improving cache-retrieval efficiency in food-caching birds.

Therapeutic efficacy of atypical antipsychotic drugs by targeting multiple stress-related metabolic pathways

PubMed Central

Cai, H L; Jiang, P; Tan, Q Y; Dang, R L; Tang, M M; Xue, Y; Deng, Y; Zhang, B K; Fang, P F; Xu, P; Xiang, D X; Li, H D; Yao, J K

2017-01-01

Schizophrenia (SZ) is considered to be a multifactorial brain disorder with defects involving many biochemical pathways. Patients with SZ show variable responses to current pharmacological treatments of SZ because of the heterogeneity of this disorder. Stress has a significant role in the pathophysiological pathways and therapeutic responses of SZ. Atypical antipsychotic drugs (AAPDs) can modulate the stress response of the hypothalamic–pituitary–adrenal (HPA) axis and exert therapeutic effects on stress by targeting the prefrontal cortex (PFC) and hippocampus. To evaluate the effects of AAPDs (such as clozapine, risperidone and aripiprazole) on stress, we compared neurochemical profile variations in the PFC and hippocampus between rat models of chronic unpredictable mild stress (CUMS) for HPA axis activation and of long-term dexamethasone exposure (LTDE) for HPA axis inhibition, using an ultraperformance liquid chromatography–mass spectrometry (UPLC–MS/MS)-based metabolomic approach and a multicriteria assessment. We identified a number of stress-induced biomarkers comprising creatine, choline, inosine, hypoxanthine, uric acid, allantoic acid, lysophosphatidylcholines (LysoPCs), phosphatidylethanolamines (PEs), corticosterone and progesterone. Specifically, pathway enrichment and correlation analyses suggested that stress induces oxidative damage by disturbing the creatine–phosphocreatine circuit and purine pathway, leading to excessive membrane breakdown. Moreover, our data suggested that the AAPDs tested partially restore stress-induced deficits by increasing the levels of creatine, progesterone and PEs. Thus, the present findings provide a theoretical basis for the hypothesis that a combined therapy using adenosine triphosphate fuel, antioxidants and omega-3 fatty acids as supplements may have synergistic effects on the therapeutic outcome following AAPD treatment. PMID:28509906

Effects of duloxetine on microRNA expression profile in frontal lobe and hippocampus in a mouse model of depression.

PubMed

Pan, Bing; Liu, Yamei

2015-01-01

Depression is a major mood disorder affecting people worldwide. The posttranscriptional gene regulation mediated by microRNAs (miRNAs) which may have critical roles in the pathogenesis of depression. However, to date, little is known about the effects of the antidepressant drug duloxetine on miRNA expression profile in chronic unpredictable mild stress (CUMS)-induced depression model in mice. Healthy adult male Kunming mice were randomly divided into three groups: control group, model group and duloxetine group. Sucrose preference test and open field test were used to represent the behavioral change. MiRNAs levels in frontal lobe and hippocampus of mice were analyzed using miRNA microarrays assay. We observed that long-term treatment with duloxetine significantly ameliorated the CUMS procedure-induced sucrose preference decreases and mice treated with duloxetine demonstrated a reversal of the number of crossings, and rearings reduced by CUMS. A significant upregulation of miR-132 and miR-18a in hippocampus in the duloxetine treatment group compared with model group, whereas the levels of miR-134 and miR-124a were significantly downregulated. Furthermore, miR-18a showed significant upregulation in frontal lobe in the duloxetine treatment group relative to model group. Our data showed that miRNA expression profile in frontal lobe and hippocampus was affected by duloxetine in mice model of depression. The effect was especially pronounced in the hippocampus, suggesting that hippocampus might be the action site of duloxetine, which presumably worked by regulating the expression of miRNA levels.

Role of Bai-Shao towards the antidepressant effect of Chaihu-Shu-Gan-San using metabonomics integrated with chemical fingerprinting.

PubMed

Chang, Xing; Jia, Hongmei; Zhou, Chao; Zhang, Hongwu; Yu, Meng; Yang, Junshan; Zou, Zhongmei

2015-12-01

Chaihu-Shu-Gan-San (CSGS) is a classical traditional Chinese medicine formula for the treatment of depression. As one of the single herbs in CSGS, Bai-Shao displayed antidepressant effect. In order to explore the role of Bai-Shao towards the antidepressant effect of CSGS, the metabolic regulation and chemical profiles of CSGS with and without Bai-Shao (QBS) were investigated using metabonomics integrated with chemical fingerprinting. At first, partial least squares regression (PLSR) analysis was applied to characterize the potential biomarkers associated with chronic unpredictable mild stress (CUMS)-induced depression. Among 46 differential metabolites found in the ultra-performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC-Q-TOF/MS) and (1)H NMR-based urinary metabonomics, 20 were significantly correlated with the preferred sucrose consumption observed in behavior experiments and were considered as biomarkers to evaluate the antidepressant effect of CSGS. Based on differential regulation on CUMS-induced metabolic disturbances with CSGS and QBS treatments, we concluded that Bai-Shao made crucial contribution to CSGS in the improvement of the metabolic deviations of six biomarkers (i.e., glutamate, acetoacetic acid, creatinine, xanthurenic acid, kynurenic acid, and N-acetylserotonin) disturbed in CUMS-induced depression. While the chemical constituents of Bai-Shao contributed to CSGS were paeoniflorin, albiflorin, isomaltopaeoniflorin, and benzoylpaeoniflorin based on the multivariate analysis of the UPLC-Q-TOF/MS chemical profiles from CSGS and QBS extracts. These findings suggested that Bai-Shao played an indispensable role in the antidepressant effect of CSGS. Copyright © 2015 Elsevier B.V. All rights reserved.

Mechanism of depression as a risk factor in the development of Alzheimer's disease: the function of AQP4 and the glymphatic system.

PubMed

Xia, Maosheng; Yang, Li; Sun, Guangfeng; Qi, Shuang; Li, Baoman

2017-02-01

Many studies have indicated that a history of depression increases the risk of developing Alzheimer's disease (AD); however, the potential pathogenestic mechanism by which depression functions as a high risk factor for AD remains unknown. Recently, a "cerebral lymphatic system" referred to as "glymphatic system" has been demonstrated to be responsible for neuronal extracellular waste protein clearance via a paravascular pathway. However, the function of glymphatic pathway has not been determined in depressive disorders. The present study used an animal model of chronic unpredictable mild stress (CUMS) to determine the function of glymphatic pathway by using fluorescence tracers. Immunohistochemistry was used to assess the accumulation of endogenous mouse and exogenous human amyloid beta 42 (Aβ42) in CUMS-treated mice with or without treatment with antidepressant fluoxetine. Glymphatic pathway circulation was impaired in mice treated with CUMS; moreover, glymphatic pathway dysfunction suppressed Aβ42 metabolism, because the accumulation of endogenous and exogenous Aβ42 was increased in the brains of the CUMS-treated mice. However, treatment with fluoxetine reversed these destructive effects of CUMS on glymphatic system. In anhedonic mice, the expression of the water channel aquaporin 4 (AQP4), a factor in glymphatic pathway dysfunction, was down-regulated in cortex and hippocampus. The dysfunction of glymphatic system suggested why a history of depression may be a strong risk factor for AD in anhedonic mice. We hope our study will contribute to an understanding of the risk mechanism of depressive disorder in the development of AD and the mechanisms of antidepressant therapies in AD.

BDNF–ERK–CREB signalling mediates the role of miR-132 in the regulation of the effects of oleanolic acid in male mice

PubMed Central

Yi, Li-Tao; Li, Jing; Liu, Bin-Bin; Luo, Liu; Liu, Qing; Geng, Di

2014-01-01

Background Although previous study has demonstrated that brain-derived neurotrophic factor (BDNF) is involved in the antidepressant-like effect of oleanolic acid, there is little information regarding the details of the molecular mechanism involved in this effect. Methods We used a chronic unpredictable mild stress (CUMS) model to test the antidepressant-like effect of oleanolic acid on depressant-like behaviour, miR-132 expression and synaptic protein expression in the male mouse hippocampus. Furthermore, we explored the possible signalling pathways associated with miR-132 expression that mediate the effect of oleanolic acid on neuronal proliferation. Results The results demonstrated that a 3-week treatment with oleanolic acid ameliorated CUMS-induced anhedonic and anxiogenic behaviours. Furthermore, we found that oleanolic acid led to the BDNF-related phosphorylation and activation of extracellular signal-regulated kinases (ERK) and cyclic adenosine monophosphate response element binding protein (CREB), which was associated with the upregulation of miR-132 and hippocampal neuronal proliferation. Moreover, experiments with an miR-132 antagomir revealed that targeting miR-132 led to inhibition of neuronal proliferation and the postsynaptic density protein 95, but did not affect presynaptic protein synapsin I. Limitations Several other stimuli can also induce CREB phosphorylation in the hippocampus. Thus, regulation of miR-132 may not be restricted to neurotrophic signalling. Conclusion Our results show that oleanolic acid induces the upregulation of miR-132, which serves as an important regulator of neurotrophic actions, mainly through the activation of the hippocampal BDNF–ERK–CREB signalling pathways. PMID:25079084

BDNF/TrkB Pathway Mediates the Antidepressant-Like Role of H2S in CUMS-Exposed Rats by Inhibition of Hippocampal ER Stress.

PubMed

Wei, Le; Kan, Li-Yuan; Zeng, Hai-Ying; Tang, Yi-Yun; Huang, Hong-Lin; Xie, Ming; Zou, Wei; Wang, Chun-Yan; Zhang, Ping; Tang, Xiao-Qing

2018-06-01

Our previous works have shown that hydrogen sulfide (H 2 S) significantly attenuates chronic unpredictable mild stress (CUMS)-induced depressive-like behaviors and hippocampal endoplasmic reticulum (ER) stress. Brain-derived neurotrophic factor (BDNF) generates an antidepressant-like effect by its receptor tyrosine protein kinase B (TrkB). We have previously found that H 2 S upregulates the expressions of BDNF and p-TrkB in the hippocampus of CUMS-exposed rats. Therefore, the present work was to explore whether BDNF/TrkB pathway mediates the antidepressant-like role of H 2 S by blocking hippocampal ER stress. We found that treatment with K252a (an inhibitor of BDNF/TrkB pathway) significantly increased the immobility time in the forced swim test and tail suspension test and increased the latency to feed in the novelty-suppressed feeding test in the rats cotreated with sodium hydrosulfide (NaHS, a donor of H 2 S) and CUMS. Similarly, K252a reversed the protective effect of NaHS against CUMS-induced hippocampal ER stress, as evidenced by increases in the levels of ER stress-related proteins, glucose-regulated protein 78, CCAAT/enhancer binding protein homologous protein and cleaved caspase-12. Taken together, our results suggest that BDNF/TrkB pathway plays an important mediatory role in the antidepressant-like action of H 2 S in CUMS-exposed rats, which is by suppression of hippocampal ER stress. These data provide a novel mechanism underlying the protection of H 2 S against CUMS-induced depressive-like behaviors.

How we diagnose and treat neutropenia in adults.

PubMed

Palmblad, Jan; Nilsson, Christer C; Höglund, Petter; Papadaki, Helen A

2016-05-01

Neutropenias (NPs), being acute and often transient, or chronic, range from life-threatening conditions with very low absolute neutrophil blood counts (ANC) to disorders characterized by only mild NP and of no obvious significance for health. Many are caused by genetic variations/mutations, e.g. the benign familial NP and the chronic severe NPs (e.g. Kostmann disease). Some of the latter are associated with various bodily malformations. Many of the mild-to-moderate NPs are signs of underlying disorders that need specialized treatments (e.g. HIV, hepatitis, autoimmune disorders, the large granular lymphocyte syndrome). We provide here means for the evaluation of a previously unknown NP, suggest a triage and treatments.

Histological findings in two renal transplants accomplishing operational tolerance criteria

PubMed Central

Azancot, M.A.; Cantarell, C.; Torres, I.B.; Serón, D.R.

2011-01-01

Operational tolerance is defined as stable renal function in transplants without immunosuppression for at least 1 year. We present histological assessments of two patients with operational tolerance. The first withdrew immunosuppression in 2005 and presents stable renal function (creatinine 1.5 mg/dL) without proteinuria. The biopsy showed mild chronic tubulointerstitial changes without inflammation. The second withdrew immunosuppression in 2009 and maintains stable renal function (creatinine 1.6 mg/dL) with mild proteinuria. Histology showed chronic humoural rejection and Class II anti-human leukocyte antigen antibodies were detected. These cases suggest that a renal biopsy may be useful to rule out subclinical pathology in patients with operational tolerance. PMID:25984157

Histological findings in two renal transplants accomplishing operational tolerance criteria.

PubMed

Azancot, M A; Moreso, F; Cantarell, C; Torres, I B; Serón, D R

2011-06-01

Operational tolerance is defined as stable renal function in transplants without immunosuppression for at least 1 year. We present histological assessments of two patients with operational tolerance. The first withdrew immunosuppression in 2005 and presents stable renal function (creatinine 1.5 mg/dL) without proteinuria. The biopsy showed mild chronic tubulointerstitial changes without inflammation. The second withdrew immunosuppression in 2009 and maintains stable renal function (creatinine 1.6 mg/dL) with mild proteinuria. Histology showed chronic humoural rejection and Class II anti-human leukocyte antigen antibodies were detected. These cases suggest that a renal biopsy may be useful to rule out subclinical pathology in patients with operational tolerance.

Mild traumatic brain injury: a risk factor for neurodegeneration

PubMed Central

2010-01-01

Recently, it has become clear that head trauma can lead to a progressive neurodegeneration known as chronic traumatic encephalopathy. Although the medical literature also implicates head trauma as a risk factor for Alzheimer's disease, these findings are predominantly based on clinical diagnostic criteria that lack specificity. The dementia that follows head injuries or repetitive mild trauma may be caused by chronic traumatic encephalopathy, alone or in conjunction with other neurodegenerations (for example, Alzheimer's disease). Prospective longitudinal studies of head-injured individuals, with neuropathological verification, will not only improve understanding of head trauma as a risk factor for dementia but will also enhance treatment and prevention of a variety of neurodegenerative diseases. PMID:20587081

Active myocarditis in a patient with chronic active Epstein-Barr virus infection.

PubMed

Takano, Hiroyuki; Nakagawa, Keiichi; Ishio, Naoki; Daimon, Michiko; Daimon, Masao; Kobayashi, Yoshio; Hiroshima, Kenzo; Komuro, Issei

2008-10-30

Chronic active Epstein-Barr virus (CAEBV) infection is characterized by chronic or recurrent infectious mononucleosis-like symptoms and the prognosis of CAEBV infection is quite poor. The incidence of myocarditis as a complication of EBV infection is not so high and it is unusual that heart failure appears as the initial symptom. However, it is very important to detect and treat chronic active myocarditis in the early phase of CAEBV infection because chronic active myocarditis disorganizes and decreases cardiomyocytes, resulting in the progression to heart failure. We report a case of a 45-year-old man with CAEBV infection for 5 years. Echocardiography revealed moderate left ventricular systolic dysfunction with mild pericardial effusion. Endomyocardial biopsies demonstrated massive lymphocytic infiltration with adjacent myocytolysis and necrosis of cardiomyocytes suggesting active myocarditis. Immunohistological analysis of biopsies revealed that the infiltrating cells were mainly T lymphocytes. And some of the infiltrating cells showed a positive signal for the EBV-encoded small nuclear RNA by in situ hybridization. Positron emission tomography using (18)F-fluoro-2-deoxyglucose ((18)F-FDG) performed revealed increased uptake of (18)F-FDG of whole left ventricular wall with mild heterogeneity.

Insulin resistance during euglycemic clamp studies in chronically undernourished rats with mild streptozocin diabetes.

PubMed

Rao, R H

1995-11-01

Malnutrition has been shown to impair insulin sensitivity, but it is not known whether this effect has any impact on coexisting diabetes. Insulin sensitivity was therefore studied using the glucose clamp technique in rats with chronic nutritional deprivation superimposed on mild streptozocin (STZ) diabetes mellitus. In pair-feeding experiments, 4-week-old littermate rats were either allowed ad libitum access to food or restricted to 50% of ad libitum intake for 8 weeks, and were injected with STZ 40 mg/kg intraperitoneally halfway through the experiment. Fasting plasma glucose (FPG) was similar in both groups of rats, but fasting plasma insulin (FPI) was lower in the undernourished group (P = .016). Undernourished rats were significantly more insulin resistant during euglycemic hyperinsulinemia of the same degree, with glucose disposal rate being impaired by 50% as compared with that in ad libitum-fed diabetic littermates (24.4 +/- 2.8 v 51.5 +/- 4.4 mumol/kg/min, P = .0008). The insulin sensitivity index was significantly lower in the undernourished group (3.03 +/- 0.32 v 5.67 +/- 0.6, P = .0057). The results show that chronic undernutrition markedly reduces insulin sensitivity in rats with mild STZ diabetes. This is further evidence that chronic undernutrition is a deleterious modifying influence on coexisting diabetes mellitus. It suggests that the insulin resistance of malnutrition-related diabetes mellitus (MRDM) could potentially be an acquired defect mediated by the coexistent undernutrition, rather than a "distinctive" feature that is intrinsically unique to this diabetic syndrome.

Psychological stress-induced cerebrovascular dysfunction: the role of metabolic syndrome and exercise.

PubMed

Brooks, Steven; Brnayan, Kayla W; DeVallance, Evan; Skinner, Roy; Lemaster, Kent; Sheets, J Whitney; Pitzer, Christopher R; Asano, Shinichi; Bryner, Randall W; Olfert, I Mark; Frisbee, Jefferson C; Chantler, Paul D

2018-05-01

What is the central question of this study? How does chronic stress impact cerebrovascular function and does metabolic syndrome accelerate the cerebrovascular adaptations to stress? What role does exercise training have in preventing cerebrovascular changes to stress and metabolic syndrome? What is the main finding and its importance? Stressful conditions lead to pathological adaptations of the cerebrovasculature via an oxidative nitric oxide pathway, and the presence of metabolic syndrome produces a greater susceptibility to stress-induced cerebrovascular dysfunction. The results also provide insight into the mechanisms that may contribute to the influence of stress and the role of exercise in preventing the negative actions of stress on cerebrovascular function and structure. Chronic unresolvable stress leads to the development of depression and cardiovascular disease. There is a high prevalence of depression with the metabolic syndrome (MetS), but to what extent the MetS concurrent with psychological stress affects cerebrovascular function is unknown. We investigated the differential effect of MetS on cerebrovascular structure/function in rats (16-17 weeks old) following 8 weeks of unpredictable chronic mild stress (UCMS) and whether exercise training could limit any cerebrovascular dysfunction. In healthy lean Zucker rats (LZR), UCMS decreased (28%, P < 0.05) ex vivo middle cerebral artery (MCA) endothelium-dependent dilatation (EDD), but changes in MCA remodelling and stiffness were not evident, though cerebral microvessel density (MVD) decreased (30%, P < 0.05). The presence of UCMS and MetS (obese Zucker rats; OZR) decreased MCA EDD (35%, P < 0.05) and dilatation to sodium nitroprusside (20%, P < 0.05), while MCA stiffness increased and cerebral MVD decreased (31%, P < 0.05), which were linked to reduced nitric oxide and increased oxidative levels. Aerobic exercise prevented UCMS impairments in MCA function and MVD in LZR, and partly restored MCA function, stiffness and MVD in OZR. Our data suggest that the benefits of exercise with UCMS were due to a reduction in oxidative stress and increased production of nitric oxide in the cerebral vessels. In conclusion, UCMS significantly impaired MCA structure and function, but the effects of UCMS were more substantial in OZR vs. LZR. Importantly, aerobic exercise when combined with UCMS prevented the MCA dysfunction through subtle shifts in nitric oxide and oxidative stress in the cerebral microvasculature. © 2018 The Authors. Experimental Physiology © 2018 The Physiological Society.

Effect of chronic mild stress on serotonergic markers in the skin and brain of the NC/Nga atopic-like mouse strain.

PubMed

Rasul, Aram; El-Nour, Husameldin; Blakely, Randy D; Lonne-Rahm, Sol-Britt; Forsberg, Johan; Johansson, Björn; Theodorsson, Elvar; Nordlind, Klas

2011-11-01

Atopic eczema is often worsened by stress. While acute stress is associated with increased turnover of serotonin (5-hydroxytryptamine; 5-HT), chronic stress causes a decrease. In chronic stress, there is a decrease of the 5-HT1A receptor (R)- and an increase in the 5-HT2AR-responsiveness to 5-HT. In the present study, the impact of chronic mild stress on the expression of 5-HT1A and 5-HT2A receptors and serotonin transporter protein (SERT) was investigated in eczematous skin and brain of atopic-like NC/Nga mice. Twenty-four NC/Nga mice were subjected to chronic mild stress for 12 weeks, and eczema was induced by applying a mite antigen (Dermatophagoides pteronyssinus) on the ears for the last 4 weeks. The mice were divided into three groups, eight per group, stressed eczematous (SE), non-stressed eczematous (NSE) and stressed control (SC). The biopsies were analysed by immunohistochemistry, using a streptavidin-biotin technique. There was an increased number of 5-HT containing dermal mast cell-like mononuclear cells in the skin of mice with eczema (SE and NSE, respectively) compared with the SC, and a tendency to more 5-HT-positive cells in the SE compared with the NSE group. Increased 5-HT1AR immunoreactivity (IR) in the skin and hippocampus of the eczematous groups compared to the control group was seen, but no difference between the SE and NSE groups. The epidermal immunoreactivity for 5-HT2AR was highest in the SE and NSE compared to the SC group, and was also higher in the SE compared to NSE. 5-HT2AR expression was also seen on nerve bundles, the number and intensity of such bundles being decreased in the SE compared to the NSE group. In the CA1 area of the hippocampus, there was an increase in the quantity of cells immunoreactive for 5-HT2AR in the SE versus the NSE group and also in the SE versus the SC group. SERT-IR was found also on nerve bundles with a decreased number in the SE compared to the NSE and SC group. There is a modulation of the expression of serotonergic markers in the eczematous skin and brain of the atopic-like mouse during chronic mild stress.

The spectrum of disease in chronic traumatic encephalopathy.

PubMed

McKee, Ann C; Stern, Robert A; Nowinski, Christopher J; Stein, Thor D; Alvarez, Victor E; Daneshvar, Daniel H; Lee, Hyo-Soon; Wojtowicz, Sydney M; Hall, Garth; 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 in age from 17 to 98 years (mean 59.5 years), including 64 athletes, 21 military veterans (86% of whom were also athletes) and one individual who engaged in self-injurious head banging behaviour. Eighteen age- and gender-matched individuals without a history of repetitive mild traumatic brain injury served as control subjects. In chronic traumatic encephalopathy, the spectrum of hyperphosphorylated tau pathology ranged in severity from focal perivascular epicentres of neurofibrillary tangles in the frontal neocortex to severe tauopathy affecting widespread brain regions, including the medial temporal lobe, thereby allowing a progressive staging of pathology from stages I-IV. Multifocal axonal varicosities and axonal loss were found in deep cortex and subcortical white matter at all stages of chronic traumatic encephalopathy. TAR DNA-binding protein 43 immunoreactive inclusions and neurites were also found in 85% of cases, ranging from focal pathology in stages I-III to widespread inclusions and neurites in stage IV. Symptoms in stage I chronic traumatic encephalopathy included headache and loss of attention and concentration. Additional symptoms in stage II included depression, explosivity and short-term memory loss. In stage III, executive dysfunction and cognitive impairment were found, and in stage IV, dementia, word-finding difficulty and aggression were characteristic. Data on athletic exposure were available for 34 American football players; the stage of chronic traumatic encephalopathy correlated with increased duration of football play, survival after football and age at death. Chronic traumatic encephalopathy was the sole diagnosis in 43 cases (63%); eight were also diagnosed with motor neuron disease (12%), seven with Alzheimer's disease (11%), 11 with Lewy body disease (16%) and four with frontotemporal lobar degeneration (6%). There is an ordered and predictable progression of hyperphosphorylated tau abnormalities through the nervous system in chronic traumatic encephalopathy that occurs in conjunction with widespread axonal disruption and loss. The frequent association of chronic traumatic encephalopathy with other neurodegenerative disorders suggests that repetitive brain trauma and hyperphosphorylated tau protein deposition promote the accumulation of other abnormally aggregated proteins including TAR DNA-binding protein 43, amyloid beta protein and alpha-synuclein.

The spectrum of disease in chronic traumatic encephalopathy

PubMed Central

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 in age from 17 to 98 years (mean 59.5 years), including 64 athletes, 21 military veterans (86% of whom were also athletes) and one individual who engaged in self-injurious head banging behaviour. Eighteen age- and gender-matched individuals without a history of repetitive mild traumatic brain injury served as control subjects. In chronic traumatic encephalopathy, the spectrum of hyperphosphorylated tau pathology ranged in severity from focal perivascular epicentres of neurofibrillary tangles in the frontal neocortex to severe tauopathy affecting widespread brain regions, including the medial temporal lobe, thereby allowing a progressive staging of pathology from stages I–IV. Multifocal axonal varicosities and axonal loss were found in deep cortex and subcortical white matter at all stages of chronic traumatic encephalopathy. TAR DNA-binding protein 43 immunoreactive inclusions and neurites were also found in 85% of cases, ranging from focal pathology in stages I–III to widespread inclusions and neurites in stage IV. Symptoms in stage I chronic traumatic encephalopathy included headache and loss of attention and concentration. Additional symptoms in stage II included depression, explosivity and short-term memory loss. In stage III, executive dysfunction and cognitive impairment were found, and in stage IV, dementia, word-finding difficulty and aggression were characteristic. Data on athletic exposure were available for 34 American football players; the stage of chronic traumatic encephalopathy correlated with increased duration of football play, survival after football and age at death. Chronic traumatic encephalopathy was the sole diagnosis in 43 cases (63%); eight were also diagnosed with motor neuron disease (12%), seven with Alzheimer’s disease (11%), 11 with Lewy body disease (16%) and four with frontotemporal lobar degeneration (6%). There is an ordered and predictable progression of hyperphosphorylated tau abnormalities through the nervous system in chronic traumatic encephalopathy that occurs in conjunction with widespread axonal disruption and loss. The frequent association of chronic traumatic encephalopathy with other neurodegenerative disorders suggests that repetitive brain trauma and hyperphosphorylated tau protein deposition promote the accumulation of other abnormally aggregated proteins including TAR DNA-binding protein 43, amyloid beta protein and alpha-synuclein. PMID:23208308

Effects of piracetam on behavior and memory in adult zebrafish.

PubMed

Grossman, Leah; Stewart, Adam; Gaikwad, Siddharth; Utterback, Eli; Wu, Nadine; Dileo, John; Frank, Kevin; Hart, Peter; Howard, Harry; Kalueff, Allan V

2011-04-25

Piracetam, a derivative of γ-aminobutyric acid, exerts memory-enhancing and mild anxiolytic effects in human and rodent studies. To examine the drug's behavioral profile further, we assessed its effects on behavioral and endocrine (cortisol) responses of adult zebrafish (Danio rerio)--a novel model species rapidly gaining popularity in neurobehavioral research. Overall, acute piracetam did not affect zebrafish novel tank and light-dark box behavior at mild doses (25-400mg/L), but produced nonspecific behavioral inhibition at 700mg/L. No effects on cortisol levels or inter-/intra-session habituation in the novel tank test were observed for acute or chronic mild non-sedative dose of 200mg/L. In contrast, fish exposed to chronic piracetam at this dose performed significantly better in the cued learning plus-maze test. This observation parallels clinical and rodent literature on the behavioral profile of piracetam, supporting the utility of zebrafish paradigms for testing nootropic agents. Copyright © 2011 Elsevier Inc. All rights reserved.

Multidisciplinary collaboration in primary care: through the eyes of patients.

PubMed

Cheong, Lynn H; Armour, Carol L; Bosnic-Anticevich, Sinthia Z

2013-01-01

Managing chronic illness is highly complex and the pathways to access health care for the patient are unpredictable and often unknown. While multidisciplinary care (MDC) arrangements are promoted in the Australian primary health care system, there is a paucity of research on multidisciplinary collaboration from patients' perspectives. This exploratory study is the first to gain an understanding of the experiences, perceptions, attitudes and potential role of people with chronic illness (asthma) on the delivery of MDC in the Australian primary health care setting. In-depth semi-structured interviews were conducted with asthma patients from Sydney, Australia. Qualitative analysis of data indicates that patients are significant players in MDC and their perceptions of their chronic condition, perceived roles of health care professionals, and expectations of health care delivery, influence their participation and attitudes towards multidisciplinary services. Our research shows the challenges presented by patients in the delivery and establishment of multidisciplinary health care teams, and highlights the need to consider patients' perspectives in the development of MDC models in primary care.

Chronic nailbiting: a controlled comparison of competing response and mild aversion treatments.

PubMed

Allen, K W

1996-03-01

Recent studies have suggested that competing response, an abridged version of Azrin and Nunn's (1973) habit reversal method (Behaviour Research and Therapy, 11, 619-628), is a key component in the treatment of chronic nailbiting (Horne & Wilkinson, 1980, Behaviour Research and Therapy, 18, 287-291; Silber & Haynes, 1992, Behaviour Research and Therapy, 30, 15-22). This study replicated and extended the latter by adding an 8 week follow-up period and by using a non-student sample. Forty-five chronic nailbiter Ss were divided into three experimental groups. One method involved the use of mild aversion in which Ss painted a bitter substance on their nails. A second method required the subject to perform a competing response whenever they had the urge to nailbite or found themselves biting their nails. Both methods included self-monitoring of the behaviour and a third group of Ss performed self-monitoring alone as a control condition. The study lasted 12 weeks. Mild aversion resulted in significant improvements in nail length, with the competing response method just failing to show significance in this regard. There was no significant improvement for the control group. The implications for further study and the benefits of competing response in the light of these findings are discussed in terms of treatment success and use of therapist time.

Adaptive response studies may help choose astronauts for long-term space travel.

PubMed

Mortazavi, S M; Cameron, J R; Niroomand-rad, A

2003-01-01

Long-term manned exploratory missions are planned for the future. Exposure to high-energy neutrons, protons and high charge and energy particles during a deep space mission, needs protection against the detrimental effects of space radiation. It has been suggested that exposure to unpredictable extremely large solar particle events would kill the astronauts without massive shielding. To reduce this risk to astronauts and to minimize the need for shielding, astronauts with highest significant adaptive responses should be chosen. It has been demonstrated that some humans living in very high natural radiation areas have acquired high adaptive responses to external radiation. Therefore, we suggest that for a deep space mission the adaptive response of all potential crew members be measured and only those with high adaptive response be chosen. We also proclaim that chronic exposure to elevated levels of radiation can considerably decrease radiation susceptibility and better protect astronauts against the unpredictable exposure to sudden and dramatic increase in flux due to solar flares and coronal mass ejections. c2003 COSPAR. Published by Elsevier Science Ltd. All rights reserved.

[Clinical significance of calcitonin gene-related peptide level before and after treatment in patients with chronic periodontitis].

PubMed

Yan, Ying; Xiang, Xue-Rong; Wang, Chun; Ye, Guo; Fan, Xiao-Ping

2016-08-01

To explore the clinical significance of calcitonin gene-related peptide (CGRP) levels in patients with chronic periodontitis before and after treatment, and to detect the calcitonin gene-related peptide content in human venous blood. Thirty healthy controls and thirty patients with mild, moderate, severe periodontitis were enrolled from August 2014 to June 2015.CGRP level in the patients' peripheral blood was detected by ELISA. Three months after periodontal treatment, CGRP level in mild, moderate, severe periodontitis patients' peripheral blood was re-examined by ELISA. Then the correlation between calcitonin gene-related peptide and inflammation of chronic periodontitis was analyzed with SPSS 22.0 software package. The content of CGRP in healthy controls was significantly higher than that in patients with periodontitis. With the aggravation of periodontal inflammation, blood level of CGRP decreased gradually, and the lowest was in patients with severe periodontitis (P<0.01). Three months after periodontal treatment, CGRP content was significantly higher compared with that before treatment (P<0.05), but no significant difference was found in patients with different degree of periodontitis (P>0.05). The level of CGRP in venous blood decreased with the increasing severity of chronic periodontitis, and CGRP was negatively correlated with the degree of inflammation of chronic periodontitis. CGRP may be involved in the occurrence and development of chronic periodontitis. CGRP content in serum of patients with chronic periodontitis after treatment was significantly increased, CGRP may be used as the basis for clinical detection of chronic periodontitis.

Our experience with transcanalicular laser-assisted endoscopic dacryocystorhinostomy (TCLADCR) in patients of chronic dacryocystitis with deviated nasal septum.

PubMed

Goel, Ruchi; Nagpal, Smriti; Kumar, Sushil; Kamal, Saurabh; Dangda, Sonal; Bodh, Sonam Angmo

2015-12-01

The purpose of this study is to study the operative difficulties and success rate of transcanalicular laser-assisted endoscopic dacryocystorhinostomy in patients of chronic dacryocystitis with deviated nasal septum (DNS). A prospective interventional clinical study of 36 consecutive patients suffering from chronic dacryocystitis with nasolacrimal duct obstruction with DNS undergoing primary TCLADCR from March to June 2011 was carried out. Diode laser was used to create a 16-mm(2) ostium which was enlarged to 64 mm(2) using Blakesley's forceps. Success was defined as anatomical patency and absence of symptoms at 12 months of follow-up. Out of the 36 patients, 25 were females with ages 20-72 years, and 19 were left sided. There were 12 high, 12 mid and 12 basal DNS towards the side of surgery, mild to moderate in severity. Intraoperatively there was difficulty in visualising the aiming beam in the nose, tedious manipulation of endoscope and excessive bleeding in 3 patients. Increased bleeding and failures were significantly higher in high DNS (Fisher exact test-2 tailed: 0.0045). The procedure was successful in 94.4 % cases with average ostium size of 21.94 mm(2) at 12 months and no statistically significant difference in success rates between mild and moderate DNS (Fisher exact test-2 tailed: 1.000). Also there was no difference in the complication rate between mild and moderate DNS (Fisher exact test-2 tailed: 0.0841). TCLADCR is an effective procedure in patients with mild to moderate mid and basal DNS and obviates the need for multiple procedures and a cutaneous scar.

Self-Management Training of Mentally Retarded Adults with Chronic Conduct Difficulties. RT11.

ERIC Educational Resources Information Center

Cole, Christine L.; And Others

Six mildly and moderately mentally retarded adults with chronic and severe emotional/behavioral problems participated in a study of the assumption that aggression and conduct disorders reflected self-managed coping skills deficits. The study was conducted in a vocational training workshop setting located in the Waisman Center on Mental Retardation…

Influence of chronic back pain on kinematic reactions to unpredictable arm pulls.

PubMed

Götze, Martin; Ernst, Michael; Koch, Markus; Blickhan, Reinhard

2015-03-01

There is evidence that muscle reflexes are delayed in patients with chronic low back pain in response to perturbations. It is still unrevealed whether these delays accompanied by an altered kinematic or compensated by adaption of other muscle parameters. The aim of this study was to investigate whether chronic low back pain patients show an altered kinematic reaction and if such data are reliable for the classification of chronic low back pain. In an experiment involving 30 females, sudden lateral perturbations were applied to the arm of a subject in an upright, standing position. Kinematics was used to distinguish between chronic low back pain patients and healthy controls. A calculated model of a stepwise discriminant function analysis correctly predicted 100% of patients and 80% of healthy controls. The estimation of the classification error revealed a constant rate for the classification of the healthy controls and a slightly decreased rate for the patients. Observed reflex delays and identified kinematic differences inside and outside the region of pain during impaired movement indicated that chronic low back pain patients have an altered motor control that is not restricted to the lumbo-pelvic region. This applied paradigm of external perturbations can be used to detect chronic low back pain patients and also persons without chronic low back pain but with an altered motor control. Further investigations are essential to reveal whether healthy persons with changes in motor function have an increased potential to develop chronic back pain. Copyright © 2015 Elsevier Ltd. All rights reserved.

Prevalence and risk factors of mild chronic renal failure in HIV-infected patients: influence of female gender and antiretroviral therapy.

PubMed

Cristelli, Marina Pontello; Trullàs, Joan Carles; Cofán, Federico; Rico, Naira; Manzardo, Christian; Ambrosioni, Juan; Bedini, Josep Lluis; Moreno, Asunción; Diekmann, Fritz; Miro, Jose Maria

2018-05-18

In people living with HIV, much is known about chronic kidney disease, defined as a glomerular filtration rate under 60mL/min. However, there is scarce data about prevalence and risk factors for milder impairment (60-89mL/min). The present study aims to assess the influence of sex, antiretroviral therapy, and classical risk factors on the occurrence of mild decreased renal function in a large Spanish cohort of HIV-infected patients. Cross-sectional, single center study, including all adult HIV-1-infected patients under antiretroviral treatment with at least two serum creatinine measures during 2014, describing the occurrence of and the risk factors for mildly decreased renal function (eGFR by CKD-EPI creatinine equation of 60-89mL/min). Among the 4337 patients included, the prevalence rate of mildly reduced renal function was 25%. Independent risk factors for this outcome were age older than 50 years (OR 3.03, 95% CI 2.58-3.55), female sex (OR 1.23, 95% CI 1.02-1.48), baseline hypertension (OR 1.57, 95% CI 1.25-1.97) or dyslipidemia (OR 1.48, 95% CI 1.17-1.87), virologic suppression (OR 1.88, 95% CI 1.39-2.53), and exposure to tenofovir disoproxil-fumarate (OR 1.67, 95% CI 1.33-2.08) or ritonavir-boosted protease-inhibitors (OR 1.19, 95% CI 1.03-1.39). Females and patients over 50 seem to be more vulnerable to renal impairment. Potentially modifiable risk factors and exposure to tenofovir disoproxil-fumarate or ritonavir-boosted protease-inhibitors are present even in earlier stages of chronic kidney dysfunction. It remains to be determined whether early interventions including antiretroviral therapy changes (tenofovir alafenamide, cobicistat) or improving comorbidities management will improve the course of chronic kidney disease. Copyright © 2018 Sociedade Brasileira de Infectologia. Published by Elsevier Editora Ltda. All rights reserved.

Clinical Comparison of 99mTc Exametazime and 123I Ioflupane SPECT in Patients with Chronic Mild Traumatic Brain Injury

PubMed Central

Newberg, Andrew B.; Serruya, Mijail; Gepty, Andrew; Intenzo, Charles; Lewis, Todd; Amen, Daniel; Russell, David S.; Wintering, Nancy

2014-01-01

Background This study evaluated the clinical interpretations of single photon emission computed tomography (SPECT) using a cerebral blood flow and a dopamine transporter tracer in patients with chronic mild traumatic brain injury (TBI). The goal was to determine how these two different scan might be used and compared to each other in this patient population. Methods and Findings Twenty-five patients with persistent symptoms after a mild TBI underwent SPECT with both 99mTc exametazime to measure cerebral blood flow (CBF) and 123I ioflupane to measure dopamine transporter (DAT) binding. The scans were interpreted by two expert readers blinded to any case information and were assessed for abnormal findings in comparison to 10 controls for each type of scan. Qualitative CBF scores for each cortical and subcortical region along with DAT binding scores for the striatum were compared to each other across subjects and to controls. In addition, symptoms were compared to brain scan findings. TBI patients had an average of 6 brain regions with abnormal perfusion compared to controls who had an average of 2 abnormal regions (p<0.001). Patient with headaches had lower CBF in the right frontal lobe, and higher CBF in the left parietal lobe compared to patients without headaches. Lower CBF in the right temporal lobe correlated with poorer reported physical health. Higher DAT binding was associated with more depressive symptoms and overall poorer reported mental health. There was no clear association between CBF and DAT binding in these patients. Conclusions Overall, both scans detected abnormalities in brain function, but appear to reflect different types of physiological processes associated with chronic mild TBI symptoms. Both types of scans might have distinct uses in the evaluation of chronic TBI patients depending on the clinical scenario. PMID:24475210

Short-term and long-term outcome of athletic closed head injuries.

PubMed

Webbe, Frank M; Barth, Jeffrey T

2003-07-01

The continued development of the sport environment as a laboratory for clinical investigation of mild head injury has greatly advanced the use of neuropsychological assessment in evaluating brain-injured athletes, and tracking their symptoms and recovery in an objective manner. The use of neurocognitive baseline measures has become critical in determining whether a brain-injured athlete has recovered function sufficiently to return to play. The rapid growth of computerized and web-based neurocognitive assessment measures provides an efficient, valid technology to put such testing within the reach of most institutions and organizations that field sport teams. Moreover, the knowledge of the recovery curve following mild head injury in the sport environment can be generalized to the management of MTBI in general clinical environments where baseline measures are unlikely. What we know today is that sideline assessments of severity are not predictive of which athletes will show the most typical 5- to 10-day recovery period and which will report persistent PCS complaints and exhibit impaired neurocognitive performance for an extended time. The research on mechanisms of brain injury in MTBI suggests that unpredictable, diffuse white-matter damage may control much of the variability in functional impairments and recovery duration.

Ensuring Effective Prevention of Iodine Deficiency Disorders.

PubMed

Völzke, Henry; Caron, Philippe; Dahl, Lisbeth; de Castro, João J; Erlund, Iris; Gaberšček, Simona; Gunnarsdottir, Ingibjörg; Hubalewska-Dydejczyk, Alicja; Ittermann, Till; Ivanova, Ludmila; Karanfilski, Borislav; Khattak, Rehman M; Kusić, Zvonko; Laurberg, Peter; Lazarus, John H; Markou, Kostas B; Moreno-Reyes, Rodrigo; Nagy, Endre V; Peeters, Robin P; Pīrāgs, Valdis; Podoba, Ján; Rayman, Margaret P; Rochau, Ursula; Siebert, Uwe; Smyth, Peter P; Thuesen, Betina H; Troen, Aron; Vila, Lluís; Vitti, Paolo; Zamrazil, Vaclav; Zimmermann, Michael B

2016-02-01

Programs initiated to prevent iodine deficiency disorders (IDD) may not remain effective due to changes in government policies, commercial factors, and human behavior that may affect the efficacy of IDD prevention programs in unpredictable directions. Monitoring and outcome studies are needed to optimize the effectiveness of IDD prevention. Although the need for monitoring is compelling, the current reality in Europe is less than optimal. Regular and systematic monitoring surveys have only been established in a few countries, and comparability across the studies is hampered by the lack of centralized standardization procedures. In addition, data on outcomes and the cost of achieving them are needed in order to provide evidence of the beneficial effects of IDD prevention in countries with mild iodine deficiency. Monitoring studies can be optimized by including centralized standardization procedures that improve the comparison between studies. No study of iodine consumption can replace the direct measurement of health outcomes and the evaluation of the costs and benefits of the program. It is particularly important that health economic evaluation should be conducted in mildly iodine-deficient areas and that it should include populations from regions with different environmental, ethnic, and cultural backgrounds.

Chronic stress induces a selective decrease in AMPA receptor-mediated synaptic excitation at hippocampal temporoammonic-CA1 synapses.

PubMed

Kallarackal, Angy J; Kvarta, Mark D; Cammarata, Erin; Jaberi, Leelah; Cai, Xiang; Bailey, Aileen M; Thompson, Scott M

2013-10-02

Chronic stress promotes depression, but how it disrupts cognition and mood remains unknown. Chronic stress causes atrophy of pyramidal cell dendrites in the hippocampus and cortex in human and animal models, and a depressive-like behavioral state. We now test the hypothesis that excitatory temporoammonic (TA) synapses in the distal dendrites of CA1 pyramidal cells in rats are altered by chronic unpredictable stress (CUS) and restored by chronic antidepressant treatment, in conjunction with the behavioral consequences of CUS. We observed a decrease in AMPAR-mediated excitation at TA-CA1 synapses, but not Schaffer collateral-CA1 synapses, after CUS, with a corresponding layer-specific decrease in GluA1 expression. Both changes were reversed by chronic fluoxetine. CUS also disrupted long-term memory consolidation in the Morris water maze, a function of TA-CA1 synapses. The decreases in TA-CA1 AMPAR-mediated excitation and performance in the consolidation test were correlated positively with decreases in sucrose preference, a measure of anhedonia. We conclude that chronic stress selectively decreases AMPAR number and function at specific synapses and suggest that this underlies various depressive endophenotypes. Our findings provide evidence that glutamatergic dysfunction is an underlying cause of depression and that current first-line antidepressant drugs act by restoring excitatory synaptic strength. Our findings suggest novel therapeutic targets for this debilitating disease.

Cynomolgus monkeys are successfully and persistently infected with hepatitis E virus genotype 3 (HEV-3) after long-term immunosuppressive therapy

PubMed Central

Guimarães, Juliana Rodrigues; Melgaço, Juliana Gil; Kevorkian, Yohan Britto; Bottino, Fernanda de Oliveira; Vieira, Yasmine Rangel; da Silva, Aline Campos de Azevedo; Pinto, Douglas Pereira; da Fonseca, Laís Bastos; Vilhena, Leandro Schiavo; Uiechi, Edilson; da Silva, Maria Cristina Carlan; Moran, Julio; Marchevsky, Renato Sérgio; Cruz, Oswaldo Gonçalves; Otonel, Rodrigo Alejandro Arellano; Alfieri, Amauri Alcindo; de Oliveira, Jaqueline Mendes; Gaspar, Ana Maria Coimbra; Pinto, Marcelo Alves

2017-01-01

Epidemiological studies found that hepatitis E virus genotype 3 (HEV-3) infection was associated with chronic hepatitis and cirrhosis in immunocompromised patients. Our study aimed to investigate the relationship between the host immunosuppressive status and the occurrence of HEV-related chronic hepatitis. Here we describe a successful experimental study, using cynomolgus monkeys previously treated with tacrolimus, a potent calcineurin inhibitor immunosuppressant, and infected with a Brazilian HEV-3 strain isolated from naturally infected pigs. HEV infected monkeys were followed up during 160 days post infection (dpi) by clinical signs; virological, biochemical and haematological parameters; and liver histopathology. The tacrolimus blood levels were monitored throughout the experiment. Immunosuppression was confirmed by clinical and laboratorial findings, such as: moderate weight loss, alopecia, and herpes virus opportunistic infection. In this study, chronic HEV infection was characterized by the mild increase of liver enzymes serum levels; persistent RNA viremia and viral faecal shedding; and liver histopathology. Three out of four immunosuppressed monkeys showed recurrent HEV RNA detection in liver samples, evident hepatocellular ballooning degeneration, mild to severe macro and microvesicular steatosis (zone 1), scattered hepatocellular apoptosis, and lobular focal inflammation. At 69 dpi, liver biopsies of all infected monkeys revealed evident ballooning degeneration (zone 3), discrete hepatocellular apoptosis, and at most mild portal and intra-acinar focal inflammation. At 160 dpi, the three chronically HEV infected monkeys showed microscopic features (piecemeal necrosis) corresponding to chronic hepatitis in absence of fibrosis and cirrhosis in liver parenchyma. Within 4-months follow up, the tacrolimus-immunosuppressed cynomolgus monkeys infected with a Brazilian swine HEV-3 strain exhibited more severe hepatic lesions progressing to chronic hepatitis without liver fibrosis, similarly as shown in tacrolimus-immunosuppressed solid organ transplant (SOT) recipients. The cause-effect relationship between HEV infection and tacrolimus treatment was confirmed in this experiment. PMID:28328941

Chronic periodontitis and oral health-related quality of life in Chinese adults: A population-based, cross-sectional study.

PubMed

He, Songlin; Wei, Shicheng; Wang, Jinhua; Ji, Ping

2018-02-21

This population-based, cross-sectional study explored the association between chronic periodontitis and oral health-related quality of life (OHRQoL) in Chinese adults, independently of sociodemographic factors and other common oral conditions. The present study was carried out in a sample population of 480 adults aged 35 to 74 years from Chongqing municipality. A multi-stage stratified random sampling approach was adopted to select participants. The Chinese version of the short-form oral health impact profile (OHIP-14) was used to assess OHRQoL. Chronic periodontitis was trichotomized into mild, moderate, and severe periodontitis. Logistic regression models were adopted to explore the association between the severity of chronic periodontitis and OHIP-14 scores. After adjustment for sociodemographic factors and other common clinical conditions, participants with severe and moderate chronic periodontitis, respectively, had 1.63- (95% CI: 1.41 to 1.98) and 1.42-fold (95% CI: 1.29 to 1.63) higher odds for the OHIP-14 scores being above the median compared with participants without chronic periodontitis. However, participants with mild periodontitis did not have significantly higher odds for the OHIP-14 scores being above the median than participants without chronic periodontitis. Certain sociodemographic variables, including higher age, lower education level, number of missing teeth, and current smoker, had negative associations with OHRQoL. Chronic periodontitis was associated with poorer OHRQoL in Chinese adults. In addition, the impairment in OHRQoL showed a significant correlation with the severity of chronic periodontitis. © 2018 American Academy of Periodontology.

Chronic periodontitis and oral health-related quality of life in Chinese adults: A population-based, cross-sectional study.

PubMed

He, Songlin; Wei, Shicheng; Wang, Jinhua; Ji, Ping

2018-03-01

This population-based, cross-sectional study explored the association between chronic periodontitis and oral health-related quality of life (OHRQoL) in Chinese adults, independently of sociodemographic factors and other common oral conditions. The present study was carried out in a sample population of 480 adults aged 35 to 74 years from Chongqing municipality. A multi-stage stratified random sampling approach was adopted to select participants. The Chinese version of the short-form oral health impact profile (OHIP-14) was used to assess OHRQoL. Chronic periodontitis was trichotomized into mild, moderate, and severe periodontitis. Logistic regression models were adopted to explore the association between the severity of chronic periodontitis and OHIP-14 scores. After adjustment for sociodemographic factors and other common clinical conditions, participants with severe and moderate chronic periodontitis, respectively, had 1.63- (95% CI: 1.41 to 1.98) and 1.42-fold (95% CI: 1.29 to 1.63) higher odds for the OHIP-14 scores being above the median compared with participants without chronic periodontitis. However, participants with mild periodontitis did not have significantly higher odds for the OHIP-14 scores being above the median than participants without chronic periodontitis. Certain sociodemographic variables, including higher age, lower education level, number of missing teeth, and current smoker, had negative associations with OHRQoL. Chronic periodontitis was associated with poorer OHRQoL in Chinese adults. In addition, the impairment in OHRQoL showed a significant correlation with the severity of chronic periodontitis. © 2018 American Academy of Periodontology.

Acute agmatine administration, similar to ketamine, reverses depressive-like behavior induced by chronic unpredictable stress in mice.

PubMed

Neis, Vivian B; Bettio, Luis E B; Moretti, Morgana; Rosa, Priscila B; Ribeiro, Camille M; Freitas, Andiara E; Gonçalves, Filipe M; Leal, Rodrigo B; Rodrigues, Ana Lúcia S

Agmatine is an endogenous neuromodulator that has been shown to have antidepressant-like properties. We have previously demonstrated that it can induce a rapid increase in BDNF levels after acute administration, suggesting that agmatine may be a fast-acting antidepressant. To investigate this hypothesis, the present study evaluated the effects of a single administration of agmatine in mice subjected to chronic unpredictable stress (CUS), a model of depression responsive only to chronic treatment with conventional antidepressants. The ability of agmatine to reverse CUS-induced behavioral and biochemical alterations was evaluated and compared with those elicited by the fast-acting antidepressant (ketamine) and the conventional antidepressant (fluoxetine). After exposed to CUS for 14days, mice received a single oral dose of agmatine (0.1mg/kg), ketamine (1mg/kg) or fluoxetine (10mg/kg), and were submitted to behavioral evaluation after 24h. The exposure to CUS caused an increased immobility time in the tail suspension test (TST) but did not change anhedonic-related parameters in the splash test. Our findings provided evidence that, similarly to ketamine, agmatine is able to reverse CUS-induced depressive-like behavior in the TST. Western blot analyses of prefrontal cortex (PFC) demonstrated that mice exposed to CUS and/or treated with agmatine, fluoxetine or ketamine did not present alterations in the immunocontent of synaptic proteins [i.e. GluA1, postsynaptic density protein 95 (PSD-95) and synapsin]. Altogether, our findings indicate that a single administration of agmatine is able to reverse behavioral alterations induced by CUS in the TST, suggesting that this compound may have fast-acting antidepressant-like properties. However, there was no alteration in the levels of synaptic proteins in the PFC, a result that need to be further investigated in other time points. Copyright © 2016 Elsevier Inc. All rights reserved.

Treatment options for chronic pancreatitis.

PubMed

Issa, Yama; Bruno, Marco J; Bakker, Olaf J; Besselink, Marc G; Schepers, Nicolien J; van Santvoort, Hjalmar C; Gooszen, Hein G; Boermeester, Marja A

2014-09-01

This Review covers the latest developments in the treatment options for chronic pancreatitis. Pain is the most frequent and dominant symptom in patients with chronic pancreatitis, which ranges from severe disabling continuous pain to mild pain attacks and pain-free periods. Conventional treatment strategies and recent changes in the treatment of pain in patients with chronic pancreatitis are outlined. The different treatment options for pain consist of medical therapy, endoscopy or surgery. Their related merits and drawbacks are discussed. Finally, novel insights in the field of genetics and microbiota are summarized, and future perspectives are discussed.

Thiothixene in the treatment of geriatric patients with chronic organic brain syndrome.

PubMed

Rada, R T; Kellner, R

1976-03-01

Thiothixene was used in a four-week double-blind placebo-controlled study of 42 geriatric patients with chronic organic brain syndrome (psychotic or nonpsychotic). The results, according to several rating measures, showed no significant difference between placebo and thiothixene. Side effects were mild and few. These data support the safety of thiothixene therapy for geriatric patients; however, there is no conclusive evidence of its efficacy in the treatment of chronic organic brain syndrome.

Taking a proactive approach to mild to moderate chronic oedema: a case study.

PubMed

Jehu, Diane; Jenkins, Linda; Morgan, Karen; Thomas, Melanie J

2018-02-02

This case study demonstrates the benefits of early intervention and a proactive approach for a patient with chronic oedema living in the community. These benefited the patient and also supported value-based healthcare in the NHS. The patient's health and wellbeing significantly improved with an assessment of his chronic oedema and a management plan consisting of skincare, an exercise and movement programme and the introduction of a class 1 British standard compression garment.

Early and Later Life Stress Alter Brain Activity and Sleep in Rats

PubMed Central

Mrdalj, Jelena; Pallesen, Ståle; Milde, Anne Marita; Jellestad, Finn Konow; Murison, Robert; Ursin, Reidun; Bjorvatn, Bjørn; Grønli, Janne

2013-01-01

Exposure to early life stress may profoundly influence the developing brain in lasting ways. Neuropsychiatric disorders associated with early life adversity may involve neural changes reflected in EEG power as a measure of brain activity and disturbed sleep. The main aim of the present study was for the first time to characterize possible changes in adult EEG power after postnatal maternal separation in rats. Furthermore, in the same animals, we investigated how EEG power and sleep architecture were affected after exposure to a chronic mild stress protocol. During postnatal day 2–14 male rats were exposed to either long maternal separation (180 min) or brief maternal separation (10 min). Long maternally separated offspring showed a sleep-wake nonspecific reduction in adult EEG power at the frontal EEG derivation compared to the brief maternally separated group. The quality of slow wave sleep differed as the long maternally separated group showed lower delta power in the frontal-frontal EEG and a slower reduction of the sleep pressure. Exposure to chronic mild stress led to a lower EEG power in both groups. Chronic exposure to mild stressors affected sleep differently in the two groups of maternal separation. Long maternally separated offspring showed more total sleep time, more episodes of rapid eye movement sleep and higher percentage of non-rapid eye movement episodes ending in rapid eye movement sleep compared to brief maternal separation. Chronic stress affected similarly other sleep parameters and flattened the sleep homeostasis curves in all offspring. The results confirm that early environmental conditions modulate the brain functioning in a long-lasting way. PMID:23922857

Identifying Specific Combinations of Multimorbidity that Contribute to Health Care Resource Utilization: An Analytic Approach.

PubMed

Schiltz, Nicholas K; Warner, David F; Sun, Jiayang; Bakaki, Paul M; Dor, Avi; Given, Charles W; Stange, Kurt C; Koroukian, Siran M

2017-03-01

Multimorbidity affects the majority of elderly adults and is associated with higher health costs and utilization, but how specific patterns of morbidity influence resource use is less understood. The objective was to identify specific combinations of chronic conditions, functional limitations, and geriatric syndromes associated with direct medical costs and inpatient utilization. Retrospective cohort study using the Health and Retirement Study (2008-2010) linked to Medicare claims. Analysis used machine-learning techniques: classification and regression trees and random forest. A population-based sample of 5771 Medicare-enrolled adults aged 65 and older in the United States. Main covariates: self-reported chronic conditions (measured as none, mild, or severe), geriatric syndromes, and functional limitations. Secondary covariates: demographic, social, economic, behavioral, and health status measures. Medicare expenditures in the top quartile and inpatient utilization. Median annual expenditures were $4354, and 41% were hospitalized within 2 years. The tree model shows some notable combinations: 64% of those with self-rated poor health plus activities of daily living and instrumental activities of daily living disabilities had expenditures in the top quartile. Inpatient utilization was highest (70%) in those aged 77-83 with mild to severe heart disease plus mild to severe diabetes. Functional limitations were more important than many chronic diseases in explaining resource use. The multimorbid population is heterogeneous and there is considerable variation in how specific combinations of morbidity influence resource use. Modeling the conjoint effects of chronic conditions, functional limitations, and geriatric syndromes can advance understanding of groups at greatest risk and inform targeted tailored interventions aimed at cost containment.

Interaction of Metabolic Stress with Chronic Mild Stress in Altering Brain Cytokines and Sucrose Preference

PubMed Central

Remus, Jennifer L.; Stewart, Luke T.; Camp, Robert M.; Novak, Colleen M.; Johnson, John D.

2015-01-01

There is growing evidence that metabolic stressors increase an organism’s risk of depression. Chronic mild stress is a popular animal model of depression and several serendipitous findings have suggested that food deprivation prior to sucrose testing in this model is necessary to observe anhedonic behaviors. Here, we directly tested this hypothesis by exposing animals to chronic mild stress and used an overnight two bottle sucrose test (food ad libitum) on day 5 and 10, then food and water deprive animals overnight and tested their sucrose consumption and preference in a 1h sucrose test the following morning. Approximately 65% of stressed animals consumed sucrose and showed a sucrose preference similar to non-stressed controls in an overnight sucrose test, while 35% showed a decrease in sucrose intake and preference. Following overnight food and water deprivation the previously ‘resilient’ animals showed a significant decrease in sucrose preference and greatly reduced sucrose intake. In addition, we evaluated whether the onset of anhedonia following food and water deprivation corresponds to alterations in corticosterone, epinephrine, circulating glucose, or interleukin-1 beta expression in limbic brain areas. While all stressed animals showed adrenal hypertrophy and elevated circulating epinephrine, only stressed animals that were food deprived were hypoglycemic compared to food deprived controls. Additionally, food and water deprivation significantly increased hippocampus IL-1β while food and water deprivation only increased hypothalamus IL-1β in stress susceptible animals. These data demonstrate that metabolic stress of food and water deprivation interacts with chronic stressor exposure to induce physiological and anhedonic responses. PMID:25914924

Neuropathic pain promotes adaptive changes in gene expression in brain networks involved in stress and depression.

PubMed

Descalzi, Giannina; Mitsi, Vasiliki; Purushothaman, Immanuel; Gaspari, Sevasti; Avrampou, Kleopatra; Loh, Yong-Hwee Eddie; Shen, Li; Zachariou, Venetia

2017-03-21

Neuropathic pain is a complex chronic condition characterized by various sensory, cognitive, and affective symptoms. A large percentage of patients with neuropathic pain are also afflicted with depression and anxiety disorders, a pattern that is also seen in animal models. Furthermore, clinical and preclinical studies indicate that chronic pain corresponds with adaptations in several brain networks involved in mood, motivation, and reward. Chronic stress is also a major risk factor for depression. We investigated whether chronic pain and stress affect similar molecular mechanisms and whether chronic pain can affect gene expression patterns that are involved in depression. Using two mouse models of neuropathic pain and depression [spared nerve injury (SNI) and chronic unpredictable stress (CUS)], we performed next-generation RNA sequencing and pathway analysis to monitor changes in gene expression in the nucleus accumbens (NAc), the medial prefrontal cortex (mPFC), and the periaqueductal gray (PAG). In addition to finding unique transcriptome profiles across these regions, we identified a substantial number of signaling pathway-associated genes with similar changes in expression in both SNI and CUS mice. Many of these genes have been implicated in depression, anxiety, and chronic pain in patients. Our study provides a resource of the changes in gene expression induced by long-term neuropathic pain in three distinct brain regions and reveals molecular connections between pain and chronic stress. Copyright © 2017, American Association for the Advancement of Science.

Expert Statement on the Single-Agent Use of Inhaled Bronchodilator in the Treatment of Stable Mild-Moderate Chronic Obstructive Pulmonary Disease.

PubMed

Riesco Miranda, Juan Antonio; Alcázar, Bernardino; Alfageme, Inmaculada; Casanova, Ciro; Celli, Bartolomé; de-Torres, Juan P; Jiménez Ruiz, Carlos A

2017-10-01

To describe the evidence- and experience-based expert consensus on the use of single-agent bronchodilators in patients with stable mild-moderate chronic obstructive pulmonary disease (COPD). Using Delphi methodology, a panel of 7 respiratory medicine experts was established, who, in the first nominal group meeting defined the scope, users, and document sections. The panel drew up 14 questions on the use of single-agent bronchodilators in patients with mild-moderate stable COPD to be answered with a systematic review of the literature. The results of the review were discussed in a second nominal group meeting and 17 statements were generated. Agreement/disagreement with the statements was tested among16 different experts including respiratory medicine experts and primary care physicians. Statements were scored from1 (total disagreement) to10 (total agreement). Agreement was considered if at least 70% voted ≥7. The level of evidence and grade of recommendation of the systematic literature review was assessed using the Oxford Centre for Evidence-based Medicine levels. A total of 12 of the 17 statements were selected. Specific statements were generated on different profiles of patients with stable mild-moderate COPD in whom single-agent bronchodilators could be prescribed. These statements on the use of single-agent bronchodilators might improve the outcomes and prognosis of patients with stable mild-moderate COPD. Copyright © 2017 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

Defining the Pathophysiological Role of Tau in Experimental TBI

DTIC Science & Technology

2016-10-01

in AD. This pathway is a major source for excitatory innervation of hippocampus , a structure vital for memory formation. Damage to the EC or...hippocampal input pathway that is both preferentially vulnerable in early-stage AD and critically important for long-term memory . The model confines...structure and function of the hippocampus after single or repetitive mild TBI, and whether mild TBI exacerbates ongoing tauopathy to promote a chronic

Predictors of cognitive and physical fatigue in post-acute mild-moderate traumatic brain injury.

PubMed

Schiehser, Dawn M; Delano-Wood, Lisa; Jak, Amy J; Hanson, Karen L; Sorg, Scott F; Orff, Henry; Clark, Alexandra L

2017-10-01

Post-traumatic fatigue (PTF) is a common, disabling, and often chronic symptom following traumatic brain injury (TBI). Yet, the impact of chronic cognitive and physical fatigue and their associations with psychiatric, sleep, cognitive, and psychosocial sequelae in mild-moderate TBI remain poorly understood. Sixty Veterans with a history of mild-moderate TBI and 40 Veteran controls (VC) were administered the Modified Fatigue Impact Scale, a validated measure of TBI-related cognitive and physical fatigue as well as measures of neuropsychiatric, psychosocial, sleep, and objective cognitive functioning. Compared to VC, TBI Veterans endorsed significantly greater levels of cognitive and physical fatigue. In TBI, psychiatric symptoms, sleep disturbance, and post-traumatic amnesia (PTA) were associated with both cognitive and physical fatigue, while loss of consciousness (LOC) and poor attention/processing speed were related to elevations in cognitive fatigue only. In regression analyses, anxiety, sleep disturbance, and LOC significantly predicted cognitive fatigue, while only post-traumatic stress symptoms and PTA contributed to physical fatigue. Cognitive and physical fatigue are problematic symptoms following mild-moderate TBI that are differentially associated with specific injury and psychiatric sequelae. Findings provide potential symptom targets for interventions aimed at ameliorating fatigue, and further underscore the importance of assessing and treating fatigue as a multi-dimensional symptom following TBI.

Neuropeptide Y stimulation as primary target for preventive measures of maladaptative cardiovascular reactions in occupational chronic stress exposure.

PubMed

Ciumaşu-Rîmbu, Mălina; Popa, Livia; Vulpoi, Carmen

2012-01-01

Chronic stress may produce a decrease in central NPY expression and subjects exposed to it may prove hypersensitivity to a novel stressor with dysfunctions in the NPY system and cardiovascular maladaptation to stress, even hypertension. Upregulation of NPY expression may contribute to successful behavioral adaptation to stress by reducing cardiovascular tone and suppressing anxious behaviors. Adaptogens, a new class of metabolic regulators stimulate NPY expression and release. The aim of this study is to increase tolerance and adaptation to stress of hypersensitive to novel stressor, occupational chronic stress exposed subjects with cardiovascular maladaptation to mild new stressor using adaptogens as part of prevention protocol. 40 military personnel with known cardiostressor reactional mode and occupational chronic stress exposure were exposed to mild novel stressor: occupational medicine routine evaluation and clinically assessed for maladaptative cardiovascular response prior and before application of 30 day prevention protocol. Employees were randomly split in two groups, one receiving standard prevention protocol (lifestyle counseling) plus adaptogens in multiple dose administration, twice daily and the other receiving only standard prevention protocol. We found significant statistic differences in all cardiovascular parameters in adaptogen group and only in diastolic blood pressure in control group. Adaptogens could be an important factor in successful prevention protocols of chronic occupational stress dysfunctions involving NPY systems.

High frequency of GATA2 mutations in patients with mild chronic neutropenia evolving to MonoMac syndrome, myelodysplasia, and acute myeloid leukemia

PubMed Central

Pasquet, Marlène; Bellanné-Chantelot, Christine; Tavitian, Suzanne; Prade, Naïs; Beaupain, Blandine; LaRochelle, Olivier; Petit, Arnaud; Rohrlich, Pierre; Ferrand, Christophe; Van Den Neste, Eric; Poirel, Hélène A.; Lamy, Thierry; Ouachée-Chardin, Marie; Mansat-De Mas, Véronique; Corre, Jill; Récher, Christian; Plat, Geneviève; Bachelerie, Françoise; Donadieu, Jean

2013-01-01

Congenital neutropenia is a group of genetic disorders that involve chronic neutropenia and susceptibility to infections. These neutropenias may be isolated or associated with immunologic defects or extra-hematopoietic manifestations. Complications may occur as infectious diseases, but also less frequently as myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). Recently, the transcription factor GATA2 has been identified as a new predisposing gene for familial AML/MDS. In the present study, we describe the initial identification by exome sequencing of a GATA2 R396Q mutation in a family with a history of chronic mild neutropenia evolving to AML and/or MDS. The subsequent analysis of the French Severe Chronic Neutropenia Registry allowed the identification of 6 additional pedigrees and 10 patients with 6 different and not previously reported GATA2 mutations (R204X, E224X, R330X, A372T, M388V, and a complete deletion of the GATA2 locus). The frequent evolution to MDS and AML in these patients reveals the importance of screening GATA2 in chronic neutropenia associated with monocytopenia because of the frequent hematopoietic transformation, variable clinical expression at onset, and the need for aggressive therapy in patients with poor clinical outcome. PMID:23223431

Clinical investigation of the lesions responsible for sensory disturbance in Minamata disease.

PubMed

Uchino, M; Mita, S; Satoh, H; Hirano, T; Arimura, K; Nakagawa, M; Nakamura, M; Uyama, E; Ando, Y; Wakamiya, J; Futatsuka, M

2001-11-01

To clarify the lesions responsible for sensory disturbance in Minamata disease (MD), we clinically investigated the characteristics of sensory disturbance. In all patients with the classical type MD, two-point discrimination was severely disturbed, but the involvement of superficial sensation was relatively mild. On short-latency somatosensory evoked potential study, the component corresponding to N20 was completely absent with normal N9, N11, and N13 components. Although 14 of 38 chronic MD patients demonstrated intact superficial sensation, 10 of these 14 showed mild to moderate disturbance in two-point discrimination. The two-point discrimination in chronic MD patients was significantly high irrespective of the disturbance of superficial sensation. These findings suggest that the sensory disturbance of MD patients may mainly be caused by a lesion in the sensory cortex rather than in the peripheral nerves. However, other foci could be also responsible for the sensory impairment, since 9 of 38 chronic MD patients showed intact two-point discrimination.

Extracorporeal shockwave therapy in a dog with chronic bicipital tenosynovitis.

PubMed

Venzin, C; Ohlerth, S; Koch, D; Spreng, D

2004-03-01

A 15-month-old, spayed female, Bernese mountain dog was presented to the Institute of Small Animal Surgery at the University of Zurich because of chronic left forelimb lameness. The referring veterinarian diagnosed pain in the left shoulder region and had treated the dog with systemic non-steroidal anti-inflammatory drugs and restricted exercise for a two-week period. The follow-up examination revealed only minimal improvement and therefore, the dog was referred for further diagnostic evaluation. Chronic bicipital tenosynovitis and tendinitis of the infraspinatus muscle was diagnosed based on survey radiographs, arthrography, ultrasound, computed tomography (CT), and synovial fluid cytology. The dog underwent three sessions of extracorporeal shockwave therapy and substantial clinical improvement was observed. On follow-up examinations, only mild left forelimb lameness was evident following exercise, and changes in the intertubercular groove and at the supraglenoid tuberosity appeared less active on radiographs and CT. However, six months following treatment, mild degenerative joint disease was apparent.

Mild Hypothermia and Acute Kidney Injury in Liver Transplantation

ClinicalTrials.gov

2018-06-18

Cirrhosis; End Stage Liver Disease; Acute Kidney Injury; Liver Transplant; Complications; Chronic Kidney Diseases; Hepatitis c; Hepatitis B; NASH - Nonalcoholic Steatohepatitis; Alcoholic Cirrhosis; Hepatocellular Carcinoma

Diagnostic Instability and Reversals of Chronic Obstructive Pulmonary Disease Diagnosis in Individuals with Mild to Moderate Airflow Obstruction.

PubMed

Aaron, Shawn D; Tan, Wan C; Bourbeau, Jean; Sin, Don D; Loves, Robyn H; MacNeil, Jenna; Whitmore, George A

2017-08-01

Chronic obstructive pulmonary disease (COPD) is a chronic, progressive disease, and reversal of COPD diagnosis is thought to be uncommon. To determine whether a spirometric diagnosis of mild or moderate COPD is subject to variability and potential error. We examined two prospective cohort studies that enrolled subjects with mild to moderate post-bronchodilator airflow obstruction. The Lung Health Study (n = 5,861 subjects; study duration, 5 yr) and the Canadian Cohort of Obstructive Lung Disease (CanCOLD) study (n = 1,551 subjects; study duration, 4 yr) were examined to determine frequencies of (1) diagnostic instability, represented by how often patients initially met criteria for a spirometric diagnosis of COPD but then crossed the diagnostic threshold to normal and then crossed back to COPD over a series of annual visits, or vice versa; and (2) diagnostic reversals, defined as how often an individual's COPD diagnosis at the study outset reversed to normal by the end of the study. Diagnostic instability was common and occurred in 19.5% of the Lung Health Study subjects and 6.4% of the CanCOLD subjects. Diagnostic reversals of COPD from the beginning to the end of the study period occurred in 12.6% and 27.2% of subjects in the Lung Health Study and CanCOLD study, respectively. The risk of diagnostic instability was greatest for subjects whose baseline FEV 1 /FVC value was closest to the diagnostic threshold, and the risk of diagnostic reversal was greatest for subjects who quit smoking during the study. A single post-bronchodilator spirometric assessment may not be reliable for diagnosing COPD in patients with mild to moderate airflow obstruction at baseline.

Watchful waiting with periodic liver biopsy versus immediate empirical therapy for histologically mild chronic hepatitis C. A cost-effectiveness analysis.

PubMed

Wong, J B; Koff, R S

2000-11-07

Not all patients with histologically mild chronic hepatitis C progress to cirrhosis. To compare no antiviral treatment, periodic liver biopsy with subsequent antiviral treatment for moderate hepatitis or cirrhosis, and immediate antiviral therapy. Cost-effectiveness analysis. Clinical trial data and published studies. Hepatitis C virus-infected patients with histologically mild hepatitis. Lifetime. Societal. Immediate combination antiviral treatment or biopsy every 3 years plus combination antiviral therapy for moderate hepatitis or cirrhosis. Life expectancy, quality-adjusted life expectancy, and costs. Over 20 years, biopsy every 3 years with treatment of moderate hepatitis would avoid treatment in 50% of the cohort and would result in an 18% likelihood of cirrhosis compared with 16% for immediate treatment and 27% for no antiviral therapy. Immediate antiviral treatment should increase life expectancy by 1.0 quality-adjusted life-year compared with biopsy management. Over an average lifetime, biopsy management would lead to six liver biopsies costing $6200; immediate antiviral treatment would cost $5100 less than biopsy management because of savings related to biopsy and prevention of future hepatitis C-related morbidity. Immediate therapy was cost-effective compared with biopsy management and had a cost-effectiveness ratio of $7000 compared with no antiviral therapy. When age, sex, genotype, and estimates of histologic progression or compliance with follow-up are varied, immediate therapy should result in an increase of at least 0. 8 quality-adjusted life-year compared with biopsy management. For histologically mild chronic hepatitis C, initial combination treatment compared with periodic liver biopsy should reduce the future risk for cirrhosis, prolong life, and be cost-effective.

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: a randomized, double-blind trial.

PubMed

Pitt, Bertram; Kober, Lars; Ponikowski, Piotr; Gheorghiade, Mihai; Filippatos, Gerasimos; Krum, Henry; Nowack, Christina; Kolkhof, Peter; Kim, So-Young; Zannad, Faiez

2013-08-01

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-steroidal MRA. We investigated its safety and tolerability in patients with HFrEF associated with mild or moderate chronic kidney disease (CKD). This randomized, controlled, phase II trial consisted of two parts. In part A, the safety and tolerability of oral BAY 94-8862 [2.5, 5, or 10 mg once daily (q.d.)] was assessed in 65 patients with HFrEF and mild CKD. In part B, BAY 94-8862 (2.5, 5, or 10 mg q.d., or 5 mg twice daily) was compared with placebo and open-label spironolactone (25 or 50 mg/day) in 392 patients with HFrEF and moderate CKD. BAY 94-8862 was associated with significantly smaller mean increases in serum potassium concentration than spironolactone (0.04-0.30 and 0.45 mmol/L, respectively, P < 0.0001-0.0107) and lower incidences of hyperkalaemia (5.3 and 12.7%, respectively, P = 0.048) and WRF. BAY 94-8862 decreased the levels of B-type natriuretic peptide (BNP), amino-terminal proBNP, and albuminuria at least as much as spironolactone. Adverse events related to BAY 94-8862 were infrequent and mostly mild. In patients with HFrEF and moderate CKD, BAY 94-8862 5-10 mg/day was at least as effective as spironolactone 25 or 50 mg/day in decreasing biomarkers of haemodynamic stress, but it was associated with lower incidences of hyperkalaemia and WRF.

Mild brain injury and anticoagulants: Less is enough.

PubMed

Campiglio, Laura; Bianchi, Francesca; Cattalini, Claudio; Belvedere, Daniela; Rosci, Chiara Emilia; Casellato, Chiara Livia; Secchi, Manuela; Saetti, Maria Cristina; Baratelli, Elena; Innocenti, Alessandro; Cova, Ilaria; Gambini, Chiara; Romano, Luca; Oggioni, Gaia; Pagani, Rossella; Gardinali, Marco; Priori, Alberto

2017-08-01

Despite the higher theoretical risk of traumatic intracranial hemorrhage (ICH) in anticoagulated patients with mild head injury, the value of sequential head CT scans to identify bleeding remains controversial. This study evaluated the utility of 2 sequential CT scans at a 48-hour interval (CT1 and CT2) in patients with mild head trauma (Glasgow Coma Scale 13-15) taking oral anticoagulants. We retrospectively evaluated the clinical records of all patients on chronic anticoagulation treatment admitted to the emergency department for mild head injury. A total of 344 patients were included, and 337 (97.9%) had a negative CT1. CT2 was performed on 284 of the 337 patients with a negative CT1 and was positive in 4 patients (1.4%), but none of the patients developed concomitant neurologic worsening or required neurosurgery. Systematic routine use of a second CT scan in mild head trauma in patients taking anticoagulants is expensive and clinically unnecessary.

[Effect of electroacupuncture intervention on learning-memory ability and injured hippocampal neurons in depression rats].

PubMed

Bao, Wu-Ye; Jiao, Shuang; Lu, Jun; Tu, Ya; Song, Ying-Zhou; Wu, Qian; A, Ying-Ge

2014-04-01

To observe the effect of electroacupuncture (EA) stimulation of "Baihui" (GV 20)-"Yintang" (EX-HN 3) on changes of learning-memory ability and hippocampal neuron structure in chronic stress-stimulation induced depression rats. Forty-eight SD rats were randomly divided into normal, model, EA and medication (Fluoxetine) groups, with 12 rats in each group. The depression model was established by chronic unpredictable mild stress stimulation (swimming in 4 degrees C water, fasting, water deprivation, reversed day and night, etc). Treatment was applied to "Baihui" (GV 20) and "Yintang" (EX-HN 3) for 20 min, once every day for 21 days. For rats of the medication group, Fluoxetine (3.3 mg/kg) was given by gavage (p.o.), once daily for 21 days. The learning-memory ability was detected by Morris water maze tests. The pathological and ultrastructural changes of the hippocampal tissue and neurons were assessed by H.E. staining, light microscope and transmission electron microscopy, respectively. Compared to the normal group, the rats' body weight on day 14 and day 21 after modeling was significantly decreased in the model group (P < 0.01), the escape latency and total swimming distance in the 4 quadrants on day 10 and 21 were significantly increased in the model group (P < 0.01). In comparison with the model group, the body weight on day 14 and 21 were significantly increased (P < 0.05), and the escape latency and total swimming distance levels were significantly decreased in the EA group (P < 0.01), suggesting an improvement of learning-memory ability. Observations of light microscope and transmission electron microscope showed that modeling induced pathological changes such as reduction in hippocampal cell layers, vague and broken cellular membrane, and ultrastructural changes of hippocampal neurons including swelling and reduction of mitochondria and mitochondrial crests were relived after EA and Fluoxetine treatment. EA intervention can improve the learning-memory ability and relieving impairment of hippocampal neurons in depression rats, which may be one of its mechanisms underlying bettering depression.

Chronic Repetitive Mild Traumatic Brain Injury Results in Reduced Cerebral Blood Flow, Axonal Injury, Gliosis, and Increased T-Tau and Tau Oligomers

PubMed Central

Mouzon, Benoit; Algamal, Moustafa; Leary, Paige; Lynch, Cillian; Abdullah, Laila; Evans, James; Mullan, Michael; Bachmeier, Corbin; Stewart, William; Crawford, Fiona

2016-01-01

Exposure to repetitive mild traumatic brain injury (mTBI) is a risk factor for chronic traumatic encephalopathy, which is characterized by patchy deposition of hyperphosphorylated tau aggregates in neurons and astrocytes at the depths of cortical sulci. We developed an mTBI paradigm to explore effects of repetitive concussive-type injury over several months in mice with a human tau genetic background (hTau). Two injuries were induced in the hTau mice weekly over a period of 3 or 4 months and the effects were compared with those in noninjured sham animals. Behavioral and in vivo measures and detailed neuropathological assessments were conducted 6 months after the first injury. Our data confirm impairment in cerebral blood flow and white matter damage. This was accompanied by a 2-fold increase in total tau levels and mild increases in tau oligomers/conformers and pTau (Thr231) species in brain gray matter. There was no evidence of neurofibrillary/astroglial tangles, neuropil threads, or perivascular foci of tau immunoreactivity. There were neurobehavioral deficits (ie, disinhibition and impaired cognitive performance) in the mTBI animals. These data support the relevance of this new mTBI injury model for studying the consequences of chronic repetitive mTBI in humans, and the role of tau in TBI. PMID:27251042

Chronic Repetitive Mild Traumatic Brain Injury Results in Reduced Cerebral Blood Flow, Axonal Injury, Gliosis, and Increased T-Tau and Tau Oligomers.

PubMed

Ojo, Joseph O; Mouzon, Benoit; Algamal, Moustafa; Leary, Paige; Lynch, Cillian; Abdullah, Laila; Evans, James; Mullan, Michael; Bachmeier, Corbin; Stewart, William; Crawford, Fiona

2016-07-01

Exposure to repetitive mild traumatic brain injury (mTBI) is a risk factor for chronic traumatic encephalopathy, which is characterized by patchy deposition of hyperphosphorylated tau aggregates in neurons and astrocytes at the depths of cortical sulci. We developed an mTBI paradigm to explore effects of repetitive concussive-type injury over several months in mice with a human tau genetic background (hTau). Two injuries were induced in the hTau mice weekly over a period of 3 or 4 months and the effects were compared with those in noninjured sham animals. Behavioral and in vivo measures and detailed neuropathological assessments were conducted 6 months after the first injury. Our data confirm impairment in cerebral blood flow and white matter damage. This was accompanied by a 2-fold increase in total tau levels and mild increases in tau oligomers/conformers and pTau (Thr231) species in brain gray matter. There was no evidence of neurofibrillary/astroglial tangles, neuropil threads, or perivascular foci of tau immunoreactivity. There were neurobehavioral deficits (ie, disinhibition and impaired cognitive performance) in the mTBI animals. These data support the relevance of this new mTBI injury model for studying the consequences of chronic repetitive mTBI in humans, and the role of tau in TBI. © 2016 American Association of Neuropathologists, Inc. All rights reserved.

Differences in Depression, Posttraumatic Stress Disorder, and Lifetime Trauma Exposure in Formerly Abused Women with Mild versus Moderate to Severe Chronic Pain

ERIC Educational Resources Information Center

Humphreys, Janice; Cooper, Bruce A.; Miaskowski, Christine

2010-01-01

Although associations between intimate partner violence, chronic pain, depression, posttraumatic stress disorder (PTSD), and lifetime trauma exposure are well known, previous studies are limited by their recruitment of women from shelters. These relationships were explored with a community-based sample of formerly abused women ( N = 84).…

New Evidence in the Management of Chronic Hypertension in Pregnancy.

PubMed

Podymow, Tiina; August, Phyllis

2017-07-01

Chronic hypertension complicates 1% to 5% of all pregnancies, but debate continues regarding the benefits of lowering blood pressure in pregnancy as well as the optimal blood pressure targets. Women with chronic hypertension are at significant risk for maternal and fetal morbidity and mortality, yet it remains unclear whether antihypertensive treatment during pregnancy lowers these risks. Severe hypertension (systolic ≥ 160 mm Hg) should be treated, but there is considerable variability in the approach to mild-to-moderate hypertension (140-159/90-109 mm Hg). The recently published CHIPS (Control of Hypertension in Pregnancy Study) trial is an important effort to attempt to determine treatment goals in mild to moderate pregnancy hypertension. The risks and benefits of tight versus less tight control of blood pressure in nonproteinuric hypertensive women, most of whom had pre-existing hypertension, were evaluated. A main finding was an increased risk of severe hypertension (adjusted odds ratio, 1.8) when blood pressure was not tightly controlled. In this review, general management of chronic hypertension in pregnancy is discussed, including changes in treatment that may be appropriate in light of new clinical trial data. Copyright © 2017 Elsevier Inc. All rights reserved.

Occurrence and Characteristics of Chronic Pain in a Community-Based Cohort of Indigent Adults Living With HIV Infection

PubMed Central

Miaskowski, Christine; Penko, Joanne M.; Guzman, David; Mattson, Jennifer E.; Bangsberg, David R.; Kushel, Margot B.

2011-01-01

Pain is common among people living with HIV/AIDS (PLWHA), but little is known about chronic pain in socioeconomically disadvantaged HIV-infected populations with high rates of substance abuse in the post-antiretroviral era. This cross-sectional study describes the occurrence and characteristics of pain in a community-based cohort of 296 indigent PLWHA. Participants completed questionnaires about sociodemographics, substance use, depression and pain. Cut-point analysis was used to generate categories of pain severity. Of the 270 participants who reported pain or the use of a pain medication in the past week, 8.2% had mild pain, 38.1% had moderate pain, and 53.7% had severe pain. Female sex and less education were associated with more severe pain. Depression was more common among participants with severe pain than among those with mild pain. Increasing pain severity was associated with daily pain and with chronic pain. Over half of the participants reported having a prescription for an opioid analgesic. Findings from this study suggest that chronic pain is a significant problem in this high risk, socioeconomically disadvantaged group of patients with HIV disease and high rates of previous or concurrent use of illicit drugs. PMID:21684218

Chronic obstructive pulmonary disease with mild airflow limitation: current knowledge and proposal for future research - a consensus document from six scientific societies.

PubMed

Rossi, Andrea; Butorac-Petanjek, Bojana; Chilosi, Marco; Cosío, Borja G; Flezar, Matjaz; Koulouris, Nikolaos; Marin, José; Miculinic, Neven; Polese, Guido; Samaržija, Miroslav; Skrgat, Sabina; Vassilakopoulos, Theodoros; Vukić-Dugac, Andrea; Zakynthinos, Spyridon; Miravitlles, Marc

2017-01-01

Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality and morbidity worldwide, with high and growing prevalence. Its underdiagnosis and hence under-treatment is a general feature across all countries. This is particularly true for the mild or early stages of the disease, when symptoms do not yet interfere with daily living activities and both patients and doctors are likely to underestimate the presence of the disease. A diagnosis of COPD requires spirometry in subjects with a history of exposure to known risk factors and symptoms. Postbronchodilator forced expiratory volume in 1 second (FEV 1 )/forced vital capacity <0.7 or less than the lower limit of normal confirms the presence of airflow limitation, the severity of which can be measured by FEV 1 % predicted: stage 1 defines COPD with mild airflow limitation, which means postbronchodilator FEV 1 ≥80% predicted. In recent years, an elegant series of studies has shown that "exclusive reliance on spirometry, in patients with mild airflow limitation, may result in underestimation of clinically important physiologic impairment". In fact, exercise tolerance, diffusing capacity, and gas exchange can be impaired in subjects at a mild stage of airflow limitation. Furthermore, growing evidence indicates that smokers without overt abnormal spirometry have respiratory symptoms and undergo therapy. This is an essential issue in COPD. In fact, on one hand, airflow limitation, even mild, can unduly limit the patient's physical activity, with deleterious consequences on quality of life and even survival; on the other hand, particularly in younger subjects, mild airflow limitation might coincide with the early stage of the disease. Therefore, we thought that it was worthwhile to analyze further and discuss this stage of "mild COPD". To this end, representatives of scientific societies from five European countries have met and developed this document to stimulate the attention of the scientific community on COPD with "mild" airflow limitation. The aim of this document is to highlight some key features of this important concept and help the practicing physician to understand better what is behind "mild" COPD. Future research should address two major issues: first, whether mild airflow limitation represents an early stage of COPD and what the mechanisms underlying the evolution to more severe stages of the disease are; and second, not far removed from the first, whether regular treatment should be considered for COPD patients with mild airflow limitation, either to prevent progression of the disease or to encourage and improve physical activity or both.

Adventure and Extreme Sports.

PubMed

Gomez, Andrew Thomas; Rao, Ashwin

2016-03-01

Adventure and extreme sports often involve unpredictable and inhospitable environments, high velocities, and stunts. These activities vary widely and include sports like BASE jumping, snowboarding, kayaking, and surfing. Increasing interest and participation in adventure and extreme sports warrants understanding by clinicians to facilitate prevention, identification, and treatment of injuries unique to each sport. This article covers alpine skiing and snowboarding, skateboarding, surfing, bungee jumping, BASE jumping, and whitewater sports with emphasis on epidemiology, demographics, general injury mechanisms, specific injuries, chronic injuries, fatality data, and prevention. Overall, most injuries are related to overuse, trauma, and environmental or microbial exposure. Copyright © 2016 Elsevier Inc. All rights reserved.

Novel Mechanism for Reducing Acute and Chronic Neurodegeneration After Traumatic Brain Injury

DTIC Science & Technology

2016-07-01

removal of excess glutamate from the brain. Scope: We will test this novel and powerful neuroprotective treatment in a rat model of repetitive mild...neuroprotective treatment in a rat model of a single moderate TBI and in a rat model of repetitive mild (concussive) TBIs. Outcome measures include...Troubleshooting and refinement of CSF extraction resulting in reliable measurement of glutamate in CSF. 5 Effects of treatment on rotarod motor deficits

Elevated Hippocampal Cholinergic Neurostimulating Peptide precursor protein (HCNP-pp) mRNA in the amygdala in major depression.

PubMed

Bassi, Sabrina; Seney, Marianne L; Argibay, Pablo; Sibille, Etienne

2015-04-01

The amygdala is innervated by the cholinergic system and is involved in major depressive disorder (MDD). Evidence suggests a hyper-activate cholinergic system in MDD. Hippocampal Cholinergic Neurostimulating Peptide (HCNP) regulates acetylcholine synthesis. The aim of the present work was to investigate expression levels of HCNP-precursor protein (HCNP-pp) mRNA and other cholinergic-related genes in the postmortem amygdala of MDD patients and matched controls (females: N = 16 pairs; males: N = 12 pairs), and in the mouse unpredictable chronic mild stress (UCMS) model that induced elevated anxiety-/depressive-like behaviors (females: N = 6 pairs; males: N = 6 pairs). Results indicate an up-regulation of HCNP-pp mRNA in the amygdala of women with MDD (p < 0.0001), but not males, and of UCMS-exposed mice (males and females; p = 0.037). HCNP-pp protein levels were investigated in the human female cohort, but no difference was found. There were no differences in gene expression of acetylcholinesterase (AChE), muscarinic (mAChRs) or nicotinic receptors (nAChRs) between MDD subjects and controls or UCMS and control mice, except for an up-regulation of AChE in UCMS-exposed mice (males and females; p = 0.044). Exploratory analyses revealed a baseline expression difference of cholinergic signaling-related genes between women and men (p < 0.0001). In conclusion, elevated amygdala HCNP-pp expression may contribute to mechanisms of MDD in women, potentially independently from regulating the cholinergic system. The differential expression of genes between women and men could also contribute to the increased vulnerability of females to develop MDD. Copyright © 2015 Elsevier Ltd. All rights reserved.

Propofol alleviates electroconvulsive shock-induced memory impairment by modulating proBDNF/mBDNF ratio in depressive rats.

PubMed

Zhang, Fan; Luo, Jie; Min, Su; Ren, Li; Qin, Peipei

2016-07-01

This study investigated the effects of propofol and electroconvulsive shock (ECS), the analogue of electroconvulsive therapy (ECT) in animals, on tissue plasminogen activator (tPA) and its inhibitor (PAI-1) as well as the precursor of brain-derived neurotrophic factor (proBDNF)/mature BDNF (mBDNF) ratio in depressive rats. ECT is an effective treatment for depression, but can cause cognitive deficit. Some studies have indicated that propofol can ameliorate cognitive decline induced by ECT, but the underlying molecular mechanism is still unclear. Recent evidence has found that mBDNF and its precursor proBDNF are related to depression and cognitive function; they elicit opposite effects on cellular functions. Chronic unpredicted mild stress is widely used to induce depressive behaviors in rodents. This study found that the depression resulted in an increased expression of PAI-1 and upregulation of the proBDNF/mBDNF ratio, together with a decreased level of tPA, long-term potentiation (LTP) impairment, and cognitive decline. The proBDNF/mBDNF ratio was further upregulated after the ECS treatment in depressive rats, resulting in the deterioration of cognitive function and hippocampal LTP. Propofol alone did not reverse the changes in depressive rats, but when co-administered with ECS, it improved the cognitive function, alleviated the impairment of LTP, downregulated the proBDNF/mBDNF ratio, and increased the tPA expression. The results of this study suggest that propofol ameliorates cognitive decline induced by ECT, which was partly by modulating the proBDNF/mBDNF ratio and reversing the excessive changes in hippocampal synaptic plasticity, providing a new evidence for involving the proBDNF/mBDNF system in the progression and treatment of depression. Copyright © 2016 Elsevier B.V. All rights reserved.

Antidepressant effects of Kai-Xin-San in fluoxetine-resistant depression rats.

PubMed

Dong, X Z; Wang, D X; Lu, Y P; Yuan, S; Liu, P; Hu, Y

2017-08-17

This study aimed to investigate the antidepressant effect and the mechanism of action of Kai-Xin-San (KXS) in fluoxetine-resistant depressive (FRD) rats. Two hundred male Wistar rats weighing 200±10 g were exposed to chronic and unpredictable mild stresses (CUMS) for 4 weeks and given fluoxetine treatment simultaneously. The rats that did not show significant improvement in behavioral indexes were chosen as the FRD model rats. These rats were randomly divided into four groups: FRD model control; oral fluoxetine and aspirin; oral KXS at a dose of 338 mg·kg-1·day-1; and oral KXS at a dose of 676 mg·kg-1·day-1. Rats continued to be exposed to CUMS and underwent treatment once a day for 3 weeks, then cytokine (COX-2, IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-10, TGF-β, and TNF-α) levels in the hippocampus and serum, and organ coefficients were measured. Both doses of KXS improved the crossing and rearing frequencies, sucrose-preference index, and body weight in FRD rats. KXS at a dose of 338 mg·kg-1·day-1reduced COX-2, IL-2, IL-6, TNF-α levels, increased IL-10 level in the hippocampus, and reduced IL-2 and TNF-α levels in serum. KXS at a dose of 676 mg·kg-1·day-1reduced TNF-α level in the hippocampus, reduced IL-2 and TNF-α levels in serum, and increased IFN-γ and IL-10 levels in the hippocampus and serum. There were no significant differences in organ-coefficients of the spleen among and between groups. The results suggested that oral administration of KXS in FRD rats was effective in improving behavior disorders by influencing various inflammatory pathways.

Prenatal exposure to escitalopram and/or stress in rats produces limited effects on endocrine, behavioral, or gene expression measures in adult male rats

PubMed Central

Bourke, Chase H.; Stowe, Zachary N.; Neigh, Gretchen N.; Olson, Darin E.; Owens, Michael J.

2013-01-01

Stress and/or antidepressants during pregnancy have been implicated in a wide range of long-term effects in the offspring. We investigated the long-term effects of prenatal stress and/or clinically relevant antidepressant exposure on male adult offspring in a model of the pharmacotherapy of maternal depression. Female Sprague-Dawley rats were implanted with osmotic minipumps that delivered clinically relevant exposure to the antidepressant escitalopram throughout gestation. Subsequently, pregnant females were exposed on gestational days 10–20 to a chronic unpredictable mild stress paradigm. The male offspring were analyzed in adulthood. Baseline physiological measurements were largely unaltered by prenatal manipulations. Behavioral characterization of the male offspring, with or without pre-exposure to an acute stressor, did not reveal any group differences. Prenatal stress exposure resulted in a faster return towards baseline following the peak response to an acute restraint stressor, but not an airpuff startle stressor, in adulthood. Microarray analysis of the hippocampus and hypothalamus comparing all treatment groups revealed no significantly-altered transcripts. Real time PCR of the hippocampus confirmed that several transcripts in the CRFergic, serotonergic, and neural plasticity pathways were unaffected by prenatal exposures. This stress model of maternal depression and its treatment indicate that escitalopram use and/or stress during pregnancy produced no alterations in our measures of male adult behavior or the transcriptome, however prenatal stress exposure resulted in some evidence for increased glucocorticoid negative feedback following an acute restraint stress. Study design should be carefully considered before implications for human health are ascribed to prenatal exposure to stress or antidepressant medication. PMID:23906943

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

PubMed

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.

Dopamine mediated antidepressant effect of Mucuna pruriens seeds in various experimental models of depression

PubMed Central

Rana, Digvijay G.; Galani, Varsha J.

2014-01-01

Background: The effects of antidepressant treatments have traditionally been discussed primarily in terms of effects on noradrenergic and serotonergic systems. Multiple lines of investigation have also explored the role of dopaminergic systems in mental depression. Seed of Mucuna pruriens Linn. (DC) (Leguminoseae) is well-known with dopaminergic action and has several therapeutic applications in folk medicine in curing or managing a wide range of diseases including Parkinsonism. Aim: To elucidate the anti-depressent profile and possible dopaminergic modulating action of M. pruriens seeds in various experimental models of depression. Materials and Methods: In the present study, antidepressant effect of the hydroalcoholic extract of the M. pruriens seeds (MPE) (100 and 200 mg/kg, p.o.) was investigated in the Forced Swimming Test (FST), Tail Suspension Test (TST), and Chronic Unpredictable Mild Stress (CUMS) test in mice. Further, dopaminergic interaction of same doses of MPE in the FST and TST were checked by the administration of a haloperidol (0.1 mg/kg, i.p.) and bromocriptine (2 mg/kg, i.p.) on the 7th day of MPE treatment. Effect of MPE on locomotor activity was also checked using actophotometer. Results: MPE produced a significant reduction of the immobility time in the FST and TST. Further, antidepressant action of MPE was significantly inhibited by haloperidol and potentiated by bromocriptine in the FST and TST. 21 days of MPE treatment produced protection in CUMS as indicated by a significant increase of sucrose intake of stressed mice. Locomotor activities of mice were not significantly changed after 1 h and 7th day of the MPE treatment. Conclusion: The results of this study indicate that hydroalcoholic extract of MPE have antidepressant action, which may be mediated by an interaction with the dopaminergic system. PMID:25364207

Dopamine mediated antidepressant effect of Mucuna pruriens seeds in various experimental models of depression.

PubMed

Rana, Digvijay G; Galani, Varsha J

2014-01-01

The effects of antidepressant treatments have traditionally been discussed primarily in terms of effects on noradrenergic and serotonergic systems. Multiple lines of investigation have also explored the role of dopaminergic systems in mental depression. Seed of Mucuna pruriens Linn. (DC) (Leguminoseae) is well-known with dopaminergic action and has several therapeutic applications in folk medicine in curing or managing a wide range of diseases including Parkinsonism. To elucidate the anti-depressent profile and possible dopaminergic modulating action of M. pruriens seeds in various experimental models of depression. In the present study, antidepressant effect of the hydroalcoholic extract of the M. pruriens seeds (MPE) (100 and 200 mg/kg, p.o.) was investigated in the Forced Swimming Test (FST), Tail Suspension Test (TST), and Chronic Unpredictable Mild Stress (CUMS) test in mice. Further, dopaminergic interaction of same doses of MPE in the FST and TST were checked by the administration of a haloperidol (0.1 mg/kg, i.p.) and bromocriptine (2 mg/kg, i.p.) on the 7(th) day of MPE treatment. Effect of MPE on locomotor activity was also checked using actophotometer. MPE produced a significant reduction of the immobility time in the FST and TST. Further, antidepressant action of MPE was significantly inhibited by haloperidol and potentiated by bromocriptine in the FST and TST. 21 days of MPE treatment produced protection in CUMS as indicated by a significant increase of sucrose intake of stressed mice. Locomotor activities of mice were not significantly changed after 1 h and 7(th) day of the MPE treatment. The results of this study indicate that hydroalcoholic extract of MPE have antidepressant action, which may be mediated by an interaction with the dopaminergic system.

Piper sarmentosum Roxb. produces antidepressant-like effects in rodents, associated with activation of the CREB-BDNF-ERK signaling pathway and reversal of HPA axis hyperactivity.

PubMed

Li, Qing; Qu, Fa-Lin; Gao, Yue; Jiang, Yi-Ping; Rahman, Khalid; Lee, Kuo-Hsiung; Han, Ting; Qin, Lu-Ping

2017-03-06

There are many plants of genus Piper which have been reported to induce antidepressant-like effects, Piper sarmentosum (PS) is one of them. PS is a Chinese herbal medicine and a traditional edible vegetable. In the present study, the antidepressant-like effects of PS extracts and the ethyl acetate fraction of PS extracts (PSY) were assessed using the open field test (OFT), forced swimming test (FST), and tail suspension test (TST) in mice. Furthermore, we applied a 4 consecutive weeks of chronic unpredictable mild stress (CUMS) as a model of depression in rats, followed by a sucrose preference test. Then we examined the possible mechanisms of this action. The activity of the hypothalamic-pituitary-adrenal (HPA) axis was evaluated by detecting the serum corticosterone (CORT) concentrations, and the protein expression levels of brain-derived neurotrophic factor (BDNF), the phosphorylated form CREB and ERK1/2 were detected by qRT-PCR or Western blot. The results showed that PS extracts (100, 200mg/kg) and PSY (12.5, 25, 50mg/kg) treatment produced antidepressant-like effects in mice similar to fluoxetine (20mg/kg), indicated by the reduced immobility time in the FST and TST, while both had no influence on the locomotor activity in the OFT. PSY treatment significantly increased sucrose preference and reduced serum CORT levels in CUMS rats. Moreover, PSY up-regulated BDNF protein levels, and increased CREB and ERK phosphorylation levels in the hippocampus on CUMS rats. These findings suggest that the antidepressant-like effects of PS extracts and PSY are mediated, at least in part, by modulating HPA axis, BDNF, CREB and ERK phosphorylation and expression in the hippocampus. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Role of hypothalamic cannabinoid receptors in post-stroke depression in rats.

PubMed

Wang, Shanshan; Sun, Hong; Liu, Sainan; Wang, Ting; Guan, Jinqun; Jia, Jianjun

2016-03-01

One of the most common psychological consequences of stroke is post-stroke depression (PSD). While more than 30 percent of stroke patients eventually develop PSD, the neurobiological mechanisms underlying such a phenomenon have not been well investigated. Given the critical involvement of hypothalamic-pituitary-adrenal axis and endocannabinoid system in response to stressful stimuli, we evaluated the hypothesis that cannabinoid receptors in the hypothalamus are critical for modulation of post-stroke depression-like behaviors in rats. To this end, rats were treated with middle cerebral artery occlusion (MCAO) followed by chronic unpredictable mild stress (CUMS) treatment procedure. We then assessed the expression of CB1 and CB2 receptors in the hypothalamus, and evaluated the effects of pharmacological stimulations of CB1 or CB2 receptors on the expression and development of depression-like behaviors in PSD rats. We found that PSD rats exhibited decreased the expression of CB1 receptor, but not CB2 receptor, in the ventral medial hypothalamus (VMH). Such an effect was not observed in the dorsally adjacent brain regions. Furthermore, intra-VMH injections of CB2 receptor agonist, but not CB1 receptor agonist, attenuated the expression of depression-like behaviors in PSD rats. Finally, repeated intraperitoneal injections of CB1 or CB2 receptor agonists during CUMS treatment inhibited the development of depression-like behaviors in PSD rats. Taken together, these results suggest that decreased CB1 receptor expression is likely associated with the development of post-stroke depression, and CB2 receptor may be a potential therapeutic target for the treatment post-stroke depressive disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

Mild effects of gestational stress and social reactivity on the onset of mother-young interactions and bonding in sheep.

PubMed

Coulon, Marjorie; Lévy, Frédéric; Ravel, Christine; Nowak, Raymond; Boissy, Alain

2014-12-01

Consequences of prenatal stress on mother-young relationships are well-documented in altricial mammals but less so in precocial mammals. In this study, we investigated the effects of unpredictable aversive events on maternal behavior and mutual mother-young recognition in pregnant ewes while accounting for modulatory effects of ewe reactivity. From a population of 120 Romane-breed ewes, we selected 20 high-responsive (HR) and 20 low-responsive (LR) ewes according to pre-mating reactivity assessed in isolation tests. Over the final third of pregnancy, 10 HR ewes and 10 LR ewes were exposed daily to various aversive events such as social isolation, mixing and transport (stressed ewes), while the other 20 ewes were not exposed to aversive events (control ewes). Although the treatment induced chronic stress, physiologically confirmed by an increase in salivary cortisol following transport and sham shearing, maternal behavior of stressed ewes observed during the first 30 min postpartum and in the selectivity test 1 h 30 min later did not differ from controls. However, in a maternal motivation test performed 48 h postpartum, stressed ewes vocalized less than controls when separated from their lambs, and walked less readily past an unknown object to reach their lambs. Lambs of stressed ewes spent more time near their dam in a preference test performed 15 h after birth compared to control-ewe lambs. HR ewes spent more time grooming their lambs than LR ewes. We posit that domestication could have selected animals displaying robust expression of maternal behavior related to social reactivity and producing offspring that are better adapted to challenging situations.

Stress alters asenapine-induced Fos expression in the Meynert's nucleus: response of adjacent hypocretin and melanin-concentrating hormone neurons in rat.

PubMed

Majercikova, Z; Kiss, A

2016-01-01

Asenapine (ASE), an atypical antipsychotic drug used in the treatment of schizophrenia, induces Fos expression in forebrain. Effect of ASE on activity of basal nucleus of Meynert (NBM) cells, a part of the striatal-cortical circuits, was studied. We were also interested to reveal whether a chronic unpredictable variable mild stress (CMS) preconditioning might affect the ASE impact. Rats were divided into as follows: controls-vehicle, controls-ASE, stressed-vehicle and stressed-ASE groups. CMS included restrain, social isolation, crowding, swimming and cold applied for 21 days. On the 22nd day, rats were subcutaneously injected with ASE (0.3 mg/kg) or vehicle (saline 300 μl/rat), 90 min prior euthanizing. After transcardial fixation, brains were cut into 30 μm thick coronal sections. Fos protein presence, as indicator of cell activity, was detected by ABC immunohistochemistry. Hypocretin (Hcrt) and melanin-concentrating hormone (MCH) containing cells were visualized with fluorescent dyes. ASE induced significant increase in Fos expression in NBM in both controls and CMS preconditioned rats in comparison with the related vehicle-treated controls. CMS preconditioning, however, significantly lowered the Fos response to ASE in NBM. From Hrct and MCH cells, only Hcrt ones displayed Fos presence in response to ASE. This study demonstrates for the first time that ASE may target a special group of cells occupying NBM, which effect can be modulated by CMS preconditioning. This finding extends a view that ASE impact may extend beyond the classical forebrain target areas common for the action of all antipsychotics and might be helpful in the identification of sites and side effects of its therapeutic actions.

Alarin-induced antidepressant-like effects and their relationship with hypothalamus-pituitary-adrenal axis activity and brain derived neurotrophic factor levels in mice.

PubMed

Wang, Ming; Chen, Qian; Li, Mei; Zhou, Wei; Ma, Tengfei; Wang, Yun; Gu, Shuling

2014-06-01

Alarin is a newly identified member of the galanin family of peptides. Galanin has been shown to exert regulatory effects on depression. Similar to galanin in distribution, alarin is also expressed in the medial amygdala and hypothalamus, i.e., regions interrelated with depression. However, it remains a puzzle whether alarin is involved in depression. Accordingly, we established the depression-like mouse model using behavioral tests to ascertain the possible involvement of alarin, with fluoxetine as a positive control. With the positive antidepressant-like effects of alarin, we further examined its relationship to HPA axis activity and brain-derived neurotrophic factor (BDNF) levels in different brain areas in a chronic unpredictable mild stress (CUMS) paradigm. In the acute studies, alarin produced a dose-related reduction in the immobility duration in tail suspension test (TST) in mice. In the open-field test, intracerebroventricular (i.c.v.) injection of alarin (1.0 nmol) did not impair locomotion or motor coordination in the treated mice. In the CUMS paradigm, alarin administration (1.0 nmol, i.c.v.) significantly improved murine behaviors (FST and locomotor activity), which was associated with a decrease in corticotropin-releasing hormone (CRH) mRNA levels in the hypothalamus, as well as a decline in serum levels of CRH, adrenocorticotropic hormone (ACTH) and corticosterone (CORT), all of which are key hormones of the HPA axis. Furthermore, alarin upregulated BDNF mRNA levels in the prefrontal cortex and hippocampus. These findings suggest that alarin may potentiate the development of new antidepressants, which would be further secured with the identification of its receptor(s). Copyright © 2014 Elsevier Inc. All rights reserved.

Translational Identification of Transcriptional Signatures of Major Depression and Antidepressant Response

PubMed Central

Hervé, Mylène; Bergon, Aurélie; Le Guisquet, Anne-Marie; Leman, Samuel; Consoloni, Julia-Lou; Fernandez-Nunez, Nicolas; Lefebvre, Marie-Noëlle; El-Hage, Wissam; Belzeaux, Raoul; Belzung, Catherine; Ibrahim, El Chérif

2017-01-01

Major depressive disorder (MDD) is a highly prevalent mental illness whose therapy management remains uncertain, with more than 20% of patients who do not achieve response to antidepressants. Therefore, identification of reliable biomarkers to predict response to treatment will greatly improve MDD patient medical care. Due to the inaccessibility and lack of brain tissues from living MDD patients to study depression, researches using animal models have been useful in improving sensitivity and specificity of identifying biomarkers. In the current study, we used the unpredictable chronic mild stress (UCMS) model and correlated stress-induced depressive-like behavior (n = 8 unstressed vs. 8 stressed mice) as well as the fluoxetine-induced recovery (n = 8 stressed and fluoxetine-treated mice vs. 8 unstressed and fluoxetine-treated mice) with transcriptional signatures obtained by genome-wide microarray profiling from whole blood, dentate gyrus (DG), and the anterior cingulate cortex (ACC). Hierarchical clustering and rank-rank hypergeometric overlap (RRHO) procedures allowed us to identify gene transcripts with variations that correlate with behavioral profiles. As a translational validation, some of those transcripts were assayed by RT-qPCR with blood samples from 10 severe major depressive episode (MDE) patients and 10 healthy controls over the course of 30 weeks and four visits. Repeated-measures ANOVAs revealed candidate trait biomarkers (ARHGEF1, CMAS, IGHMBP2, PABPN1 and TBC1D10C), whereas univariate linear regression analyses uncovered candidates state biomarkers (CENPO, FUS and NUBP1), as well as prediction biomarkers predictive of antidepressant response (CENPO, NUBP1). These data suggest that such a translational approach may offer new leads for clinically valid panels of biomarkers for MDD. PMID:28848385

The roles of sex and serotonin transporter levels in age- and stress-related emotionality in mice.

PubMed

Joeyen-Waldorf, Jennifer; Edgar, Nicole; Sibille, Etienne

2009-08-25

Mood disorders are influenced by genetic make-up and differentially affect men and women. The s/l promoter polymorphism in the serotonin transporter (SERT) gene moderates both trait emotion and the vulnerability to develop depressive states in humans. Similarly, male mice lacking SERT (Knockout/KO) display an elevated emotionality phenotype. We now report that the SERT-KO phenotype is maintained throughout late-adulthood, and that female KO mice develop a larger emotionality phenotype with increasing age. Thus, to test the hypothesis that these findings reflected a putative sexual dimorphism in SERT-mediated modulation of emotionality, we submitted adult male and female wild-type, heterozygous (HZ) and KO mice to unpredictable chronic mild stress (UCMS) and assessed behavioral changes. In males, the elevated SERT-KO emotion-related behavior converged with other groups after UCMS. Conversely, female SERT-KO displayed a normal non-stressed baseline, but highest UCMS-induced emotionality. SERT-HZ displayed variable and intermediate phenotypes in both experiments. Thus, consistent results across different biological modalities (age, stress) revealed a high contribution of SERT genotype for baseline "trait" emotionality in males, and low contribution for females. In contrast, age-correlated and stress-induced behavioral changes resulted in a high SERT genotype-mediated behavioral variance in females, but low in males. This suggests that high emotionality states associated with low SERT were differentially achieved in males (high baseline/trait) compared to females (increased vulnerability to develop high emotionality). This sex-by-SERT double dissociation provides a framework to investigate molecular substrates of emotionality regulation in concert with serotonin function and may contribute to the sexually dimorphic features of mood disorders.

Integrated Behavioral Z-Scoring Increases the Sensitivity and Reliability of Behavioral Phenotyping in mice: Relevance to Emotionality and Sex

PubMed Central

Guilloux, Jean-Philippe; Seney, Marianne; Edgar, Nicole; Sibille, Etienne

2011-01-01

Defining anxiety- and depressive-like states in mice (“emotionality”) is best characterized by the use of complementary tests, leading sometimes to puzzling discrepancies and lack of correlation between similar paradigms. To address this issue, we hypothesized that integrating measures along the same behavioral dimensions in different tests would reduce the intrinsic variability of single tests and provide a robust characterization of the underlying “emotionality” of individual mouse, similarly as mood and related syndromes are defined in humans through various related symptoms over time. We describe the use of simple mathematical and integrative tools to help phenotype animals across related behavioral tests (syndrome diagnosis) and experiments (meta-analysis). We applied z-normalization across complementary measures of emotionality in different behavioral tests after unpredictable chronic mild stress (UCMS) or prolonged corticosterone exposure - two approaches to induce anxious-/depressive-like states in mice. Combining z-normalized test values, lowered the variance of emotionality measurement, enhanced the reliability of behavioral phenotyping, and increased analytical opportunities. Comparing integrated emotionality scores across studies revealed a robust sexual dimorphism in the vulnerability to develop high emotionality, manifested as higher UCMS-induced emotionality z-scores, but lower corticosterone-induced scores in females compared to males. Interestingly, the distribution of individual z-scores revealed a pattern of increased baseline emotionality in female mice, reminiscent of what is observed in humans. Together, we show that the z-scoring method yields robust measures of emotionality across complementary tests for individual mice and experimental groups, hence facilitating the comparison across studies and refining the translational applicability of these models. PMID:21277897

Integrated behavioral z-scoring increases the sensitivity and reliability of behavioral phenotyping in mice: relevance to emotionality and sex.

PubMed

Guilloux, Jean-Philippe; Seney, Marianne; Edgar, Nicole; Sibille, Etienne

2011-04-15

Defining anxiety- and depressive-like states in mice (emotionality) is best characterized by the use of complementary tests, leading sometimes to puzzling discrepancies and lack of correlation between similar paradigms. To address this issue, we hypothesized that integrating measures along the same behavioral dimensions in different tests would reduce the intrinsic variability of single tests and provide a robust characterization of the underlying "emotionality" of individual mouse, similarly as mood and related syndromes are defined in humans through various related symptoms over time. We describe the use of simple mathematical and integrative tools to help phenotype animals across related behavioral tests (syndrome diagnosis) and experiments (meta-analysis). We applied z-normalization across complementary measures of emotionality in different behavioral tests after unpredictable chronic mild stress (UCMS) or prolonged corticosterone exposure - two approaches to induce anxious-/depressive-like states in mice. Combining z-normalized test values, lowered the variance of emotionality measurement, enhanced the reliability of behavioral phenotyping, and increased analytical opportunities. Comparing integrated emotionality scores across studies revealed a robust sexual dimorphism in the vulnerability to develop high emotionality, manifested as higher UCMS-induced emotionality z-scores, but lower corticosterone-induced scores in females compared to males. Interestingly, the distribution of individual z-scores revealed a pattern of increased baseline emotionality in female mice, reminiscent of what is observed in humans. Together, we show that the z-scoring method yields robust measures of emotionality across complementary tests for individual mice and experimental groups, hence facilitating the comparison across studies and refining the translational applicability of these models. Copyright © 2011 Elsevier B.V. All rights reserved.

Protective effect of total flavones of Abelmoschus manihot L. Medic against poststroke depression injury in mice and its action mechanism.

PubMed

Liu, Mei; Jiang, Qiu-Hong; Hao, Ji-Li; Zhou, Lan-Lan

2009-03-01

Total flavones of Abelmoschus manihot L. Medic (TFA) is the major active component isolated from the traditional Chinese herb Abelmoschus manihot L. Medic. We investigated the protective effect of TFA against poststroke depression (PSD) injury in mice and its action mechanism. A mouse model of PSD was induced by middle cerebral artery occlusion (MACO) 30 min/reperfusion, followed by isolation feeding and chronic unpredictable mild stress for 2 weeks. Treatment groups received TFA at three different doses (160, 80, and 40 mg/kg, p.o.) or fluoxetine (Flu, 2.5 mg/kg, p.o.) daily for 24 days. Change in behavior, brain tissue malondialdehyde (MDA) levels, and the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were measured. The expression of brain-derived neurotrophic factor (BDNF) was detected by immunohistochemistry, and mRNA expression of BDNF and cAMP response element-binding protein (CREB) analyzed by reverse transcription-polymerase chain reaction (RT-PCR). Treatment with TFA (160, 80, and 40 mg/kg) significantly ameliorated mice escape-directed behavioral impairment induced by PSD, markedly reduced MDA levels, and increased the activity of SOD, GSH-Px close to normal levels. TFA administration also attenuated PSD-induced neuronal death/losses, upregulated expression of BDNF both at mRNA and protein levels, as well as CREB mRNA levels. TFA had a protective effect against PSD injury in mice. Cardioprotection involves the inhibition of lipid peroxidation and upregulation of BDNF-CREB levels in the hippocampus, which may also be important mechanism of its antidepressants. This potential protection makes TFA a promising therapeutic agent for the PSD. (c) 2009 Wiley-Liss, Inc.

29 CFR 4022.27 - Phase-in of guarantee of unpredictable contingent event benefits.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 29 Labor 9 2014-07-01 2014-07-01 false Phase-in of guarantee of unpredictable contingent event... Guaranteed Benefits § 4022.27 Phase-in of guarantee of unpredictable contingent event benefits. (a) Scope... event benefit (UCEB) and that is payable with respect to an unpredictable contingent event (UCE) that...

Vitamins and Microelement Bioavailability in Different Stages of Chronic Kidney Disease.

PubMed

Jankowska, Magdalena; Rutkowski, Bolesław; Dębska-Ślizień, Alicja

2017-03-15

Chronic kidney disease (CKD) predisposes one to either deficiency or toxic excess of different micronutrients. The knowledge on micronutrients-specifically water-soluble vitamins and trace elements-in CKD is very limited. Consequently, current guidelines and recommendations are mostly based on expert opinions or poor-quality evidence. Abnormalities of micronutrient resources in CKD develop for several reasons. Dietary restrictions and anorexia lead to an insufficient micronutrient intake, while diuretics use and renal replacement therapy lead to their excessive losses. Absorption is unpredictable, and metabolism impaired. Better understanding of the micronutrient needs of CKD patients could have an impact on many complications linked to vitamin and trace element disorders, including high mortality, increased risk of atherosclerosis, inflammation, oxidative stress, anemia, polyneuropathy, encephalopathy, weakness and fragility, muscle cramps, bone disease, depression, or insomnia. Here, we summarize the up-to-date knowledge on micronutrient resources in different stages of CKD, and share our experience with the assessment of micronutrient status.

Laryngotracheal separation in neonatal brainstem dysfunction.

PubMed

Patron, G Cariou; Teissier, N; Malard, O; Van Den Abbeele, T

2010-03-01

Neonatal brainstem dysfunction (NBD) associates four symptoms of variable presence and intensity: suction-swallowing dysfunction, abnormal laryngeal sensitivity and motility, gastroesophageal reflux, and cardiac vagal overactivity. We report three cases of severe NBD with chronic aspiration which required surgical management. Successive failures and clinical deterioration led us to perform laryngotracheal separation. The surgical procedure consisted in suturing the distal segment of the trachea to the cervical skin after complete closure of the larynx. After surgery, these children did not present any pulmonary infection and were allowed oral nutrition. However, oral communication was no longer possible. Although it is a theoretically reversible procedure, the decision is ethically difficult in children free of mental deficiency, because of the vocal loss and the unpredictable NBD outcome. Laryngotracheal separation may be recommended after multidisciplinary decision for severe chronic aspiration in the particular case of children presenting with NBD. Copyright © 2010. Published by Elsevier Masson SAS.

Chronic Diarrhea and Skin Hyperpigmentation: A New Association

PubMed Central

Al Qoaer, Khaled; Al Mehaidib, Ali; Shabib, Sohail; Banemai, Mohammed

2008-01-01

Background/Aims: The objective of this study was to describe patients with chronic diarrhea and abnormal skin hyperpigmentation with distinct distribution. Methods: This is a retrospective review of children who presented with diarrhea and skin hyperpigmentation. The clinical presentation, laboratory investigations as well as endoscopic and histological data were reviewed. Results: Seven patients with chronic diarrhea had abnormal skin hyperpigmentation with distinct distribution and presented in the first two months of life. Six patients had other features such as abnormal hair and facial dysmorphism. Mental retardation was reported in one patient. Consanguinity was positive in six patients, and there was family history of consanguinity in four patients, with two patients being siblings. No significant immunodeficiency was reported. Intestinal biopsies were obtained in six patients and showed active chronic inflammation in three patients, partial villous atrophy in two patients, and eosinophilic infiltrate with mild villous atrophy in one patient. Colonic biopsies showed mild focal colitis in three patients and mild colitis with eosinophilic infiltrate in one patient. Skin biopsies showed a greater number of melanophagies with fibrosis of papillary derma in two patients but skin biopsy was normal in one patient. The hair of two patients was analyzed by electron microscopy, which showed an abnormal pattern with decreased pigmentation and diameter; however, its chemical analysis was normal. Two other patients had trichorrhexis nodosa, but no abnormalities were seen in one patient. Chromosomal number was normal in three patients. One patient died because of sepsis, and only one patient was dependent on total parenteral nutrition. Conclusions: We believe that this association might represent a new syndrome with an autosomal recessive inheritance that warrants further studies. PMID:19568536

Evaluation of the aspartate aminotransferase/platelet ratio index and enhanced liver fibrosis tests to detect significant fibrosis due to chronic hepatitis C.

PubMed

Petersen, John R; Stevenson, Heather L; Kasturi, Krishna S; Naniwadekar, Ashutosh; Parkes, Julie; Cross, Richard; Rosenberg, William M; Xiao, Shu-Yuan; Snyder, Ned

2014-04-01

The assessment of liver fibrosis in chronic hepatitis C patients is important for prognosis and making decisions regarding antiviral treatment. Although liver biopsy is considered the reference standard for assessing hepatic fibrosis in patients with chronic hepatitis C, it is invasive and associated with sampling and interobserver variability. Serum fibrosis markers have been utilized as surrogates for a liver biopsy. We completed a prospective study of 191 patients in which blood draws and liver biopsies were performed on the same visit. Using liver biopsies the sensitivity, specificity, and negative and positive predictive values for both aspartate aminotransferase/platelet ratio index (APRI) and enhanced liver fibrosis (ELF) were determined. The patients were divided into training and validation patient sets to develop and validate a clinically useful algorithm for differentiating mild and significant fibrosis. The area under the ROC curve for the APRI and ELF tests for the training set was 0.865 and 0.880, respectively. The clinical sensitivity in separating mild (F0-F1) from significant fibrosis (F2-F4) was 80% and 86.0% with a clinical specificity of 86.7% and 77.8%, respectively. For the validation sets the area under the ROC curve for the APRI and ELF tests was, 0.855 and 0.780, respectively. The clinical sensitivity of the APRI and ELF tests in separating mild (F0-F1) from significant (F2-F4) fibrosis for the validation set was 90.0% and 70.0% with a clinical specificity of 73.3% and 86.7%, respectively. There were no differences between the APRI and ELF tests in distinguishing mild from significant fibrosis for either the training or validation sets (P=0.61 and 0.20, respectively). Using APRI as the primary test followed by ELF for patients in the intermediate zone, would have decreased the number of liver biopsies needed by 40% for the validation set. Overall, use of our algorithm would have decreased the number of patients who needed a liver biopsy from 95 to 24-a 74.7% reduction. This study has shown that the APRI and ELF tests are equally accurate in distinguishing mild from significant liver fibrosis, and combining them into a validated algorithm improves their performance in distinguishing mild from significant fibrosis.

Pulmonary sarcoidosis.

PubMed

Spagnolo, Paolo; Rossi, Giulio; Trisolini, Rocco; Sverzellati, Nicola; Baughman, Robert P; Wells, Athol U

2018-05-01

Sarcoidosis is a granulomatous disease of unknown cause, occurs worldwide and has a highly variable prevalence. The disease is typically dominant in the lungs, although it can affect virtually any organ and is unpredictable in its clinical course. The severity of pulmonary sarcoidosis ranges from incidentally discovered radiographic abnormalities in asymptomatic patients to a chronic progressive disease that is refractory to treatment. Mortality from sarcoidosis appears to have increased in the past three decades, with respiratory failure being the most common cause of sarcoidosis-related death. Pulmonary fibrosis, extensive disease on high-resolution chest CT, impaired lung function, and pulmonary hypertension are well established predictors of poor clinical outcomes. In patients who need systemic therapy to control their disease, corticosteroids are the most commonly used first-line treatment, with antimetabolites generally representing an alternative for patients who are unresponsive to corticosteroids or who cannot tolerate them. Indeed, corticosteroid therapy is associated with toxic effects that correlate with both the cumulative dose and duration of treatment. The scarcity of truly effective therapies and shortage of reliable predictors of the unpredictable development of disease in individual patients greatly contribute to making sarcoidosis such a difficult disease to manage. Copyright © 2018 Elsevier Ltd. All rights reserved.

Mood Disorders

MedlinePlus

... disorder; dysthymic disorder (a chronic, mild depression); and bipolar disorder (also called manic depression). Major depressive disorder is, ... to the World Health Organization. YESTERDAY Depression and bipolar disorder weren’t considered distinct brain illnesses, and distinct ...

Chiropractic and rehabilitation management of a patient with extraforaminal entrapment of L4 nerve with balance problem.

PubMed

Alagha, Babak

2015-01-01

Disc herniation is one of the most common causes of low back pain with radicular pain. Among various types of disc herniation, the extraforaminal disc herniation is a rare cause of lumbar radiculopathy. The aim of presenting this case study is to demonstrate the benefits of Chiropractic care including spine and extremity manipulation and rehabilitation in the treatment of a rare case of extraforaminal L4 nerve entrapment causing severe L4 radiculopathy and chronic mild low back pain (LBP). The aim of presenting this case study is to demonstrate the benefits of Chiropractic care including spine and extremity manipulation and rehabilitation in treatment of rare case of extraforaminal L4 nerve entrapment which caused severe L4 radiculopathy and chronic mild low back pain (LBP). A 45-year old female patient arrived at the clinic with chronic mild low back pain and right buttock pain, all of which had presented for two years' duration. During the preceding month, the radicular pain initiated in medium to high intensity, radiating to her right leg following the L4 dermatomal pattern with a periodic tingling sensation in her right foot. A neuro exam demonstrated a proprioception deficit in her right leg. A Romberg test was positive. The patient was treated by low amplitude high velocity spinal and extremity manipulation for 10 consecutive sessions (2 weeks), followed by rehabilitation and exercise therapy including advanced myofascial release therapy for an additional 12 sessions (4 weeks). After treatment, the patient reported a significant improvement in her low back pain and radiculopathy. In addition, she achieved some improvement in balance. It seems that Chiropractic care and rehabilitation therapy may be a safe and effective modality in treatment of an L4 radiculopathy in a patient with an extraforaminal L4 nerve entrapment. Although it is rare, an L4 extraforaminal disc herniation should be considered as a possible cause of symptoms in patients with chronic mild low back pain and severe L4 radiculopathy.

Regulation of ethanol intake under chronic mild stress: roles of dopamine receptors and transporters.

PubMed

Delis, Foteini; Rombola, Christina; Bellezza, Robert; Rosko, Lauren; Grandy, David K; Volkow, Nora D; Thanos, Panayotis K

2015-01-01

Studies have shown that exposure to chronic mild stress decreases ethanol intake and preference in dopamine D2 receptor wild-type mice (Drd2 (+/+)), while it increases intake in heterozygous (Drd2 (+/-)) and knockout (Drd2 (-/-)) mice. Dopaminergic neurotransmission in the basal forebrain plays a major role in the reinforcing actions of ethanol as well as in brain responses to stress. In order to identify neurochemical changes associated with the regulation of ethanol intake, we used in vitro receptor autoradiography to measure the levels and distribution of dopamine D1 and D2 receptors and dopamine transporters (DAT). Receptor levels were measured in the basal forebrain of Drd2 (+/+), Drd2 (+/-), and Drd2 (-/-) mice belonging to one of four groups: control (C), ethanol intake (E), chronic mild stress exposure (S), and ethanol intake under chronic mild stress (ES). D2 receptor levels were higher in the lateral and medial striatum of Drd2 (+/+) ES mice, compared with Drd2 (+/+) E mice. Ethanol intake in Drd2 (+/+) mice was negatively correlated with striatal D2 receptor levels. D2 receptor levels in Drd2(+/-) mice were the same among the four treatment groups. DAT levels were lower in Drd2(+/-) C and Drd2 (-/-) C mice, compared with Drd2 (+/+) C mice. Among Drd2(+/-) mice, S and ES groups had higher DAT levels compared with C and E groups in most regions examined. In Drd2(-/-) mice, ethanol intake was positively correlated with DAT levels in all regions studied. D1 receptor levels were lower in Drd2(+/-) and Drd2(-/-) mice, compared with Drd2(+/+), in all regions examined and remained unaffected by all treatments. The results suggest that in normal mice, ethanol intake is associated with D2 receptor-mediated neurotransmission, which exerts a protective effect against ethanol overconsumption under stress. In mice with low Drd2 expression, where DRD2 levels are not further modulated, ethanol intake is associated with DAT function which is upregulated under stress leading to ethanol overconsumption.

Use of the UPOINT Classification in Turkish Chronic Prostatitis or Chronic Pelvic Pain Syndrome Patients.

PubMed

Arda, Ersan; Cakiroglu, Basri; Tas, Tuncay; Ekici, Sinan; Uyanik, Bekir Sami

2016-11-01

To determine the positive subdomain numbers and distribution of the UPOINT classification in chronic prostatitis and to compare the erectile dysfunction (ED) pattern. From 2008 to 2013, 839 patients with symptomatic chronic prostatitis or chronic pelvic pain syndrome were included in this study. The correlation between UPOINT domains and National Institutes of Health chronic prostatitis symptom index (NIH-CPSI) total score, subscores, and the 5-item International Index of Erectile Function scores were evaluated retrospectively. The mean patient age was calculated as 37.7 ± 7.4 (range 21-65). The average total NIH-CPSI score was determined as 9.07 (range 1-40) and the average positive UPOINT subdomain number was determined as 2.87 ± 0.32 (range 1-6). Subdomain patient numbers and rates were calculated as 529 urinary (63%), 462 psychosocial (55%), 382 organ specific (45%), 290 infection (34%), 288 neurological or systemic (34%), and 418 tenderness (skeletal muscle) (50%), respectively. It was determined that ED, determining the subdomain of sexual dysfunction in patients, was positive in a total of 326 (39.9%) patients, with 220 patients having mild (26.2%), 76 mild to moderate (9.1%), 19 moderate (2.3%), and 5 with severe (0.6%) ED. A statistically significant correlation was not determined between the 5-item International Index of Erectile Function score and UPOINT subdomain number and NIH-CPSI score. It has been determined that although there is a strong and significant correlation between UPOINT classification and NIH-CPSI score in Turkish patients with chronic prostatitis or chronic pelvic pain syndrome, the inclusion of ED as an independent subdomain to the UPOINT classification is not statistically significant. Copyright © 2016 Elsevier Inc. All rights reserved.

Parkinsonsim due to a Chronic Subdural Hematoma

PubMed Central

Park, Bosuk; Song, Sook Keun; Hong, Jin Yong; Lee, Phil Hyu

2009-01-01

Subdural hematoma is a rare cause of parkinsonism. We present the case of a 78-year-old man with right-side dominant parkinsonism about 3 months after a minor head injury. MRI reveals a chronic subdural hematoma on the left side with mildly displaced midline structures. The parkinsonian features were almost completely disappeared after neurosurgical evacuation of the hematoma without any anti-parkinson drug. PMID:24868353

Novel Mechanism for Reducing Acute and Chronic Neurodegeneration After Traumatic Brain Injury

DTIC Science & Technology

2017-07-01

glutamate from the brain. Scope: We will test this novel and powerful neuroprotective treatment in a rat model of repetitive mild (concussive) TBIs...variability. 2. Completed statistical analysis of behavioral experiments examining effects of rGOT and rGOT + OxAc on outcome on rotarod and Morris water ...neuroprotective treatment in a rat model of a single moderate TBI and in a rat model of repetitive mild (concussive) TBIs. Outcome measures include blood and

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

DTIC Science & Technology

2015-10-01

hyperbaric oxygen therapy; TBI: traumatic brain injury; PPCS: persistent post- concussion syndrome 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF...persistent post- concussion syndrome (PPCS). Evidence-based medicine exists for PTSD, but there is no effective treatment for the persistent post... concussion syndrome (PPCS) of mild-moderate TBI nor the combined diagnoses of PPCS and PTSD. Between the Fall of 2008 and end of 2010, the P.I

Usability of World Health Organization Disability Assessment Schedule in chronic traumatic brain injury.

PubMed

Tarvonen-Schröder, Sinikka; Tenovuo, Olli; Kaljonen, Anne; Laimi, Katri

2018-06-15

To investigate functioning measured with the 12-item World Health Organization Disability Assessment Schedule (WHODAS 2.0) in patients with mild, moderate and severe traumatic brain injury, and to compare patients' experiences with assessments made by their significant others and by consultant neurologists. A total of 112 consecutive patients with traumatic brain injury (29 mild, 43 moderate, 40 severe) and their significant others completed a 12-item WHODAS 2.0 survey. A neurologist assessed functioning with the International Classification of Functioning, Disability and Health minimal generic set. The total patient and proxy WHODAS 2.0 sum score was rated as severe, and impairments in household tasks, learning, community life, emotional functions, concentrating, dealing with strangers, maintaining friendships, and working ability as around moderate in all 3 severity groups. In standing, walking, washing, and dressing oneself the reported impairments increased from mild in mild traumatic brain injury to moderate in severe traumatic brain injury. A neurologist rated the overall functioning, working ability, and motor activities most impaired in severe traumatic brain injury, while there were no between-group differences in energy and drive functions and emotional functions. Patients with chronic traumatic brain injury perceive a diversity of significant difficulties in activities and participation irrespective of the severity of the injury. We recommend assessing disability in traumatic brain injury with the short and understandable WHODAS 2.0 scale, when planning client-oriented services.

High frequency of GATA2 mutations in patients with mild chronic neutropenia evolving to MonoMac syndrome, myelodysplasia, and acute myeloid leukemia.

PubMed

Pasquet, Marlène; Bellanné-Chantelot, Christine; Tavitian, Suzanne; Prade, Naïs; Beaupain, Blandine; Larochelle, Olivier; Petit, Arnaud; Rohrlich, Pierre; Ferrand, Christophe; Van Den Neste, Eric; Poirel, Hélène A; Lamy, Thierry; Ouachée-Chardin, Marie; Mansat-De Mas, Véronique; Corre, Jill; Récher, Christian; Plat, Geneviève; Bachelerie, Françoise; Donadieu, Jean; Delabesse, Eric

2013-01-31

Congenital neutropenia is a group of genetic disorders that involve chronic neutropenia and susceptibility to infections. These neutropenias may be isolated or associated with immunologic defects or extra-hematopoietic manifestations. Complications may occur as infectious diseases, but also less frequently as myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). Recently, the transcription factor GATA2 has been identified as a new predisposing gene for familial AML/MDS. In the present study, we describe the initial identification by exome sequencing of a GATA2 R396Q mutation in a family with a history of chronic mild neutropenia evolving to AML and/or MDS. The subsequent analysis of the French Severe Chronic Neutropenia Registry allowed the identification of 6 additional pedigrees and 10 patients with 6 different and not previously reportedGATA2 mutations (R204X, E224X, R330X, A372T, M388V, and a complete deletion of the GATA2 locus). The frequent evolution to MDS and AML in these patients reveals the importance of screening GATA2 in chronic neutropenia associated with monocytopenia because of the frequent hematopoietic transformation, variable clinical expression at onset, and the need for aggressive therapy in patients with poor clinical outcome. Mutations of key transcription factor in myeloid malignancies.

A Policy Relevant US Trauma Care System Pragmatic Trial for PTSD and Comorbidity

ClinicalTrials.gov

2016-05-18

Posttraumatic Stress Disorder; Depression; Alcohol-Related Disorders; Suicidal Ideation; Substance-Related Disorders; Mild Cognitive Impairment; Quality of Life; Pain; Wounds and Injury; Brain Injuries; Chronic Disease

Impaired adrenal medullary function in a mouse model of depression induced by unpredictable chronic stress.

PubMed

Santana, Magda M; Rosmaninho-Salgado, Joana; Cortez, Vera; Pereira, Frederico C; Kaster, Manuella P; Aveleira, Célia A; Ferreira, Marisa; Álvaro, Ana Rita; Cavadas, Cláudia

2015-10-01

Stress has been considered determinant in the etiology of depression. The adrenal medulla plays a key role in response to stress by releasing catecholamines, which are important to maintain homeostasis. We aimed to study the adrenal medulla in a mouse model of depression induced by 21 days of unpredictable chronic stress (UCS). We observed that UCS induced a differential and time-dependent change in adrenal medulla. After 7 days of UCS, mice did not show depressive-like behavior, but the adrenal medullae show increased protein and/or mRNA levels of catecholamine biosynthetic enzymes (TH, DβH and PNMT), Neuropeptide Y, the SNARE protein SNAP-25, the catecholamine transporter VMAT2 and the chromaffin progenitor cell markers, Mash1 and Phox2b. Moreover, 7 days of UCS induced a decrease in the chromaffin progenitor cell markers, Sox9 and Notch1. This suggests an increased capacity of chromaffin cells to synthesize, store and release catecholamines. In agreement, after 7 days, UCS mice had higher NE and EP levels in adrenal medulla. Opposite, when mice were submitted to 21 days of UCS, and showed a depressive like behavior, adrenal medullae had lower protein and/or mRNA levels of catecholamine biosynthetic enzymes (TH, DβH, PNMT), catecholamine transporters (NET, VMAT1), SNARE proteins (synthaxin1A, SNAP25, VAMP2), catecholamine content (EP, NE), and lower EP serum levels, indicating a reduction in catecholamine synthesis, re-uptake, storage and release. In conclusion, this study suggests that mice exposed to UCS for a period of 21 days develop a depressive-like behavior accompanied by an impairment of adrenal medullary function. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

Modulation of nitrergic signalling pathway by American ginseng attenuates chronic unpredictable stress-induced cognitive impairment, neuroinflammation, and biochemical alterations.

PubMed

Rinwa, Puneet; Kumar, Anil

2014-02-01

Prolonged stress causes extensive loss of neurons leading to deficits in cognitive performance. Increasing evidence indicates that accumulation of intercellular messenger, nitric oxide (NO), plays a crucial role in the pathogenesis of memory disorders. American ginseng (AG) is known to show protection in different animal models of neurological diseases; however, its exact mechanism of action is not clearly understood. Therefore, the current study was designed to investigate the interaction of AG against chronic unpredictable stress (CUS)-associated behavioral and biochemical alterations and the probable role of nitrergic pathway in this effect. Male Laca mice were exposed to a series of stressors along with drug/vehicle treatment daily for 28 days. CUS paradigm caused significant impairment in both acquisition and retention memory as measured in Morris water maze and elevated plus maze task. This was coupled with alterations in oxidative stress markers, mitochondrial enzyme complex activities, pro-inflammatory cytokine (TNF-α), and acetylcholinesterase levels in the hippocampus as compared with naïve group. Besides, there was a marked increase in serum corticosterone levels. AG (100, 200 mg/kg; p.o.) treatment significantly improved cognitive impairment; reduced TNF-α, acetylcholinesterase, and corticosterone levels; and attenuated oxidative-nitrergic stress. Furthermore, pre-treatment of L-arginine (100 mg/kg; i.p.), a nitric oxide donor, with subeffective dose of AG (100 mg/kg; p.o.) reversed its protective effects. However, L-NAME (10 mg/kg, i.p.), a non-specific NO synthase inhibitor, potentiated the effects of AG. Our findings suggest that modulation of nitrergic signalling cascade is involved in the protective effects of AG against CUS-induced cognitive dysfunction, oxidative stress, and neuroinflammation.

Antidepressant-like effects of long-term sarcosine treatment in rats with or without chronic unpredictable stress.

PubMed

Chen, Kuang-Ti; Wu, Ching-Hsiang; Tsai, Mang-Hung; Wu, Ya-Chieh; Jou, Ming-Jia; Huang, Chih-Chia; Wei, I-Hua

2017-01-01

Sarcosine, an N-methyl-d-aspartate receptor enhancer, can improve depression-like behavior in rodent models and depression in humans. We found that a single dose of sarcosine exerted antidepressant-like effects with rapid concomitant increases in the mammalian target of rapamycin (mTOR) signaling pathway activation and enhancement of α-amino-3-hydroxy-5-methylisoxazole-4-propionate receptor (AMPAR) membrane insertion. Sarcosine may play a crucial role in developing novel therapy for depression. For a detailed understanding of sarcosine, this study examined the effects of long-term sarcosine treatment on the forced swim test (FST), mTOR signaling, and AMPAR membrane insertion in rats. The effects of long-term sarcosine treatment were examined in naive rats and rats exposed to chronic unpredictable stress (CUS). Long-term sarcosine treatment (560mg/kg/d for 21 d) significantly ameliorated the increased immobility induced by CUS in the FST, reaffirming the potential role of sarcosine as an antidepressant for depressed patients. The same long-term treatment exhibited no such effect in naive rats despite increased mTOR activation and AMPAR membrane insertion in both groups. Our findings clearly show CUS-exposed rats are sensitive to long-term sarcosine treatment in FST and the response at the same dose is absent in naïve rats. Nevertheless, the distinct sensitivity to long-term sarcosine treatment in rats with or without CUS is not associated with the activated mTOR signaling pathway or increased AMPAR membrane insertion. Additionally, understanding the behavioral and molecular basis of distinct responses is vital important for developing personalized treatment programs to increase the probability of success when treating depression. Copyright © 2016. Published by Elsevier B.V.

Non-autonomous equations with unpredictable solutions

NASA Astrophysics Data System (ADS)

Akhmet, Marat; Fen, Mehmet Onur

2018-06-01

To make research of chaos more amenable to investigating differential and discrete equations, we introduce the concepts of an unpredictable function and sequence. The topology of uniform convergence on compact sets is applied to define unpredictable functions [1,2]. The unpredictable sequence is defined as a specific unpredictable function on the set of integers. The definitions are convenient to be verified as solutions of differential and discrete equations. The topology is metrizable and easy for applications with integral operators. To demonstrate the effectiveness of the approach, the existence and uniqueness of the unpredictable solution for a delay differential equation are proved as well as for quasilinear discrete systems. As a corollary of the theorem, a similar assertion for a quasilinear ordinary differential equation is formulated. The results are demonstrated numerically, and an application to Hopfield neural networks is provided. In particular, Poincaré chaos near periodic orbits is observed. The completed research contributes to the theory of chaos as well as to the theory of differential and discrete equations, considering unpredictable solutions.

Pulmonary Gas Exchange Abnormalities in Mild Chronic Obstructive Pulmonary Disease. Implications for Dyspnea and Exercise Intolerance.

PubMed

Elbehairy, Amany F; Ciavaglia, Casey E; Webb, Katherine A; Guenette, Jordan A; Jensen, Dennis; Mourad, Sahar M; Neder, J Alberto; O'Donnell, Denis E

2015-06-15

Several studies in mild chronic obstructive pulmonary disease (COPD) have shown a higher than normal ventilatory equivalent for carbon dioxide ([Formula: see text]e/[Formula: see text]co2) during exercise. Our objective was to examine pulmonary gas exchange abnormalities and the mechanisms of high [Formula: see text]e/[Formula: see text]co2 in mild COPD and its impact on dyspnea and exercise intolerance. Twenty-two subjects (11 patients with GOLD [Global Initiative for Chronic Obstructive Lung Disease] grade 1B COPD, 11 age-matched healthy control subjects) undertook physiological testing and a symptom-limited incremental cycle exercise test with arterial blood gas collection. Patients (post-bronchodilator FEV1: 94 ± 10% predicted; mean ± SD) had evidence of peripheral airway dysfunction and reduced peak oxygen uptake compared with control subjects (80 ± 18 vs. 113 ± 24% predicted; P<0.05). Arterial blood gases were within the normal range and effective alveolar ventilation was not significantly different from control subjects throughout exercise. The alveolar-arterial O2 tension gradient was elevated at rest and throughout exercise in COPD (P<0.05). [Formula: see text]e/[Formula: see text]co2, dead space to tidal volume ratio (Vd/Vt), and arterial to end-tidal CO2 difference were all higher (P<0.05) in patients with COPD than in control subjects during exercise. In patients with COPD versus control subjects, there was significant dynamic hyperinflation and greater tidal volume constraints (P<0.05). Standardized dyspnea intensity ratings were also higher (P<0.05) in patients with COPD versus control subjects in association with higher ventilatory requirements. Within all subjects, Vd/Vt correlated with the [Formula: see text]e/[Formula: see text]co2 ratio during submaximal exercise (r=0.780, P<0.001). High Vd/Vt was the most consistent gas exchange abnormality in smokers with only mild spirometric abnormalities. Compensatory increases in minute ventilation during exercise maintained alveolar ventilation and arterial blood gas homeostasis but at the expense of earlier dynamic mechanical constraints, greater dyspnea, and exercise intolerance in mild COPD.

Poincaré chaos and unpredictable functions

NASA Astrophysics Data System (ADS)

Akhmet, Marat; Fen, Mehmet Onur

2017-07-01

The results of this study are continuation of the research of Poincaré chaos initiated in the papers (M. Akhmet and M.O. Fen, Commun Nonlinear Sci Numer Simulat 40 (2016) 1-5; M. Akhmet and M.O. Fen, Turk J Math, doi:10.3906/mat-1603-51, in press). We focus on the construction of an unpredictable function, continuous on the real axis. As auxiliary results, unpredictable orbits for the symbolic dynamics and the logistic map are obtained. By shaping the unpredictable function as well as Poisson function we have performed the first step in the development of the theory of unpredictable solutions for differential and discrete equations. The results are preliminary ones for deep analysis of chaos existence in differential and hybrid systems. Illustrative examples concerning unpredictable solutions of differential equations are provided.

Water: an essential but overlooked nutrient.

PubMed

Kleiner, S M

1999-02-01

Water is an essential nutrient required for life. To be well hydrated, the average sedentary adult man must consume at least 2,900 mL (12 c) fluid per day, and the average sedentary adult woman at least 2,200 mL (9 c) fluid per day, in the form of noncaffeinated, nonalcoholic beverages, soups, and foods. Solid foods contribute approximately 1,000 mL (4 c) water, with an additional 250 mL (1 c) coming from the water of oxidation. The Nationwide Food Consumption Surveys indicate that a portion of the population may be chronically mildly dehydrated. Several factors may increase the likelihood of chronic, mild dehydration, including a poor thirst mechanism, dissatisfaction with the taste of water, common consumption of the natural diuretics caffeine and alcohol, participation in exercise, and environmental conditions. Dehydration of as little as 2% loss of body weight results in impaired physiological and performance responses. New research indicates that fluid consumption in general and water consumption in particular can have an effect on the risk of urinary stone disease; cancers of the breast, colon, and urinary tract; childhood and adolescent obesity; mitral valve prolapse; salivary gland function; and overall health in the elderly. Dietitians should be encouraged to promote and monitor fluid and water intake among all of their clients and patients through education and to help them design a fluid intake plan. The influence of chronic mild dehydration on health and disease merits further research.

Psychobiological stress in vital exhaustion. Findings from the Men Stress 40+ study.

PubMed

Noser, Emilou; Fischer, Susanne; Ruppen, Jessica; Ehlert, Ulrike

2018-02-01

Despite the increased risk for cardiovascular morbidity associated with vital exhaustion (VE), the underlying pathophysiological mechanisms remain unclear. Allostatic load may constitute the missing link between VE and cardiovascular diseases. The aim of the present study was to investigate whether men with different degrees of VE would differ in terms of allostatic load, chronic stress, and social support. The Men Stress 40+ study sample consisted of N=121 apparently healthy men aged 40 to 75years. The following allostatic load markers were aggregated to create a cumulative index of biological stress: salivary cortisol, salivary dehydroepiandrosterone sulfate (DHEA-S), waist-to-hip-ratio, systolic and diastolic blood pressure. Long-term cortisol and DHEA were additionally measured in hair. Chronic stress and social support were assessed via validated questionnaires. Groups of mildly, substantially, and severely exhausted men were compared using one-way ANOVAs with appropriate post-hoc tests. Men who reported mild or severe levels of vital exhaustion had the highest scores on the cumulative index of biological stress. Hair cortisol was unrelated to vital exhaustion; hair DHEA was highest in men with substantial levels of exhaustion. Men with mild exhaustion reported the lowest levels of chronic stress, while men with severe exhaustion reported the lowest levels of social support. Signs of allostatic load are detectable in vitally exhausted men at a stage where no major cardiovascular consequences have yet ensued. Copyright © 2017 Elsevier Inc. All rights reserved.

Efficacy and safety of pimecrolimus cream 1% in mild-to-moderate chronic hand dermatitis: a randomized, double-blind trial.

PubMed

Hordinsky, Maria; Fleischer, Alan; Rivers, Jason K; Poulin, Yves; Belsito, Donald; Hultsch, Thomas

2010-08-01

Chronic hand dermatitis is common and difficult to treat. Our aim was to assess the efficacy of pimecrolimus cream 1% in mild-to-moderate chronic hand dermatitis. Adult patients (n = 652) were randomized to pimecrolimus 1% or vehicle cream twice daily with overnight occlusion for 6 weeks, followed by a 6-week open-label pimecrolimus treatment. Primary efficacy was 5-point Investigators' Global Assessment of prospectively selected 'target hand' as treatment success (Investigators' Global Assessment 0 or 1) and treatment failure. Pruritus relief was also assessed. Following double-blind phase treatment, target hand treatment success was achieved in 29.8 and 23.2% of the patients in the pimecrolimus and vehicle groups, respectively (p = 0.057). The proportion of patients experiencing pruritus relief was significantly higher in the pimecrolimus group compared to the vehicle group at all time points throughout the double-blind phase. The groups were comparable with respect to treating disease signs. Pruritus relief, however, was significantly greater in the pimecrolimus group. Copyright 2010 S. Karger AG, Basel.

Progression of initially mild hepatic fibrosis in patients with chronic hepatitis C infection.

PubMed

Williams, M J; Lang-Lenton, M

2011-01-01

A significant number of patients with chronic hepatitis C infection have minimal fibrosis at presentation. Although the short-term outlook for such patients is good, there are limited data available on long-term progression. We assessed the risk of fibrosis progression in 282 patients with chronic hepatitis C with Ishak stage 0 or 1 fibrosis on initial liver biopsy. Progression of fibrosis stage occurred in 118 patients (42%) over a median interval of 52.5 months. Thirteen (5%) progressed to severe (Ishak stage 4 or more) fibrosis. Progression was significantly associated with both age at initial biopsy [odds ratio (OR) for progression of 1.31 per 10 year increase in age] and median alanine transaminase (ALT) levels during follow-up (OR of 1.06 per 10 IU/L increase). There was no significant association with gender, histological inflammatory grade, hepatic steatosis or body mass index. We conclude that hepatitis C with initially mild fibrosis does progress in a substantial proportion of patients and should not be viewed as a benign disease. Early antiviral therapy should be considered in older patients and those with high ALT levels.

Spaceflight-Induced Intracranial Hypertension and Visual Impairment: Pathophysiology and Countermeasures.

PubMed

Zhang, Li-Fan; Hargens, Alan R

2018-01-01

Visual impairment intracranial pressure (VIIP) syndrome is considered an unexplained major risk for future long-duration spaceflight. NASA recently redefined this syndrome as Spaceflight-Associated Neuro-ocular Syndrome (SANS). Evidence thus reviewed supports that chronic, mildly elevated intracranial pressure (ICP) in space (as opposed to more variable ICP with posture and activity on Earth) is largely accounted for by loss of hydrostatic pressures and altered hemodynamics in the intracranial circulation and the cerebrospinal fluid system. In space, an elevated pressure gradient across the lamina cribrosa, caused by a chronic but mildly elevated ICP, likely elicits adaptations of multiple structures and fluid systems in the eye which manifest themselves as the VIIP syndrome. A chronic mismatch between ICP and intraocular pressure (IOP) in space may acclimate the optic nerve head, lamina cribrosa, and optic nerve subarachnoid space to a condition that is maladaptive to Earth, all contributing to the pathogenesis of space VIIP syndrome. Relevant findings help to evaluate whether artificial gravity is an appropriate countermeasure to prevent this seemingly adverse effect of long-duration spaceflight. Copyright © 2018 the American Physiological Society.

Struggling for a normal life: work as an individual self-care management strategy among persons living with non-malignant chronic pain.

PubMed

Nilsen, Gudrun; Anderssen, Norman

2014-01-01

A significant part of the population suffers from non-malignant chronic pain that is not treated by pain specialists. No successful long-term treatment exists. The patients have to deal with their condition in collaboration with health personnel establishing treatment programmes under uncertain circumstances with few guidelines. Thus, there is a strong need for knowledge on how patients with chronic non-malignant pain manage their condition. The aim of the study was to explore how patients with chronic non-malignant pain deal with their condition. Twenty patients with chronic non-malignant pain (aged 26-63 in year 2006) told in an open-ended interview situation, how they lived with and dealt with their condition. The interviews were analysed within a phenomenological meaning condensation framework. For all patients the pain was as an integrated part of their life that required huge efforts to cope with. Typically, the patients experienced loneliness, fear of stigmatization and despair because of their unpredictable condition, and they wanted to come back to a normalized daily life, first and foremost by getting back to paid work. In general, the patients developed individual strategies that were influenced by their local contexts and life situation as well as the pain itself. This may be interpreted in line with Bourdieu's notions of habitus, strategies and social capital.

Biographical disruption, adjustment and reconstruction of everyday occupations and work participation after mild traumatic brain injury. A focus group study.

PubMed

Sveen, Unni; Søberg, Helene Lundgaard; Østensjø, Sigrid

2016-11-01

To explore traumatic brain injury (TBI) as a biographical disruption and to study the reconstruction of everyday occupations and work participation among individuals with mild TBI. Seven focus groups were conducted with 12 women and 8 men (22-60 years) who had sustained mild TBI and participated in a return-to-work program. Interviews were analyzed using qualitative content analysis. Four interrelated themes emerged: disruption of occupational capacity and balance; changes in self-perceptions; experience of time; and occupational adjustment and reconstruction. The meaning of the impairments lies in their impact on the individual's everyday occupations. The abandonment of meaningful daily occupations and the feeling of not recognizing oneself were experienced as threats to the sense of self. Successful integration of the past, present and future was paramount to continuing life activities. The unpredictability of the future seemed to permeate the entire process of adjustment and reconstruction of daily life. Our findings show that the concept of time is important in understanding and supporting the reconstruction of daily life after TBI. The fundamental work of rehabilitation is to ameliorate the disruptions caused by the injury, restoring a sense of personal narrative and supporting the ability to move forward with life. Implications for Rehabilitation Individuals with a protracted recovery after a mild traumatic brain injury must reconstruct a new way of being and acting in the world to achieve biographical continuity. The perceived anxiety regarding changes in self and occupational identity, as well as loss of control over the future, can be attenuated through informational sessions during the hospital stay and at follow-up visits. The significant personal costs of returning to full-time employment too early indicate the need for early and ongoing vocational support in achieving a successful return to work.

Approach to treatment of hypophosphatemia.

PubMed

Felsenfeld, Arnold J; Levine, Barton S

2012-10-01

Hypophosphatemia can be acute or chronic. Acute hypophosphatemia with phosphate depletion is common in the hospital setting and results in significant morbidity and mortality. Chronic hypophosphatemia, often associated with genetic or acquired renal phosphate-wasting disorders, usually produces abnormal growth and rickets in children and osteomalacia in adults. Acute hypophosphatemia may be mild (phosphorus level, 2-2.5 mg/dL), moderate (1-1.9 mg/dL), or severe (<1 mg/dL) and commonly occurs in clinical settings such as refeeding, alcoholism, diabetic ketoacidosis, malnutrition/starvation, and after surgery (particularly after partial hepatectomy) and in the intensive care unit. Phosphate replacement can be given either orally, intravenously, intradialytically, or in total parenteral nutrition solutions. The rate and amount of replacement are empirically determined, and several algorithms are available. Treatment is tailored to symptoms, severity, anticipated duration of illness, and presence of comorbid conditions, such as kidney failure, volume overload, hypo- or hypercalcemia, hypo- or hyperkalemia, and acid-base status. Mild/moderate acute hypophosphatemia usually can be corrected with increased dietary phosphate or oral supplementation, but intravenous replacement generally is needed when significant comorbid conditions or severe hypophosphatemia with phosphate depletion exist. In chronic hypophosphatemia, standard treatment includes oral phosphate supplementation and active vitamin D. Future treatment for specific disorders associated with chronic hypophosphatemia may include cinacalcet, calcitonin, or dypyrimadole. Published by Elsevier Inc.

Sound stress-induced long-term enhancement of mechanical hyperalgesia in rats is maintained by sympathoadrenal catecholamines.

PubMed

Khasar, Sachia G; Dina, Olayinka A; Green, Paul G; Levine, Jon D

2009-10-01

Although stress plays an important role in chronic widespread pain syndromes, such as fibromyalgia, the underlying mechanism has remained elusive. We have recently demonstrated, in a model of chronic widespread pain, that prolonged enhancement of immune mediator hyperalgesia, induced by unpredictable sound stress, requires a contribution of both the sympathoadrenal (epinephrine) and the hypothalamic-pituitary adrenal (corticosterone) neuroendocrine stress axes. Because this stress protocol produced sustained elevation of plasma epinephrine, in the current study we tested the hypothesis that the sympathoadrenal axis also plays a role in maintenance of symptoms in this model of chronic widespread pain. After establishment, adrenal medullectomy abolished the enhancement of epinephrine-induced cutaneous and muscle hyperalgesia. Administration of stress levels of epinephrine to adrenal medullectomized rats reconstituted the pain phenotype. These observations suggest that the sympathoadrenal stress axis plays a major role in the induction as well as maintenance of stress-induced enhancement of mechanical hyperalgesia, mediated by prolonged elevation of circulating epinephrine. We present data showing mechanical hyperalgesia persisting for up to 28 days after exposure to sound stress, with evidence that the sympathoadrenal axis mediator epinephrine plays a major role. These findings could have clinical implications with regard to novel potential treatments for chronic widespread pain syndromes, such as fibromyalgia.

Resistance Training Exercise Program for Intervention to Enhance Gait Function in Elderly Chronically Ill Patients: Multivariate Multiscale Entropy for Center of Pressure Signal Analysis

PubMed Central

Jiang, Bernard C.

2014-01-01

Falls are unpredictable accidents, and the resulting injuries can be serious in the elderly, particularly those with chronic diseases. Regular exercise is recommended to prevent and treat hypertension and other chronic diseases by reducing clinical blood pressure. The “complexity index” (CI), based on multiscale entropy (MSE) algorithm, has been applied in recent studies to show a person's adaptability to intrinsic and external perturbations and widely used measure of postural sway or stability. The multivariate multiscale entropy (MMSE) was advanced algorithm used to calculate the complexity index (CI) values of the center of pressure (COP) data. In this study, we applied the MSE & MMSE to analyze gait function of 24 elderly, chronically ill patients (44% female; 56% male; mean age, 67.56 ± 10.70 years) with either cardiovascular disease, diabetes mellitus, or osteoporosis. After a 12-week training program, postural stability measurements showed significant improvements. Our results showed beneficial effects of resistance training, which can be used to improve postural stability in the elderly and indicated that MMSE algorithms to calculate CI of the COP data were superior to the multiscale entropy (MSE) algorithm to identify the sense of balance in the elderly. PMID:25295070

A Case of Complete and Durable Molecular Remission of Chronic Lymphocytic Leukemia Following Treatment with Epigallocatechin-3-gallate, an Extract of Green Tea

PubMed Central

Block, Keith I; Kressel, Bruce R; Sukhatme, Vikas P; White, Jeffrey D

2015-01-01

We report the case of a 48-year-old man who achieved a complete molecular remission 20 years after a diagnosis of chronic lymphocytic leukemia while using epigallicatechin-3-gallate, an extract of green tea. The patient presented at age 28 with lymphocytosis, mild anemia, mild thrombocytopenia, and massive splenomegaly, for which a splenectomy was performed. He was then followed expectantly. Over the next two decades, he suffered two symptomatic chronic lymphocytic leukemia-related events. The first occurred twelve years after diagnosis (at age 40) when the patient developed fevers, night sweats, and moderate anemia. He was diagnosed with autoimmune hemolytic anemia secondary to chronic lymphocytic leukemia. The patient declined conventional therapy in favor of a diet, exercise, and supplement regimen, and recovered from the autoimmune hemolytic anemia though the underlying chronic lymphocytic leukemia remained evident. This is the first published case report of "spontaneous" recovery from secondary autoimmune hemolytic anemia in an adult.  Over the second decade following chronic lymphocytic leukemia diagnosis, serial bone marrow biopsies demonstrated increasing lymphocytosis, with minimal peripheral lymphocytosis. However, twenty years after diagnosis, peripheral lymphocytosis accelerated, with white blood cell counts rising to 55,000/µL. Because the patient continued to refuse conventional therapy, he was treated instead with a supplement regimen that included high doses of epigallocatechin-3-gallate, a green tea extract. Peripheral lymphocytosis resolved. More remarkably, a bone marrow examination, including flow cytometry, showed no evidence of a malignant clone. Two years later (at age 51), the peripheral blood and bone marrow were without molecular evidence of chronic lymphocytic leukemia or any malignancy. The patient remains well at age 52.  PMID:26858922

Chronic obstructive pulmonary disease with mild airflow limitation: current knowledge and proposal for future research – a consensus document from six scientific societies

PubMed Central

Rossi, Andrea; Butorac-Petanjek, Bojana; Chilosi, Marco; Cosío, Borja G; Flezar, Matjaz; Koulouris, Nikolaos; Marin, José; Miculinic, Neven; Polese, Guido; Samaržija, Miroslav; Skrgat, Sabina; Vassilakopoulos, Theodoros; Vukić-Dugac, Andrea; Zakynthinos, Spyridon; Miravitlles, Marc

2017-01-01

Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality and morbidity worldwide, with high and growing prevalence. Its underdiagnosis and hence under-treatment is a general feature across all countries. This is particularly true for the mild or early stages of the disease, when symptoms do not yet interfere with daily living activities and both patients and doctors are likely to underestimate the presence of the disease. A diagnosis of COPD requires spirometry in subjects with a history of exposure to known risk factors and symptoms. Postbronchodilator forced expiratory volume in 1 second (FEV1)/forced vital capacity <0.7 or less than the lower limit of normal confirms the presence of airflow limitation, the severity of which can be measured by FEV1% predicted: stage 1 defines COPD with mild airflow limitation, which means postbronchodilator FEV1 ≥80% predicted. In recent years, an elegant series of studies has shown that “exclusive reliance on spirometry, in patients with mild airflow limitation, may result in underestimation of clinically important physiologic impairment”. In fact, exercise tolerance, diffusing capacity, and gas exchange can be impaired in subjects at a mild stage of airflow limitation. Furthermore, growing evidence indicates that smokers without overt abnormal spirometry have respiratory symptoms and undergo therapy. This is an essential issue in COPD. In fact, on one hand, airflow limitation, even mild, can unduly limit the patient’s physical activity, with deleterious consequences on quality of life and even survival; on the other hand, particularly in younger subjects, mild airflow limitation might coincide with the early stage of the disease. Therefore, we thought that it was worthwhile to analyze further and discuss this stage of “mild COPD”. To this end, representatives of scientific societies from five European countries have met and developed this document to stimulate the attention of the scientific community on COPD with “mild” airflow limitation. The aim of this document is to highlight some key features of this important concept and help the practicing physician to understand better what is behind “mild” COPD. Future research should address two major issues: first, whether mild airflow limitation represents an early stage of COPD and what the mechanisms underlying the evolution to more severe stages of the disease are; and second, not far removed from the first, whether regular treatment should be considered for COPD patients with mild airflow limitation, either to prevent progression of the disease or to encourage and improve physical activity or both. PMID:28919728

Mood and Memory Deficits in a Model of Gulf War Illness Are Linked with Reduced Neurogenesis, Partial Neuron Loss, and Mild Inflammation in the Hippocampus

PubMed Central

Parihar, Vipan K; Hattiangady, Bharathi; Shuai, Bing; Shetty, Ashok K

2013-01-01

Impairments in mood and cognitive function are the key brain abnormalities observed in Gulf war illness (GWI), a chronic multisymptom health problem afflicting ∼25% of veterans who served in the Persian Gulf War-1. Although the precise cause of GWI is still unknown, combined exposure to a nerve gas prophylaxis drug pyridostigmine bromide (PB) and pesticides DEET and permethrin during the war has been proposed as one of the foremost causes of GWI. We investigated the effect of 4 weeks of exposure to Gulf war illness-related (GWIR) chemicals in the absence or presence of mild stress on mood and cognitive function, dentate gyrus neurogenesis, and neurons, microglia, and astrocytes in the hippocampus. Combined exposure to low doses of GWIR chemicals PB, DEET, and permethrin induced depressive- and anxiety-like behavior and spatial learning and memory dysfunction. Application of mild stress in the period of exposure to chemicals exacerbated the extent of mood and cognitive dysfunction. Furthermore, these behavioral impairments were associated with reduced hippocampal volume and multiple cellular alterations such as chronic reductions in neural stem cell activity and neurogenesis, partial loss of principal neurons, and mild inflammation comprising sporadic occurrence of activated microglia and significant hypertrophy of astrocytes. The results show the first evidence of an association between mood and cognitive dysfunction and hippocampal pathology epitomized by decreased neurogenesis, partial loss of principal neurons, and mild inflammation in a model of GWI. Hence, treatment strategies that are efficacious for enhancing neurogenesis and suppressing inflammation may be helpful for alleviation of mood and cognitive dysfunction observed in GWI. PMID:23807240

Chronic traumatic encephalopathy in a National Football League player.

PubMed

Omalu, Bennet I; DeKosky, Steven T; Minster, Ryan L; Kamboh, M Ilyas; Hamilton, Ronald L; Wecht, Cyril H

2005-07-01

We present the results of the autopsy of a retired professional football player that revealed neuropathological changes consistent with long-term repetitive concussive brain injury. This case draws attention to the need for further studies in the cohort of retired National Football League players to elucidate the neuropathological sequelae of repeated mild traumatic brain injury in professional football. The patient's premortem medical history included symptoms of cognitive impairment, a mood disorder, and parkinsonian symptoms. There was no family history of Alzheimer's disease or any other head trauma outside football. A complete autopsy with a comprehensive neuropathological examination was performed on the retired National Football League player approximately 12 years after retirement. He died suddenly as a result of coronary atherosclerotic disease. Studies included determination of apolipoprotein E genotype. Autopsy confirmed the presence of coronary atherosclerotic disease with dilated cardiomyopathy. The brain demonstrated no cortical atrophy, cortical contusion, hemorrhage, or infarcts. The substantia nigra revealed mild pallor with mild dropout of pigmented neurons. There was mild neuronal dropout in the frontal, parietal, and temporal neocortex. Chronic traumatic encephalopathy was evident with many diffuse amyloid plaques as well as sparse neurofibrillary tangles and tau-positive neuritic threads in neocortical areas. There were no neurofibrillary tangles or neuropil threads in the hippocampus or entorhinal cortex. Lewy bodies were absent. The apolipoprotein E genotype was E3/E3. This case highlights potential long-term neurodegenerative outcomes in retired professional National Football League players subjected to repeated mild traumatic brain injury. The prevalence and pathoetiological mechanisms of these possible adverse long-term outcomes and their relation to duration of years of playing football have not been sufficiently studied. We recommend comprehensive clinical and forensic approaches to understand and further elucidate this emergent professional sport hazard.

Comparison of Low Resolution Electromagnetic Tomography Imaging Between Subjects With Mild and Severe Obstructive Sleep Apnea Syndrome: A Preliminary Study

PubMed Central

Lee, Hyun-Kwon; 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 41.7±13.6 years) right-handed male OSAS subjects were selected by interview and questionnaires including the NPSG, Beck Depression Inventory, Beck Anxiety Inventory, Epworth Sleepiness Scale, and Pittsburgh Sleep Quality Index. The LORETA and QEEG were compared between the severe and mild OSAS groups by frequency bands (delta 1-3 Hz, theta 4-7 Hz, alpha 8-12 Hz, beta1 13-18 Hz, beta2 19-21 Hz, beta3 22-30 Hz, and total 1-30 Hz) made by spectral analysis during resting with the eyes closed. Results The LORETA analysis showed decreased alpha activity at the right posterior cingulate gyrus (Brodmann area 23) in cases with severe OSAS compared to mild OSAS (p<0.05). For the QEEG, the absolute power of the alpha activity (8-12 Hz) was decreased in P3 (p=0.047), PZ (p=0.039) and O2 (p=0.04) in cases with severe OSAS compared to mild OSAS cases. The LORETA and QEEG analyses had similar results with regard to band, activation and location. Conclusion The decreased activity of the alpha frequency in the right posterior cingulate gyrus, in patients with severe OSAS compared to those with mild OSAS, suggests that chronic repeated short-term hypoxia during sleep, in OSAS, could provoke cortical brain dysfunction associated with cognitive dysfunction such as memory and attention. PMID:20046408

Prevalence of Pulmonary Hypertension and its Influence on Survival in Patients With Advanced Chronic Obstructive Pulmonary Disease Prior to Lung Transplantation.

PubMed

Hayes, Don; Black, Sylvester M; Tobias, Joseph D; Mansour, Heidi M; Whitson, Bryan A

2016-01-01

Prevalence of pulmonary hypertension (PH) and its influence on survival in chronic obstructive pulmonary disease (COPD) are not well studied in the lung allocation score (LAS) era. The UNOS database was queried from 2005 to 2013 to identify first-time adult lung transplant candidates with COPD who were tracked from wait list entry date until death or censoring to determine both prevalence and influence of PH. Using right heart catheterization measurements, mild PH was defined as mean pulmonary artery pressure (mPAP) ≥ 25 mmHg and severe ≥ 35 mmHg. Of 1315 COPD candidates not transplanted, 1243 were used for survival analysis using Cox proportional hazards models, and 1010 (mild PH) and 244 (severe PH) were used for propensity score matching, respectively. A total of 52% (652) of subjects had PH mPAP ≥ 25 mmHg. Univariate analysis revealed significant differences in survival for mild PH (HR = 1.769; 95% CI: 1.331, 2.351; p < 0.001) and severe PH (HR = 3.271; 95% CI: 2.311, 4.630; p < 0.001). Kaplan-Meier survival function demonstrated significant disparities for mild PH (Log-rank test: Chi-square1: 15.87, p < 0.0001) and severe PH (Log-rank test: Chi-square1: 50.13, p < 0.0001). Multivariate Cox models identified significant risk for death for mild PH (HR = 1.987; 95% CI: 1.484, 2.662; p < 0.001) and severe PH (HR = 3.432; 95% CI: 2.410, 4.888; p < 0.001). Propensity score matching confirmed increased mortality hazard associated with mild PH (HR = 2.280; 95% CI: 1.425, 3.649; p = 0.001) and severe PH (HR = 7.000; 95% CI: 2.455, 19.957; p < 0.001). PH is highly prevalent in advanced COPD and associated with a significantly higher risk for mortality.

Mild water restriction with or without urea for the longterm treatment of syndrome of inappropriate antidiuretic hormone secretion (SIADH): Can urine osmolality help the choice?

PubMed

Decaux, G; Gankam Kengne, F; Couturier, B; Musch, W; Soupart, A; Vandergheynst, F

2018-02-01

Treatment options for chronic SIADH include water restriction (WR) and urea. The usefulness of urine osmolality to guide the choice of the treatment option is not clearly defined. We hypothesized that urine osmolality can indicate whether treatment with mild water restriction alone could be successful. Retrospective Review of clinical and biochemical (blood and urine) data of patients with chronic SIADH treated for at least one year with mild WR (1.5-2l/day) either with or without urea. Twenty nine patients were included. Nine patients were treated by mild WR. Mean serum sodium (SNa) and mean Uosm were 129±2mEq/l and 274±78mOsm/kgH2O respectively before WR, and increased to 138.5±3mEq/l and 505±87mOsm/kgH 2 O (P<0.001). Eight patients were treated with mild WR and 15g urea daily, the SNa and Uosm before treatment were 127.5±3mEq/l and 340±100mOsm/kgH 2 O respectively and increased to 136.5±1mEq/l and 490±151mOsm/kgH 2 O (P<0.001). Four of the eight patients had a permanent low solute intake which contributed to hyponatremia. Twelve patients needed 30g urea daily combined with mild WR. The SNa and Uosm were respectively 126±2mEq/l and 595±176mOsm/kgH 2 O and increased to 136.5±2mEq/l and 698±157mOsm/kgH 2 O (P<0.05). Uosm increased in most of the treated patients. About 30% of patients could be treated by moderate WR alone. All these patients presented an initial urine osmolality lower than 400mOsm/kgH 2 O. Copyright © 2017. Published by Elsevier B.V.

Oral N-acetylcysteine and exercise tolerance in mild chronic obstructive pulmonary disease.

PubMed

Hirai, Daniel M; Jones, Joshua H; Zelt, Joel T; da Silva, Marianne L; Bentley, Robert F; Edgett, Brittany A; Gurd, Brendon J; Tschakovsky, Michael E; O'Donnell, Denis E; Neder, J Alberto

2017-05-01

Heightened oxidative stress is implicated in the progressive impairment of skeletal muscle vascular and mitochondrial function in chronic obstructive pulmonary disease (COPD). Whether accumulation of reactive oxygen species contributes to exercise intolerance in the early stages of COPD is unknown. The purpose of the present study was to determine the effects of oral antioxidant treatment with N -acetylcysteine (NAC) on respiratory, cardiovascular, and locomotor muscle function and exercise tolerance in patients with mild COPD. Thirteen patients [forced expiratory volume in 1 s (FEV 1 )-to-forced vital capacity ratio < lower limit of normal (LLN) and FEV 1 ≥ LLN) were enrolled in a double-blind, randomized crossover study to receive NAC (1,800 mg/day) or placebo for 4 days. Severe-intensity constant-load exercise tests were performed with noninvasive measurements of central hemodynamics (stroke volume, heart rate, and cardiac output via impedance cardiography), arterial blood pressure, pulmonary ventilation and gas exchange, quadriceps muscle oxygenation (near-infrared spectroscopy), and estimated capillary blood flow. Nine patients completed the study with no major adverse clinical effects. Although NAC elevated plasma glutathione by ~27% compared with placebo ( P < 0.05), there were no differences in exercise tolerance (placebo: 325 ± 47 s, NAC: 336 ± 51 s), central hemodynamics, arterial blood pressure, pulmonary ventilation or gas exchange, locomotor muscle oxygenation, or capillary blood flow from rest to exercise between conditions ( P > 0.05 for all). In conclusion, modulation of plasma redox status with oral NAC treatment was not translated into beneficial effects on central or peripheral components of the oxygen transport pathway, thereby failing to improve exercise tolerance in nonhypoxemic patients with mild COPD. NEW & NOTEWORTHY Acute antioxidant treatment with N -acetylcysteine (NAC) elevated plasma glutathione but did not modulate central or peripheral components of the O 2 transport pathway, thereby failing to improve exercise tolerance in patients with mild chronic obstructive pulmonary disease (COPD). Copyright © 2017 the American Physiological Society.

Differential modulation of right ventricular strain and right atrial mechanics in mild vs. severe pressure overload

PubMed Central

Voeller, Rochus K.; Aziz, Abdulhameed; Maniar, Hersh S.; Ufere, Nneka N.; Taggar, Ajay K.; Bernabe, Noel J.; Cupps, Brian P.

2011-01-01

Increased right atrial (RA) and ventricular (RV) chamber volumes are a late maladaptive response to chronic pulmonary hypertension. The purpose of the current investigation was to characterize the early compensatory changes that occur in the right heart during chronic RV pressure overload before the development of chamber dilation. Magnetic resonance imaging with radiofrequency tissue tagging was performed on dogs at baseline and after 10 wk of pulmonary artery banding to yield either mild RV pressure overload (36% rise in RV pressure; n = 5) or severe overload (250% rise in RV pressure; n = 4). The RV free wall was divided into three segments within a midventricular plane, and circumferential myocardial strain was calculated for each segment, the septum, and the left ventricle. Chamber volumes were calculated from stacked MRI images, and RA mechanics were characterized by calculating the RA reservoir, conduit, and pump contribution to RV filling. With mild RV overload, there were no changes in RV strain or RA function. With severe RV overload, RV circumferential strain diminished by 62% anterior (P = 0.04), 42% inferior (P = 0.03), and 50% in the septum (P = 0.02), with no change in the left ventricle (P = 0.12). RV filling became more dependent on RA conduit function, which increased from 30 ± 9 to 43 ± 13% (P = 0.01), than on RA reservoir function, which decreased from 47 ± 6 to 33 ± 4% (P = 0.04), with no change in RA pump function (P = 0.94). RA and RV volumes and RV ejection fraction were unchanged from baseline during either mild (P > 0.10) or severe RV pressure overload (P > 0.53). In response to severe RV pressure overload, RV myocardial strain is segmentally diminished and RV filling becomes more dependent on RA conduit rather than reservoir function. These compensatory mechanisms of the right heart occur early in chronic RV pressure overload before chamber dilation develops. PMID:21926343

Reduction of cervical and respiratory muscle strength in patients with chronic nonspecific neck pain and having moderate to severe disability.

PubMed

López-de-Uralde-Villanueva, Ibai; Sollano-Vallez, Ernesto; Del Corral, Tamara

2017-06-11

To investigate whether patients with chronic nonspecific neck pain and having moderate to severe disability have a greater cervical motor function impairment and respiratory disturbances compared with patients with chronic nonspecific neck pain having mild disability and asymptomatic subjects; and the association between these outcomes in patients with chronic nonspecific neck pain and healthy controls. Cross-sectional study, 44 patients with chronic nonspecific neck pain and 31 healthy subjects participated. The neck disability index was used to divide the patients into 2 groups: 1) mild disability group (scores between 5 and 14 points); and 2) moderate to severe disability group (scores >14 points). Cervical motor function was measured by cervical range of motion, forward head posture, neck flexor, and extensor muscle strength. Respiratory function and maximum respiratory pressures were also measured. Statistically differences were found between the patients with chronic nonspecific neck pain having a moderate to severe disability and the asymptomatic subjects for cervical and respiratory muscle strength. Comparisons between chronic nonspecific neck pain and the asymptomatic groups showed differences for all the variables, except for forward head posture. The regression model determined that strength of cervical flexion explained 36.4 and 45.6% of the variance of maximum inspiratory pressures and maximum expiratory pressures, respectively. Only the chronic nonspecific neck pain group with moderate to severe disability showed differences compared with the healthy subjects. Neck muscle strength could be a good predictor of respiratory muscle function. Implications for rehabilitation Neck pain severity could be closely associated with decreased respiratory pressure in patients with chronic nonspecific neck pain. These findings suggest a new therapeutic approach for patients with moderate to severe disability, such as respiratory muscle training. The regression models show that a simple measurement of neck muscle strength could provide a reasonably accurate prediction for the respiratory function of these patients. Hence, this could provide an easy tool to assess respiratory function to physiotherapists without the need for sophisticated instrumentation.

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

PubMed Central

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

Pulmonary Toxicity of Simulated Lunar and Martian Dusts Intratracheally Instilled into Mice

NASA Technical Reports Server (NTRS)

Lam, Chiu-Wing; James, John; Holian, Andrij; Latch, Judith N.; Balis, John; Muro-Cacho, Carlos; Cowper, Shawn; McCluskey, Richard

2000-01-01

The National Aeronautics and Space Administration (NASA) is contemplating sending humans to Mars and to the Moon for further exploration. Equipment designated for these extraterrestrial bases will require testing in simulated Martian or lunar environments. The properties of Hawaiian and San Francisco Mountain volcanic ashes make them suitable to be used in these test environments as Martian and lunar dust simulants, respectively. The present toxicity study was conducted to address NASA's concern about the health risk of dust exposures in the test facilities. In addition, the results obtained on these simulants can be used to design a toxicity study of actual moon dust and Martian dust, which will probably be available in a few years. Respirable portions of lunar soil simulant (LSS) and Martian soil simulant (MSS) were separated from their respective raw materials. These soil simulants, together- with fine titanium dioxide (negative control for fibrogenesis in mice), and crystalline silica (positive control) were each intratracheally instilled in saline to groups of 4 male mice (C57BL/6J, 2-3 months old) at 0.1 mg/mouse (LD) or lmg/mouse (HD). The lungs were harvested 7 or 90 days after the single dust treatment for histopathological examination. Lungs of the LSS-LD groups on either the 7- or 90-day study showed no evidence of inflammation, edema, or fibrosis. Clumps of particles and an increased number of macrophages, visible in the lungs examined after 7 days, were absent after 90 days. The LSS-HD-7d group showed mild to moderate alveolitis with neutrophilic and lymphocytic infiltration, and mild perivascular and peribronchiolar inflammation. The LSS-HD-90d group showed signs of chronic inflammation: septal thickening, mild perivascular and peribronchiolar inflammation, mild alveolitis and some fibrosis. Foci of particle-laden macrophages (PLMs) were still visible. Lungs of the MSS-LD-7d group revealed mild focal intraalveolar inflammation with neutrophilic and lymphocytic infiltration, and mild perivascular and peribronchiolar inflammation. The MSS-LD-90d group showed PLMs and scattered foci of mild fibrosis. The MSS-HD-7d group showed large foci of PLMs, intraalveolar debris, mild to moderate focal alveolitis, and mild to moderate perivascular and peribronchiolar inflammation. The MSS-HD-90d group showed focal chronic mild to moderate alveolitis and fibrosis. To mimic the oxidative and reactive properties of Martian surface dust in the test animals, groups of 4 mice were exposed to ozone (0.5 ppm for 3 hours) prior to instillation of the MSS. Lung lesions in the MSS groups were more severe with the ozone pretreatment. The O3-MSS-HD-90d group had wide spread intraalveolar debris, focal moderate alveolitis and fibrosis. The results for the titanium dioxide and quartz controls were consistent with the known pulmonary toxicity of these compounds. The overall severity of toxic injury to the lungs was TiO2

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

PubMed

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.

Monitoring long-term effects of mild traumatic brain injury with magnetic resonance spectroscopy: a pilot study.

PubMed

Dean, Philip J A; Otaduy, Maria C G; Harris, Lisa M; McNamara, Adam; Seiss, Ellen; Sterr, Annette

2013-08-21

This pilot study explores the metabolic changes associated with persistent postconcussion syndrome (PCS) after mild traumatic brain injury (mTBI; >12 months after injury) using magnetic resonance spectroscopy. We hypothesized that those mTBI participants with PCS will have larger metabolic differences than those without. Data were collected from mTBI participants with PCS, mTBI participants without PCS and non-head-injured participants (all groups: n=8). Magnetic resonance spectroscopy metabolite profiles within the dorsolateral prefrontal cortex showed a reduced creatine/choline ratio in mTBI patients compared with control participants. This data provides initial evidence for residual metabolic changes in chronic mTBI patients, but there was no conclusive relationship between these metabolic changes and PCS symptom report. Creatine is involved in maintaining energy levels in cells with high or fluctuating energy demand, suggesting that there may be some residual energy impairment in chronic mTBI.

CADASIL with a novel NOTCH3 mutation (Cys478Tyr).

PubMed

Ozaki, Kokoro; Irioka, Takashi; Ishikawa, Kinya; Mizusawa, Hidehiro

2015-03-01

Recently, an increasing number of NOTCH3 mutations have been described to cause cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Here, we report 2 CADASIL patients from a Japanese family, who were found to possess a novel NOTCH3 mutation. The proband only had chronic headache, and her mother had previously suffered a minor stroke. Although the patients' clinical symptoms were mild, their distinctive magnetic resonance imaging (MRI) features suggested CADASIL. Genetic analysis revealed that both patients had a novel heterozygous NOTCH3 mutation (p.Cys478Tyr) leading to stereotypical cysteine loss. The present finding suggests that genetic testing for NOTCH3 mutations in patients with distinctive MRI features, even if the symptoms are as mild as chronic headache, should help to broaden the mutational and clinical spectrum of CADASIL. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Effects of supplementation with fish oil and n-3 PUFAs enriched egg yolk phospholipids on anhedonic-like response and body weight in the rat chronic mild stress model of depression.

PubMed

Rutkowska, M; Trocha, M; Szandruk, M; Słupski, W; Rymaszewska, J

2013-08-01

Polyunsaturated fatty acids play an important role in the human organism. They guarantee a normal function of nervous cells, influence neurotransmission, and build some elements of cellular membranes. Several reports indicate an association between a deficiency of polyunsaturated fatty acids and depression. The aim of this study was to examine the effects of diet supplemented with fish oil, which is rich in omega-3 polyunsaturated fatty acids (n-3 PUFAs) and n-3 PUFAs enriched phospholipids ("super lecithin") obtained from designed eggs on anhedonic-like response and body weight in the rat chronic mild stress (CMS) model of depression. The results showed that neither fish oil nor n-3 PUFAs enriched egg yolk phospholipids supplementation reversed disturbances caused by CMS, such as anhedonic-like state or reduction of body weight gain.

Models of acute and chronic pancreatitis.

PubMed

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. Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.

[Study of the clinical phenotype of symptomatic chronic airways disease by hierarchical cluster analysis and two-step cluster analyses].

PubMed

Ning, P; Guo, Y F; Sun, T Y; Zhang, H S; Chai, D; Li, X M

2016-09-01

To study the distinct clinical phenotype of chronic airway diseases by hierarchical cluster analysis and two-step cluster analysis. A population sample of adult patients in Donghuamen community, Dongcheng district and Qinghe community, Haidian district, Beijing from April 2012 to January 2015, who had wheeze within the last 12 months, underwent detailed investigation, including a clinical questionnaire, pulmonary function tests, total serum IgE levels, blood eosinophil level and a peak flow diary. Nine variables were chosen as evaluating parameters, including pre-salbutamol forced expired volume in one second(FEV1)/forced vital capacity(FVC) ratio, pre-salbutamol FEV1, percentage of post-salbutamol change in FEV1, residual capacity, diffusing capacity of the lung for carbon monoxide/alveolar volume adjusted for haemoglobin level, peak expiratory flow(PEF) variability, serum IgE level, cumulative tobacco cigarette consumption (pack-years) and respiratory symptoms (cough and expectoration). Subjects' different clinical phenotype by hierarchical cluster analysis and two-step cluster analysis was identified. (1) Four clusters were identified by hierarchical cluster analysis. Cluster 1 was chronic bronchitis in smokers with normal pulmonary function. Cluster 2 was chronic bronchitis or mild chronic obstructive pulmonary disease (COPD) patients with mild airflow limitation. Cluster 3 included COPD patients with heavy smoking, poor quality of life and severe airflow limitation. Cluster 4 recognized atopic patients with mild airflow limitation, elevated serum IgE and clinical features of asthma. Significant differences were revealed regarding pre-salbutamol FEV1/FVC%, pre-salbutamol FEV1% pred, post-salbutamol change in FEV1%, maximal mid-expiratory flow curve(MMEF)% pred, carbon monoxide diffusing capacity per liter of alveolar(DLCO)/(VA)% pred, residual volume(RV)% pred, total serum IgE level, smoking history (pack-years), St.George's respiratory questionnaire(SGRQ) score, acute exacerbation in the past one year, PEF variability and allergic dermatitis (P<0.05). (2) Four clusters were also identified by two-step cluster analysis as followings, cluster 1, COPD patients with moderate to severe airflow limitation; cluster 2, asthma and COPD patients with heavy smoking, airflow limitation and increased airways reversibility; cluster 3, patients having less smoking and normal pulmonary function with wheezing but no chronic cough; cluster 4, chronic bronchitis patients with normal pulmonary function and chronic cough. Significant differences were revealed regarding gender distribution, respiratory symptoms, pre-salbutamol FEV1/FVC%, pre-salbutamol FEV1% pred, post-salbutamol change in FEV1%, MMEF% pred, DLCO/VA% pred, RV% pred, PEF variability, total serum IgE level, cumulative tobacco cigarette consumption (pack-years), and SGRQ score (P<0.05). By different cluster analyses, distinct clinical phenotypes of chronic airway diseases are identified. Thus, individualized treatments may guide doctors to provide based on different phenotypes.

Context conditioning and behavioral avoidance in a virtual reality environment: effect of predictability.

PubMed

Grillon, Christian; Baas, Johanna M P; Cornwell, Brian; Johnson, Linda

2006-10-01

Sustained anxiety can be modeled using context conditioning, which can be studied in a virtual reality environment. Unpredictable stressors increase context conditioning in animals. This study examined context conditioning to predictable and unpredictable shocks in humans using behavioral avoidance, potentiated startle, and subjective reports of anxiety. Subjects were guided through three virtual rooms (no-shock, predictable, unpredictable contexts). Eight-sec duration colored lights served as conditioned stimuli (CS). During acquisition, no shock was administered in the no-shock context. Shocks were paired with the CS in the predictable context and were administered randomly in the unpredictable context. No shock was administered during extinction. Startle stimuli were delivered during CS and between CS to assess cued and context conditioning, respectively. To assess avoidance, subjects freely navigated into two of the three contexts to retrieve money. Startle between CS was potentiated in the unpredictable context compared to the two other contexts. Following acquisition, subjects showed a strong preference for the no-shock context and avoidance of the unpredictable context. Consistent with animal data, context conditioning is increased by unpredictability. These data support virtual reality as a tool to extend research on physiological and behavioral signs of fear and anxiety in humans.

[Clinical experience of the use of agomelatine in the treatment of patients with depression and chronic brain ischemia].

PubMed

Antonen, E G; Nikitina, M V; Kruchek, M M

2015-01-01

To study the efficacy and tolerability of agomelatine (valdoxan) in treatment of mild depressive states in patients with chronic brain ischemia (CBI). The study comprised 33 patients (23 women, 10 men, average age 54.5 years), including 12 people (36.4%) with CBI, stage I, and 21 (63.6%) with CBI, stage II. All patients had a single depressive episode of mild severity. Diagnosis of affective and cognitive impairment was carried out using clinical and neuropsychological methods (the Hamilton Depression Rating Scale (HDRS-17), the Hospital Anxiety and Depression Scale (HADS), the night sleep questionnaire developed by A.M. Vein, the Mini-mental state examination (MMSE), the modified Mini-Cog method, the Montreal Cognitive Assessment Scale (MoCA), the Clinical Global Impression scale (CGI-S, CGI-I) to assess the degree and dynamics of the disease, the Patient Global Impression (PGI) scale. The survey had been performed after 2,4 and 8 weeks of treatment. Agomelatine (valdoxan) was used 1 time per day in the evening in a dose of 25 mg (1 tablet). Agomelatine improved sleep from the second week of treatment, reduced anxiety symptoms after six weeks and depressive symptoms after eight weeks. The improvement of cognitive functions was noted as well. No side-effects was observed. The results revealed the high antidepressive activity of the drug in treatment of mild depressive states in patients with chronic brain ischemia, the balanced spectrum of effects on anxiety, depression, insomnia, the positive effect on cognitive functions that allows to recommend agomelatine in treatment of patients with CBI.

Vertical leadership in highly complex and unpredictable health systems.

PubMed

Till, Alex; Dutta, Nina; McKimm, Judy

2016-08-02

This article explores how the concept of vertical leadership development might help health organizations cope with and thrive within highly complex and unpredictable health systems, looking at concepts of VUCA (volatility, uncertainty, complexity and ambiguity) and RUPT (rapid, unpredictable, paradoxical and tangled).

Changes in Male Rat Sexual Behavior and Brain Activity Revealed by Functional Magnetic Resonance Imaging in Response to Chronic Mild Stress.

PubMed

Chen, Guotao; Yang, Baibing; Chen, Jianhuai; Zhu, Leilei; Jiang, Hesong; Yu, Wen; Zang, Fengchao; Chen, Yun; Dai, Yutian

2018-02-01

Non-organic erectile dysfunction (noED) at functional imaging has been related to abnormal brain activity and requires animal models for further research on the associated molecular mechanisms. To develop a noED animal model based on chronic mild stress and investigate brain activity changes. We used 6 weeks of chronic mild stress to induce depression. The sucrose consumption test was used to assess the hedonic state. The apomorphine test and sexual behavior test were used to select male rats with ED. Rats with depression and ED were considered to have noED. Blood oxygen level-dependent-based resting-state functional magnetic resonance imaging (fMRI) studies were conducted on these rats, and the amplitude of low-frequency fluctuations and functional connectivity were analyzed to determine brain activity changes. The sexual behavior test and resting-state fMRI were used for outcome measures. The induction of depression was confirmed by the sucrose consumption test. A low intromission ratio and increased mount and intromission latencies were observed in male rats with depression. No erection was observed in male rats with depression during the apomorphine test. Male rats with depression and ED were considered to have noED. The possible central pathologic mechanism shown by fMRI involved the amygdaloid body, dorsal thalamus, hypothalamus, caudate-putamen, cingulate gyrus, insular cortex, visual cortex, sensory cortex, motor cortex, and cerebellum. Similar findings have been found in humans. The present study provided a novel noED rat model for further research on the central mechanism of noED. The present study developed a novel noED rat model and analyzed brain activity changes based at fMRI. The observed brain activity alterations might not extend to humans. The present study developed a novel noED rat model with brain activity alterations related to sexual arousal and erection, which will be helpful for further research involving the central mechanism of noED. Chen G, Yang B, Chen J, et al. Changes in Male Rat Sexual Behavior and Brain Activity Revealed by Functional Magnetic Resonance Imaging in Response to Chronic Mild Stress. J Sex Med 2018;15:136-147. Copyright © 2017 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

[Gap junctions: A new therapeutic target in major depressive disorder?].

PubMed

Sarrouilhe, D; Dejean, C

2015-11-01

Major depressive disorder is a multifactorial chronic and debilitating mood disease with high lifetime prevalence and is associated with excess mortality, especially from cardiovascular diseases and through suicide. The treatments of this disease with tricyclic antidepressants and monoamine oxidase inhibitors are poorly tolerated and those that selectively target serotonin and norepinephrine re-uptake are not effective in all patients, showing the need to find new therapeutic targets. Post-mortem studies of brains from patients with major depressive disorders described a reduced expression of the gap junction-forming membrane proteins connexin 30 and connexin 43 in the prefrontal cortex and the locus coeruleus. The use of chronic unpredictable stress, a rodent model of depression, suggests that astrocytic gap junction dysfunction contributes to the pathophysiology of major depressive disorder. Chronic treatments of rats with fluoxetine and of rat cultured cortical astrocytes with amitriptyline support the hypothesis that the upregulation of gap junctional intercellular communication between brain astrocytes could be a novel mechanism for the therapeutic effect of antidepressants. In conclusion, astrocytic gap junctions are emerging as a new potential therapeutic target for the treatment of patients with major depressive disorder. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

A New Arbiter PUF for Enhancing Unpredictability on FPGA

PubMed Central

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. PMID:26491720

Anxiety and Depression Symptom Dimensions Demonstrate Unique Relationships with the Startle Reflex in Anticipation of Unpredictable Threat in 8 to 14 Year-Old Girls.

PubMed

Nelson, Brady D; Hajcak, Greg

2017-02-01

There is growing evidence that heightened sensitivity to unpredictability is a core mechanism of anxiety disorders. In adults, multiple anxiety disorders have been associated with a heightened startle reflex in anticipation of unpredictable threat. Child and adolescent anxiety has been linked to an increased startle reflex across baseline, safety, and threat conditions. However, it is unclear whether anxiety in youth is related to the startle reflex as a function of threat predictability. In a sample of 90 8 to 14 year-old girls, the present study examined the association between anxiety symptom dimensions and startle potentiation during a no, predictable, and unpredictable threat task. Depression symptom dimensions were also examined given their high comorbidity with anxiety and mixed relationship with the startle reflex and sensitivity to unpredictability. To assess current symptoms, participants completed the self-report Screen for Child Anxiety Related Emotional Disorders and Children's Depression Inventory. Results indicated that social phobia symptoms were associated with heightened startle potentiation in anticipation of unpredictable threat and attenuated startle potentiation in anticipation of predictable threat. Negative mood and negative self-esteem symptoms were associated with attenuated and heightened startle potentiation in anticipation of unpredictable threat, respectively. All results remained significant after controlling for the other symptom dimensions. The present study provides initial evidence that anxiety and depression symptom dimensions demonstrate unique associations with the startle reflex in anticipation of unpredictable threat in children and adolescents.

Anxiety and Depression Symptom Dimensions Demonstrate Unique Relationships with the Startle Reflex in Anticipation of Unpredictable Threat in 8 to 14 Year-Old Girls

PubMed Central

Nelson, Brady D.; Hajcak, Greg

2016-01-01

There is growing evidence that heightened sensitivity to unpredictability is a core mechanism of anxiety disorders. In adults, multiple anxiety disorders have been associated with a heightened startle reflex in anticipation of unpredictable threat. Child and adolescent anxiety has been linked to an increased startle reflex across baseline, safety, and threat conditions. However, it is unclear whether anxiety in youth is related to the startle reflex as a function of threat predictability. In a sample of 90 8 to 14 year-old girls, the present study examined the association between anxiety symptom dimensions and startle potentiation during a no, predictable, and unpredictable threat task. Depression symptom dimensions were also examined given their high comorbidity with anxiety and mixed relationship with the startle reflex and sensitivity to unpredictability. To assess current symptoms, participants completed the self-report Screen for Child Anxiety Related Emotional Disorders and Children’s Depression Inventory. Results indicated that social phobia symptoms were associated with heightened startle potentiation in anticipation of unpredictable threat and attenuated startle potentiation in anticipation of predictable threat. Negative mood and negative self-esteem symptoms were associated with attenuated and heightened startle potentiation in anticipation of unpredictable threat, respectively. All results remained significant after controlling for the other symptom dimensions. The present study provides initial evidence that anxiety and depression symptom dimensions demonstrate unique associations with the startle reflex in anticipation of unpredictable threat in children and adolescents. PMID:27224989

A putative low-carbohydrate ketogenic diet elicits mild nutritional ketosis but does not impair the acute or chronic hypertrophic responses to resistance exercise in rodents.

PubMed

Roberts, Michael D; Holland, A Maleah; Kephart, Wesley C; Mobley, C Brooks; Mumford, Petey W; Lowery, Ryan P; Fox, Carlton D; McCloskey, Anna E; Shake, Joshua J; Mesquita, Paulo; Patel, Romil K; Martin, Jeffrey S; Young, Kaelin C; Kavazis, Andreas N; Wilson, Jacob M

2016-05-15

We examined whether acute and/or chronic skeletal muscle anabolism is impaired with a low-carbohydrate diet formulated to elicit ketosis (LCKD) vs. a mixed macronutrient Western diet (WD). Male Sprague-Dawley rats (9-10 wk of age, 300-325 g) were provided isoenergetic amounts of a LCKD or a WD for 6 wk. In AIM 1, basal serum and gastrocnemius assessments were performed. In AIM 2, rats were resistance exercised for one bout and were euthanized 90-270 min following exercise for gastrocnemius analyses. In AIM 3, rats voluntarily exercised daily with resistance-loaded running wheels, and hind limb muscles were analyzed for hypertrophy markers at the end of the 6-wk protocol. In AIM 1, basal levels of gastrocnemius phosphorylated (p)-rps6, p-4EBP1, and p-AMPKα were similar between diets, although serum insulin (P < 0.01), serum glucose (P < 0.001), and several essential amino acid levels (P < 0.05) were lower in LCKD-fed rats. In AIM 2, LCKD- and WD-fed rats exhibited increased postexercise muscle protein synthesis levels (P < 0.0125), but no diet effect was observed (P = 0.59). In AIM 3, chronically exercise-trained LCKD- and WD-fed rats presented similar increases in relative hind limb muscle masses compared with their sedentary counterparts (12-24%, P < 0.05), but there was no between-diet effects. Importantly, the LCKD induced "mild" nutritional ketosis, as the LCKD-fed rats in AIM 2 exhibited ∼1.5-fold greater serum β-hydroxybutyrate levels relative to WD-fed rats (diet effect P = 0.003). This study demonstrates that the tested LCKD in rodents, while only eliciting mild nutritional ketosis, does not impair the acute or chronic skeletal muscle hypertrophic responses to resistance exercise. Copyright © 2016 the American Physiological Society.

Low-dose lipopolysaccharide (LPS) inhibits aggressive and augments depressive behaviours in a chronic mild stress model in mice.

PubMed

Couch, Yvonne; Trofimov, Alexander; Markova, Natalyia; Nikolenko, Vladimir; Steinbusch, Harry W; Chekhonin, Vladimir; Schroeter, Careen; Lesch, Klaus-Peter; Anthony, Daniel C; Strekalova, Tatyana

2016-05-16

Aggression, hyperactivity, impulsivity, helplessness and anhedonia are all signs of depressive-like disorders in humans and are often reported to be present in animal models of depression induced by stress or by inflammatory challenges. However, chronic mild stress (CMS) and clinically silent inflammation, during the recovery period after an infection, for example, are often coincident, but comparison of the behavioural and molecular changes that underpin CMS vs a mild inflammatory challenge and impact of the combined challenge is largely unexplored. Here, we examined whether stress-induced behavioural and molecular responses are analogous to lipopolysaccharide (LPS)-induced behavioural and molecular effects and whether their combination is adaptive or maladaptive. Changes in measures of hedonic sensitivity, helplessness, aggression, impulsivity and CNS and systemic cytokine and 5-HT-system-related gene expression were investigated in C57BL/6J male mice exposed to chronic stress alone, low-dose LPS alone or a combination of LPS and stress. When combined with a low dose of LPS, chronic stress resulted in an enhanced depressive-like phenotype but significantly reduced manifestations of aggression and hyperactivity. At the molecular level, LPS was a strong inducer of TNFα, IL-1β and region-specific 5-HT2A mRNA expression in the brain. There was also increased serum corticosterone as well as increased TNFα expression in the liver. Stress did not induce comparable levels of cytokine expression to an LPS challenge, but the combination of stress with LPS reduced the stress-induced changes in 5-HT genes and the LPS-induced elevated IL-1β levels. It is evident that when administered independently, both stress and LPS challenges induced distinct molecular and behavioural changes. However, at a time when LPS alone does not induce any overt behavioural changes per se, the combination with stress exacerbates depressive and inhibits aggressive behaviours.

Progressive brain atrophy in patients with chronic neuropsychiatric symptoms after mild traumatic brain injury: a preliminary study.

PubMed

Ross, David E; Ochs, Alfred L; Seabaugh, Jan M; Demark, Michael F; Shrader, Carole R; Marwitz, Jennifer H; Havranek, Michael D

2012-01-01

NeuroQuant® is a recently developed, FDA-approved software program for measuring brain MRI volume in clinical settings. The aims of this study were as follows: (1) to examine the test-retest reliability of NeuroQuant®; (2) to test the hypothesis that patients with mild traumatic brain injury (TBI) would have abnormally rapid progressive brain atrophy; and (3) to test the hypothesis that progressive brain atrophy in patients with mild TBI would be associated with vocational outcome. Sixteen patients with mild TBI were compared to 20 normal controls. Vocational outcome was assessed with the Glasgow Outcome Scale-Extended (GOSE) and Disability Rating Scale (DRS). NeuroQuant® showed high test-re-test reliability. Patients had abnormally rapid progressive atrophy in several brain regions and the rate of atrophy was associated with inability to return to work. NeuroQuant®, is a reliable and valid method for assessing the anatomic effects of TBI. Progression of atrophy may continue for years after injury, even in patients with mild TBI.

Vitamins and Microelement Bioavailability in Different Stages of Chronic Kidney Disease

PubMed Central

Jankowska, Magdalena; Rutkowski, Bolesław; Dębska-Ślizień, Alicja

2017-01-01

Chronic kidney disease (CKD) predisposes one to either deficiency or toxic excess of different micronutrients. The knowledge on micronutrients—specifically water-soluble vitamins and trace elements—in CKD is very limited. Consequently, current guidelines and recommendations are mostly based on expert opinions or poor-quality evidence. Abnormalities of micronutrient resources in CKD develop for several reasons. Dietary restrictions and anorexia lead to an insufficient micronutrient intake, while diuretics use and renal replacement therapy lead to their excessive losses. Absorption is unpredictable, and metabolism impaired. Better understanding of the micronutrient needs of CKD patients could have an impact on many complications linked to vitamin and trace element disorders, including high mortality, increased risk of atherosclerosis, inflammation, oxidative stress, anemia, polyneuropathy, encephalopathy, weakness and fragility, muscle cramps, bone disease, depression, or insomnia. Here, we summarize the up-to-date knowledge on micronutrient resources in different stages of CKD, and share our experience with the assessment of micronutrient status. PMID:28294976

Conditional Inhibition of Adult Neurogenesis by Inducible and Targeted Deletion of ERK5 MAP Kinase Is Not Associated with Anxiety/Depression-Like Behaviors1,2

PubMed Central

Zou, Junhui; Wang, Wenbin; Pan, Yung-Wei; Abel, Glen M.

2015-01-01

Abstract Although there is evidence that adult neurogenesis contributes to the therapeutic efficacy of chronic antidepressant treatment for anxiety and depression disorders, the role of adult neurogenesis in the onset of depression-related symptoms is still open to question. To address this issue, we utilized a transgenic mouse strain in which adult neurogenesis was specifically and conditionally impaired by Nestin-CreER-driven, inducible knockout (icKO) of erk5 MAP kinase in Nestin-expressing neural progenitors of the adult mouse brain upon tamoxifen administration. Here, we report that inhibition of adult neurogenesis by this mechanism is not associated with an increase of the baseline anxiety or depression in non-stressed animals, nor does it increase the animal’s susceptibility to depression after chronic unpredictable stress treatment. Our findings indicate that impaired adult neurogenesis does not lead to anxiety or depression. PMID:26464972

Effects of chronic mild stress on the development of drug dependence in rats.

PubMed

Papp, Mariusz; Gruca, Piotr; Lason-Tyburkiewicz, Magdalena; Litwa, Ewa; Willner, Paul

2014-09-01

There is high comorbidity between depression and addiction. Features of addiction relevant to depression have been studied extensively, but less is known about features of depression relevant to addiction. Here, we have studied the effects of chronic mild stress (CMS), a valid animal model of depression, on measures of physical and psychological dependence resulting from subchronic treatment of rats with three drugs of abuse that act through disparate neurobiological mechanisms: morphine, nicotine and diazepam. In animals not treated subchronically with drugs of abuse, CMS increased the withdrawal-like effects of the opiate antagonist naloxone, but not those of the nicotinic antagonist mecamylamine or the benzodiazepine antagonist flumazenil. In animals treated subchronically with drugs of abuse, CMS exacerbated, precipitated and conditioned withdrawal effects associated with all three antagonists. CMS also potentiated withdrawal-induced and cue-induced place aversions associated with all three antagonists. All of the effects of CMS were reversed by chronic treatment with the specific serotonin reuptake inhibitor citalopram. These results suggest that treatment of comorbid depression, although not a primary treatment for addiction, may facilitate other treatments for addiction, by decreasing the severity of withdrawal symptoms and the likelihood of relapse.

Military and Veterans Rehabilitation and Recovery from Injury Network (MAVERICK): Chronic Effects of Neurotrauma Consortium (CENC)

DTIC Science & Technology

2014-10-01

veterans with combat- related mTBI and non-TBI combat-exposed controls on comprehensive neuropsychological, neuroimaging, genomics , biomarkers, and...existing VA healthcare data to study the chronic effects of mild traumatic brain injury (mTBI) on neurodegenerative disease and other comorbidities... mice at different time points pre- and post- single mTBI and repetitive mTBI, and g. Began analysis of tissues samples obtained via the protocol. IX

Mild Head Trauma and Chronic Headaches in Returning US Soldiers

DTIC Science & Technology

2009-04-01

incidence and types of head or neck trauma among a cohort of US soldiers evaluated for chronic head - aches at a military neurology clinic following a...29.1 years. Head or neck trauma occurred during deployment in 33 of 81 (41%) of the soldiers referred to our clinic for head - aches . The causes of...consciousness. Ten soldiers also experienced a whiplash or neck injury while deployed. Multiple head or neck inju- Fig—Mechanism of head or neck

Novel antidepressant candidate RO-05 modulated glucocorticoid receptors activation and FKBP5 expression in chronic mild stress model in rats.

PubMed

Xing, Y; Hou, J; Meng, Q; Yang, M; Kurihara, H; Tian, J

2015-04-02

In this study, a novel TRI (triple reuptake inhibitors) antidepressant candidate RO-05 (4-[1-[1-(benzoyloxy)cyclohexyl]-2-(dimethylamino)ethyl]-phenyl benzoate) was investigated in TST (tail suspension test), FST (forced swimming test) and CMS (chronic mild stress) model. Results showed RO-05 significantly decreased the immobility time in FST and TST at 4.5-, 9-, 18-mg/kg in rats and 9-, 18-, 36-mg/kg in mice. Chronic administration of 18-mg/kg RO-05 improved the behavioral index, anhedonia and normalized the hyperactivity of HPA (hypothalamic-pituitary-adrenal axis) of CMS rats. We further investigated the possible mechanisms of RO-05 in the CMS model. Eighteen milligrams per kilogram of RO-05 chronic administration significantly reversed the increase of mRNA and protein expression of FKBP5 in the CMS rat hippocampus, which facilitated the activation of GR- (glucocorticoid receptor) and GR-responsive gene Foxo1 expression. RO-05 also elevated the expression of BDNF (brain-derived neurotrophic factor) in CMS rat hippocampus. In summary, our results indicated that RO-05 is a promising antidepressant candidate. The possible antidepressant mechanisms of RO-05 were the modulation of FKBP5 expression, GR activation, corresponding inhibition of HPA axis hyperactivity, and the increase of BDNF expression. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Adolescent environmental enrichment prevents behavioral and physiological sequelae of adolescent chronic stress in female (but not male) rats.

PubMed

Smith, Brittany L; Morano, Rachel L; Ulrich-Lai, Yvonne M; Myers, Brent; Solomon, Matia B; Herman, James P

2017-11-22

The late adolescent period is characterized by marked neurodevelopmental and endocrine fluctuations in the transition to early adulthood. Adolescents are highly responsive to the external environment, which enhances their ability to adapt and recover from challenges when given nurturing influences, but also makes them vulnerable to aberrant development when exposed to prolonged adverse situations. Female rats are particularly sensitive to the effects of chronic stress in adolescence, which manifests as passive coping strategies and blunted hypothalamo-pituitary adrenocortical (HPA) stress responses in adulthood. We sought to intervene by exposing adolescent rats to environmental enrichment (EE) immediately prior to and during chronic stress, hypothesizing that EE would minimize or prevent the long-term effects of stress that emerge in adult females. To test this, we exposed male and female rats to EE on postnatal days (PND) 33-60 and implemented chronic variable stress (CVS) on PND 40-60. CVS consisted of twice-daily unpredictable stressors. Experimental groups included: CVS/unenriched, unstressed/EE, CVS/EE and unstressed/unenriched (n = 10 of each sex/group). In adulthood, we measured behavior in the open field test and forced swim test (FST) and collected blood samples following the FST. We found that environmental enrichment given during the adolescent period prevented the chronic stress-induced transition to passive coping in the FST and reversed decreases in peak adrenocortical responsiveness observed in adult females. Adolescent enrichment had little to no effect on males or unstressed females tested in adulthood, indicating that beneficial effects are specific to females that were exposed to chronic stress.

Antidepressant-like effects and possible mechanisms of amantadine on cognitive and synaptic deficits in a rat model of chronic stress.

PubMed

Yu, Mei; Zhang, Yuan; Chen, Xiaoyu; Zhang, Tao

2016-01-01

The aim of this study was to examine whether amantadine (AMA), as a low-affinity noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist, is able to improve cognitive deficits caused by chronic stress in rats. Male Wistar rats were divided into four groups: control, control + AMA, stress and stress + AMA groups. The chronic stress model combined chronic unpredictable stress (CUS) with isolated feeding. Animals were exposed to CUS continued for 21 days. AMA (25 mg/kg) was administrated p.o. for 20 days from the 4th day of CUS to the 23rd. Weight and sucrose consumption were measured during model establishing period. Spatial memory was evaluated using the Morris water maze (MWM) test. Following MWM testing, both long-term potentiation (LTP) and depotentiation were recorded in the hippocampal CA1 region. NR2B and postsynaptic density protein 95 (PSD-95) proteins were measured by Western-blot analysis. AMA increased weight and sucrose consumption of stressed rats. Spatial memory and reversal learning in stressed rats were impaired relative to controls, whereas AMA significantly attenuated cognitive impairment. AMA also mitigated the chronic stress-induced impairment of hippocampal synaptic plasticity, in which both the LTP and depotentiation were significantly inhibited in stressed rats. Moreover, AMA enhanced the expression of hippocampal NR2B and PSD-95 in stressed rats. The data suggest that AMA may be an effective therapeutic agent for depression-like symptoms and associated cognitive disturbances.

A meta-ethnography of patients' experiences of chronic pelvic pain: struggling to construct chronic pelvic pain as 'real'.

PubMed

Toye, Francine; Seers, Kate; Barker, Karen

2014-12-01

To review systematically and integrate the findings of qualitative research to increase our understanding of patients' experiences of chronic pelvic pain. Chronic pelvic pain is a prevalent pain condition with a high disease burden for men and women. Its multifactorial nature makes it challenging for clinicians and patients. Synthesis of qualitative research using meta-ethnography. Five electronic bibliographic databases from inception until March 2014 supplemented by citation tracking. Of 488 papers retrieved, 32 met the review aim. Central to meta-ethnography is identifying 'concepts' and developing a conceptual model through constant comparison. Concepts are the primary data of meta-ethnography. Two team members read each paper to identify and collaboratively describe the concepts. We next compared concepts across studies and organized them into categories with shared meaning. Finally, we developed a conceptual model, or line of argument, to explain the conceptual categories. Our findings incorporate the following categories into a conceptual model: relentless and overwhelming pain; threat to self; unpredictability, struggle to construct pain as normal or pathological; a culture of secrecy; validation by diagnosis; ambiguous experience of health care; elevation of experiential knowledge and embodiment of knowledge through a community. The innovation of our model is to demonstrate, for the first time, the central struggle to construct 'pathological' vs. 'normal' chronic pelvic pain, a struggle that is exacerbated by a culture of secrecy. More research is needed to explore men's experience and to compare this with women's experience. © 2014 John Wiley & Sons Ltd.

Beneficial effects of benzodiazepine diazepam on chronic stress-induced impairment of hippocampal structural plasticity and depression-like behavior in mice.

PubMed

Zhao, Yunan; Wang, Zhongli; Dai, Jianguo; Chen, Lin; Huang, Yufang; Zhan, Zhen

2012-03-17

Whether benzodiazepines (BZDs) have beneficial effects on the progress of chronic stress-induced impairment of hippocampal structural plasticity and major depression is uncertain. The present study designed four preclinical experiments to determine the effects of BZDs using chronic unpredictable stress model. In Experiment 1, several time course studies on behavior and hippocampus response to stress were conducted using the forced swim and tail suspension tests (FST and TST) as well as hippocampal structural plasticity markers. Chronic stress induced depression-like behavior in the FST and TST as well as decreased hippocampal structural plasticity that returned to normal within 3 wk. In Experiment 2, mice received p.o. administration of three diazepam dosages prior to each variate stress session for 4 wk. This treatment significantly antagonized the elevation of stress-induced corticosterone levels. Only low- (0.5mg/kg) and medium-dose (1mg/kg) diazepam blocked the detrimental effects of chronic stress. In Experiment 3, after 7 wk of stress sessions, daily p.o. diazepam administration during 1 wk recovery phase dose-dependently accelerated the recovery of stressed mice. In Experiment 4, 1 wk diazepam administration to control mice enhanced significantly hippocampal structural plasticity and induced an antidepressant-like behavioral effect, whereas 4 wk diazepam administration produced opposite effects. Hence, diazepam can slow the progress of chronic stress-induced detrimental consequences by normalizing glucocorticoid hormones. Considering the adverse effect of long-term diazepam administration on hippocampal plasticity, the preventive effects of diazepam may depend on the proper dose. Short-term diazepam treatment enhances hippocampal structural plasticity and is beneficial to recovery following chronic stress. Copyright © 2011 Elsevier B.V. All rights reserved.

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

PubMed

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.

MMPI-2 profiles 23 years after paediatric mild traumatic brain injury.

PubMed

Hessen, Erik; Anderson, Vicki; Nestvold, Knut

2008-01-01

Research suggest that post-concussive syndrome after mild traumatic brain injury (mTBI) is more common than chronic cognitive impairment. The aim of this study was to investigate very long-term outcome of subjective complaints after paediatric mTBI. The study was a follow-up 23 years after a prospective head injury study at a general hospital in Norway. Forty-one patients were assessed with the Minnesota Multiphasic Personality Inventory-2 (MMPI-2) 23 years after sustaining mTBI as children. A good overall outcome was found with scores close to the normative mean, average length of education and normal employment rate. However, the children that sustained complicated mTBI showed slightly more pathological scores, typical for mild post-concussive syndrome. The most important predictors of poor outcome were skull fracture and a combination of post-traumatic amnesia > 30 minutes and EEG pathology within 24 hours after TBI. No influence of pre- and post-injury risk factors on current MMPI-2 profiles was evident. The results give support for the notion of potentially differential impact of uncomplicated vs complicated mTBI. The findings suggest that children and adolescents sustaining complicated mTBI may be at risk of developing subtle chronic symptoms typical of post-concussive syndrome.

[Health and exercise: effects of exercise on high blood pressure].

PubMed

Ikeda, M; Nanri, H; Himeno, E

1993-09-01

Many factors, such as genetic, psychological, environmental, and socioeconomical factors, influence the health of individuals. Recently behavioral risks which cause preventable chronic diseases or premature death have been increasing. These risk factors are mainly due to living habits, such as over-eating, less exercise and psychological stress. Physical activity or fitness is reported to be inversely associated with morbidity and mortality from chronic diseases, such as cardiovascular diseases diabetes mellitus, cancer and so on. Hypertension has also been reported to be associated with low physical fitness in cross-sectional studies. We have so far reported a significant blood pressure reduction in mild hypertensive patients who completed mild intensity exercise training in well controlled studies. Exercise seemed to modify the multiple factors that might participate in raising and maintaining high blood pressure. The mechanisms of lowering blood pressure by exercise training are mainly due to a depletion of blood volume or the reduction of both cardiac output and the sympathetic tone. They were supported by the evidence of increased levels of prostaglandin E, dopamine, taurine, and decreased levels of plasma norepinephrine and endogenous ouavain-like substance. In this article, we have reviewed the physiological and biochemical roles of exercise, the effects of exercise on high blood pressure, and the hypotensive mechanism of mild aerobic exercise hypertensive patients.

Mild chronic obstructive pulmonary disease: why spirometry is not sufficient!

PubMed

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

2017-07-01

Chronic obstructive pulmonary disease (COPD) - an inflammatory disease of the airways, alveoli and lung microvasculature - is a leading cause of death worldwide. Smokers with milder airway obstruction constitute the majority of patients with this disease. Many studies have shown increased morbidity, activity-related dyspnea, exercise intolerance and mortality in such patients, compared with age-matched healthy populations. Clinical evaluation of symptomatic smokers with ostensibly mild airway obstruction poses a challenge in clinical practice as spirometry can obscure extensive heterogeneous pathophysiological impairment. Areas covered: A detailed review of the evidence for complex biological, physiological and radiological abnormalities in smokers who barely fit arbitrary spirometric criteria for COPD diagnosis. A brief discussion of the debate about current diagnostic spirometric criteria for COPD that can lead to diagnostic confusion and, in-some-instances, to inappropriate management. Finally, we provide a review of the clinical implications of these structural and functional abnormalities and try to build a solid rationale for earlier detection and effective, timely management. Expert commentary: The prevalence of mild COPD among smokers is high, yet under-diagnosis remains a major problem and there is lack of evidence-based management recommendations for this sub-population. Further tests beyond spirometry are useful in uncovering patho-physiological derangements that are clinically relevant.

Life stories of people on sick leave from work because of mild mental illness, pain and fatigue.

PubMed

Brataas, Hildfrid V; Evensen, Aud E

2015-01-01

Many people experience some form of mild mental illness, chronic pain and fatigue feelings that lead to long-term absences from the workplace. The article examines narrations about developmental experiences and adult life of people in need of back to work rehabilitation. Narrative interviews were analyzed within a qualitative content analyses design. The sample was purposive, with 16 working-age adults at rehabilitation because of mild mental illnesses, chronic pain, and fatigue feelings. Ethical approval, was obtained from The Regional Committee for Medical Research Ethics, Health Region Central Norway. Reference no.: 2010/1323. There were stories about more or less stressful childhoods. In adult life, there were turns at various ages from meaningful work engagement, to struggle in private life from long lasting strain, stressful family situations or crises. Illness may develop when experiencing crises or strain over time in private situations, this in combination with expectations and requirements in working life. Not only working environments, but also the private situations, life history events, and self-esteem of individuals, should be taken into consideration in the rehabilitation program. There is a need of research on working life that support the employee's positive self-image, and on effective rehabilitation when needed.

Single nucleotide polymorphisms in multiple sclerosis: disease susceptibility and treatment response biomarkers.

PubMed

Pravica, Vera; Popadic, Dusan; Savic, Emina; Markovic, Milos; Drulovic, Jelena; Mostarica-Stojkovic, Marija

2012-04-01

Multiple sclerosis (MS) is a chronic inflammatory demyelinating and neurodegenerative disease of the central nervous system characterized by unpredictable and variable clinical course. Etiology of MS involves both genetic and environmental factors. New technologies identified genetic polymorphisms associated with MS susceptibility among which immunologically relevant genes are significantly overrepresented. Although individual genes contribute only a small part to MS susceptibility, they might be used as biomarkers, thus helping to identify accurate diagnosis, predict clinical disease course and response to therapy. This review focuses on recent progress in research on MS genetics with special emphasis on the possibility to use single nucleotide polymorphism of candidate genes as biomarkers of susceptibility to disease and response to therapy.

The prevalence of fibromyalgia in other chronic pain conditions.

PubMed

Yunus, Muhammad B

2012-01-01

Central sensitivity syndromes (CSS) include fibromyalgia syndrome (FMS), irritable bowel syndrome, temporomandibular disorder, restless legs syndrome, chronic fatigue syndrome, and other similar chronic painful conditions that are based on central sensitization (CS). CSS are mutually associated. In this paper, prevalence of FMS among other members of CSS has been described. An important recent recognition is an increased prevalence of FMS in other chronic pain conditions with structural pathology, for example, rheumatoid arthritis, systemic lupus, ankylosing spondylitis, osteoarthritis, diabetes mellitus, and inflammatory bowel disease. Diagnosis and proper management of FMS among these diseases are of crucial importance so that unwarranted use of such medications as corticosteroids can be avoided, since FMS often occurs when RA or SLE is relatively mild.

The Prevalence of Fibromyalgia in Other Chronic Pain Conditions

PubMed Central

Yunus, Muhammad B.

2012-01-01

Central sensitivity syndromes (CSS) include fibromyalgia syndrome (FMS), irritable bowel syndrome, temporomandibular disorder, restless legs syndrome, chronic fatigue syndrome, and other similar chronic painful conditions that are based on central sensitization (CS). CSS are mutually associated. In this paper, prevalence of FMS among other members of CSS has been described. An important recent recognition is an increased prevalence of FMS in other chronic pain conditions with structural pathology, for example, rheumatoid arthritis, systemic lupus, ankylosing spondylitis, osteoarthritis, diabetes mellitus, and inflammatory bowel disease. Diagnosis and proper management of FMS among these diseases are of crucial importance so that unwarranted use of such medications as corticosteroids can be avoided, since FMS often occurs when RA or SLE is relatively mild. PMID:22191024

A heart breaking case of rapidly developing severe hemophagocytic syndrome secondary to chronic active EBV infection; a case report and review of the literature.

PubMed

Tawfik, Khoury; Liron, Yosha; Ayman, Abu Rmieleh; Schneider, Ronen; Wolf, D G; Ronen, Levi

2015-06-01

Epstein-Barr virus (EBV, HHV-4) is a gamma Herpesvirus with a 90% >seroprevalence in adults. Reactivations in non-immuno compromised individuals usually cause mild or no symptoms at all. Rarely, host immunity-virus balance is interrupted, resulting in a chronic active EBV infection. The following case illustrates the rapid development of severe hemophagocytic syndrome during chronic active EBV infection in a 73 year old woman who presented with lower extremity pain and edema, splenomegaly and abnormal liver enzymes. A diagnosis of chronic active EBV infection was made following an extensive investigation and the patient died secondary to rapidly progressive hemophagocytic syndrome. Copyright © 2015 Elsevier B.V. All rights reserved.

Mild carbon monoxide exposure diminishes selectively the integrity of the cochlea of the developing rat.

PubMed

Lopez, Ivan; Acuna, Dora; Webber, Douglas S; Korsak, Rose A; Edmond, John

2003-12-01

Rat pups were chronically exposed to carbon monoxide (CO) concentrations (12 or 25 ppm) in air starting at day 8, through 22 days of age, to examine the changes in the peripheral auditory system. Gastrostomy-reared rat pups, with or without CO exposure, were used and compared with mother-reared pups. The organ of Corti and the neurons of the spiral ganglion were analyzed for their morphology by using immunochemical and histological techniques. The inner and outer hair cells in the organ of Corti of animals exposed to 12 and 25 ppm CO were not different from the controls. However, at 25 ppm CO exposure, the nerve terminals innervating the inner hair cells were swollen. The somata of neurons in the spiral ganglion showed mild changes in the cytoplasm, and signs of mild vacuolization were observed in myelin covering their central processes. Synaptophysin, a marker for synaptic vesicles, and choline acetyltransferase, a marker for cholinergic terminals, showed no difference in immunoreactivity in CO exposed animals at 12 and at 25 ppm when compared with their age-matched controls. Also, Na(+)K(+) ATPase immunoreactivity patterns were normal compared with controls. Three enzymes were significantly reduced at the 25 ppm CO exposure: Cytochrome oxidase, NADH-TR, and calcium ATPase were decreased in both the organ of Corti and the neurons of the spiral ganglion, and decreased immunostaining for the neurofilament and myelin basic proteins was found. We conclude that components of the cochlea are selectively affected by mild chronic CO exposure during development. Copyright 2003 Wiley-Liss, Inc.

Pharyngeal swallowing phase and chronic cough

PubMed Central

Drozdz, Daniela Rejane Constantino; Costa, Cintia Conceição; Jesus, Paulo Roberto de Oliveira; Trindade, Mateus Silva; Weiss, Guilherme; Neto, Abdias Baptista M.; da Silva, Ana Maria T.; Mancopes, Renata

2012-01-01

Summary Introduction: The act of swallowing depends on a complex and dynamic process which uses common structures to the act of breathing; respiratory problems can cause swallowing difficulties. Aim: To assess the swallowing pharyngeal phase in patients with chronic cough. Method: Retrospective study with 15 patients of both genders, patients with chronic cough and risk factors for aspiration defined by the pneumologic diagnosis. The patients were submitted to anamnesis on complaints related to swallowing, chewing and breathing, or related to food and to videofluoroscopic examination. Results: It was observed that 33.3% had normal and functional swallowing, being the last one of most prevalence. The mild dysphagia was observed in 20% of the patients, the mild to moderate dysphagia in 6.7% of them. In relation to the Rosenbek scale, 73.3% of patients presented degree 1, 6.7% presented degrees 2 and 3, and 13.3% presented degree 8. The most found pathology was the chronic cough with 40%, followed by asthma with 20%; 69.2% of patients presented stasis and of these, five used protection maneuvers, of these, seven were effective and only three were used in the presence of stasis. The most used maneuver was the multiple swallowing, being effective in 100%. Conclusion: There are peculiarities in the patients' swallowing with chronic cough that, although not presenting complaints relating to swallowing, it presents an important aspiration risk due to the presence of changes in breathing pattern that can intervene in the coordination between breathing and swallowing, which is essential to protect the lower airway. PMID:25991980

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

PubMed

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.

Chlorpyrifos chronic toxicity in broilers and effect of vitamin C.

PubMed

Kammon, A M; Brar, R S; Sodhi, S; Banga, H S; Singh, J; Nagra, N S

2011-01-01

An experiment was conducted to study chlorpyrifos chronic toxicity in broilers and the protective effect of vitamin C. Oral administration of 0.8 mg/kg body weight (bw) (1/50 LD50) chlorpyrifos (Radar(®)), produced mild diarrhea and gross lesions comprised of paleness, flaccid consistency and slightly enlargement of liver. Histopathologically, chlorpyrifos produced degenerative changes in various organs. Oral administration of 100 mg/kg bw vitamin C partially ameliorated the degenerative changes in kidney and heart. There was insignificant alteration in biochemical and haematological profiles. It is concluded that supplementation of vitamin C reduced the severity of lesions induced by chronic chlorpyrifos toxicity in broilers.

Chronic subdural haematoma evolving from traumatic subdural hydroma.

PubMed

Wang, Yaodong; Wang, Chuanwei; Liu, Yuguang

2015-01-01

This study aimed to investigate the incidence and clinical characteristics of chronic subdural haematoma (CSDH) evolving from traumatic subdual hydroma (TSH). The clinical characteristics of 44 patients with CSDH evolving from TSH were analysed retrospectively and the relevant literature was reviewed. In 22.6% of patients, TSH evolved into CSDH. The time required for this evolution was 14-100 days after injury. All patients were cured with haematoma drainage. TSH is one possible origin of CSDH. The clinical characteristics of TSH evolving into CSDH include polarization of patient age and chronic small effusion. The injuries usually occur during deceleration and are accompanied by mild cerebral damage.

76 FR 27256 - Saflufenacil; Pesticide Tolerances

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-11

... reflection of a mild and transient general systemic toxicity and not a substance- specific neurotoxic effect. In the subchronic neurotoxicity study, systemic toxicity (anemia), but no evidence of neurotoxicity... systemic toxicity in males. A LOAEL was not established for females. Chronic dietary (All populations...

Fluorescence in situ hybridization is superior for monitoring Epstein Barr viral load in infectious mononucleosis patients.

PubMed

Cao, Pengfei; Zhang, Meili; Wang, Wei; Dai, Yafei; Sai, Buqing; Sun, Jun; Wang, Lujuan; Wang, Fan; Li, Guiyuan; Xiang, Juanjuan

2017-05-03

Epstein Barr virus (EBV) plays a causal role in some diseases, including infectious mononucleosis, lymphoproliferative diseases and nasopharyngeal carcinoma. Detection of EBV infection has been shown to be a useful tool for diagnosing EBV-related diseases. In the present study, we compared the performance of molecular tests, including fluorescence in situ hybridization (FISH) and EBV real-time PCR, to those of serological assays for the detection of EBV infection. Thirty-eight patients with infectious mononucleosis (IM) were enrolled, of whom 31 were diagnosed with a mild type, and seven were diagnosed with IM with haemophagocytic lymphohistiocytosis and chronic active EBV infection. Twenty healthy controls were involved in the study. The atypical lymphocytes in peripheral blood were detected under a microscope and the percentage of positive cells was calculated. EBV DNA load in peripheral blood was detected using real-time PCR. The FISH assay was developed to detect the EBV genome from peripheral blood mononuclear cells (PBMC). Other diagnosis methods including the heterophil agglutination (HA) test and EBV-VCA-IgM test, to detect EBV were also compared. SPSS17.0 was used for statistical analysis. In all, 5-41% atypical lymphocytes were found among the PBMC in mild IM patients, whereas 8-51% atypical lymphocytes were found in IM patients with haemophagocytic lymphohistiocytosis and chronic active EBV infection patients. There was no significant difference in the ratios of atypical lymphoma between patients of the different types. We observed that 71.2% of mild IM patients and 85.7% of IM patients with haemophagocytic lymphohistiocytosis and chronic active EBV infection patients were positive for EBV-VCA-IgM. EBV-VCA-IgM was negative in all healthy control subjects. In addition, 67.1% of mild IM patients tested heterophile antibody positive, whereas 71.4% of IM patients with haemophagocytic lymphohistiocytosis and chronic active EBV infection tested positive. EBV DNA detected using real-time PCR was observed in 89.5% of these IM patients. The EBV genome was detected by the FISH assay in 97.4% of the IM patients. The EB viral loads detected by FISH and real-time PCR increased with the severity of IM. The EBV genome was detected in almost all the PBMC of IM with haemophagocytic lymphohistiocytosis and chronic active EBV infection patients. Molecular tests, including FISH and EBV real-time PCR, are more sensitive than serological assays for the detection of EBV infection. The FISH assay detecting EBV copies in unfractionated whole blood is preferable and superior to plasma real-time PCR in its reflection of the absolute viral burden circulating in the patients.

Efficacy and safety of oral ketamine versus diclofenac to alleviate mild to moderate depression in chronic pain patients: A double-blind, randomized, controlled trial.

PubMed

Jafarinia, Morteza; Afarideh, Mohsen; Tafakhori, Abbas; Arbabi, Mohammad; Ghajar, Alireza; Noorbala, Ahmad Ali; Saravi, Maryam Alamdar; Agah, Elmira; Akhondzadeh, Shahin

2016-11-01

Ketamine is a glutamate N-methyl-d-aspartate receptor antagonist capable of exerting antidepressive effects in single or repeated intravenous infusions. The objective of this study was to investigate the safety and the efficacy of oral ketamine vs. diclofenac monotherapy in reducing symptoms of mild to moderate depression among patients with chronic pain. This study is a 6-week, randomized, double-blind, controlled, parallel-group trial with two intervention arms (ketamine, fixed daily dosage of 150mg vs. diclofenac, fixed daily dosage of 150mg). Twenty participants in each arm completed the trial program all of whom had two post-baseline measurements at week 3 and week 6. Reduction in depression symptoms was assessed using the Hamilton Depression Rating Scale (HDRS) and the hospital anxiety and depression subscale for depression (HADSDepression) scores at baseline and week 3 and week 6 post-intervention. Significantly lower HDRS scores were observed in the ketamine treatment group as early as 6 weeks post-intervention (P=0.008). By comparison, mean (±standard deviation) HADS depression subscale scores were significantly lower for individuals receiving ketamine compared to diclofenac for both post-baseline measures at week 3 (6.95±1.47 vs. 8.40±1.6, P=0.005) and week 6 (6.20±1.15 vs. 7.35±1.18, p=0.003). The limitations of the present study were its small sample size and the short-term follow-up period. Oral ketamine appears to be a safe and effective option in improving depressive symptoms of patients with chronic pain with mild-to-moderate depression. Copyright © 2016 Elsevier B.V. All rights reserved.

Clinical characteristics and risk factors of pulmonary hypertension associated with chronic respiratory diseases: a retrospective study.

PubMed

Chen, Yonghua; Liu, Chunli; Lu, Wenju; Li, Mengxi; Hadadi, Cyrus; Wang, Elizabeth Wenqian; Yang, Kai; Lai, Ning; Huang, Junyi; Li, Shiyue; Zhong, Nanshan; Zhang, Nuofu; Wang, Jian

2016-03-01

Chronic respiratory disease-associated pulmonary hypertension (PH) is an important subtype of PH, which lacks clinical epidemiological data in China. Six hundred and ninety three patients hospitalized from 2010 to 2013 were classified by echocardiography according to pulmonary arterial systolic pressure (PASP): mild (36≤ PASP <50 mmHg); moderate (50≤ PASP <70 mmHg) and severe (PASP ≥70 mmHg). Dyspnea (93.51%) was the most common symptom. Hemoptysis observed in the severe group (6.42%) was significantly higher than the other two groups (P<0.05). COPD (78.35%), lung bullae (44.16%), tuberculosis (including obsolete pulmonary tuberculosis) (38.82%), and bronchiectasis (30.45%) were frequently present. Mild group occupied the highest proportion (84.7%) in COPD, while severe group occupied the highest proportion (19.3%) in pulmonary embolism (P<0.01). Age, partial pressure of oxygen (PaO2), hematocrit (HCT), partial pressure of carbon dioxide (PaCO2), increase of N-terminal pro brain natriuretic peptide (NT-proBNP) and right ventricular (RV) diameter (>20 mm) were associated with moderate-to-severe PH, while RV [odds ratio (OR) =3.53, 95% CI, 2.17-5.74], NT-proBNP (OR=2.44, 95% CI, 1.51-3.95), HCT (OR=1.03, 95% CI, 1.00-1.07) and PaCO2 (OR=1.01, 95% CI, 1.00-1.03) were independent risk factors. PH related to respiratory diseases is mostly mild to moderate, and the severity is associated with the category of respiratory disease. Increased HCT can be an independent risk factor for PH related to chronic respiratory diseases.

Sex-Dependent Effects of Stress on Immobility Behavior and VTA Dopamine Neuron Activity: Modulation by Ketamine.

PubMed

Rincón-Cortés, Millie; Grace, Anthony A

2017-10-01

Stress constitutes a risk factor across several psychiatric disorders. Moreover, females are more susceptible to stress-related disorders, such as depression, than males. Although dopamine system underactivation is implicated in the pathophysiology of depression, little is known about the female dopamine system at baseline and post-stress. The effects of chronic mild stress were examined on ventral tegmental area dopamine neuron activity and forced swim test immobility by comparing male and female rats. The impact of a single dose of the rapid antidepressant ketamine (10 mg/kg, i.p.) on forced swim test immobility and ventral tegmental area function was then tested. Baseline ventral tegmental area dopamine activity was comparable in both sexes. At baseline, females exhibited roughly double the forced swim test immobility duration than males, which corresponded to ~50% decrease in ventral tegmental area dopamine population activity compared with similarly treated (i.e., post-forced swim test) males. Following chronic mild stress, there was greater immobility duration in both sexes and reduced ventral tegmental area dopamine neuron activity by approximately 50% in males and nearly 75% in females. Ketamine restored behavior and post-forced swim test ventral tegmental area dopamine activity for up to 7 days in females as well as in both male and female chronic mild stress-exposed rats. These data suggest increased female susceptibility to depression-like phenotypes (i.e., greater immobility, ventral tegmental area hypofunction) is associated with higher dopamine system sensitivity to both acute and repeated stress relative to males. Understanding the neural underpinnings of sex differences in stress vulnerability will provide insight into mechanisms of disease and optimizing therapeutic approaches in both sexes. © The Author 2017. Published by Oxford University Press on behalf of CINP.

Validity and Reliability of the Chronic Respiratory Disease Questionnaire in Elderly Individuals with Mild to Moderate Non-Cystic Fibrosis Bronchiectasis.

PubMed

Vodanovich, Domagoj A; Bicknell, Thomas J; Holland, Anne E; Hill, Catherine J; Cecins, Nola; Jenkins, Sue; McDonald, Christine F; Burge, Angela T; Thompson, Philip; Stirling, Robert G; Lee, Annemarie L

2015-01-01

The chronic respiratory disease questionnaire (CRDQ) is designed to assess health-related quality of life (HRQOL) in chronic respiratory conditions, but its reliability, validity and responsiveness in individuals with mild to moderate non-cystic fibrosis (CF) bronchiectasis are unclear. This study aimed to determine measurement properties of the CRDQ in non-CF bronchiectasis. Participants with non-CF bronchiectasis involved in a randomised controlled trial of exercise training were recruited. Internal consistency was assessed using Cronbach's α. Over 8 weeks, reliability was evaluated using intra-class correlation coefficients and Bland-Altman analysis for measures of agreement. Convergent and divergent validity was assessed by correlations with the other HRQOL questionnaires and the Hospital Anxiety and Depression Scale (HADS). The responsiveness to exercise training was assessed using effect sizes and standardised response means. Eighty-five participants were included (mean age ± SD, 64 ± 13 years). Internal consistency was adequate (>0.7) for all CRDQ domains and the total score. Test-retest reliability ranged from 0.69 to 0.85 for each CRDQ domain and was 0.82 for the total score. Dyspnoea (CRDQ) was related to St George's respiratory questionnaire (SGRQ) symptoms only (r = 0.38), with no relationship to the Leicester cough questionnaire (LCQ) or HADS. Moderate correlations were found between the total score of the CRDQ, the SGRQ (rs = -0.49) and the LCQ score (rs = 0.51). Lower CRDQ scores were associated with higher anxiety and depression (rs = -0.46 to -0.56). The responsiveness of the CRDQ was small (effect size 0.1-0.24). The CRDQ is a valid and reliable measure of HRQOL in mild to moderate non-CF bronchiectasis, but responsiveness was limited. © 2015 S. Karger AG, Basel.

Medical condition and care of undocumented migrants in ambulatory clinics in Tel Aviv, Israel: assessing unmet needs.

PubMed

Mor, Zohar; Raveh, Yuval; Lurie, Ido; Leventhal, Alex; Gamzu, Roni; Davidovitch, Nadav; Benari, Orel; Grotto, Itamar

2017-07-14

Approximately 150,000 undocumented migrants (UM) who are medically uninsured reside in Israel, including ~50,000 originating from the horn of Africa (MHA). Free medical-care is provided by two walk-in clinics in Tel-Aviv. This study aims to compare the medical complaints of UM from different origins, define their community health needs and assess gaps between medical needs and available services. This cross-sectional study included a random sample of 610 UM aged 18-64 years, who were treated in these community clinics between 2008 and 2011. The study compared UM who had complex medical conditions which necessitated referral to more equipped medical settings with UM having mild/simple medical conditions, who were treated at the clinics. MHA were younger, unemployed and more commonly males compared with UM originating from other countries. MHA also had longer referral-delays and visited the clinics less frequently. UM with complex medical conditions were more commonly females, had chronic diseases and demonstrated longer referral-delays than those who had mild/simple medical conditions. The latter more commonly presented with complained of respiratory, muscular and skeletal discomfort. In multivariate analysis, the variables which predicted complex medical conditions included female gender, chronic illnes and self-referral to the clinics. The ambulatory clinics were capable of responding to mild/simple medical conditions. Yet, the health needs of women and migrants suffering from complex medical conditions and chronic diseases necessitated referrals to secondary/tertiary medical settings, while jeopardizing the continuity of care. The health gaps can be addressed by a more holistic social approach, which includes integration of UM in universal health insurance.

Therapeutic potential of inhibitors of endocannabinoid degradation for the treatment of stress-related hyperalgesia in an animal model of chronic pain.

PubMed

Lomazzo, Ermelinda; Bindila, Laura; Remmers, Floor; Lerner, Raissa; Schwitter, Claudia; Hoheisel, Ulrich; Lutz, Beat

2015-01-01

The occurrence of chronic stress, depression, and anxiety can increase nociception in humans and may facilitate the transition from localized to chronic widespread pain. The mechanisms underlying chronic widespread pain are still unknown, hindering the development of effective pharmacological therapies. Here, we exposed C57BL/6J mice to chronic unpredictable stress (CUS) to investigate how persistent stress affects nociception. Next, mice were treated with multiple intramuscular nerve growth factor (NGF) injections, which induced chronic widespread nociception. Thus, combination of CUS and NGF served as a model where psychophysiological impairment coexists with long-lasting hyperalgesia. We found that CUS increased anxiety- and depression-like behavior and enhanced basal nociception in mice. When co-applied with repeated NGF injections, CUS elicited a sustained long-lasting widespread hyperalgesia. In order to evaluate a potential therapeutic strategy for the treatment of chronic pain associated with stress, we hypothesized that the endocannabinoid system (ECS) may represent a target signaling system. We found that URB597, an inhibitor of the anandamide-degrading enzyme fatty acid amide hydrolase (FAAH), and JZL184, an inhibitor of the 2-arachidonoyl glycerol-degrading enzyme monoacylglycerol lipase (MAGL), increased eCB levels in the brain and periphery and were both effective in reducing CUS-induced anxiety measured by the light-dark test and CUS-induced thermal hyperalgesia. Remarkably, the long-lasting widespread hyperalgesia induced by combining CUS and NGF was effectively reduced by URB597, but not by JZL184. Simultaneous inhibition of FAAH and MAGL did not improve the overall therapeutic response. Therefore, our findings indicate that enhancement of anandamide signaling with URB597 is a promising pharmacological approach for the alleviation of chronic widespread nociception in stress-exposed mice, and thus, it could represent a potential treatment strategy for chronic pain associated with neuropsychiatric disorders in humans.

Effect of Shodhana Treatment on Chronic Toxicity and Recovery of Aconite

PubMed Central

Sarkar, P.K.; Prajapati, P.K.; Shukla, V.J.; Ravishankar, B.

2012-01-01

Aconite is one of the poisonous plants used therapeutically in practice of Ayurveda after proper treatment called as ‘Shodhana’. To determine the effect of Shodhana treatment on chronic toxicity and to assess the effect of recovery period after chronic toxicity of aconite. Raw aconite (RV), urine treated aconite (SM), and milk treated aconite (SD) were administered in 6.25 mg/kg dose in Charles Foster strain albino rats for 90 days for chronic toxicity. Six rats from each were kept for another 30 days without test drugs treatment to observe recovery from chronic toxicity. RV was found to be highly toxic in chronic exposure, SM had no apparent toxicity, but SD had mild toxicity in kidney. The toxicities of RV and SD were reversible, but sudden withdrawal of SM caused adverse effects, suggestive of tapering withdrawal. Shodhana treatments remove toxic effects from raw aconite. Chronic toxicity of aconite is reversible. Confirmed the arrangement of abstract PMID:22736901

Receptor activator of nuclear factor kappa B ligand and osteoprotegerin levels in gingival crevicular fluid

PubMed Central

Sarlati, Fatemeh; Sattari, Mandana; Razzaghi, Shilan; Nasiri, Malihe

2012-01-01

Background: Osteoclastogenesis is coordinated by the interaction of three members of the tumor necrosis factor (TNF) superfamily: Osteoprotegerin (OPG)/receptor activator of nuclear factor kappa B ligand (RANKL)/receptor activator of nuclear factor kappa B (RANK). The aim of this study was to investigate RANKL and OPG levels, and their relative ratio in gingival crevicular fluid (GCF) of patients with chronic and aggressive periodontitis, as well as healthy controls. Materials and Methods: In this analytical study, GCF was obtained from healthy (n = 10), mild chronic periodontitis (n = 18), moderate chronic periodontitis (n = 18), severe chronic periodontitis (n = 20), and generalized aggressive periodontitis (n = 20) subjects. RANKL and OPG concentrations were measured by enzyme-linked immunosorbent assay. Statistical tests used were Kruskal–Wallis test, Mann–Whitney U rank sum test, and Spearman's rank correlation analysis. The level of statistical significance was set at P < 0.05. Results: Mean RANKL concentration showed no statistically significant differences between groups (P = 0.58). There were also no significant differences between mean OPG concentration in the five groups (P = 0.0.56). Moreover, relative RANKL/OPG ratio did not reveal a significant difference between the three study group subjects: healthy, chronic periodontitis (mild, moderate, severe), and aggressive periodontitis (P = 0.41). There was statistically significant correlation between the concentration of sRANKL and Clinical Attachment Level (CAL) in moderate chronic periodontitis patients (R = 0.48, P = 0.04). There was also negative correlation between OPG concentration and CAL in moderate chronic periodontitis patients, although not significant (R = −0.13). Conclusion: RANKL was prominent in periodontitis sites, especially in moderate periodontitis patients, whereas OPG was not detectable in some diseased sites with bleeding on probing, supporting the role of these two molecules in the bone loss developed in this disease. PMID:23559954

Association of maternal chronic disease with risk of congenital heart disease in offspring

PubMed Central

Chou, Hsin-Hsu; Chiou, Meng-Jiun; Liang, Fu-Wen; Chen, Lea-Hua; Lu, Tsung-Hsueh; Li, Chung-Yi

2016-01-01

Background: Information about known risk factors for congenital heart disease is scarce. In this population-based study, we aimed to investigate the relation between maternal chronic disease and congenital heart disease in offspring. Methods: The study cohort consisted of 1 387 650 live births from 2004 to 2010. We identified chronic disease in mothers and mild and severe forms of congenital heart disease in their offspring from Taiwan’s National Health Insurance medical claims. We used multivariable logistic regression analysis to assess the associations of all cases and specific types of congenital heart disease with various maternal chronic diseases. Results: For mothers with the following chronic diseases, the overall prevalence of congenital heart disease in their children was significantly higher than for mothers without these diseases: diabetes mellitus type 1 (adjusted odds ratio [OR] 2.32, 95% confidence interval [CI] 1.66–3.25), diabetes mellitus type 2 (adjusted OR 2.85, 95% CI 2.60–3.12), hypertension (adjusted OR 1.87, 95% CI 1.69–2.07), congenital heart defects (adjusted OR 3.05, 95% CI 2.45–3.80), anemia (adjusted OR 1.31, 95% CI 1.25–1.38), connective tissue disorders (adjusted OR 1.39, 95% CI 1.19–1.62), epilepsy (adjusted OR 1.37, 95% CI 1.08–1.74) and mood disorders (adjusted OR 1.25, 95% CI 1.11–1.41). The same pattern held for mild forms of congenital heart disease. A higher prevalence of severe congenital heart disease was seen only among offspring of mothers with congenital heart defects or type 2 diabetes. Interpretation: The children of women with several kinds of chronic disease appear to be at risk for congenital heart disease. Preconception counselling and optimum treatment of pregnant women with chronic disease would seem prudent. PMID:27729382

Association of maternal chronic disease with risk of congenital heart disease in offspring.

PubMed

Chou, Hsin-Hsu; Chiou, Meng-Jiun; Liang, Fu-Wen; Chen, Lea-Hua; Lu, Tsung-Hsueh; Li, Chung-Yi

2016-12-06

Information about known risk factors for congenital heart disease is scarce. In this population-based study, we aimed to investigate the relation between maternal chronic disease and congenital heart disease in offspring. The study cohort consisted of 1 387 650 live births from 2004 to 2010. We identified chronic disease in mothers and mild and severe forms of congenital heart disease in their offspring from Taiwan's National Health Insurance medical claims. We used multivariable logistic regression analysis to assess the associations of all cases and specific types of congenital heart disease with various maternal chronic diseases. For mothers with the following chronic diseases, the overall prevalence of congenital heart disease in their children was significantly higher than for mothers without these diseases: diabetes mellitus type 1 (adjusted odds ratio [OR] 2.32, 95% confidence interval [CI] 1.66-3.25), diabetes mellitus type 2 (adjusted OR 2.85, 95% CI 2.60-3.12), hypertension (adjusted OR 1.87, 95% CI 1.69-2.07), congenital heart defects (adjusted OR 3.05, 95% CI 2.45-3.80), anemia (adjusted OR 1.31, 95% CI 1.25-1.38), connective tissue disorders (adjusted OR 1.39, 95% CI 1.19-1.62), epilepsy (adjusted OR 1.37, 95% CI 1.08-1.74) and mood disorders (adjusted OR 1.25, 95% CI 1.11-1.41). The same pattern held for mild forms of congenital heart disease. A higher prevalence of severe congenital heart disease was seen only among offspring of mothers with congenital heart defects or type 2 diabetes. The children of women with several kinds of chronic disease appear to be at risk for congenital heart disease. Preconception counselling and optimum treatment of pregnant women with chronic disease would seem prudent. © 2016 Canadian Medical Association or its licensors.

Antidepressant, anxiolytic and procognitive effects of subacute and chronic ketamine in the chronic mild stress model of depression.

PubMed

Papp, Mariusz; Gruca, Piotr; Lason-Tyburkiewicz, Magdalena; Willner, Paul

2017-02-01

Ketamine is the prototype of a new generation of antidepressant drugs, which is reported in clinical studies to be effective in treatment-resistant patients, with an effect that appears within hours and lasts for a few days. Chronic mild stress (CMS) is a well-established and widely used animal model of depression, in which anhedonia, anxiogenesis and cognitive dysfunction can be observed reliably. Studies using acute or brief ketamine treatment following withdrawal from CMS have replicated the clinical finding of a rapid onset of antidepressant action. However, there have been no CMS studies of chronic daily ketamine treatment or continued stress following ketamine treatment, which would have greater translational potential in relation to the long-term maintenance of antidepressant effects. Wistar rats were drug treated following an initial 2 weeks of CMS exposure, which continued alongside daily drug treatment. A first experiment tested a range of chronic (5 weeks) ketamine doses (5-30 mg/kg); a second compared the effects of subacute (3-5 days) and chronic (5 weeks) treatment. CMS-induced anhedonic, anxiogenic and dyscognitive effects, as measured, respectively, by decreased sucrose intake, avoidance of open arms in the elevated plus maze and loss of discrimination in the novel object recognition test. A sustained antidepressant-like effect of ketamine in the sucrose intake test was observed in both experiments, with an onset at around 1 week, faster than imipramine, and an optimum dose of 10 mg/kg. Anxiogenic and dyscognitive effects of CMS, in the elevated plus maze and novel object recognition test, respectively, were fully reversed by both subacute and chronic ketamine treatment. Daily treatment with ketamine in the CMS model causes sustained long-term antidepressant, anxiolytic and procognitive effects. The demonstration of a procognitive effect of ketamine may have particular translational value.

Heart Rate and Oxygen Saturation Change Patterns During 6-min Walk Test in Subjects With Chronic Thromboembolic Pulmonary Hypertension.

PubMed

Inagaki, Takeshi; Terada, Jiro; Yahaba, Misuzu; Kawata, Naoko; Jujo, Takayuki; Nagashima, Kengo; Sakao, Seiichiro; Tanabe, Nobuhiro; Tatsumi, Koichiro

2018-05-01

The 6-min walk test (6MWT) is commonly performed to assess functional status in patients with chronic thromboembolic pulmonary hypertension. However, changes in heart rate and oxygen saturation (S pO 2 ) patterns during 6MWT in patients with chronic thromboembolic pulmonary hypertension remain unclear. Thirty-one subjects with chronic thromboembolic pulmonary hypertension were retrospectively evaluated to examine the relationships between the change in heart rate (Δheart rate), heart rate acceleration time, slope of heart rate acceleration, heart rate recovery during the first minute after 6MWT (HRR1), change in S pO 2 (ΔS pO 2 ), S pO 2 reduction time, and S pO 2 recovery time during 6MWT, and the severity of pulmonary hemodynamics assessed by right heart catheterization and echocardiography. Subjects with severe chronic thromboembolic pulmonary hypertension had significantly longer heart rate acceleration time (144.9 ± 63.9 s vs 96.0 ± 42.5 s, P = .033), lower Δheart rate (47.4 ± 16.9 vs 61.8 ± 13.6 beats, P = .02), and lower HRR1 (13.3 ± 9.0 beats vs 27.1 ± 9.2 beats, P < .001) compared to subjects with mild chronic thromboembolic pulmonary hypertension. Subjects with severe chronic thromboembolic pulmonary hypertension also had significantly longer S pO 2 reduction time (178.3 ± 70.3 s vs 134.3 ± 58.4 s, P = .03) and S pO 2 recovery time (107.6 ± 35.3 s vs 69.8 ± 32.7 s, P = .004) than did subjects with mild chronic thromboembolic pulmonary hypertension. Multivariate linear regression analysis showed only mean pulmonary arterial pressure independently was associated with heart rate acceleration time and slope of heart rate acceleration. Heart rate and S pO 2 change patterns during 6MWT are predominantly associated with pulmonary hemodynamics in subjects with chronic thromboembolic pulmonary hypertension. Evaluating heart rate and S pO 2 change patterns during 6MWT may serve as a safe and convenient way to follow the change in pulmonary hemodynamics. Copyright © 2018 by Daedalus Enterprises.

Evaluation and Treatment of Mild Traumatic Brain Injury: The Role of Neuropsychology

PubMed Central

Prince, Carolyn; Bruhns, Maya E.

2017-01-01

Awareness of mild traumatic brain injury (mTBI) and persisting post-concussive syndrome (PCS) has increased substantially in the past few decades, with a corresponding increase in research on diagnosis, management, and treatment of patients with mTBI. The purpose of this article is to provide a narrative review of the current literature on behavioral assessment and management of patients presenting with mTBI/PCS, and to detail the potential role of neuropsychologists and rehabilitation psychologists in interdisciplinary care for this population during the acute, subacute, and chronic phases of recovery. PMID:28817065

Behavioral Effects of Sub-Acute Inhalation of Toluene in Adult Rats

EPA Science Inventory

Reports of behavioral effects of repeated inhalation of toluene in rats have Yielded inconsistent fmdings. A recent study from this laboratory (Beasley et al., 2010) observed that after 13 weeks of inhaled toluene ("sub-chronic" exposure scenario), rats showed mild but persiste...

Ethical Implications of the Mild Encephalitis Hypothesis of Schizophrenia

PubMed Central

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 compulsory treatment orders might have to be reconsidered in light of causal therapies; leading to increased legal approval and reduced need for compulsory treatment orders due to better patient compliance. (7) The social inclusion of patients might improve, if treatment became more effective regarding cognitive and social functioning. (8) The stigmatization of patients and their relatives might decrease. PMID:28348532

Defensive motivation and attention in anticipation of different types of predictable and unpredictable threat: A startle and event-related potential investigation.

PubMed

Nelson, Brady D; Hajcak, Greg

2017-08-01

Predictability is an important characteristic of threat that impacts defensive motivation and attentional engagement. Supporting research has primarily focused on actual threat (e.g., shocks), and it is unclear whether the predictability of less intense threat (e.g., unpleasant pictures) similarly affects motivation and attention. The present study utilized a within-subject design and examined defensive motivation (startle reflex and self-reported anxiety) and attention (probe N100 and P300) in anticipation of shocks and unpleasant pictures during a no, predictable, and unpredictable threat task. This study also examined the impact of predictability on the P300 to shocks and late positive potential (LPP) to unpleasant pictures. The startle reflex and self-reported anxiety were increased in anticipation of both types of threat relative to no threat. Furthermore, startle potentiation in anticipation of unpredictable threat was greater for shocks compared to unpleasant pictures, but there was no difference for predictable threat. The probe N100 was enhanced in anticipation of unpredictable threat relative to predictable threat and no threat, and the probe P300 was suppressed in anticipation of predictable and unpredictable threat relative to no threat. These effects did not differ between the shock and unpleasant picture trials. Finally, the P300 and early LPP component were increased in response to unpredictable relative to predictable shocks and unpleasant pictures, respectively. The present study suggests that the unpredictability of unpleasant pictures increases defensive motivation, but to a lesser degree relative to actual threat. Moreover, unpredictability enhances attentional engagement in anticipation of, and in reaction to, both types of threat. © 2017 Society for Psychophysiological Research.

CT-Definable Subtypes of Chronic Obstructive Pulmonary Disease: A Statement of the Fleischner Society

PubMed Central

Austin, John H. M.; Hogg, James C.; Grenier, Philippe A.; Kauczor, Hans-Ulrich; Bankier, Alexander A.; Barr, R. Graham; Colby, Thomas V.; Galvin, Jeffrey R.; Gevenois, Pierre Alain; Coxson, Harvey O.; Hoffman, Eric A.; Newell, John D.; Pistolesi, Massimo; Silverman, Edwin K.; Crapo, James D.

2015-01-01

The purpose of this statement is to describe and define the phenotypic abnormalities that can be identified on visual and quantitative evaluation of computed tomographic (CT) images in subjects with chronic obstructive pulmonary disease (COPD), with the goal of contributing to a personalized approach to the treatment of patients with COPD. Quantitative CT is useful for identifying and sequentially evaluating the extent of emphysematous lung destruction, changes in airway walls, and expiratory air trapping. However, visual assessment of CT scans remains important to describe patterns of altered lung structure in COPD. The classification system proposed and illustrated in this article provides a structured approach to visual and quantitative assessment of COPD. Emphysema is classified as centrilobular (subclassified as trace, mild, moderate, confluent, and advanced destructive emphysema), panlobular, and paraseptal (subclassified as mild or substantial). Additional important visual features include airway wall thickening, inflammatory small airways disease, tracheal abnormalities, interstitial lung abnormalities, pulmonary arterial enlargement, and bronchiectasis. © RSNA, 2015 PMID:25961632

[Lung dysfunction in patients with mild chronic obstructive bronchitis].

PubMed

Nefedov, V B; Popova, L A; Shergina, E A

2004-01-01

VC, FVC, FEV1, FEV1/VC%, PEF, MEF25, MEF50, MEF75, TCL, TGV, RV, Ravt, Riin, Rex, DLCO-SS, PaO2, and PaO2 were determined in 33 patients with mild chronic obstructive lung disease (FEV1 > 70% of the normal value). All the patients were found to have impaired bronchial patency; most (63.6%) patients had lung volume and capacity changes, almost half (45.5%) the patients had pulmonary gas exchange dysfunction. Impaired bronchial patency mainly appeared as decreased MEF50, MEF15, and FEV1/VC%; altered lung volumes and capacities manifested chiefly by increased RV and decreased VC; pulmonary gas exchange dysfunction showed up primarily as lowered PaO2. The magnitude of the observed functional changes was generally slight. MEF50, MEF75, FEV1/VC%, and VC dropped to 59-20 and 79-70% of the normal value, respectively. RV increased up to 142-196% of the normal value; PaO2 reduced up to 79-60% mm Hg.

3.0T 1H magnetic resonance spectroscopy for assessment of steatosis in patients with chronic hepatitis C

PubMed Central

Zhang, Qian; Zhang, Hui-Mao; Qi, Wen-Qian; Zhang, Yong-Gui; Zhao, Ping; Jiao, Jian; Wang, Jiang-Bin; Zhang, Chun-Yu

2015-01-01

AIM: To investigate the utility of 1H magnetic resonance spectroscopy (1H MRS) as a noninvasive test for steatosis in patients infected with hepatitis C virus. METHODS: Ninety patients with chronic hepatitis C and pathology data underwent 3.0T 1H MRS, and the results of MRS and pathological analysis were compared. RESULTS: This group of patients included 26 people with mild fatty liver (28.89%), 16 people with moderate fatty liver (17.78%), 18 people with severe fatty liver (20.0%), and 30 people without fatty liver (33.33%). The water peak was near 4.7 parts per million (ppm), and the lipid peak was near 1.3 ppm. Analysis of variance revealed that differences in the lipid peak, the area under the lipid peak, ratio of the lipid peak to the water peak, and ratio of the area under the lipid peak to the area under the water peak were statistically significant among the groups. Specifically, as the severity of fatty liver increased, the value of each index increased correspondingly. In the pairwise comparisons, the mean lipid peak, area under the lipid peak, ratio of the lipid peak to the water peak, and ratio of the area under the lipid peak to the area under the water peak were significantly different between the no fatty liver and moderate fatty liver groups, whereas no differences were noted between the severe fatty liver group and the mild or moderate fatty liver group. Area under the ROC curve (AUC) of area ratio in lipid and water and ratio in lipid and water in the no fatty liver group to mild fatty liver group, mild fatty liver group to moderate fatty liver group, and moderate fatty liver disease group to severe fatty liver group, were 0.705, 0.900, and 0.975, respectively. CONCLUSION: 1H MRS is a noninvasive technique that can be used to provide information on the effect of liver steatosis on hepatic metabolic processes. This study indicates that the 1H MRS can be used as an indicator of steatosis in patients with chronic hepatitis C. PMID:26074712

Combined Effects of Acamprosate and Escitalopram on Ethanol Consumption in Mice

PubMed Central

Ho, Ada Man-Choi; Qiu, Yanyan; Jia, Yun-Fang; Aguiar, Felipe S.; Hinton, David J.; Karpyak, Victor M.; Weinshilboum, Richard M.; Choi, Doo-Sup

2016-01-01

Background Major depression is one of the most prevalent psychiatry comorbidities of alcohol use disorders (AUD). Since negative emotions can trigger craving and increase the risk of relapse, treatments that target both conditions simultaneously may augment treatment success. Previous studies showed a potential synergist effect of FDA approved medication for AUD acamprosate and the antidepressant escitalopram. In this study, we investigated the effects of combining acamprosate and escitalopram on ethanol consumption in stress-induced depressed mice. Methods Forty singly-housed C57BL/6J male mice were subjected to chronic unpredictable stress. In parallel, 40 group-housed male mice were subjected to normal husbandry. After 3 weeks, depressive- and anxiety-like behaviors and ethanol consumption were assessed. For the next 7 days, mice were injected with saline, acamprosate (200 mg/kg; twice/day), escitalopram (5 mg/kg; twice/day), or their combination (n = 9–11/drug group/stress group). Two-bottle choice limited access drinking of 15% ethanol and tap water was performed 3 hours into dark phase for 2 hours immediately after the dark phase daily injection. Ethanol drinking was monitored for another 7 days without drug administration. Results Mice subjected to the chronic unpredictable stress paradigm for 3 weeks showed apparent depression- and anxiety-like behaviors compared to their non-stressed counterparts including longer immobility time in the forced swim test and lower sucrose preference. Stressed mice also displayed higher ethanol consumption and preference in a 2-bottle choice drinking test. During the drug administration period, the escitalopram-only and combined drug groups showed significant reduction in ethanol consumption in non-stressed mice, while only the combined drug group showed significantly reduced consumption in stressed mice. However, such reduction did not persist into the post-drug administration period. Conclusions The combination of acamprosate and escitalopram suppressed ethanol intake in both non-stressed and stressed mice, hence this combination is potentially helpful for AUD individuals with or without comorbid depression to reduce alcohol use. PMID:27184383

Short- and long-term antidepressant effects of ketamine in a rat chronic unpredictable stress model.

PubMed

Jiang, Yinghong; Wang, Yiqiang; Sun, Xiaoran; Lian, Bo; Sun, Hongwei; Wang, Gang; Du, Zhongde; Li, Qi; Sun, Lin

2017-08-01

This research was aimed to evaluate the behaviors of short- or long-term antidepressant effects of ketamine in rats exposed to chronic unpredictable stress (CUS). Ketamine, a glutamate noncompetitive NMDA receptor antagonist, regulates excitatory amino acid functions, such as anxiety disorders and major depression, and plays an important role in synaptic plasticity and learning and memory. After 42 days of CUS model, male rats received either a single injection of ketamine (10 mg/kg; day 43) or 15 daily injections (days 43-75). The influence of ketamine on behavioral reactivity was assessed 24 hr (short-term) or 7 weeks after ketamine treatment (long-term). Behavioral tests used to assess the effects of these treatments included the sucrose preference (SP), open field (OF), elevated plus maze (EPM), forced swimming (FS), and water maze (WM) to detect anxiety-like behavior (OF and EPM), forced swimming (FS), and water maze (WM). Results: Short-term ketamine administration resulted in increases of body weight gain, higher sensitivity to sucrose, augmented locomotor activity in the OF, more entries into the open arms of the EPM, along increased activity in the FS test; all responses indicative of reductions in depression/despair in anxiety-eliciting situations. No significant differences in these behaviors were obtained under conditions of long-term ketamine administration ( p  > .05). The CUS + Ketamine group showed significantly increased activity as compared with the CUS + Vehicle group for analysis of the long-term effects of ketamine (* p  < .05). Nor were significant differences obtained in learning and memory performance in rats receiving ketamine ( p  > .05). Taken together these findings demonstrate that a short-term administration of ketamine induced rapid antidepressant-like effects in adult male rats exposed to CUS conditions, effects that were not observed in response to the long-term treatment regime.

Reproductive Resilience to Food Shortage in a Small Heterothermic Primate

PubMed Central

Perret, Martine; Henry, Pierre-Yves

2012-01-01

The massive energetic costs entailed by reproduction in most mammalian females may increase the vulnerability of reproductive success to food shortage. Unexpected events of unfavorable climatic conditions are expected to rise in frequency and intensity as climate changes. The extent to which physiological flexibility allows organisms to maintain reproductive output constant despite energetic bottlenecks has been poorly investigated. In mammals, reproductive resilience is predicted to be maximal during early stages of reproduction, due to the moderate energetic costs of ovulation and gestation relative to lactation. We experimentally tested the consequences of chronic-moderate and short-acute food shortages on the reproductive output of a small seasonally breeding primate, the grey mouse lemur (Microcebus murinus) under thermo-neutral conditions. These two food treatments were respectively designed to simulate the energetic constraints imposed by a lean year (40% caloric restriction over eight months) or by a sudden, severe climatic event occurring shortly before reproduction (80% caloric restriction over a month). Grey mouse lemurs evolved under the harsh, unpredictable climate of the dry forest of Madagascar and should thus display great potential for physiological adjustments to energetic bottlenecks. We assessed the resilience of the early stages of reproduction (mating success, fertility, and gestation) to these contrasted food treatments, and on the later stages (lactation and offspring growth) in response to the chronic food shortage only. Food deprived mouse lemurs managed to maintain constant most reproductive parameters, including oestrus timing, estrogenization level at oestrus, mating success, litter size, and litter mass as well as their overall number of surviving offspring at weaning. However, offspring growth was delayed in food restricted mothers. These results suggest that heterothermic, fattening-prone mammals display important reproductive resilience to energetic bottlenecks. More generally, species living in variable and unpredictable habitats may have evolved a flexible reproductive physiology that helps buffer environmental fluctuations. PMID:22848507

Reproductive resilience to food shortage in a small heterothermic primate.

PubMed

Canale, Cindy I; Huchard, Elise; Perret, Martine; Henry, Pierre-Yves

2012-01-01

The massive energetic costs entailed by reproduction in most mammalian females may increase the vulnerability of reproductive success to food shortage. Unexpected events of unfavorable climatic conditions are expected to rise in frequency and intensity as climate changes. The extent to which physiological flexibility allows organisms to maintain reproductive output constant despite energetic bottlenecks has been poorly investigated. In mammals, reproductive resilience is predicted to be maximal during early stages of reproduction, due to the moderate energetic costs of ovulation and gestation relative to lactation. We experimentally tested the consequences of chronic-moderate and short-acute food shortages on the reproductive output of a small seasonally breeding primate, the grey mouse lemur (Microcebus murinus) under thermo-neutral conditions. These two food treatments were respectively designed to simulate the energetic constraints imposed by a lean year (40% caloric restriction over eight months) or by a sudden, severe climatic event occurring shortly before reproduction (80% caloric restriction over a month). Grey mouse lemurs evolved under the harsh, unpredictable climate of the dry forest of Madagascar and should thus display great potential for physiological adjustments to energetic bottlenecks. We assessed the resilience of the early stages of reproduction (mating success, fertility, and gestation) to these contrasted food treatments, and on the later stages (lactation and offspring growth) in response to the chronic food shortage only. Food deprived mouse lemurs managed to maintain constant most reproductive parameters, including oestrus timing, estrogenization level at oestrus, mating success, litter size, and litter mass as well as their overall number of surviving offspring at weaning. However, offspring growth was delayed in food restricted mothers. These results suggest that heterothermic, fattening-prone mammals display important reproductive resilience to energetic bottlenecks. More generally, species living in variable and unpredictable habitats may have evolved a flexible reproductive physiology that helps buffer environmental fluctuations.

Allopurinol Against Progression of Chronic Kidney Disease.

PubMed

Golmohammadi, Sima; Almasi, Afshin; Manouchehri, M; Omrani, Hamid Reza; Zandkarimi, Mohammad Reza

2017-07-01

Hyperuricemia is common in approximately 50% of patients with kidney failure due to decreased uric acid excretion, and it has been recently known as an independent factor in the progression of renal insufficiency. Allopurinol inhibits the production of uric acid. The aim of this study was to evaluate the effect of allopurinol on chronic kidney disease progression. In a clinical trial, patients with stages 3 and 4 of chronic kidney disease were divided into two groups to receive allopurinol, 100 mg, daily and placebo for 12 months. Patients' kidney function and serum uric acid levels were assessed at baseline and 3, 6, and 12 months after initial administration. Subgroups of patients with severe and mild glomerular filtration rate (GFR) impairment (GFR, 15 mL/min/1.73 m2 to 30 mL/min/1.73 m2 and 30 mL/min/1.73 m2 to 60 mL/min/1.73 m2, respectively), were compared between the groups. Serum uric acid levels decreased significantly during after 12 months of allopurinol administration (P = .004). In patients with severe GFR impairment, serum creatinine levels did not decrease significantly and there was no significant increase in GFR, but in those with mild GFR impairment, serum creatinine levels decreased and GFR increase significantly (P < .001) after administration of allopurinol. These effects were not observed in the control subgroups. Allopurinol may slow down stage 3 chronic kidney disease progression and could be administered with other effective medications for controlling the kidney disease.

Rate of recurrence in Indian patients presenting with acute pancreatitis and identification of chronicity on follow up: Possible risk factors for progression.

PubMed

Kalaria, Rishikesh; Abraham, Philip; Desai, Devendra C; Joshi, Anand; Gupta, Tarun

2018-03-01

To study the profile and long-term outcome of Indian patients presenting with acute pancreatitis and the possible risk factors for progression. Consecutive patients with acute or recurrent acute pancreatitis seen in our department during July 2013 to December 2014 were included. Details of past episodes were collected and patients were followed up till March 2015. In the 97 patients included (mean age 47.2 [SD 16.9] years; 74 men), gallstones (37 [38.1%]) and alcohol (19 [19.6%]) were the major identified etiologies; the idiopathic (31 [32%]) group constituted a third of patients. Recurrences were more common with idiopathic etiology (14 patients out of 30 had recurrences [46.7%]) as compared to alcoholic (5 out of 19 [26.3%]) and biliary (4 out of 37 [10.8%]) pancreatitis and with mild index episode. Following the episode of acute pancreatitis, identification of chronic pancreatitis was more common with alcoholic (6 out of 18 [33%]) and idiopathic (9 out of 30 [30%]) etiology as compared to other etiologies. Longer duration of follow up, but not number of recurrent episodes, was associated with identification of chronicity in patients presenting as acute pancreatitis. Out of 97 patients with acute pancreatitis, 27 (27.8%) developed recurrences with risk factors being idiopathic etiology and mild index episode. Eighteen of 97 (18.6%) patients had evidence of chronic pancreatitis on follow up, risk factors being the alcoholic and idiopathic varieties, and longer duration of follow up.

Chronic mild stress facilitates melanoma tumor growth in mouse lines selected for high and low stress-induced analgesia.

PubMed

Ragan, Agnieszka R; Lesniak, Anna; Bochynska-Czyz, Marta; Kosson, Anna; Szymanska, Hanna; Pysniak, Kazimiera; Gajewska, Marta; Lipkowski, Andrzej W; Sacharczuk, Mariusz

2013-09-01

Both chronic stress conditions and hyperergic reaction to environmental stress are known to enhance cancer susceptibility. We described two mouse lines that displayed high (HA) and low (LA) swim stress-induced analgesia (SSIA) to investigate the relationship between inherited differences in sensitivity to stress and proneness to an increased growth rate of subcutaneously inoculated melanoma. These lines display several genetic and physiological differences, among which distinct sensitivity to mutagens and susceptibility to cancer are especially noticeable. High analgesic mice display high proneness both to stress and a rapid local spread of B16F0 melanoma. However, stress-resistant LA mice do not develop melanoma tumors after inoculation, or if so, tumors regress spontaneously. We found that the chronic mild stress (CMS) procedure leads to enhanced interlinear differences in melanoma susceptibility. Tumors developed faster in stress conditions in both lines. However, LA mice still displayed a tendency for spontaneous regression, and 50% of LA mice did not develop a tumor, even under stressed conditions. Moreover, we showed that chronic stress, but not tumor progression, induces depressive behavior, which may be an important clue in cancer therapy. Our results clearly indicate how the interaction between genetic susceptibility to stress and environmental stress determine the risk and progression of melanoma. To our knowledge, HA/LA mouse lines are the first animal models of distinct melanoma progression mediated by inherited differences in stress reactivity.

[Association of occupational chronic psychological stress with heat shock protein 70 in serum and tumor necrosis factor-alpha expression levels].

PubMed

Qiu, F Y; Tian, R L; Qiang, Y; He, K P; Liu, H R; Zhang, W; Song, H

2016-05-01

To investigate the relationship between occupational chronic psychological stress with heat shock protein 70 (HSP70) and tumor necrosis factor-alpha (TNF-α). Using case-control study design, we selected 622 cases in 20 to 60 years old and unrelated patients with metabolic syndrome as the case group between October 2011 and October 2012 at two hospitals of Ningxia hui autonomous region. At the same time, we selected 600 healthy people from health check-up crowd in the above two hospitals as control group. The the research objects were sex, age, nation, height, weight, smoking, drinking, exercise, and so on. After informed consent, all the research objects were collected fasting venous blood samples 10 ml in order to proceed laboratory testing of biochemical indicators. The expression of HSP70 and TNF-α in serum was determined by ELISA. Using the revised occupational stress inventory (OSI) to survey the occupational chronic psychological stress factors and stress level of research object. The correlation of occupational chronic psychological stress scores with HSP70 and TNF-α was investigated by partial correlation analysis. We built a multivariate linear regression equation With HSP70 and TNF alpha as the independent variable and occupational chronic psychological stress scores as the dependent variable, using equation of the determination coefficient R(2) to judge the degree of fitting equation. The total points of chronic stress factors in all respondents was (136.65±16.19). Among them, the mild stress level group was 313, moderate was 588, severe was 321, chronic heart stress factors scores were (119.96±13.30), (135.33±3.23), (155.33±13.55) points, respectively. In the case group subjects, the expression of HSP70 in mild, moderate and severe occupational chronic psychological stress levels were (29.88±30.08), (36.38±30.08), (27.16±23.77) ng/ml (F=6.85, P=0.001). The control group were (27.64±9.89), (39.78±29.77), (3.94±3.09) ng/ml (F=125.71, P<0.001). Multiple linear regression analysis showed the expression of psychological stress and HSP70 was a negative linear relationship, while positive linear relationship with TNF-α, the fitting of the regression equation was y=-0.07x1+ 0.011x2+ 136.88. Partial correlation analysis results showed that the occupational chronic psychological stress scores and negatively correlated with HSP70 (r=-0.11, P<0.001) and was positively related with TNF-α (r=0.11, P<0.001). In all survey respondents, the expression of HSP70 in mild, moderate and severe occupational chronic psychological stress levels group were (28.49±20.10), (37.99±29.96), (17.98±21.77) ng/ml (F=64.08, P<0.001). The expression of TNF-α were (133.61±129.51), (171.23±133.69), (169.31±196.09) pg/ml (F=6.93, P=0.001). The expression levels of HSP70 and TNF-α in serum were affected by occupational chronic psychological stress. While the level of occupational chronic psychological stress increased, the expression level of HSP70 in serum reduced, the expression level of TNF-α raised.

Protracted effects of chronic stress on serotonin-dependent thermoregulation.

PubMed

Natarajan, Reka; Northrop, Nicole A; Yamamoto, Bryan K

2015-01-01

Chronic stress is known to affect serotonin (5HT) neurotransmission in the brain and to alter body temperature. The body temperature is controlled in part, by the medial preoptic area (mPOA) of the hypothalamus. To investigate the effect of chronic stress on 5HT and how it affects body temperature regulation, we examined whether exposure to a chronic unpredictable stress (CUS) paradigm produces long-term alterations in thermoregulatory function of the mPOA through decreased 5HT neurotransmission. Adult male Sprague-Dawley rats underwent 21 d of CUS. Four days after the last stress exposure, basal body temperature in the home cage and body temperature in a cold room maintained at 10 °C were recorded. The CUS rats had significantly higher subcutaneous basal body temperature at 13:00 h compared to unstressed (NoStress) rats. Whereas the NoStress rats were able to significantly elevate body temperature from basal levels at 30 and 60 min of exposure to the cold room, the CUS rats showed a hypothermic response to the cold. Treatment during CUS with metyrapone, a corticosterone synthesis inhibitor, blocked stress-induced decrease in body temperature in response to the cold challenge. CUS also decreased 5HT transporter protein immunoreactivity in the mPOA and 5HT2A/C agonist injection into the mPOA after CUS exposure caused stressed rats to exhibit a sensitized hyperthermic response to cold. These results indicate that the CUS induced changes to the 5HTergic system alter mPOA function in thermoregulation. These findings help us to explain the mechanisms underlying chronic stress-induced disorders such as chronic fatigue syndrome wherein long lasting thermoregulatory deficits are observed.

Protracted effects of chronic stress on serotonin dependent thermoregulation

PubMed Central

Natarajan, Reka; Northrop, Nicole A.; Yamamoto, Bryan K.

2016-01-01

Chronic stress is known to affect serotonin (5HT) neurotransmission in the brain and to alter body temperature. Body temperature is controlled in part, by the medial preoptic area of the hypothalamus (mPOA). To investigate the effect of chronic stress on 5HT and how it affects body temperature regulation, we examined whether exposure to a chronic unpredictable stress paradigm (CUS) produces long-term alterations in thermoregulatory function of the mPOA through decreased 5HT neurotransmission. Adult male Sprague-Dawley rats underwent 21 days of CUS. Four days after last stress exposure, basal body temperature in the home cage and body temperature in a cold room maintained at 10°C were recorded. CUS rats had significantly higher subcutaneous basal body temperature at 13:00 h compared to unstressed (NoStress) rats. Whereas the NoStress rats were able to significantly elevate body temperature from basal levels at 30 and 60 min of exposure to the cold room, the CUS rats showed a hypothermic response to the cold. Treatment during CUS with metyrapone, a corticosterone synthesis inhibitor, blocked stress-induced decrease in body temperature in response to the cold challenge. CUS also decreased 5HT transporter protein immunoreactivity in the mPOA and 5HT2A/C agonist injection into the mPOA after CUS exposure caused stressed rats to exhibit a sensitized hyperthermic response to cold. These results indicate that CUS induced changes to the 5HTergic system alters mPOA function in thermoregulation. These findings help explain mechanisms underlying chronic stress induced disorders such as chronic fatigue syndrome wherein long lasting thermoregulatory deficits are observed. PMID:26414686

Too much of a good thing: blocking noradrenergic facilitation in medial prefrontal cortex prevents the detrimental effects of chronic stress on cognition.

PubMed

Jett, Julianne D; Morilak, David A

2013-03-01

Cognitive impairments associated with dysfunction of the medial prefrontal cortex (mPFC) are prominent in stress-related psychiatric disorders. We have shown that enhancing noradrenergic tone acutely in the rat mPFC facilitated extra-dimensional (ED) set-shifting on the attentional set-shifting test (AST), whereas chronic unpredictable stress (CUS) impaired ED. In this study, we tested the hypothesis that the acute facilitatory effect of norepinephrine (NE) in mPFC becomes detrimental when activated repeatedly during CUS. Using microdialysis, we showed that the release of NE evoked in mPFC by acute stress was unchanged at the end of CUS treatment. Thus, to then determine if repeated elicitation of this NE activity in mPFC during CUS may have contributed to the ED deficit, we infused a cocktail of α(1)-, β(1)-, and β(2)-adrenergic receptor antagonists into the mPFC prior to each CUS session, then tested animals drug free on the AST. Antagonist treatment prevented the CUS-induced ED deficit, suggesting that NE signaling during CUS compromised mPFC function. We confirmed that this was not attributable to sensitization of adrenergic receptor function following chronic antagonist treatment, by administering an additional microinjection into the mPFC immediately prior to ED testing. Acute antagonist treatment did not reverse the beneficial effects of chronic drug treatment during CUS, nor have any effect on baseline ED performance in chronic vehicle controls. Thus, we conclude that blockade of noradrenergic receptors in mPFC protected against the detrimental cognitive effects of CUS, and that repeated elicitation of noradrenergic facilitatory activity is one mechanism by which chronic stress may promote mPFC cognitive dysfunction.

Association between chronic periodontitis and oral health-related quality of life in Sri Lankan adults.

PubMed

Wellapuli, Nimali; Ekanayake, Lilani

2016-12-01

To determine the impact of chronic periodontitis on oral health-related quality of life in Sri Lankan adults. A cross-sectional study was conducted among 1,400 participants, 35-60 years of age, residing in the Colombo district of Sri Lanka. Data were collected using two interviewer-administered questionnaires and an oral examination. The prevalence, extent and severity of oral impacts increased with the increase in severity of chronic periodontitis. The most commonly experienced impacts were within the domain of physical pain. The adjusted Poisson regression model indicated that chronic periodontitis was significantly associated with the prevalence of oral impacts. The prevalence of oral impacts was 48% and 69% higher in those with moderate and severe periodontitis, respectively, compared with those with no/mild periodontitis. Oral health-related quality of life deteriorates with the increase in severity of chronic periodontitis. © 2016 FDI World Dental Federation.

Chronic traumatic encephalopathy: The unknown disease.

PubMed

Martínez-Pérez, R; Paredes, I; Munarriz, P M; Paredes, B; Alén, J F

2017-04-01

Chronic traumatic encephalopathy is a neurodegenerative disease produced by accumulated minor traumatic brain injuries; no definitive premortem diagnosis and no treatments are available for chronic traumatic encephalopathy. Risk factors associated with chronic traumatic encephalopathy include playing contact sports, presence of the apolipoprotein E4, and old age. Although it shares certain histopathological findings with Alzheimer disease, chronic traumatic encephalopathy has a more specific presentation (hyperphosphorylated tau protein deposited as neurofibrillary tangles, associated with neuropil threads and sometimes with beta-amyloid plaques). Its clinical presentation is insidious; patients show mild cognitive and emotional symptoms before progressing to parkinsonian motor signs and finally dementia. Results from new experimental diagnostic tools are promising, but these tools are not yet available. The mainstay of managing this disease is prevention and early detection of its first symptoms. Copyright © 2014 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Hyperoside protects against chronic mild stress-induced learning and memory deficits.

PubMed

Gong, Yeli; Yang, Youhua; Chen, Xiaoqing; Yang, Min; Huang, Dan; Yang, Rong; Zhou, Lianying; Li, Changlei; Xiong, Qiuju; Xiong, Zhe

2017-07-01

Hyperoside (quercetin-3-O-b-d-galactosidepyranose) is a plant-derived flavonoid mainly found in fruits, fruit juices (most notably flavanols, flavanones, and anthocyanins) and Chinese traditional medicines. It has been applied to relieve pain and improve cardiovascular functions in clinic. However, the effects of hyperoside on cognitive impairment induced by chronic stress and the underlying molecular mechanisms remain unclear. In the current study, we used chronic mild stress (CMS) rats to investigate the effects of hyperoside on learning and memory and further explore the possible mechanisms. Our results demonstrated that hyperoside reduced the escape latency and the swimming distance of CMS rats in Morris water maze test and reversed depressive symptoms in forced swim test (FST) and sucrose preference test. In addition, hyperoside increased the expression of brain-derived neurotrophic factor (BDNF) in hippocampus of CMS rats without influencing the corticosterone (CORT) level in blood plasma. Furthermore, K252a, an inhibitor of the BDNF receptor TrkB, prevented the protective effects of hyperoside on learning and memory in CMS rats. Taken together, these results indicate that hyperoside reverses the cognitive impairment induced by CMS, which is associated with the regulation of BDNF signaling pathway. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Differences in Brain Metabolic Impairment between Chronic Mild/Moderate TBI Patients with and without Visible Brain Lesions Based on MRI.

PubMed

Ito, Keiichi; Asano, Yoshitaka; Ikegame, Yuka; Shinoda, Jun

2016-01-01

Introduction. Many patients with mild/moderate traumatic brain injury (m/mTBI) in the chronic stage suffer from executive brain function impairment. Analyzing brain metabolism is important for elucidating the pathological mechanisms associated with their symptoms. This study aimed to determine the differences in brain glucose metabolism between m/mTBI patients with and without visible traumatic brain lesions based on MRI. Methods. Ninety patients with chronic m/mTBI due to traffic accidents were enrolled and divided into two groups based on their MRI findings. Group A comprised 50 patients with visible lesions. Group B comprised 40 patients without visible lesions. Patients underwent FDG-PET scans following cognitive tests. FDG-PET images were analyzed using voxel-by-voxel univariate statistical tests. Results. There were no significant differences in the cognitive tests between Group A and Group B. Based on FDG-PET findings, brain metabolism significantly decreased in the orbital gyrus, cingulate gyrus, and medial thalamus but increased in the parietal and occipital convexity in Group A compared with that in the control. Compared with the control, patients in Group B exhibited no significant changes. Conclusions. These results suggest that different pathological mechanisms may underlie cognitive impairment in m/mTBI patients with and without organic brain damage.

38 CFR 4.130 - Schedule of ratings-mental disorders.

Code of Federal Regulations, 2010 CFR

2010-07-01

...; impairment of short- and long-term memory (e.g., retention of only highly learned material, forgetting to... (including maintenance of minimal personal hygiene); disorientation to time or place; memory loss for names... or less often), chronic sleep impairment, mild memory loss (such as forgetting names, directions...

The Fetal Alcohol Syndrome.

ERIC Educational Resources Information Center

Umbreit, John; Ostrow, Lisa S.

1980-01-01

Fetal alcohol syndrome is a pattern of altered growth and morphogenesis found in about half the offspring of severely and chronically alcoholic women who continue drinking throughout their pregnancy. Of children studied, mild to moderate mental retardation was the most common disorder, occurring in 44 percent of the cases. (PHR)

78 FR 46274 - Pyroxasulfone; Pesticide Tolerances

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-31

... following a 4-week dermal exposure producing local inflammation and systemic effects of minimal to mild...- linear approach (i.e., Reference dose (RfD)) will adequately account for all chronic toxicity, including... and other relevant data. Cancer risk is quantified using a linear or nonlinear approach. If sufficient...

Blastocystis prevalence and subtype distribution among pre-weaned dairy calves in the United States

USDA-ARS?s Scientific Manuscript database

Blastocystis is an enteric parasite commonly found in humans and many animals worldwide. Infection with Blastocystis has been associated with both mild and severe gastrointestinal manifestations and is linked to chronic spontaneous urticaria (hives). How Blastocystis is transmitted is still unclea...

Unpredictability and the transmission of numbers

NASA Astrophysics Data System (ADS)

Myers, John M.; Madjid, F. Hadi

2016-03-01

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 forth. In digital communications, the players are computers, and the required coordination involves unpredictably adjusting "live clocks" that step these computers through phases of a cycle. We show how this phasing, which we call logical synchronization, constrains number-carrying networks, and, if a spacetime manifold in invoked, put "stripes" on spacetime. Via its logically synchronized channels, a network of live clocks serves as a reference against which to locate events. Such a network in any case underpins a coordinate frame, and in some cases the direct use of a network can be tailored to investigate an unpredictable environment. Examples include explorations of gravitational variations near Earth.

Patients' Perspectives and Experiences Living with Systemic Sclerosis: A Systematic Review and Thematic Synthesis of Qualitative Studies.

PubMed

Nakayama, Ayano; Tunnicliffe, David J; Thakkar, Vivek; Singh-Grewal, Davinder; O'Neill, Sean; Craig, Jonathan C; Tong, Allison

2016-07-01

Systemic sclerosis (SSc) is a chronic, progressive autoimmune disease with major end-organ involvement. Much attention has been focused on the management of physical and clinical manifestations; however, the effect of the disease and treatment on the patient's identity, relationships, functioning, and mental well-being are less known. We aimed to describe the patients' perspectives and experiences of living with SSc. Electronic databases were searched to October 2014. Thematic synthesis was used to analyze the findings. We included 26 studies involving 463 patients. Six key themes were identified: distressing appearance transformation (disturbing facial changes, stigmatizing sickness, unrecognizable self), palpable physical limitations (bodily restrictions, frustrating mind-body disconnect, pervasive fatigue, disabling pain), social impairment (breaking intimacy, struggling to fulfill family responsibilities, maintaining work, losing independence), navigating uncertainty (diagnostic ambiguity, medically fending for oneself, unpredictable course of illness), alone and misunderstood (fearful avoidance of fellow patients, invisible suffering), and gradual acceptance and relative optimism (adapting to change and accepting limitations, taking a positive spin, cautious hoping, empowering relationships, valuing medical support). SSc is a rare and unpredictable illness that undermines patients' sense of certainty and control and impairs their self-image, identity, and daily functioning. Patient-centered care that encompasses strategies to promote self-esteem, resilience, and self-efficacy may help to improve treatment satisfaction and health and quality of life outcomes for patients with SSc.

Antidepressant-like actions by silencing of neuronal ELAV-like RNA-binding proteins HuB and HuC in a model of depression in male mice.

PubMed

Sanna, Maria Domenica; Quattrone, Alessandro; Galeotti, Nicoletta

2018-06-01

Currently available antidepressant drugs often fail to achieve full remission and patients might evolve to treatment resistance, showing the need to achieve a better therapy of depressive disorders. Increasing evidence supports that post-transcriptional regulation of gene expression is important in neuronal development and survival and a relevant role is played by RNA binding proteins (RBP). To explore new therapeutic strategies, we investigated the role of the neuron-specific ELAV-like RBP (HuB, HuC, HuD) in a mouse model of depression. In this study, a 4-week unpredictable chronic mild stress (UCMS) protocol was applied to mice to induce a depressive-like phenotype. In the last 2 weeks of the UCMS regimen, silencing of HuB, HuC or HuD was performed by using specific antisense oligonucleotides (aODN). Treatment of UCMS-exposed mice with anti-HuB and anti-HuC aODN improved both anhedonia and behavioural despair, used as measures of depressive-like behaviour, without modifying the response of stressed mice to an anxiety-inducing environment. On the contrary, HuD silencing promoted an anxiolytic-like behaviour in UCMS-exposed mice without improving depressive-like behaviours. The antidepressant-like phenotype of anti-HuB and anti-HuC mice was not shown concurrently with the promotion of adult hippocampal neurogenesis in the dentate gyrus, and no increase in the BDNF and CREB content was detected. Conversely, in the CA3 hippocampal region, projection area of newly born neurons, HuB and HuC silencing increased the number of BrdU/NeuN positive cells. These results give the first indication of a role of nELAV in the modulation of emotional states in a mouse model of depression. Copyright © 2018 Elsevier Ltd. All rights reserved.

Xiaoyaosan Improves Depressive-Like Behaviors in Mice through Regulating Apelin-APJ System in Hypothalamus.

PubMed

Yan, Zhiyi; Jiao, Haiyan; Ding, Xiufang; Ma, Qingyu; Li, Xiaojuan; Pan, Qiuxia; Wang, Tingye; Hou, Yajing; Jiang, Youming; Liu, Yueyun; Chen, Jiaxu

2018-05-03

Background: The apelin-APJ system has been considered to play a crucial role in HPA axis function, and how the traditional Chinese compound prescription Xiaoyaosan regulates the apelin-APJ system as a supplement to treat depressive disorders. Objective: To investigate the depression-like behaviors and expression of apelin and APJ in hypothalamus of chronic unpredictable mild stress (CUMS) mice and study whether these changes related to the regulation of Xiaoyaosan. Methods: 60 adult C57BL/6J mice were randomly divided into four groups, including control group, CUMS group, Xiaoyaosan treatment group and fluoxetine treatment group. Mice in the control group and CUMS group received 0.5 mL physiological saline once a day by intragastric administration. Mice in two treatment groups received Xiaoyaosan (0.25 g/kg/d) and fluoxetine (2.6 mg/kg/d), respectively. After 21 days of modeling with CUMS, the expression of apelin and APJ in hypothalamus were measured by real-time fluorescence quantitative PCR, western blot and immunohistochemical staining. The physical condition, body weight, food intake and behavior tests such as open field test, sucrose preference test and force swimming test were measured to evaluate depressive-like behaviors. Results: In this study, significant behavioral changes were found in CUMS-induced mice, meanwhile the expressions of apelin and APJ in the hypothalamus were changed after modeling. The body weight, food-intake and depressive-like behaviors in CUMS-induced mice could be improved by Xiaoyaosan treatment which is similar with the efficacy of fluoxetine, while the expressions of apelin and APJ in hypothalamus were modified by Xiaoyaosan. Conclusions: The data suggest that apelin-APJ system changes in the hypothalamus may be a target of depressive disorders, and the beneficial effects of Chinese compound prescription Xiaoyaosan on depressive-like behaviors may be mediated by the apelin-APJ system.

Neonatal testosterone partially organizes sex differences in stress-induced emotionality in mice.

PubMed

Seney, Marianne L; Walsh, Christopher; Stolakis, Ryan; Sibille, Etienne

2012-05-01

Major depressive disorder (MDD) is a debilitating disorder of altered mood regulation. Despite well established sex differences in MDD prevalence, the mechanism underlying the increased female vulnerability remains unknown. Although evidence suggests an influence of adult circulating hormone levels on mood (i.e. activational effects of hormones), MDD prevalence is consistently higher in women across life stages (and therefore hormonal states), suggesting that additional underlying structural or biological differences place women at higher risk. Studies in human subjects and in rodent models suggest a developmental origin for mood disorders, and interestingly, a developmental process also establishes sex differences in the brain. Hence, based on these parallel developmental trajectories, we hypothesized that a proportion of the female higher vulnerability to MDD may originate from the differential organization of mood regulatory neural networks early in life (i.e. organizational effects of hormones). To test this hypothesis in a rodent system, we took advantage of a well-established technique used in the field of sexual differentiation (neonatal injection with testosterone) to masculinize sexually dimorphic brain regions in female mice. We then investigated adult behavioral consequences relating to emotionality by comparing neonatal testosterone-treated females to normal males and females. Under baseline/trait conditions, neonatal testosterone treatment of female mice did not influence adult emotionality, but masculinized adult locomotor activity, as revealed by the activational actions of hormones. Conversely, the increased vulnerability of female mice to develop high emotionality following unpredictable chronic mild stress (UCMS) was partially masculinized by neonatal testosterone exposure, with no effect on post-UCMS locomotion. The elevated female UCMS-induced vulnerability did not differ between adult hormone treated groups. These results demonstrate that sex differences in adult emotionality in mice are partially caused by the organizational effects of sex hormones during development, hence supporting a developmental hypothesis of the human adult female prevalence of MDD. Copyright © 2012 Elsevier Inc. All rights reserved.

Neonatal testosterone partially organizes sex differences in stress-induced emotionality in mice

PubMed Central

Seney, Marianne L.; Walsh, Christopher; Stolakis, Ryan; Sibille, Etienne

2012-01-01

Major depressive disorder (MDD) is a debilitating disorder of altered mood regulation. Despite well established sex differences in MDD prevalence, the mechanism underlying the increased female vulnerability remains unknown. Although evidence suggests an influence of adult circulating hormone levels on mood (i.e. activational effects of hormones), MDD prevalence is consistently higher in women across life stages (and therefore hormonal states), suggesting that additional underlying structural or biological differences place women at higher risk. Studies in human subjects and in rodent models suggest a developmental origin for mood disorders, and interestingly, a developmental process also establishes sex differences in the brain. Hence, based on these parallel developmental trajectories, we hypothesized that a proportion of the female higher vulnerability to MDD may originate from the differential organization of mood regulatory neural networks early in life (i.e. organizational effects of hormones). To test this hypothesis in a rodent system, we took advantage of a well-established technique used in the field of sexual differentiation (neonatal injection with testosterone) to masculinize sexually dimorphic brain regions in female mice. We then investigated adult behavioral consequences relating to emotionality by comparing neonatal testosterone-treated females to normal males and females. Under baseline/trait conditions, neonatal testosterone treatment of female mice did not influence adult emotionality, but masculinized adult locomotor activity, as revealed by the activational actions of hormones. Conversely, the increased vulnerability of female mice to develop high emotionality following unpredictable chronic mild stress (UCMS) was partially masculinized by neonatal testosterone exposure, with no effect on post-UCMS locomotion. The elevated female UCMS-induced vulnerability did not differ between adult hormone treated groups. These results demonstrate that sex differences in adult emotionality in mice are partially caused by the organizational effects of sex hormones during development, hence supporting a developmental hypothesis of the human adult female prevalence of MDD. PMID:22394611

[Malnutrition and poverty in Colombia].

PubMed

Rico Velasco, J; Acciarri, G; Fajardo, L F

1982-01-01

A history of colonial exploitation and a development model that concentrates wealth and excludes a large proportion of the population from the development process are the principal determinants of income distribution in Colombia. This work analyzes the extent of malnutrition among the poorest 30% of the Colombian population. The National Plan for Feeding and Nutrition (PAN), an important component of the national development plan, strives to improve the nutritional status of the most vulnerable population groups living in rural areas and marginal urban neighborhoods, with particular emphasis on mothers and children. The program initially was focussed on 11 priority regions where 5 types of interventions were developed: primary health care, environmental sanitation, food production, food distribution, and nutrition education. Because of the good results initially obtained, PAN now covers the entire national territory. A 1977 survey stratified by socioeconomic levels indicated that among the poorest 30% of the population, 67% of the children examined had low weight for age caused by a combination of chronic and acute malnutrition. 12% were considered to have severe and 23% moderate malnutrition. 8% had severe and 17% had moderate problems of height for age. 26% had deficient weight for height. Comparison of the data to normal values published by the World Health Organization clearly demonstrates the pattern of overall malnutrition indicated by weight for age figures. It can be concluded at 33% of children in the poorest 30% of the population are normal, 31% have mild malnutrition, 23% moderate malnutrition, and 12% severe malnutrition. Data on height for age indicated that 43% were normal, 32% had mild chronic malnutrition, 17% had moderate chronic malnutrition, and 8% had severe chronic malnutrition. The prevalence of acute malnutrition in the poor population measured by the ratio of weight to height was less than that of chronic or overall malnutrition. 21% were considered to show mild, 4% moderate, and 1% severe acute malnutrition. Nutritional status was greatly influenced by age, with the lowest rates of malnutrition occurring in children under 1. Mortality among children aged 1-2 years probably was responsible for a decline in malnutrition rates in children over 2. Patterns of malnutrition in children of the poorest 30% of the Colombian population were quite similar in the 11 departments included in the 1977 survey. Comparison with earlier data indicates that the nutritional status of children in the poorest population sector has not improved since the 1960s.

Living with chronic pain: Evaluating patient experiences with a medical group visit focused on mindfulness and non-pharmacological strategies.

PubMed

Lestoquoy, Anna Sophia; Laird, Lance D; Mitchell, Suzanne; Gergen-Barnett, Katherine; Negash, N Lily; McCue, Kelly; Enad, Racquel; Gardiner, Paula

2017-12-01

Little is known about the acceptance of non-pharmacological group strategies delivered to low income racially diverse patients with chronic pain and depression. This paper examines how the Integrative Medical Group Visit (IMGV) addresses many of the deficits identified with usual care. Six IMGVs cohorts were held at a safety net hospital and two federally funded community health centres. Data was gathered through focus groups. Transcripts were analysed using both a priori codes and inductive coding. The intervention included ten sessions of Integrative Medical Group Visits with a primary care provider and a meditation instructor. The curriculum uses principles of Mindfulness Based Stress Reduction and evidence based integrative medicine. The visit is structured similarly to other group medical visits. Data was gathered through four focus groups held after the cohorts were completed. Participants (N=20) were largely low income minority adults with chronic pain and comorbid depression. Six themes emerged from the coding including: chronic pain is isolating; group treatment contributes to better coping with pain; loss of control and autonomy because of the unpredictability of pain as well as dependence on medication and frequent medical appointments; groups improve agency and control over one's health condition; navigating the healthcare system and unsatisfactory treatment options; and changes after the IMGV due to non-pharmacological health management. The IMGV is a promising format of delivering integrative care for chronic pain and depression which addresses many of the problems identified by patients in usual care. Copyright © 2017 Elsevier Ltd. All rights reserved.

Predictive factors for and incidence of hospital readmissions of patients with acute and chronic pancreatitis.

PubMed

Suchsland, Till; Aghdassi, Ali; Kühn, Kristina; Simon, Peter; Lerch, Markus M; Mayerle, Julia; Flessa, Steffen

2015-01-01

Acute and chronic pancreatitis are common gastroenterological disorders that have a fairly unpredictable long-term course often associated with unplanned hospital readmissions. Little is known about the factors that increase or decrease the risk for a hospital readmission. The aim of this study was to identify positive and negative predictive factors for hospital readmissions of patients with acute and chronic pancreatitis after in-hospital treatment. In a retrospective analysis data from the hospital information and reimbursement data system (HIS) were evaluated for 606 hospital stays for either acute or chronic pancreatitis between 2006 and 2011. Additional clinical data were obtained from a questionnaire covering quality of life and socio-economic status. A total of 973 patient variables were assessed by bivariate and multivariate analysis. Between 2006 and 2011, 373 patients were admitted for acute or chronic pancreatitis; 107 patients of them were readmitted and 266 had only one hospitalization. Predictors for readmission were concomitant liver disease, presence of a pseudocyst or a suspected tumor of the pancreas as well as alcohol, tobacco or substance abuse or coexisting mental disorders. Patients who had undergone a CT-scan were more susceptible to readmission. Lower readmissions rates were found in patients with diabetes mellitus or gallstone disease as co-morbidity. While factors like age and severity of the initial disease cannot be influenced to reduce the readmission rate for pancreatitis, variables like alcohol, tobacco and drug abuse can be addressed in outpatient programs to reduce disease recurrence and readmission rates for pancreatitis. Copyright © 2015 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Descriptive epidemiology of chronic hypertension, gestational hypertension, and preeclampsia in New York State, 1995-2004.

PubMed

Savitz, David A; Danilack, Valery A; Engel, Stephanie M; Elston, Beth; Lipkind, Heather S

2014-05-01

We examined social, demographic, and behavioral predictors of specific forms of hypertensive disorders in pregnancy in New York State. Administrative data on 2.3 million births over the period 1995-2004 were available for New York State, USA, with linkage to birth certificate data for New York City (964,071 births). ICD-9 hospital discharge diagnosis codes were used to assign hypertensive disorders hierarchically as chronic hypertension, chronic hypertension with superimposed preeclampsia, preeclampsia (eclampsia/severe or mild), or gestational hypertension. Sociodemographic and behavioral predictors of these outcomes were examined separately for upstate New York and New York City by calculating adjusted odds ratios. The most commonly diagnosed conditions were preeclampsia (2.57 % of upstate New York births, 3.68 % of New York City births) and gestational hypertension (2.46 % of upstate births, 1.42 % of New York City births). Chronic hypertension was much rarer. Relative to non-Hispanic Whites, Hispanics in New York City and Black women in all regions had markedly increased risks for all hypertensive disorders, whereas Asian women were at consistently decreased risk. Pregnancy-associated conditions decreased markedly with parity and modestly among smokers. A strong positive association was found between pre-pregnancy weight and risk of hypertensive disorders, with slightly weaker associations among Blacks and stronger associations among Asians. While patterns of chronic and pregnancy-induced hypertensive disorders differed, the predictors of gestational hypertension and both mild and severe preeclampsia were similar to one another. The increased risk for Black and some Hispanic women warrants clinical consideration, and the markedly increased risk with greater pre-pregnancy weight suggests an opportunity for primary prevention among all ethnic groups.

Protein-energy wasting significantly increases healthcare utilization and costs among patients with chronic kidney disease: a propensity-score matched cohort study.

PubMed

Chao, Chia-Ter; Tang, Chao-Hsiun; Cheng, Rhoda Wen-Yi; Wang, Michael Yao-Hsien; Hung, Kuan-Yu

2017-09-01

Disease-related malnutrition is highly prevalent, and has prognostic implications for patients with chronic kidney disease (CKD); however, few studies have investigated the impact of malnutrition, or protein-energy wasting (PEW), on healthcare utilization and medical expenditure among CKD patients. Using claim data from the National Health Insurance in Taiwan, this study identified patients with CKD between 2009-2013 and categorized them into those with mild, moderate, or severe CKD. Cases with PEW after CKD was diagnosed were propensity-score matched with controls in a 1:4 ratio. Healthcare resource utilization metrics were compared, including outpatient and emergency department visits, frequency and duration of hospitalization, and the cumulative costs associated with different CKD severity. From among 347,501 CKD patients, eligible cohorts of 66,872 with mild CKD (49.2%), 27,122 with moderate CKD (19.9%), and 42,013 with severe CKD (30.9%) were selected. Malnourished CKD patients had significantly higher rates of hospitalization (p < .001 for all severities) and re-admission (p = .015 for mild CKD, p = .002 for severe CKD) than non-malnourished controls. Cumulative medical costs for outpatient and emergency visits, and hospitalization, were significantly higher among all malnourished CKD patients than non-malnourished ones (p < .001); total medical costs were also higher among malnourished patients with mild (62.9%), moderate (59.6%), or severe (43.6%) CKD compared to non-malnourished patients (p < .001). In a nationally-representative cohort, CKD patients with PEW had significantly more healthcare resource utilization and higher aggregate medical costs than those without, across the spectrum of CKD: preventing PEW in CKD patients should receive high priority if we would like to reduce medical costs.

Is balance performance reduced after mild traumatic brain injury?: Interim analysis from chronic effects of neurotrauma consortium (CENC) multi-centre study.

PubMed

Walker, William C; Nowak, Kayla J; Kenney, Kimbra; Franke, Laura Manning; Eapen, Blessen C; Skop, Karen; Levin, Harvey; Agyemang, Amma A; Tate, David F; Wilde, Elisabeth A; Hinds, Sidney; Nolen, Tracy L

2018-06-12

Determine if mild traumatic brain injury (mTBI) history is associated with balance disturbances. Chronic Effects of Neurotrauma Consortium (CENC) centres. The CENC multi-centre study enrols post-9/11 era Service Members and Veterans with combat exposure. This sample (n = 322) consisted of enrolees completing initial evaluation by September 2016 at the three sites conducting computerized dynamic post-urography (CDP) testing. Observational study with cross-sectional analyses using structural equation modelling. Comprehensive structured interviews were used to diagnose all lifetime mild traumatic brain injuries (mTBIs). The outcome, Sensory Organization Test (SOT), was measured on CDP dual-plate force platform. Other studied variables were measured by structured interviews, record review and questionnaires. The overall positive/negative mTBI classification did not have a significant effect on the composite equilibrium score. However, the repetitive mTBI classification showed lower scores for participants with ≥ 3 mTBI versus 1-2 lifetime mTBIs. For repetitive mTBI, pain interference acted as a mediator for the indirect effect, and a direct effect was evident on some sensory condition equilibrium scores. These findings show that repeated mTBI, partially mediated by pain, may lead to later balance disturbances among military combatants. Further study of CDP outcomes within this accruing cohort is warranted.

Computed tomographic findings and treatment of a bull with pituitary gland abscess.

PubMed

Braun, Ueli; Malbon, Alexandra; Kochan, Manon; Riond, Barbara; Janett, Fredi; Iten, Cornelia; Dennler, Matthias

2017-01-13

In cattle, the prognosis of brain abscess is unfavourable and treatment is therefore not recommended. To the knowledge of the authors, there has been no report of successful treatment of a brain abscess in cattle.This report describes the clinical, computed tomographic and postmortem findings in a Holstein-Friesian bull with a hypophyseal abscess. The main clinical findings were generalised ataxia, ptyalism, prolapse of the tongue, dropped jaw, dysphagia, head tilt and unilateral ptosis. Cerebrospinal fluid evaluation revealed 2437 leukocytes/µl and severe pleocytosis. CT examination of the head showed a cavitary lesion consistent with an abscess in the hypophysis. Treatment consisted of gentamicin and flunixin meglumine for 3 days and amoxicillin for 40 days. The neurological signs resolved within 8 days of the start of treatment. The bull was slaughtered 11 months later because of infertility, and a postmortem examination was carried out. Histologically, a mild chronic non suppurative meningoencephalitis restricted to the ventral diencephalon was diagnosed. In addition, there was mild to moderate multifocal chronic lymphoplasmacytic hypophysitis with mild multifocal fibrosis. This case report stresses the significance of CT in confirming the clinical and laboratory diagnosis of central nervous system disorders in cattle and for localising brain lesions. Treatment of the brain abscess resulted, with respect to the central nervous disorder, in a successful outcome and was encouraging considering that most cases have an unfavourable prognosis.

Patterns in response to chronic terrorism threats: A construct of emotional, cognitive, and behavioral responses among Israeli citizens.

PubMed

Cohen-Louck, Keren; Saka, Yael

2017-10-01

Israeli citizens are exposed to unpredictable and chronic terrorism threats that significantly jeopardize their personal sense of safety. The purpose of the present study is to present how Israeli discourse is structured with regard to emotional, cognitive, and behavioral responses to chronic terrorism threats and to understand the range of responses as well as map the risk and protective factors of this existential threat. Semistructured in-depth interviews were conducted with 40 Israeli adults (22 women and 18 men). Qualitative analysis revealed three patterns of responses to ongoing terrorism: emotional, cognitive, and behavioral. Emotional responses include fear, worry, sense of empathy, and detachment. Cognitive responses include situational assessment and pursuit of solutions, the use of traumatic imagining, beliefs in fate and luck, and optimism. Behavioral responses include looking for information, alertness, and habituation. The findings also revealed another response, which combines cognitive and behavioral responses. Some of the responses are innovative and unique to the threat of terrorism. Mapping the responses revealed mental health risk factors, as well as protective factors that can help structure personal and national resilience. These findings have implications on the treatment and prevention of personal and social pathologies, and how to effectively cope with terrorism threats. Copyright © 2016 John Wiley & Sons, Ltd.

Why do young people with CFS/ME feel anxious? A qualitative study.

PubMed

Fisher, Hanne; Crawley, Esther

2013-10-01

Young people with chronic fatigue syndrome or myalagic encephalopathy (CFS/ME) (CFS/ME) experience higher levels of psychological distress than healthy controls and young people with other chronic illnesses, and it was recently demonstrated that 38% of this population scored above the clinical cut-off on the Spence Child Anxiety Scale. Subscales of social and separation anxiety were consistently high across gender and age groups. In this study, we used qualitative methods to help us understand more about these two types of anxiety in young people with CFS/ME. Eleven young people (age 12-18) were interviewed. Interviews were self-directed by the participants and were wide ranging. The transcripts were analysed using interpretative phenomenological analysis. Five superordinate themes were identified: social loss and adjustment; introduction of uncertainty and unpredictability; the vulnerable self; individual differences; and contributions towards recovery. Many themes were identical to those described in young people coping with other chronic illnesses in adolescence. In addition, young people with CFS/ME describe experiences associated with the perceived illegitimacy of this condition, namely: feeling unable to explain their illness; bullying from peers; disbelief; and distrust from adults around them. This becomes an additional challenge for these young people. Clinicians need to be aware of these problems, and offer appropriate support.

Behavioral effects of chronic stress in the Fmr1 mouse model for fragile X syndrome.

PubMed

Lemaire-Mayo, Valerie; Subashi, Enejda; Henkous, Nadia; Beracochea, Daniel; Pietropaolo, Susanna

2017-03-01

Fragile X Syndrome (FXS) is a pervasive developmental disorder due to a mutation in the FMR1 X-linked gene. Despite its clear genetic cause, the expression of FXS symptoms is known to be modulated by environmental factors, including stress. Furthermore, several studies have shown disturbances in stress regulatory systems in FXS patients and Fmr1 mice. These studies have mostly focused on the hormonal responses to stress, using the acute exposure to a single type of stressor. Hence, little is known about the behavioral effects of stress in FXS, and the importance of the nature of the stressing procedure, especially in the context of a repeated exposure that more closely resembles real life conditions. Here we evaluated the effects of chronic exposure to different types of stress (i.e., either repeated restraint or unpredictable stress) on the behavioral phenotype of adult Fmr1 mice. Our results demonstrated that chronic stress induced deficits in social interaction and working memory only in WT mice and the impact of stress depended on the type of stressors and the specific behavior tested. Our data suggest that the behavioral sensitivity to stress is dramatically reduced in FXS, opening new views on the impact of gene-environment interactions in this pathology. Copyright © 2016. Published by Elsevier B.V.

Review of chronic ulcerative colitis cases at King Hussein Medical Centre, Jordan.

PubMed

Ghazzawi, I; Al-Mrayat, Z

2007-01-01

Chronic ulcerative colitis is being encountered with increasing frequency in developing countries. In Amman, Jordan, the records of 372 patients with chronic ulcerative colitis diagnosed between 1994 and 2001 were reviewed. Bloody diarrhoea and crampy abdominal pain were the most common presenting symptoms (84% of patients). The mean age at onset was 31.8 years. In two thirds of patients the diagnosis was made more than 1 year after the onset of symptoms. The pattern of the disease differed from that in industrialized countries in the mild course of the disease, the absence of skin manifestations, and the rarity of colorectal cancer in our patients. The mortality rate was 6%.

AID protein expression in chronic lymphocytic leukemia/small lymphocytic lymphoma is associated with poor prognosis and complex genetic alterations.

PubMed

Leuenberger, Mona; Frigerio, Simona; Wild, Peter J; Noetzli, Franziska; Korol, Dimitri; Zimmermann, Dieter R; Gengler, Carole; Probst-Hensch, Nicole M; Moch, Holger; Tinguely, Marianne

2010-02-01

The biological behavior of chronic lymphocytic leukemia and small lymphocytic lymphoma is unpredictable. Nonetheless, non-mutated IgV(H) gene rearrangement, ATM (11q22-23) and p53 (17p13) deletion are recognized as unfavorable prognosticators in chronic lymphocytic leukemia. The mRNA expression of activation-induced cytidine deaminase (AID), an enzyme indispensable for somatic hypermutation processes, was claimed to be predictive of non-mutated chronic lymphocytic leukemia cells in blood. Here, we evaluated AID protein expression compared with known molecular and immunohistochemical prognostic indicators in 71 chronic lymphocytic leukemia/small lymphocytic lymphoma patients using a tissue microarray approach. We found AID heterogeneously expressed in tumor cells as shown by colocalization analysis for CD5 and CD23. Ki-67 positive paraimmunoblasts of the proliferation centers displayed the highest expression. This observation is reflected by a significant association of AID positivity with a high proliferation rate (P=0.012). ATM deletion was detected in 10% (6/63) of patients and p53 deletion in 19% (13/67) of patients. Moreover, both ATM (P=0.002) and p53 deletion (P=0.004) were significantly associated with AID. IgV(H) gene mutation was seen in 45% (27/60) of patients. Twenty-five percent (17/69) of patients with AID-positive chronic lymphocytic leukemia/small lymphocytic lymphoma displayed a shorter survival than AID-negative chronic lymphocytic leukemia/small lymphocytic lymphoma patients (61 vs 130 months, P=0.001). Although there was a trend, we could not show an association with the IgV(H) gene mutation status. Taken together, our study shows that AID expression is an indicator of an unfavorable prognosis in chronic lymphocytic leukemia/small lymphocytic lymphoma patients, although it is not a surrogate marker for the IgV(H) status. Furthermore, the microenvironment of proliferation centers seems to influence AID regulation and might be an initiating factor in its transformation.

Treatment outcomes of chronic post-traumatic headaches after mild head trauma in US soldiers: an observational study.

PubMed

Erickson, Jay C

2011-06-01

he effectiveness of medical therapies for chronic post-traumatic headaches (PTHs) attributable to mild head trauma in military troops has not been established. To determine the treatment outcomes of acute and prophylactic medical therapies prescribed for chronic PTHs after mild head trauma in US Army soldiers. A retrospective cohort study was conducted with 100 soldiers undergoing treatment for chronic PTH at a single US Army neurology clinic. Headache frequency and Migraine Disability Assessment (MIDAS) scores were determined at the initial clinic visit and then again by phone 3 months after starting headache prophylactic medication. Response rates of headache abortive medications were also determined. Treatment outcomes were compared between subjects with blast-related PTH and non-blast PTH. Ninety-nine of 100 subjects were male. Seventy-seven of 100 subjects had blast PTH and 23/100 subjects had non-blast PTH. Headache characteristics were similar for blast PTH and non-blast PTH with 96% and 95%, respectively, resembling migraine. Headache frequency among all PTH subjects decreased from 17.1 days/month at baseline to 14.5 days/month at follow-up (P = .009). Headache frequency decreased by 41% among non-blast PTH compared to 9% among blast PTH. Fifty-seven percent of non-blast PTH subjects had a 50% or greater decline in headache frequency compared to 29% of blast PTH subjects (P =.023). A significant decline in headache frequency occurred in subjects treated with topiramate (n = 29, -23%, P = .02) but not among those treated with a low-dose tricyclic antidepressant (n = 48, -12%, P = .23). Seventy percent of PTH subjects who used a triptan class medication experienced reliable headache relief within 2 hours compared to 42% of subjects using other headache abortive medications (P = .01). Triptan medications were effective for both blast PTH and non-blast PTH (66% response rate vs 86% response rate, respectively; P = .20). Headache-related disability, as measured by mean MIDAS scores, declined by 57% among all PTH subjects with no significant difference between blast PTH (-56%) and non-blast PTH (-61%). Triptan class medications are usually effective for aborting headaches in military troops with chronic PTH attributed to a concussion from a blast injury or non-blast injury. Topiramate appears to be an effective headache prophylactic therapy in military troops with chronic PTH, whereas low doses of tricyclic antidepressants appear to have little efficacy. Chronic PTH triggered by a blast injury may be less responsive to commonly prescribed headache prophylactic medications compared to non-blast PTH. These conclusions require validation by prospective, controlled clinical trials. © 2011 American Headache Society.

A Live Attenuated Chimeric West Nile Virus Vaccine, rWN/DEN4Δ30, Is Well Tolerated and Immunogenic in Flavivirus-Naive Older Adult Volunteers.

PubMed

Pierce, Kristen K; Whitehead, Stephen S; Kirkpatrick, Beth D; Grier, Palmtama L; Jarvis, Adrienne; Kenney, Heather; Carmolli, Marya P; Reynolds, Cynthia; Tibery, Cecilia M; Lovchik, Janece; Janiak, Anna; Luke, Catherine J; Durbin, Anna P; Pletnev, Alexander G

2017-01-01

West Nile virus (WNV) is a major cause of mosquito-borne illness in the United States. Human disease ranges from mild febrile illness to severe fatal neurologic infection. Adults aged >60 years are more susceptible to neuroinvasive disease accompanied by a high mortality rate or long-lasting neurologic sequelae. A chimeric live attenuated West Nile virus vaccine, rWN/DEN4Δ30, was shown to be safe and immunogenic in healthy adults aged 18-50 years. This study evaluated rWN/DEN4Δ30 in flavivirus-naive adults aged 50-65 years and found it to be safe and immunogenic. Outbreaks of WNV infection tend to be unpredictable, and a safe and effective vaccine will be an important public health tool. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Low-dose, Chronic Exposure to Silver Nanoparticles Causes Mild Mitochondrial Alterations in the Liver of Sprague-Dawley Rat

DTIC Science & Technology

2014-05-10

of Sprague-Dawley rat CARLOS PALMEIRA CENTRO DE NEUROCIENCIAS E BIOLOGIA CELULAR (CNC) DEPARTAMENTO DE ZOOLOGIA COIMBRA 3000 - 329...CENTRO DE NEUROCIENCIAS E BIOLOGIA CELULAR (CNC) DEPARTAMENTO DE ZOOLOGIA COIMBRA 3000 - 329 PORTUGAL 8. PERFORMING ORGANIZATION REPORT NUMBER

No effect of bicarbonate treatment on insulin sensitivity and glucose control in non-diabetic older adults

USDA-ARS?s Scientific Manuscript database

Chronic mild metabolic acidosis is common among older adults, and limited evidence suggests that it may contribute to insulin resistance and type 2 diabetes. This analysis was conducted to determine whether bicarbonate supplementation, an alkalinizing treatment, improves insulin sensitivity or gluco...

Bupropion-SR plus naltrexone-SR for the treatment of mild-to-moderate obesity.

PubMed

Ali, Khawla F; Shukla, Alpana P; Aronne, Louis J

2016-01-01

Naltrexone-bupropion is a recently approved drug combination for chronic weight management. In this article, we discuss the rationale for its use as a combination followed by a comprehensive review of safety and efficacy data from major preclinical, phase II and III clinical trials.

Periodontal Regeneration Of 1-, 2-, and 3-Walled Intrabony Defects Using Accell Connexus (registered trademark) Versus Demineralized Freeze-Dried Bone Allograft: A Randomized Parallel Arm Clinical Control Trial

DTIC Science & Technology

2015-06-01

localized or generalized), duration ( chronic or aggressive) and severity (mild, moderate or severe) of periodontal disease which will assist in rendering...intrabony defects can be seen in chronic forms of periodontal disease. 9 Figure 4a shows a normal bony pattern in which the bone level follows the... PERIODONTAL REGENERATION OF 1-, 2-, AND 3-WALLED INTRABONY DEFECTS USING ACCELL CONNEXUS® VERSUS DEMINERALIZED FREEZE- DRIED BONE ALLOGRAFT: A

The relationship of temporomandibular disorders and fibromyalgia: implications for diagnosis and treatment.

PubMed

Fricton, James R

2004-10-01

Although most cases of temporomandibular disorders (TMD) are mild and self-limiting, approximately 10% of patients develop severe disorders associated with chronic pain. It has been found that the widespread pain, depression, and sleep disorders associated with fibromyalgia (FM) may play a significant role in the chronicity of patients with TMD. This paper reviews the characteristics and relationship between TMD and FM and discusses how the similar mechanisms and diagnostic and treatment strategies for both disorders suggest that there is a close relationship between them.

Chronic West Nile virus infection in kea (Nestor notabilis).

PubMed

Bakonyi, Tamás; Gajdon, Gyula K; Schwing, Raoul; Vogl, Wolfgang; Häbich, Annett-Carolin; Thaller, Denise; Weissenböck, Herbert; Rudolf, Ivo; Hubálek, Zdenek; Nowotny, Norbert

2016-02-01

Six kea (Nestor notabilis) in human care, naturally infected with West Nile virus (WNV) lineage 2 in Vienna, Austria, in 2008, developed mild to fatal neurological signs. WNV RNA persisted and the virus evolved in the birds' brains, as demonstrated by (phylo)genetic analyses of the complete viral genomes detected in kea euthanized between 2009 and 2014. WNV antibodies persisted in the birds, too. Chronic WNV infection in the brain might contribute to the circulation of the virus through oral transmission to predatory birds. Copyright © 2015 Elsevier B.V. All rights reserved.

Low-dose hydrocortisone replacement improves wellbeing and pain tolerance in chronic pain patients with opioid-induced hypocortisolemic responses. A pilot randomized, placebo-controlled trial.

PubMed

Nenke, Marni A; Haylock, Clare L; Rankin, Wayne; Inder, Warrick J; Gagliardi, Lucia; Eldridge, Crystal; Rolan, Paul; Torpy, David J

2015-06-01

Long-term opioid therapy has been associated with low cortisol levels due to central suppression of the hypothalamic-pituitary-adrenal axis. The implications of hypocortisolism on wellbeing have not been established. Our aim was to determine whether intervention with physiologic glucocorticoid replacement therapy improves wellbeing and analgesic responses in patients with chronic non-cancer pain on long-term opioid therapy with mild cortisol deficiency. We performed a pilot randomized, double-blind, placebo-controlled crossover study of oral hydrocortisone replacement therapy in 17 patients recruited from a Pain Clinic at a single tertiary center in Adelaide, Australia. Patients were receiving long-term opioid therapy (≥ 20 mg morphine equivalents per day for ≥ 4 weeks) for chronic non-cancer pain with mild hypocortisolism, as defined by a plasma cortisol response ≤ 350 nmol/L at 60 min following a cold pressor test. The crossover intervention included 28-day treatment with either 10mg/m(2)/day of oral hydrocortisone in three divided doses or placebo. Improvement in wellbeing was assessed using Version 2 of the Short Form-36 (SF-36v2), Brief Pain Inventory-Short Form, and Addison's disease quality of life questionnaires; improvement in analgesic response was assessed using cold pressor threshold and tolerance times. Following treatment with hydrocortisone, the bodily pain (P=0.042) and vitality (P=0.013) subscales of the SF-36v2 were significantly better than scores following treatment with placebo. There was also an improvement in pain interference on general activity (P=0.035), mood (P=0.03) and work (P=0.04) following hydrocortisone compared with placebo. This is the first randomized, double-blind placebo-controlled trial of glucocorticoid replacement in opioid users with chronic non-cancer pain and mild hypocortisolism. Our data suggest that physiologic hydrocortisone replacement produces improvements in vitality and pain experiences in this cohort compared with placebo. Therapeutic Goods Administration Clinical Trials Notification Scheme (Drugs), Trial Number 2012/0476. Copyright © 2015 Elsevier Ltd. All rights reserved.

Acute Exacerbations and Lung Function Loss in Smokers with and without Chronic Obstructive Pulmonary Disease.

PubMed

Dransfield, Mark T; Kunisaki, Ken M; Strand, Matthew J; Anzueto, Antonio; Bhatt, Surya P; Bowler, Russell P; Criner, Gerard J; Curtis, Jeffrey L; Hanania, Nicola A; Nath, Hrudaya; Putcha, Nirupama; Roark, Sarah E; Wan, Emily S; Washko, George R; Wells, J Michael; Wendt, Christine H; Make, Barry J

2017-02-01

Acute exacerbations of chronic obstructive pulmonary disease (COPD) increase the risk of death and drive healthcare costs, but whether they accelerate loss of lung function remains controversial. Whether exacerbations in subjects with mild COPD or similar acute respiratory events in smokers without airflow obstruction affect lung function decline is unknown. To determine the association between acute exacerbations of COPD (and acute respiratory events in smokers without COPD) and the change in lung function over 5 years of follow-up. We examined data on the first 2,000 subjects who returned for a second COPDGene visit 5 years after enrollment. Baseline data included demographics, smoking history, and computed tomography emphysema. We defined exacerbations (and acute respiratory events in those without established COPD) as acute respiratory symptoms requiring either antibiotics or systemic steroids, and severe events by the need for hospitalization. Throughout the 5-year follow-up period, we collected self-reported acute respiratory event data at 6-month intervals. We used linear mixed models to fit FEV 1 decline based on reported exacerbations or acute respiratory events. In subjects with COPD, exacerbations were associated with excess FEV 1 decline, with the greatest effect in Global Initiative for Chronic Obstructive Lung Disease stage 1, where each exacerbation was associated with an additional 23 ml/yr decline (95% confidence interval, 2-44; P = 0.03), and each severe exacerbation with an additional 87 ml/yr decline (95% confidence interval, 23-151; P = 0.008); statistically significant but smaller effects were observed in Global Initiative for Chronic Obstructive Lung Disease stage 2 and 3 subjects. In subjects without airflow obstruction, acute respiratory events were not associated with additional FEV 1 decline. Exacerbations are associated with accelerated lung function loss in subjects with established COPD, particularly those with mild disease. Trials are needed to test existing and novel therapies in subjects with early/mild COPD to potentially reduce the risk of progressing to more advanced lung disease. Clinical trial registered with www.clinicaltrials.gov (NCT 00608764).

Three-dimensional, virtual reality vestibular rehabilitation for chronic imbalance problem caused by Ménière's disease: a pilot study^.

PubMed

Hsu, Su-Yi; Fang, Te-Yung; Yeh, Shih-Ching; Su, Mu-Chun; Wang, Pa-Chun; Wang, Victoria Y

2017-08-01

The purpose of this study was to evaluate a three-dimensional, virtual reality system for vestibular rehabilitation in patients with intractable Ménière's disease and chronic vestibular dysfunction. We included 70 patients (36 for study, 34 as control) with a chronic imbalance problem caused by uncompensated Ménière's disease. The virtual reality vestibular rehabilitation comprised four training tasks (modified Cawthorne-Cooksey exercises: eye, head, extension, and coordination exercises) performed in six training sessions (in 4 weeks). Measurements of the task scores and balance parameters obtained at the baseline and after final training sessions were compared. A significant improvement was observed in extension and coordination scores. Patients in the early stages of Ménière's disease had a significantly greater improvement in the center of gravity sway and trajectory excursion in the mediolateral direction than did patients in the late stages of Ménière's disease. Mild functional disability attributable to Ménière's disease was a predictor of improvement in the statokinesigram and maximum trajectory excursion in the anteroposterior direction after rehabilitation. The control group showed no significant improvement in almost all parameters. Virtual reality vestibular rehabilitation may be useful in patients with Ménière's disease, particular those in the early stages or having mild functional disability. Implication for rehabilitation Chronic imbalance caused by uncompensated Ménière's disease is an indication for vestibular rehabilitation. The interactive virtual reality video game, when integrated into vestibular rehabilitation exercise protocol, may assist patients who have mild disability Ménière's disease and who cannot benefit from treatment with drugs or surgery. The initial data from this study support the applicability of three-dimensional virtual reality technology in vestibular rehabilitation programs. The technology gives professionals a new tool to guide patients for vestibular rehabilitation exercises through three-dimensional virtual reality video game playing. The virtual reality vestibular exercise game can provide patients a step-wise, interactive, dynamic, three-dimensional, and interesting rehabilitation environment.

[Unpredicted pregnancy among Chilean young women].

PubMed

Palma, Irma

2012-03-01

Unpredicted pregnancy is an evolution of the concepts undesired and unplanned pregnancy. It is more common among vulnerable strata of our society and related to lack of education. To explore the prevalence and social concomitants of unpredicted pregnancy among young women. Analysis of the databases of the Sixth National Youth Survey carried out by the Instituto Nacional de la Juventud in Chile during 2009. The universe corresponds to 7570 participants aged between 15 and 29 years, of both genders. Unpredicted pregnancy occurred in 43% of sexually active surveyed women. It was more common among women with a lower educational level and those aged 15 to 24 years, especially during the onset of active sexual life. There was also an inverse relationship between the degree of education, the use of contraception and the age when sexual activity starts. Unpredicted pregnancy is frequent among teenagers and more common among less educated individuals. The frequency of use of contraception is associated in greater measure to the degree of education rather than the age of onset of sexual activity.

The processing of mispredicted and unpredicted sensory inputs interact differently with attention.

PubMed

Hsu, Yi-Fang; Hämäläinen, Jarmo A; Waszak, Florian

2018-03-01

Prediction and attention are fundamental brain functions in the service of perception. Interestingly, previous investigations found prediction effects independent of attention in some cases but attention-dependent in other cases. The discrepancy might be related to whether the prediction effect was revealed by comparing mispredicted event (where there is incorrect prediction) or unpredicted event (where there is no precise prediction) against predicted event, which are associated with different precision-weighted prediction error. Here we conducted a joint analysis on four published electroencephalography (EEG) datasets which allow for proper dissociation of mispredicted and unpredicted conditions when there was orthogonal manipulation of prediction and attention. We found that the mispredicted-versus-predicted contrast revealed an attention-independent effect of prediction suppression, whereas the unpredicted-versus-predicted contrast revealed a prediction effect that was reversed by attention on auditory N1. The results suggest that mispredicted and unpredicted processing interact with attention in distinct manners. Copyright © 2018 Elsevier Ltd. All rights reserved.

Safety profile and protocol prevention of adverse reactions to uroangiographic contrast media in diagnostic imaging.

PubMed

Rossi, C; Reginelli, A; D'Amora, M; Di Grezia, G; Mandato, Y; D'Andrea, A; Brunese, L; Grassi, R; Rotondi, A

2014-01-01

The purpose of the study is to examine the incidence of adverse reactions caused by non-ionic contrast media in selected patients after desensitization treatment and to evaluate the safety profile of organ iodine contrast media (i.c.m.) in a multistep prevention protocol. In a population of 2000 patients that had received a CT scan, 100 patients with moderate/high risk for adverse reactions against iodinated contrast agents followed a premedication protocol and all adverse reactions are reported and classified as mild, moderate or severe. 1.7 percent of the pre-treated patients reported a mild, immediate type reaction to iodine contrast; of these five patients with allergy 0.71 percent had received iomeprol, 0.35 percent received ioversol and 0.71 percent received iopromide. The incidence of adverse reactions was reported to be higher (4 out of 5 patients) among those that referred a history of hypersensitivity against iodinated i.c.m. Although intravenous contrast materials have greatly improved, especially in terms of their safety profile, they should not be administered if there isn't a clear or justified indication. In conclusion, even if we know that the majority of these reactions are idiosyncratic and unpredictable we propose, with the aim of improving our knowledge on this subject, a multicenter study, based on skin allergy tests (prick test, patch test, intradermal reaction) in selected patients that have had previous experiences of hypersensitivity against parenteral organ iodine contrast media.

Current treatment of chronic hepatitis C in China: Dilemma and potential problems

PubMed Central

Han, Qun-Ying; Liu, Zheng-Wen

2016-01-01

Major advances have been made in the treatment of chronic hepatitis C virus (HCV) infection with the advent of direct-acting antiviral agents (DAAs). China has the most cases of HCV infection worldwide, but none of the DAAs has been approved in mainland China so far, and interferon (IFN)-α-based treatment remains the standard of care. HCV patients without response or with contraindications to IFN-based therapy have no alternative options. However, many patients buy DAAs, especially the generic forms of sofosbuvir, from other countries or areas. Under these circumstances, the use of these drugs may cause many predictable and unpredictable problems in ethics, law and medical practice. Given the obstacles of legal accessibility to DAAs and the potential problems of obtaining and using DAAs in China, the early launching of the DAAs in China or the legalization of buying drugs from areas outside China and using these drugs in China is an urgent issue and needs to be dealt with as soon as possible, in the interest of the patients. PMID:27217693