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Sample records for axotomy-induced neurotrophic withdrawal

  1. Axotomy-induced neurotrophic withdrawal causes the loss of phenotypic differentiation and downregulation of NGF signalling, but not death of septal cholinergic neurons

    Directory of Open Access Journals (Sweden)

    Inestrosa Nibaldo C

    2010-01-01

    Full Text Available Abstract Background Septal cholinergic neurons account for most of the cholinergic innervations of the hippocampus, playing a key role in the regulation of hippocampal synaptic activity. Disruption of the septo-hippocampal pathway by an experimental transection of the fimbria-fornix drastically reduces the target-derived trophic support received by cholinergic septal neurons, mainly nerve growth factor (NGF from the hippocampus. Axotomy of cholinergic neurons induces a reduction in the number of neurons positive for cholinergic markers in the medial septum. In several studies, the reduction of cholinergic markers has been interpreted as analogous to the neurodegeneration of cholinergic cells, ruling out the possibility that neurons lose their cholinergic phenotype without dying. Understanding the mechanism of cholinergic neurodegeneration after axotomy is relevant, since this paradigm has been extensively explored as an animal model of the cholinergic impairment observed in neuropathologies such as Alzheimer's disease. The principal aim of this study was to evaluate, using modern quantitative confocal microscopy, neurodegenerative changes in septal cholinergic neurons after axotomy and to assess their response to delayed infusion of NGF in rats. Results We found that there is a slow reduction of cholinergic cells labeled by ChAT and p75 after axotomy. However, this phenomenon is not accompanied by neurodegenerative changes or by a decrease in total neuronal number in the medial septum. Although the remaining axotomized-neurons appear healthy, they are unable to respond to delayed NGF infusion. Conclusions Our results demonstrate that at 3 weeks, axotomized cholinergic neurons lose their cholinergic phenotype without dying and down-regulate their NGF-receptors, precluding the possibility of a response to NGF. Therefore, the physiological role of NGF in the adult septal cholinergic system is to support phenotypic differentiation and not survival of neurons. This evidence raises questions about the relationship between transcriptional regulation of the cholinergic phenotype by retrograde-derived trophic signaling and the transcriptional changes experienced when retrograde transport is impaired due to neuropathological conditions.

  2. Ciliary neurotrophic factor prevents retrograde neuronal death in the adult central nervous system.

    OpenAIRE

    Clatterbuck, R E; Price, D L; Koliatsos, V E

    1993-01-01

    The neurocytokine ciliary neurotrophic factor (CNTF) was described originally as an activity that supports the survival of neurons of the chicken ciliary ganglia in vitro. The widespread expression of CNTF and its principal binding protein, CNTF receptor alpha, in the central and peripheral nervous systems suggests a broader trophic role for this peptide. In the present study, we report that CNTF prevents axotomy-induced cell death of neurons in the anteroventral and anterodorsal thalamic nuc...

  3. Title: Sex differences in stress-induced social withdrawal: role of brain derived neurotrophic factor in the bed nucleus of the stria terminalis

    Directory of Open Access Journals (Sweden)

    Gian David Greenberg

    2014-01-01

    Full Text Available Depression and anxiety disorders are more common in women than men, and little is known about the neurobiological mechanisms that contribute to this disparity. Recent data suggest that stress-induced changes in neurotrophins have opposing effects on behavior by acting in different brain networks. Social defeat has been an important approach for understanding neurotrophin action, but low female aggression levels in rats and mice have limited the application of these methods primarily to males. We examined the effects of social defeat in monogamous California mice (Peromyscus californicus, a species in which both males and females defend territories. We demonstrate that defeat stress increases mature brain-derived neurotrophic factor (BDNF protein but not mRNA in the bed nucleus of the stria terminalis (BNST in females but not males. Changes in BDNF protein were limited to anterior subregions of the BNST, and there were no changes in the adjacent nucleus accumbens (NAc. The effects of defeat on social withdrawal behavior and BDNF were reversed by chronic, low doses of the antidepressant sertraline. However, higher doses of sertraline restored social withdrawal and elevated BDNF levels. Acute treatment with a low dose of sertraline failed to reverse the effects of defeat. Infusions of the selective tyrosine-related kinase B receptor (TrkB antagonist ANA-12 into the anterior BNST specifically increased social interaction in stressed females but had no effect on behavior in females naïve to defeat. These results suggest that stress-induced increases in BDNF in the anterior BNST contribute to the exaggerated social withdrawal phenotype observed in females.

  4. A Single Brain-Derived Neurotrophic Factor Infusion into the Dorsomedial Prefrontal Cortex Attenuates Cocaine Self-Administration-Induced Phosphorylation of Synapsin in the Nucleus Accumbens during Early Withdrawal

    OpenAIRE

    Sun, Wei-Lun; Eisenstein, Sarah A.; Zelek-Molik, Agnieszka; McGinty, Jacqueline F.

    2015-01-01

    Background: Dysregulation in the prefrontal cortex-nucleus accumbens pathway has been implicated in cocaine addiction. We have previously demonstrated that one intra-dorsomedial prefrontal cortex brain-derived neurotrophic factor (BDNF) infusion immediately following the last cocaine self-administration session caused a long-lasting inhibition of cocaine-seeking and normalized the cocaine-induced disturbance of glutamate transmission in the nucleus accumbens after extinction and a cocaine pri...

  5. Brain derived neurotrophic factor

    DEFF Research Database (Denmark)

    Mitchelmore, Cathy; Gede, Lene

    2014-01-01

    Brain Derived Neurotrophic Factor (BDNF) is a neurotrophin with important functions in neuronal development and neuroplasticity. Accumulating evidence suggests that alterations in BDNF expression levels underlie a variety of psychiatric and neurological disorders. Indeed, BDNF therapies are...

  6. Brain derived neurotrophic factor

    DEFF Research Database (Denmark)

    Mitchelmore, Cathy; Gede, Lene

    2014-01-01

    Brain Derived Neurotrophic Factor (BDNF) is a neurotrophin with important functions in neuronal development and neuroplasticity. Accumulating evidence suggests that alterations in BDNF expression levels underlie a variety of psychiatric and neurological disorders. Indeed, BDNF therapies are curre......Brain Derived Neurotrophic Factor (BDNF) is a neurotrophin with important functions in neuronal development and neuroplasticity. Accumulating evidence suggests that alterations in BDNF expression levels underlie a variety of psychiatric and neurological disorders. Indeed, BDNF therapies...

  7. Trigeminal Neurotrophic Ulceration

    OpenAIRE

    El-Daly, Ahmed; Snyderman, Carl H.

    1997-01-01

    A 74 year-old female developed a trigeminal neurotrophic ulcer (TNU) 20 years following surgical ablation of the trigeminal nerve. The diagnosis of this unusual disorder is suggested when an ulcerative lesion develops. In the ala nasi in a patient with trigeminal sensory loss. A history of self-induced trauma to that area and some form of mental impairment further support the diagnosis.

  8. Cocaine withdrawal

    Science.gov (United States)

    ... may not be as unstable as withdrawal from alcohol. However, the withdrawal from any chronic substance abuse is very serious. There is a risk of suicide or overdose. Symptoms usually disappear over time. People who have cocaine ...

  9. Cocaine withdrawal

    Science.gov (United States)

    Cocaine withdrawal occurs when someone who has used a lot of cocaine cuts down or quits taking the drug. Symptoms ... even if the user is not completely off cocaine and still has some of the drug in ...

  10. Alcohol withdrawal

    Science.gov (United States)

    ... parts A severe form of alcohol withdrawal called delirium tremens can cause: Agitation Fever Seeing or feeling things ... watched closely for hallucinations and other signs of delirium tremens. Treatment may include: Monitoring of blood pressure, body ...

  11. Rat ciliary neurotrophic factor (CNTF)

    OpenAIRE

    Carroll, P.; Sendtner, M.; Meyer, Michael; Thoenen, Hans

    1993-01-01

    The structure of the rat ciliary neurotrophic factor (CNTF) gene and the regulation of CNTF mRNA levels in cultured glial cells were investigated. The rat mRNA is encoded by a simple two-exon transcription unit. Sequence analysis of the region upstream of the transcription start-site did not reveal a typical TATA-box consensus sequence. Low levels of CNTF mRNA were detected in cultured Schwann cells, and CNTF mRNA was not increased by a variety of treatments. Three-week-old astrocyte-enriched...

  12. 29 CFR 4219.11 - Withdrawal liability upon mass withdrawal.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 9 2010-07-01 2010-07-01 false Withdrawal liability upon mass withdrawal. 4219.11 Section... Redetermination of Withdrawal Liability Upon Mass Withdrawal § 4219.11 Withdrawal liability upon mass withdrawal. (a) Initial withdrawal liability. The plan sponsor of a multiemployer plan that experiences a...

  13. Optimizing neurotrophic factor combinations for neurite outgrowth

    Science.gov (United States)

    Deister, C.; Schmidt, C. E.

    2006-06-01

    Most neurotrophic factors are members of one of three families: the neurotrophins, the glial cell-line derived neurotrophic factor family ligands (GFLs) and the neuropoietic cytokines. Each family activates distinct but overlapping cellular pathways. Several studies have shown additive or synergistic interactions between neurotrophic factors from different families, though generally only a single combination has been studied. Because of possible interactions between the neurotrophic factors, the optimum concentration of a factor in a mixture may differ from the optimum when applied individually. Additionally, the effect of combinations of neurotrophic factors from each of the three families on neurite extension is unclear. This study examines the effects of several combinations of the neurotrophin nerve growth factor (NGF), the GFL glial cell-line derived neurotrophic factor (GDNF) and the neuropoietic cytokine ciliary neurotrophic factor (CNTF) on neurite outgrowth from young rat dorsal root ganglion (DRG) explants. The combination of 50 ng ml-1 NGF and 10 ng ml-1 of each GDNF and CNTF induced the highest level of neurite outgrowth at a 752 ± 53% increase over untreated DRGs and increased the longest neurite length to 2031 ± 97 µm compared to 916 ± 64 µm for untreated DRGs. The optimum concentrations of the three factors applied in combination corresponded to the optimum concentration of each factor when applied individually. These results indicate that the efficacy of future therapies for nerve repair would be enhanced by the controlled release of a combination of neurotrophins, GFLs and neuropoietic cytokines at higher concentrations than used in previous conduit designs.

  14. Measurements of brain-derived neurotrophic factor

    DEFF Research Database (Denmark)

    Trajkovska, Viktorija; Klein, Anders Bue; Vinberg, Maj;

    2007-01-01

    Although numerous studies have dealt with changes in blood brain-derived neurotrophic factor (BDNF), methodological issues about BDNF measurements have only been incompletely resolved. We validated BDNF ELISA with respect to accuracy, reproducibility and the effect of storage and repeated freezin...

  15. Expression of cFos and brain-derived neurotrophic factor in cortex and hippocampus of ethanol-withdrawn male and female rats

    OpenAIRE

    Alele, Paul E.; Devaud, Leslie L.

    2013-01-01

    Objective: To map areas of brain activation (cFos) alongside changes in levels of brain-derived neurotrophic factor (BDNF) to provide insights into neuronal mechanisms contributing to previously observed sex differences in behavioral measures of ethanol withdrawal (EW). Materials and Methods: Immunohistochemical analysis of cFos and BDNF levels using protein-specific antibodies and visualization with nickel-enhanced DAB staining in 3 cortical and 4 hippocampal regions was used to assess EW-in...

  16. CONSUMER'S RIGHT TO WITHDRAW

    OpenAIRE

    ANCA NICOLETA GHEORGHE; CAMELIA SPASICI

    2013-01-01

    The right of withdrawal (of a contract) belongs to the consumer, and is an essential means for the improvement of regulations that protect the consumer.. Right of withdrawal is not a recent creation and is not even specific to the consumer field. He was previously recognized in civil and commercial law (without special regulation). The right to withdraw may even have as ground the parties will. Thus, based on the contractual freedom, the parties may agree that one of them has the right to ter...

  17. Ciliary neurotrophic factor is an endogenous pyrogen.

    OpenAIRE

    Shapiro, L; Zhang, X. X.; Rupp, R G; Wolff, S. M.; Dinarello, C A

    1993-01-01

    Fever is initiated by the action of polypeptide cytokines called endogenous pyrogens, which are produced by the host during inflammation, trauma, or infection and which elevate the thermoregulatory set point in the hypothalamus. Ciliary neurotrophic factor (CNTF) supports the differentiation and survival of central and peripheral neurons. We describe the activity of CNTF as intrinsically pyrogenic in the rabbit. CNTF induced a monophasic fever which rose rapidly (within the first 12 min) foll...

  18. Withdrawing Nutrition, Hydration

    Science.gov (United States)

    Module eleven of the EPEC-O Self-Study Original Version discusses the general aspects of withholding or withdrawing of life-sustaining therapies, and presents a specific application to artificial nutrition and hydration.

  19. Neurotrophic effects of neudesin in the central nervous system

    OpenAIRE

    Kimura, Ikuo; Nakayama, Yoshiaki; Zhao, Ying; Konishi, Morichika; Itoh, Nobuyuki

    2013-01-01

    Neudesin (neuron-derived neurotrophic factor; NENF) was identified as a neurotrophic factor that is involved in neuronal differentiation and survival. It is abundantly expressed in the central nervous system, and its neurotrophic activity is exerted via the mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) pathways. Neudesin is also an anorexigenic factor that suppresses food intake in the hypothalamus. It is a member of the membrane-associated progesterone rece...

  20. Inpatient alcohol withdrawal syndrome.

    Science.gov (United States)

    Monte-Secades, R; Rabuñal-Rey, R; Guerrero-Sande, H

    2015-03-01

    A 55-year-old man was admitted for a femur fracture; an alcohol fetor was noted on admission. The following day, the patient began to experience tremors and nervousness. Intravenous haloperidol was administered. Shortly afterwards, the patient experienced two generalized seizures and then began to experience delirium and uncontrollable agitation. The patient was diagnosed with alcohol withdrawal syndrome; high doses of intravenous midazolam were prescribed and infused. A few hours later, the patient presented signs of respiratory depression, requiring a transfer to the intensive care unit. After a review of the medical history, it was determined that the patient had been admitted on 3 previous occasions due to alcohol withdrawal and had progressed to delirium tremens after experiencing seizures. Can the risk of alcohol withdrawal syndrome and the need for prophylactic treatment be assessed on admission? Were appropriate monitoring and treatment measures employed? Would it have been possible to change his outcome? PMID:25559647

  1. The alcohol withdrawal syndrome.

    LENUS (Irish Health Repository)

    McKeon, A

    2008-08-01

    The alcohol withdrawal syndrome (AWS) is a common management problem in hospital practice for neurologists, psychiatrists and general physicians alike. Although some patients have mild symptoms and may even be managed in the outpatient setting, others have more severe symptoms or a history of adverse outcomes that requires close inpatient supervision and benzodiazepine therapy. Many patients with AWS have multiple management issues (withdrawal symptoms, delirium tremens, the Wernicke-Korsakoff syndrome, seizures, depression, polysubstance abuse, electrolyte disturbances and liver disease), which requires a coordinated, multidisciplinary approach. Although AWS may be complex, careful evaluation and available treatments should ensure safe detoxification for most patients.

  2. Enteric glia mediate neuronal outgrowth through release of neurotrophic factors

    Institute of Scientific and Technical Information of China (English)

    Christopher R.Hansebout; Caixin Su; Kiran Reddy; Donald Zhang; Cai Jiang; Michel P.Rathbone; Shucui Jiang

    2012-01-01

    Previous studies have shown that transplanted enteric glia enhance axonal regeneration,reduce tissue damage,and promote functional recovery following spinal cord injury.However,the mechanisms by which enteric glia mediate these beneficial effects are unknown.Neurotrophic factors can promote neuronal differentiation,survival and neurite extension.We hypothesized that enteric glia may exert their protective effects against spinal cord injury partially through the secretion of neurotrophic factors.In the present study,we demonstrated that primary enteric glia cells release nerve growth factor,brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor over time with their concentrations reaching approximately 250,100 and 50 pg/mL of culture medium respectively after 48 hours.The biological relevance of this secretion was assessed by incubating dissociated dorsal root ganglion neuronal cultures in enteric glia-conditioned medium with and/or without neutralizing antibodies to each of these proteins and evaluating the differences in neurite growth.We discovered that conditioned medium enhances neurite outgrowth in dorsal root ganglion neurons.Even though there was no detectable amount of neurotrophin-3 secretion using ELISA analysis,the neurite outgrowth effect can be attenuated by the antibody-mediated neutralization of each of the aforementioned neurotrophic factors.Therefore,enteric glia secrete nerve growth factor,brain-derived neurotrophic factor,glial cell line-derived neurotrophic factor and neurotrophin-3 into their surrounding environment in concentrations that can cause a biological effect.

  3. Neurotrophic factors in tension-type headache

    Directory of Open Access Journals (Sweden)

    Renan B. Domingues

    2015-05-01

    Full Text Available Neurotrophic factors (NF are involved in pain regulation and a few studies have suggested that they may play a pathophysiological role in primary headaches. The aim of this study was to investigate NF levels in patients with tension type headache (TTH. We carried out a cross sectional study including 48 TTH patients and 48 age and gender matched controls. Beck Depression and Anxiety Inventories, and Headache Impact Test were recorded. Serum levels of NF were determined by ELISA. There were not significant differences between NF levels between TTH patients and controls. Patients with chronic and episodic TTH had not significant differences in NF levels. The presence of headache at the time of evaluation did not significantly alter the levels of NF. Depression and anxiety scores as well as headache impact did not correlate with NF levels. Our study suggest that the serum levels of NF are not altered in TTH.

  4. The Brain Derived Neurotrophic Factor and Personality

    Directory of Open Access Journals (Sweden)

    Christian Montag

    2014-01-01

    Full Text Available The study of the biological basis of personality is a timely research endeavor, with the aim of deepening our understanding of human nature. In recent years, a growing body of research has investigated the role of the brain derived neurotrophic factor (BDNF in the context of individual differences across human beings, with a focus on personality traits. A large number of different approaches have been chosen to illuminate the role of BDNF for personality, ranging from the measurement of BDNF in the serum/plasma to molecular genetics to (genetic brain imaging. The present review provides the reader with an overview of the current state of affairs in the context of BDNF and personality.

  5. Neurotrophic factor control of satiety and body weight.

    Science.gov (United States)

    Xu, Baoji; Xie, Xiangyang

    2016-05-01

    Energy balance - that is, the relationship between energy intake and energy expenditure - is regulated by a complex interplay of hormones, brain circuits and peripheral tissues. Leptin is an adipocyte-derived cytokine that suppresses appetite and increases energy expenditure. Ironically, obese individuals have high levels of plasma leptin and are resistant to leptin treatment. Neurotrophic factors, particularly ciliary neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF), are also important for the control of body weight. CNTF can overcome leptin resistance in order to reduce body weight, although CNTF and leptin activate similar signalling cascades. Mutations in the gene encoding BDNF lead to insatiable appetite and severe obesity. PMID:27052383

  6. Diagnosis and management of neurotrophic keratitis

    Directory of Open Access Journals (Sweden)

    Sacchetti M

    2014-03-01

    Full Text Available Marta Sacchetti,1 Alessandro Lambiase2 1Cornea and Ocular Surface Unit, Ospedale San Raffaele di Milano-IRCCS, Milan, 2Ophthalmology, University La Sapienza of Rome, Italy Abstract: Neurotrophic keratitis (NK is a degenerative disease characterized by corneal sensitivity reduction, spontaneous epithelium breakdown, and impairment of corneal healing. Several causes of NK, including herpetic keratitis, diabetes, and ophthalmic and neurosurgical procedures, share the common mechanism of trigeminal damage. Diagnosis of NK requires accurate investigation of clinical ocular and systemic history, complete eye examination, and assessment of corneal sensitivity. All diagnostic procedures to achieve correct diagnosis and classification of NK, including additional examinations such as in vivo confocal microscopy, are reviewed. NK can be classified according to severity of corneal damage, ie, epithelial alterations (stage 1, persistent epithelial defect (stage 2, and corneal ulcer (stage 3. Management of NK should be based on clinical severity, and aimed at promoting corneal healing and preventing progression of the disease to stromal melting and perforation. Concomitant ocular diseases, such as exposure keratitis, dry eye, and limbal stem cell deficiency, negatively influence the outcome of NK and should be treated. Currently, no specific medical treatment exists, and surgical approaches, such as amniotic membrane transplantation and conjunctival flap, are effective in preserving eye integrity, without ameliorating corneal sensitivity or visual function. This review describes experimental and clinical reports showing several novel and potential therapies for NK, including growth factors and metalloprotease inhibitors, as well as three ongoing Phase II clinical trials. Keywords: neurotrophic keratitis, cornea sensitivity, cornea innervation, persistent epithelial defect

  7. Resveratrol Produces Neurotrophic Effects on Cultured Dopaminergic Neurons through Prompting Astroglial BDNF and GDNF Release

    Directory of Open Access Journals (Sweden)

    Feng Zhang

    2012-01-01

    Full Text Available Increasing evidence indicated astroglia-derived neurotrophic factors generation might hold a promising therapy for Parkinson’s disease (PD. Resveratrol, naturally present in red wine and grapes with potential benefit for health, is well known to possess a number of pharmacological activities. Besides the antineuroinflammatory properties, we hypothesized the neuroprotective potency of resveratrol is partially due to its additional neurotrophic effects. Here, primary rat midbrain neuron-glia cultures were applied to investigate the neurotrophic effects mediated by resveratrol on dopamine (DA neurons and further explore the role of neurotrophic factors in its actions. Results showed resveratrol produced neurotrophic effects on cultured DA neurons. Additionally, astroglia-derived neurotrophic factors release was responsible for resveratrol-mediated neurotrophic properties as evidenced by the following observations: (1 resveratrol failed to exert neurotrophic effects on DA neurons in the cultures without astroglia; (2 the astroglia-conditioned medium prepared from astroglia-enriched cultures treated with resveratrol produced neurotrophic effects in neuron-enriched cultures; (3 resveratrol increased neurotrophic factors release in the concentration- and time-dependent manners; (4 resveratrol-mediated neurotrophic effects were suppressed by blocking the action of the neurotrophic factors. Together, resveratrol could produce neurotrophic effects on DA neurons through prompting neurotrophic factors release, and these effects might open new alternative avenues for neurotrophic factor-based therapy targeting PD.

  8. CONSUMER'S RIGHT TO WITHDRAW

    Directory of Open Access Journals (Sweden)

    ANCA NICOLETA GHEORGHE

    2013-05-01

    Full Text Available The right of withdrawal (of a contract belongs to the consumer, and is an essential means for the improvement of regulations that protect the consumer.. Right of withdrawal is not a recent creation and is not even specific to the consumer field. He was previously recognized in civil and commercial law (without special regulation. The right to withdraw may even have as ground the parties will. Thus, based on the contractual freedom, the parties may agree that one of them has the right to terminate the contract unilaterally The possibility of unilateral denunciation of the contract, gives the consumer, added protection by being able to reflect the decision and to check how the trader fulfil its obligations. In this context, through its effects, the right of denunciation, forces the professional parties to conduct themselves as fair as possible to the consumer and to execute the contract properly. In the study of the consumer protection, the time of conclusion is essential because in this stage is manifested, the inequality between the consumer and professional. Thus, the lack of information, the major of products and activities, commercial practices, influence the formation of consumer will, preventing the expression of a freely and knowingly consent.

  9. Neurotrophic and antioxidant potential of neuropeptides and trace elements

    Directory of Open Access Journals (Sweden)

    O. A. Gromova

    2016-01-01

    Full Text Available Neurotrophic therapy with brain extract-based drugs has been performed for decades. The basis for their neurotrophic activity is amino acids and neuropeptides. However, incomplete information on the composition of these drugs precludes a detailed description of mechanisms through which their pharmacological effects occur. The review considers the results of the most recent molecular pharmacological investigations and the mechanisms of therapeutic action of cerebrolysin.

  10. Neurotrophic and antioxidant potential of neuropeptides and trace elements

    OpenAIRE

    O. A. Gromova; A. V. Pronin; I. Yu. Torshin; A. G. Kalacheva; T. R. Grishina

    2016-01-01

    Neurotrophic therapy with brain extract-based drugs has been performed for decades. The basis for their neurotrophic activity is amino acids and neuropeptides. However, incomplete information on the composition of these drugs precludes a detailed description of mechanisms through which their pharmacological effects occur. The review considers the results of the most recent molecular pharmacological investigations and the mechanisms of therapeutic action of cerebrolysin.

  11. Effect of ciliary neurotrophic factor (CNTF) on motoneuron survival

    OpenAIRE

    Sendtner, Michael; Arakawa, Yoshihiro; Stöckli, Kurt A.; Kreutzberg, Georg W.; Thoenen, Hans

    2010-01-01

    We have demonstrated that the extensive degeneration of motoneurons in the rat facial nucleus after transection of the facial nerve in newborn rats can be prevented by local ciliary neurotrophic factor (CNTF) administration. CNTF differs distinctly from known neurotrophic molecules such as NGF, BDNF and NT-3 in both its molecular characteristics (CNTF is a cytosolic rather than a secretory molecule) and its broad spectrum of biological activities. CNTF is expressed selectively by Schwann cell...

  12. Alcohol Dependence, Withdrawal, and Relapse

    OpenAIRE

    Howard C Becker

    2008-01-01

    Continued excessive alcohol consumption can lead to the development of dependence that is associated with a withdrawal syndrome when alcohol consumption is ceased or substantially reduced. This syndrome comprises physical signs as well as psychological symptoms that contribute to distress and psychological discomfort. For some people the fear of withdrawal symptoms may help perpetuate alcohol abuse; moreover, the presence of withdrawal symptoms may contribute to relapse after periods of absti...

  13. Synergistic neurotrophic effects of piracetam and thiotriazoline

    Directory of Open Access Journals (Sweden)

    O. A. Gromova

    2016-01-01

    Full Text Available The paper considers the synergy between the nootropic drug piracetam and the metabolic agent thiotriazoline that maintains energy metabolism and survival of neurons and other types of cells. Piracetam, a nootropic drug, a chemical pyrrolidone derivative, is used in neurological, psychiatric, and narcological practice. There is evidence on the positive effect of piracetam in elderly and senile patients with coronary heart disease. This drug is supposed to stimulate redox processes, to enhance glucose utilization, and to improve regional blood flow in the ischemic brain regions. Due to its action, the drug activates glycolytic processes and elevates ATP concentrations in brain tissue. Thiotriazoline is a compound that has antioxidant, anti-ischemic properties. The co-administration of piracetam and thiothriazoline is an innovation area in the treatment of stroke and other brain damages, especially in insulin resistance and high blood glucose levels. The paper considers the neurobiological properties of thiotriazoline and piracetam, which synergistically exert neuroprotective and neurotrophic effects.

  14. Expression of BDNF and TrkB Phosphorylation in the Rat Frontal Cortex During Morphine Withdrawal are NO Dependent.

    Science.gov (United States)

    Peregud, Danil I; Yakovlev, Alexander A; Stepanichev, Mikhail Yu; Onufriev, Mikhail V; Panchenko, Leonid F; Gulyaeva, Natalia V

    2016-08-01

    Nitric oxide (NO) mediates pharmacological effects of opiates including dependence and abstinence. Modulation of NO synthesis during the induction phase of morphine dependence affects manifestations of morphine withdrawal syndrome, though little is known about mechanisms underlying this phenomenon. Neurotrophic and growth factors are involved in neuronal adaptation during opiate dependence. NO-dependent modulation of morphine dependence may be mediated by changes in expression and activity of neurotrophic and/or growth factors in the brain. Here, we studied the effects of NO synthesis inhibition during the induction phase of morphine dependence on the expression of brain-derived neurotrophic factor (BDNF), glial-derived neurotrophic factor (GDNF), nerve growth factor (NGF), and insulin-like growth factor 1 (IGF1) as well as their receptors in rat brain regions after spontaneous morphine withdrawal in dependent animals. Morphine dependence in rats was induced within 6 days by 12 injections of morphine in increasing doses (10-100 mg/kg), and NO synthase inhibitor L-N(G)-nitroarginine methyl ester (L-NAME) (10 mg/kg) was given 1 h before each morphine injection. The expression of the BDNF, GDNF, NGF, IGF1, and their receptors in the frontal cortex, striatum, hippocampus, and midbrain was assessed 40 h after morphine withdrawal. L-NAME treatment during morphine intoxication resulted in an aggravation of the spontaneous morphine withdrawal severity. Morphine withdrawal was accompanied by upregulation of BDNF, IGF1, and their receptors TrkB and IGF1R, respectively, on the mRNA level in the frontal cortex, and only BDNF in hippocampus and midbrain. L-NAME administration during morphine intoxication decreased abstinence-induced upregulation of these mRNAs in the frontal cortex, hippocampus and midbrain. L-NAME prevented from abstinence-induced elevation of mature but not pro-form of BDNF polypeptide in the frontal cortex. While morphine abstinence did not affect Trk

  15. Neurotrophic keratitis in a patient with disseminated lymphangiomatosis

    Directory of Open Access Journals (Sweden)

    Jared E Knickelbein

    2009-10-01

    Full Text Available Jared E Knickelbein1,2, Susan T Stefko1, Puwat Charukamnoetkanok11Department of Ophthalmology, 2Medical Scientist Training Program, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA Introduction: Neurotrophic keratitis, a degenerative corneal disease caused by trigeminal nerve impairment, has many etiologies and remains very difficult to treat.Methods: Case report of a 23-year-old male with a right corneal ulcer that failed to improve despite broad-spectrum antimicrobials.Results: Prior diagnosis of disseminated lymphangiomatosis with a lesion in the right petrous apex effacing Meckel’s (trigeminal cave in conjunction with a history of nonhealing corneal abrasions suggested a neurotrophic etiology. Drawstring temporary tarsorrhaphy, in addition to antibiotics and autologous serum, lead to successful clearing of the infection and resolution of the corneal ulcer. Visual acuity improved from light perception (LP at the peak of infection to 20/40 six weeks after treatment.Conclusions: To our knowledge, we report the first case of neurotrophic keratitis in a patient with disseminated lymphangiomatosis that caused a mass effect in Meckel’s (trigeminal cave leading to compression of the trigeminal nerve. The antibiotic-resistant corneal ulcer was successfully treated with drawstring tarsorrhaphy, confirming the utility of this therapeutic measure in treating neurotrophic keratitis.Keywords: neurotrophic keratitis, corneal abrasion, drawstring tarsorrhaphy, disseminated lymphangiomatosis

  16. Hippocampal neurogenesis, neurotrophic factors and depression: possible therapeutic targets?

    Science.gov (United States)

    Serafini, Gianluca; Hayley, Shawn; Pompili, Maurizio; Dwivedi, Yogesh; Brahmachari, Goutam; Girardi, Paolo; Amore, Mario

    2014-01-01

    Major depression is one of the leading causes of disability and psychosocial impairment worldwide. Although many advances have been made in the neurobiology of this complex disorder, the pathophysiological mechanisms are still unclear. Among the proposed theories, impaired neuroplasticity and hippocampal neurogenesis have received considerable attention. The possible association between hippocampal neurogenesis, neurotrophic factors, major depression, and antidepressant responses was critically analyzed using a comprehensive search of articles/book chapters in English language between 1980 and 2014. One common emerging theme was that chronic stress and major depression are associated with structural brain changes such as a loss of dendritic spines and synapses, as well as reduced dendritic arborisation, together with diminished glial cells in the hippocampus. Both central monoamines and neurotrophic factors were associated with a modulation of hippocampal progenitor proliferation and cell survival. Accordingly, antidepressants are generally suggested to reverse stress-induced structural changes augmenting dendritic arborisation and synaptogenesis. Such antidepressant consequences are supposed to stem from their stimulatory effects on neurotrophic factors, and possibly modulation of glial cells. Of course, accumulating evidence also suggested that glutamatergic systems are implicated in not only basic neuroplastic processes, but also in the core features of depression. Hence, it is critical that antidepressant strategies focus on links between the various neurotransmitter systems, neurotrophic processes of hippocampal neurogenesis, and neurotrophic factors with regards to depressive symptomology. The identification of novel alternative antidepressant medications that target these systems is discussed in this review. PMID:25470403

  17. Neurotrophic regulation of synapse development and plasticity

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Neurotrophic factors are traditionally thought to be secretory proteins that regulate long-tern survival and differe, ntiation of neurons. Recent studies have revealed a previously unexpected role for these factors in synaptie de velopment ami plasticity in diverse neuronal populations. Here we review experimeuts carried oul in our own laboratory in the last few years.. We have made two important discoveries.First,we were among the first to report that brain-derived. neurotrophie faclor (BDNF) facilitates hippocampal hmg-term potentiation (LTP), a form of synaptic plaslicity believed to be involved in learning and memory. BDNF modulates LTP al CAI synapses by enhaneing synaptic responses to high frequency, tetanic slimulalion. This is achieved primafily by facilitating synaptie vesicle doeking, possibly due to an in crease in the levels of the vesicle prolein synaptobrevin and synaptoplysin in the nerve terminals. Gene knockout study demonstrates thai the effects of BDNF are primarily mediated through presynaptic mechanisms. Second, we demonstrated a form of long-term, neurotrophin-mediated synaptic regulation. We showed that long-term treatment of the neuromuscu lar synapses with neurotrophin-3 (NT3) resulted in an enhancement of both spontaneous and evoked synaptic currcuts, as well as profound changes in thc number of synaptic varicosities and syuaptic vesicle proteins in motoneurons, all of which are indicative of more mature synapses. Our current work addresses the following issues:(i) activity-dependent trafficking of neurotrophin receptors, and its role in synapse-specific modulation; (ii) signal transduction mechanisms medialing the acute enhancement of synaplic transmission by neurotrophins; (iii) acute and long-tenn synaptie actions of the GDNF family; (iv) role of BDNF in late-phase LTP and in the development of hippocampal circuit.

  18. 5 CFR 1650.11 - Withdrawal elections.

    Science.gov (United States)

    2010-01-01

    ... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Withdrawal elections. 1650.11 Section 1650.11 Administrative Personnel FEDERAL RETIREMENT THRIFT INVESTMENT BOARD METHODS OF WITHDRAWING FUNDS FROM THE THRIFT SAVINGS PLAN Post-Employment Withdrawals § 1650.11 Withdrawal elections....

  19. Withdrawal: Expanding a Key Addiction Construct.

    Science.gov (United States)

    Piper, Megan E

    2015-12-01

    Withdrawal is an essential component of classical addiction theory; it is a vital manifestation of dependence and motivates relapse. However, the traditional conceptualization of withdrawal as a cohesive collection of symptoms that emerge during drug deprivation and decline with either the passage of time or reinstatement of drug use, may be inadequate to explain scientific findings or fit with modern theories of addiction. This article expands the current understanding of tobacco withdrawal by examining: (1) withdrawal variability; (2) underlying causes of withdrawal variability, including biological and person factors, environmental influences, and the influence of highly routinized behavioral patterns; (3) new withdrawal symptoms that allow for enhanced characterization of the withdrawal experience; and (4) withdrawal-related cognitive processes. These topics provide guidance regarding the optimal assessment of withdrawal and illustrate the potential impact modern withdrawal conceptualization and assessment could have on identifying treatment targets. PMID:25744958

  20. Mimicking the Neurotrophic Factor Profile of Embryonic Spinal Cord Controls the Differentiation Potential of Spinal Progenitors into Neuronal Cells

    OpenAIRE

    Nakamura, Masaya; Tsuji, Osahiko; BREGMAN, BARBARA S.; Toyama, Yoshiaki; Okano, Hideyuki

    2011-01-01

    Recent studies have indicated that the choice of lineage of neural progenitor cells is determined, at least in part, by environmental factors, such as neurotrophic factors. Despite extensive studies using exogenous neurotrophic factors, the effect of endogenous neurotrophic factors on the differentiation of progenitor cells remains obscure. Here we show that embryonic spinal cord derived-progenitor cells express both ciliary neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BD...

  1. Who withdraws? Psychological individual differences and employee withdrawal behaviors.

    Science.gov (United States)

    Zimmerman, Ryan D; Swider, Brian W; Woo, Sang Eun; Allen, David G

    2016-04-01

    Psychological individual differences, such as personality, affectivity, and general mental ability, have been shown to predict numerous work-related behaviors. Although there is substantial research demonstrating relationships between psychological individual differences and withdrawal behaviors (i.e., lateness, absenteeism, and turnover), there is no integrative framework providing scholars and practitioners a guide for conceptualizing how, why, and under what circumstances we observe such relationships. In this integrative conceptual review we: (a) utilize the Cognitive-Affective Processing System framework (Mischel & Shoda, 1995) to provide an overarching theoretical basis for how psychological individual differences affect withdrawal behaviors; (b) create a theoretical model of the situated person that summarizes the existing empirical literature examining the effect of psychological differences on withdrawal behavior; and (c) identify future research opportunities based on our review and integrative framework. (PsycINFO Database Record PMID:26595754

  2. Alcohol Withdrawal Mimicking Organophosphate Poisoning

    Directory of Open Access Journals (Sweden)

    Nezihat Rana Disel

    2014-02-01

    Full Text Available Organophosphates, which can cause occupational poisoning due to inappropriate personal protective measures, are widely used insecticides in agricultural regions of southern Turkey. Therefore, the classical clinical findings of this cholinergic poisoning are myosis, excessive secretions, bradicardia and fasciculations are easy to be recognized by local medical stuff. Diseases and conditions related to alcoholism such as mental and social impairments, coma, toxicity, withdrawal, and delirium are frequent causes of emergency visits of chronic alcoholic patients. Here we present a case diagnosed and treated as organophosphate poisoning although it was an alcohol withdrawal in the beginning and became delirium tremens, due to similar symptoms.

  3. Systemic administration of ciliary neurotrophic factor induces cachexia in rodents.

    OpenAIRE

    Henderson, J T; Seniuk, N A; Richardson, P.M.; Gauldie, J; Roder, J. C.

    1994-01-01

    Ciliary neurotrophic factor (CNTF) has previously been shown to promote the survival of several classes of neurons and glial. We report here that in addition to its effects on the nervous system, CNTF can induce potent effects in extra-neural tissues. Implantation of C6 glioma cells engineered to secrete CNTF either subcutaneously or into the peritoneal cavity of adult mice, or systemic injections of purified rat or human recombinant CNTF, resulted in a rapid syndrome of weight loss resulting...

  4. Ciliary Neurotrophic Factor Receptor Regulation of Adult Forebrain Neurogenesis

    OpenAIRE

    Lee, Nancy; Batt, Myra K.; Cronier, Brigitte A.; Jackson, Michele C.; Bruno Garza, Jennifer L; Trinh, Dennis S.; Mason, Carter O.; Spearry, Rachel P.; Bhattacharya, Shayon; Robitz, Rachel; Nakafuku, Masato; MacLennan, A. John

    2013-01-01

    Appropriately targeted manipulation of endogenous neural stem progenitor (NSP) cells may contribute to therapies for trauma, stroke, and neurodegenerative disease. A prerequisite to such therapies is a better understanding of the mechanisms regulating adult NSP cells in vivo. Indirect data suggest that endogenous ciliary neurotrophic factor (CNTF) receptor signaling may inhibit neuronal differentiation of NSP cells. We challenged subventricular zone (SVZ) cells in vivo with low concentrations...

  5. Brain-Derived Neurotrophic Factor in the Airways

    OpenAIRE

    Y S Prakash; Richard J Martin

    2014-01-01

    In addition to their well-known roles in the nervous system, there is increasing recognition that neurotrophins such as brain derived neurotrophic factor (BDNF) as well as their receptors are expressed in peripheral tissues including the lung, and can thus potentially contribute to both normal physiology and pathophysiology of several diseases. The relevance of this family of growth factors lies in emerging clinical data indicating altered neurotrophin levels and function in a range of diseas...

  6. Brain-derived neurotrophic factor and cocaine addiction

    OpenAIRE

    McGinty, Jacqueline F.; Whitfield, Timothy W.; Berglind, William J.

    2009-01-01

    The effects of brain-derived neurotrophic factor (BDNF) on cocaine-seeking are brain region-specific. Infusion of BDNF into subcortical structures, like the nucleus accumbens and ventral tegmental area, enhances cocaine-induced behavioral sensitization and cocaine seeking. Conversely, repeated administration of BDNF antiserum into the nucleus accumbens during chronic cocaine self-administration attenuates cocaine-induced reinstatement. In contrast, BDNF infusion into the dorsomedial prefronta...

  7. Rodent Models of Depression: Neurotrophic and Neuroinflammatory Biomarkers

    OpenAIRE

    Mikhail Stepanichev; Nikolay N Dygalo; Grigory Grigoryan; Shishkina, Galina T.; Natalia Gulyaeva

    2014-01-01

    Rodent models are an indispensable tool for studying etiology and progress of depression. Since interrelated systems of neurotrophic factors and cytokines comprise major regulatory mechanisms controlling normal brain plasticity, impairments of these systems form the basis for development of cerebral pathologies, including mental diseases. The present review focuses on the numerous experimental rodent models of depression induced by different stress factors (exteroceptive and interoceptive) du...

  8. Improving Nursing Knowledge of Alcohol Withdrawal

    OpenAIRE

    Berl, Kimberly; Collins, Michelle L.; Melson, Jo; Mooney, Ruth; Muffley, Cheryl; Wright-Glover, Angela

    2015-01-01

    Christiana Care Health System implemented a Care Management Guideline for Alcohol Withdrawal Symptom Management, which provided direction for inpatient screening for alcohol withdrawal risk, assessment, and treatment. Nurses educated on its use expressed confusion with the use of the assessment tools, pharmacokinetics, and pathophysiology of alcohol withdrawal and delirium tremens. Reeducation was provided by nursing professional development specialists. Pre- and postsurveys revealed that nur...

  9. Brain-derived neurotrophic factor inhibits glucose intolerance after cerebral ischemia

    OpenAIRE

    Shu, Xiaoliang; Zhang, Yongsheng; Xu, Han; Kang, Kai; Cai, Donglian

    2013-01-01

    Brain-derived neurotrophic factor is associated with the insulin signaling pathway and glucose tabolism. We hypothesized that expression of brain-derived neurotrophic factor and its receptor may be involved in glucose intolerance following ischemic stress. To verify this hypothesis, this study aimed to observe the changes in brain-derived neurotrophic factor and tyrosine kinase B receptor expression in glucose metabolism-associated regions following cerebral ischemic stress in mice. At day 1 ...

  10. The Effect of Erythropoietin on Neurotrophic Factors in N9 Murine Microglial Cells

    OpenAIRE

    Kuralay, Filiz; ÇAKIRLI, Başak BİNGOL; GENÇ, Şermin

    2008-01-01

    Aim: In this study, we investigated whether interferon gamma (IFNg), lipopolysaccharides (LPS) and amyloid beta (AMYb), as toxic stimulator agents, and erythropoietin (EPO), as a neurotrophic agent, have an effect on the production of the following neurotrophic factors in the N9 murine microglia cell line: neurotrophin 3 (NT3), neurotrophin 4 (NT4), and brain-derived neurotrophic factor (BDNF). Materials and Methods: Microglial cells were incubated with 50 μg/ml AMYb, or 1 _...

  11. Discrete Cues Paired with Naloxone-Precipitated Withdrawal from Acute Morphine Dependence Elicit Conditioned Withdrawal Responses

    OpenAIRE

    Amitai, Nurith; Liu, Jian; Schulteis, Gery

    2006-01-01

    Acute bolus doses of morphine induce a state of acute opioid dependence as measured by naloxone-precipitated withdrawal. Repeated morphine and precipitated withdrawal experience further enhances naloxone-induced withdrawal severity, in part due to direct neuroadaptation to repeated morphine, and in part due to conditioned associations of context and withdrawal experience. To determine whether a discrete tone/light conditioned stimulus (CS) could elicit conditioned withdrawal responses in acut...

  12. Alcohol Withdrawal and Cerebellar Mitochondria.

    Science.gov (United States)

    Jung, Marianna E

    2015-08-01

    Cerebellar disorders trigger the symptoms of movement problems, imbalance, incoordination, and frequent fall. Cerebellar disorders are shown in various CNS illnesses including a drinking disorder called alcoholism. Alcoholism is manifested as an inability to control drinking in spite of adverse consequences. Human and animal studies have shown that cerebellar symptoms persist even after complete abstinence from drinking. In particular, the abrupt termination (ethanol withdrawal) of long-term excessive ethanol consumption has shown to provoke a variety of neuronal and mitochondrial damage to the cerebellum. Upon ethanol withdrawal, excitatory neurotransmitter molecules such as glutamate are overly released in brain areas including cerebellum. This is particularly relevant to the cerebellar neuronal network as glutamate signals are projected to Purkinje neurons through granular cells that are the most populated neuronal type in CNS. This excitatory neuronal signal may be elevated by ethanol withdrawal stress, which promotes an increase in intracellular Ca(2+) level and a decrease in a Ca(2+)-binding protein, both of which result in the excessive entry of Ca(2+) to the mitochondria. Subsequently, mitochondria undergo a prolonged opening of mitochondrial permeability transition pore and the overproduction of harmful free radicals, impeding adenosine triphosphate (ATP)-generating function. This in turn provokes the leakage of mitochondrial molecule cytochrome c to the cytosol, which triggers a cascade of adverse cytosol reactions. Upstream to this pathway, cerebellum under the condition of ethanol withdrawal has shown aberrant gene modifications through altered DNA methylation, histone acetylation, or microRNA expression. Interplay between these events and molecules may result in functional damage to cerebellar mitochondria and consequent neuronal degeneration, thereby contributing to motoric deficit. Mitochondria-targeting research may help develop a powerful new

  13. Brain-derived neurotrophic factor Val66Met polymorphism and alcohol-related phenotypes.

    Science.gov (United States)

    Nedic, Gordana; Perkovic, Matea Nikolac; Sviglin, Korona Nenadic; Muck-Seler, Dorotea; Borovecki, Fran; Pivac, Nela

    2013-01-10

    Alcoholism is a chronic psychiatric disorder affecting neural pathways that regulate motivation, stress, reward and arousal. Brain-derived neurotrophic factor (BDNF) regulates mood, response to stress and interacts with neurotransmitters and stress systems involved in reward pathways and addiction. Aim of the study was to evaluate the association between a single nucleotide polymorphism (BDNF Val66Met or rs6265) and alcohol related phenotypes in Caucasian patients. In ethnically homogenous Caucasian subjects of the Croatian origin, the BDNF Val66Met genotype distribution was determined in 549 male and 126 female patients with alcohol dependence and in 655 male and 259 female healthy non-alcoholic control subjects. Based on the structured clinical interview, additional detailed clinical interview, the Brown-Goodwin Scale, the Hamilton Rating Scale for Depression and the Clinical Global Impression scores, alcoholic patients were subdivided into those with or without comorbid depression, aggression, delirium tremens, withdrawal syndrome, early/late onset of alcohol abuse, prior suicidal attempt during lifetime, current suicidal behavior, and severity of alcohol dependence. The results showed no significant association between BDNF Val66Met variants and alcohol dependence and/or any of the alcohol related phenotypes in either Caucasian women, or men, with alcohol dependence. There are few limitations of the study. The overall study sample size was large (N=1589) but not well-powered to detect differences in BDNF Val66Met genotype distribution between studied groups. Healthy control women were older than female alcoholic patients. Only one BDNF polymorphism (rs6265) was studied. In conclusion, these data do not support the view that BDNF Val66Met polymorphism correlates with the specific alcohol related phenotypes in ethnically homogenous medication-free Caucasian subjects with alcohol dependence. PMID:23023098

  14. Method of withdrawing fuel rods

    International Nuclear Information System (INIS)

    Purpose: To facilitate the withdrawal of fuel rods from a fuel bundle by heating a lower tie plate. Constitution: A lower tie plate for a fuel bundle is disposed within a heating coil. Magnetic fluxes and eddy currents passing through the lower tie plate are induced by applying an alternating current to the heating coil to generate eddy current loss and hysteresis loss in the lower tie plate thereby generating heat to the inside of the lower tie plate per se with no external heating. The lower tie plate is heated in this way. Since the lower tie plate has a greater linear expansion coefficient than that of the lower end plug, a gap is resulted at the engaging portion between the lower tie plate and the lower end plug, by which the fastening of the lower end plug is released to facilitate the withdrawal of the fuel rod. (Yoshino, Y.)

  15. Neurotrophic factors and their receptors in human sensory neuropathies.

    Science.gov (United States)

    Anand, Praveen

    2004-01-01

    Neurotrophic factors may play key roles in pathophysiological mechanisms of human neuropathies. Nerve growth factor (NGF) is trophic to small-diameter sensory fibers and regulates nociception. This review focuses on sensory dysfunction and the potential of neurotrophic treatments. Genetic neuropathy. Mutations of the NGF high-affinity receptor tyrosine kinase A (Trk A) have been found in congenital insensitivity to pain and anhidrosis; these are likely to be partial loss-of-function mutations, as axon-reflex vasodilatation and sweating can be elicited albeit reduced, suggesting rhNGF could restore nociception in some patients. Leprous neuropathy. Decreased NGF in leprosy skin may explain cutaneous hypoalgesia even with inflammation and rhNGF may restore sensation, as spared nerve fibers show Trk A-staining. Diabetic neuropathy. NGF is depleted in early human diabetic neuropathy skin, in correlation with dysfunction of nociceptor fibers. We proposed rhNGF prophylaxis may prevent diabetic foot ulceration. Clinical trials have been disappointed, probably related to difficulty delivering adequate doses and need for multiple trophic factors. NGF and glial cell line-derived neurotrophic factor (GDNF) are both produced by basal keratinocytes and neurotrophin (NT-3) by suprabasal keratinocytes: relative mRNA expression was significantly lower in early diabetic neuropathy skin compared to controls, for NGF (P 0.05). Posttranslational modifications of mature and pro-NGF may also affect bioactivity and immunoreactivity. A 53 kD band that could correspond to a prepro-NGF-like molecule was reduced in diabetic skin. Traumatic neuropathy and pain. While NGF levels are acutely reduced in injured nerve trunks, neuropathic patients with chronic skin hyperalgesia and allodynia show marked local increases of NGF levels; here anti-NGF agents may provide analgesia. Physiological combinations of NGF, NT-3 and GDNF, to mimic a 'surrogate target organ', may provide a novel 'homeostatic

  16. Neonatal withdrawal syndrome: Case report

    Directory of Open Access Journals (Sweden)

    Radunović-Gojković Tatjana

    2009-01-01

    Full Text Available Introduction. Maternal drug abuse has increased over the past decade. It has a multiple negative influence on a pregnant woman, as well as her newborn. Practically, every drug taken during pregnancy crosses the placenta, and the developing fetus may also be affected by the effects of a drug. After delivery, an infant of a drug-abusing mother may potentially develop neonatal withdrawal syndrome. Existing studies on the neonatal effects of drug exposure in utero are subject to many factors. Many studies have relied on the history obtained from the mother, which is innacurate. Urine testing for drug abuse does not reflect exposure to a drug through pregnancy and does not provide quantitative information. Social and economic deprivation is common among drug abusers, and this factor has a major effect on long term studies of infant outcome. The purpose of this article is to underline the problems during management of a neonatal withdrawal syndrom, and growing incidence of it in our society. Case report. A case of an infant of a heroin-abusing mother is reported. Conclusion. It is very important to take care of an infant with neonatal withdrawal syndrome, but it is also of a great importance to supervise these children for a long period of time.

  17. Continued administration of ciliary neurotrophic factor protects mice from inflammatory pathology in experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Kuhlmann, Tanja; Remington, Leah; Cognet, Isabelle;

    2006-01-01

    Multiple sclerosis is an inflammatory disease of the central nervous system that leads to loss of myelin and oligodendrocytes and damage to axons. We show that daily administration (days 8 to 24) of murine ciliary neurotrophic factor (CNTF), a neurotrophic factor that has been described as a...

  18. [Extension of the concept of withdrawal signs].

    Science.gov (United States)

    Kato, Shin

    2015-12-01

    If the conditions including normal-dose dependence in which withdrawal signs are observed in the absence of definite psychic dependence are classified as dependence, this classification should be regarded as inappropriate extension of the concept of drug dependence. These conditions should be diagnosed as 'withdrawal' as specified by the DSM-5 or ICD-10. Advancements of research have clarified that an increased number of drugs cause withdrawal signs. Some Japanese researchers use the concept of 'withdrawal signs of psychic dependence.' Their definition of drug dependence and concept of withdrawal signs, however, are different from the definition established by the WHO and the researchers specializing in this field. Thus, the concept of 'withdrawal signs of psychic dependence' raises a lot of questions. PMID:26964289

  19. Brain-Derived Neurotrophic Factor in Chronic Periodontitis

    Directory of Open Access Journals (Sweden)

    Jôice Dias Corrêa

    2014-01-01

    Full Text Available Brain-derived neurotrophic factor (BDNF is a member of the neurotrophic factor family. Outside the nervous system, BDNF has been shown to be expressed in various nonneural tissues, such as periodontal ligament, dental pulp, and odontoblasts. Although a role for BDNF in periodontal regeneration has been suggested, a function for BDNF in periodontal disease has not yet been studied. The aim of this study was to analyze the BDNF levels in periodontal tissues of patients with chronic periodontitis (CP and periodontally healthy controls (HC. All subjects were genotyped for the rs4923463 and rs6265 BDNF polymorphisms. Periodontal tissues were collected for ELISA, myeloperoxidase (MPO, and microscopic analysis from 28 CP patients and 29 HC subjects. BDNF levels were increased in CP patients compared to HC subjects. A negative correlation was observed when analyzing concentration of BDNF and IL-10 in inflamed periodontium. No differences in frequencies of BDNF genotypes between CP and HC subjects were observed. However, BDNF genotype GG was associated with increased levels of BDNF, TNF-α, and CXCL10 in CP patients. In conclusion, BDNF seems to be associated with periodontal disease process, but the specific role of BDNF still needs to be clarified.

  20. Astrocytes produce an insulin-like neurotrophic factor

    International Nuclear Information System (INIS)

    They have previously reported that survival of dissociated neurons from fetal rat telencephalon plated at low density in serum-free, hormone-free defined medium is enhanced in the presence of insulin. In the absence of insulin a similar effect on neuronal survival is observed if cells are grown in medium conditioned by glial cells. The present study was carried out to characterize the insulin-like neurotrophic activity present in the glial conditioned medium (GLCM). Conditioned medium from confluent cultures of astrogial cells maintained in a serum free defined medium without insulin was collected every two or three days. A 5 to 30kDa fraction of this medium was obtained by filtering it sequentially through YM30 and YM5 membrane filters. Binding of 125I-insulin to high density neuronal cultures was inhibited 43% by this fraction. Radioimmunoassay for insulin indicated that 1-2 ng of immuno-reactive insulin were present per ml of GLCM. Immunosequestration of the factor by insulin antibodies bound to protein A agarose gel resulted in loss of neurotrophic activity of the 5 to 30 kDa fraction. These results indicate that cultured astrocytes produce a factor immunologically and biochemically similar to insulin. This factor enhances the survival of neurons in culture and may be important for their normal development and differentiation

  1. Withdrawal history, private information, and bank runs

    OpenAIRE

    Carlos Garriga; Chao Gu

    2012-01-01

    This paper provides a simple two-depositor, two-stage model to understand how a bank’s withdrawal history affects an individual’s decision about withdrawals, which could possibly trigger bank runs. Individual depositors have private information about their personal consumption types and receive noisy private signals about the quality of the bank’s portfolio. Depositors make publicly observable withdrawal decisions in sequence. Computed examples indicate that the optimal contract contingent on...

  2. Cannabis withdrawal in adolescent treatment seekers

    OpenAIRE

    Vandrey, Ryan; Budney, Alan J.; Kamon, Jody L.; Stanger, Catherine

    2004-01-01

    A valid cannabis withdrawal syndrome has been demonstrated in controlled studies with adult marijuana abusers, yet few published reports have examined cannabis withdrawal among adolescents. Adolescents presenting for outpatient substance abuse treatment, whose primary substance of abuse was cannabis, completed a questionnaire reporting the presence and severity of withdrawal symptoms during past periods of cannabis abstinence. Nearly two-thirds of the sample indicated that they had experience...

  3. 29 CFR 4219.12 - Employers liable upon mass withdrawal.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 9 2010-07-01 2010-07-01 false Employers liable upon mass withdrawal. 4219.12 Section 4219... Redetermination of Withdrawal Liability Upon Mass Withdrawal § 4219.12 Employers liable upon mass withdrawal. (a... experiences successive mass withdrawals, an employer that has been determined to be liable under this...

  4. NS-417, a novel compound with neurotrophic-like effects

    DEFF Research Database (Denmark)

    Dagø, Lone; Peters, Dan; Meyer, Morten;

    2002-01-01

    NS-417 (5-(4-Chlorophenyl)-8-methyl-6-7-8-9-tetrahydro-1-H-pyrrolo[3.2-h]isoquinoline-2,3-dione-3-oxim hydrochloric acid salt) belongs to a new chemical series of compounds. NS-417 rescued differentiated PC12 cells from death induced by withdrawal of serum and nerve growth factor. Furthermore, NS...

  5. Improving Nursing Knowledge of Alcohol Withdrawal

    Science.gov (United States)

    Berl, Kimberly; Collins, Michelle L.; Melson, Jo; Mooney, Ruth; Muffley, Cheryl; Wright-Glover, Angela

    2015-01-01

    Christiana Care Health System implemented a Care Management Guideline for Alcohol Withdrawal Symptom Management, which provided direction for inpatient screening for alcohol withdrawal risk, assessment, and treatment. Nurses educated on its use expressed confusion with the use of the assessment tools, pharmacokinetics, and pathophysiology of alcohol withdrawal and delirium tremens. Reeducation was provided by nursing professional development specialists. Pre- and postsurveys revealed that nurses were more confident in caring for patients with alcohol withdrawal. (See CE Video, Supplemental Digital Content 1, http://links.lww.com/JNPD/A9) PMID:25816126

  6. Oxidative stress during alcohol withdrawal and its relationship with withdrawal severity

    Directory of Open Access Journals (Sweden)

    Ramamourty Parthasarathy

    2015-01-01

    Full Text Available Background: Oxidative parameters are altered during alcohol withdrawal and are said to contribute towards withdrawal symptoms in alcoholic patients. Aims: To study levels of five selected oxidative parameters during alcohol withdrawal state and after treatment of the withdrawal state and to assess the association of the oxidative parameters with the severity of alcohol withdrawal. Materials and Methods: This was a case-control study done in a De-addiction clinic of a tertiary teaching centre, Southern India. 50 persons having alcohol withdrawal symptoms were included. The oxidative stress parameters malondialdehyde, protein carbonyl, glutathione peroxidase, superoxide dismutase and catalase were assessed in during the withdrawal phase and again after the withdrawal had subsided. The same oxidative stress parameters were measured in the control group. Statistical analysis: Statistical analysis was done using SPSS version 17.0. One way ANOVA and Pearson correlation test were used for finding the association between the oxidative stress parameters levels and the severity of alcohol withdrawal. Multiple linear regression analysis done to predict variables associated with level of oxidative parameters. Results: During alcohol withdrawal the pro-oxidant malondialdehyde was elevated compared to that in the control group. Among the antioxidant enzymes the superoxide dismutase was higher and catalase was lower than the control group levels. After remission of the alcohol withdrawal both malondialdehyde remained higher and superoxide dismutase lower than in the control group. The levels of oxidative stress parameters not correlated with the severity of alcohol withdrawal. Conclusions: oxidative stress parameters show changes during alcohol withdrawal and during the remission of withdrawal. However, levels of oxidative stress parameters not correlated with the severity of withdrawal.

  7. Brain-derived neurotrophic factor inhibits glucose intolerance after cerebral ischemia

    Science.gov (United States)

    Shu, Xiaoliang; Zhang, Yongsheng; Xu, Han; Kang, Kai; Cai, Donglian

    2013-01-01

    Brain-derived neurotrophic factor is associated with the insulin signaling pathway and glucose tabolism. We hypothesized that expression of brain-derived neurotrophic factor and its receptor may be involved in glucose intolerance following ischemic stress. To verify this hypothesis, this study aimed to observe the changes in brain-derived neurotrophic factor and tyrosine kinase B receptor expression in glucose metabolism-associated regions following cerebral ischemic stress in mice. At day 1 after middle cerebral artery occlusion, the expression levels of brain-derived neurotrophic factor were significantly decreased in the ischemic cortex, hypothalamus, liver, skeletal muscle, and pancreas. The expression levels of tyrosine kinase B receptor were decreased in the hypothalamus and liver, and increased in the skeletal muscle and pancreas, but remained unchanged in the cortex. Intrahypothalamic administration of brain-derived neurotrophic factor (40 ng) suppressed the decrease in insulin receptor and tyrosine-phosphorylated insulin receptor expression in the liver and skeletal muscle, and inhibited the overexpression of gluconeogenesis-associated phosphoenolpyruvate carboxykinase and glucose-6-phosphatase in the liver of cerebral ischemic mice. However, serum insulin levels remained unchanged. Our experimental findings indicate that brain-derived neurotrophic factor can promote glucose metabolism, reduce gluconeogenesis, and decrease blood glucose levels after cerebral ischemic stress. The low expression of brain-derived neurotrophic factor following cerebral ischemia may be involved in the development of glucose intolerance. PMID:25206547

  8. Brain-derived neurotrophic factor inhibits glucose intolerance after cerebral ischemia***

    Institute of Scientific and Technical Information of China (English)

    Xiaoliang Shu; Yongsheng Zhang; Han Xu; Kai Kang; Donglian Cai

    2013-01-01

    Brain-derived neurotrophic factor is associated with the insulin signaling pathway and glucose tabolism. We hypothesized that expression of brain-derived neurotrophic factor and its receptor may be involved in glucose intolerance fol owing ischemic stress. To verify this hypothesis, this study aimed to observe the changes in brain-derived neurotrophic factor and tyrosine kinase B receptor expression in glucose metabolism-associated regions fol owing cerebral ischemic stress in mice. At day 1 after middle cerebral artery occlusion, the expression levels of brain-derived neurotrophic factor were significantly decreased in the ischemic cortex, hypothalamus, liver, skeletal muscle, and pancreas. The expression levels of tyrosine kinase B receptor were decreased in the hypothalamus and liver, and increased in the skeletal muscle and pancreas, but remained unchanged in the cortex. Intrahypothalamic administration of brain-derived neurotrophic factor (40 ng) suppressed the de-crease in insulin receptor and tyrosine-phosphorylated insulin receptor expression in the liver and skeletal muscle, and inhibited the overexpression of gluconeogenesis-associated phosphoenolpy-ruvate carboxykinase and glucose-6-phosphatase in the liver of cerebral ischemic mice. However, serum insulin levels remained unchanged. Our experimental findings indicate that brain-derived neurotrophic factor can promote glucose metabolism, reduce gluconeogenesis, and decrease blood glucose levels after cerebral ischemic stress. The low expression of brain-derived neurotrophic factor fol owing cerebral ischemia may be involved in the development of glucose intolerance.

  9. Acute withdrawal: diagnosis and treatment.

    Science.gov (United States)

    Brust, John C M

    2014-01-01

    Symptoms of alcohol withdrawal range in severity from mild "hangover" to fatal delirium tremens (DTs). Tremor, hallucinosis, and seizures usually occur within 48 hours of abstinence. Seizures tend to be generalized without focality, occurring singly or in a brief cluster, but status epilepticus is not unusual. DTs usually appears after 48 hours of abstinence and consists of marked inattentiveness, agitation, hallucinations, fluctuating level of alertness, marked tremulousness, and sympathetic overactivity. The mainstay of treatment for alcohol withdrawal is benzodiazepine pharmacotherapy, which can be used to control mild early symptoms, to prevent progression to DTs, or to treat DTs itself. Alternative less evidence-based pharmacotherapies include phenobarbital, anticonvulsants, baclofen, gamma-hydroxybutyric acid, beta-blockers, alpha-2-agonists, and N-methyl-d-aspartate receptor blockers. Treatment of DTs is a medical emergency requiring heavy sedation in an intensive care unit, with close attention to autonomic instability, fever, fluid loss, and electrolyte imbalance. Frequent comorbid disorders include hypoglycemia, liver failure, pancreatitis, sepsis, meningitis, intracranial hemorrhage, and Wernicke-Korsakoff syndrome. PMID:25307572

  10. 42 CFR 457.170 - Withdrawal process.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 4 2010-10-01 2010-10-01 false Withdrawal process. 457.170 Section 457.170 Public... Plans for Child Health Insurance Programs and Outreach Strategies § 457.170 Withdrawal process. (a... amendment, or any portion of a proposed State plan or plan amendment, at any time during the review...

  11. 76 FR 14592 - Safety Management System; Withdrawal

    Science.gov (United States)

    2011-03-17

    ..., and 145 RIN 2120-AJ15 Safety Management System; Withdrawal AGENCY: Federal Aviation Administration... (``product/ service providers'') to develop a Safety Management System (SMS). The FAA is withdrawing the... proposed rulemaking (ANPRM) published on July 23, 2009 (74 FR 36414) is withdrawn as of March 17, 2011....

  12. Peripheral blood brain-derived neurotrophic factor in bipolar disorder

    DEFF Research Database (Denmark)

    Munkholm, K; Vinberg, M; Kessing, L V

    2016-01-01

    Peripheral blood brain-derived neurotrophic factor (BDNF) has been proposed as a potential biomarker related to disease activity and neuroprogression in bipolar disorder, speculated to mirror alterations in brain expression of BDNF. The research area is rapidly evolving; however, recent...... investigations have yielded conflicting results with substantial variation in outcomes, highlighting the need to critically assess the state of current evidence. The aims of the study were to investigate differences in peripheral blood BDNF concentrations between bipolar disorder patients and healthy control...... subjects and between affective states in bipolar disorder patients, including assessment of the effect of treatment of acute episodes on BDNF levels. A systematic review of English language studies without considering publication status was conducted in PubMed (January 1950-November 2014), Embase (1974...

  13. Brain-derived neurotrophic factor (BDNF) and type 2 diabetes

    DEFF Research Database (Denmark)

    Krabbe, K. S.; Nielsen, A. R.; Krogh-Madsen, R.;

    2006-01-01

    Aims/hypothesis  Decreased levels of brain-derived neurotrophic factor (BDNF) have been implicated in the pathogenesis of Alzheimer's disease and depression. These disorders are associated with type 2 diabetes, and animal models suggest that BDNF plays a role in insulin resistance. We therefore...... and a hyperinsulinaemic-euglycaemic clamp. Results  Plasma levels of BDNF in Study 1 were decreased in humans with type 2 diabetes independently of obesity. Plasma BDNF was inversely associated with fasting plasma glucose, but not with insulin. No association was found between the BDNF G196A (Val66Met) polymorphism...... and diabetes or obesity. In Study 2 an output of BDNF from the human brain was detected at basal conditions. This output was inhibited when blood glucose levels were elevated. In contrast, when plasma insulin was increased while maintaining normal blood glucose, the cerebral output of BDNF was not inhibited...

  14. A novel neurotrophic drug for cognitive enhancement and Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Qi Chen

    Full Text Available Currently, the major drug discovery paradigm for neurodegenerative diseases is based upon high affinity ligands for single disease-specific targets. For Alzheimer's disease (AD, the focus is the amyloid beta peptide (Aß that mediates familial Alzheimer's disease pathology. However, given that age is the greatest risk factor for AD, we explored an alternative drug discovery scheme that is based upon efficacy in multiple cell culture models of age-associated pathologies rather than exclusively amyloid metabolism. Using this approach, we identified an exceptionally potent, orally active, neurotrophic molecule that facilitates memory in normal rodents, and prevents the loss of synaptic proteins and cognitive decline in a transgenic AD mouse model.

  15. Treatment of acute opioid withdrawal with ibogaine.

    Science.gov (United States)

    Alper, K R; Lotsof, H S; Frenken, G M; Luciano, D J; Bastiaans, J

    1999-01-01

    Ibogaine is an alkaloid with putative effect in acute opioid withdrawal. Thirty-three cases of treatments for the indication of opioid detoxification performed in non-medical settings under open label conditions are summarized involving an average daily use of heroin of .64 +/- .50 grams, primarily by the intravenous route. Resolution of the signs of opioid withdrawal without further drug seeking behavior was observed within 24 hours in 25 patients and was sustained throughout the 72-hour period of posttreatment observation. Other outcomes included drug seeking behavior without withdrawal signs (4 patients), drug abstinence with attenuated withdrawal signs (2 patients), drug seeking behavior with continued withdrawal signs (1 patient), and one fatality possibly involving surreptitious heroin use. The reported effectiveness of ibogaine in this series suggests the need for systematic investigation in a conventional clinical research setting. PMID:10506904

  16. Brain-derived neurotrophic factor: role in depression and suicide

    Directory of Open Access Journals (Sweden)

    Yogesh Dwivedi

    2009-08-01

    Full Text Available Yogesh DwivediPsychiatric Institute, Department of Psychiatry, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, USAAbstract: Depression and suicidal behavior have recently been shown to be associated with disturbances in structural and synaptic plasticity. Brain-derived neurotrophic factor (BDNF, one of the major neurotrophic factors, plays an important role in the maintenance and survival of neurons and in synaptic plasticity. Several lines of evidence suggest that BDNF is involved in depression, such that the expression of BDNF is decreased in depressed patients. In addition, antidepressants up-regulate the expression of BDNF. This has led to the proposal of the “neurotrophin hypothesis of depression”. Increasing evidence demonstrates that suicidal behavior is also associated with lower expression of BDNF, which may be independent from depression. Recent genetic studies also support a link of BDNF to depression/suicidal behavior. Not only BDNF, but abnormalities in its cognate receptor tropomycin receptor kinase B (TrkB and its splice variant (TrkB.T1 have also been reported in depressed/suicidal patients. It has been suggested that epigenetic modulation of the Bdnf and Trkb genes may contribute to their altered expression and functioning. More recently, impairment in the functioning of pan75 neurotrophin receptor has been reported in suicide brain specimens. pan75 neurotrophin receptor is a low-affinity neurotrophin receptor that, when expressed in conjunction with low availability of neurotropins/Trks, induces apoptosis. Overall, these studies suggest the possibility that BDNF and its mediated signaling may participate in the pathophysiology of depression and suicidal behavior. This review focuses on the critical evidence demonstrating the involvement of BDNF in depression and suicide.Keywords: BDNF, neurotrophins, p75NTR, Trk receptor, depression, antidepressants, suicide, genetics, epigenetics

  17. Secretion of nerve growth factor, brain-derived neurotrophic factor, and glial cell-line derived neurotrophic factor in co-culture of four cell types in cerebrospinal fluid-containing medium

    Institute of Scientific and Technical Information of China (English)

    Sanjiang Feng; Minghua Zhuang; Rui Wu

    2012-01-01

    The present study co-cultured human embryonic olfactory ensheathing cells, human Schwann cells, human amniotic epithelial cells and human vascular endothelial cells in complete culture medium- containing cerebrospinal fluid. Enzyme linked immunosorbent assay was used to detect nerve growth factor, brain-derived neurotrophic factor, and glial cell line-derived neurotrophic factor secretion in the supernatant of co-cultured cells. Results showed that the number of all cell types reached a peak at 7–10 days, and the expression of nerve growth factor, brain-derived neurotrophic factor, and glial cell line-derived neurotrophic factor peaked at 9 days. Levels of secreted nerve growth factor were four-fold higher than brain-derived neurotrophic factor, which was three-fold higher than glial cell line-derived neurotrophic factor. Increasing concentrations of cerebrospinal fluid (10%, 20% and 30%) in the growth medium caused a decrease of neurotrophic factor secretion. Results indicated co-culture of human embryonic olfactory ensheathing cells, human Schwann cells, human amniotic epithelial cells and human vascular endothelial cells improved the expression of nerve growth factor, brain-derived neurotrophic factor, and glial cell line-derived neurotrophic factor. The reduction of cerebrospinal fluid extravasation at the transplant site after spinal cord injury is beneficial for the survival and secretion of neurotrophic factors from transplanted cells.

  18. Brain-derived neurotrophic factor and substantia nigra dopaminergic neurons in Parkinson's disease

    Institute of Scientific and Technical Information of China (English)

    Haixia Ding; Meijiang Feng; Xinsheng Ding

    2008-01-01

    BACKGROUND:Parkinson's disease (PD) is a chronic, progressive neurodegenerative central nervous system disease which occurs in the substantia nigra-corpus striatum system. The main pathological feature of PD is selective dopaminergic neuronal loss with distinctive Lewy bodies in populations of surviving dopaminergic neurons. In the clinical and neuropathological diagnosis of PD, brain-derived neurotrophic factor mRNA expression in the substantia nigra pars compacta is reduced by 70%, and surviving dopaminergic neurons in the PD substantia nigra pars compacta express less brain-derived neurotrophic factor (BDNF) mRNA (20%) than their normal counterparts. In recent years, knowledge surrounding the relationship between neurotrophic factors and PD has increased, and detailed pathogenesis of the role of neurotrophic factors in PD becomes more important.

  19. Withdrawal from Genetic Counselling for Cancer

    Directory of Open Access Journals (Sweden)

    Bleiker Eveline

    2005-02-01

    Full Text Available Abstract Background A substantial minority of individuals who initially apply for genetic counselling for breast/ovarian cancer withdraw at an early stage from the counselling process. This study investigated the self-reported reasons for early withdrawal and the factors associated significantly with such withdrawal. Methods Self-report questionnaires were mailed to 83 women who had applied for genetic counselling for breast/ovarian cancer but who subsequently withdrew from the counselling process (the "withdrawers". A comparison group of 105 women who had completed the genetic counselling (the "attendees" received a similar questionnaire. The questionnaire assessed sociodemographic characteristics, reasons for applying for genetic counselling, general distress (MHI-5, cancer-specific distress (IES, and cancer worries. For those women who discontinued the counselling, reasons for withdrawal were also assessed. Results The primary reasons given for withdrawing from counselling were difficulties in anticipating the consequences of genetic counselling (28%, and worries about being unable to adequately cope with an unfavourable test result (20%. Compared to the attendees, the withdrawers were significantly younger, more frequently asymptomatic, more often the first and only member of the family to apply for counselling, and less worried about cancer. Current levels of cancer-specific distress and general distress were comparable between the two groups. Conclusion Younger women, those without a history of cancer, and those who are first in their family to apply are more likely to withdraw prematurely from genetic counselling for breast/ovarian cancer. These withdrawers have no elevated levels of distress. However, a substantial percentage of individuals discontinue counselling due to concerns about their (inability to cope with a possible unfavourable test outcome. This suggests that greater attention should be paid to ways of coping with test

  20. Quantifying the clinical significance of cannabis withdrawal.

    Directory of Open Access Journals (Sweden)

    David J Allsop

    Full Text Available BACKGROUND AND AIMS: Questions over the clinical significance of cannabis withdrawal have hindered its inclusion as a discrete cannabis induced psychiatric condition in the Diagnostic and Statistical Manual of Mental Disorders (DSM IV. This study aims to quantify functional impairment to normal daily activities from cannabis withdrawal, and looks at the factors predicting functional impairment. In addition the study tests the influence of functional impairment from cannabis withdrawal on cannabis use during and after an abstinence attempt. METHODS AND RESULTS: A volunteer sample of 49 non-treatment seeking cannabis users who met DSM-IV criteria for dependence provided daily withdrawal-related functional impairment scores during a one-week baseline phase and two weeks of monitored abstinence from cannabis with a one month follow up. Functional impairment from withdrawal symptoms was strongly associated with symptom severity (p=0.0001. Participants with more severe cannabis dependence before the abstinence attempt reported greater functional impairment from cannabis withdrawal (p=0.03. Relapse to cannabis use during the abstinence period was associated with greater functional impairment from a subset of withdrawal symptoms in high dependence users. Higher levels of functional impairment during the abstinence attempt predicted higher levels of cannabis use at one month follow up (p=0.001. CONCLUSIONS: Cannabis withdrawal is clinically significant because it is associated with functional impairment to normal daily activities, as well as relapse to cannabis use. Sample size in the relapse group was small and the use of a non-treatment seeking population requires findings to be replicated in clinical samples. Tailoring treatments to target withdrawal symptoms contributing to functional impairment during a quit attempt may improve treatment outcomes.

  1. Continuous Brain-derived Neurotrophic Factor (BDNF) Infusion After Methylprednisolone Treatment in Severe Spinal Cord Injury

    OpenAIRE

    Kim, Daniel H.; Jahng, Tae-Ahn

    2004-01-01

    Although methylprednisolone (MP) is the standard of care in acute spinal cord injury (SCI), its functional outcome varies in clinical situation. Recent report demonstrated that MP depresses the expression of growth-promoting neurotrophic factors after acute SCI. The present study was designed to investigate whether continuous infusion of brain-derived neurotrophic factor (BDNF) after MP treatment promotes functional recovery in severe SCI. Contusion injury was produced at the T10 vertebral le...

  2. Resveratrol Produces Neurotrophic Effects on Cultured Dopaminergic Neurons through Prompting Astroglial BDNF and GDNF Release

    OpenAIRE

    Feng Zhang; Yan-Ying Wang; Hang Liu; Yuan-Fu Lu; Qin Wu; Jie Liu; Jing-Shan Shi

    2012-01-01

    Increasing evidence indicated astroglia-derived neurotrophic factors generation might hold a promising therapy for Parkinson’s disease (PD). Resveratrol, naturally present in red wine and grapes with potential benefit for health, is well known to possess a number of pharmacological activities. Besides the antineuroinflammatory properties, we hypothesized the neuroprotective potency of resveratrol is partially due to its additional neurotrophic effects. Here, primary rat midbrain neuron-glia c...

  3. Transfection of the glial cell line-derived neurotrophic factor gene promotes neuronal differentiation

    OpenAIRE

    Du, Jie; Gao, Xiaoqing; Deng, Li; Chang, Nengbin; Xiong, Huailin; Zheng, Yu

    2014-01-01

    Glial cell line-derived neurotrophic factor recombinant adenovirus vector-transfected bone marrow mesenchymal stem cells were induced to differentiate into neuron-like cells using inductive medium containing retinoic acid and epidermal growth factor. Cell viability, microtubule-associated protein 2-positive cell ratio, and the expression levels of glial cell line-derived neurotrophic factor, nerve growth factor and growth-associated protein-43 protein in the supernatant were significantly hig...

  4. Continued Administration of Ciliary Neurotrophic Factor Protects Mice from Inflammatory Pathology in Experimental Autoimmune Encephalomyelitis

    OpenAIRE

    Kuhlmann, Tanja; Remington, Leah; Cognet, Isabelle; Bourbonniere, Lyne; Zehntner, Simone; Guilhot, Florence; Herman, Alexandra; Guay-Giroux, Angélique; Antel, Jack P.; Owens, Trevor; Gauchat, Jean-François

    2006-01-01

    Multiple sclerosis is an inflammatory disease of the central nervous system that leads to loss of myelin and oligodendrocytes and damage to axons. We show that daily administration (days 8 to 24) of murine ciliary neurotrophic factor (CNTF), a neurotrophic factor that has been described as a survival and differentiation factor for neurons and oligodendrocytes, significantly ameliorates the clinical course of a mouse model of multiple sclerosis. In the acute phase of experimental autoimmune en...

  5. Sox10 regulates ciliary neurotrophic factor gene expression in Schwann cells

    OpenAIRE

    Ito, Yasuhiro; Wiese, Stefan; Funk, Natalja; Chittka, Alexandra; Rossoll, Wilfried; Bömmel, Heike; Watabe, Kazuhiko; Wegner, Michael; Sendtner, Michael

    2006-01-01

    Ciliary neurotrophic factor (Cntf) plays an essential role in postnatal maintenance of spinal motoneurons. Whereas the expression of this neurotrophic factor is low during embryonic development, it is highly up-regulated after birth in myelinating Schwann cells of rodents. To characterize the underlying transcriptional mechanisms, we have analyzed and compared the effects of various glial transcription factors. In contrast to Pit-1, Oct-1, Unc-86 homology region (POU) domain class 3, transcri...

  6. Association analysis between polymorphisms in the conserved dopamine neurotrophic factor (CDNF) gene and cocaine dependence

    OpenAIRE

    Lohoff, Falk W.; Bloch, Paul J.; Ferraro, Thomas N.; Berrettini, Wade H.; Pettinati, Helen M.; Dackis, Charles A.; O’Brien, Charles P.; Kampman, Kyle M.; Oslin, David W

    2009-01-01

    Cocaine induced neuroplasticity changes in the mesocorticolimbic dopamine systems are thought to be involved in the pathophysiology of cocaine dependence. Since neurotrophic factors have been observed to prevent/reverse and mimic cocaine-induced neurobiological changes in the brain, related genes are plausible candidates for susceptibility to cocaine dependence. The novel conserved dopamine neurotrophic factor protein (CDNF) promotes the survival, growth, and function of dopamine-specific neu...

  7. Decreased Cerebrovascular Brain-Derived Neurotrophic Factor–Mediated Neuroprotection in the Diabetic Brain

    OpenAIRE

    Hayakawa, Kazhuhide; Navaratna, Deepti; Guo, Shu-Zhen; WANG, XIAOYING; Gerhardinger, Chiara; Lo, Eng H.

    2011-01-01

    Objective: Diabetes is an independent risk factor for stroke. However, the underlying mechanism of how diabetes confers that this risk is not fully understood. We hypothesize that secretion of neurotrophic factors by the cerebral endothelium, such as brain-derived neurotrophic factor (BDNF), is suppressed in diabetes. Consequently, such accrued neuroprotective deficits make neurons more vulnerable to injury. Research Design and Methods: We examined BDNF protein levels in a streptozotocin-indu...

  8. Involvement of Brain-Derived Neurotrophic Factor in Late-Life Depression

    OpenAIRE

    Dwivedi, Yogesh

    2013-01-01

    Brain-derived neurotrophic factor (BDNF), one of the major neurotrophic factors, plays an important role in the maintenance and survival of neurons, synaptic integrity, and synaptic plasticity. Evidence suggests that BDNF is involved in major depression, such that the level of BDNF is decreased in depressed patients and that antidepressants reverse this decrease. Stress, a major factor in depression, also modulates BDNF expression. These studies have led to the proposal of the neurotrophin hy...

  9. Changes in neurotrophic factors of adult rat laryngeal muscles during nerve regeneration.

    Science.gov (United States)

    Hernandez-Morato, Ignacio; Sharma, Sansar; Pitman, Michael J

    2016-10-01

    Injury to the recurrent laryngeal nerve (RLN) leads to the loss of ipsilateral laryngeal fold movement, with dysphonia, and occasionally dysphagia. Functional movement of the vocal folds is never restored due to misrouting of regenerating axons to agonist and antagonist laryngeal muscles. Changes of neurotrophic factor expression within denervated muscles occur after nerve injury and may influence nerve regeneration, axon guidance and muscle reinnervation. This study investigates the expression of certain neurotrophic factors in the laryngeal muscles during the course of axonal regeneration using RT-PCR. The timing of neurotrophic factor expression was correlated to the reinnervation of the laryngeal muscles by motor axons. Nerve Growth Factor (NGF), Brain-Derived Neurotrophic Factor (BDNF) and Netrin-1 (NTN-1) increased their expression levels in laryngeal muscles after nerve section and during regeneration of RLN. The upregulation of trophic factors returned to control levels following regeneration of RLN. The expression levels of the neurotrophic factors were correlated with the innervation of regenerating axons into the denervated muscles. The results suggest that certain neurotrophic factor expression is strongly correlated to the reinnervation pattern of the regenerating RLN. These factors may be involved in guidance and neuromuscular junction formation during nerve regeneration. In the future, their manipulation may enhance the selective reinnervation of the larynx. PMID:27421227

  10. Motor impairment: a new ethanol withdrawal phenotype in mice

    OpenAIRE

    Philibin, Scott D.; Cameron, Andy J.; Metten, Pamela; Crabbe, John C.

    2008-01-01

    Alcoholism is a complex disorder with genetic and environmental risk factors. The presence of withdrawal symptoms is one criterion for alcohol dependence. Genetic animal models have followed a reductionist approach by quantifying various effects of ethanol withdrawal separately. Different ethanol withdrawal symptoms may have distinct genetic etiologies, and therefore differentiating distinct neurobiological mechanisms related to separate signs of withdrawal would increase our understanding of...

  11. 19 CFR 144.27 - Withdrawal from warehouse by transferee.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Withdrawal from warehouse by transferee. 144.27...; DEPARTMENT OF THE TREASURY (CONTINUED) WAREHOUSE AND REWAREHOUSE ENTRIES AND WITHDRAWALS Transfer of Right To Withdraw Merchandise from Warehouse § 144.27 Withdrawal from warehouse by transferee. At any time...

  12. 2017-2022 Proposed Program - Withdrawal Areas

    Data.gov (United States)

    Bureau of Ocean Energy Management, Department of the Interior — This file represents the areas of the Outer Continental Shelf that have been withdrawn from disposition by leasing. The withdrawal of these areas prevents...

  13. Episodic Withdrawal Promotes Psychomotor Sensitization to Morphine

    OpenAIRE

    Rothwell, Patrick E.; Gewirtz, Jonathan C.; Thomas, Mark J

    2010-01-01

    The relative intermittency or continuity of drug delivery is a major determinant of addictive liability, and also influences the impact of drug exposure on brain function and behavior. Events that occur during the offset of drug action (ie, acute withdrawal) may have an important role in the consequences of intermittent drug exposure. We assessed whether recurrent episodes of acute withdrawal contribute to the development of psychomotor sensitization in rodents during daily morphine exposure....

  14. On Auctions with Withdrawable Winning Bids

    OpenAIRE

    Michael H. Rothkopf

    1991-01-01

    This paper considers sealed bidding in which bidders may submit two or more bids and after the bids are opened may, perhaps at a cost, withdraw bids that are more aggressive than would be necessary to win. Such withdrawal strategies are sometimes followed, but currently are surreptitious. However, legitimization of them would create potentially useful market mechanisms of potential interest to government agencies. These market mechanisms are also of theoretical interest since they are interme...

  15. Ciliary neurotrophic factor (CNTF) for human retinal degeneration: Phase I trial of CNTF delivered by encapsulated cell intraocular implants

    OpenAIRE

    Sieving, Paul A.; Caruso, Rafael C.; Tao, Weng; Coleman, Hanna R.; Thompson, Darby J. S.; Fullmer, Keri R.; Bush, Ronald A.

    2006-01-01

    Neurotrophic factors are agents with a promising ability to retard progression of neurodegenerative diseases and are effective in slowing photoreceptor degeneration in animal models of retinitis pigmentosa. Here we report a human clinical trial of a neurotrophic factor for retinal neurodegeneration. In this Phase I safety trial, human ciliary neurotrophic factor (CNTF) was delivered by cells transfected with the human CNTF gene and sequestered within capsules that were surgically implanted in...

  16. Alcohol Withdrawal Syndrome: Benzodiazepines and Beyond.

    Science.gov (United States)

    Sachdeva, Ankur; Choudhary, Mona; Chandra, Mina

    2015-09-01

    Alcohol dependence is an increasing and pervasive problem. Alcohol withdrawal symptoms are a part of alcohol dependence syndrome and are commonly encountered in general hospital settings, in most of the departments. Alcohol withdrawal syndrome ranges from mild to severe. The severe complicated alcohol withdrawal may present with hallucinations, seizures or delirium tremens. Benzodiazepines have the largest and the best evidence base in the treatment of alcohol withdrawal, and are considered the gold standard. Others, such as anticonvulsants, barbiturates, adrenergic drugs, and GABA agonists have been tried and have evidence. Supportive care and use of vitamins is essential in the management. Symptom triggered regime is favoured over fixed tapering dose regime, although monitoring through scales is cumbersome. This article aims to review the evidence base for appropriate clinical management of the alcohol withdrawal syndrome. We searched Pubmed for articles published in English on 'Alcohol withdrawal syndrome' in humans during the last 10 years. A total of 1182 articles came up. Articles not relevant to clinical utility and management were excluded based on the titles and abstract available. Full text articles, meta-analyses, systematic reviews and randomized controlled trials were obtained from this list and were considered for review. PMID:26500991

  17. Brain-derived neurotrophic factor, food intake regulation, and obesity.

    Science.gov (United States)

    Rosas-Vargas, Haydeé; Martínez-Ezquerro, José Darío; Bienvenu, Thierry

    2011-08-01

    Brain-derived neurotrophic factor (BDNF) is a neurotrophin that plays a fundamental role in development and plasticity of the central nervous system (CNS). It is currently recognized as a major participant in the regulation of food intake. Multiple studies have shown that different regulators of appetite such as leptin, insulin and pancreatic polypeptide (PP) potentially exert anorexigenic effects through BDNF. Low circulating levels of BDNF are associated with a higher risk of eating disorders such as anorexia nervosa (AN) and bulimia nervosa (BN). Strict food restriction reduces BDNF and may trigger binge-eating episodes and weight gain. The existence of mutations that cause haploinsufficiency of BDNF as well as some genetic variants, notably the BDNF p.Val66Met polymorphism, are also associated with the development of obese phenotypes and hyperphagia. However, association of the Met allele with AN and BN, which have different phenotypic characteristics, shows clearly the existence of other relevant factors that regulate eating behavior. This may, in part, be explained by the epigenetic regulation of BDNF through mechanisms like DNA methylation and histone acetylation. Environmental factors, primarily during early development, are crucial to the establishment of these stable but reversible changes that alter the transcriptional expression and are transgenerationally heritable, with potential concomitant effects on the development of eating disorders and body weight control. PMID:21945389

  18. Brain-derived neurotrophic factor and cocaine addiction

    Science.gov (United States)

    McGinty, Jacqueline F.; Whitfield, Timothy W.; Berglind, William J.

    2009-01-01

    The effects of brain-derived neurotrophic factor (BDNF) on cocaine-seeking are brain region-specific. Infusion of BDNF into subcortical structures, like the nucleus accumbens and ventral tegmental area, enhances cocaine-induced behavioral sensitization and cocaine seeking. Conversely, repeated administration of BDNF antiserum into the nucleus accumbens during chronic cocaine self-administration attenuates cocaine-induced reinstatement. In contrast, BDNF infusion into the dorsomedial prefrontal cortex immediately following a final session of cocaine self-administration attenuates relapse to cocaine seeking after abstinence, as well as cue- and cocaine prime-induced reinstatement of cocaine-seeking following extinction. BDNF-induced alterations in the ERK-MAP kinase cascade and in prefronto-accumbens glutamatergic transmission are implicated in BDNF’s ability to alter cocaine seeking. Within 22 hr after infusion into the prefrontal cortex, BDNF increases BDNF protein in prefrontal cortical targets, including nucleus accumbens, and restores cocaine-mediated decreases in phospho-ERK expression in the nucleus accumbens. Furthermore, three weeks after BDNF infusion in animals with a cocaine self-administration history, suppressed basal levels of glutamate are normalized and a cocaine-prime-induced increase in extracellular glutamate levels in the nucleus accumbens is prevented. Thus, BDNF may have local effects at the site of infusion and distal effects in target areas that are critical to mediating or preventing cocaine-induced dysfunctional neuroadaptations. PMID:19732758

  19. Nerve growth factor, brain-derived neurotrophic factor, and the chronobiology of mood: a new insight into the "neurotrophic hypothesis"

    Directory of Open Access Journals (Sweden)

    Tirassa P

    2015-10-01

    Full Text Available Paola Tirassa,1 Adele Quartini,2 Angela Iannitelli2–4 1National Research Council (CNR, Institute of Cell Biology and Neurobiology (IBCN, 2Department of Medical-Surgical Sciences and Biotechnologies, Faculty of Pharmacy and Medicine – "Sapienza" University of Rome, 3Italian Psychoanalytical Society (SPI, Rome, Italy; 4International Psychoanalytical Association (IPA, London, UKAbstract: The light information pathways and their relationship with the body rhythms have generated a new insight into the neurobiology and the neurobehavioral sciences, as well as into the clinical approaches to human diseases associated with disruption of circadian cycles. Light-based strategies and/or drugs acting on the circadian rhythms have widely been used in psychiatric patients characterized by mood-related disorders, but the timing and dosage use of the various treatments, although based on international guidelines, are mainly dependent on the psychiatric experiences. Further, many efforts have been made to identify biomarkers able to disclose the circadian-related aspect of diseases, and therefore serve as diagnostic, prognostic, and therapeutic tools in clinic to assess the different mood-related symptoms, including pain, fatigue, sleep disturbance, loss of interest or pleasure, appetite, psychomotor changes, and cognitive impairments. Among the endogenous factors suggested to be involved in mood regulation, the neurotrophins, nerve growth factor, and brain-derived neurotrophic factor show anatomical and functional link with the circadian system and mediate some of light-induced effects in brain. In addition, in humans, both nerve growth factor and brain-derived neurotrophic factor have showed a daily rhythm, which correlate with the morningness–eveningness dimensions, and are influenced by light, suggesting their potential role as biomarkers for chronotypes and/or chronotherapy. The evidences of the relationship between the diverse mood-related disorders

  20. Carisoprodol: abuse potential and withdrawal syndrome.

    Science.gov (United States)

    Reeves, Roy R; Burke, Randy S

    2010-03-01

    Carisoprodol (N-isopropyl-2 methyl-2-propyl-1,3-propanediol dicarbamate; N-isopropylmeprobamate) is a centrally acting skeletal muscle relaxant whose primary active metabolite is meprobamate, a substance with well established abuse potential similar to that of benzodiazepines. A number of reports show that carisoprodol has been abused for its sedative and relaxant effects, to augment or alter the effects of other drugs, and by the intentional combination of carisoprodol and other noncontrolled medications because of the relative ease (as compared to controlled substances) of obtaining prescriptions. The diversion and abuse of carisoprodol and its adverse health effects appear to have dramatically increased over the last several years. Clinicians have begun to see a withdrawal syndrome consisting of insomnia, vomiting, tremors, muscle twitching, anxiety, and ataxia in patients who abruptly cease intake of large doses of carisoprodol. Hallucinations and delusions may also occur. The withdrawal symptoms are very similar to those previously described for meprobamate withdrawal, suggesting that what may actually be occurring is withdrawal from meprobamate accumulated as a result of intake of excessive amounts of carisoprodol. However carisoprodol itself is capable of modulating GABA(A) function, and this may contribute both to the drugs abuse potential and to the occurrence of a withdrawal syndrome with abrupt cessation of intake. Carisoprodol has been classified as a controlled substance in several states in the US and restrictions on the use of the drug have been imposed in some European countries. Carisoprodol is metabolized to a controlled substance, has clear evidence of abuse potential and increasing incidence of abuse, and has shown evidence of a withdrawal syndrome with abrupt cessation from intake. This article will discuss the abuse potential of carisoprodol and the associated withdrawal syndrome, and consider implications for future use of the drug. PMID

  1. Intra-administration associations and withdrawal symptoms: morphine-elicited morphine withdrawal.

    Science.gov (United States)

    McDonald, Robert V; Siegel, Shepard

    2004-02-01

    On the basis of a conditioning analysis, some drug "withdrawal symptoms" are conditional responses elicited by stimuli paired with the drug effect. Prior demonstrations of conditional elicitation of withdrawal symptoms evaluated the role of environmental cues; however, pharmacological cues also typically signal a drug effect. Within each administration, early drug onset cues (DOCs) may become associated with the later, larger drug effect (intra-administration associations). This experiment evaluated the contribution of intra-administration associations to withdrawal symptoms. The results indicated that (a). 5 mg/kg morphine elicited behavioral and thermic withdrawal symptoms in rats previously injected on a number of occasions with 50 mg/kg morphine and that (b). DOC-elicited withdrawal symptoms are not a sensitized response to the opiate but rather an associative phenomenon. PMID:14769091

  2. Dopamine D3 receptor-preferring agonists induce neurotrophic effects on mesencephalic dopamine neurons.

    Science.gov (United States)

    Du, Fang; Li, Rui; Huang, Yuangui; Li, Xuping; Le, Weidong

    2005-11-01

    Anti-parkinsonian agents, pramipexole (PPX) and ropinirole (ROP), have been reported to possess neuroprotective properties, both in vitro and in vivo. The mechanisms underlying neuroprotection afforded by the D3-preferring receptor agonists remain poorly understood. The present study demonstrates that incubation of primary mesencephalic cultures with PPX and ROP or the conditioned medium from PPX- or ROP-treated primary cultures induced a marked increase in the number of dopamine (DA) neurons in the cultures. Similar effects can be observed after incubating with the conditioned medium derived from PPX- and ROP-treated substantia nigra astroglia. Meanwhile, PPX and ROP can protect the primary cells from insult of 1-methyl-4-phenylpyridinium (MPP+), the active metabolite of the neurotoxin 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP). Furthermore, the neurotrophic effects of PPX and ROP on mesencephalic dopamine neurons could be significantly blocked by D3 receptor antagonist, but not by D2 receptor antagonist. Moreover, we found that the levels of glial cell line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF) in the conditioned medium of mesencephalic cultures treated with PPX and ROP were significantly increased. Blocking GDNF and BDNF with the neutralizing antibodies, the neurotrophic effects of PPX and ROP were greatly diminished. These results suggest that D3 dopamine receptor-preferring agonists, PPX and ROP, exert neurotrophic effects on cultured DA neurons by modulating the production of endogenous GDNF and BDNF, which may participate in their neuroprotection. PMID:16307585

  3. Hyperbaric oxygen preserves neurotrophic activity of carbon monoxide-exposed astrocytes.

    Science.gov (United States)

    Jurič, Damijana M; Šuput, Dušan; Brvar, Miran

    2016-06-24

    In astrocytes, carbon monoxide (CO) poisoning causes oxidative stress and mitochondrial dysfunction accompanied by caspase and calpain activation. Impairment in astrocyte function can be time-dependently reduced by hyperbaric (3bar) oxygen (HBO). Due to the central role of astrocytes in maintaining neuronal function by offering neurotrophic support we investigated the hypothesis that HBO therapy may exert beneficial effect on acute CO poisoning-induced impairment in intrinsic neurotrophic activity. Exposure to 3000ppm CO in air followed by 24-72h of normoxia caused a progressive decline of gene expression, synthesis and secretion of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) to different extent. 1h treatment with 100% oxygen disclosed a pressure- and time-dependent efficacy in preserving astrocytic neurotrophic support. The beneficial effect was most evident when the astrocytes were exposed to HBO 1-5h after exposure to CO. The results further support an active role of hyperbaric, not normobaric, oxygenation in reducing dysfunction of astrocytes after acute CO poisoning. By preserving endogenous neurotrophic activity HBO therapy might promote neuronal protection and thus prevent the occurrence of late neuropsychological sequelae. PMID:27113706

  4. Effect of neurotrophic factor, MDP, on rats’ nerve regeneration

    Directory of Open Access Journals (Sweden)

    A.A. Fornazari

    2011-04-01

    Full Text Available Our objective was to determine the immune-modulating effects of the neurotrophic factor N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP on median nerve regeneration in rats. We used male Wistar rats (120-140 days of age, weighing 250-332 g and compared the results of three different techniques of nerve repair: 1 epineural neurorrhaphy using sutures alone (group S - 10 rats, 2 epineural neurorrhaphy using sutures plus fibrin tissue adhesive (FTA; group SF - 20 rats, and 3 sutures plus FTA, with MDP added to the FTA (group SFM - 20 rats. Functional assessments using the grasp test were performed weekly for 12 weeks to identify recovery of flexor muscle function in the fingers secondary to median nerve regeneration. Histological analysis was also utilized. The total number and diameter of myelinated fibers were determined in each proximal and distal nerve segment. Two indices, reported as percentage, were calculated from these parameters, namely, the regeneration index and the diameter change index. By the 8th week, superiority of group SFM over group S became apparent in the grasping test (P = 0.005. By the 12th week, rats that had received MDP were superior in the grasping test compared to both group S (P < 0.001 and group SF (P = 0.001. Moreover, group SF was better in the grasping test than group S (P = 0.014. However, no significant differences between groups were identified by histological analysis. In the present study, rats that had received MDP obtained better function, in the absence of any significant histological differences.

  5. Treatment of diabetic polyneuropathy with the neurotrophic peptide ORG 2766.

    Science.gov (United States)

    Valk, G D; Kappelle, A C; Tjon-A-Tsien, A M; Bravenboer, B; Bakker, K; Michels, R P; Groenhout, C M; Bertelsmann, F W

    1996-03-01

    The efficacy of the neurotrophic peptide ORG 2766 in diabetic patients with polyneuropathy was evaluated in a double-blind, placebo-controlled, multicentre trial. One hundred and twenty four patients were randomised in five groups to receive 0.1, 0.4, 2 or 5 mg ORG 2766 or placebo, once daily, administered subcutaneously 52 weeks. Thermal discrimination thresholds (TDT) and vibration perception thresholds (VPT), motor and sensory nerve conduction velocity, Hoffmann reflex, heart rate variation during deep breathing and heart rate response after standing up, neurological examination score and neuropathic symptom score were determined at baseline and after 17, 34 and 52 weeks of treatment. Of the nerve function indices studied, at week 52 the TDTwarmth of the hand in the ORG 2766 0.1, 0.4 and 5 mg groups and the TDTcold of the foot in the ORG 2766 0.1 and 0.4 mg groups significantly improved compared with placebo. Further significant improvement as compared with placebo was observed in the paraesthesia score at week 34 and week 52 in the ORG 2766 2 mg group. Only at week 34 had both the heartbeat variation during deep breathing and the VPT of the foot in the ORG 2766 0.1 mg group improved significantly, compared with placebo. No further statistically significant differences were observed at time for the other measures. No adverse reactions were observed. The only recorded drug-induced side effect was pain at the injection site. Taking all measures of efficacy into account, the statistically significant results observed did not show consistency within each measure. Therefore, it is concluded that ORG 2766, in contrast to earlier reports, is not effective in treating diabetic polyneuropathy. PMID:8936356

  6. Inpatient management of acute alcohol withdrawal syndrome.

    Science.gov (United States)

    Perry, Elizabeth C

    2014-05-01

    Alcohol withdrawal is a common condition encountered in the hospital setting after abrupt discontinuation of alcohol in an alcohol-dependent individual. Patients may present with mild symptoms of tremulousness and agitation or more severe symptoms including withdrawal seizures and delirium tremens. Management revolves around early identification of at-risk individuals and symptom assessment using a validated tool such as the revised Clinical Institute Withdrawal Assessment for Alcohol score. Benzodiazepines remain the mainstay of treatment and can be administered using a front-loading, fixed-dose, or symptom-triggered approach. Long-acting benzodiazepines such as chlordiazepoxide or diazepam are commonly used and may provide a smoother withdrawal than shorter-acting benzodiazepines, but there are no data to support superiority of one benzodiazepine over another. Elderly patients or those with significant liver disease may have increased accumulation and decreased clearance of the long-acting benzodiazepines, and lorazepam or oxazepam may be preferred in these patients. Patients with symptoms refractory to high doses of benzodiazepines may require addition of a rescue medication such as phenobarbital, propofol or dexmedetomidine. Anticonvulsants (carbamazepine, valproate, gabapentin) may have a role in the management of mild to moderate withdrawal. Other medications such as β-antagonists or neuroleptics may offer additional benefit in select patients but should not be used a monotherapy. PMID:24781751

  7. Cyclosporine alters opiate withdrawal in rodents.

    Science.gov (United States)

    Dafny, N; Wagle, V G; Drath, D B

    1985-05-01

    Opiates exert numerous effects on all levels of the central nervous system with tolerance, physical dependence and withdrawal being characteristics of this drug class. The degree of dependence is directly correlated to the intensity of withdrawal. Therefore, success in modifying the withdrawal syndrome may shed light on the dynamics of opiate addiction. The present study demonstrates that cyclosporine, a widely used immunosuppressive drug, considerably modified the behavioral signs of a naloxone-induced abstinence syndrome in morphine-addicted rats. In previous experiments, alpha-interferon has shown similar results. The similarity in actions of these two immunomodulator drugs is discussed and we suggest that opiate addiction may involve the immune system. PMID:4039025

  8. Codon optimization and factorial screening for enhanced soluble expression of human ciliary neurotrophic factor in Escherichia coli

    OpenAIRE

    Itkonen, Jaakko M; Urtti, Arto; Bird, Louise E.; Sarkhel, Sanjay

    2014-01-01

    Abstract Background Neurotrophic factors influence survival, differentiation, proliferation and death of neuronal cells within the central nervous system. Human ciliary neurotrophic factor (hCNTF) has neuroprotective properties and is also known to influence energy balance. Consequently, hCNTF has potential therapeutic applications in neurodegenerative, obesity and diabetes relat...

  9. Flavonoids Induce the Synthesis and Secretion of Neurotrophic Factors in Cultured Rat Astrocytes: A Signaling Response Mediated by Estrogen Receptor

    Directory of Open Access Journals (Sweden)

    Sherry L. Xu

    2013-01-01

    Full Text Available Neurotrophic factors are playing vital roles in survival, growth, and function of neurons. Regulation of neurotrophic factors in the brain has been considered as one of the targets in developing drug or therapy against neuronal disorders. Flavonoids, a family of multifunctional natural compounds, are well known for their neuronal beneficial effects. Here, the effects of flavonoids on regulating neurotrophic factors were analyzed in cultured rat astrocytes. Astrocyte is a major secreting source of neurotrophic factors in the brain. Thirty-three flavonoids were screened in the cultures, and calycosin, isorhamnetin, luteolin, and genistein were identified to be highly active in inducing the synthesis and secretion of neurotrophic factors, including nerve growth factor (NGF, glial-derived neurotrophic factor (GDNF, and brain-derived neurotrophic factor (BDNF. The inductions were in time- and dose-dependent manners. In cultured astrocytes, the phosphorylation of estrogen receptor was triggered by application of flavonoids. The phosphorylation was blocked by an inhibitor of estrogen receptor, which in parallel reduced the flavonoid-induced expression of neurotrophic factors. The results proposed the role of flavonoids in protecting brain diseases, and therefore these flavonoids could be developed for health food supplement for patients suffering from neurodegenerative diseases.

  10. Children's judgements of social withdrawal behaviours.

    Science.gov (United States)

    Watling, Dawn

    2015-06-01

    Ding et al. (Brit. J. Dev. Psychol., 2015; 33, 159-173) demonstrated that Chinese children discriminate between the three subtypes of social withdrawal: Shyness, unsociability, and social avoidance. This commentary on the Ding et al.'s paper highlights the need to further explore the following: (1) children's understanding of the implications of being shy, unsociable, or socially avoidant, including assessing these which we know are associated with outcomes for socially withdrawn children; (2) what additional subtypes might exist naturally within the Chinese culture; and (3) consider the implications of social withdrawal on children's developing social skills. PMID:25853224

  11. Mesencephalic Astrocyte-derived Neurotrophic Factor (MANF) Has a Unique Mechanism to Rescue Apoptotic Neurons

    OpenAIRE

    Hellman, M.; Arumae, U.; Yu, L.-y.; Lindholm, P.; Peranen, J.; Saarma, M.; Permi, P. (Perttu)

    2010-01-01

    Mesencephalic astrocyte-derived neurotrophic factor (MANF) protects neurons and repairs the Parkinson disease-like symptoms in a rat 6-hydroxydopamine model. We show a three-dimensional solution structure of human MANF that differs drastically from other neurotrophic factors. Remarkably, the C-terminal domain of MANF (C-MANF) is homologous to the SAP domain of Ku70, a well known inhibitor of proapoptotic Bax (Bcl-2-associated X protein). Cellular studies confirm that MANF and C-MANF protect n...

  12. 17 CFR 41.47 - Withdrawal of margin.

    Science.gov (United States)

    2010-04-01

    ... PRODUCTS Customer Accounts and Margin Requirements § 41.47 Withdrawal of margin. (a) By the customer... after such withdrawal is sufficient to satisfy the required margin for the security futures and...

  13. 48 CFR 14.303 - Modification or withdrawal of bids.

    Science.gov (United States)

    2010-10-01

    ... CONTRACTING METHODS AND CONTRACT TYPES SEALED BIDDING Submission of Bids 14.303 Modification or withdrawal of... for the bid. (c) Upon withdrawal of an electronically transmitted bid, the data received shall not...

  14. Brain derived neurotrophic factor in newly diagnosed diabetes and prediabetes.

    Science.gov (United States)

    Liu, Wei; Han, Xueyao; Zhou, Xianghai; Zhang, Simin; Cai, Xiaoling; Zhang, Lihua; Li, Yufeng; Li, Meng; Gong, Siqian; Ji, Linong

    2016-07-01

    Brain derived neurotrophic factor (BDNF) is thought to play an important role in glucose metabolism, but the exact mechanism has not been elucidated. The aim was to assess differences in serum BDNF levels across individuals with varying levels of glucose tolerance, and the association of serum BDNF levels with genetic variants and DNA methylation. Participants were selected from an ongoing population-based cohort study in rural China. In a randomly selected subsample of healthy participants (n = 33 males, n = 52 female), we assessed serum BDNF and in n = 50 of these, also DNA methylation. In a second subsample (all women; n = 28 with diabetes, n = 104 with prediabetes, and n = 105 age- and body mass index (BMI)-matched controls), we assessed serum BDNF and genetic variants. In a third subsample (all with diabetes; n = 7 normal BMI + low insulin level, n = 9 normal BMI + high insulin level, n = 9 obese + high insulin level), we assessed DNA methylation. Compared to age- and BMI-matched controls (24.71 (IQR, 20.44, 29.80) ng/ml), serum BDNF was higher in participants with prediabetes (27.38 (IQR, 20.64, 34.29) ng/ml), but lower in those with diabetes (23.40 (IQR, 18.12, 30.34) ng/ml) (P < 0.05). Two genetic variants near BDNF (rs4074134 and rs6265) were confirmed to be associated with BMI. BDNF CpG-6 methylation was positively associated with waist-to-hip ratio (P < 0.05). Furthermore, hyper-methylation in this site was found in participants with diabetes and high fasting insulin levels compared to those with diabetes and low fasting insulin levels, regardless of BMI status (P < 0.001 and P = 0.001, respectively). Observed differences in serum BDNF levels, genetic variants, and DNA methylation patterns across different glucose metabolic state suggest that BDNF may be involved in the pathophysiological process of insulin resistance and type 2 diabetes. PMID:27062899

  15. Tobacco Withdrawal Symptoms Mediate Motivation to Reinstate Smoking During Abstinence

    OpenAIRE

    Aguirre, Claudia; Madrid, Jillian; Leventhal, Adam M.

    2015-01-01

    Withdrawal-based theories of addiction hypothesize that motivation to reinstate drug use following acute abstinence is mediated by withdrawal symptoms. Experimental tests of this hypothesis in the tobacco literature are scant and may be subject to methodological limitations. This study utilized a robust within-subject laboratory experimental design to investigate the extent to which composite tobacco withdrawal symptomatology level and three unique withdrawal components (i.e., low positive af...

  16. Improving Nursing Knowledge of Alcohol Withdrawal: Second Generation Education Strategies.

    Science.gov (United States)

    Berl, Kimberly; Collins, Michelle L; Melson, Jo; Mooney, Ruth; Muffley, Cheryl; Wright-Glover, Angela

    2015-01-01

    Christiana Care Health System implemented a Care Management Guideline for Alcohol Withdrawal Symptom Management, which provided direction for inpatient screening for alcohol withdrawal risk, assessment, and treatment. Nurses educated on its use expressed confusion with the use of the assessment tools, pharmacokinetics, and pathophysiology of alcohol withdrawal and delirium tremens. Reeducation was provided by nursing professional development specialists. Pre- and postsurveys revealed that nurses were more confident in caring for patients with alcohol withdrawal. PMID:25816126

  17. 19 CFR 144.36 - Withdrawal for transportation.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Withdrawal for transportation. 144.36 Section 144... § 144.36 Withdrawal for transportation. (a) Time limit. Merchandise may be withdrawn from warehouse for transportation to another port of entry if withdrawal for consumption or exportation can be accomplished at...

  18. Teachers' Withdrawal Behaviors and Their Relationship with Work Ethic

    Science.gov (United States)

    Erdemli, Özge

    2015-01-01

    Problem Situation: People experience ups and downs in their job satisfaction and motivation levels at different points of their work lives for various reasons. One of the outputs of low job satisfaction and motivation is defined as "withdrawal behaviors" in the literature. Withdrawal behaviors are any employee behavior of withdrawal from…

  19. Sodium Valproate Withdrawal Correlates with Reduced Aggression

    Science.gov (United States)

    Pritchard, Duncan; Hoerger, Marguerite; Dyer, Tim; Graham, Nicola; Penney, Heather; Mace, F. Charles

    2014-01-01

    People with learning disabilities are sometimes prescribed psychotropic medication to help manage their challenging behaviour. This case study describes how a multicomponent behavioural intervention in conjunction with the systematic withdrawal of sodium valproate was strongly correlated with reduced aggression. No symptoms of bipolar disorder or…

  20. Design of withdrawal-weighted SAW filters.

    Science.gov (United States)

    Lee, Youngjin; Lee, Seunghee; Roh, Yongrae

    2002-03-01

    This paper presents a new design algorithm for a withdrawal-weighted surface acoustic wave (SAW) transversal filter. The proposed algorithm is based on the effective transmission loss theory and a delta function model of a SAW transversal filter. The design process consists of three steps, which eventually determine eight geometrical design parameters for the filter in order to satisfy given performance specifications. First, the number of fingers in the input and output interdigital transducers (IDTs), plus their geometrical sizes is determined using the insertion loss specification. Second, the number and positions of the polarity reverses in the output IDT are determined using the bandwidth and ripple specifications. Third, the number and position for withdrawing and switching specific fingers in the output IDT and attached electrode area are determined to achieve the desired sidelobe level. The efficiency of the technique is illustrated using a sample design of an IF filter consisting of a uniform input IDT and withdrawal-weighted output IDT. The proposed algorithm is distinct from conventional techniques in that it can optimize the structural geometry of a withdrawal-weighted SAW filter in a direct manner by considering all the performance specifications simultaneously. PMID:12322883

  1. 31 CFR 103.84 - Withdrawing requests.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Withdrawing requests. 103.84 Section 103.84 Money and Finance: Treasury Regulations Relating to Money and Finance FINANCIAL RECORDKEEPING AND REPORTING OF CURRENCY AND FOREIGN TRANSACTIONS Administrative Rulings § 103.84...

  2. Gender and environmental effects on regional brain-derived neurotrophic factor expression after experimental traumatic brain injury.

    Science.gov (United States)

    Chen, X; Li, Y; Kline, A E; Dixon, C E; Zafonte, R D; Wagner, A K

    2005-01-01

    Alterations in brain-derived neurotrophic factor expression have been reported in multiple brain regions acutely after traumatic brain injury, however neither injury nor post-injury environmental enrichment has been shown to affect hippocampal brain-derived neurotrophic factor gene expression in male rats chronically post-injury. Studies have demonstrated hormone-related neuroprotection for female rats after traumatic brain injury, and estrogen and exercise both influence brain-derived neurotrophic factor levels. Despite recent studies suggesting that exposure post-traumatic brain injury to environmental enrichment improves cognitive recovery in male rats, we have shown that environmental enrichment mediated improvements with spatial learning are gender specific and only positively affect males. Therefore the purpose of this study was to evaluate the effect of gender and environmental enrichment on chronic post-injury cortical and hippocampal brain-derived neurotrophic factor protein expression. Sprague-Dawley male and cycling female rats were placed into environmental enrichment or standard housing after controlled cortical impact or sham surgery. Four weeks post-surgery, hippocampal and frontal cortex brain-derived neurotrophic factor expression were examined using Western blot. Results revealed significant increases in brain-derived neurotrophic factor expression in the frontal cortex ipsilateral to injury for males (P=0.03). Environmental enrichment did not augment this effect. Neither environmental enrichment nor injury significantly affected cortical brain-derived neurotrophic factor expression for females. In the hippocampus ipsilateral to injury brain-derived neurotrophic factor expression for both males and females was half (49% and 51% respectively) of that observed in shams housed in the standard environment. For injured males, there was a trend in this region for environmental enrichment to restore brain-derived neurotrophic factor levels to sham values

  3. Neuroimmune Regulation of GABAergic Neurons Within the Ventral Tegmental Area During Withdrawal from Chronic Morphine.

    Science.gov (United States)

    Taylor, Anna M W; Castonguay, Annie; Ghogha, Atefeh; Vayssiere, Pia; Pradhan, Amynah A A; Xue, Lihua; Mehrabani, Sadaf; Wu, Juli; Levitt, Pat; Olmstead, Mary C; De Koninck, Yves; Evans, Christopher J; Cahill, Catherine M

    2016-03-01

    Opioid dependence is accompanied by neuroplastic changes in reward circuitry leading to a negative affective state contributing to addictive behaviors and risk of relapse. The current study presents a neuroimmune mechanism through which chronic opioids disrupt the ventral tegmental area (VTA) dopaminergic circuitry that contributes to impaired reward behavior. Opioid dependence was induced in rodents by treatment with escalating doses of morphine. Microglial activation was observed in the VTA following spontaneous withdrawal from chronic morphine treatment. Opioid-induced microglial activation resulted in an increase in brain-derived neurotrophic factor (BDNF) expression and a reduction in the expression and function of the K(+)Cl(-) co-transporter KCC2 within VTA GABAergic neurons. Inhibition of microglial activation or interfering with BDNF signaling prevented the loss of Cl(-) extrusion capacity and restored the rewarding effects of cocaine in opioid-dependent animals. Consistent with a microglial-derived BDNF-induced disruption of reward, intra-VTA injection of BDNF or a KCC2 inhibitor resulted in a loss of cocaine-induced place preference in opioid-naïve animals. The loss of the extracellular Cl(-) gradient undermines GABAA-mediated inhibition, and represents a mechanism by which chronic opioid treatments can result in blunted reward circuitry. This study directly implicates microglial-derived BDNF as a negative regulator of reward in opioid-dependent states, identifying new therapeutic targets for opiate addictive behaviors. PMID:26202104

  4. Neuroimmune Regulation of GABAergic Neurons Within the Ventral Tegmental Area During Withdrawal from Chronic Morphine

    Science.gov (United States)

    Taylor, Anna M W; Castonguay, Annie; Ghogha, Atefeh; Vayssiere, Pia; Pradhan, Amynah A A; Xue, Lihua; Mehrabani, Sadaf; Wu, Juli; Levitt, Pat; Olmstead, Mary C; De Koninck, Yves; Evans, Christopher J; Cahill, Catherine M

    2016-01-01

    Opioid dependence is accompanied by neuroplastic changes in reward circuitry leading to a negative affective state contributing to addictive behaviors and risk of relapse. The current study presents a neuroimmune mechanism through which chronic opioids disrupt the ventral tegmental area (VTA) dopaminergic circuitry that contributes to impaired reward behavior. Opioid dependence was induced in rodents by treatment with escalating doses of morphine. Microglial activation was observed in the VTA following spontaneous withdrawal from chronic morphine treatment. Opioid-induced microglial activation resulted in an increase in brain-derived neurotrophic factor (BDNF) expression and a reduction in the expression and function of the K+Cl− co-transporter KCC2 within VTA GABAergic neurons. Inhibition of microglial activation or interfering with BDNF signaling prevented the loss of Cl− extrusion capacity and restored the rewarding effects of cocaine in opioid-dependent animals. Consistent with a microglial-derived BDNF-induced disruption of reward, intra-VTA injection of BDNF or a KCC2 inhibitor resulted in a loss of cocaine-induced place preference in opioid-naïve animals. The loss of the extracellular Cl− gradient undermines GABAA-mediated inhibition, and represents a mechanism by which chronic opioid treatments can result in blunted reward circuitry. This study directly implicates microglial-derived BDNF as a negative regulator of reward in opioid-dependent states, identifying new therapeutic targets for opiate addictive behaviors. PMID:26202104

  5. Decreased levels of brain-derived neurotrophic factor in the remitted state of unipolar depressive disorder

    DEFF Research Database (Denmark)

    Hasselbalch, Jacob; Knorr, U; Bennike, B;

    2012-01-01

    Decreased levels of peripheral brain-derived neurotrophic factor (BDNF) have been associated with depression. It is uncertain whether abnormally low levels of BDNF in blood are present beyond the depressive state and whether levels of BDNF are associated with the course of clinical illness....

  6. Brain-derived neurotrophic factor in human subjects with function-altering melanocortin-4 receptor variants

    Science.gov (United States)

    In rodents, hypothalamic brain-derived neurotrophic factor (BDNF) expression appears to be regulated by melanocortin-4 receptor (MC4R) activity. The impact of MC4R genetic variation on circulating BDNF in humans is unknown. The objective of this study is to compare BDNF concentrations of subjects wi...

  7. Chemically extracted acellular allogeneic nerve graft combined with ciliary neurotrophic factor promotes sciatic nerve repair.

    Science.gov (United States)

    Zhang, Yanru; Zhang, Hui; Katiella, Kaka; Huang, Wenhua

    2014-07-15

    A chemically extracted acellular allogeneic nerve graft can reduce postoperative immune rejection, similar to an autologous nerve graft, and can guide neural regeneration. However, it remains poorly understood whether a chemically extracted acellular allogeneic nerve graft combined with neurotrophic factors provides a good local environment for neural regeneration. This study investigated the repair of injured rat sciatic nerve using a chemically extracted acellular allogeneic nerve graft combined with ciliary neurotrophic factor. An autologous nerve anastomosis group and a chemical acellular allogeneic nerve bridging group were prepared as controls. At 8 weeks after repair, sciatic functional index, evoked potential amplitude of the soleus muscle, triceps wet weight recovery rate, total number of myelinated nerve fibers and myelin sheath thickness were measured. For these indices, values in the three groups showed the autologous nerve anastomosis group > chemically extracted acellular nerve graft + ciliary neurotrophic factor group > chemical acellular allogeneic nerve bridging group. These results suggest that chemically extracted acellular nerve grafts combined with ciliary neurotrophic factor can repair sciatic nerve defects, and that this repair is inferior to autologous nerve anastomosis, but superior to chemically extracted acellular allogeneic nerve bridging alone. PMID:25221592

  8. Chemically extracted acellular allogeneic nerve graft combined with ciliary neurotrophic factor promotes sciatic nerve repair

    Institute of Scientific and Technical Information of China (English)

    Yanru Zhang; Hui Zhang; Kaka Katiella; Wenhua Huang

    2014-01-01

    A chemically extracted acellular allogeneic nerve graft can reduce postoperative immune re-jection, similar to an autologous nerve graft, and can guide neural regeneration. However, it remains poorly understood whether a chemically extracted acellular allogeneic nerve graft combined with neurotrophic factors provides a good local environment for neural regenera-tion. This study investigated the repair of injured rat sciatic nerve using a chemically extracted acellular allogeneic nerve graft combined with ciliary neurotrophic factor. An autologous nerve anastomosis group and a chemical acellular allogeneic nerve bridging group were prepared as controls. At 8 weeks after repair, sciatic functional index, evoked potential amplitude of the soleus muscle, triceps wet weight recovery rate, total number of myelinated nerve fibers and myelin sheath thickness were measured. For these indices, values in the three groups showed the autologous nerve anastomosis group > chemically extracted acellular nerve graft + ciliary neurotrophic factor group > chemical acellular allogeneic nerve bridging group. These results suggest that chemically extracted acellular nerve grafts combined with ciliary neurotrophic factor can repair sciatic nerve defects, and that this repair is inferior to autologous nerve anasto-mosis, but superior to chemically extracted acellular allogeneic nerve bridging alone.

  9. [Correction of neurotrophic disorders in patients, suffering consequences of a spinal cord and peripheral nerves trauma].

    Science.gov (United States)

    2014-08-01

    On clinical base of cathedra of the disasters medicine, military medicine, anesthesiology and reanimatology in 2010 - 2013 yrs 62 patients were treated for neurotrophic disorders, in 12 of them the method was applied, elaborated in the clinic. For neurotrophic ulcers in 5 patients autodermoplasty was performed, using splitted cutaneous flap, in 1 for the wound defect on a forearm--plasty, using rotational cutaneo-adipose flap, based on axial blood supply. In 44 patients after a spinal cord trauma a neurotrophic defects degree III - IV have formed. The kind of operative intervention was selected depending on size of the defect, the wound depth and functional peculiarities of the injured area. Introduction of a new method of treatment of neurotrophic ulcers of the lower extremities, using preparation of hyaluronic acid with sodium succinate, expands the perspectives of treatment in patients, suffering defects of cover tissues. Differentiated approach to choice of the wound closure method, caused by damage of central and peripheral neural system, have permitted to achieve positive results in 98.1% of patients. PMID:25507021

  10. Human obesity associated with an intronic SNP in the brain-derived neurotrophic factor locus

    Science.gov (United States)

    Brain-derived neurotrophic factor (BDNF) plays a key role in energy balance. In population studies, SNPs of the BDNF locus have been linked to obesity, but the mechanism by which these variants cause weight gain is unknown. Here, we examined human hypothalamic BDNF expression in association with 44 ...

  11. Polylactic-co-glycolic acid microspheres containing three neurotrophic factors promote sciatic nerve repair after injury

    Institute of Scientific and Technical Information of China (English)

    Qun Zhao; Zhi-yue Li; Ze-peng Zhang; Zhou-yun Mo; Shi-jie Chen; Si-yu Xiang; Qing-shan Zhang; Min Xue

    2015-01-01

    A variety of neurotrophic factors have been shown to repair the damaged peripheral nerve. However, in clinical practice, nerve growth factor, neurotrophin-3 and brain-derived neuro-trophic factor are all peptides or proteins that may be rapidly deactivated at the focal injury site;their local effective concentration time following a single medication cannot meet the required time for spinal axons to regenerate and cross the glial scar. In this study, we produced polymer sustained-release microspheres based on the polylactic-co-glycolic acid copolymer; the micro-spheres at 300-µm diameter contained nerve growth factor, neurotrophin-3 and brain-derived neurotrophic factor. Six microspheres were longitudinally implanted into the sciatic nerve at the anastomosis site, serving as the experimental group; while the sciatic nerve in the control group was subjected to the end-to-end anastomosis using 10/0 suture thread. At 6 weeks after implanta-tion, the lower limb activity, weight of triceps surae muscle, sciatic nerve conduction velocity and the maximum amplitude were obviously better in the experimental group than in the control group. Compared with the control group, more regenerating nerve ifbers were observed and dis-tributed in a dense and ordered manner with thicker myelin sheaths in the experimental group. More angiogenesis was also visible. Experimental findings indicate that polylactic-co-glycolic acid composite microspheres containing nerve growth factor, neurotrophin-3 and brain-derived neurotrophic factor can promote the restoration of sciatic nerve in rats after injury.

  12. Mimicking the neurotrophic factor profile of embryonic spinal cord controls the differentiation potential of spinal progenitors into neuronal cells.

    Directory of Open Access Journals (Sweden)

    Masaya Nakamura

    Full Text Available Recent studies have indicated that the choice of lineage of neural progenitor cells is determined, at least in part, by environmental factors, such as neurotrophic factors. Despite extensive studies using exogenous neurotrophic factors, the effect of endogenous neurotrophic factors on the differentiation of progenitor cells remains obscure. Here we show that embryonic spinal cord derived-progenitor cells express both ciliary neurotrophic factor (CNTF and brain-derived neurotrophic factor (BDNF mRNA before differentiation. BDNF gene expression significantly decreases with their differentiation into the specific lineage, whereas CNTF gene expression significantly increases. The temporal pattern of neurotrophic factor gene expression in progenitor cells is similar to that of the spinal cord during postnatal development. Approximately 50% of spinal progenitor cells differentiated into astrocytes. To determine the effect of endogenous CNTF on their differentiation, we neutralized endogenous CNTF by administration of its polyclonal antibody. Neutralization of endogenous CNTF inhibited the differentiation of progenitor cells into astrocytes, but did not affect the numbers of neurons or oligodendrocytes. Furthermore, to mimic the profile of neurotrophic factors in the spinal cord during embryonic development, we applied BDNF or neurotrophin (NT-3 exogenously in combination with the anti-CNTF antibody. The exogenous application of BDNF or NT-3 promoted the differentiation of these cells into neurons or oligodendrocytes, respectively. These findings suggest that endogenous CNTF and exogenous BDNF and NT-3 play roles in the differentiation of embryonic spinal cord derived progenitor cells into astrocytes, neurons and oligodendrocytes, respectively.

  13. Brain-derived neurotrophic factor expression is higher in brain tissue from patients with refractory epilepsy than in normal controls

    Institute of Scientific and Technical Information of China (English)

    Yudan Lv; Jiqing Qiu; Zan Wang; Li Cui; Hongmei Meng; Weihong Lin

    2011-01-01

    The role of the brain-derived neurotrophic factor in epilepsy remains controversial. The present study utilized light and electron microscopy to investigate pathological and ultrastructural changes in brain tissue obtained from the seizure foci of 24 patients with temporal epilepsy. We found that epileptic tissue showed neuronal degeneration, glial cell proliferation, nuclear vacuolization, and neural cell tropism. Immunoelectron microscopy and immunohistochemistry showed that brain-derived neurotrophic factor was expressed at significantly higher levels in patients with refractory temporal epilepsy compared with normal controls, demonstrating that the pathological changes within seizure foci in patients with refractory epilepsy are associated with brain-derived neurotrophic factor expression alterations.

  14. Opiate withdrawal behavior after focal brain stimulation.

    Science.gov (United States)

    Williams, D A; Thorn, B E

    1984-11-01

    Electrical stimulation of the brainstem abolishes pain, while continued stimulation induces tolerance to the analgesic effect. Analgesic drugs producing tolerance also induce physical dependence, suggesting that the phenomenon of tolerance is associated with addiction. There is evidence that the neural mechanism for stimulation-produced analgesia is related to the release of opiate substances within the brain. We therefore propose that repeated or protracted brain stimulation elicits dependence upon the endorphins released by electrical stimulation of the neurons themselves. To investigate this possibility, rats were given repetitive bursts of analgesic electrical brain stimulation for two hours. Immediately thereafter, they were injected with the opiate antagonist, naloxone. Behaviors associated with low grade opiate withdrawal were observed. These data suggest that prolonged analgesic stimulation can result in naloxone-precipitated behaviors similar to the behaviors exhibited during opiate withdrawal. PMID:6542676

  15. Identification and management of alcohol withdrawal syndrome.

    Science.gov (United States)

    Mirijello, Antonio; D'Angelo, Cristina; Ferrulli, Anna; Vassallo, Gabriele; Antonelli, Mariangela; Caputo, Fabio; Leggio, Lorenzo; Gasbarrini, Antonio; Addolorato, Giovanni

    2015-03-01

    Symptoms of alcohol withdrawal syndrome (AWS) may develop within 6-24 h after the abrupt discontinuation or decrease of alcohol consumption. Symptoms can vary from autonomic hyperactivity and agitation to delirium tremens. The gold-standard treatment for AWS is with benzodiazepines (BZDs). Among the BZDs, different agents (i.e., long-acting or short-acting) and different regimens (front-loading, fixed-dose or symptom-triggered) may be chosen on the basis of patient characteristics. Severe withdrawal could require ICU admission and the use of barbiturates or propofol. Other drugs, such as α2-agonists (clonidine and dexmetedomidine) and β-blockers can be used as adjunctive treatments to control neuroautonomic hyperactivity. Furthermore, neuroleptic agents can help control hallucinations. Finally, other medications for the treatment for AWS have been investigated with promising results. These include carbamazepine, valproate, sodium oxybate, baclofen, gabapentin and topiramate. The usefulness of these agents are discussed. PMID:25666543

  16. The Complex of Ciliary Neurotrophic Factor-Ciliary Neurotrophic Factor Receptor α Up-Regulates Connexin43 and Intercellular Coupling in Astrocytes via the Janus Tyrosine Kinase/Signal Transducer and Activator of Transcription PathwayD⃞

    OpenAIRE

    Ozog, Mark A.; Bernier, Suzanne M; Bates, Dave C.; Chatterjee, Bishwanath; Lo, Cecilia W.; Naus, Christian C.G.

    2004-01-01

    Cytokines regulate numerous cell processes, including connexin expression and gap junctional coupling. In this study, we examined the effect of ciliary neurotrophic factor (CNTF) on connexin43 (Cx43) expression and intercellular coupling in astrocytes. Murine cortical astrocytes matured in vitro were treated with CNTF (20 ng/ml), soluble ciliary neurotrophic factor receptor α (CNTFRα) (200 ng/ml), or CNTF-CNTFRα. Although CNTF and CNTFRα alone had no effect on Cx43 expression, the heterodimer...

  17. Clinical management of alcohol withdrawal: A systematic review

    Directory of Open Access Journals (Sweden)

    Shivanand Kattimani

    2013-01-01

    Full Text Available Alcohol withdrawal is commonly encountered in general hospital settings. It forms a major part of referrals received by a consultation-liaison psychiatrist. This article aims to review the evidence base for appropriate clinical management of the alcohol withdrawal syndrome. We searched Pubmed for articles published in English on pharmacological management of alcohol withdrawal in humans with no limit on the date of publication. Articles not relevant to clinical management were excluded based on the titles and abstract available. Full-text articles were obtained from this list and the cross-references. There were four meta-analyses, 9 systematic reviews, 26 review articles and other type of publications like textbooks. Alcohol withdrawal syndrome is a clinical diagnosis. It may vary in severity. Complicated alcohol withdrawal presents with hallucinations, seizures or delirium tremens. Benzodiazepines have the best evidence base in the treatment of alcohol withdrawal, followed by anticonvulsants. Clinical institutes withdrawal assessment-alcohol revised is useful with pitfalls in patients with medical comorbidities. Evidence favors an approach of symptom-monitored loading for severe withdrawals where an initial dose is guided by risk factors for complicated withdrawals and further dosing may be guided by withdrawal severity. Supportive care and use of vitamins is also discussed.

  18. Clinical management of alcohol withdrawal: A systematic review.

    Science.gov (United States)

    Kattimani, Shivanand; Bharadwaj, Balaji

    2013-07-01

    Alcohol withdrawal is commonly encountered in general hospital settings. It forms a major part of referrals received by a consultation-liaison psychiatrist. This article aims to review the evidence base for appropriate clinical management of the alcohol withdrawal syndrome. We searched Pubmed for articles published in English on pharmacological management of alcohol withdrawal in humans with no limit on the date of publication. Articles not relevant to clinical management were excluded based on the titles and abstract available. Full-text articles were obtained from this list and the cross-references. There were four meta-analyses, 9 systematic reviews, 26 review articles and other type of publications like textbooks. Alcohol withdrawal syndrome is a clinical diagnosis. It may vary in severity. Complicated alcohol withdrawal presents with hallucinations, seizures or delirium tremens. Benzodiazepines have the best evidence base in the treatment of alcohol withdrawal, followed by anticonvulsants. Clinical institutes withdrawal assessment-alcohol revised is useful with pitfalls in patients with medical comorbidities. Evidence favors an approach of symptom-monitored loading for severe withdrawals where an initial dose is guided by risk factors for complicated withdrawals and further dosing may be guided by withdrawal severity. Supportive care and use of vitamins is also discussed. PMID:25013309

  19. Electroacupuncture-regulated neurotrophic factor mRNA expression in the substantia nigra of Parkinson's disease rats.

    Science.gov (United States)

    Wang, Shuju; Fang, Jianqiao; Ma, Jun; Wang, Yanchun; Liang, Shaorong; Zhou, Dan; Sun, Guojie

    2013-02-25

    Acupuncture for the treatment of Parkinson's disease has a precise clinical outcome. This study investigated the effect of electroacupuncture at Fengfu (GV16) and Taichong (LR3) acupoints in rat models of Parkinson's disease induced by subcutaneous injection of rotenone into rat neck and back. Reverse transcription-PCR demonstrated that brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor mRNA expression was significantly increased in the substantia nigra of rat models of Parkinson's disease, and that abnormal behavior of rats was significantly improved following electroacupuncture treatment. These results indicated that electroacupuncture treatment upregulated brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor mRNA expression in the substantia nigra of rat models of Parkinson's disease. Thus, electroacupuncture may be useful in the treatment of Parkinson's disease. PMID:25206697

  20. Brain-Derived Neurotrophic Factor (BDNF) Promotes Cochlear Spiral Ganglion Cell Survival and Function in Deafened, Developing Cats

    OpenAIRE

    Leake, Patricia A.; Hradek, Gary T.; Hetherington, Alexander M.; Stakhovskaya, Olga

    2011-01-01

    Postnatal development and survival of spiral ganglion (SG) neurons depend upon both neural activity and neurotrophic support. Our previous studies showed that electrical stimulation from a cochlear implant only partly prevents SG degeneration after early deafness. Thus, neurotrophic agents that might be combined with an implant to improve neural survival are of interest. Recent studies reporting that BDNF promotes SG survival after deafness, have been conducted in rodents and limited to relat...

  1. Electroacupuncture-regulated neurotrophic factor mRNA expression in the substantia nigra of Parkinson's disease rats☆

    OpenAIRE

    Wang, Shuju; Fang, Jianqiao; Ma, Jun; Wang, Yanchun; Liang, Shaorong; Zhou, Dan; Sun, Guojie

    2013-01-01

    Acupuncture for the treatment of Parkinson's disease has a precise clinical outcome. This study investigated the effect of electroacupuncture at Fengfu (GV16) and Taichong (LR3) acupoints in rat models of Parkinson's disease induced by subcutaneous injection of rotenone into rat neck and back. Reverse transcription-PCR demonstrated that brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor mRNA expression was significantly increased in the substantia nigra of rat m...

  2. Ciliary neurotrophic factor cell-based delivery prevents synaptic impairment and improves memory in mouse models of Alzheimer's disease.

    OpenAIRE

    Garcia, Pierre

    2010-01-01

    The development of novel therapeutic strategies for Alzheimer’s disease (AD) represents one of the biggest unmet medical needs today. Application of neurotrophic factors able to modulate neuronal survival and synaptic connectivity is a promising therapeutic approach for AD. We aimed to determine whether the loco-regional delivery of ciliary neurotrophic factor (CNTF) could prevent amyloid-beta oligomer-induced synaptic damages and associated cognitive impairments that typify AD. To ensure lo...

  3. Effect of glial cell line-derived neurotrophic factor on retinal function after experimental branch retinal vein occlusion

    DEFF Research Database (Denmark)

    Ejstrup, Rasmus; Dornonville de la Cour, Morten; Kyhn, Maria Voss;

    2012-01-01

    The objective of the study was to investigate the effect of glial cell line-derived neurotrophic factor (GDNF) on the multifocal electroretinogram (mfERG) following an induced branch retinal vein occlusion (BRVO) in pigs.......The objective of the study was to investigate the effect of glial cell line-derived neurotrophic factor (GDNF) on the multifocal electroretinogram (mfERG) following an induced branch retinal vein occlusion (BRVO) in pigs....

  4. Acute strength exercise and the involvement of small or large muscle mass on plasma brain‐derived neurotrophic factor levels

    OpenAIRE

    Paulo Roberto Correia; Aline Pansani; Felipe Machado; Marilia Andrade; Antonio Carlos da Silva; Fulvio Alexandre Scorza; Esper Abrão Cavalheiro; Ricardo Mario Arida

    2010-01-01

    OBJECTIVE: Blood neurotrophins, such as the brain-derived neurotrophic factor, are considered to be of great importance in mediating the benefits of physical exercise. In this study, the effect of acute strength exercise and the involvement of small versus large muscle mass on the levels of plasma brain-derived neurotrophic factor were evaluated in healthy individuals. METHODS: The concentric strengths of knee (large) and elbow (small) flexor and extensor muscles were measured on two separate...

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

    OpenAIRE

    Pei Jiang; Rui-Li Dang; Huan-De Li; Li-Hong Zhang; Wen-Ye Zhu; Ying Xue; Mi-Mi Tang

    2014-01-01

    Depression is associated with stress-induced neural atrophy in limbic brain regions, whereas exercise has antidepressant effects as well as increasing hippocampal synaptic plasticity by strengthening neurogenesis, metabolism, and vascular function. A key mechanism mediating these broad benefits of exercise on the brain is induction of neurotrophic factors, which instruct downstream structural and functional changes. To systematically evaluate the potential neurotrophic factors that were invol...

  6. Neural mechanisms underlying morphine withdrawal in addicted patients: a review

    Directory of Open Access Journals (Sweden)

    Nima Babhadiashar

    2015-06-01

    Full Text Available Morphine is one of the most potent alkaloid in opium, which has substantial medical uses and needs and it is the first active principle purified from herbal source. Morphine has commonly been used for relief of moderate to severe pain as it acts directly on the central nervous system; nonetheless, its chronic abuse increases tolerance and physical dependence, which is commonly known as opiate addiction. Morphine withdrawal syndrome is physiological and behavioral symptoms that stem from prolonged exposure to morphine. A majority of brain regions are hypofunctional over prolonged abstinence and acute morphine withdrawal. Furthermore, several neural mechanisms are likely to contribute to morphine withdrawal. The present review summarizes the literature pertaining to neural mechanisms underlying morphine withdrawal. Despite the fact that morphine withdrawal is a complex process, it is suggested that neural mechanisms play key roles in morphine withdrawal.

  7. The Role of Neurotrophic Factors Conjugated to Iron Oxide Nanoparticles in Peripheral Nerve Regeneration: In Vitro Studies

    Directory of Open Access Journals (Sweden)

    Ofra Ziv-Polat

    2014-01-01

    Full Text Available Local delivery of neurotrophic factors is a pillar of neural repair strategies in the peripheral nervous system. The main disadvantage of the free growth factors is their short half-life of few minutes. In order to prolong their activity, we have conjugated to iron oxide nanoparticles three neurotrophic factors: nerve growth factor (βNGF, glial cell-derived neurotrophic factor (GDNF, and basic fibroblast growth factor (FGF-2. Comparative stability studies of free versus conjugated factors revealed that the conjugated neurotrophic factors were significantly more stable in tissue cultures and in medium at 37°C. The biological effects of free versus conjugated neurotrophic factors were examined on organotypic dorsal root ganglion (DRG cultures performed in NVR-Gel, composed mainly of hyaluronic acid and laminin. Results revealed that the conjugated neurotrophic factors enhanced early nerve fiber sprouting compared to the corresponding free factors. The most meaningful result was that conjugated-GDNF, accelerated the onset and progression of myelin significantly earlier than the free GDNF and the other free and conjugated factors. This is probably due to the beneficial and long-acting effect that the stabilized conjugated-GDNF had on neurons and Schwann cells. These conclusive results make NVR-Gel enriched with conjugated-GDNF, a desirable scaffold for the reconstruction of severed peripheral nerve.

  8. Acute strength exercise and the involvement of small or large muscle mass on plasma brain-derived neurotrophic factor levels

    Directory of Open Access Journals (Sweden)

    Paulo Roberto Correia

    2010-01-01

    Full Text Available OBJECTIVE: Blood neurotrophins, such as the brain-derived neurotrophic factor, are considered to be of great importance in mediating the benefits of physical exercise. In this study, the effect of acute strength exercise and the involvement of small versus large muscle mass on the levels of plasma brain-derived neurotrophic factor were evaluated in healthy individuals. METHODS: The concentric strengths of knee (large and elbow (small flexor and extensor muscles were measured on two separate days. Venous blood samples were obtained from 16 healthy subjects before and after exercise. RESULTS: The levels of brain-derived neurotrophic factor in the plasma did not significantly increase after both arm and leg exercise. There was no significant difference in the plasma levels of the brain-derived neurotrophic factor in the arms and legs. CONCLUSION: The present results demonstrate that acute strength exercise does not induce significant alterations in the levels of brain-derived neurotrophic factor plasma concentrations in healthy individuals. Considering that its levels may be affected by various factors, such as exercise, these findings suggest that the type of exercise program may be a decisive factor in altering peripheral brain-derived neurotrophic factor.

  9. Gastrodin promotes the secretion of brain-derived neurotrophic factor in the injured spinal cord

    Institute of Scientific and Technical Information of China (English)

    Changwei Song; Shiqiang Fang; Gang Lv; Xifan Mei

    2013-01-01

    Gastrodin, an active component of tall gastrodia tuber, is widely used in the treatment of dizziness, paralysis, epilepsy, stroke and dementia, and exhibits a neuroprotective effect. A rat model of spinal cord injury was established using Allen's method, and gastrodin was administered via the subarachnoid cavity and by intraperitoneal injection for 7 days. Results show that gastrodin promoted the secretion of brain-derived neurotrophic factor in rats with spinal cord injury. After gastrodin treatment, the maximum angle of the inclined plane test, and the Basso, Beattie and Bresnahan scores increased. Moreover, gastrodin improved neural tissue recovery in the injured spinal cord. These results demonstrate that gastrodin promotes the secretion of brain-derived neurotrophic factor, contributes to the recovery of neurological function, and protects neural cells against injury.

  10. Shuganjieyu capsule increases neurotrophic factor expression in a rat model of depression

    Institute of Scientific and Technical Information of China (English)

    Jinhua Fu; Yingjin Zhang; Renrong Wu; Yingjun Zheng; Xianghui Zhang; Mei Yang; Jingping Zhao; Yong Liu

    2014-01-01

    Shuganjieyu capsule has been approved for clinical treatment by the State Food and Drug Ad-ministration of China since 2008. In the clinic, Shuganjieyu capsule is often used to treat mild to moderate depression. In the rat model of depression established in this study, Shuganjieyu capsule was administered intragastrically daily before stress. Behavioral results conifrmed that depressive symptoms lessened after treatment with high-dose (150 mg/kg) Shuganjieyu capsule. Immunohistochemistry results showed that high-dose Shuganjieyu capsule signiifcantly increased phosphorylation levels of phosphorylation cyclic adenosine monophosphate response element binding protein and brain-derived neurotrophic factor expression in the medial prefrontal cortex and hippocampal CA3 area. Overall, our results suggest that in rats, Shuganjieyu capsule effec-tively reverses depressive-like behaviors by increasing expression levels of neurotrophic factors in the brain.

  11. A Case of Withdrawal Psychosis from Internet Addiction Disorder

    OpenAIRE

    Paik, Ahyoung; Oh, Daeyoung; Kim, Daeho

    2014-01-01

    Similar to substance use disorder, patients with Internet addiction disorder (IAD) show excessive use, tolerance and withdrawal symptoms. We report a case of a patient with withdrawal psychosis who showed persecutory delusion and disorganized behaviors in addition to common withdrawal symptoms such as agitation and irritability. A 25-year-old male developed a full-blown psychotic episode within one day after discontinuing an Internet game that he had been playing for at least eight hours a da...

  12. Are withholding and withdrawing therapy always morally equivalent?

    OpenAIRE

    Sulmasy, D P; Sugarman, J

    1994-01-01

    Many medical ethicists accept the thesis that there is no moral difference between withholding and withdrawing life-sustaining therapy. In this paper, we offer an interesting counterexample which shows that this thesis is not always true. Withholding is distinguished from withdrawing by the simple fact that therapy must have already been initiated in order to speak coherently about withdrawal. Provided that there is a genuine need and that therapy is biomedically effective, the historical fac...

  13. Activity-dependent brain-derived neurotrophic factor expression regulates cortistatin-interneurons and sleep behavior

    OpenAIRE

    Martinowich Keri; Schloesser Robert J; Jimenez Dennisse V; Weinberger Daniel R; Lu Bai

    2011-01-01

    Abstract Background Sleep homeostasis is characterized by a positive correlation between sleep length and intensity with the duration of the prior waking period. A causal role for brain-derived neurotrophic factor (BDNF) in sleep homeostasis has been suggested, but the underlying mechanisms remain unclear. Cortistatin, a neuropeptide expressed primarily in a subset of cortical GABAergic interneurons, is another molecule implicated in sleep homeostasis. Results We confirmed that sleep deprivat...

  14. Decreased Plasma Brain-Derived Neurotrophic Factor and Vascular Endothelial Growth Factor Concentrations during Military Training

    OpenAIRE

    Suzuki, Go; Tokuno, Shinichi; Nibuya, Masashi; Ishida, Toru; Yamamoto, Tetsuo; Mukai, Yasuo; Mitani, Keiji; Tsumatori, Gentaro; Scott, Daniel; Shimizu, Kunio

    2014-01-01

    Decreased concentrations of plasma brain-derived neurotrophic factor (BDNF) and serum BDNF have been proposed to be a state marker of depression and a biological indicator of loaded psychosocial stress. Stress evaluations of participants in military mission are critically important and appropriate objective biological parameters that evaluate stress are needed. In military circumstances, there are several problems to adopt plasma BDNF concentration as a stress biomarker. First, in addition to...

  15. Neurotrophic effects of Cerebrolysin in the Mecp2308/Y transgenic model of Rett Syndrome

    OpenAIRE

    Doppler, Edith; Rockenstein, Edward; Ubhi, Kiren; Inglis, Chandra; Mante, Michael; Adame, Anthony; Crews, Leslie; Hitzl, Monika; Moessler, Herbert; Masliah, Eliezer

    2008-01-01

    Rett syndrome is a childhood neurodevelopmental disorder caused by mutations in the gene encoding for methyl CpG binding protein (MeCP2). Neuropathological studies in patients with Rett syndrome and in MeCP2 mutant models have shown reduced dendritic arborization and abnormal neuronal packing. We have previously shown that Cerebrolysin (CBL), a neurotrophic peptide mixture, ameliorates the synaptic and dendritic pathology in models of aging and neurodegeneration. This study aimed to determine...

  16. Neurotrophic Electrode: Method of assembly and implantation into human motor speech cortex

    OpenAIRE

    Bartels, Jess; Andreasen, Dinal; Ehirim, Princewill; Mao, Hui; Seibert, Steven; Wright, E. Joe; Kennedy, Philip

    2008-01-01

    The Neurotrophic Electrode (NE) is designed for longevity and stability of recorded signals. To achieve this aim it induces neurites to grow through its glass tip, thus anchoring it in neuropil. The glass tip contains insulated gold wires for recording the activity of the myelinated neurites that grow into the tip. Neural signals inside the tip are electrically insulated from surrounding neural activity by the glass. The most recent version of the electrode has four wires inside its tip to ma...

  17. Learned helplessness is independent of levels of brain-derived neurotrophic factor in the hippocampus

    OpenAIRE

    Greenwood, Benjamin N.; Strong, Paul V; Foley, Teresa E.; Thompson, Robert; Fleshner, Monika

    2006-01-01

    Reduced levels of brain-derived neurotrophic factor (BDNF) in the hippocampus have been implicated in human affective disorders and behavioral stress responses. The current studies examined the role of BDNF in the behavioral consequences of inescapable stress, or learned helplessness. Inescapable stress decreased BDNF mRNA and protein in the hippocampus of sedentary rats. Rats allowed voluntary access to running wheels for either 3 or 6 weeks prior to exposure to stress were protected against...

  18. Brain-derived neurotrophic factor promoter methylation and cortical thickness in recurrent major depressive disorder

    OpenAIRE

    Kyoung-Sae Na; Eunsoo Won; June Kang; Hun Soo Chang; Ho-Kyoung Yoon; Woo Suk Tae; Yong-Ku Kim; Min-Soo Lee; Sook-Haeng Joe; Hyun Kim; Byung-Joo Ham

    2016-01-01

    Recent studies have reported that methylation of the brain-derived neurotrophic factor (BDNF) gene promoter is associated with major depressive disorder (MDD). This study aimed to investigate the association between cortical thickness and methylation of BDNF promoters as well as serum BDNF levels in MDD. The participants consisted of 65 patients with recurrent MDD and 65 age- and gender-matched healthy controls. Methylation of BDNF promoters and cortical thickness were compared between the gr...

  19. Role of Hypoxia-Induced Brain Derived Neurotrophic Factor in Human Pulmonary Artery Smooth Muscle

    OpenAIRE

    Hartman, William; Helan, Martin; Smelter, Dan; Sathish, Venkatachalem; Thompson, Michael; Pabelick, Christina M.; Johnson, Bruce; Y S Prakash

    2015-01-01

    Background Hypoxia effects on pulmonary artery structure and function are key to diseases such as pulmonary hypertension. Recent studies suggest that growth factors called neurotrophins, particularly brain-derived neurotrophic factor (BDNF), can influence lung structure and function, and their role in the pulmonary artery warrants further investigation. In this study, we examined the effect of hypoxia on BDNF in humans, and the influence of hypoxia-enhanced BDNF expression and signaling in hu...

  20. Maternal separation produces alterations of forebrain brain-derived neurotrophic factor expression in differently aged rats

    OpenAIRE

    Wang, Qiong; Shao, Feng; Wang, Weiwen

    2015-01-01

    Early life adversity, such as postnatal maternal separation (MS), play a central role in the development of psychopathologies during individual ontogeny. In this study, we investigated the effects of repeated MS (4 h per day from postnatal day (PND) 1–21) on the brain-derived neurotrophic factor (BDNF) expression in the medial prefrontal cortex (mPFC), the nucleus accumbens (NAc) and the hippocampus of male and female juvenile (PND 21), adolescent (PND 35) and young adult (PND 56) Wistar rats...

  1. Conditional, genetic disruption of ciliary neurotrophic factor receptors reveals a role in adult motor neuron survival

    OpenAIRE

    Lee, Nancy; Robitz, Rachel; Zurbrugg, Rebekah J; Karpman, Adam M; Mahler, Ashley M.; Cronier, Samantha A.; Vesey, Rachel; Spearry, Rachel P.; Zolotukhin, Sergei; MacLennan, A. John

    2008-01-01

    Indirect evidence suggests that endogenous ciliary neurotrophic factor (CNTF) receptor signaling can promote motor neuron (MN) survival in the adult. If so, proper targeting of this signaling may selectively counteract the effects of adult MN diseases. However, direct evidence for CNTF receptor involvement in adult MN survival is lacking, presumably because the unconditional blockade of the mouse CNTF receptor in vivo [through genetic disruption of the essential CNTF receptor α (CNTFRα) gene]...

  2. Circulating levels of ciliary neurotrophic factor in normal pregnancy and preeclampsia

    OpenAIRE

    Akahori, Yoichiro; Takamoto, Norio; Masumoto,Akio; Inoue,Seiji; Nakatsukasa, Hideki; MASUYAMA, HISASHI; Hiramatsu,Yuji

    2010-01-01

    Ciliary neurotrophic factor (CNTF) has been shown to decrease food intake in mouse models of obesity and to improve insulin sensitivity. It is well known that tight regulation of glucose metabolism is essential for successful gestational outcomes (e.g. fetal growth), and that abnormal insulin resistance is associated with preeclampsia (PE). To investigate the possibility that CNTF might be involved in the regulation of insulin resistance during pregnancy, circulating levels of CNTF w...

  3. Ciliary neurotrophic factor has intrinsic and extrinsic roles in regulating B cell differentiation and bone structure.

    OpenAIRE

    Maria Askmyr; White, Kirby E; Tanja Jovic; King, Hannah A.; Quach, Julie M.; Maluenda, Ana C.; Baker, Emma K; Smeets, Monique F.; Walkley, Carl R.; Purton, Louise E.

    2015-01-01

    The gp130 receptor and its binding partners play a central role in cytokine signalling. Ciliary neurotrophic factor (CNTF) is one of the cytokines that signals through the gp130 receptor complex. CNTF has previously been shown to be a negative regulator of trabecular bone remodelling and important for motor neuron development. Since haematopoietic cell maintenance and differentiation is dependent on the bone marrow (BM) microenvironment, where cells of the osteoblastic lineage are important r...

  4. Expression of ciliary neurotrophic factor and its receptor in experimental obstructive nephropathy

    OpenAIRE

    Lee, Byoung-Seung; Choi, Jae-Youn; Cha, Jung-Ho

    2011-01-01

    Ciliary neurotrophic factor (CNTF) is well known as a growth/survival factor of neuronal tissue. We investigated the expression of CNTF and its specific receptor alpha (CNTFRα) in a unilateral ureteral obstruction (UUO) model. Complete UUO was produced by left ureteral ligation in Sprague-Dawley rats. The animals were sacrificed on days 1, 3, 5, 7, 14, 21, and 28 after UUO. The kidneys were fixed, and processed for both immunohistochemistry and in situ hybridization. CNTF immunoreactivity in ...

  5. Perivascular Cells Increase Expression of Ciliary Neurotrophic Factor Following Partial Denervation of the Rat Neurohypophysis

    OpenAIRE

    Lo, David; SunRhodes, Neil; Watt, John A.

    2008-01-01

    The expression of ciliary neurotrophic factor (CNTF) was investigated immunocytochemically during the axonal degeneration and collateral axonal sprouting response that follows partial denervation of the rat neurohypophysis. A significant increase in the number of CNTF-immunoreactive (CNTF-ir) cells was observed in the neurohypophysis of partially denervated animals compared to age-matched sham-operated controls by 5 days post-denervation, remaining elevated throughout the 30 day post denervat...

  6. Vasoactive Intestinal Peptide Induction by Ciliary Neurotrophic Factor in Donor Human Corneal Endothelium in situ

    OpenAIRE

    Koh, Shay-Whey M.; Guo, Yan; Bernstein, Steve L.; Waschek, James A.; Liu, Xiuhuai; Symes, Aviva J

    2007-01-01

    After peripheral nerve axotomy, vasoactive intestinal peptide (VIP) gene expression is upregulated in neurons, whereas ciliary neurotrophic factor (CNTF) accumulates extracellularly at the lesion site. Although CNTF-induced VIP gene expression has been reported in cultured sympathetic neurons and neuroblastoma cells, it still remains to be determined if CNTF and VIP play interrelated roles in nerve injury. The corneal endothelium, like sympathetic neurons, derives from the neural crest. Previ...

  7. Crystal structure of dimeric human ciliary neurotrophic factor determined by MAD phasing.

    OpenAIRE

    McDonald, N. Q.; Panayotatos, N; Hendrickson, W A

    1995-01-01

    Ciliary neurotrophic factor (CNTF) promotes the survival and differentiation of developing motor neurons and is a potential therapeutic for treating neurodegeneration and nerve injury. The crystal structure of human CNTF has been determined at 2.4 A resolution using multi-wavelength anomalous diffraction (MAD) phasing from a single Yb3+ ions. The structure reveals that CNTF is dimeric, with a novel anti-parallel arrangement of the subunits, not previously observed for other cytokines. Each su...

  8. Ciliary Neurotrophic Factor Protects Striatal Neurons against Excitotoxicity by Enhancing Glial Glutamate Uptake

    OpenAIRE

    Beurrier, Corinne; Faideau, Mathilde; Bennouar, Khaled-Ezaheir; Escartin, Carole; Kerkerian-Le Goff, Lydia; Bonvento, Gilles; Gubellini, Paolo

    2010-01-01

    Ciliary neurotrophic factor (CNTF) is a potent neuroprotective cytokine in different animal models of glutamate-induced excitotoxicity, although its action mechanisms are still poorly characterized. We tested the hypothesis that an increased function of glial glutamate transporters (GTs) could underlie CNTF-mediated neuroprotection. We show that neuronal loss induced by in vivo striatal injection of the excitotoxin quinolinic acid (QA) was significantly reduced (by ∼75%) in CNTF-treated anima...

  9. Ciliary neurotrophic factor prevents the degeneration of motor neurons in mouse mutant progressive motor neuronopathy

    OpenAIRE

    Sendtner, Michael; Stöckli, Kurt A.; Thoenen, Hans; Schmalbruch, H.; Carroll, P.; Kreutzberg, Georg W.

    2010-01-01

    CILIARY neurotrophic factor (CNTF) supports the survival of embryonic motor neurons in vitro and in vivo and prevents lesion-mediated degeneration of rat motor neuron~ during early post-natal stages. Here we report that CNTF greatly reduces all the functional and morphological changes in pmnlpmn mice5, an autosomal recessive mutant leading to progressive caudo-cranial motor neuron degeneration. The first manifestations of progressive motor neuronopathy in homozygous pmnl pmn mice become appar...

  10. The relationship between ciliary neurotrophic factor (CNTF) genotype and motor unit physiology: preliminary studies

    OpenAIRE

    Ferrell Robert; Hurley Ben; Roth Stephen; Stashuk Daniel; Ling Shari; Conwit Robin A; Metter E Jeffrey

    2005-01-01

    Abstract Background Ciliary neurotrophic factor (CNTF) is important for neuronal and muscle development, and genetic variation in the CNTF gene has been associated with muscle strength. The effect of CNTF on nerve development suggests that CNTF genotype may be associated with force production via its influence on motor unit size and firing patterns. The purpose of this study is to examine whether CNTF genotype differentially affects motor unit activation in the vastus medialis with increasing...

  11. Ciliary neurotrophic factor corrects obesity and diabetes associated with leptin deficiency and resistance

    OpenAIRE

    Gloaguen, Isabelle; Costa, Patrizia; Demartis, Anna; Lazzaro, Domenico; Di Marco, Annalise; Graziani, Rita; Paonessa, Giacomo; Chen, Fang; Rosenblum, Charles I.; Van der Ploeg, Lex H. T.; Cortese, Riccardo; Ciliberto, Gennaro; Laufer, Ralph

    1997-01-01

    Receptor subunits for the neurocytokine ciliary neurotrophic factor (CNTF) share sequence similarity with the receptor for leptin, an adipocyte-derived cytokine involved in body weight homeostasis. We report here that CNTF and leptin activate a similar pattern of STAT factors in neuronal cells, and that mRNAs for CNTF receptor subunits, similarly to the mRNA of leptin receptor, are localized in mouse hypothalamic nuclei involved in the regulation of energy balance. Systemic administration of ...

  12. CNTF Mediates Neurotrophic Factor Secretion and Fluid Absorption in Human Retinal Pigment Epithelium

    OpenAIRE

    Li, Rong; Wen, Rong; Banzon, Tina; Maminishkis, Arvydas; Miller, Sheldon S.

    2011-01-01

    Ciliary neurotrophic factor (CNTF) protects photoreceptors and regulates their phototransduction machinery, but little is known about CNTF's effects on retinal pigment epithelial (RPE) physiology. Therefore, we determined the expression and localization of CNTF receptors and the physiological consequence of their activation in primary cultures of human fetal RPE (hfRPE). Cultured hfRPE express CNTF, CT1, and OsM and their receptors, including CNTFRα, LIFRβ, gp130, and OsMRβ, all localized mai...

  13. Ciliary neurotrophic factor prevents degeneration of adult rat substantia nigra dopaminergic neurons in vivo.

    OpenAIRE

    T. Hagg; Varon, S

    1993-01-01

    We have investigated the neuroprotective effects of recombinant human ciliary neurotrophic factor (CNTF) for injured dopaminergic neurons of the adult rat substantia nigra compacta. Fourteen days after a unilateral transection of the nigrostriatal pathway two-thirds of the neurons (identified by retrograde labeling) had degenerated. In sharp contrast, 73% (a few cases, > 90%) of this cell loss was prevented by continuous infusion of CNTF close to the injured neurons. However, CNTF did not pre...

  14. Isolated Bilateral Trigeminal Neuropathy in Sarcoidosis Presenting with Neurotrophic Corneal Ulcers

    OpenAIRE

    L. Esakowit; M. Gupta; Lascaratos, G.; A. Syrogiannis

    2010-01-01

    Sarcoidosis is a multisystem granulomatous disease that may affect various organs. Nevertheless, involvement of the trigeminal nerve is exceedingly uncommon. This report presents a rare case of isolated bilateral trigeminal neuropathy presenting with neurotrophic corneal ulcers. The patient was treated with topical chloramphenicol and lubricants, as well as botulinum toxin injection to the upper eyelid to induce ptosis. Our case illustrates the importance of recognizing that bilateral corneal...

  15. Effects of Brain-Derived Neurotrophic Factor on Local Inflammation in Experimental Stroke of Rat

    OpenAIRE

    Xinfeng Liu; Gelin Xu; Zhaoyao Chen; Tingting Lu; Ning Wei; Juehua Zhu; Yongjun Jiang

    2011-01-01

    This study was aimed to investigate whether brain-derived neurotrophic factor (BDNF) can modulate local cerebral inflammation in ischemic stroke. Rats were subjected to ischemia by occluding the right middle cerebral artery (MCAO) for 2 hours. Rats were randomized as control, BDNF, and antibody groups. The local inflammation was evaluated on cellular, cytokine, and transcription factor levels with immunofluorescence, enzyme-linked immunosorbent assay, real-time qPCR, and electrophoretic mobil...

  16. Endogenous Brain Derived Neurotrophic Factor in the Nucleus Tractus Solitarius Tonically Regulates Synaptic and Autonomic Function

    OpenAIRE

    Clark, Catharine G.; Hasser, Eileen M.; Kunze, Diana L.; Katz, David M.; Kline, David D.

    2011-01-01

    Brain derived neurotrophic factor (BDNF) and its receptor, TrkB, are highly expressed in the nucleus tractus solitarius (nTS), the principal target of cardiovascular primary afferent input to the brainstem. However, little is known about the role of BDNF signaling in nTS in cardiovascular homeostasis. We examined whether BDNF in nTS modulates cardiovascular function in vivo and regulates synaptic and/or neuronal activity in isolated brainstem slices. Microinjection of BDNF into the rat medial...

  17. Chemically extracted acellular allogeneic nerve graft combined with ciliary neurotrophic factor promotes sciatic nerve repair

    OpenAIRE

    Zhang, Yanru; Zhang, Hui; Katiella, Kaka; Huang, Wenhua

    2014-01-01

    A chemically extracted acellular allogeneic nerve graft can reduce postoperative immune rejection, similar to an autologous nerve graft, and can guide neural regeneration. However, it remains poorly understood whether a chemically extracted acellular allogeneic nerve graft combined with neurotrophic factors provides a good local environment for neural regeneration. This study investigated the repair of injured rat sciatic nerve using a chemically extracted acellular allogeneic nerve graft com...

  18. Short term memory, physical fitness, and serum brain-derived neurotrophic factor in obese adolescents

    OpenAIRE

    Rini Rossanti; Dida Akhmad Gurnida; Eddy Fadlyana

    2015-01-01

    Background Obesity in adolescents is a major health problem and has been associated with low academic achievement. Brainderived neurotrophic factor (BDNF), a neurotrophin, plays a role in appetite suppression and memory, and its secretion is enhanced by physical activity. This neurotrophin may be associated with academic achievement in obese. Objective To compare physical fitness and serum BDNF levels to short term memory levels in obese adolescents aged 10–14 years. Methods This comparative,...

  19. Short term memory, physical fitness, and serum brain-derived neurotrophic factor in obese adolescents

    OpenAIRE

    Rini Rossanti; Dida Akhmad Gurnida; Eddy Fadlyana

    2015-01-01

    Background Obesity in adolescents is a major health problem and has been associated with low academic achievement. Brain-derived neurotrophic factor (BDNF), a neurotrophin, plays a role in appetite suppression and memory, and its secretion is enhanced by physical activity. This neurotrophin may be associated with academic achievement in obese. Objective To compare physical fitness and serum BDNF levels to short term memory levels in obese adolescents aged 10–14 years. Methods This com...

  20. Brain-derived neurotrophic factor augments rotational behavior and nigrostriatal dopamine turnover in vivo.

    OpenAIRE

    Altar, C A; Boylan, C B; Jackson, C; Hershenson, S; Miller, J.; Wiegand, S. J.; Lindsay, R M; Hyman, C.

    1992-01-01

    Brain-derived neurotrophic factor (BDNF), a member of the nerve growth factor (NGF)-related family of neutrophins, promotes the survival and differentiation of cultured nigral dopamine neurons. Two-week infusions of BDNF were made above the right pars compacta of the substantia nigra in adult rats. Systemic injection of these animals with (+)-amphetamine, a dopamine-releasing drug, induced 3 or 4 body rotations per minute directed away from the nigral infusion site. Neither supranigral NGF no...

  1. The effect of regular aerobic exercise on urinary brain-derived neurotrophic factor in children

    OpenAIRE

    Yunita Fediani; Masayu Rita Dewi; Muhammad Irfannuddin; Masagus Irsan Saleh; Safri Dhaini

    2014-01-01

    Background Nervous system development in early life influences the quality of cognitive ability during adulthood. Neuronal development and neurogenesis are highly influenced by neurotrophins. The most active neurotrophin is brain-derived neurotrophic factor (BDNF). Physical activity has a positive effect on cognitive function. However, few experimental studies have been done on children to assess the effect of aerobic regular exercise on BDNF levels. Objective To assess the effect of regu...

  2. Association study between brain-derived neurotrophic factor gene polymorphisms and methamphetamine abusers in Japan

    OpenAIRE

    Itoh, Kanako; Hashimoto, Kenji; Shimizu, Eiji; Sekine, Yoshimoto; Ozaki, Norio; Inada, Toshiya; Harano, Mutsuo; Iwata, Nakao; Komiyama, Tokutaro; Yamada, Mitsuhiko; Sora,Ichiro; Nakata, Kenji; Ujike, Hiroshi; Iyo, Masaomi

    2005-01-01

    Several lines of evidence suggest that genetic factors might contribute to drug abuse vulnerability. Recent genomic scans for association demonstrated that the brain-derived neurotrophic factor (BDNF) gene was associated with drug abuse vulnerability. In this study, we analyzed association of two BDNF gene single nucleotide polymorphisms (SNPs), 132C>T (C270T named formerly) in the noncoding region of exon V and 196G >A (val66met) in the coding region of exon XIIIA, with methamphetamine (MAP)...

  3. Gastrodin promotes the secretion of brain-derived neurotrophic factor in the injured spinal cord

    OpenAIRE

    Song, Changwei; Fang, Shiqiang; Gang LV; Mei, Xifan

    2013-01-01

    Gastrodin, an active component of tall gastrodia tuber, is widely used in the treatment of dizziness, paralysis, epilepsy, stroke and dementia, and exhibits a neuroprotective effect. A rat model of spinal cord injury was established using Allen's method, and gastrodin was administered via the subarachnoid cavity and by intraperitoneal injection for 7 days. Results show that gastrodin promoted the secretion of brain-derived neurotrophic factor in rats with spinal cord injury. After gastrodin t...

  4. Neurotrophic Effect of Bone Marrow Stromal Cells on Proliferation and Committed Differentiation of Ventral Mesencephalic Precursors

    OpenAIRE

    Xiao-dong Wang; Heng-zhu Zhang; Zhi-gang Gong; Xi-gang Yan; Qing Lan; Qiang Huang

    2011-01-01

    OBJECTIVE To explore the potential neurotrophic effect of bone marrow stromal cells (BMSCs) on cell proliferation and committed neuronal differentiation of ventral mesencephalic precursors (VMPs) in vitro.METHODS Ventral mesencephalic precursors from E11 inbred rat embryos and BMSCs from adult rats were cultured both separately and in co-culture. After a 7-day incubation in vitro, three conditioned culture media were obtained, termed VMP or common medium, BMSC medium, and BMSC+VMP medium. V...

  5. Therapeutic effects of neurotrophic factors in experimental spinal cord injury models

    OpenAIRE

    Enomoto M

    2016-01-01

    Mitsuhiro Enomoto1,21Department of Orthopaedic and Spinal Surgery, Graduate School, 2Hyperbaric Medical Center, Tokyo Medical and Dental University, Tokyo, JapanAbstract: Neurotrophic factors (NFs) play important roles in regenerative medicine approaches to mitigate primary and secondary damage after spinal cord injury (SCI) because their receptors are still present in the injured spinal cord even though the expression of the NFs themselves is decreased. Several reports have shown that NF adm...

  6. Glial cell line-derived neurotrophic factor gene therapy ameliorates chronic hyperprolactinemia in senile rats

    OpenAIRE

    Morel, Gustavo R.; Sosa, Yolanda E.; Bellini, Maria J.; Carri, Nestor G.; Rodriguez, Silvia S.; Bohn, Martha C.; Goya, Rodolfo G.

    2010-01-01

    Progressive dysfunction of hypothalamic tuberoinfundibular dopaminergic (TIDA) neurons during normal aging is associated in the female rat with chronic hyperprolactinemia. We assessed the effectiveness of glial cell line-derived neurotrophic factor (GDNF) gene therapy to restore TIDA neuron function in senile female rats and reverse their chronic hyperprolactinemia. Young (2.5 months) and senile (29 months) rats received a bilateral intrahypothalamic injection (1010 pfu) of either an adenovir...

  7. Brain-Derived Neurotrophic Factor as a Biomarker in Children with Attention Deficit-Hyperactivity Disorder

    OpenAIRE

    Farshid Saadat; Maryam Kosha; Ali Amiry; Gholamreza Torabi

    2015-01-01

    Background: Evidence suggests that Brain-Derived Neurotrophic Factor (BDNF) is involved in the pathogenesis of Attention-Deficit Hyperactivity Disorder (ADHD), although experimental data regarding the contribution of BDNF concentration to this psychiatric disorder are controversial. Aim: To evaluate the plasma levels of BDNF in patients with ADHD. Material and Methods: In this cross sectional study, ADHD and controls were recruited from the outpatient clinic of the ...

  8. Brain-Derived Neurotrophic Factor Val66Met and Blood Glucose: A Synergistic Effect on Memory

    OpenAIRE

    Naftali Raz; Dahle, Cheryl L.; Rodrigue, Karen M.; Kennedy, Kristen M.; Land, Susan J.; Jacobs, Bradley S.

    2008-01-01

    Age-related declines in episodic memory performance are frequently reported, but their mechanisms remain poorly understood. Although several genetic variants and vascular risk factors have been linked to mnemonic performance in general and age differences therein, it is unknown whether and how they modify age-related memory declines. To address that question, we investigated the effect of Brain-Derived Neurotrophic Factor (BDNF) Val66Met polymorphism that affects secretion of BDNF, and fastin...

  9. Neurotrophic requirements of human motor neurons defined using amplified and purified stem cell-derived cultures.

    Directory of Open Access Journals (Sweden)

    Nuno Jorge Lamas

    Full Text Available Human motor neurons derived from embryonic and induced pluripotent stem cells (hESCs and hiPSCs are a potentially important tool for studying motor neuron survival and pathological cell death. However, their basic survival requirements remain poorly characterized. Here, we sought to optimize a robust survival assay and characterize their response to different neurotrophic factors. First, to increase motor neuron yield, we screened a small-molecule collection and found that the Rho-associated kinase (ROCK inhibitor Y-27632 enhances motor neuron progenitor proliferation up to 4-fold in hESC and hiPSC cultures. Next, we FACS-purified motor neurons expressing the Hb9::GFP reporter from Y-27632-amplified embryoid bodies and cultured them in the presence of mitotic inhibitors to eliminate dividing progenitors. Survival of these purified motor neurons in the absence of any other cell type was strongly dependent on neurotrophic support. GDNF, BDNF and CNTF all showed potent survival effects (EC(50 1-2 pM. The number of surviving motor neurons was further enhanced in the presence of forskolin and IBMX, agents that increase endogenous cAMP levels. As a demonstration of the ability of the assay to detect novel neurotrophic agents, Y-27632 itself was found to support human motor neuron survival. Thus, purified human stem cell-derived motor neurons show survival requirements similar to those of primary rodent motor neurons and can be used for rigorous cell-based screening.

  10. Ectopic Muscle Expression of Neurotrophic Factors Improves Recovery After Nerve Injury.

    Science.gov (United States)

    Glat, Micaela Johanna; Benninger, Felix; Barhum, Yael; Ben-Zur, Tali; Kogan, Elena; Steiner, Israel; Yaffe, David; Offen, Daniel

    2016-01-01

    Sciatic nerve damage is a common medical problem. The main causes include direct trauma, prolonged external nerve compression, and pressure from disk herniation. Possible complications include leg numbness and the loss of motor control. In mild cases, conservative treatment is feasible. However, following severe injury, recovery may not be possible. Neuronal regeneration, survival, and maintenance can be achieved by neurotrophic factors (NTFs). In this study, we examined the potency of combining brain-derived neurotrophic factor (BDNF), glial-derived neurotrophic factor (GDNF), vascular endothelial growth factor (VEGF), and insulin-like growth factor-1 (IGF-1) on the recovery of motor neuron function after crush injury of the sciatic nerve. We show that combined NTF application increases the survival of motor neurons exposed to a hypoxic environment. The ectopic expression of NTFs in the injured muscle improves the recovery of the sciatic nerve after crush injury. A significantly faster recovery of compound muscle action potential (CMAP) amplitude and conduction velocity is observed after muscle injections of viral vectors expressing a mixture of the four NTF genes. Our findings suggest a rationale for using genetic treatment with a combination of NTF-expressing vectors, as a potential therapeutic approach for severe peripheral nerve injury. PMID:26385386

  11. Upregulation of Neurotrophic Factors Selectively in Frontal Cortex in Response to Olfactory Discrimination Learning

    Directory of Open Access Journals (Sweden)

    Ari Naimark

    2007-01-01

    Full Text Available We have previously shown that olfactory discrimination learning is accompanied by several forms of long-term enhancement in synaptic connections between layer II pyramidal neurons selectively in the piriform cortex. This study sought to examine whether the previously demonstrated olfactory-learning-task-induced modifications are preceded by suitable changes in the expression of mRNA for neurotrophic factors and in which brain areas this occurs. Rats were trained to discriminate positive cues in pair of odors for a water reward. The relationship between the learning task and local levels of mRNA for brain-derived neurotrophic factor, tyrosine kinase B, nerve growth factor, and neurotrophin-3 in the frontal cortex, hippocampal subregions, and other regions were assessed 24 hours post olfactory learning. The olfactory discrimination learning activated production of endogenous neurotrophic factors and induced their signal transduction in the frontal cortex, but not in other brain areas. These findings suggest that different brain areas may be preferentially involved in different learning/memory tasks.

  12. Erythropoietin protects adult retinal ganglion cells against NMDA-, trophic factor withdrawal-, and TNF-α-induced damage.

    Directory of Open Access Journals (Sweden)

    Zhi-Yang Chang

    Full Text Available PURPOSE: This study aimed to evaluate the neuroprotective effect of EPO in the presence of N-methyl-d-aspartate (NMDA-, trophic factor withdrawal (TFW-, and tumor necrosis factor-alpha (TNF-α-induced toxicity on total, small, and large retinal ganglion cells (RGCs. METHODS: Retinal cells from adult rats were cultured in a medium containing brain-derived neurotrophic factor (BDNF, ciliary neurotrophic factor (CNTF, basic fibroblast growth factor (bFGF, and forskolin. Expression of RGC markers and EPOR was examined using immunocytochemistry. RGCs were classified according to their morphological properties. Cytotoxicity was induced by NMDA, TFW, or TNF-α. RGC survival was assessed by counting thy-1 and neurofilament-l double-positive cells. RESULTS: EPO offered dose-dependent (EC₅₀ = 5.7 ng/mL protection against NMDA toxicity for small RGCs; protection was not significant for large RGCs. Time-course analysis showed that the presence of EPO either before or after NMDA exposure gave effective protection. For both small and large RGCs undergoing trophic factor withdrawal, EPO at concentrations of 1, 10, or 100 ng/mL improved survival. However, EPO had to be administered soon after the onset of injury to provide effective protection. For TNF-α-induced toxicity, survival of small RGCs was seen only for the highest examined concentration (100 ng/mL of EPO, whereas large RGCs were protected at concentrations of 1, 10, or 100 ng/mL of EPO. Time-course analysis showed that pretreatment with EPO provided protection only for large RGCs; early post-treatment with EPO protected both small and large RGCs. Inhibitors of signal transduction and activators of transcription such as (STAT-5, mitogen-activated protein kinases (MAPK/extracellular-regulated kinase (ERK, and phosphatidyl inositol-3 kinase (PI3K/Akt impaired the protective effect of EPO on RGCs exposed to different insults. CONCLUSION: EPO provided neuroprotection to cultured adult rat RGCs

  13. Intramammary antibiotics in dairy goats : withdrawal periods of three intramammary antibiotics compared to recommended withdrawal periods for cows

    OpenAIRE

    J. Karzis; E.F. Donkin; I.M. Petzer

    2007-01-01

    Intramammary antibiotics are registered and tested for use in dairy cattle. This study investigated withdrawal periods of three intramammary antibiotics (Curaclox LC [Norbrook Pharmacia AH]), Spectrazol Milking Cow (Schering-Plough Animal Health) and Rilexine 200 LC (Logos Agvet [Virbac]) in dairy goats and compared them to withdrawal periods recommended for use in cattle. Three trials were carried out in two different herds. The withdrawal periods for Curaclox LC in eight relatively lo...

  14. 19 CFR 19.6 - Deposits, withdrawals, blanket permits to withdraw and sealing requirements.

    Science.gov (United States)

    2010-04-01

    ... and sealing requirements. 19.6 Section 19.6 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION... withdraw and sealing requirements. (a)(1) Deposit in warehouse. The port director may authorize the deposit... any seal found, upon arrival of the vehicle or container at the warehouse, to be broken, missing,...

  15. Spontaneous reduction of prolactinoma post cabergoline withdrawal

    Directory of Open Access Journals (Sweden)

    Sampath Kumar Venkatesh

    2012-01-01

    Full Text Available Prolactinomas are common pituitary tumors usually highly responsive to dopamine agonists. Around 70-90% of the prolactinomas exhibit decrease in tumor size, though variably with these agents. Uncommonly, there may be little or no shrinkage in pituitary tumor. In the absence of medical therapy, pituitary apoplexy may also result in tumor shrinkage, albeit rarely. We report here a case showing only modest reduction in prolactinoma with cabergoline given for a period of one and a half years. Surprisingly, this tumor showed a 40% reduction in the tumor size 3 months after cabergoline withdrawal in the absence of clinical or radiological evidence of apoplexy.

  16. Brain-Derived Neurotrophic Factor Transgenic Mice Exhibit Passive Avoidance Deficits, Increased Seizure Severity and In Vitro Hyperexcitability in the Hippocampus and Entorhinal Cortex

    OpenAIRE

    Croll, S. D.; Suri, C; Compton, D. L.; Simmons, M. V.; Yancopoulos, G D; Lindsay, R M; Wiegand, S. J.; RUDGE, J. S.; Scharfman, H. E.

    1999-01-01

    Transgenic mice overexpressing brain-derived neurotrophic factor from the β-actin promoter were tested for behavioral, gross anatomical and physiological abnormalities. Brain-derived neurotrophic factor messenger RNA overexpression was widespread throughout brain. Overexpression declined with age, such that levels of overexpression decreased sharply by nine months. Brain-derived neurotrophic factor transgenic mice had no gross deformities or behavioral abnormalities. However, they showed a si...

  17. Sex differences in stress-induced social withdrawal: role of brain derived neurotrophic factor in the bed nucleus of the stria terminalis

    OpenAIRE

    Greenberg, Gian D.; Laman-Maharg, Abigail; Campi, Katharine L.; Voigt, Heather; Orr, Veronica N.; Schaal, Leslie; Trainor, Brian C.

    2014-01-01

    Depression and anxiety disorders are more common in women than men, and little is known about the neurobiological mechanisms that contribute to this disparity. Recent data suggest that stress-induced changes in neurotrophins have opposing effects on behavior by acting in different brain networks. Social defeat has been an important approach for understanding neurotrophin action, but low female aggression levels in rats and mice have limited the application of these methods primarily to males....

  18. Title: Sex differences in stress-induced social withdrawal: role of brain derived neurotrophic factor in the bed nucleus of the stria terminalis

    OpenAIRE

    Gian David Greenberg; Campi, Katharine L.

    2014-01-01

    Depression and anxiety disorders are more common in women than men, and little is known about the neurobiological mechanisms that contribute to this disparity. Recent data suggest that stress-induced changes in neurotrophins have opposing effects on behavior by acting in different brain networks. Social defeat has been an important approach for understanding neurotrophin action, but low female aggression levels in rats and mice have limited the application of these methods primarily to males....

  19. Sex differences in stress-induced social withdrawal: Role of brain derived neurotrophic factor in the bed nucleus of the stria terminalis

    OpenAIRE

    Greenberg, GD; Laman-Maharg, A; Campi, KL; Voigt, H; Orr, VN; Schaal, L; Trainor, BC

    2014-01-01

    Depression and anxiety disorders are more common in women than men, and little is known about the neurobiological mechanisms that contribute to this disparity. Recent data suggest that stress-induced changes in neurotrophins have opposing effects on behavior by acting in different brain networks. Social defeat has been an important approach for understanding neurotrophin action, but low female aggression levels in rats and mice have limited the application of these methods primarily to males....

  20. Adenovirus-mediated human brain-derived neurotrophic factor gene-modified bone marrow mesenchymal stem cell transplantation for spinal cord injury

    Institute of Scientific and Technical Information of China (English)

    Changsheng Wang; Jianhua Lin; Chaoyang Wu; Rongsheng Chen

    2011-01-01

    Rat bone marrow mesenchymal stem cells expressing brain-derived neurotrophic factor were successfully obtained using a gene transfection method, then intravenously transplanted into rats with spinal cord injury. At 1, 3, and 5 weeks after transplantation, the expression of ??brain-derived neurotrophic factor and neurofilament-200 was upregulated in the injured spinal cord, spinal cord injury was alleviated, and Basso-Beattie-Bresnahan scores of hindlimb motor function were significantly increased. This evidence suggested that intravenous transplantation of adenovirus- mediated brain-derived neurotrophic factor gene-modified rat bone marrow mesenchymal stem cells could play a dual role, simultaneously providing neural stem cells and neurotrophic factors.

  1. Time Course of Behavioral Alteration and mRNA Levels of Neurotrophic Factor Following Stress Exposure in Mouse.

    Science.gov (United States)

    Hashikawa, Naoya; Ogawa, Takumi; Sakamoto, Yusuke; Ogawa, Mami; Matsuo, Yumi; Zamami, Yoshito; Hashikawa-Hobara, Narumi

    2015-08-01

    Stress is known to affect neurotrophic factor expression, which induces depression-like behavior. However, whether there are time-dependent changes in neurotrophic factor mRNA expression following stress remains unclear. In the present study, we tested whether chronic stress exposure induces long-term changes in depression-related behavior, serum corticosterone, and hippocampal proliferation as well as neurotrophic factor family mRNA levels, such as brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), neurotrophin-3 (NT-3), and ciliary neurotrophic factor (CNTF), in the mouse hippocampus. The mRNA level of neurotrophic factors (BDNF, NGF, NT-3, and CNTF) was measured using the real-time PCR. The serum corticosterone level was evaluated by enzyme-linked immunosorbent assay, and, for each subject, the hippocampal proliferation was examined by 5-bromo-2-deoxyuridine immunostaining. Mice exhibited depression-like behavior in the forced-swim test (FST) and decreased BDNF mRNA and hippocampal proliferation in the middle of the stress exposure. After 15 days of stress exposure, we observed increased immobility in the FST, serum corticosterone levels, and BDNF mRNA levels and degenerated hippocampal proliferation, maintained for at least 2 weeks. Anhedonia-like behavior in the sucrose preference test and NGF mRNA levels were decreased following 15 days of stress. NGF mRNA levels were significantly higher 1 week after stress exposure. The current data demonstrate that chronic stress exposure induces prolonged BDNF and NGF mRNA changes and increases corticosterone levels and depression-like behavior in the FST, but does not alter other neurotrophic factors or performance in the sucrose preference test. PMID:25820756

  2. Up-regulation of neurotrophic factors by cinnamon and its metabolite sodium benzoate: therapeutic implications for neurodegenerative disorders.

    Science.gov (United States)

    Jana, Arundhati; Modi, Khushbu K; Roy, Avik; Anderson, John A; van Breemen, Richard B; Pahan, Kalipada

    2013-06-01

    This study underlines the importance of cinnamon, a widely-used food spice and flavoring material, and its metabolite sodium benzoate (NaB), a widely-used food preservative and a FDA-approved drug against urea cycle disorders in humans, in increasing the levels of neurotrophic factors [e.g., brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3)] in the CNS. NaB, but not sodium formate (NaFO), dose-dependently induced the expression of BDNF and NT-3 in primary human neurons and astrocytes. Interestingly, oral administration of ground cinnamon increased the level of NaB in serum and brain and upregulated the levels of these neurotrophic factors in vivo in mouse CNS. Accordingly, oral feeding of NaB, but not NaFO, also increased the level of these neurotrophic factors in vivo in the CNS of mice. NaB induced the activation of protein kinase A (PKA), but not protein kinase C (PKC), and H-89, an inhibitor of PKA, abrogated NaB-induced increase in neurotrophic factors. Furthermore, activation of cAMP response element binding (CREB) protein, but not NF-κB, by NaB, abrogation of NaB-induced expression of neurotrophic factors by siRNA knockdown of CREB and the recruitment of CREB and CREB-binding protein to the BDNF promoter by NaB suggest that NaB exerts its neurotrophic effect through the activation of CREB. Accordingly, cinnamon feeding also increased the activity of PKA and the level of phospho-CREB in vivo in the CNS. These results highlight a novel neutrophic property of cinnamon and its metabolite NaB via PKA - CREB pathway, which may be of benefit for various neurodegenerative disorders. PMID:23475543

  3. ETRR-2 control rod withdrawal accident

    International Nuclear Information System (INIS)

    A safety evaluation of Egypt new reactor, Egypt Test and Research Reactor number 2 (ETRR-2), has been completed successfully. Intensive efforts have been made for design basis accidents (DBA) analysis. The present work presents analysis of one of these accidents, i.e. the uncontrolled reactivity insertion accident (RIA) due to erroneous withdrawal of control rod (CR) during normal operating conditions. The reactivity insertion may be fast or slow, depending on the speed of CR withdrawal. The availability of the scam system is considered. The reactivity insertion function (RIF) is modeled by: 1 - an approximate ramp functions (RF), and 2 - actual S(cosine) function (CF). A computer code TRANSP19 is developed for the analysis. It models RIA of material test and research reactors (MTR). The code was verified against results obtained from RETRAN 02 and PARET codes and showed a good agreement. The study shows that ETRR-2 core, MTR type, withstands this type of perturbation, fast or slow, in condition that the shutdown system (SHDS) is available. Otherwise the coolant, clad, and fuel temperatures may exceed their design goal values [safety limits (SL)] and the clad may ruptures, coolant may boil, and the fuel may damage. The core reciprocal period never exceeds 140 s-1 for all accident cases (minimum period is 21.98 s) which demonstrates that no explosion other than sonic blockage could occur

  4. 21 CFR 870.1800 - Withdrawal-infusion pump.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Withdrawal-infusion pump. 870.1800 Section 870.1800 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... pump. (a) Identification. A withdrawal-infusion pump is a device designed to inject accurately...

  5. 17 CFR 242.405 - Withdrawal of margin.

    Science.gov (United States)

    2010-04-01

    ... account after such withdrawal is sufficient to satisfy the required margin for the security futures and...) REGULATIONS M, SHO, ATS, AC, AND NMS AND CUSTOMER MARGIN REQUIREMENTS FOR SECURITY FUTURES Customer Margin Requirements for Security Futures § 242.405 Withdrawal of margin. (a) By the customer. Except as...

  6. 27 CFR 19.997 - Withdrawal of fuel alcohol.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Withdrawal of fuel alcohol. 19.997 Section 19.997 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU... and Transfers § 19.997 Withdrawal of fuel alcohol. For each shipment or other removal of fuel...

  7. Emergency management of acute alcohol problems. Part 1: Uncomplicated withdrawal.

    OpenAIRE

    Etherington, J. M.

    1996-01-01

    Alcohol-related problems are common among patients in emergency departments. Primary care physicians must recognize and treat a variety of alcohol-related and alcohol-induced problems: alcohol withdrawal, alcohol-related seizures, delirium tremens, malnutrition, concomitant illness, poisoning, trauma, and lack of social support. This paper focuses an recognizing and managing acute alcohol withdrawal.

  8. 19 CFR 177.6 - Withdrawal of ruling requests.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Withdrawal of ruling requests. 177.6 Section 177.6 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY (CONTINUED) ADMINISTRATIVE RULINGS General Ruling Procedure § 177.6 Withdrawal of ruling...

  9. 21 CFR 900.6 - Withdrawal of approval.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Withdrawal of approval. 900.6 Section 900.6 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... committed fraud, or has submitted material false statements to the agency, FDA may withdraw its approval...

  10. 15 CFR 10.13 - Withdrawal of a published standard.

    Science.gov (United States)

    2010-01-01

    ... DEVELOPMENT OF VOLUNTARY PRODUCT STANDARDS § 10.13 Withdrawal of a published standard. (a) Standards published... organization, or that lack of government sponsorship would result in significant public disadvantage for legal... advantages and disadvantages of amendment, revision, development of a new standard, or withdrawal with...

  11. Acute coronary ischemia during alcohol withdrawal: a case report

    Directory of Open Access Journals (Sweden)

    Sriram Ganeshalingam

    2011-08-01

    Full Text Available Abstract Introduction The potential of alcohol withdrawal to cause acute coronary events is an area that needs the urgent attention of clinicians and researchers. Case presentation We report the case of a 52-year-old heavy-alcohol-using Sri Lankan man who developed electocardiogram changes suggestive of an acute coronary event during alcohol withdrawal. Despite the patient being asymptomatic, subsequent echocardiogram showed evidence of ischemic myocardial dysfunction. We review the literature on precipitation of myocardial ischemia during alcohol withdrawal and propose possible mechanisms. Conclusions Alcohol withdrawal is a commonly observed phenomenon in hospitals. However, the number of cases reported in the literature of acute coronary events occurring during withdrawal is few. Many cases of acute ischemia or sudden cardiac deaths may be attributed to other well known complications of delirium tremens. This is an area needing the urgent attention of clinicians and epidemiologists.

  12. Opiate Withdrawal Complicated by Tetany and Cardiac Arrest

    Directory of Open Access Journals (Sweden)

    Irfanali R. Kugasia

    2014-01-01

    Full Text Available Patients with symptoms of opiate withdrawal, after the administration of opiate antagonist by paramedics, are a common presentation in the emergency department of hospitals. Though most of opiate withdrawal symptoms are benign, rarely they can become life threatening. This case highlights how a benign opiate withdrawal symptom of hyperventilation led to severe respiratory alkalosis that degenerated into tetany and cardiac arrest. Though this patient was successfully resuscitated, it is imperative that severe withdrawal symptoms are timely identified and immediate steps are taken to prevent catastrophes. An easier way to reverse the severe opiate withdrawal symptom would be with either low dose methadone or partial opiate agonists like buprenorphine. However, if severe acid-base disorder is identified, it would be safer to electively intubate these patients for better control of their respiratory and acid-base status.

  13. Exposure to Early Life Stress Results in Epigenetic Changes in Neurotrophic Factor Gene Expression in a Parkinsonian Rat Model

    Directory of Open Access Journals (Sweden)

    Thabisile Mpofana

    2016-01-01

    Full Text Available Early life adversity increases the risk of mental disorders later in life. Chronic early life stress may alter neurotrophic factor gene expression including those for brain derived neurotrophic factor (BDNF and glial cell derived neurotrophic factor (GDNF that are important in neuronal growth, survival, and maintenance. Maternal separation was used in this study to model early life stress. Following unilateral injection of a mild dose of 6-hydroxydopamine (6-OHDA, we measured corticosterone (CORT in the blood and striatum of stressed and nonstressed rats; we also measured DNA methylation and BDNF and GDNF gene expression in the striatum using real time PCR. In the presence of stress, we found that there was increased corticosterone concentration in both blood and striatal tissue. Further to this, we found higher DNA methylation and decreased neurotrophic factor gene expression. 6-OHDA lesion increased neurotrophic factor gene expression in both stressed and nonstressed rats but this increase was higher in the nonstressed rats. Our results suggest that exposure to early postnatal stress increases corticosterone concentration which leads to increased DNA methylation. This effect results in decreased BDNF and GDNF gene expression in the striatum leading to decreased protection against subsequent insults later in life.

  14. Withdrawal of cerivastatin from the world market

    Directory of Open Access Journals (Sweden)

    Pitt Bertram

    2001-09-01

    Full Text Available Abstract Cerivastatin was recently withdrawn from the market because of 52 deaths attributed to drug-related rhabdomyolysis that lead to kidney failure. The risk was found to be higher among patients who received the full dose (0.8 mg/day and those who received gemfibrozil concomitantly. Rhabdomyolysis was 10 times more common with cerivastatin than the other five approved statins. We address three important questions raised by this withdrawal. Should we continue to approve drugs on surrogate efficacy? Are all statins interchangeable? Do the benefits outweigh the risks of statins? We conclude that decisions regarding the use of drugs should be based on direct evidence from long-term clinical outcome trials.

  15. Enhancement of Neurogenesis and Memory by a Neurotrophic Peptide in Mild to Moderate Traumatic Brain Injury

    Science.gov (United States)

    Chohan, Muhammad Omar; Bragina, Olga; Kazim, Syed Faraz; Statom, Gloria; Baazaoui, Narjes; Bragin, Denis; Iqbal, Khalid; Nemoto, Edwin; Yonas, Howard

    2016-01-01

    Background Traumatic Brain Injury (TBI) is a risk factor for Alzheimer disease (AD), a neurocognitive disorder with similar cellular abnormalities. We recently discovered a small molecule (Peptide 6) corresponding to an active region of human ciliary neurotrophic factor, with neurogenic and neurotrophic properties in mouse models of AD and Down syndrome. Objective To describe hippocampal abnormalities in a mouse model of mild to moderate TBI and their reversal by Peptide 6. Methods TBI was induced in adult C57Bl6 mice using controlled cortical impact (CCI) with 1.5 mm of cortical penetration. The animals were treated with 50 nmol/animal/day of Peptide 6 or saline for 30 days. Dentate gyrus (DG) neurogenesis, dendritic and synaptic density and AD biomarkers were quantitatively analyzed and behavioral tests were performed. Results Ipsilateral neuronal loss in CA1 and parietal cortex, and elevation of Alzheimer-type hyperphosphorylated tau and A-beta were seen in TBI-mice. When compared to saline, Peptide 6 treatment increased number of newborn neurons, but not uncommitted progenitors, in DG by 80%. Peptide 6 treatment also reversed TBI-induced dendritic and synaptic density loss while increasing activity in tri-synaptic hippocampal circuitry, ultimately leading to improvement in memory recall on behavioral testing. Conclusion Long-term treatment with Peptide 6 enhances the pool of newborn neurons in DG, prevents neuronal loss in CA1 and parietal cortex, preserves dendritic and synaptic architecture in the hippocampus, and improves performance on a hippocampus-dependent memory task in TBI mice. These findings necessitate further inquiry into therapeutic potential of small molecules based on neurotrophic factors. PMID:25255260

  16. Physical exercise in overweight to obese individuals induces metabolic- and neurotrophic-related structural brain plasticity

    Science.gov (United States)

    Mueller, Karsten; Möller, Harald E.; Horstmann, Annette; Busse, Franziska; Lepsien, Jöran; Blüher, Matthias; Stumvoll, Michael; Villringer, Arno; Pleger, Burkhard

    2015-01-01

    Previous cross-sectional studies on body-weight-related alterations in brain structure revealed profound changes in the gray matter (GM) and white matter (WM) that resemble findings obtained from individuals with advancing age. This suggests that obesity may lead to structural brain changes that are comparable with brain aging. Here, we asked whether weight-loss-dependent improved metabolic and neurotrophic functioning parallels the reversal of obesity-related alterations in brain structure. To this end we applied magnetic resonance imaging (MRI) together with voxel-based morphometry and diffusion-tensor imaging in overweight to obese individuals who participated in a fitness course with intensive physical training twice a week over a period of 3 months. After the fitness course, participants presented, with inter-individual heterogeneity, a reduced body mass index (BMI), reduced serum leptin concentrations, elevated high-density lipoprotein-cholesterol (HDL-C), and alterations of serum brain-derived neurotrophic factor (BDNF) concentrations suggesting changes of metabolic and neurotrophic function. Exercise-dependent changes in BMI and serum concentration of BDNF, leptin, and HDL-C were related to an increase in GM density in the left hippocampus, the insular cortex, and the left cerebellar lobule. We also observed exercise-dependent changes of diffusivity parameters in surrounding WM structures as well as in the corpus callosum. These findings suggest that weight-loss due to physical exercise in overweight to obese participants induces profound structural brain plasticity, not primarily of sensorimotor brain regions involved in physical exercise, but of regions previously reported to be structurally affected by an increased body weight and functionally implemented in gustation and cognitive processing. PMID:26190989

  17. Molecular mechanisms underlying the regulation of brain-derived neurotrophic factor (BDNF) translation in dendrites

    OpenAIRE

    Pinheiro, Vera Lúcia Margarido

    2010-01-01

    A especificidade espacial e temporal subjacente à diversidade de processos de plasticidade sináptica que ocorrem no sistema nervoso central está profundamente relacionada com a disponibilidade da proteína brain-derived neurotrophic factor (BDNF) em domínios sub-celulares distintos, especialmente na área pós-sináptica. Contudo, os mecanismos moleculares que regulam a síntese proteica de BDNF nas dendrites estão ainda por desvendar. Assim, o principal objectivo deste trabalho foi...

  18. Neuroblastoma cells contain a trophic factor sharing biological and molecular properties with ciliary neurotrophic factor.

    OpenAIRE

    Heymanns, J.; Unsicker, K

    1987-01-01

    Ciliary neurotrophic factor (CNTF) is a protein supporting the in vitro survival of a characteristic spectrum of embryonic chicken and rat peripheral neurons. High-speed supernatants of extracts from two neuroblastoma (NB) cell lines--the mouse C 1300 N2a and the human IMR 32--mimic the effects of CNTF on identical target neurons. Promotion of survival is dose-dependent with an ED50 of 80 micrograms (IMR 32) and 140 micrograms (C 1300 N2a) of protein per ml and saturable at plateau values for...

  19. Ciliary neurotrophic factor induces cholinergic differentiation of rat sympathetic neurons in culture

    OpenAIRE

    S. Saadat; Sendtner, Michael; H. Rohrer(Universität Mainz, Germany)

    1989-01-01

    Ciliary neurotrophic factor (CNTF) influences the levels of choline acetyltransferase (ChAT) and tyrosine hydroxylase (TH) in cultures of dissociated sympathetic neurons from newborn rats. In the presence of CNTF both the total and specific activity of ChAT was increased 7 d after culture by 15- and 18-fold, respectively, as compared to cultures kept in the absence of CNTF. Between 3 and 21 d in culture in the presence of CNTF the total ChAT activity increased by a factor of greater than 100....

  20. Ciliary neurotrophic factor (CNTF) prevents the degeneration of motor neurons after axotomy

    OpenAIRE

    Sendtner, Michael; Kreutzberg, Georg W.; Thoenen, Hans

    2009-01-01

    The period of natural cell death in the development of rodent motor neurons is followed by a period of sensitivity to axonal injury1-3. In the rat this early postnatal period of vulnerability coincides with that of very low ciliary neurotrophic factor (CNTF) levels in the sciatic nerve before CNTF increases to the high, adult levels4. The developmental time course of CNTF expression, its regional tissue distribution and its cytosolic localization (as suggested by its primary structure)4*5 fav...

  1. Increased serum brain-derived neurotrophic factor (BDNF) levels in patients with narcolepsy

    DEFF Research Database (Denmark)

    Klein, Anders B; Jennum, Poul; Knudsen, Stine;

    2013-01-01

    Narcolepsy is a lifelong sleep disorder characterized by excessive daytime sleepiness, sudden loss of muscle tone (cataplexy), fragmentation of nocturnal sleep and sleep paralysis. The symptoms of the disease strongly correlate with a reduction in hypocretin levels in CSF and a reduction in...... hypocretin neurons in hypothalamus in post-mortem tissue. Brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) are important for activity-dependent neuronal function and synaptic modulation and it is considered that these mechanisms are important in sleep regulation. We hypothesised that...

  2. The intricacies of neurotrophic factor therapy for retinal ganglion cell rescue in glaucoma: a case for gene therapy

    Science.gov (United States)

    Foldvari, Marianna; Chen, Ding Wen

    2016-01-01

    Regeneration of damaged retinal ganglion cells (RGC) and their axons is an important aspect of reversing vision loss in glaucoma patients. While current therapies can effectively lower intraocular pressure, they do not provide extrinsic support to RGCs to actively aid in their protection and regeneration. The unmet need could be addressed by neurotrophic factor gene therapy, where plasmid DNA, encoding neurotrophic factors, is delivered to retinal cells to maintain sufficient levels of neurotrophins in the retina. In this review, we aim to describe the intricacies in the design of the therapy including: the choice of neurotrophic factor, the site and route of administration and target cell populations for gene delivery. Furthermore, we also discuss the challenges currently being faced in RGC-related therapy development with special considerations to the existence of multiple RGC subtypes and the lack of efficient and representative in vitro models for rapid and reliable screening in the drug development process.

  3. Mitragynine attenuates withdrawal syndrome in morphine-withdrawn zebrafish.

    Science.gov (United States)

    Khor, Beng-Siang; Jamil, Mohd Fadzly Amar; Adenan, Mohamad Ilham; Shu-Chien, Alexander Chong

    2011-01-01

    A major obstacle in treating drug addiction is the severity of opiate withdrawal syndrome, which can lead to unwanted relapse. Mitragynine is the major alkaloid compound found in leaves of Mitragyna speciosa, a plant widely used by opiate addicts to mitigate the harshness of drug withdrawal. A series of experiments was conducted to investigate the effect of mitragynine on anxiety behavior, cortisol level and expression of stress pathway related genes in zebrafish undergoing morphine withdrawal phase. Adult zebrafish were subjected to two weeks chronic morphine exposure at 1.5 mg/L, followed by withdrawal for 24 hours prior to tests. Using the novel tank diving tests, we first showed that morphine-withdrawn zebrafish display anxiety-related swimming behaviors such as decreased exploratory behavior and increased erratic movement. Morphine withdrawal also elevated whole-body cortisol levels, which confirms the phenotypic stress-like behaviors. Exposing morphine-withdrawn fish to mitragynine however attenuates majority of the stress-related swimming behaviors and concomitantly lower whole-body cortisol level. Using real-time PCR gene expression analysis, we also showed that mitragynine reduces the mRNA expression of corticotropin releasing factor receptors and prodynorphin in zebrafish brain during morphine withdrawal phase, revealing for the first time a possible link between mitragynine's ability to attenuate anxiety during opiate withdrawal with the stress-related corticotropin pathway. PMID:22205946

  4. Tobacco withdrawal symptoms mediate motivation to reinstate smoking during abstinence.

    Science.gov (United States)

    Aguirre, Claudia G; Madrid, Jillian; Leventhal, Adam M

    2015-08-01

    Withdrawal-based theories of addiction hypothesize that motivation to reinstate drug use following acute abstinence is mediated by withdrawal symptoms. Experimental tests of this hypothesis in the tobacco literature are scant and may be subject to methodological limitations. This study utilized a robust within-subject laboratory experimental design to investigate the extent to which composite tobacco withdrawal symptomatology level and 3 unique withdrawal components (i.e., low positive affect, negative affect, and urge to smoke) mediated the effect of smoking abstinence on motivation to reinstate smoking. Smokers (≥10 cigarettes per day; N = 286) attended 2 counterbalanced sessions at which abstinence duration was differentially manipulated (1 hr vs. 17 hr). At both sessions, participants reported current withdrawal symptoms and subsequently completed a task in which they were monetarily rewarded proportional to the length of time they delayed initiating smoking, with shorter latency reflecting stronger motivation to reinstate smoking. Abstinence reduced latency to smoking initiation and positive affect and increased composite withdrawal symptom level, urge, and negative affect. Abstinence-induced reductions in latency to initiating smoking were mediated by each withdrawal component, with stronger effects operating through urge. Combined analyses suggested that urge, negative affect, and low positive affect operate through empirically unique mediational pathways. Secondary analyses suggested similar effects on smoking quantity, few differences among specific urge and affect subtypes, and that dependence amplifies some abstinence effects. This study provides the first experimental evidence that within-person variation in abstinence impacts motivation to reinstate drug use through withdrawal. Urge, negative affect, and low positive affect may reflect unique withdrawal-mediated mechanisms underlying tobacco addiction. PMID:25961814

  5. The Cytokine Ciliary Neurotrophic Factor (CNTF) Activates Hypothalamic Urocortin-Expressing Neurons Both In Vitro and In Vivo

    OpenAIRE

    Purser, Matthew J.; Dalvi, Prasad S.; Wang, Zi C.; Belsham, Denise D.

    2013-01-01

    Ciliary neurotrophic factor (CNTF) induces neurogenesis, reduces feeding, and induces weight loss. However, the central mechanisms by which CNTF acts are vague. We employed the mHypoE-20/2 line that endogenously expresses the CNTF receptor to examine the direct effects of CNTF on mRNA levels of urocortin-1, urocortin-2, agouti-related peptide, brain-derived neurotrophic factor, and neurotensin. We found that treatment of 10 ng/ml CNTF significantly increased only urocortin-1 mRNA by 1.84-fold...

  6. 77 FR 11554 - Final Decision on Withdrawal of Breast Cancer Indication for AVASTIN (Bevacizumab) Following...

    Science.gov (United States)

    2012-02-27

    ... HUMAN SERVICES Food and Drug Administration Final Decision on Withdrawal of Breast Cancer Indication for... final decision withdrawing approval of the breast cancer indication for AVASTIN (Bevacizumab). The... proposal to withdraw the approval. DATES: Withdrawal of AVASTIN's breast cancer indication was...

  7. Decreased plasma brain-derived neurotrophic factor and vascular endothelial growth factor concentrations during military training.

    Directory of Open Access Journals (Sweden)

    Go Suzuki

    Full Text Available Decreased concentrations of plasma brain-derived neurotrophic factor (BDNF and serum BDNF have been proposed to be a state marker of depression and a biological indicator of loaded psychosocial stress. Stress evaluations of participants in military mission are critically important and appropriate objective biological parameters that evaluate stress are needed. In military circumstances, there are several problems to adopt plasma BDNF concentration as a stress biomarker. First, in addition to psychosocial stress, military missions inevitably involve physical exercise that increases plasma BDNF concentrations. Second, most participants in the mission do not have adequate quality or quantity of sleep, and sleep deprivation has also been reported to increase plasma BDNF concentration. We evaluated plasma BDNF concentrations in 52 participants on a 9-week military mission. The present study revealed that plasma BDNF concentration significantly decreased despite elevated serum enzymes that escaped from muscle and decreased quantity and quality of sleep, as detected by a wearable watch-type sensor. In addition, we observed a significant decrease in plasma vascular endothelial growth factor (VEGF during the mission. VEGF is also neurotrophic and its expression in the brain has been reported to be up-regulated by antidepressive treatments and down-regulated by stress. This is the first report of decreased plasma VEGF concentrations by stress. We conclude that decreased plasma concentrations of neurotrophins can be candidates for mental stress indicators in actual stressful environments that include physical exercise and limited sleep.

  8. Elevated levels of plasma brain derived neurotrophic factor in rapid cycling bipolar disorder patients

    DEFF Research Database (Denmark)

    Munkholm, Klaus; Pedersen, Bente Klarlund; Kessing, Lars Vedel;

    2014-01-01

    Impaired neuroplasticity may be implicated in the pathophysiology of bipolar disorder, involving peripheral alterations of the neurotrophins brain derived neurotrophic factor (BDNF) and neurotrophin 3 (NT-3). Evidence is limited by methodological issues and is based primarily on case-control desi......Impaired neuroplasticity may be implicated in the pathophysiology of bipolar disorder, involving peripheral alterations of the neurotrophins brain derived neurotrophic factor (BDNF) and neurotrophin 3 (NT-3). Evidence is limited by methodological issues and is based primarily on case......-control designs. The aim of this study was to investigate whether BDNF and NT-3 levels differ between patients with rapid cycling bipolar disorder and healthy control subjects and whether BDNF and NT-3 levels alter with affective states in rapid cycling bipolar disorder patients. Plasma levels of BDNF and NT-3...... were measured in 37 rapid cycling bipolar disorder patients and in 40 age- and gender matched healthy control subjects using enzyme-linked immunosorbent assay (ELISA). In a longitudinal design, repeated measurements of BDNF and NT-3 were evaluated in various affective states in bipolar disorder...

  9. Inflammatory and neuropathic cold allodynia are selectively mediated by the neurotrophic factor receptor GFRα3.

    Science.gov (United States)

    Lippoldt, Erika K; Ongun, Serra; Kusaka, Geoffrey K; McKemy, David D

    2016-04-19

    Tissue injury prompts the release of a number of proalgesic molecules that induce acute and chronic pain by sensitizing pain-sensing neurons (nociceptors) to heat and mechanical stimuli. In contrast, many proalgesics have no effect on cold sensitivity or can inhibit cold-sensitive neurons and diminish cooling-mediated pain relief (analgesia). Nonetheless, cold pain (allodynia) is prevalent in many inflammatory and neuropathic pain settings, with little known of the mechanisms promoting pain vs. those dampening analgesia. Here, we show that cold allodynia induced by inflammation, nerve injury, and chemotherapeutics is abolished in mice lacking the neurotrophic factor receptor glial cell line-derived neurotrophic factor family of receptors-α3 (GFRα3). Furthermore, established cold allodynia is blocked in animals treated with neutralizing antibodies against the GFRα3 ligand, artemin. In contrast, heat and mechanical pain are unchanged, and results show that, in striking contrast to the redundant mechanisms sensitizing other modalities after an insult, cold allodynia is mediated exclusively by a single molecular pathway, suggesting that artemin-GFRα3 signaling can be targeted to selectively treat cold pain. PMID:27051069

  10. Responses of serum neurotrophic factors to exercise in pregnant and postpartum women.

    Science.gov (United States)

    Vega, Sandra Rojas; Kleinert, Jens; Sulprizio, Marion; Hollmann, Wildor; Bloch, Wilhelm; Strüder, Heiko K

    2011-02-01

    It was recently shown in humans that exercise affects the neurotrophic factors known to function as neurogenesis regulators. No data related to exercise and pregnancy, however, is yet available. Thus, we investigated the effects of acute exercise on pregnant women during late pregnancy and women postpartum, on the serum concentration of the brain-derived neurotrophic factor (BDNF), the insulin-like growth factor 1 (IGF-1), the vascular endothelial growth factor (VEGF), prolactin (PRL) and cortisol (COR). Twenty women with uncomplicated pregnancies underwent a graded submaximal exercise test during pregnancy (weeks 32-36 of gestation; T(1)) and postpartum (10-12 weeks after childbirth; T(2)). On two of these test days the women carried out an intensifying exercise test (25 W steps) on a cycle ergometer until a heart rate of 150 bpm was reached. Blood samples were taken in the rest period before beginning the exercise, immediately at the end of the exercise and after recovery periods of 5 and 10 min, respectively. Basal maternal IGF-1, PRL and COR were found to be higher during T(1) (pexercise, was at a higher level after exercise (pExercise increased the BDNF and IGF-1 during T(1) and T(2) (pexercise increases the serum concentrations of IGF-1 and BDNF during pregnancy and postpartum as well as VEGF postpartum. Thus, exercise might be a beneficial lifestyle factor with therapeutic/public health implications i.e. with regard to maternal mood and cognitive performance. PMID:20692101

  11. CNTF mediates neurotrophic factor secretion and fluid absorption in human retinal pigment epithelium.

    Directory of Open Access Journals (Sweden)

    Rong Li

    Full Text Available Ciliary neurotrophic factor (CNTF protects photoreceptors and regulates their phototransduction machinery, but little is known about CNTF's effects on retinal pigment epithelial (RPE physiology. Therefore, we determined the expression and localization of CNTF receptors and the physiological consequence of their activation in primary cultures of human fetal RPE (hfRPE. Cultured hfRPE express CNTF, CT1, and OsM and their receptors, including CNTFRα, LIFRβ, gp130, and OsMRβ, all localized mainly at the apical membrane. Exogenous CNTF, CT1, or OsM induces STAT3 phosphorylation, and OsM also induces the phosphorylation of ERK1/2 (p44/42 MAP kinase. CNTF increases RPE survivability, but not rates of phagocytosis. CNTF increases secretion of NT3 to the apical bath and decreases that of VEGF, IL8, and TGFβ2. It also significantly increases fluid absorption (J(V across intact monolayers of hfRPE by activating CFTR chloride channels at the basolateral membrane. CNTF induces profound changes in RPE cell biology, biochemistry, and physiology, including the increase in cell survival, polarized secretion of cytokines/neurotrophic factors, and the increase in steady-state fluid absorption mediated by JAK/STAT3 signaling. In vivo, these changes, taken together, could serve to regulate the microenvironment around the distal retinal/RPE/Bruch's membrane complex and provide protection against neurodegenerative disease.

  12. Brain Ciliary Neurotrophic Factor (CNTF and hypothalamic control of energy homeostasis

    Directory of Open Access Journals (Sweden)

    Vacher Claire-Marie

    2011-09-01

    Full Text Available Cytokines play an important role in energy-balance regulation. Notably leptin, an adipocyte-secreted cytokine, regulates the activity of hypothalamic neurons that are involved in the modulation of appetite. Leptin decreases appetite and stimulates weight loss in rodents. Unfortunately, numerous forms of obesity in humans seem to be resistant to leptin action. The ciliary neurotrophic factor (CNTF is a neurocytokine that belongs to the same family as leptin and that was originally characterized as a neurotrophic factor that promotes the survival of a broad spectrum of neuronal cell types and that enhances neurogenesis in adult rodents. It presents the advantage of stimulating weight loss in humans, despite the leptin resistance. Moreover, the weight loss persists several weeks after the cessation of treatment. Hence, CNTF has been considered as a promising therapeutic tool for the treatment of obesity and has prompted intense research aimed at identifying the cellular and molecular mechanisms underlying its potent anorexigenic properties. It has been found that CNTF shares signaling pathways with leptin and is expressed in the arcuate nucleus (ARC, a key hypothalamic region controlling food intake. Endogenous CNTF may also participate in the control of energy balance. Indeed, its expression in the ARC is inversely correlated to body weight in rats fed a high-sucrose diet. Thus hypothalamic CNTF may act, in some individuals, as a protective factor against weight gain during hypercaloric diet and could account for individual differences in the susceptibility to obesity.

  13. Regulation of neurotrophic factors and energy metabolism by antidepressants in astrocytes

    KAUST Repository

    Martin, Jean Luc

    2013-09-01

    There is growing evidence that astrocytes are involved in the neuropathology of major depression. In particular, decreases in glial cell density observed in the cerebral cortex of individuals with major depressive disorder are accompanied by a reduction of several astrocytic markers suggesting that astrocyte dysfunction may contribute to the pathophysiology of major depression. In rodents, glial loss in the prefrontal cortex is sufficient to induce depressive-like behaviors and antidepressant treatment prevents the stress-induced reduction of astrocyte number in the hippocampus. Collectively, these data support the existence of a link between astrocyte loss or dysfunction, depressive-like behavior and antidepressant treatment. Astrocytes are increasingly recognized to play important roles in neuronal development, neurotransmission, synaptic plasticity and maintenance of brain homeostasis. It is also well established that astrocytes provide trophic, structural, and metabolic support to neurons. In this article, we review evidence that antidepressants regulate energy metabolism and neurotrophic factor expression with particular emphasis on studies in astrocytes. These observations support a role for astrocytes as new targets for antidepressants. The contribution of changes in astrocyte glucose metabolism and neurotrophic factor expression to the therapeutic effects of antidepressants remains to be established. © 2013 Bentham Science Publishers.

  14. Direct withdrawal of zones during preparative capillary type isotachophoresis.

    Directory of Open Access Journals (Sweden)

    Yamada,Teruo

    1982-10-01

    Full Text Available This study used a Shimadzu IP-1B capillary type isotachophoretic apparatus with a potential gradient detector. An ipp-1 withdrawal cell was fitted to this and a technique for withdrawing individual components directly through this port was developed using a microsyringe. The recovery rate was up to 45% for individual target components. When 100% withdrawal of the target component was attempted by withdrawing a volume four times the calculated volume (so that the zones both before and after the target component were also included, the best recovery rate was only 78%. In all cases, the results varied less than 3%. The limit for analysis of individual components of a 0.01 M solution was around 3 microliters. If this volume was exceeded, the ion quantity was too large for the volume of the microcapillary tube and mixed zones formed such that complete separation and analysis of individual components became impossible.

  15. Steroid withdrawal in renal transplant patients: the Irish experience.

    LENUS (Irish Health Repository)

    Phelan, P J

    2012-02-01

    BACKGROUND: Steroid therapy is associated with significant morbidity in renal transplant recipients. However, there is concern that steroid withdrawal will adversely affect outcome. METHODS: We report on 241 renal transplant recipients on different doses of corticosteroids at 3 months (zero, <\\/= 5 mg\\/day, > 5 mg\\/day). Parameters analysed included blood pressure, lipid profile, weight change, new onset diabetes after transplantation (NODAT), allograft survival and acute rejection. RESULTS: Elimination of corticosteroids had no impact on allograft survival at 1 year. There were no cases of NODAT in the steroid withdrawal group compared with over 7% in each of the steroid groups. There were no significant improvements in weight gain, blood pressure control or total cholesterol with withdrawal of steroids before 3 months. CONCLUSIONS: In renal transplant patients treated with tacrolimus and mycophenolate, early withdrawal of steroids does not appear to adversely affect allograft outcome at 1 year. It may result in less NODAT.

  16. State National Pollutant Discharge Elimination System (NPDES) Program Withdrawal Petitions

    Data.gov (United States)

    U.S. Environmental Protection Agency — Search for pending and resolved NPDES withdrawal petitions by state, region, date, or keyword. "Pending" means EPA has received the petition and is working with the...

  17. 2017-2022 Draft Proposed Program - Withdrawal Areas

    Data.gov (United States)

    Bureau of Ocean Energy Management, Department of the Interior — This file represents the areas of the Outer Continental Shelf that have been withdrawn from disposition by leasing. The withdrawal of these areas prevents...

  18. The mechanism of pollination drop withdrawal in Ginkgo biloba L.

    Directory of Open Access Journals (Sweden)

    Jin Biao

    2012-05-01

    Full Text Available Abstract Background The pollination drop (PD is a characteristic feature of many wind-pollinated gymnosperms. Although accumulating evidence shows that the PD plays a critical role in the pollination process, the mechanism of PD withdrawal is still unclear. Here, we carefully observed the PD withdrawal process and investigated the underlying mechanism of PD withdrawal, which will aid the understanding of wind-pollination efficiency in gymnosperms. Results In Ginkgo biloba, PDs were secreted on the micropyle during the pollination period and persisted for about 240 h when not pollinated under laboratory conditions. The withdrawal of an isolated PD required only 1 h for evaporation, much less than a PD on the living ovule, which required 100 h. When pollinated with viable pollen, PDs withdrew rapidly within 4 h. In contrast, nonviable pollen and acetone-treated pollen did not cause PD withdrawal. Although 100% relative humidity significantly inhibited PD withdrawal, pollinated PDs still could withdraw completely within 48 h. Pollen grains of Cycas revoluta, which are similar to those of G. biloba, could induce PD withdrawal more rapidly than those of two distantly related gymnosperms (Pinus thunbergii and Abies firma or two angiosperms (Paeonia suffruticosa and Orychophragmus violaceus. Furthermore, pollen of G. biloba and C. revoluta submerged immediately when encountering the PD, then sank to the bottom and entered the micropyle. The saccate pollen of P. thunbergii and A. firma submerged into the PD, but remained floating at the top and finally accumulated on the micropyle after PD withdrawal. In contrast, pollen of the angiosperms P. suffruticosa, Salix babylonica, and O. violaceus did not submerge, instead remaining clustered at the edge without entering the PD. Conclusions We conclude that PD withdrawal is primarily determined by the dynamic balance between evaporation and ovule secretion, of which pollen is a critical stimulator

  19. Acute coronary ischemia during alcohol withdrawal: a case report

    OpenAIRE

    Sriram Ganeshalingam; Epa Dhanesha; Rodrigo Chaturaka; Jayasinghe Saroj

    2011-01-01

    Abstract Introduction The potential of alcohol withdrawal to cause acute coronary events is an area that needs the urgent attention of clinicians and researchers. Case presentation We report the case of a 52-year-old heavy-alcohol-using Sri Lankan man who developed electocardiogram changes suggestive of an acute coronary event during alcohol withdrawal. Despite the patient being asymptomatic, subsequent echocardiogram showed evidence of ischemic myocardial dysfunction. We review the literatur...

  20. Bupropion-Associated Withdrawal Symptoms: A Case Report

    OpenAIRE

    Berigan, Timothy R.; Harazin, Jeffrey S.

    1999-01-01

    Withdrawal symptoms associated with the cessation of therapy have been widely described for most antidepressants. The authors report irritable mood, anxiety, sleeplessness, headache, and generalized aches and pains associated with the abrupt discontinuation of bupropion treatment in a 32-year-old man being treated for nicotine dependence. The authors recommend a slow taper for antidepressant discontinuation, along with vigilance for withdrawal symptoms and educating patients to the benefits o...

  1. Withholding or withdrawing therapy in intensive care units

    DEFF Research Database (Denmark)

    Jensen, Hanne Irene; Ammentorp, Jette; Erlandsen, Mogens; Ording, Helle

    2011-01-01

    The purpose of the study was to determine the views of intensive care nurses, intensivists, and primary physicians regarding collaboration and other aspects of withholding and withdrawing therapy in the intensive care unit (ICU).......The purpose of the study was to determine the views of intensive care nurses, intensivists, and primary physicians regarding collaboration and other aspects of withholding and withdrawing therapy in the intensive care unit (ICU)....

  2. Oral health behavior of drug addicts in withdrawal treatment

    OpenAIRE

    Shekarchizadeh Hajar; Khami Mohammad R; Mohebbi Simin Z; Virtanen Jorma I

    2013-01-01

    Abstract Background Oral health behavior (OHB), one major factor contributing to proper oral health status, has been addressed insufficiently in addiction literature. The aim of our study was to investigate OHB and its determinants among drug addicts in withdrawal treatment. Methods Through a stratified cluster sampling method, we collected the data from 685 patients in withdrawal treatment in Tehran using self-administered questionnaires on OHB components and conducting interviews about pati...

  3. Reversible cardiomyopathy complicating intrathecal baclofen withdrawal: A case report

    OpenAIRE

    Pizon, Anthony F.; LoVecchio, Frank

    2007-01-01

    This case report is about reversible cardiomyopathy associated with intrathecal baclofen withdrawal. Previous literature has reported that enteral baclofen does not adequately control intrathecal baclofen withdrawal. In our case, coronary atherosclerosis did not play a role in the development of the cardiomyopathy. However, reinstitution of intrathecal baclofen promptly resulted in improvement. One could hypothesize that myocardial stunning from sympathetic hyperactivity led to a similar card...

  4. Mitragynine Attenuates Withdrawal Syndrome in Morphine-Withdrawn Zebrafish

    OpenAIRE

    Khor, Beng-Siang; Amar Jamil, Mohd Fadzly; Adenan, Mohamad Ilham; Chong Shu-Chien, Alexander

    2011-01-01

    A major obstacle in treating drug addiction is the severity of opiate withdrawal syndrome, which can lead to unwanted relapse. Mitragynine is the major alkaloid compound found in leaves of Mitragyna speciosa, a plant widely used by opiate addicts to mitigate the harshness of drug withdrawal. A series of experiments was conducted to investigate the effect of mitragynine on anxiety behavior, cortisol level and expression of stress pathway related genes in zebrafish undergoing morphine withdrawa...

  5. A request for hospice admission from hospital to withdraw ventilation

    OpenAIRE

    Gannon, C.

    2005-01-01

    A request to admit a hospital inpatient with motor neurone disease to the hospice generated unusual unease. Significantly, withdrawal of ventilation had already been planned. The presumption that ventilation would be withdrawn after transfer presented a dilemma. Should the hospice accept the admission? If so, should the hospice staff stop the ventilation, and then when and how? Debate centred on the continuity of best interests and the logistics of withdrawing ventilation. The factors making ...

  6. [What happened after meprobamate's withdrawal? Survey in two nursing homes].

    Science.gov (United States)

    Lounis, Yacine; Bonnet-Zamponi, Dominique; Pautas, Éric; Gaubert-Dahan, Marie-Line

    2016-01-01

    We have conducted in two nursing homes a survey to study the impact of meprobamate's withdrawal, at the beginning of 2012, in terms of extent of prescribing to others psychotropic drugs and occurrence of adverse events. After meprobamate's withdrawal, 65 % of residents did not receive alternative medication and within three months after meprobamate stopping, adverse events (drowsiness, falls and hospitalization) decreased while agitation did not increase. PMID:26976315

  7. Investigations into the behavioural and neurobiological effects of repeated ethanol withdrawal

    OpenAIRE

    Hoang, Leigh

    2011-01-01

    This thesis presents a rat model, by which the effects of repeated ethanol withdrawal on withdrawal severity was investigated, in relation to the cognitive and behavioural deficits associated with repeated episodes of withdrawal. Repeated ethanol withdrawal in the rat has been well established to model the effects of repeated episodes of human alcohol detoxification. This model has enabled the study of withdrawal severity and the role of the prefrontal cortex in the form of rat behaviour. ...

  8. Anhedonia as a component of the tobacco withdrawal syndrome.

    Science.gov (United States)

    Cook, Jessica W; Piper, Megan E; Leventhal, Adam M; Schlam, Tanya R; Fiore, Michael C; Baker, Timothy B

    2015-02-01

    Animal research suggests that anhedonia is a tobacco withdrawal symptom, but this topic has not been addressed definitively in research with humans. This research sought to determine whether anhedonia is (a) an element of the tobacco withdrawal syndrome in humans and (b) an impediment to successful tobacco cessation. Data were from 1,175 smokers (58.3% women; 85.5% White) participating in a randomized double-blind, placebo-controlled trial of smoking cessation pharmacotherapies. Ecological momentary assessments for 5 days before and 10 days after the target quit day were used to assess anhedonia and other established withdrawal symptoms. Consistent with drug withdrawal, anhedonia showed an inverted-U pattern of change in response to tobacco cessation and was associated with the severity of other withdrawal symptoms and tobacco dependence. Postquit anhedonia was associated with decreased latency to relapse (hazard ratio = 1.09, 95% confidence interval [CI] [1.02, 1.17]) and with lower 8-week point-prevalence abstinence (odds ratio = .91, 95% CI [.86, .97])-relations that remained significant when other withdrawal symptoms were included as predictors. Finally, nicotine replacement therapy nearly fully suppressed the increase in abstinence-related anhedonia (β = -.66, p understanding and treating tobacco addiction. PMID:25384069

  9. Craving and nicotine withdrawal in a Spanish smoking cessation sample.

    Science.gov (United States)

    Piñeiro, Bárbara; López-Durán, Ana; Fernández del Río, Elena; Martínez, Úrsula; Brandon, Thomas H; Becoña, Elisardo

    2014-01-01

    Craving and nicotine withdrawal syndrome (NWS) are components of the tobacco use disorder in DSM-5. They both appear after smoking cessation or an abrupt reduction in tobacco use, and they are associated with both short and long-term smoking-cessation outcomes. The aim of the present study was to examine the association of craving and withdrawal with smoking cessation at the end of the treatment and relapse at 3 months follow-up in a Spanish sample of smokers. The sample comprised 342 smokers (37.7% men; 62.3% women) receiving a cognitive-behavioral treatment for smoking cessation. The assessments of craving and withdrawal were conducted using the Minnesota Nicotine Withdrawal Scale. Abstainers at the end of the treatment, compared to non abstainers, showed significantly lower post-treatment withdrawal, and post-treatment craving. Furthermore, they had lower scores in pre-treatment nicotine dependence. Among abstainers, craving decreased significantly from pre-cessation levels, while in those participants who did not quit smoking it remained on the same levels. High nicotine dependence was a predictor of smoking at the end of the treatment, whereas high nicotine withdrawal predicted relapse at 3 months. Findings support the robust role of craving and NWS in smoking cessation and relapse, although they differ in their specific patterns of change over time. PMID:25314038

  10. Geomechanics of subsurface water withdrawal and injection

    Science.gov (United States)

    Gambolati, Giuseppe; Teatini, Pietro

    2015-06-01

    Land subsidence and uplift, ground ruptures, and induced seismicity are the principal geomechanic effects of groundwater withdrawal and injection. The major environmental consequence of groundwater pumping is anthropogenic land subsidence. The first observation concerning land settlement linked to subsurface processes was made in 1926 by the American geologists Pratt and Johnson, who wrote that "the cause of subsidence is to be found in the extensive extraction of fluid from beneath the affected area." Since then, impressive progress has been made in terms of: (a) recognizing the basic hydrologic and geomechanic principles underlying the occurrence; (b) measuring aquifer compaction and ground displacements, both vertical and horizontal; (c) modeling and predicting the past and future event; and (d) mitigating environmental impact through aquifer recharge and/or surface water injection. The first milestone in the theory of pumped aquifer consolidation was reached in 1923 by Terzaghi, who introduced the principle of "effective intergranular stress." In the early 1970s, the emerging computer technology facilitated development of the first mathematical model of the subsidence of Venice, made by Gambolati and Freeze. Since then, the comprehension, measuring, and simulation of the occurrence have improved dramatically. More challenging today are the issues of ground ruptures and induced/triggered seismicity, which call for a shift from the classical continuum approach to discontinuous mechanics. Although well known for decades, anthropogenic land subsidence is still threatening large urban centers and deltaic areas worldwide, such as Bangkok, Jakarta, and Mexico City, at rates in the order of 10 cm/yr.

  11. Light-induced retinal injury enhanced neurotrophins secretion and neurotrophic effect of mesenchymal stem cells in vitro

    Directory of Open Access Journals (Sweden)

    Wei Xu

    2013-04-01

    Full Text Available PURPOSE: To investigate neurotrophins expression and neurotrophic effect change in mesenchymal stem cells (MSCs under different types of stimulation. METHODS: Rats were exposed in 10,000 lux white light to develop light-induced retinal injury. Supernatants of homogenized retina (SHR, either from normal or light-injured retina, were used to stimulate MSCs. Quantitative real time for polymerase chain reaction (RT-PCR and enzyme-linked immunosorbent assay (ELISA were conducted for analysis the expression change in basic fibroblast growth factor (bFGF, brain-derived neurotrophic factor (BDNF and ciliary neurotrophic factor (CNTF in MSCs after stimulation. Conditioned medium from SHR-stimulated MSCs and control MSCs were collected for evaluation their effect on retinal explants. RESULTS: Supernatants of homogenized retina from light-injured rats significantly promoted neurotrophins secretion from MSCs (p<0.01. Conditioned medium from mesenchymal stem cells stimulated by light-injured SHR significantly reduced DNA fragmentation (p<0.01, up-regulated bcl-2 (p<0.01 and down-regulated bax (p<0.01 in retinal explants, displaying enhanced protective effect. CONCLUSIONS: Light-induced retinal injury is able to enhance neurotrophins secretion from mesenchymal stem cells and promote the neurotrophic effect of mesenchymal stem cells.

  12. Brain-derived neurotrophic factor as a regulator of systemic and brain energy metabolism and cardiovascular health

    OpenAIRE

    Rothman, Sarah M.; Kathleen J Griffioen; Wan, Ruiqian; Mattson, Mark P.

    2012-01-01

    Overweight sedentary individuals are at increased risk for cardiovascular disease, diabetes, and some neurological disorders. Beneficial effects of dietary energy restriction (DER) and exercise on brain structural plasticity and behaviors have been demonstrated in animal models of aging and acute (stroke and trauma) and chronic (Alzheimer's and Parkinson's diseases) neurological disorders. The findings described later, and evolutionary considerations, suggest brain-derived neurotrophic factor...

  13. SorLA Controls Neurotrophic Activity by Sorting of GDNF and Its Receptors GFRα1 and RET

    DEFF Research Database (Denmark)

    Glerup, Simon; Lume, Maria; Olsen, Ditte; Nyengaard, Jens R; Vaegter, Christian B; Gustafsen, Camilla; Christensen, Erik I; Kjolby, Mads; Hay-Schmidt, Anders; Bender, Dirk; Madsen, Peder; Saarma, Mart; Nykjaer, Anders; Petersen, Claus M

    2013-01-01

    targeted to lysosomes and degraded while GFRα1 recycles, creating an efficient GDNF clearance pathway. The SorLA/GFRα1 complex further targets RET for endocytosis but not for degradation, affecting GDNF-induced neurotrophic activities. SorLA-deficient mice display elevated GDNF levels, altered dopaminergic...

  14. Association analysis of the brain-derived neurotrophic factor gene polymorphisms with early-onset schizophrenia in the Chinese population

    Institute of Scientific and Technical Information of China (English)

    易正辉

    2012-01-01

    Objective To investigate the relationship between the brain-derived neurotrophic factor (BDNF) gene Tag SNPs(rs 11030101 and rs6265) and early-onset schizophrenia in the Chinese Han population. Methods The tag single nucleotide polymorphisms (tag SNPs) rs11030101 and rs6265 in the BDNF gene were genotyped

  15. Human umbilical cord blood stem cells and brain-derived neurotrophic factor for optic nerve injury: a biomechanical evaluation

    Directory of Open Access Journals (Sweden)

    Zhong-jun Zhang

    2015-01-01

    Full Text Available Treatment for optic nerve injury by brain-derived neurotrophic factor or the transplantation of human umbilical cord blood stem cells has gained progress, but analysis by biomechanical indicators is rare. Rabbit models of optic nerve injury were established by a clamp. At 7 days after injury, the vitreous body received a one-time injection of 50 μg brain-derived neurotrophic factor or 1 × 10 6 human umbilical cord blood stem cells. After 30 days, the maximum load, maximum stress, maximum strain, elastic limit load, elastic limit stress, and elastic limit strain had clearly improved in rabbit models of optical nerve injury after treatment with brain-derived neurotrophic factor or human umbilical cord blood stem cells. The damage to the ultrastructure of the optic nerve had also been reduced. These findings suggest that human umbilical cord blood stem cells and brain-derived neurotrophic factor effectively repair the injured optical nerve, improve biomechanical properties, and contribute to the recovery after injury.

  16. Human umbilical cord blood stem cells and brain-derived neurotrophic factor for optic nerve injury:a biomechanical evaluation

    Institute of Scientific and Technical Information of China (English)

    Zhong-jun Zhang; Ya-jun Li; Xiao-guang Liu; Feng-xiao Huang; Tie-jun Liu; Dong-mei Jiang; Xue-man Lv; Min Luo

    2015-01-01

    Treatment for optic nerve injury by brain-derived neurotrophic factor or the transplantation of human umbilical cord blood stem cells has gained progress, but analysis by biomechanical indicators is rare. Rabbit models of optic nerve injury were established by a clamp. At 7 days after injury, the vitreous body received a one-time injection of 50 μg brain-derived neurotrophic factor or 1 × 106 human umbilical cord blood stem cells. After 30 days, the maximum load, max-imum stress, maximum strain, elastic limit load, elastic limit stress, and elastic limit strain had clearly improved in rabbit models of optical nerve injury after treatment with brain-derived neu-rotrophic factor or human umbilical cord blood stem cells. The damage to the ultrastructure of the optic nerve had also been reduced. These ifndings suggest that human umbilical cord blood stem cells and brain-derived neurotrophic factor effectively repair the injured optical nerve, im-prove biomechanical properties, and contribute to the recovery after injury.

  17. Treadmill exercise induced functional recovery after peripheral nerve repair is associated with increased levels of neurotrophic factors.

    Directory of Open Access Journals (Sweden)

    Jae-Sung Park

    Full Text Available Benefits of exercise on nerve regeneration and functional recovery have been reported in both central and peripheral nervous system disease models. However, underlying molecular mechanisms of enhanced regeneration and improved functional outcomes are less understood. We used a peripheral nerve regeneration model that has a good correlation between functional outcomes and number of motor axons that regenerate to evaluate the impact of treadmill exercise. In this model, the median nerve was transected and repaired while the ulnar nerve was transected and prevented from regeneration. Daily treadmill exercise resulted in faster recovery of the forelimb grip function as evaluated by grip power and inverted holding test. Daily exercise also resulted in better regeneration as evaluated by recovery of compound motor action potentials, higher number of axons in the median nerve and larger myofiber size in target muscles. Furthermore, these observations correlated with higher levels of neurotrophic factors, glial derived neurotrophic factor (GDNF, brain derived neurotrophic factor (BDNF and insulin-like growth factor-1 (IGF-1, in serum, nerve and muscle suggesting that increase in muscle derived neurotrophic factors may be responsible for improved regeneration.

  18. Comparative Analysis of the Effects of Neurotrophic Factors CDNF and GDNF in a Nonhuman Primate Model of Parkinson's Disease.

    Directory of Open Access Journals (Sweden)

    Enrique Garea-Rodríguez

    Full Text Available Cerebral dopamine neurotrophic factor (CDNF belongs to a newly discovered family of evolutionarily conserved neurotrophic factors. We demonstrate for the first time a therapeutic effect of CDNF in a unilateral 6-hydroxydopamine (6-OHDA lesion model of Parkinson's disease in marmoset monkeys. Furthermore, we tested the impact of high chronic doses of human recombinant CDNF on unlesioned monkeys and analyzed the amino acid sequence of marmoset CDNF. The severity of 6-OHDA lesions and treatment effects were monitored in vivo using 123I-FP-CIT (DaTSCAN SPECT. Quantitative analysis of 123I-FP-CIT SPECT showed a significant increase of dopamine transporter binding activity in lesioned animals treated with CDNF. Glial cell line-derived neurotrophic factor (GDNF, a well-characterized and potent neurotrophic factor for dopamine neurons, served as a control in a parallel comparison with CDNF. By contrast with CDNF, only single animals responded to the treatment with GDNF, but no statistical difference was observed in the GDNF group. However, increased numbers of tyrosine hydroxylase immunoreactive neurons, observed within the lesioned caudate nucleus of GDNF-treated animals, indicate a strong bioactive potential of GDNF.

  19. Brain-Derived Neurotrophic Factor Gene Expression in Pediatric Bipolar Disorder: Effects of Treatment and Clinical Response

    Science.gov (United States)

    Pandey, Ghanshyam N.; Rizavi, Hooriyah S.; Dwivedi, Yogesh; Pavuluri, Mani N.

    2008-01-01

    The study determines the gene expression of brain-derived neurotrophic factor (BDNF) in the lymphocytes of subjects with pediatric bipolar disorder (PBD) before and during treatment with mood stabilizers and in drug-free normal control subjects. Results indicate the potential of BDNF levels as a biomarker for PBD and as a treatment predictor and…

  20. Chronic neonatal nicotine exposure increases mRNA expression of neurotrophic factors in the postnatal rat hippocampus.

    Science.gov (United States)

    Son, Jong-Hyun; Winzer-Serhan, Ursula H

    2009-06-30

    Nicotine, the psychoactive ingredient in tobacco, can be neuroprotective but the mechanism is unknown. In the adult hippocampus, chronic nicotine can increase expression of growth factors which could contribute to nicotine's neuroprotective effects. During development, nicotine could also increase expression of neurotrophic factors. Therefore, we determined whether chronic neonatal nicotine (CNN) exposure increased mRNA expression levels of brain-derived neurotrophic factor (BDNF), nerve-growth factor (NGF), neurotrophin-3 (NT-3), fibroblast growth factor-2 (FGF-2), and insulin-like growth factor-1 (IGF-1). Nicotine (6 mg/kg/day in milk formula) or milk formula (controls) were delivered in three daily doses via oral gastric intubation to rat pups from postnatal day (P)1 to P8, and then sacrificed. Brains were processed for in situ hybridization using specific (35)S-labeled cRNA probes. At P8, CNN had a significant stimulant treatment effect on the expression of BDNF, FGF-2, NT-3 and IGF-1 [pCNN increased the number of IGF-1-expressing cells in CA1 (18.0%), CA3 (20.9%) and DG (17.7%). Thus, nicotine exposure during early postnatal development differentially up-regulated expression of neurotrophic factor mRNAs in the hippocampus, which could increase neurotrophic tone and alter developmental processes. PMID:19410565

  1. Dysregulation of neurotrophic and inflammatory systems accompanied by decreased CREB signaling in ischemic rat retina.

    Science.gov (United States)

    Guo, Xian Jun; Tian, Xue Song; Ruan, Zhi; Chen, Yu Ting; Wu, Lei; Gong, Qi; Wang, Wei; Zhang, Hai Yan

    2014-08-01

    Although permanent bilateral common carotid artery occlusion (2VO) has been demonstrated to induce retinal injury, there is still a lack of systematic research on the complex processing of retinal degeneration. In the present study, time-dependent (at three, 14, 60 days after 2VO surgery) changes of neurotrophic and inflammatory systems, as well as cAMP-responsive element binding protein (CREB) signaling, which has been previously reported to effectively regulate these two systems, were evaluated. First, a morphological study confirmed that 2VO surgery progressively induced severe inner retinal degeneration and down-regulation of synaptic proteins, PSD95 and synaptophysin. The mRNA or protein levels of neurotrophic factors (NGF, BDNF, NT-3 and GDNF) and their receptors (TrkA, TrkB and TrkC) showed marked and persistent down-regulation in the rat retina since three days after 2VO surgery, whereas the gene transcription levels of CNTF were increased and p75(NTR) mRNA levels remained unchanged. In contrast to inner retinal degeneration, retinal Müller cells displayed rapid and prolonged activation since three days after 2VO lesion, whereas the microglia cell number, and TNF-α and IL-1β levels showed a robust increase with a maximal effect at three days and returned to levels that were slightly over baseline at 14 and 60 days after 2VO lesion. Interestingly, the gene expression levels of iNOS significantly decreased in the rat retina at both three and 14 days after 2VO surgery. Finally, as we hypothesized, remarkable reduction of CREB and extracellular signal-regulated kinase (ERK) phosphorylation levels were observed in the rat retina at three days after 2VO surgery. Thus, for the first time, our study demonstrated that chronic ischemia induced long-term aberrant CREB signaling and time-dependent progressive dysregulation of neurotrophic and inflammatory systems in the retina, which may provide important clues for a better understanding of the pathogenesis of

  2. Measurement of nicotine withdrawal symptoms: linguistic validation of the Wisconsin Smoking Withdrawal Scale (WSWS in Malay

    Directory of Open Access Journals (Sweden)

    Shafie Asrul A

    2010-05-01

    Full Text Available Abstract Background The purpose of the linguistic validation of the Wisconsin Smoking Withdrawal Scale (WSWS was to produce a translated version in Malay language which was "conceptually equivalent" to the original U.S. English version for use in clinical practice and research. Methods A seven-member translation committee conducted the translation process using the following methodology: production of two independent forward translations; comparison and reconciliation of the translations; backward translation of the first reconciled version; comparison of the original WSWS and the backward version leading to the production of the second reconciled version; pilot testing and review of the translation, and finalization. Results Linguistic and conceptual issues arose during the process of translating the instrument, particularly pertaining to the title, instructions, and some of the items of the scale. In addition, the researchers had to find culturally acceptable equivalents for some terms and idiomatic phrases. Notable among these include expressions such as "irritability", "feeling upbeat", and "nibbling on snacks", which had to be replaced by culturally acceptable expressions. During cognitive debriefing and clinician's review processes, the Malay translated version of WSWS was found to be easily comprehensible, clear, and appropriate for the smoking withdrawal symptoms intended to be measured. Conclusions We applied a rigorous translation method to ensure conceptual equivalence and acceptability of WSWS in Malay prior to its utilization in research and clinical practice. However, to complete the cultural adaptation process, future psychometric validation is planned to be conducted among Malay speakers.

  3. Morphine withdrawal dramatically reduces lymphocytes in morphine-dependent macaques.

    Science.gov (United States)

    Weed, Michael R; Carruth, Lucy M; Adams, Robert J; Ator, Nancy A; Hienz, Robert D

    2006-09-01

    The immune effects of chronic opiate exposure and/or opiate withdrawal are not well understood. The results of human studies with opiate abusers are variable and may not be able to control for important factors such as subjects' drug histories, health and nutritional status. Nonhuman primate models are necessary to control these important factors. A model of opiate dependence in macaques was developed to study the effects of opiate dependence and withdrawal on measures of immune function. Four pigtailed macaques drank a mixture of morphine (20 mg/kg/session) and orange-flavored drink every 6 h for several months. During stable morphine dependence, absolute numbers of neutrophils, monocytes and lymphocytes did not change relative to pre-morphine levels. However, there was a significant decrease in the absolute number and percentage of natural killer (NK) cells in morphine dependence. Either precipitated withdrawal or abstinence for 24 h resulted in behavioral withdrawal signs in all animals. Absolute lymphocyte counts decreased and absolute netrophil counts increased significantly in withdrawal, relative to levels during morphine dependence. Lymphocyte subset (CD4+, CD8+, CD20+) cells were also decreased in absolute numbers with little change in their percentage distributions. There was, however, a significant increase in the percentage of NK cells in withdrawal relative to levels during morphine dependence. This study demonstrates the usefulness of voluntary oral self-dosing procedures for maintaining morphine dependence in nonhuman primates and demonstrates that the morphine withdrawal syndrome includes large alterations in blood parameters of immune system function, including nearly 50% reduction in numbers of CD4+, CD8+ and CD20+ cells. PMID:18040802

  4. Activity-dependent brain-derived neurotrophic factor expression regulates cortistatin-interneurons and sleep behavior

    Directory of Open Access Journals (Sweden)

    Martinowich Keri

    2011-03-01

    Full Text Available Abstract Background Sleep homeostasis is characterized by a positive correlation between sleep length and intensity with the duration of the prior waking period. A causal role for brain-derived neurotrophic factor (BDNF in sleep homeostasis has been suggested, but the underlying mechanisms remain unclear. Cortistatin, a neuropeptide expressed primarily in a subset of cortical GABAergic interneurons, is another molecule implicated in sleep homeostasis. Results We confirmed that sleep deprivation leads to an increase in cortical cortistatin mRNA expression. Disruption of activity-dependent BDNF expression in a genetically modified mouse line impairs both baseline levels of cortistatin mRNA as well as its levels following sleep deprivation. Disruption of activity-dependent BDNF also leads to a decrease in sleep time during the active (dark phase. Conclusion Our studies suggest that regulation of cortistatin-expressing interneurons by activity-dependent BDNF expression may contribute to regulation of sleep behavior.

  5. [Mechanisms of neurotrophic and neuroprotective effects of cerebrolysin in cerebral ischemia.

    Science.gov (United States)

    Gromova, O A; Torshin, I Iu; Gogoleva, I V

    2014-01-01

    Cerebrolysin is the drug which contains peptides derived from the brain of a pig. It is used in neurological practice for recovery of stroke patients and treatment of dementia. Despite the evidence-basis and some experimental studies, the distinct mechanisms of pharmacological action of this drug remain unclear for most neurologists. In this paper, we present results of a molecular-biological analysis of peptide content of cerebrolysin. We have demonstrated the presence of active peptide fragments of nerve growth factor, enkephalins, orexin, halanin. The results of current clinical and experimental studies of cerebrolysin have been compared. The activity of above-mentioned neuropeptides explain experimental and clinical details of all known effects (neurotrophic, neuroprotective and immunomodulating) of cerebrolysin in ischemic and neurodegenerative CNS injuries. The analysis allowed to make conclusions about mechanisms of cerebrolysin action that were important for increasing the efficacy of this drug in clinical practice. PMID:24781241

  6. Serum brain-derived neurotrophic factor (BDNF) is not regulated by testosterone in transmen.

    Science.gov (United States)

    Auer, Matthias K; Hellweg, Rainer; Briken, Peer; Stalla, Günter K; T'Sjoen, Guy; Fuss, Johannes

    2016-01-01

    Brain morphology significantly differs between the sexes. It has been shown before that some of these differences are attributable to the sex-specific hormonal milieu. Brain-derived neurotrophic factor (BDNF) is involved in myriads of neuroplastic processes and shows a sexual dimorphism. Transsexual persons may serve as a model to study sex steroid-mediated effects on brain plasticity. We have recently demonstrated that serum levels of BDNF are reduced in transwomen following 12 months of cross-sex hormone treatment. We now wanted to look at the effects of testosterone treatment on BDNF in transmen. In contrast to our initial hypothesis, BDNF levels did not significantly change, despite dramatic changes in the sex-hormonal milieu. Our data indicate that testosterone does not seem to play a major role in the regulation of BDNF in females. PMID:26753091

  7. Brain-derived neurotrophic factor: a bridge between inflammation and neuroplasticity

    Directory of Open Access Journals (Sweden)

    Francesca eCalabrese

    2014-12-01

    Full Text Available Cytokines are key regulatory mediators involved in the host response to immunological challenges, but also play a critical role in the communication between the immune and the central nervous system. For this, their expression in both systems is under a tight regulatory control. However, pathological conditions may lead to an overproduction of pro-inflammatory cytokines that may have a detrimental impact on central nervous system. In particular, they may damage neuronal structure and function leading to deficits of neuroplasticity, the ability of nervous system to perceive, respond and adapt to external or internal stimuli.In search of the mechanisms by which pro-inflammatory cytokines may affect this crucial brain capability, we will discuss one of the most interesting hypotheses: the involvement of the neurotrophin brain-derived neurotrophic factor, which represents one of the major mediators of neuroplasticity.

  8. The effects of physical activity and exercise on brain-derived neurotrophic factor in healthy humans

    DEFF Research Database (Denmark)

    Huang, T; Larsen, K T; Ried-Larsen, M;

    2014-01-01

    The purpose of this study was to summarize the effects of physical activity and exercise on peripheral brain-derived neurotrophic factor (BDNF) in healthy humans. Experimental and observational studies were identified from PubMed, Web of Knowledge, Scopus, and SPORT Discus. A total of 32 articles...... studies suggested an inverse relationship between the peripheral BDNF level and habitual physical activity or cardiorespiratory fitness. More research is needed to confirm the findings from the observational studies....... met the inclusion criteria. Evidence from experimental studies suggested that peripheral BDNF concentrations were elevated by acute and chronic aerobic exercise. The majority of the studies suggested that strength training had no influence on peripheral BDNF. The results from most observational...

  9. Brain-derived neurotrophic factor and neural plasticity in a rat model of spinal cord transection

    Institute of Scientific and Technical Information of China (English)

    Ruxin Xing; Jia Liu; Hua Jin; Ping Dai; Tinghua Wang

    2011-01-01

    The present study employed a rat model of T10 spinal cord transection. Western blot analyses revealed increased brain-derived neurotrophic factor (BDNF) expression in spinal cord segments caudal to the transection site following injection of replication incompetent herpes simplex virus vector (HSV-BDNF) into the subarachnoid space. In addition, hindlimb locomotor functions were improved. In contrast, BDNF levels decreased following treatment with replication defective herpes simplex virus vector construct small interference BDNF (HSV-siBDNF). Moreover, hindlimb locomotor functions gradually worsened. Compared with the replication incompetent herpes simplex virus vector control group, extracellular signal regulated kinase1/2 expression increased in the HSV-BDNF group on days 14 and 28 after spinal cord transection, but expression was reduced in the HSV-siBDNF group. These results suggested that BDNF plays an important role in neural plasticity via extracellular signal regulated kinase1/2 signaling pathway in a rat model of adult spinal cord transection.

  10. Evidence for a release of brain-derived neurotrophic factor from the brain during exercise

    DEFF Research Database (Denmark)

    Rasmussen, Peter; Brassard, Patrice; Adser, Helle; Pedersen, Martin V; Leick, Lotte; Hart, Emma; Secher, Niels H; Pedersen, Bente K; Pilegaard, Henriette

    2009-01-01

    Brain-derived neurotrophic factor (BDNF) has an important role in regulating maintenance, growth and survival of neurons. However, the main source of circulating BDNF in response to exercise is unknown. To identify whether the brain is a source of BDNF during exercise, eight volunteers rowed for 4...... h while simultaneous blood samples were obtained from the radial artery and the internal jugular vein. To further identify putative cerebral region(s) responsible for BDNF release, mouse brains were dissected and analysed for BDNF mRNA expression following treadmill exercise. In humans, a BDNF...... release from the brain was observed at rest (P < 0.05), and increased two- to threefold during exercise (P < 0.05). Both at rest and during exercise, the brain contributed 70-80% of circulating BDNF, while that contribution decreased following 1 h of recovery. In mice, exercise induced a three- to...

  11. No effect of escitalopram versus placebo on brain-derived neurotrophic factor in healthy individuals

    DEFF Research Database (Denmark)

    Knorr, Ulla; Koefoed, Pernille; Soendergaard, Mia H Greisen;

    2016-01-01

    OBJECTIVE: Brain-derived neurotrophic factor (BDNF) seems to play an important role in the course of depression including the response to antidepressants in patients with depression. We aimed to study the effect of an antidepressant intervention on peripheral BDNF in healthy individuals with a...... family history of depression. METHODS: We measured changes in BDNF messenger RNA (mRNA) expression and whole-blood BDNF levels in 80 healthy first-degree relatives of patients with depression randomly allocated to receive daily tablets of escitalopram 10 mg versus placebo for 4 weeks. RESULTS: We found...... no statistically significant difference between the escitalopram and the placebo group in the change in BDNF mRNA expression and whole-blood BDNF levels. Post hoc analyses showed a statistically significant negative correlation between plasma escitalopram concentration and change in whole-blood BDNF...

  12. Effect of Brain-derived Neurotrophic Factor (BDNF in Organotypic Retinal Cultures

    Directory of Open Access Journals (Sweden)

    N.A. Gavrilova

    2009-02-01

    Full Text Available ABSTRACT Purpose To study the influence of recombinant brain-derived neurotrophic factor (BDNF on organotypic retinal cultures. Material and methods Experiments were performed in human and rat retinal explants cultured in culture dishes, flasks and flasks for roller cultivation. BDNF was added at the concentration of 100 ng⁄ml. Cultures were tested for viability and stained immunohistochemically for neuronal markers. Culture conditions and results of cultivation were controlled using phase contrast and fluorescent microscopes. Conclusions Results of the study showed that cultivation of organotypic cultures of the human and rat retina in the presence of BDNF at the concentration of 100 ng⁄ml increases viability of retinal cells. Active cell migration and outgrowth of β-III-tubulin-positive axon-like processes of neuronal origin outside the borders of explants were observed.

  13. Postnatal roles of glial cell line-derived neurotrophic factor family members in nociceptors plasticity

    Institute of Scientific and Technical Information of China (English)

    Sacha A. Malin; Brian M. Davis

    2008-01-01

    The neurotrophin and glial cell line-derived neurotrophic factor (GDNF) family of growth factors have been extensively studied because of their proven ability to regulate development of the peripheral nervous system. The neurotrophin family,which includes nerve growth factor (NGF), NT-3, NT4/5 and BDNF, is also known for its ability to regulate the function of adult sensory neurons. Until recently, little was known concerning the role of the GNDF-family (that includes GDNF, artemin, neurturin and persephin) in adult sensory neuron function. Here we describe recent data that indicates that the GDNF family can regulate sensory neuron function, that some of its members are elevated in inflammatory pain models and that application of these growth factors produces pain in vivo. Finally we discuss how these two families of growth factors may converge on a single membrane receptor, TRPV 1, to produce long-lasting hyperalgesia.

  14. Glial cell line-derived neurotrophic factor (GDNF therapy for Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Shingo,Tetsuro

    2007-04-01

    Full Text Available Many studies using animals clarify that glial cell line-derived neurotrophic factor (GDNF has strong neuroprotective and neurorestorative effects on dopaminergic neurons. Several pilot studies clarified the validity of continuous intraputaminal GDNF infusion to patients with Parkinson's disease (PD, although a randomized controlled trial of GDNF therapy published in 2006 resulted in negative outcomes, and controversy remains about the efficacy and safety of the treatment. For a decade, our laboratory has investigated the efficacy and the most appropriate method of GDNF administration using animals, and consequently we have obtained some solid data that correspond to the results of clinical trials. In this review, we present an outline of our studies and other key studies related to GDNF, the current state of the research, problems to be overcome, and predictions regarding the use of GDNF therapy for PD in the future.

  15. Possible Role of Brain-Derived Neurotrophic Factor (BDNF) in Autism Spectrum Disorder: Current Status

    International Nuclear Information System (INIS)

    Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family of survival-promoting molecules, plays a vital role in the growth, development, maintenance, and function of several neuronal systems. The purpose of this review is to document the support for the involvement of this molecule in the maintenance of normal cognitive, emotional functioning, and to outline recent developments in the content of Autism spectrum disorder (ASD). Current and future treatment development can be guided by developing understanding of this molecules actions in the brain and the ways the expression of BDNF can be planned. Over the years, research findings suggested a critical role played by BDNF in the development of autism including increased serum concentrations of BDNF in children with autism and identification of different forms of BDNF in families of autistic individuals. (author)

  16. Immune modulation and increased neurotrophic factor production in multiple sclerosis patients treated with testosterone

    Directory of Open Access Journals (Sweden)

    Giesser Barbara S

    2008-07-01

    Full Text Available Abstract Background Multiple sclerosis is a chronic inflammatory disease of the central nervous system with a pronounced neurodegenerative component. It has been suggested that novel treatment options are needed that target both aspects of the disease. Evidence from basic and clinical studies suggests that testosterone has an immunomodulatory as well as a potential neuroprotective effect that could be beneficial in MS. Methods Ten male MS patients were treated with 10 g of gel containing 100 mg of testosterone in a cross-over design (6 month observation period followed by 12 months of treatment. Blood samples were obtained at three-month intervals during the observation and the treatment period. Isolated blood peripheral mononuclear cells (PBMCs were used to examine lymphocyte subpopulation composition by flow cytometry and ex vivo protein production of cytokines (IL-2, IFNγ, TNFα, IL-17, IL-10, IL-12p40, TGFβ1 and growth factors (brain-derived neurotrophic factor BDNF, platelet-derived growth factor PDGF-BB, nerve growth factor NGF, and ciliary neurotrophic factor CNTF. Delayed type hypersensitivity (DTH skin recall tests were obtained before and during treatment as an in vivo functional immune measure. Results Testosterone treatment significantly reduced DTH recall responses and induced a shift in peripheral lymphocyte composition by decreasing CD4+ T cell percentage and increasing NK cells. In addition, PBMC production of IL-2 was significantly decreased while TGFβ1 production was increased. Furthermore, PBMCs obtained during the treatment period produced significantly more BDNF and PDGF-BB. Conclusion These results are consistent with an immunomodulatory effect of testosterone treatment in MS. In addition, increased production of BDNF and PDGF-BB suggests a potential neuroprotective effect. Trial Registration NCT00405353 http://www.clinicaltrials.gov

  17. Targeted delivery of brain-derived neurotrophic factor for the treatment of blindness and deafness

    Directory of Open Access Journals (Sweden)

    Khalin I

    2015-04-01

    Full Text Available Igor Khalin,1 Renad Alyautdin,2 Ganna Kocherga,3 Muhamad Abu Bakar1 1Faculty of Medicine and Defence Health, National Defence University of Malaysia, Kuala Lumpur, Malaysia; 2Scientific Centre for Expertise of Medical Application Products, Moscow, Russia; 3Ophthalmic Microsurgery Department, International Medical Center Oftalmika, Kharkiv, UkraineAbstract: Neurodegenerative causes of blindness and deafness possess a major challenge in their clinical management as proper treatment guidelines have not yet been found. Brain-derived neurotrophic factor (BDNF has been established as a promising therapy against neurodegenerative disorders including hearing and visual loss. Unfortunately, the blood–retinal barrier and blood–cochlear barrier, which have a comparable structure to the blood–brain barrier prevent molecules of larger sizes (such as BDNF from exiting the circulation and reaching the targeted cells. Anatomical features of the eye and ear allow use of local administration, bypassing histo-hematic barriers. This paper focuses on highlighting a variety of strategies proposed for the local administration of the BDNF, like direct delivery, viral gene therapy, and cell-based therapy, which have been shown to successfully improve development, survival, and function of spiral and retinal ganglion cells. The similarities and controversies for BDNF treatment of posterior eye diseases and inner ear diseases have been analyzed and compared. In this review, we also focus on the possibility of translation of this knowledge into clinical practice. And finally, we suggest that using nanoparticulate drug-delivery systems may substantially contribute to the development of clinically viable techniques for BDNF delivery into the cochlea or posterior eye segment, which, ultimately, can lead to a long-term or permanent rescue of auditory and optic neurons from degeneration. Keywords: brain-derived neurotrophic factor, neurodegeneration, posterior eye segment

  18. Withdrawal-like effects of pentylenetetrazol and valproate in the naive organism: a model of motivation produced by opiate withdrawal?

    Science.gov (United States)

    Mucha, R F; Fassos, F F; Perl, F M

    1995-07-01

    Pentylenetetrazol (PTZ) and sodium valproate (VPA) produce acutely in the naive rat various behavioural effects resembling signs of opiate withdrawal in the morphine-treated subject. Suggestions in the literature that these substances may activate directly some of the neural consequences of opiate and drug withdrawal prompted us to look for and examine possible aversive effects of these substances at non-toxic doses. With a sensitive two-flavour, three-trial taste aversion procedure, relatively low doses of PTZ and VPA (5 and 160 mg/kg, respectively) do indeed have aversive effects. The maximum aversions were produced by 10 and 20 mg/kg PTZ and 320 mg/kg VPA and were equivalent to those of morphine withdrawal precipitated by 0.01-0.03 mg/kg naloxone in a morphine pellet-implanted animal. Moreover, the maximum aversions with PTZ and VPA were significantly higher than the maximum aversions seen with naloxone in the drug-naive animal under the same training conditions. Thus, the data from the present study confirmed the notion that low doses of PTZ and VPA in the naive animal may activate processes activated by drug withdrawal, including those important for the motivational effect of withdrawal. However, it was also pointed out that the lowest dose VPA producing aversion was higher than that found here to produce writhes and ataxia (80 mg/kg) but the same as that required for shaking (160 mg/kg), while the PTZ aversion was at a dose lower than that known to produce a PTZ cue. Implications were discussed for using withdrawal-like phenomena as a model in the non-treated organism of clinically-relevant withdrawal effects. PMID:7587968

  19. Age-Related Changes in Demand-Withdraw Communication Behaviors.

    Science.gov (United States)

    Holley, Sarah R; Haase, Claudia M; Levenson, Robert W

    2013-08-01

    Demand-withdraw communication is a set of conflict-related behaviors in which one partner blames or pressures while the other partner withdraws or avoids. The present study examined age-related changes in these behaviors longitudinally over the course of later life stages. One hundred twenty-seven middle-aged and older long-term married couples were observed at 3 time points across 13 years as they engaged in a conversation about an area of relationship conflict. Husbands' and wives' demand-withdraw behaviors (i.e., blame, pressure, withdrawal, avoidance) were objectively rated by trained coders at each time point. Data were analyzed using dyad-level latent growth curve models in a structural equation modeling framework. For both husbands and wives, the results showed a longitudinal pattern of increasing avoidance behavior over time and stability in all other demand and withdraw behaviors. This study supports the notion that there is an important developmental shift in the way that conflict is handled in later life. PMID:23913982

  20. Takotsubo Cardiomyopathy and Catatonia in the Setting of Benzodiazepine Withdrawal

    Science.gov (United States)

    Peng, Teng J.

    2016-01-01

    We report two serious and unusual complications of benzodiazepine withdrawal in a single patient: takotsubo cardiomyopathy and catatonia. This 61-year-old female patient was brought to the emergency department with lethargy and within hours had declined into a state of catatonia. Although there was never a complaint of chest pain, ECG showed deep anterior T-wave inversions and cardiac enzymes were elevated. An echocardiogram was consistent with takotsubo cardiomyopathy. She later received 1 mg of midazolam and within minutes had resolution of catatonic symptoms. Careful history revealed that she had omitted her daily dose of lorazepam for 3 days prior to admission. To our knowledge, the case presented herein is the first report of simultaneous catatonia and takotsubo cardiomyopathy in the setting of benzodiazepine withdrawal. The pathogenesis of both conditions is poorly understood but may be indirectly related to the sudden decrease in γ-aminobutyric acid (GABA) signaling during benzodiazepine withdrawal. PMID:27547472

  1. Phenobarbital compared to benzodiazepines in alcohol withdrawal treatment

    DEFF Research Database (Denmark)

    Askgaard, Gro; Hallas, Jesper; Fink-Jensen, Anders; Molander, Anna Camilla; Madsen, Kenneth Grønkjær; Pottegård, Anton

    2016-01-01

    BACKGROUND: Long-acting benzodiazepines such as chlordiazepoxide are recommended as first-line treatment for alcohol withdrawal. These drugs are known for their abuse liability and might increase alcohol consumption among problem drinkers. Phenobarbital could be an alternative treatment option......, possibly with the drawback of a more pronounced acute toxicity. We evaluated if phenobarbital compared to chlordiazepoxide decreased the risk of subsequent use of benzodiazepines, alcohol recidivism and mortality. METHODS: The study was a register-based cohort study of patients admitted for alcohol...... withdrawal 1998-2013 and treated with either phenobarbital or chlordiazepoxide. Patients were followed for one year. We calculated hazard ratios (HR) for benzodiazepine use, alcohol recidivism and mortality associated with alcohol withdrawal treatment, while adjusting for confounders. RESULTS: A total of...

  2. Deadly pressure pneumothorax after withdrawal of misplaced feeding tube

    DEFF Research Database (Denmark)

    Andresen, Erik Nygaard; Frydland, Martin; Usinger, Lotte

    2016-01-01

    BACKGROUND: Many patients have a nasogastric feeding tube inserted during admission; however, misplacement is not uncommon. In this case report we present, to the best of our knowledge, the first documented fatality from pressure pneumothorax following nasogastric tube withdrawal. CASE PRESENTATION......, but our patient died less than an hour after withdrawal. The autopsy report stated that cause of death was tension pneumothorax, which developed following withdrawal of the misplaced feeding tube. CONCLUSIONS: The indications for insertion of nasogastric feeding tubes are many and the procedure is...... considered harmless; however, if the tube is misplaced there is good reason to be cautious on removal as this can unmaskpuncture of the pleura eliciting pneumothorax and, as this case report shows, result in an ultimately deadly tension pneumothorax....

  3. Factor Structure of CIWA-Ar in Alcohol Withdrawal.

    Science.gov (United States)

    Bakhla, Ajay Kumar; Khess, Christoday R J; Verma, Vijay; Hembram, Mahesh; Praharaj, Samir Kumar; Soren, Subhas

    2014-01-01

    Objective. To identify the underlying factor structure of alcohol withdrawal syndrome, as measured with CIWA-Ar. Methods. Exploratory factor analysis was conducted on the items of CIWA-Ar. On 201 alcohol-dependent male patients seeking treatment for alcohol withdrawal at 36 hours of abstinence. Results. A three-factor solution was obtained that accounted for 68.74% of total variance. First factor had loading from four items (34.34% variance), second factor also had four items (24.25% variance), and the third had two items (10.04% variance). Conclusions. Factor analysis reveals the existence of multidimensionality of alcohol withdrawal as measured with CIWA-Ar and we found three factors that can be named as delirious, autonomic and nonspecific factors. PMID:24826372

  4. Factor Structure of CIWA-Ar in Alcohol Withdrawal

    Directory of Open Access Journals (Sweden)

    Ajay Kumar Bakhla

    2014-01-01

    Full Text Available Objective. To identify the underlying factor structure of alcohol withdrawal syndrome, as measured with CIWA-Ar. Methods. Exploratory factor analysis was conducted on the items of CIWA-Ar. On 201 alcohol-dependent male patients seeking treatment for alcohol withdrawal at 36 hours of abstinence. Results. A three-factor solution was obtained that accounted for 68.74% of total variance. First factor had loading from four items (34.34% variance, second factor also had four items (24.25% variance, and the third had two items (10.04% variance. Conclusions. Factor analysis reveals the existence of multidimensionality of alcohol withdrawal as measured with CIWA-Ar and we found three factors that can be named as delirious, autonomic and nonspecific factors.

  5. Ciliary neurotrophic factor (CNTF) plus soluble CNTF receptor α increases cyclooxygenase-2 expression, PGE2 release and interferon-γ-induced CD40 in murine microglia

    OpenAIRE

    Li Hong; Jain Mohit; Lin Hsiao-Wen; Levison Steven W

    2009-01-01

    Abstract Background Ciliary neurotrophic factor (CNTF) has been regarded as a potent trophic factor for motor neurons. However, recent studies have shown that CNTF exerts effects on glial cells as well as neurons. For instance, CNTF stimulates astrocytes to secrete FGF-2 and rat microglia to secrete glial cell line-derived neurotrophic factor (GDNF), which suggest that CNTF exerts effects on astrocytes and microglia to promote motor neuron survival indirectly. As CNTF is structurally related ...

  6. Combining acellular nerve allografts with brain-derived neurotrophic factor transfected bone marrow mesenchymal stem cells restores sciatic nerve injury better than either intervention alone

    OpenAIRE

    Zhang, Yanru; Zhang, Hui; Zhang, Gechen; Ka, Ka; Huang, Wenhua

    2014-01-01

    In this study, we chemically extracted acellular nerve allografts from bilateral sciatic nerves, and repaired 10-mm sciatic nerve defects in rats using these grafts and brain-derived neurotrophic factor transfected bone marrow mesenchymal stem cells. Experiments were performed in three groups: the acellular nerve allograft bridging group, acellular nerve allograft + bone marrow mesenchymal stem cells group, and the acellular nerve allograft + brain-derived neurotrophic factor transfected bone...

  7. Comparative Analysis of the Effects of Neurotrophic Factors CDNF and GDNF in a Nonhuman Primate Model of Parkinson’s Disease

    OpenAIRE

    Garea-Rodríguez, Enrique; Eesmaa, Ave; Lindholm, Päivi; Schlumbohm, Christina; König, Jessica; Meller, Birgit; Krieglstein, Kerstin; Helms, Gunther; Saarma, Mart; Fuchs, Eberhard

    2016-01-01

    Cerebral dopamine neurotrophic factor (CDNF) belongs to a newly discovered family of evolutionarily conserved neurotrophic factors. We demonstrate for the first time a therapeutic effect of CDNF in a unilateral 6-hydroxydopamine (6-OHDA) lesion model of Parkinson’s disease in marmoset monkeys. Furthermore, we tested the impact of high chronic doses of human recombinant CDNF on unlesioned monkeys and analyzed the amino acid sequence of marmoset CDNF. The severity of 6-OHDA lesions and treatmen...

  8. Modeling reasons for Russian bank license withdrawal: Unaccounted factors

    OpenAIRE

    Peresetsky , Anatoly

    2013-01-01

    In the paper we analyze the reasons of Russian bank license withdrawal, formulated in orders of CB RF at the period 2005.2–2008.4. During this period, after establishing deposit insurance system in Russia, two main reasons were «money laundering» and «financial insolvency». We design binary choice logit models and multinomial logit models to model probability of license withdrawal one year ahead of the event. We use in model macro indicators to control for the varying economic environment and...

  9. Gender differences in zebrafish responses to cocaine withdrawal

    OpenAIRE

    López Patiño, Marcos A.; Yu, Lili; Yamamoto, Bryan K.; Zhdanova, Irina V.

    2008-01-01

    The acute responses to cocaine and its withdrawal contribute to cocaine dependence and potentiate relapse, with gender being one of the genetic factors affecting the outcome. Here we report that in both male and female zebrafish (Danio rerio, AB strain), an initial low-dose cocaine treatment (1.5μM, immersion) does not acutely change their behavior. The cocaine withdrawal, however, is associated with an anxiety-like state that develops earlier in female zebrafish but is more robust and persis...

  10. Age-Related Changes in Demand–Withdraw Communication Behaviors

    OpenAIRE

    Holley, Sarah R.; Haase, Claudia M.; Levenson, Robert W.

    2013-01-01

    Demand–withdraw communication is a set of conflict-related behaviors in which one partner blames or pressures while the other partner withdraws or avoids. The present study examined age-related changes in these behaviors longitudinally over the course of later life stages. One hundred twenty-seven middle-aged and older long-term married couples were observed at 3 time points across 13 years as they engaged in a conversation about an area of relationship conflict. Husbands’ and wives’ demand–w...

  11. Factor Structure of CIWA-Ar in Alcohol Withdrawal

    OpenAIRE

    Ajay Kumar Bakhla; Khess, Christoday R.J.; Vijay Verma; Mahesh Hembram; Samir Kumar Praharaj; Subhas Soren

    2014-01-01

    Objective. To identify the underlying factor structure of alcohol withdrawal syndrome, as measured with CIWA-Ar. Methods. Exploratory factor analysis was conducted on the items of CIWA-Ar. On 201 alcohol-dependent male patients seeking treatment for alcohol withdrawal at 36 hours of abstinence. Results. A three-factor solution was obtained that accounted for 68.74% of total variance. First factor had loading from four items (34.34% variance), second factor also had four items (24.25% variance...

  12. Prospective Assessment of Cannabis Withdrawal in Adolescents with Cannabis Dependence: A Pilot Study

    Science.gov (United States)

    Milin, Robert; Manion, Ian; Dare, Glenda; Walker, Selena

    2008-01-01

    A study to identify and assess the withdrawal symptoms in adolescents afflicted with cannabis dependence is conducted. Results conclude that withdrawal symptoms of cannabis were present in adolescents seeking treatment for this substance abuse.

  13. 26 CFR 54.4980B-9 - Business reorganizations and employer withdrawals from multiemployer plans.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 17 2010-04-01 2010-04-01 false Business reorganizations and employer...-9 Business reorganizations and employer withdrawals from multiemployer plans. The following... affected qualified beneficiaries in the context of business reorganizations and employer withdrawals...

  14. [The effect of neurotrophic treatment on the activation of reparative processes in patients with acute traumatic brain injury].

    Science.gov (United States)

    Selianina, N V; Karakulova, Iu V

    2012-01-01

    The complex study of cognitive and emotional status, levels of serum serotonin and brain-derived neurotrophic factor (BDNF) were performed in 72 patients with acute traumatic brain injury, with a special focus on middle brain injuries (MBI), treated with Cerebrolysin. The neurological and cognitive impairment, mild state anxiety and depression and increased levels of humoral serotonin, which depends on the severity of the injury, were identified in patients with MBI before treatment. After the treatment, there were the decrease in the severity of neurological symptoms and a significant positive dynamics on the FAB scale as well as the increase in blood BDNF and serotonin levels. It has been concluded that using cerebrolysin in complex treatment of acute MBI promotes activation of neurotrophic processes and improves outcomes of closed craniocerebral injury. PMID:22951781

  15. Plasma level of brain-derived neurotrophic factor and the related analysis in depressive patients with suicide attempt

    Institute of Scientific and Technical Information of China (English)

    操军

    2014-01-01

    Objective To explore the association between brainderived neurotrophic factor(BDNF)and suicidal behavior through analyzing and detecting the alteration of plasma BDNF level in depressive patients with suicide attempt.Methods Using enzyme-linked immunosorbent analysis(ELISA)to test the plasma level of BDNF in 27suicidal depressed patients,33 non-suicidal depressed patients and 30 normal controls.Meanwhile,the Hamilton Depression Scale(HAMD)and Beck

  16. Association of decreased serum brain-derived neurotrophic factor (BDNF) concentrations in early pregnancy with antepartum depression

    OpenAIRE

    Fung, Jenny; Gelaye, Bizu; Zhong, Qiu-Yue; Rondon, Marta B; Sanchez, Sixto E; Barrios, Yasmin V; Hevner, Karin; Qiu, Chunfang; Williams, Michelle A.

    2015-01-01

    Background Antepartum depression is one of the leading causes of maternal morbidity and mortality in the prenatal period. There is accumulating evidence for the role of brain-derived neurotrophic factor (BDNF) in the pathophysiology of depression. The present study examines the extent to which maternal early pregnancy serum BDNF levels are associated with antepartum depression. Method A total of 968 women were recruited and interviewed in early pregnancy. Antepartum depression prevalence and ...

  17. Association of decreased serum brain-derived neurotrophic factor (BDNF) concentrations in early pregnancy with antepartum depression

    OpenAIRE

    Fung, Jenny; Gelaye, Bizu; Zhong, Qiu-Yue; Rondon, Marta B; Sanchez, Sixto E; Barrios, Yasmin V; Hevner, Karin; Qiu, Chunfang; Williams, Michelle A.

    2015-01-01

    Background: Antepartum depression is one of the leading causes of maternal morbidity and mortality in the prenatal period. There is accumulating evidence for the role of brain-derived neurotrophic factor (BDNF) in the pathophysiology of depression. The present study examines the extent to which maternal early pregnancy serum BDNF levels are associated with antepartum depression. Method A total of 968 women were recruited and interviewed in early pregnancy. Antepartum depression prevalence and...

  18. Focal release of neurotrophic factors by biodegradable microspheres enhance motor and sensory axonal regeneration in vitro and in vivo

    OpenAIRE

    Santos, Daniel; GIUDETTI Guido; Micera, Silvestro; Navarro Acebes, Xavier; Valle Macia, Jaume del

    2016-01-01

    Neurotrophic factors (NTFs) promote nerve regeneration and neuronal survival after peripheral nerve injury. However, drawbacks related with administration and bioactivity during long periods limit their therapeutic application. In this study, PLGA microspheres (MPs) were used to locally release different NTFs and evaluate whether they accelerate axonal regeneration in comparison with free NTFs or controls. ELISA, SEM, UV/visible light microscopy, organotypic cultures of DRG explants and spina...

  19. Zirconium oxide ceramic foam: a promising supporting biomaterial for massive production of glial cell line-derived neurotrophic factor*

    OpenAIRE

    Liu, Zhong-Wei; Li, Wen-qiang; Wang, Jun-kui; Ma, Xian-cang; Liang, Chen; Liu, Peng; Chu, Zheng; Dang, Yong-hui

    2014-01-01

    This study investigated the potential application of a zirconium oxide (ZrO2) ceramic foam culturing system to the production of glial cell line-derived neurotrophic factor (GDNF). Three sets of ZrO2 ceramic foams with different pore densities of 10, 20, and 30 pores per linear inch (PPI) were prepared to support a 3D culturing system. After primary astrocytes were cultured in these systems, production yields of GDNF were evaluated. The biomaterial biocompatibility, cell proliferation and act...

  20. Effects of ciliary neurotrophic factor on retrograde cell reaction after facial nerve crush in young adults rats

    OpenAIRE

    Gispen, W.H.; Ulenkate, H.J.L.M.; Jennekens, F.G.I.

    1996-01-01

    Locally applied ciliary neurotrophic factor (CNTF) has a powerful effect on retrograde axonal reaction following facial nerve crush in neonatal rats. We examined whether it also exerts a strong effect on retrograde axonal reaction in young adult rats when administered subcutaneously. The dose was 1 mg/kg body weight, three times a week, similar to that used in a previous experiment in which CNTF was reported to have an effect. We studied changes in the morphology of the motor nerve cell bodie...

  1. Effect of Locally Administered Ciliary Neurotrophic Factor on the Survival of Transected and Repaired Adult Sheep Facial Nerve

    OpenAIRE

    Rashid Al Abri; Arif Ali Kolethekkat; Kelleher, Michael O.; Lynn M. Myles; Michael A. Glasby

    2014-01-01

    Objective: to determine whether the administration of Ciliary Neurotrophic Factor (CNTF) at the site of repaired facial nerve enhances regeneration in the adult sheep model. Methods: Ten adult sheep were divided into 2 groups: control and study group (CNTF group). In the CNTF group, the buccal branch of the facial nerve was transected and then repaired by epineural sutures. CNTF was injected over the left depressor labii maxillaris muscle in the vicinity of the transected and repaired ner...

  2. Use of suppression subtractive hybridization to identify genes regulated by ciliary neurotrophic factor in postnatal retinal explants

    OpenAIRE

    Roger, Jérôme; Goureau, Olivier; Sahel, José-Alain; Guillonneau, Xavier

    2007-01-01

    Purpose The retinal progenitors are multipotential, and the decision taken by a progenitor to differentiate along a particular path depends on both cell-intrinsic and cell-extrinsic factors. Ciliary neurotrophic factor (CNTF), a member of the interleukin-6 (IL-6) family, added to rat postnatal retinal progenitors inhibits rod photoreceptor cell differentiation, promotes Müller glia genesis and enhances the expression of bipolar neuron markers. We hypothesized that those transcripts regulated ...

  3. Opposite effects of a high-fat diet and calorie restriction on ciliary neurotrophic factor signalling in the mouse hypothalamus

    OpenAIRE

    AntonioGiordano; SaverioCinti

    2013-01-01

    In the mouse hypothalamus, ciliary neurotrophic factor (CNTF) is mainly expressed by ependymal cells and tanycytes of the ependymal layer covering the third ventricle. Since exogenously administered CNTF causes reduced food intake and weight loss, we tested whether endogenous CNTF might be involved in energy balance regulation. We thus evaluated CNTF production and responsiveness in the hypothalamus of mice fed a high-fat diet (HFD), of ob/ob obese mice, and of mice fed a calorie restriction ...

  4. Antineuroinflammatory and neurotrophic effects of CNTF and C16 peptide in an acute experimental autoimmune encephalomyelitis rat model

    OpenAIRE

    Marong Fang; Zhiying Hu

    2013-01-01

    Experimentalallergic encephalomyelitis (EAE) is an animal model for inflammatory demyelinating autoimmune disease, i.e., multiple sclerosis (MS). In the present study, we investigated the antineuroinflammatory/neuroprotective effects of C16, an ανβ3 integrin-binding peptide, and recombinant rat ciliary neurotrophic factor (CNTF), a cytokine that was originally identified as a survival factor for neurons, in an acute rodent EAE model. In this model, C16 peptide was injected intravenously every...

  5. gp130 signaling in proopiomelanocortin neurons mediates the acute anorectic response to centrally applied ciliary neurotrophic factor

    OpenAIRE

    Janoschek, Ruth; Plum, Leona; Koch, Linda; Münzberg, Heike; Diano, Sabrina; Shanabrough, Marya; Müller, Werner; Horvath, Tamas L.; Brüning, Jens C.

    2006-01-01

    Ciliary neurotrophic factor (CNTF) exerts anorectic effects by overcoming leptin resistance via activation of hypothalamic neurons. However, the exact site of CNTF action in the hypothalamus has not yet been identified. Using Cre-loxP-mediated recombination in vivo, we have selectively ablated the common cytokine signaling chain gp130, which is required for functional CNTF signaling, in proopiomelanocortin (POMC)-expressing neurons. POMC-specific gp130 knockout mice exhibit unaltered numbers ...

  6. Expression of ciliary neurotrophic factor (CNTF) and its tripartite receptor complex by cells of the human optic nerve head

    OpenAIRE

    Liu, Xiaochun; Clark, Abbot F.; Wordinger, Robert J.

    2007-01-01

    Purpose Ciliary neurotrophic factor (CNTF) promotes gene expression, cell survival and differentiation in various types of peripheral and central neurons, glia and nonneural cells. The level of CNTF rises rapidly upon injury to neural tissue, suggesting that CNTF exerts its cytoprotective effects after release from cells via mechanisms induced by cell injury. The purpose of this study was to determine if cells in the optic nerve head express CNTF and its tripartite receptor complex. Methods W...

  7. Opposite effects of a high-fat diet and calorie restriction on ciliary neurotrophic factor signaling in the mouse hypothalamus

    OpenAIRE

    Severi, Ilenia; Perugini, Jessica; Mondini, Eleonora; Smorlesi, Arianna; Frontini, Andrea; Cinti, Saverio; Giordano, Antonio

    2013-01-01

    In the mouse hypothalamus, ciliary neurotrophic factor (CNTF) is mainly expressed by ependymal cells and tanycytes of the ependymal layer covering the third ventricle. Since exogenously administered CNTF causes reduced food intake and weight loss, we tested whether endogenous CNTF might be involved in energy balance regulation. We thus evaluated CNTF production and responsiveness in the hypothalamus of mice fed a high-fat diet (HFD), of ob/ob obese mice, and of mice fed a calorie restriction ...

  8. Synthesis and localization of ciliary neurotrophic factor in the sciatic nerve of the adult rat after lesion and during regeneration

    OpenAIRE

    Sendtner, Michael; Stöckli, K. A.; Thoenen, Hans

    2009-01-01

    Ciliary neurotrophic factor (CNTF) is expressed in high quantities in Schwann cells of peripheral nerves during postnatal development of the rat. The absence of a hydrophobic leader sequence and the immunohistochemical localization of CNTF within the cytoplasm of these cells indicate that the factor might not be available to responsive neurons under physiological conditions. However, CNTF supports the survival of a variety of embryonic neurons, including spinal motoneurons in culture. Moreove...

  9. Postnatal Expression of Neurotrophic Factors Accessible to Spiral Ganglion Neurons in the Auditory System of Adult Hearing and Deafened Rats

    OpenAIRE

    Bailey, Erin M.; Green, Steven H.

    2014-01-01

    Spiral ganglion neurons (SGNs) receive input from cochlear hair cells and project from the cochlea to the cochlear nucleus. After destruction of hair cells with aminoglycoside antibiotics or noise, SGNs gradually die. It has been assumed that SGN death is attributable to loss of neurotrophic factors (NTFs) derived from hair cells or supporting cells in the organ of Corti (OC). We used quantitative PCR (qPCR) to assay NTF expression—neurotrophin-3 (NT-3), BDNF, GDNF, neurturin, artemin, and CN...

  10. Long-term lentiviral-mediated expression of ciliary neurotrophic factor in the striatum of Huntington's disease transgenic mice

    OpenAIRE

    Zala, Diana; Bensadoun, Jean-Charles; Pereira de Almeida, Luis; Leavitt, Blair R.; Gutekunst, Claire-Anne; Aebischer, Patrick; Hayden, Michael R; Déglon, Nicole

    2004-01-01

    Ciliary neurotrophic factor (CNTF) has been shown to prevent behavioral deficits and striatal degeneration in neurotoxic models of Huntington's disease (HD), but its effect in a genetic model has not been evaluated. Lentiviral vectors expressing the human CNTF or LacZ reporter gene were therefore injected in the striatum of wild-type (WT) and transgenic mice expressing full-length huntingtin with 72 CAG repeats (YAC72). Behavioral analysis showed increased locomotor activity in 5- to 6-month-...

  11. Ciliary Neurotrophic Factor Stimulates Muscle Glucose Uptake by a PI3-Kinase–Dependent Pathway That Is Impaired With Obesity

    OpenAIRE

    Steinberg, Gregory R.; Watt, Matthew J.; Ernst, Matthias; Birnbaum, Morris J.; Kemp, Bruce E.; Jørgensen, Sebastian Beck

    2009-01-01

    OBJECTIVE Ciliary neurotrophic factor (CNTF) reverses muscle insulin resistance by increasing fatty acid oxidation through gp130-LIF receptor signaling to the AMP-activated protein kinase (AMPK). CNTF also increases Akt signaling in neurons and adipocytes. Because both Akt and AMPK regulate glucose uptake, we investigated muscle glucose uptake in response to CNTF signaling in lean and obese mice. RESEARCH DESIGN AND METHODS Mice were injected intraperitoneally with saline or CNTF, and blood g...

  12. Identification of ciliary neurotrophic factor (CNTF) residues essential for leukemia inhibitory factor receptor binding and generation of CNTF receptor antagonists.

    OpenAIRE

    Di Marco, A; Gloaguen, I; Graziani, R; Paonessa, G; Saggio, I; Hudson, K R; Laufer, R

    1996-01-01

    Ciliary neurotrophic factor (CNTF) drives the sequential assembly of a receptor complex containing the ligand-specific alpha-receptor subunit (CNTFR alpha) and the signal transducers gp130 and leukemia inhibitory factor receptor-beta (LIFR). The D1 structural motif, located at the beginning of the D-helix of human CNTF, contains two amino acid residues, F152 and K155, which are conserved among all cytokines that signal through LIFR. The functional importance of these residues was assessed by ...

  13. Brain-Derived Neurotrophic Factor Inhibits Calcium Channel Activation, Exocytosis, and Endocytosis at a Central Nerve Terminal

    OpenAIRE

    Baydyuk, Maryna; Wu, Xin-sheng; He, Liming; Wu, Ling-Gang

    2015-01-01

    Brain-derived neurotrophic factor (BDNF) is a neurotrophin that regulates synaptic function and plasticity and plays important roles in neuronal development, survival, and brain disorders. Despite such diverse and important roles, how BDNF, or more generally speaking, neurotrophins affect synapses, particularly nerve terminals, remains unclear. By measuring calcium currents and membrane capacitance during depolarization at a large mammalian central nerve terminal, the rat calyx of Held, we re...

  14. TARGETING OF NEUROTROPHIC FACTORS, THEIR RECEPTORS, AND SIGNALING PATHWAYS IN THE DEVELOPMENTAL NEUROTOXICITY OF ORGANOPHOSPHATES IN VIVO AND IN VITRO

    OpenAIRE

    Slotkin, Theodore A.; Seidler, Frederic J; Fumagalli, Fabio

    2008-01-01

    Neurotrophic factors control neural cell differentiation and assembly of neural circuits. We previously showed that organophosphate pesticides differentially regulate members of the fibroblast growth factor (fgf) gene family. We administered chlorpyrifos and diazinon to neonatal rats on postnatal days 1–4 at doses devoid of systemic toxicity or growth impairment, and spanning the threshold for barely-detectable cholinesterase inhibition. We evaluated the impact on gene families for different ...

  15. Ciliary neurotrophic factor promotes motor reinnervation of the musculocutaneous nerve in an experimental model of end-to-side neurorrhaphy

    OpenAIRE

    Čelakovský Pavel; Stejskal Lubomír; Raška Otakar; Klusáková Ilona; Dubový Petr; Haninec Pavel

    2011-01-01

    Abstract Background It is difficult to repair nerve if proximal stump is unavailable or autogenous nerve grafts are insufficient for reconstructing extensive nerve damage. Therefore, alternative methods have been developed, including lateral anastomosis based on axons' ability to send out collateral sprouts into denervated nerve. The different capacity of a sensory or motor axon to send a sprout is controversial and may be controlled by cytokines and/or neurotrophic factors like ciliary neuro...

  16. Brain-derived neurotrophic factor and its receptor in the human and the sand rat intervertebral disc

    OpenAIRE

    Gruber, Helen E.; Ingram, Jane A; Hoelscher, Gretchen; Zinchenko, Natalia; Norton, H. James; Hanley, Edward N

    2008-01-01

    Introduction Brain-derived neurotrophic factor (BDNF) was first identified in the intervertebral disc (IVD) when its molecular upregulation was observed in sections of nucleus pulposus cultured under conditions of increased osmolarity. BDNF is now known to be involved in a number of biologic functions, including regulation of differentiation/survival of sensory neurons, regulation of nociceptive function and central pain modulation, and modulation of inflammatory pain hypersensitivity. In add...

  17. Effects of the Brain Derived Neurotrophic Growth Factor Val66Met Variation on Hippocampus Morphology in Bipolar Disorder

    OpenAIRE

    Chepenik, Lara G.; Fredericks, Carolyn; Papademetris, Xenophon; Spencer, Linda; Lacadie, Cheryl; Wang, Fei; Pittman, Brian; Duncan, James S.; Staib, Lawrence H.; Duman, Ronald S.; Gelernter, Joel; Blumberg, Hilary P.

    2008-01-01

    Histological and behavioral research in bipolar disorder (BD) implicates structural abnormalities in the hippocampus. Brain-derived neurotrophic growth factor (BDNF) protein is associated with hippocampal development and plasticity, and in mood disorder pathophysiology. We tested the hypotheses both the BDNF val66met polymorphism and BD diagnosis are associated with decreased hippocampus volume, and individuals with BD who carry the met allele have the smallest hippocampus volumes compared to...

  18. The Effect of Exercise Training Modality on Serum Brain Derived Neurotrophic Factor Levels in Individuals with Type 2 Diabetes

    OpenAIRE

    Swift, Damon L.; Johannsen, Neil M.; Myers, Valerie H.; Earnest, Conrad P.; Smits, Jasper A. J.; Blair, Steven N.; Church, Timothy S.

    2012-01-01

    INTRODUCTION: Brain derived neurotrophic factor (BDNF) has been implicated in memory, learning, and neurodegenerative diseases. However, the relationship of BDNF with cardiometabolic risk factors is unclear, and the effect of exercise training on BDNF has not been previously explored in individuals with type 2 diabetes. METHODS: Men and women (N = 150) with type 2 diabetes were randomized to an aerobic exercise (aerobic), resistance exercise (resistance), or a combination of both (combination...

  19. The association between brain-derived neurotrophic factor Val66Met variants and psychotic symptoms in posttraumatic stress disorder

    OpenAIRE

    Pivac, Nela; Kozarić-Kovačić, Dragica; Grubišić-Ilić, Mirjana; Nedić, Gordana; Rakoš, Iva; Nikolac, Matea; Blažev, Martina; Muck-Šeler, Dorotea

    2012-01-01

    Objective: Psychotic symptoms frequently occur in veterans with combat-related posttraumatic stress disorder (PTSD). Brain-derived neurotrophic factor (BDNF) plays a major role in neurodevelopment, neuro-regeneration, neurotransmission, learning, regulation of mood and stress responses. The Met allele of the functional polymorphism, BDNF Val66Met, is associated with psychotic disorders. This study intended to assess whether the Met allele is overrepresented in unrelated Caucasian male veteran...

  20. Brain-derived neurotrophic factor functions as a metabotrophin to mediate the effects of exercise on cognition

    OpenAIRE

    Gomez-Pinilla, Fernando; Vaynman, Shoshanna; Ying, Zhe

    2008-01-01

    Brain-derived neurotrophic factor (BDNF) has been shown to mediate the effects of exercise on synaptic plasticity and cognitive function, in a process in which energy metabolism probably plays an important role. The purpose of the present study was to examine the influence of exercise on rat hippocampal expression of molecules involved in the regulation of energy management and cognitive function, and to determine the role of BDNF in these events. One week of voluntary exercise that enhanced ...

  1. The Brain-Derived Neurotrophic Factor Val66Met Polymorphism Moderates an Effect of Physical Activity on Working Memory Performance

    OpenAIRE

    Erickson, Kirk I.; Banducci, Sarah E.; Weinstein, Andrea M.; MacDonald, Angus W.; Ferrell, Robert E.; Halder, Indrani; Flory, Janine D.; Manuck, Stephen B.

    2013-01-01

    Physical activity enhances cognitive performance, yet individual variability in its effectiveness limits its widespread therapeutic application. Genetic differences might be one source of this variation. For example, carriers of the methionine-specifying (Met) allele of the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism have reduced secretion of BDNF and poorer memory, yet physical activity increases BDNF levels. To determine whether the BDNF polymorphism moderated an associat...

  2. Brain-Derived Neurotrophic Factor Serum Levels and Genotype: Association with Depression during Interferon-α Treatment

    OpenAIRE

    Lotrich, Francis E.; Albusaysi, Salwa; Ferrell, Robert E.

    2013-01-01

    Depression has been associated with inflammation, and inflammation may both influence and interact with growth factors such as brain-derived neurotrophic factor (BDNF). Both the functional Val66Met BDNF polymorphism (rs6265) and BDNF levels have been associated with depression. It is thus plausible that decreased BDNF could mediate and/or moderate cytokine-induced depression. We therefore prospectively employed the Beck Depression Inventory-II (BDI-II), the Hospital Anxiety and Depression Sca...

  3. Effects of Music Aerobic Exercise on Depression and Brain-Derived Neurotrophic Factor Levels in Community Dwelling Women

    OpenAIRE

    2015-01-01

    A randomized clinical trial was utilized to compare the improvement of depression and brain-derived neurotrophic factor (BDNF) levels between community women with and without music aerobic exercise (MAE) for 12 weeks. The MAE group involved 47 eligible participants, whereas the comparison group had 59 participants. No significant differences were recorded in the demographic characteristics between the participants in the MAE group and the comparison group. Forty-one participants in the MAE gr...

  4. The effect of regular Taekwondo exercise on Brain-derived neurotrophic factor and Stroop test in undergraduate student

    OpenAIRE

    Kim, Youngil

    2015-01-01

    [Purpose] The purpose of this study was to investigate the effect of Taekwondo exercise on Brain-derived neurotrophic factor and the Stroop test in undergraduate students. [Methods] Fourteen male subjects participated in this study. They were separated into a Control group (N = 7) and an Exercise group (N = 7). Subjects participated in Taekwondo exercise training for 8 weeks. They underwent to Taekwondo exercise training for 85 minutes per day, 5 times a week at RPE of 11~15. The taekwondo ex...

  5. Brain-derived neurotrophic factor gene transfection promotes neuronal repair and neurite regeneration after diffuse axonal injury

    Institute of Scientific and Technical Information of China (English)

    Yin Yu; Chao Du; Xingli Zhao; Jiajia Shao; Qiang Shen; Tao Jiang; Wei Wu; Dong Zhu; Yu Tian; Yongchuan Guo

    2011-01-01

    This study sought to assess the potential of brain-derived neurotrophic factor (BDNF) to promote neuronal repair and regeneration in rats with diffuse axonal injury, and to examine the accompanying neurobiological changes. BDNF gene transfection reduced the severity of the pathological changes associated with diffuse axonal injury in cortical neurons of the frontal lobe and increased neurofilament protein expression. These findings demonstrate that BDNF can effectively promote neuronal repair and neurite regeneration after diffuse axonal injury.

  6. An Association Study of the Brain-Derived Neurotrophic Factor Val66Met Polymorphism and Amphetamine Response

    OpenAIRE

    Brody A Flanagin; Cook, Edwin H.; de Wit, Harriet

    2006-01-01

    Although genetic factors are known to be important in addiction, no candidate genes have yet been consistently linked to drug use or abuse. Brain-derived neurotrophic factor (BDNF), which has been implicated in the behavioral response to psychomotor stimulants and potentiates neurotransmitters that are strongly linked to addiction, is a logical candidate gene to study. Using a drug challenge approach, we tested for association between BDNF G196A (val66met) genotype and subjective responses to...

  7. Neuroprotective effects of brain-derived neurotrophic factor in rodent and primate models of Alzheimer’s disease

    OpenAIRE

    Nagahara, Alan H.; Merrill, David A.; Coppola, Giovanni; Tsukada, Shingo; Schroeder, Brock E; Shaked, Gideon M.; Wang, Ling; Blesch, Armin; Kim, Albert; Conner, James M; Rockenstein, Edward; Chao, Moses V.; Koo, Edward H.; Geschwind, Daniel; Masliah, Eliezer

    2009-01-01

    Profound neuronal dysfunction in the entorhinal cortex contributes to early loss of short-term memory in Alzheimer’s disease1–3. Here we show broad neuroprotective effects of entorhinal brain-derived neurotrophic factor (BDNF) administration in several animal models of Alzheimer’s disease, with extension of therapeutic benefits into the degenerating hippocampus. In amyloid-transgenic mice, BDNF gene delivery, when administered after disease onset, reverses synapse loss, partially normalizes a...

  8. Comparing Symptoms of Withdrawal, Rapid Detoxi-fication and Detoxification with Clonidine in Drug Dependent Patients

    OpenAIRE

    Ziaaddini, Hassan; Qahestani, Abbas; Moin Vaziri, Maryam

    2009-01-01

    Background: Considering the fear of drug addicts from hangover symptoms and the costs of withdrawal treatment and their importance in deciding to withdraw, it is helpful to identify various ways of withdrawal and their effects. This study investigated the withdrawal symptoms of two methods of detoxification with clonidine and rapid detoxification of clonidine with naltrexone. Methods: This was a clinical trial study. Patients referred to Shahid Beheshti hospital for narcotic addiction treatme...

  9. Course and Treatment of Buprenorphine/naloxone Withdrawal: An Analysis of Case Reports

    OpenAIRE

    Westermeyer, Joseph; McCance-Katz, Elinore F.

    2012-01-01

    Currently published information on buprenorphine-naloxone withdrawal recommends a gradually decreasing dosage over weeks to months. In this case report, abrupt cessation of buprenorphine/naloxone at various doses, and after variable durations of treatment, resulted in mild opiate withdrawal lasting over approximately 1–2 days that did not require additional opioid medication or only specific symptom-relieving, non-opioid, medications. Lengthy withdrawal regimens might prolong withdrawal sympt...

  10. Regulation of proteolytic cleavage of brain-derived neurotrophic factor precursor by antidepressants in human neuroblastoma cells

    Directory of Open Access Journals (Sweden)

    Lin PY

    2015-10-01

    Full Text Available Pao-Yen Lin1,2 1Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, 2Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan Abstract: Evidence has supported the role of brain-derived neurotrophic factor (BDNF in antidepressant effect. The precursor of BDNF (proBDNF often exerts opposing biological effects on mature BDNF (mBDNF. Hence, the balance between proBDNF and mBDNF might be critical in total neurotrophic effects, leading to susceptibility to or recovery from depression. In the current study, we measured the protein expression levels of proBDNF, and its proteolytic products, truncated BDNF, and mBDNF, in human SH-SY5Y cells treated with different antidepressants. We found that the treatment significantly increased the production of mBDNF, but decreased the production of truncated BDNF and proBDNF. These results support that antidepressants can promote proBDNF cleavage. Further studies are needed to clarify whether proBDNF cleavage plays a role in antidepressant mechanisms. Keywords: antidepressant, mature BDNF, neurotrophic effect, proBDNF cleavage 

  11. Human umbilical cord blood-derived stem cells and brain-derived neurotrophic factor protect injured optic nerve: viscoelasticity characterization.

    Science.gov (United States)

    Lv, Xue-Man; Liu, Yan; Wu, Fei; Yuan, Yi; Luo, Min

    2016-04-01

    The optic nerve is a viscoelastic solid-like biomaterial. Its normal stress relaxation and creep properties enable the nerve to resist constant strain and protect it from injury. We hypothesized that stress relaxation and creep properties of the optic nerve change after injury. More-over, human brain-derived neurotrophic factor or umbilical cord blood-derived stem cells may restore these changes to normal. To validate this hypothesis, a rabbit model of optic nerve injury was established using a clamp approach. At 7 days after injury, the vitreous body re-ceived a one-time injection of 50 μg human brain-derived neurotrophic factor or 1 × 10(6) human umbilical cord blood-derived stem cells. At 30 days after injury, stress relaxation and creep properties of the optic nerve that received treatment had recovered greatly, with patho-logical changes in the injured optic nerve also noticeably improved. These results suggest that human brain-derived neurotrophic factor or umbilical cord blood-derived stem cell intervention promotes viscoelasticity recovery of injured optic nerves, and thereby contributes to nerve recovery. PMID:27212930

  12. Human umbilical cord blood-derived stem cells and brain-derived neurotrophic factor protect injured optic nerve: viscoelasticity characterization

    Directory of Open Access Journals (Sweden)

    Xue-man Lv

    2016-01-01

    Full Text Available The optic nerve is a viscoelastic solid-like biomaterial. Its normal stress relaxation and creep properties enable the nerve to resist constant strain and protect it from injury. We hypothesized that stress relaxation and creep properties of the optic nerve change after injury. More-over, human brain-derived neurotrophic factor or umbilical cord blood-derived stem cells may restore these changes to normal. To validate this hypothesis, a rabbit model of optic nerve injury was established using a clamp approach. At 7 days after injury, the vitreous body re-ceived a one-time injection of 50 µg human brain-derived neurotrophic factor or 1 × 106 human umbilical cord blood-derived stem cells. At 30 days after injury, stress relaxation and creep properties of the optic nerve that received treatment had recovered greatly, with patho-logical changes in the injured optic nerve also noticeably improved. These results suggest that human brain-derived neurotrophic factor or umbilical cord blood-derived stem cell intervention promotes viscoelasticity recovery of injured optic nerves, and thereby contributes to nerve recovery.

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

    Directory of Open Access Journals (Sweden)

    Pei Jiang

    2014-01-01

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

  14. The impacts of swimming exercise on hippocampal expression of neurotrophic factors in rats exposed to chronic unpredictable mild stress.

    Science.gov (United States)

    Jiang, Pei; Dang, Rui-Li; Li, Huan-De; Zhang, Li-Hong; Zhu, Wen-Ye; Xue, Ying; Tang, Mi-Mi

    2014-01-01

    Depression is associated with stress-induced neural atrophy in limbic brain regions, whereas exercise has antidepressant effects as well as increasing hippocampal synaptic plasticity by strengthening neurogenesis, metabolism, and vascular function. A key mechanism mediating these broad benefits of exercise on the brain is induction of neurotrophic factors, which instruct downstream structural and functional changes. To systematically evaluate the potential neurotrophic factors that were involved in the antidepressive effects of exercise, in this study, we assessed the effects of swimming exercise on hippocampal mRNA expression of several classes of the growth factors (BDNF, GDNF, NGF, NT-3, FGF2, VEGF, and IGF-1) and peptides (VGF and NPY) in rats exposed to chronic unpredictable mild stress (CUMS). Our study demonstrated that the swimming training paradigm significantly induced the expression of BDNF and BDNF-regulated peptides (VGF and NPY) and restored their stress-induced downregulation. Additionally, the exercise protocol also increased the antiapoptotic Bcl-xl expression and normalized the CUMS mediated induction of proapoptotic Bax mRNA level. Overall, our data suggest that swimming exercise has antidepressant effects, increasing the resistance to the neural damage caused by CUMS, and both BDNF and its downstream neurotrophic peptides may exert a major function in the exercise related adaptive processes to CUMS. PMID:25477997

  15. 40 CFR 97.86 - Withdrawal from NOX Budget Trading Program.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Withdrawal from NOX Budget Trading... PROGRAMS (CONTINUED) FEDERAL NOX BUDGET TRADING PROGRAM AND CAIR NOX AND SO2 TRADING PROGRAMS Individual Unit Opt-ins. § 97.86 Withdrawal from NOX Budget Trading Program. (a) Requesting withdrawal....

  16. Bupropion Dose-Dependently Reverses Nicotine Withdrawal Deficits in Contextual Fear Conditioning

    OpenAIRE

    Portugal, George S.; Gould, Thomas J.

    2007-01-01

    Bupropion, a norepinephrine and dopamine reuptake inhibitor and nicotinic acetylcholine receptor antagonist, facilitates smoking cessation and reduces some symptoms of nicotine withdrawal. However, the effects of bupropion on nicotine withdrawal-associated deficits in learning remain unclear. The present study investigated whether bupropion has effects on contextual and cued fear conditioning following withdrawal from chronic nicotine or when administered alone. Bupropion was administered alo...

  17. 75 FR 57469 - Guidance on Withdrawal of Subjects From Research: Data Retention and Other Related Issues

    Science.gov (United States)

    2010-09-21

    ... HUMAN SERVICES Guidance on Withdrawal of Subjects From Research: Data Retention and Other Related Issues... availability of a guidance document entitled, ``Guidance on Withdrawal of Subjects From Research: Data... guidance document entitled, ``Guidance on Withdrawal of Subjects From Research: Data Retention and...

  18. 27 CFR 19.532 - Withdrawals of spirits for use in wine production.

    Science.gov (United States)

    2010-04-01

    ... use in wine production. 19.532 Section 19.532 Alcohol, Tobacco Products and Firearms ALCOHOL AND... Withdrawals Withdrawal of Spirits Without Payment of Tax § 19.532 Withdrawals of spirits for use in wine production. Wine spirits may be withdrawn to a bonded wine cellar without payment of tax for use in...

  19. 18 CFR 341.13 - Withdrawal of proposed tariff publications.

    Science.gov (United States)

    2010-04-01

    ... tariff publications. 341.13 Section 341.13 Conservation of Power and Water Resources FEDERAL ENERGY... TARIFFS: OIL PIPELINE COMPANIES SUBJECT TO SECTION 6 OF THE INTERSTATE COMMERCE ACT § 341.13 Withdrawal of proposed tariff publications. (a) Proposed tariff publications. A proposed tariff publication which is...

  20. Appendicitis in a Patient with Drug Withdrawal Symptoms

    Directory of Open Access Journals (Sweden)

    Viroj Wiwanitkit

    2010-11-01

    Full Text Available Physical disorders can be seen in psychiatric patients. In addition, a delayed diagnosis can cause a serious complication of the physical disorder among such patients. In this report, a case of appendicitis in a psychiatric case with drug withdrawal symptoms was reported.

  1. Simulation on the HTTR Control Rod Withdrawal Test

    International Nuclear Information System (INIS)

    This paper describes the GAMMA+ code simulation of HTTR control rod withdrawal test. The simulation is done to examine the effect of GAMMA+ code's single-zone and multi-zone point kinetics models on the prediction of the reactor power response during HTTR control rod withdrawal test. In addition, it has an objective to examine how the reactor power response is affected by the application of the fuel temperature coefficients on TRISO kernel or compact rod. The calculation results of reactivity response and reactor power response are compared with the test results which were obtained at the initial power of 15.2 MW with the amount of reactivity insertion by control rod withdrawal to 3.4e-04 (dk/k) in 6.59 seconds. All GAMMA+ simulation results on a HTTR CRW test showed good predictions with the measured data. In particular, TRISO Kernel Model where the fuel temperature coefficients applied on the TRISO particle produced a better prediction within a 1.5% measured data and made no difference between the single-zone model and the multi-zone point kinetics model. During the control rod withdrawal event which is a fast transient, the total reactivity is mainly affected by the inserted reactivity and the reactivity response due to the change of the fuel temperature and the graphite moderator temperature

  2. 75 FR 60113 - Pesticide Science Policy; Notice of Withdrawal

    Science.gov (United States)

    2010-09-29

    ...EPA announces the withdrawal of the pesticide science policy document ``Use of the Pesticide Data Program (PDP) in Acute Risk Assessment.'' In estimating dietary exposure to pesticides, the Agency uses a variety of data and different models. This science policy document was developed to explain a particular statistical methodology, known as decomposition, for using information from the U.S.......

  3. Steroid withdrawal in renal transplant patients: the Irish experience.

    LENUS (Irish Health Repository)

    Phelan, P J

    2010-10-29

    BACKGROUND: Steroid therapy is associated with significant morbidity in renal transplant recipients. However, there is concern that steroid withdrawal will adversely affect outcome. METHODS: We report on 241 renal transplant recipients on different doses of corticosteroids at 3 months (zero, ≤5 mg\\/day, >5 mg\\/day). Parameters analysed included blood pressure, lipid profile, weight change, new onset diabetes after transplantation (NODAT), allograft survival and acute rejection. RESULTS: Elimination of corticosteroids had no impact on allograft survival at 1 year. There were no cases of NODAT in the steroid withdrawal group compared with over 7% in each of the steroid groups. There were no significant improvements in weight gain, blood pressure control or total cholesterol with withdrawal of steroids before 3 months. CONCLUSIONS: In renal transplant patients treated with tacrolimus and mycophenolate, early withdrawal of steroids does not appear to adversely affect allograft outcome at 1 year. It may result in less NODAT.

  4. 31 CFR 281.6 - Withdrawals from Treasury accounts.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false Withdrawals from Treasury accounts. 281.6 Section 281.6 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) FISCAL SERVICE, DEPARTMENT OF THE TREASURY FINANCIAL MANAGEMENT SERVICE FOREIGN EXCHANGE OPERATIONS §...

  5. It's self defense: how perceived discrimination promotes employee withdrawal.

    Science.gov (United States)

    Volpone, Sabrina D; Avery, Derek R

    2013-10-01

    Integrating theory on stress, stigma, and coping, the present study sheds light on how employees react to perceived discrimination (PD) in the workplace. Using three national samples, we found that PD based on race, sex, age, family obligation, and sexual orientation related to physical withdrawal (i.e., lateness, absenteeism,and intent to quit) indirectly through psychological withdrawal (i.e., burnout and engagement) such that PD corresponded in less engagement and more burnout, which related to increased lateness, absenteeism, and intent to quit [corrected].Further, these indirect relationships were moderated by employees' coping mechanisms with those who were more apt to change the situation or to avoid the stressor exhibiting weaker relationships between PD and psychological withdrawal. Though each of these studies is cross-sectional in nature and therefore cannot provide strong evidence of causal ordering of the variables in our model, the replication and extension of results over three databases and multiple forms of discrimination, coping, psychological, and physical withdrawal demonstrates that understanding the relationships explored in these studies can aid researchers and practitioners in enhancing employee quality of life and productivity. PMID:24099162

  6. 78 FR 28163 - Zentox Corporation; Withdrawal of Food Additive Petition

    Science.gov (United States)

    2013-05-14

    ... proposed to amend the food additive regulations in part 173--Secondary Direct Food Additives Permitted in... Additive Petition AGENCY: Food and Drug Administration, HHS. ACTION: Notice of withdrawal. SUMMARY: The... filing, of a food additive petition (FAP 8A4775) proposing that the food additive regulations be...

  7. Polymerization catalysts containing electron-withdrawing amide ligands

    Science.gov (United States)

    Watkin, John G.; Click, Damon R.

    2002-01-01

    The present invention describes methods of making a series of amine-containing organic compounds which are used as ligands for group 3-10 and lanthanide metal compounds. The ligands have electron-withdrawing groups bonded to them. The metal compounds, when combined with a cocatalyst, are catalysts for the polymerization of olefins.

  8. 19 CFR 144.38 - Withdrawal for consumption.

    Science.gov (United States)

    2010-04-01

    ... for tax purposes required by § 275.81 of the regulations of the Internal Revenue Service (26 CFR § 275... textile category. Editorial Note: For Federal Register citations affecting § 144.38, see the List of CFR... provided in § 141.61(e) of this chapter. (b) Withdrawal for exportation to Canada or Mexico. A...

  9. 75 FR 33273 - Preferred Supplier Program (PSP); Withdrawal

    Science.gov (United States)

    2010-06-11

    ... Register (75 FR 100) on May 25, 2010, concerning a policy that would establish a Preferred Supplier Program (PSP) with contractors that have demonstrated exemplary performance, at the corporate level; in the... Department of the Navy Preferred Supplier Program (PSP); Withdrawal AGENCY: Department of the Navy,...

  10. 12 CFR 925.26 - Voluntary withdrawal from membership.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Voluntary withdrawal from membership. 925.26 Section 925.26 Banks and Banking FEDERAL HOUSING FINANCE BOARD FEDERAL HOME LOAN BANK MEMBERS AND HOUSING... entitled to have continued access to the benefits of membership until the effective date of its...

  11. Oral health behavior of drug addicts in withdrawal treatment

    Directory of Open Access Journals (Sweden)

    Shekarchizadeh Hajar

    2013-01-01

    Full Text Available Abstract Background Oral health behavior (OHB, one major factor contributing to proper oral health status, has been addressed insufficiently in addiction literature. The aim of our study was to investigate OHB and its determinants among drug addicts in withdrawal treatment. Methods Through a stratified cluster sampling method, we collected the data from 685 patients in withdrawal treatment in Tehran using self-administered questionnaires on OHB components and conducting interviews about patients’ characteristics and addiction history. The T-test, ANOVA, and a linear regression model served for statistical analysis. Results Of the patients, 48% reported brushing their teeth less than once a day, more than 90% used fluoride toothpaste almost or always, and 81% flossed their teeth rarely or never. Eating sugary products twice a day or more was reported by 57% of the patients and 85% of them were current smokers. Poor OHB was associated with male gender, lower education, being addicted mainly to crystalline heroin, starting drug abuse at a younger age, and having a longer history of addiction (p  Conclusion Poor OHB was found among the participants in drug withdrawal treatment. Preventive strategies on oral health should be planned and be integrated into other health promotion programs for addicts along with their withdrawal treatment taking into account special groups at higher risk.

  12. Social Anxiety and Adolescents' Friendships: The Role of Social Withdrawal

    Science.gov (United States)

    Biggs, Bridget K.; Vernberg, Eric M.; Wu, Yelena P.

    2012-01-01

    Research indicates social anxiety is associated with lower friendship quality, but little is known about the underlying mechanisms. This 2-month longitudinal study examined social withdrawal as a mediator of the social anxiety-friendship quality link in a sample of 214 adolescents (M[subscript age] = 13.1 years, SD = 0.73) that included an…

  13. A 'symptom-triggered' approach to alcohol withdrawal management.

    Science.gov (United States)

    Murdoch, Jay; Marsden, Janet

    In acute hospital settings, alcohol withdrawal often causes significant management problems and complicates a wide variety of concurrent conditions, placing a huge burden on the NHS. A significant number of critical incidents around patients who were undergoing detoxification in a general hospital setting led to the need for a project to implement and evaluate an evidence-based approach to the management of alcohol detoxification-a project that included a pre-intervention case note audit, the implementation of an evidence-based symptom-triggered detoxification protocol, and a post-intervention case note audit. This change in practice resulted in an average reduction of almost 60% in length of hospital stay and a 66% reduction in the amount of chlordiazepoxide used in detoxification, as well as highlighting that 10% of the sample group did not display any signs of withdrawal and did not require any medication. Even with these reductions, no patient post-intervention developed any severe signs of withdrawal phenomena, such as seizures or delirium tremens. The savings to the trust (The Pennine Acute Hospital Trust) are obvious,but the development of a consistent, quality service will lead to fewer long-term negative effects for patients that can be caused by detoxification. This work is a project evaluation of a locally implemented strategy, which, it was hypothesised,would improve care by providing an individualised treatment plan for the management of alcohol withdrawal symptoms. PMID:24809146

  14. Priapism Associated with MethylphenidateSR (Concerta Withdrawal

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2004-07-01

    Full Text Available A 15-year-old boy with attention deficit hyperactivity disorder, inattention subtype (ADHD, developed stuttering priapism (intermittent, prolonged, painful erections after withdrawal of OROS methylphenidate (ConcertaR 36 mg/day, and is reported from Inova Fairfax Hospital for Children, Falls Church, VA, and Children’s National Medical Center, Washington, DC.

  15. Caffeine withdrawal symptoms and self-administration following caffeine deprivation.

    Science.gov (United States)

    Mitchell, S H; de Wit, H; Zacny, J P

    1995-08-01

    This study examined the effects of complete or partial caffeine deprivation on withdrawal symptomatology and self-administration of coffee in caffeine-dependent coffee drinkers. Nine habitual coffee drinkers abstained from dietary sources of caffeine for 33.5 h. Caffeine deprivation was manipulated by administering capsules containing 0%, 50%, or 100% of each subject's daily caffeine intake (complete, partial, and no deprivation conditions). Caffeine withdrawal symptomatology was measured using self-report questionnaires. Caffeine self-administration was measured using: i) the amount of coffee subjects earned on a series of concurrent random-ratio schedules that yielded coffee and money reinforcers; ii) the amount of earned coffee they consumed. Saliva samples revealed that subjects complied with the caffeine abstinence instructions. Caffeine withdrawal symptoms occurred reliably following complete caffeine deprivation, though not in the partial deprivation condition. Caffeine self-administration was not related to deprivation condition. We conclude that caffeine withdrawal symptomatology is not necessarily associated with increased caffeine consumption. PMID:7675881

  16. Occupational Asthma after Withdrawal from the Occupational Allergen Exposure

    Czech Academy of Sciences Publication Activity Database

    Klusáčková, P.; Pelclová, D.; Lebedová, J.; Marečková, H.; Brabec, Marek

    2006-01-01

    Roč. 44, č. 4 (2006), s. 629-638. ISSN 0019-8366 Source of funding: V - iné verejné zdroje Keywords : occupational asthma * allergen exposure withdrawal Subject RIV: BB - Applied Statistics, Operational Research Impact factor: 0.911, year: 2006 http://www.jniosh.go.jp/en/indu_hel/pdf/indhealth_44_4_629.pdf

  17. 48 CFR 619.506 - Withdrawing or modifying set asides.

    Science.gov (United States)

    2010-10-01

    ... set asides. 619.506 Section 619.506 Federal Acquisition Regulations System DEPARTMENT OF STATE SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS Set-Asides for Small Business 619.506 Withdrawing or modifying set asides. (b) The Procurement Executive shall resolve disagreements between the A/SDBU...

  18. Cerebrolysin, a mixture of neurotrophic factors induces marked neuroprotection in spinal cord injury following intoxication of engineered nanoparticles from metals.

    Science.gov (United States)

    Menon, Preeti Kumaran; Muresanu, Dafin Fior; Sharma, Aruna; Mössler, Herbert; Sharma, Hari Shanker

    2012-02-01

    Spinal cord injury (SCI) is the world's most disastrous disease for which there is no effective treatment till today. Several studies suggest that nanoparticles could adversely influence the pathology of SCI and thereby alter the efficacy of many neuroprotective agents. Thus, there is an urgent need to find suitable therapeutic agents that could minimize cord pathology following trauma upon nanoparticle intoxication. Our laboratory has been engaged for the last 7 years in finding suitable therapeutic strategies that could equally reduce cord pathology in normal and in nanoparticle-treated animal models of SCI. We observed that engineered nanoparticles from metals e.g., aluminum (Al), silver (Ag) and copper (Cu) (50-60 nm) when administered in rats daily for 7 days (50 mg/kg, i.p.) resulted in exacerbation of cord pathology after trauma that correlated well with breakdown of the blood-spinal cord barrier (BSCB) to serum proteins. The entry of plasma proteins into the cord leads to edema formation and neuronal damage. Thus, future drugs should be designed in such a way to be effective even when the SCI is influenced by nanoparticles. Previous research suggests that a suitable combination of neurotrophic factors could induce marked neuroprotection in SCI in normal animals. Thus, we examined the effects of a new drug; cerebrolysin that is a mixture of different neurotrophic factors e.g., brain-derived neurotrophic factor (BDNF), glial cell line derived neurotrophic factor (GDNF), nerve growth factor (NGF), ciliary neurotrophic factor (CNTF) and other peptide fragments to treat normal or nanoparticle-treated rats after SCI. Our observations showed that cerebrolysin (2.5 ml/kg, i.v.) before SCI resulted in good neuroprotection in normal animals, whereas nanoparticle-treated rats required a higher dose of the drug (5.0 ml/kg, i.v.) to induce comparable neuroprotection in the cord after SCI. Cerebrolysin also reduced spinal cord water content, leakage of plasma proteins

  19. Low-level laser therapy promotes dendrite growth via upregulating brain-derived neurotrophic factor expression

    Science.gov (United States)

    Meng, Chengbo; He, Zhiyong; Xing, Da

    2014-09-01

    Downregulation of brain-derived neurotrophic factor (BDNF) in the hippocampus occurs early in the progression of Alzheimer's disease (AD). Since BDNF plays a critical role in neuronal survival and dendrite growth, BDNF upregulation may contribute to rescue dendrite atrophy and cell loss in AD. Low-level laser therapy (LLLT) has been demonstrated to regulate neuronal function both in vitro and in vivo. In the present study, we found that LLLT rescued neurons loss and dendritic atrophy via the increase of both BDNF mRNA and protein expression. In addition, dendrite growth was improved after LLLT, characterized by upregulation of PSD95 expression, and the increase in length, branching, and spine density of dendrites in hippocampal neurons. Together, these studies suggest that upregulation of BDNF with LLLT can ameliorate Aβ-induced neurons loss and dendritic atrophy, thus identifying a novel pathway by which LLLT protects against Aβ-induced neurotoxicity. Our research may provide a feasible therapeutic approach to control the progression of Alzheimer's disease.

  20. [Hematopoietic growth factor EPO has neuro-protective and neuro-trophic effects--review].

    Science.gov (United States)

    Zhou, Zhuo-Yan; Yang, Mo; Fok, Tai-Fai

    2005-04-01

    Erythropoietin (EPO) is an acidic glycoprotein that was first detected as a hematopoietic factor and its synthesis is triggered in response to cellular hypoxia-sensing. EPO binds to type I cytokine receptors, which associate with the non-receptor tyrosine kinase Jak2, and thereby activate Stat 5a/5b, Ras/MAPK, and PI3-K/Akt signaling pathways. The recent discovery shows that there is a specific EPO/EPO-receptor system in the central nervous system (CNS), independently of the haematopoietic system. Hypoxia and anemia can up-regulate EPO/EPOR expressions in the CNS. Further studies demonstrate that EPO has substantial neuro-protective effects and acts as a neurotrophic factor on central cholinergic neurons, influencing their differentiation and regeneration. EPO also exerts neuro-protective activities in different models of brain damage in vivo and in vitro, such as hypoxia, cerebral ischaemia and sub-arachnoid haemorrhage. EPO may also be involved in synaptic plasticity via the inhibition or stimulation of various neurotransmitters. Therefore, human recombinant EPO that activate its receptors in the central nervous system might be utilized in the future clinical practice involving neuroprotection and brain repair. PMID:15854305

  1. Brain derived neurotrophic factor (BDNF contributes to the pain hypersensitivity following surgical incision in the rats

    Directory of Open Access Journals (Sweden)

    Zhang Jian-Yi

    2008-07-01

    Full Text Available Abstract Background The pathogenic role of brain derived neurotrophic factor (BDNF in the incisional pain is poorly understood. The present study explores the role of the BDNF in the incision-induced pain hypersensitivity. Methods A longitudinal incision was made in one plantar hind paw of isoflurane-anesthetized rats. Dorsal root ganglias (DRG and spinal cords were removed at various postoperative times (1–72 h. Expression pattern of BDNF was determined by immunohistochemistry and double-labeling immunofluorescence. Lidocaine-induced blockade of sciatic nerve function was used to determine the importance of afferent nerve activity on BDNF expression in the DRG and spinal cord after incision. BDNF antibody was administered intrathecally (IT or intraperitoneal (IP to modulate the spinal BDNF or peripheral BDNF after incision. Results After hind-paw incision, the BDNF was upregulated in the ipsilateral lumbar DRG and spinal cord whereas thoracic BDNF remained unchanged in response to incision. The upregulated BDNF was mainly expressed in the large-sized neurons in DRG and the neurons and the primary nerve terminals in the spinal cord. Sciatic nerve blockade prevented the increase of BDNF in the DRG and spinal cord. IT injection of BDNF antibody greatly inhibited the mechanical allodynia induced by incision whereas IP administration had only marginal effect. Conclusion The present study showed that incision induced the segmental upregulation of BDNF in the DRG and spinal cord through somatic afferent nerve transmission, and the upregulated BDNF contributed to the pain hypersensitivity induced by surgical incision.

  2. Ciliary neurotrophic factor has intrinsic and extrinsic roles in regulating B cell differentiation and bone structure.

    Science.gov (United States)

    Askmyr, Maria; White, Kirby E; Jovic, Tanja; King, Hannah A; Quach, Julie M; Maluenda, Ana C; Baker, Emma K; Smeets, Monique F; Walkley, Carl R; Purton, Louise E

    2015-01-01

    The gp130 receptor and its binding partners play a central role in cytokine signalling. Ciliary neurotrophic factor (CNTF) is one of the cytokines that signals through the gp130 receptor complex. CNTF has previously been shown to be a negative regulator of trabecular bone remodelling and important for motor neuron development. Since haematopoietic cell maintenance and differentiation is dependent on the bone marrow (BM) microenvironment, where cells of the osteoblastic lineage are important regulators, we hypothesised that CNTF may also have important roles in regulating haematopoiesis. Analysis of haematopoietic parameters in male and female Cntf(-/-) mice at 12 and 24 weeks of age revealed altered B lymphopoiesis. Strikingly, the B lymphocyte phenotype differed based on sex, age and also the BM microenvironment in which the B cells develop. When BM cells from wildtype mice were transplanted into Cntf(-/-) mice, there were minimal effects on B lymphopoiesis or bone parameters. However, when Cntf(-/-) BM cells were transplanted into a wildtype BM microenvironment, there were changes in both haematopoiesis and bone parameters. Our data reveal that haematopoietic cell-derived CNTF has roles in regulating BM B cell lymphopoiesis and both trabecular and cortical bone, the latter in a sex-dependent manner. PMID:26487326

  3. Ciliary neurotrophic factor protects striatal neurons against excitotoxicity by enhancing glial glutamate uptake.

    Directory of Open Access Journals (Sweden)

    Corinne Beurrier

    Full Text Available Ciliary neurotrophic factor (CNTF is a potent neuroprotective cytokine in different animal models of glutamate-induced excitotoxicity, although its action mechanisms are still poorly characterized. We tested the hypothesis that an increased function of glial glutamate transporters (GTs could underlie CNTF-mediated neuroprotection. We show that neuronal loss induced by in vivo striatal injection of the excitotoxin quinolinic acid (QA was significantly reduced (by approximately 75% in CNTF-treated animals. In striatal slices, acute QA application dramatically inhibited corticostriatal field potentials (FPs, whose recovery was significantly higher in CNTF rats compared to controls (approximately 40% vs. approximately 7%, confirming an enhanced resistance to excitotoxicity. The GT inhibitor DL-threo-beta-benzyloxyaspartate greatly reduced FP recovery in CNTF rats, supporting the role of GT in CNTF-mediated neuroprotection. Whole-cell patch-clamp recordings from striatal medium spiny neurons showed no alteration of basic properties of striatal glutamatergic transmission in CNTF animals, but the increased effect of a low-affinity competitive glutamate receptor antagonist (gamma-D-glutamylglycine also suggested an enhanced GT function. These data strongly support our hypothesis that CNTF is neuroprotective via an increased function of glial GTs, and further confirms the therapeutic potential of CNTF for the clinical treatment of progressive neurodegenerative diseases involving glutamate overflow.

  4. Effects of Brain-Derived Neurotrophic Factor on Local Inflammation in Experimental Stroke of Rat

    Directory of Open Access Journals (Sweden)

    Yongjun Jiang

    2010-01-01

    Full Text Available This study was aimed to investigate whether brain-derived neurotrophic factor (BDNF can modulate local cerebral inflammation in ischemic stroke. Rats were subjected to ischemia by occluding the right middle cerebral artery (MCAO for 2 hours. Rats were randomized as control, BDNF, and antibody groups. The local inflammation was evaluated on cellular, cytokine, and transcription factor levels with immunofluorescence, enzyme-linked immunosorbent assay, real-time qPCR, and electrophoretic mobility shift assay, respectively. Exogenous BDNF significantly improved motor-sensory, sensorimotor function, and vestibulomotor function, while BDNF did not decrease the infarct volume. Exogenous BDNF increased the number of both activated and phagocytotic microglia in brain. BDNF upregulated interleukin10 and its mRNA expression, while downregulated tumor necrosis factor α and its mRNA expression. BDNF also increased DNA-binding activity of nuclear factor-kappa B. BDNF antibody, which blocked the activity of endogenous BDNF, showed the opposite effect of exogenous BDNF. Our data indicated that BDNF may modulate local inflammation in ischemic brain tissues on the cellular, cytokine, and transcription factor levels.

  5. Overexpression of brain-derived neurotrophic factor in the hippocampus protects against post-stroke depression

    Institute of Scientific and Technical Information of China (English)

    Hao-hao Chen; Ning Zhang; Wei-yun Li; Ma-rong Fang; Hui Zhang; Yuan-shu Fang; Ming-xing Ding; Xiao-yan Fu

    2015-01-01

    Post-stroke depression is associated with reduced expression of brain-derived neurotrophic factor (BDNF). In this study, we evaluated whether BDNF overexpression affects depression-like behavior in a rat model of post-stroke depression. The middle cerebral artery was occluded to produce a model of focal cerebral ischemia. These rats were then subjected to isolation-housing combined with chronic unpredictable mild stress to generate a model of post-stroke depression. ABDNF gene lentiviral vector was injected into the hippocampus. At 7 days after injection, western blot assay and real-time quantitative PCR revealed that BDNF expression in the hippo-campus was increased in depressive rats injected with BDNF lentivirus compared with depressive rats injected with control vector. Furthermore, sucrose solution consumption was higher, and horizontal and vertical movement scores were increased in the open ifeld test in these rats as well. These ifndings suggest that BDNF overexpression in the hippocampus of post-stroke depressive rats alleviates depression-like behaviors.

  6. Circulating levels of ciliary neurotrophic factor in normal pregnancy and preeclampsia

    Directory of Open Access Journals (Sweden)

    Akahori,Yoichiro

    2010-04-01

    Full Text Available

    Ciliary neurotrophic factor (CNTF has been shown to decrease food intake in mouse models of obesity and to improve insulin sensitivity. It is well known that tight regulation of glucose metabolism is essential for successful gestational outcomes (e.g. fetal growth, and that abnormal insulin resistance is associated with preeclampsia (PE. To investigate the possibility that CNTF might be involved in the regulation of insulin resistance during pregnancy, circulating levels of CNTF were assessed in non-pregnant, normal pregnant, postpartum, and pregnant women with PE. Sera from healthy non-pregnant women (n10, pregnant women (n30:1st trimester;n10, 2nd trimester n10;3rd trimester;n10, postpartum women (n10, and patients with PE (n11 were studied with Western blotting. Circulating CNTF was detected by Western blotting, and the levels of CNTF in pregnant women were decreased as compared with those in non-pregnant women, and tended to decrease as pregnancy progressed. A significant decrease was found in PE as compared with normal pregnancy. Circulating CNTF might be associated with physiological and abnormal insulin resistance during pregnancy.

  7. An Overview of Brain-Derived Neurotrophic Factor and Implications for Excitotoxic Vulnerability in the Hippocampus

    Directory of Open Access Journals (Sweden)

    Patrick S. Murray

    2011-01-01

    Full Text Available The present paper examines the nature and function of brain-derived neurotrophic factor (BDNF in the hippocampal formation and the consequences of changes in its expression. The paper focuses on literature describing the role of BDNF in hippocampal development and neuroplasticity. BDNF expression is highly sensitive to developmental and environmental factors, and increased BDNF signaling enhances neurogenesis, neurite sprouting, electrophysiological activity, and other processes reflective of a general enhancement of hippocampal function. Such increases in activity may mediate beneficial effects such as enhanced learning and memory. However, the increased activity also comes at a cost: BDNF plasticity renders the hippocampus more vulnerable to hyperexcitability and/or excitotoxic damage. Exercise dramatically increases hippocampal BDNF levels and produces behavioral effects consistent with this phenomenon. In analyzing the literature regarding exercise-induced regulation of BDNF, this paper provides a theoretical model for how the potentially deleterious consequences of BDNF plasticity may be modulated by other endogenous factors. The peptide galanin may play such a role by regulating hippocampal excitability.

  8. Brain-derived neurotrophic factor into adult neocortex strengthens a taste aversion memory.

    Science.gov (United States)

    Martínez-Moreno, Araceli; Rodríguez-Durán, Luis F; Escobar, Martha L

    2016-01-15

    Nowadays, it is known that brain derived neurotrophic-factor (BDNF) is a protein critically involved in regulating long-term memory related mechanisms. Previous studies from our group in the insular cortex (IC), a brain structure of the temporal lobe implicated in acquisition, consolidation and retention of conditioned taste aversion (CTA), demonstrated that BDNF is essential for CTA consolidation. Recent studies show that BDNF-TrkB signaling is able to mediate the enhancement of memory. However, whether BDNF into neocortex is able to enhance aversive memories remains unexplored. In the present work, we administrated BDNF in a concentration capable of inducing in vivo neocortical LTP, into the IC immediately after CTA acquisition in two different conditions: a "strong-CTA" induced by 0.2M lithium chloride i.p. as unconditioned stimulus, and a "weak-CTA" induced by 0.1M lithium chloride i.p. Our results show that infusion of BDNF into the IC converts a weak CTA into a strong one, in a TrkB receptor-dependent manner. The present data suggest that BDNF into the adult insular cortex is sufficient to increase an aversive memory-trace. PMID:26433146

  9. Role of Stress-Related Brain-Derived Neurotrophic Factor (BDNF) in the Rat Submandibular Gland

    International Nuclear Information System (INIS)

    The nerve growth factor (NGF) family comprises NGF, brain-derived neurotrophic factor (BDNF) and neurotrophins (NTs)-3, -4/5, -6 and -7, all of which are collectively referred to as neurotrophins. However, the expression of neurotrophins other than NGF in the salivary gland has not been described in detail. Through interaction with the TrkB receptor, BDNF plays an important role in long-term potentiation. We found that BDNF expression increased within submandibular gland tissue in response to stress, suggesting that the salivary glands are sensitive to stress. In addition, stress caused increases in plasma BDNF derived from the submandibular gland and in TrkB receptor mRNA in the adrenal medulla. Plasma BDNF might activate TrkB receptors in the adrenal medulla during acute stress. The salivary glands are likely to influence not only oral health, but also systemic organs. This review addressed the relationship between hormone-like effects and stress-related BDNF expression in the rat submandibular gland

  10. EXPRESSING HUMAN MATURED BRAIN-DERIVED NEUROTROPHIC FACTOR GENE IN E. Coli AND DETERMINING ITS BIOACTIVITY

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective Expressing the human matured brain-derived neurotrophic factor (mBDNF) gene in E.Coli and determining its bioactivity. Methods The resulting gene of mBDNF was subcloned into the EcoRI-BamHI site of the expression vector plasmid pBV220. The ligation products were used to transform the competent E. Coli DH5α. The proteins of mBDNF were experessed by temperature inducing. The expression products were dealed with solubilizing inclusion bodies and refolding protein. It was introduced into the embryonic chicken DRG to test whether the expressed mBDNF is a biologically active protein. Results The recombinant plasmid pBV/mBDNF was successfully constructed. By temperature inducing,under the control of the bacteriophage λ PL promoter, the experessed mBDNF protein was a 14Kd non-fusion protein,which existed in E. Coli as inclusion bodies. The size of expressed mBDNF is identical to the prediction. Bioactivity of the products was proved that it could support the cell survival and neurite growth in the primary cultures of embryonic 8-day-old chicken DRG neurons as compared to control.Conclusion The mBDNF gene can be expressed bioactively in E. Coli.

  11. Spiral ganglion neuron survival and function in the deafened cochlea following chronic neurotrophic treatment.

    Science.gov (United States)

    Landry, Thomas G; Wise, Andrew K; Fallon, James B; Shepherd, Robert K

    2011-12-01

    Cochlear implants electrically stimulate residual spiral ganglion neurons (SGNs) to provide auditory cues for the severe-profoundly deaf. However, SGNs gradually degenerate following cochlear hair cell loss, leaving fewer neurons available for stimulation. Providing an exogenous supply of neurotrophins (NTs) has been shown to prevent SGN degeneration, and when combined with chronic intracochlear electrical stimulation (ES) following a short period of deafness (5 days), may also promote the formation of new neurons. The present study assessed the histopathological response of guinea pig cochleae treated with NTs (brain-derived neurotrophic factor and neurotrophin-3) with and without ES over a four week period, initiated two weeks after deafening. Results were compared to both NT alone and artificial perilymph (AP) treated animals. AP/ES treated animals exhibited no evidence of SGN rescue compared with untreated deafened controls. In contrast, NT administration showed a significant SGN rescue effect in the lower and middle cochlear turns (two-way ANOVA, p evoked auditory brainstem response (EABR) thresholds. EABR thresholds following NT treatment were significantly lower than animals treated with AP (two-way ANOVA, p = 0.033). Finally, the potential for induced neurogenesis following the combined treatment was investigated using a marker of DNA synthesis. However, no evidence of neurogenesis was observed in the SGN population. The results indicate that chronic NT delivery to the cochlea may be beneficial to cochlear implant patients by increasing the number of viable SGNs and decreasing activation thresholds compared to chronic ES alone. PMID:21762764

  12. Brain-derived neurotrophic factor differentially modulates excitability of two classes of hippocampal output neurons.

    Science.gov (United States)

    Graves, A R; Moore, S J; Spruston, N; Tryba, A K; Kaczorowski, C C

    2016-08-01

    Brain-derived neurotrophic factor (BDNF) plays an important role in hippocampus-dependent learning and memory. Canonically, this has been ascribed to an enhancing effect on neuronal excitability and synaptic plasticity in the CA1 region. However, it is the pyramidal neurons in the subiculum that form the primary efferent pathways conveying hippocampal information to other areas of the brain, and yet the effect of BDNF on these neurons has remained unexplored. We present new data that BDNF regulates neuronal excitability and cellular plasticity in a much more complex manner than previously suggested. Subicular pyramidal neurons can be divided into two major classes, which have different electrophysiological and morphological properties, different requirements for the induction of plasticity, and different extrahippocampal projections. We found that BDNF increases excitability in one class of subicular pyramidal neurons yet decreases excitability in the other class. Furthermore, while endogenous BDNF was necessary for the induction of synaptic plasticity in both cell types, BDNF enhanced intrinsic plasticity in one class of pyramidal neurons yet suppressed intrinsic plasticity in the other. Taken together, these data suggest a novel role for BDNF signaling, as it appears to dynamically and bidirectionally regulate the output of hippocampal information to different regions of the brain. PMID:27146982

  13. Decreased serum levels of brain-derived neurotrophic factor in schizophrenic patients with deficit syndrome

    Science.gov (United States)

    Akyol, Esra Soydaş; Albayrak, Yakup; Beyazyüz, Murat; Aksoy, Nurkan; Kuloglu, Murat; Hashimoto, Kenji

    2015-01-01

    Background Brain-derived neurotrophic factor (BDNF) is a well-established neurotrophin that plays a role in the pathophysiology of numerous psychiatric disorders. Many studies have investigated the serum BDNF levels in patients with schizophrenia. However, there are restricted data in the literature that compare the serum BDNF levels in patients with deficit and nondeficit syndromes. In this study, we aimed to compare the serum BDNF levels between schizophrenic patients with deficit or nondeficit syndrome and healthy controls. Methods After fulfilling the inclusion and exclusion criteria, 58 patients with schizophrenia and 36 healthy controls were included in the study. The patients were grouped as deficit syndrome (N=23) and nondeficit syndrome (N=35) according to the Schedule for the Deficit Syndrome. Three groups were compared in terms of the sociodemographic and clinical variants and serum BDNF levels. Results The groups were similar in terms of age, sex, body mass index, and smoking status. The serum BDNF levels in patients with deficit syndrome were significantly lower than those in healthy controls. In contrast, the serum BDNF levels in patients with nondeficit syndrome were similar to those in healthy controls. Conclusion This study suggests that decreased BDNF levels may play a role in the pathophysiology of schizophrenic patients with deficit syndrome. Nonetheless, additional studies using a larger patient sample size are needed to investigate the serum BDNF levels in schizophrenic patients with deficit syndrome. PMID:25848285

  14. Maternal separation produces alterations of forebrain brain-derived neurotrophic factor expression in differently aged rats

    Directory of Open Access Journals (Sweden)

    Qiong eWang

    2015-09-01

    Full Text Available Early postnatal maternal separation (MS can play an important role in the development of psychopathologies during ontogeny. In the present study, we investigated the effects of repeated MS (4 h per day from postnatal day [PND] 1–21 on the brain-derived neurotrophic factor (BDNF expression in the medial prefrontal cortex (mPFC, the nucleus accumbens (NAc and the hippocampus of male and female juvenile (PND 21, adolescent (PND 35 and young adult (PND 56 Wistar rats. The results indicated that MS increased BDNF in the CA1 and the dentate gyrus (DG of adolescent rats as well as in the DG of young adult rats. However, the expression of BDNF in the mPFC in the young adult rats was decreased by MS. Additionally, in the hippocampus, there was decreased BDNF expression with age in both the MS and socially reared rats. However, in the mPFC, the BDNF expression was increased with age in the socially reared rats; nevertheless, the BDNF expression was significantly decreased in the MS young adult rats. In the NAc, the BDNF expression was increased with age in the male NMS rats, and the young adult female MS rats had less BDNF expression than the adolescent female MS rats. The

  15. Withdrawing to a virtual world: Associations between subtypes of withdrawal, media use, and maladjustment in emerging adults.

    Science.gov (United States)

    Nelson, Larry J; Coyne, Sarah M; Howard, Emily; Clifford, Brandon N

    2016-06-01

    An approach-avoidance model of social withdrawal (Asendorpf, 1990) identifies 3 types of social withdrawal including shyness, unsociability, and avoidance. Each appears to be uniquely associated with varying indicators of maladjustment in emerging adulthood (Nelson, 2013) but little, if any, work has been done to see how they might be linked to media use in the third decade of life. Therefore, the purpose of this study was to examine longitudinally the links between subtypes of social withdrawal, connective media (e.g., e-mail, social networking) and problematic (forms of media such as violent video games that, when used in high amounts, have been found to be linked to indices of maladjustment) media use, and internalizing and externalizing behaviors. The participants in the study (Mage = 20.70, SD = 1.98, range = 18-29 at Time 2) consisted of 204 undergraduate students (58% female) recruited from 2 large public universities in the United States who completed questionnaires at 2 points of time separated by 1 year. Results revealed that avoidant individuals use problematic forms of media more than average, unsociable, and shy individuals. Furthermore, problematic media use predicted more withdrawn behavior at Time 2 and mediated the relation between avoidance and externalizing behaviors over time. Few problems were found for unsociable behavior. The need to differentiate between multiple forms of withdrawal in emerging adulthood and their links with problematic forms of media and subsequent risk factors is discussed. (PsycINFO Database Record PMID:27148777

  16. "Is That A Method of Birth Control?" A Qualitative Exploration of Young Women's Use of Withdrawal.

    Science.gov (United States)

    Arteaga, Stephanie; Gomez, Anu Manchikanti

    2016-01-01

    Despite its ubiquity, withdrawal is understudied as a family planning method. We investigated the context of and decision making around withdrawal use, drawing on in-depth, qualitative interviews with 38 Black and Latina women (ages 18 to 24). We examined contraceptive use histories to understand when and why participants used withdrawal. The majority of participants (n = 29; 76%) had used withdrawal in their lifetimes, though two-thirds of users mentioned withdrawal in their contraceptive histories only after interviewer prompts. Withdrawal was primarily used during transitions between contraceptive methods and when other methods were not desired. Relationship context was also an important factor, as many used withdrawal to increase intimacy with their partners; because they felt condoms were no longer necessary due to monogamy; or to fulfill their partners' preferences to increase sexual pleasure. Our findings indicate that decision making around withdrawal is embedded in situational and relational contexts. Future research should explore how health care providers and sex educators can engage young women in discussions of withdrawal's benefits and constraints. A harm reduction framework, which recognizes that optimal use of withdrawal is preferable to not using a pregnancy prevention method at all, may inform the ways that withdrawal can be addressed in clinical and educational settings. PMID:26515120

  17. Incarceration and opioid withdrawal: the experiences of methadone patients and out-of-treatment heroin users.

    Science.gov (United States)

    Mitchell, Shannon Gwin; Kelly, Sharon M; Brown, Barry S; Reisinger, Heather Schacht; Peterson, James A; Ruhf, Adrienne; Agar, Michael H; Schwartz, Robert P

    2009-06-01

    Both heroin-addicted individuals and methadone maintenance patients are likely to face untreated opioid withdrawal while incarcerated. Limited research exists concerning the withdrawal experiences of addicted inmates and their impact on individuals' attitudes and plans concerning drug abuse treatment. In the present study, 53 opioid dependent adults (32 in methadone treatment and 21 out of treatment) were interviewed in an ethnographic investigation of withdrawal experiences during incarceration. When treatment for opioid withdrawal was unavailable, detoxification experiences were usually described as negative and were often associated with a variety of unhealthy behaviors designed to relieve withdrawal symptoms. Negative methadone withdrawal experiences also negatively influenced participants' receptivity to seeking methadone treatment upon release. A minority of participants took a positive view of their withdrawal experience and saw it as an opportunity to detox from heroin or discontinue methadone. Findings support the importance of providing appropriate opioid detoxification and/or maintenance therapy to opioid-dependent inmates. PMID:19705676

  18. Intraspinal transplantation of motoneuron-like cell combined with delivery of polymer-based glial cell line-derived neurotrophic factor for repair of spinal cord contusion injury

    Institute of Scientific and Technical Information of China (English)

    Alireza Abdanipour; Taki Tiraihi; Taher Taheri

    2014-01-01

    To evaluate the effects of glial cell line-derived neurotrophic factor transplantation combined with adipose-derived stem cells-transdifferentiated motoneuron delivery on spinal cord con-tusion injury, we developed rat models of spinal cord contusion injury, 7 days later, injected adipose-derived stem cells-transdifferentiated motoneurons into the epicenter, rostral and caudal regions of the impact site and simultaneously transplanted glial cell line-derived neuro-trophic factor-gelfoam complex into the myelin sheath. Motoneuron-like cell transplantation combined with glial cell line-derived neurotrophic factor delivery reduced cavity formations and increased cell density in the transplantation site. The combined therapy exhibited superior promoting effects on recovery of motor function to transplantation of glial cell line-derived neurotrophic factor, adipose-derived stem cells or motoneurons alone. These ifndings suggest that motoneuron-like cell transplantation combined with glial cell line-derived neurotrophic factor delivery holds a great promise for repair of spinal cord injury.

  19. Short term memory, physical fitness, and serum brain-derived neurotrophic factor in obese adolescents

    Directory of Open Access Journals (Sweden)

    Rini Rossanti

    2015-10-01

    Full Text Available Background Obesity in adolescents is a major health problem and has been associated with low academic achievement. Brainderived neurotrophic factor (BDNF, a neurotrophin, plays a role in appetite suppression and memory, and its secretion is enhanced by physical activity. This neurotrophin may be associated with academic achievement in obese. Objective To compare physical fitness and serum BDNF levels to short term memory levels in obese adolescents aged 10–14 years. Methods This comparative, cross-sectional, analytic study was carried out on 40 elementary and high school students in Bandung, West Java, who were recruited by stratified random sampling. Short term memory was assessed by a psychologist using the Wechsler Intelligence Scale for Children-III Digit Span test (WISC-III Digit Span. Physical fitness was assessed by a clinical exercise physiologist using the Asian Committee on the Standardization of Physical Fitness Test (ACSPFT. Serum BDNF levels were measured by ELISA test in a certified laboratory. ANOVA test was used to assess for a correlation between serum BDNF concentration and short term memory, as well as between physical fitness level and short term memory. Pearson’s correlation test was used to analyze for a correlation between serum BDNF and physical fitness levels. Results The majority of subjects were in the physical fitness categories of moderate or poor. Subjects had a mean BDNF level of 44,227.8 (SD 10,359 pg/mL. There was no statistically significant difference in physical fitness with either serum BDNF or with short term memory levels (P=0.139 and P=0.383, respectively. Also, no correlation was determined between serum BDNF and physical fitness levels (r=0.222; P=0.169. Conclusion In obese adolescents, short term memory levels are not significantly different between physical fitness levels nor between serum BDNF levels.

  20. Short term memory, physical fitness, and serum brain-derived neurotrophic factor in obese adolescents

    Directory of Open Access Journals (Sweden)

    Rini Rossanti

    2015-09-01

    Full Text Available Background Obesity in adolescents is a major health problem and has been associated with low academic achievement. Brain-derived neurotrophic factor (BDNF, a neurotrophin, plays a role in appetite suppression and memory, and its secretion is enhanced by physical activity. This neurotrophin may be associated with academic achievement in obese. Objective To compare physical fitness and serum BDNF levels to short term memory levels in obese adolescents aged 10–14 years. Methods This comparative, cross-sectional, analytic study was carried out on 40 elementary and high school students in Bandung, West Java, who were recruited by stratified random sampling. Short term memory was assessed by a psychologist using the Wechsler Intelligence Scale for Children-III Digit Span test (WISC-III Digit Span. Physical fitness was assessed by a clinical exercise physiologist using the Asian Committee on the Standardization of Physical Fitness Test (ACSPFT. Serum BDNF levels were measured by ELISA test in a certified laboratory. ANOVA test was used to assess for a correlation between serum BDNF concentration and short term memory, as well as between physical fitness level and short term memory. Pearson’s correlation test was used to analyze for a correlation between serum BDNF and physical fitness levels. Results The majority of subjects were in the physical fitness categories of moderate or poor. Subjects had a mean BDNF level of 44,227.8 (SD 10,359 pg/mL. There was no statistically significant difference in physical fitness with either serum BDNF or with short term memory levels (P=0.139 and P=0.383, respectively. Also, no correlation was determined between serum BDNF and physical fitness levels (r=0.222; P=0.169. Conclusion In obese adolescents, short term memory levels are not significantly different between physical fitness levels nor between serum BDNF levels.

  1. Attenuated brain-derived neurotrophic factor and hypertrophic remodelling: the SABPA study.

    Science.gov (United States)

    Smith, A J; Malan, L; Uys, A S; Malan, N T; Harvey, B H; Ziemssen, T

    2015-01-01

    Brain-derived neurotrophic factor (BDNF) has been linked to neurological pathologies, but its role in cardiometabolic disturbances is limited. We aimed to assess the association between serum BDNF levels and structural endothelial dysfunction (ED) as determined by cross-sectional wall area (CSWA) and albumin/creatinine ratio (ACR) in black Africans. Ambulatory blood pressure (BP) and ultrasound CSWA values were obtained from 82 males and 90 females. Fasting blood and 8 h overnight urine samples were collected to determine serum BDNF and cardiometabolic risk markers, that is, glycated haemoglobin (HbA1c), lipids, inflammation and ACR. BDNF median split × gender interaction effects for structural ED justified stratification of BDNF into low and high (⩽/>1.37 ng ml(-1)) gender groups. BDNF values (0.86-1.98 ng ml(-1)) were substantially lower than reference ranges (6.97-42.6 ng ml(-1)) in the African gender cohort, independent of age and body mass index. No relationship was revealed between BDNF and renal function and was opposed by an inverse relationship between BDNF and CSWA (r=-0.17; P=0.03) in the African cohort. Linear regression analyses revealed a positive relationship between systolic BP and structural remodelling in the total cohort and low-BDNF gender groups. In the high-BDNF females, HbA1C was associated with structural remodelling. Attenuated or possible downregulated BDNF levels were associated with hypertrophic remodelling, and may be a compensatory mechanism for the higher BP in Africans. In addition, metabolic risk and hypertrophic remodelling in women with high BDNF underpin different underlying mechanisms for impaired neurotrophin homeostasis in men and women. PMID:24898921

  2. Exenatide enhances cognitive performance and upregulates neurotrophic factor gene expression levels in diabetic mice.

    Science.gov (United States)

    Gumuslu, Esen; Mutlu, Oguz; Celikyurt, Ipek K; Ulak, Guner; Akar, Furuzan; Erden, Faruk; Ertan, Merve

    2016-08-01

    Exenatide is a potent and selective agonist for the GLP-1 (glucagon-like peptide-1) receptor. Recent studies are focused on the effects of GLP-1 analogues on hippocampal neurogenesis, cognition, learning and memory functions. The aim of this study was to assess the effects of chronic exenatide treatment (0.1 μg/kg, s.c, twice daily for 2 weeks) on spatial memory functions by using the modified elevated plus maze (mEPM) test and emotional memory functions by using the passive avoidance (PA) test in streptozotocin/nicotinamide (STZ-NA)-induced diabetic mice. As the genes involved in neurite remodelling are among the primary targets of regulation, the effects of diabetes and chronic administration of exenatide on brain-derived neurotrophic factor (BDNF) and cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) messenger ribonucleic acid (mRNA) levels in the hippocampus of mice were also determined using quantitative real-time polymerase chain reaction (RT-PCR). This study revealed that in the mEPM and PA tests, type-2 diabetes-induced mice exhibited significant impairment of learning and memory which were ameliorated by GLP-1 receptor agonist exenatide. Quantitative RT-PCR revealed that CREB and BDNF gene expression levels were downregulated in diabetic mice, and these alterations were increased by exenatide treatment. Since, exenatide improves cognitive ability in STZ/NA-induced diabetic mice and activates molecular mechanisms of memory storage in response to a learning experience, it may be a candidate for alleviation of mood and cognitive disorder. PMID:26935863

  3. The relationship between ciliary neurotrophic factor (CNTF genotype and motor unit physiology: preliminary studies

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    Ferrell Robert

    2005-09-01

    Full Text Available Abstract Background Ciliary neurotrophic factor (CNTF is important for neuronal and muscle development, and genetic variation in the CNTF gene has been associated with muscle strength. The effect of CNTF on nerve development suggests that CNTF genotype may be associated with force production via its influence on motor unit size and firing patterns. The purpose of this study is to examine whether CNTF genotype differentially affects motor unit activation in the vastus medialis with increasing isometric force during knee extension. Results Sixty-nine healthy subjects were genotyped for the presence of the G and A (null alleles in the CNTF gene (n = 57 G/G, 12 G/A. They were tested using a dynamometer during submaximal isometric knee extension contractions that were from 10–50% of their maximal strength. During the contractions, the vastus medialis was studied using surface and intramuscular electromyography with spiked triggered averaging to assess surface-detected motor unit potential (SMUP area and mean firing rates (mFR from identified motor units. CNTF genotyping was performed using standard PCR techniques from DNA obtained from leucocytes of whole blood samples. The CNTF G/A genotype was associated with smaller SMUP area motor units and lower mFR at higher force levels, and fewer but larger units at lower force levels than G/G homozygotes. The two groups used motor units with different size and activation characteristics with increasing force generation. While G/G subjects tended to utilize larger motor units with increasing force, G/A subjects showed relatively less increase in size by using relatively larger units at lower force levels. At higher force levels, G/A subjects were able to generate more force per motor unit size suggesting more efficient motor unit function with increasing muscle force. Conclusion Differential motor unit responses were observed between CNTF genotypes at force levels utilized in daily activities.

  4. Anti-neurotrophic effects from autoantibodies in adult diabetes having primary open angle glaucoma or dementia

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    Mark B Zimering

    2013-05-01

    Full Text Available Aims: To test for anti-endothelial and anti-neurotrophic effects from autoantibodies in subsets of diabetes having open- angle glaucoma, dementia or control subjects.Methods: Protein-A eluates from plasma of 20 diabetic subjects having glaucoma or suspects and 34 age-matched controls were tested for effects on neurite outgrowth in rat pheochromocytoma PC12 cells or endothelial cell survival. The mechanism of the diabetic glaucoma autoantibodies' neurite inhibitory effect was investigated in coincubations with the selective Rho kinase inhibitor Y27632 or the sulfated proteoglycan synthesis inhibitor sodium chlorate. Stored protein-A eluates from certain diabetic glaucoma or dementia subjects which contained long-lasting, highly stable cell inhibitory substances were characterized using mass spectrometry and amino acid sequencing.Results: Diabetic primary open angle glaucoma or suspects (n=20 or diabetic dementia (n=3 autoantibodies caused significantly greater mean inhibition of neurite outgrowth in PC12 cells (p < .0001 compared to autoantibodies in control diabetic (n=24 or nondiabetic (n=10 subjects without glaucoma (p < .01. Neurite inhibition by the diabetic glaucoma autoantibodies was completely abolished by 10 µM concentrations of Y27632 (n=4. It was substantially reduced by 30 mM concentrations of sodium chlorate (n=4. Peak, long-lasting activity survived storage x 5 years at 0-4 deg C and was associated with a restricted subtype of Ig kappa light chain. Diabetic glaucoma or dementia autoantibodies (n=5 caused contraction and process retraction in quiescent cerebral cortical astrocytes effects which were blocked by 5 µM concentrations of Y27632. Conclusion: These data suggest that autoantibodies in adult diabetes having primary open angle glaucoma (glaucoma suspects and/or dementia inhibit neurite outgrowth and promote a reactive astrocyte morphology by a mechanism which may involve activation of the RhoA/p160 ROCK signaling pathway.

  5. Brain-derived neurotrophic factor modulates auditory function in the hearing cochlea.

    Science.gov (United States)

    Sly, David J; Hampson, Amy J; Minter, Ricki L; Heffer, Leon F; Li, Jack; Millard, Rodney E; Winata, Leon; Niasari, Allen; O'Leary, Stephen J

    2012-02-01

    Neurotrophins prevent spiral ganglion neuron (SGN) degeneration in animal models of ototoxin-induced deafness and may be used in the future to improve the hearing of cochlear implant patients. It is increasingly common for patients with residual hearing to undergo cochlear implantation. However, the effect of neurotrophin treatment on acoustic hearing is not known. In this study, brain-derived neurotrophic factor (BDNF) was applied to the round window membrane of adult guinea pigs for 4 weeks using a cannula attached to a mini-osmotic pump. SGN survival was first assessed in ototoxically deafened guinea pigs to establish that the delivery method was effective. Increased survival of SGNs was observed in the basal and middle cochlear turns of deafened guinea pigs treated with BDNF, confirming that delivery to the cochlea was successful. The effects of BDNF treatment in animals with normal hearing were then assessed using distortion product otoacoustic emissions (DPOAEs), pure tone, and click-evoked auditory brainstem responses (ABRs). DPOAE assessment indicated a mild deficit of 5 dB SPL in treated and control groups at 1 and 4 weeks after cannula placement. In contrast, ABR evaluation showed that BDNF lowered thresholds at specific frequencies (8 and 16 kHz) after 1 and 4 weeks posttreatment when compared to the control cohort receiving Ringer's solution. Longer treatment for 4 weeks not only widened the range of frequencies ameliorated from 2 to 32 kHz but also lowered the threshold by at least 28 dB SPL at frequencies ≥16 kHz. BDNF treatment for 4 weeks also increased the amplitude of the ABR response when compared to either the control cohort or prior to treatment. We show that BDNF applied to the round window reduces auditory thresholds and could potentially be used clinically to protect residual hearing following cochlear implantation. PMID:22086147

  6. Correlation of brain-derived neurotrophic factor to cognitive impairment following traumatic brain injury in rats

    Institute of Scientific and Technical Information of China (English)

    Dezhi Kang; Zhang Guo

    2008-01-01

    BACKGROUND: In vitro and in vivo studies have confirmed that brain-derived neurotrophic factor (BDNF) can promote survival and differentiation of cholinergic, dopaminergic and motor neurons, and axonal regeneration. BDNF has neuroprotective effects on the nervous system. OBJECTIVE: To explore changes in BDNF expression and cognitive function in rats after brain injury DESIGN, TIME AND SETTING: The neuropathology experiment was performed at the Second Research Room, Department of Neurosurgery, Fujian Medical University (China) from July 2007 to July 2008. MATERIALS: A total of 72 healthy, male, Sprague Dawley, rats were selected for this study. METHODS: Rat models of mild and moderate traumatic brain injury were created by percussion, according to Feeney's method (n = 24, each group). A bone window was made in rats from the sham operation group (n = 24), but no attack was conducted. MAIN OUTCOME MEASURES: At days 1,2, 4 and 7 following injury, BDNF expression in the rat frontal lobe cortex, hippocampus and basal forebrain was examined by immunohistochemistry (streptavidin-biotin-peroxidase complex method). Changes in rat cognitive function were assessed by the walking test, balance-beam test and memory function detection. RESULTS: Cognitive impairment was aggravated at day 2, and recovered to normal at days 3 and 7 in rats from the mild and moderate traumatic brain injury groups. BDNF expression in the rat frontal lobe cortex, hippocampus and basal forebrain was increased at 1 day, decreased at day 2, and then gradually increased in the mild and moderate traumatic brain injury groups. BDNF expression was greater in rats from the moderate traumatic brain injury group than in the sham operation and mild traumatic brain injury groups (P < 0.05). CONCLUSION: BDNF expression in the rat frontal lobe cortex, hippocampus and basal forebrain is correlated to cognitive impairment after traumatic brain injury. BDNF has a protective effect on cognitive function in rats

  7. Brain-derived neurotrophic factor signaling is altered in the forebrain of Engrailed-2 knockout mice.

    Science.gov (United States)

    Zunino, G; Messina, A; Sgadò, P; Baj, G; Casarosa, S; Bozzi, Y

    2016-06-01

    Engrailed-2 (En2), a homeodomain transcription factor involved in regionalization and patterning of the midbrain and hindbrain regions has been associated to autism spectrum disorders (ASDs). En2 knockout (En2(-/-)) mice show ASD-like features accompanied by a significant loss of GABAergic subpopulations in the hippocampus and neocortex. Brain-derived neurotrophic factor (BDNF) is a crucial factor for the postnatal development of forebrain GABAergic neurons, and altered GABA signaling has been hypothesized to underlie the symptoms of ASD. Here we sought to determine whether interneuron loss in the En2(-/-) forebrain might be related to altered expression of BDNF and its signaling receptors. We first evaluated the expression of different BDNF mRNA isoforms in the neocortex and hippocampus of wild-type (WT) and En2(-/-) mice. Quantitative RT-PCR showed a marked down-regulation of several splicing variants of BDNF mRNA in the neocortex but not hippocampus of adult En2(-/-) mice, as compared to WT controls. Accordingly, levels of mature BDNF protein were lower in the neocortex but not hippocampus of En2(-/-) mice, as compared to WT. Increased levels of phosphorylated TrkB and decreased levels of p75 receptor were also detected in the neocortex of mutant mice. Accordingly, the expression of low density lipoprotein receptor (LDLR) and RhoA, two genes regulated via p75 was significantly altered in forebrain areas of mutant mice. These data indicate that BDNF signaling alterations might be involved in the anatomical changes observed in the En2(-/-) forebrain and suggest a pathogenic role of altered BDNF signaling in this mouse model of ASD. PMID:26987954

  8. Repetitive acute intermittent hypoxia increases growth/neurotrophic factor expression in non-respiratory motor neurons.

    Science.gov (United States)

    Satriotomo, I; Nichols, N L; Dale, E A; Emery, A T; Dahlberg, J M; Mitchell, G S

    2016-05-13

    Repetitive acute intermittent hypoxia (rAIH) increases growth/trophic factor expression in respiratory motor neurons, thereby eliciting spinal respiratory motor plasticity and/or neuroprotection. Here we demonstrate that rAIH effects are not unique to respiratory motor neurons, but are also expressed in non-respiratory, spinal alpha motor neurons and upper motor neurons of the motor cortex. In specific, we used immunohistochemistry and immunofluorescence to assess growth/trophic factor protein expression in spinal sections from rats exposed to AIH three times per week for 10weeks (3×wAIH). 3×wAIH increased brain-derived neurotrophic factor (BDNF), its high-affinity receptor, tropomyosin receptor kinase B (TrkB), and phosphorylated TrkB (pTrkB) immunoreactivity in putative alpha motor neurons of spinal cervical 7 (C7) and lumbar 3 (L3) segments, as well as in upper motor neurons of the primary motor cortex (M1). 3×wAIH also increased immunoreactivity of vascular endothelial growth factor A (VEGFA), the high-affinity VEGFA receptor (VEGFR-2) and an important VEGF gene regulator, hypoxia-inducible factor-1α (HIF-1α). Thus, rAIH effects on growth/trophic factors are characteristic of non-respiratory as well as respiratory motor neurons. rAIH may be a useful tool in the treatment of disorders causing paralysis, such as spinal injury and motor neuron disease, as a pretreatment to enhance motor neuron survival during disease, or as preconditioning for cell-transplant therapies. PMID:26944605

  9. Both 5' and 3' flanks regulate Zebrafish brain-derived neurotrophic factor gene expression

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    Heinrich Gerhard

    2004-05-01

    Full Text Available Abstract Background Precise control of developmental and cell-specific expression of the brain-derived neurotrophic factor (BDNF gene is essential for normal neuronal development and the diverse functions of BDNF in the adult organism. We previously showed that the zebrafish BDNF gene has multiple promoters. The complexity of the promoter structure and the mechanisms that mediate developmental and cell-specific expression are still incompletely understood. Results Comparison of pufferfish and zebrafish BDNF gene sequences as well as 5' RACE revealed three additional 5' exons and associated promoters. RT-PCR with exon-specific primers showed differential developmental and organ-specific expression. Two exons were detected in the embryo before transcription starts. Of the adult organs examined, the heart expressed a single 5' exon whereas the brain, liver and eyes expressed four of the seven 5' exons. Three of the seven 5' exons were not detectable by RT-PCR. Injection of promoter/GFP constructs into embryos revealed distinct expression patterns. The 3' flank profoundly affected expression in a position-dependent manner and a highly conserved sequence (HCS1 present in 5' exon 1c in a dehancer-like manner. Conclusions The zebrafish BDNF gene is as complex in its promoter structure and patterns of differential promoter expression as is its murine counterpart. The expression of two of the promoters appears to be regulated in a temporally and/or spatially highly circumscribed fashion. The 3' flank has a position-dependent effect on expression, either by affecting transcription termination or post-transcriptional steps. HCS1, a highly conserved sequence in 5' exon 1c, restricts expression to primary sensory neurons. The tools are now available for detailed genetic and molecular analyses of zebrafish BDNF gene expression.

  10. The effect of regular aerobic exercise on urinary brain-derived neurotrophic factor in children

    Directory of Open Access Journals (Sweden)

    Yunita Fediani

    2014-11-01

    Full Text Available Background Nervous system development in early life influences the quality of cognitive ability during adulthood. Neuronal development and neurogenesis are highly influenced by neurotrophins. The most active neurotrophin is brain-derived neurotrophic factor (BDNF. Physical activity has a positive effect on cognitive function. However, few experimental studies have been done on children to assess the effect of aerobic regular exercise on BDNF levels. Objective To assess the effect of regular aerobic exercise on urinary BDNF levels in children. Methods This clinical study was performed in 67 children aged 6-8 years in Palembang. The intervention group (n=34 engaged in aerobic gymnastics three times per week for 8 weeks, while the control group (n=33 engaged in gymnastic only once per week. Measurements of urinary BDNF were performed on both groups before and after intervention. Mann-Whitney and Wilcoxon rank tests were used to analyze the differences between groups. Results There was no difference in urinary BDNF levels between the two groups prior to the intervention. After intervention, the mean urinary BDNF levels were significantly higher in the intervention group than in the control group, 230.2 (SD 264.4 pg/mL vs. 88.0 (SD 35.4 pg/mL, respectively (P=0.027. We also found that engaging in aerobic gymnastics significantly increased urinary BDNF levels from baseline in both groups (P=0.001. Conclusion Regular aerobic exercise can increase urinary BDNF levels and potentially improve cognitive function. Aerobic exercise should be a routine activity in school curriculums in combination with the learning process to improve children’s cognitive ability.[Paediatr Indones. 2014;54:351-7.].

  11. Acute aerobic exercise increases brain-derived neurotrophic factor levels in elderly with Alzheimer's disease.

    Science.gov (United States)

    Coelho, Flávia Gomes de Melo; Vital, Thays Martins; Stein, Angelica Miki; Arantes, Franciel José; Rueda, André Veloso; Camarini, Rosana; Teodorov, Elizabeth; Santos-Galduróz, Ruth Ferreira

    2014-01-01

    Studies indicate the involvement of brain-derived neurotrophic factor (BDNF) in the pathogenesis of Alzheimer's disease (AD). Decreased BDNF levels may constitute a lack of trophic support and contribute to cognitive impairment in AD. The benefits of acute and chronic physical exercise on BDNF levels are well-documented in humans, however, exercise effects on BDNF levels have not been analyzed in older adults with AD. The aim of this study was to investigate the effects of acute aerobic exercise on BDNF levels in older adults with AD and to verify associations among BDNF levels, aerobic fitness, and level of physical activity. Using a controlled design, twenty-one patients with AD (76.3 ± 6.2 years) and eighteen healthy older adults (74.6 ± 4.7 years) completed an acute aerobic exercise. The outcomes included measures of BDNF plasma levels, aerobic fitness (treadmill grade, time to exhaustion, VO2, and maximal lactate) and level of physical activity (Baecke Questionnaire Modified for the Elderly). The independent t-test shows differences between groups with respect to the BDNF plasma levels at baseline (p = 0.04; t = 4.53; df = 37). In two-way ANOVA, a significant effect of time was found (p = 0.001; F = 13.63; df = 37), the aerobic exercise significantly increased BDNF plasma levels in AD patients and healthy controls. A significant correlation (p = 0.04; r = 0.33) was found between BDNF levels and the level of physical activity. The results of our study suggest that aerobic exercise increases BDNF plasma levels in patients with AD and healthy controls. In addition to that, BDNF levels had association with level of physical activity. PMID:24164734

  12. Effects of the neurotrophic factor artemin on sensory afferent development and sensitivity

    Institute of Scientific and Technical Information of China (English)

    Shuying WANG; Christopher M. Elitt; Sacha A. Malin; Kathryn M. Albers

    2008-01-01

    Artemin is a neuronal survival and differentiation factor in the glial cell line-derived neurotrophic factor family. Its receptor GFRα3 is expressed by a subpopulation of nociceptor type sensory neurons in the dorsal root and trigeminal ganglia (DRG and TG). These neurons co-express the heat, capsaicin and proton-sensitive channel TRPV 1 and the cold and chemical-sensitive channel TRPA1. To further investigate the effects of artemin on sensory neurons, we isolated transgenic mice (ARTN-OE mice) that overexpress artemin in keratinocytes of the skin and tongue. Enhanced levels of artemin led to a 20% increase in the total number of DRG neurons and increases in the level of mRNA encoding TRPV1 and TRPAI. Calcium imaging showed that isolated sensory neurons from ARTN-OE mice were hypersensitive to the TRPV 1 agonist capsaicin and the TRPA1 agonist mustard oil. Behavioral testing of ARTN-OE mice also showed an increased sensitivity to heat, cold, capsaicin and mustard oil stimuli applied either to the skin or in the drinking water. Sensory neurons from wildtype mice also exhibited potentiated capsaicin responses following artemin addition to the media. In addition, injection of artemin into hindpaw skin produced transient thermal hyperalgesia. These findings indicate that artemin can modulate sensory function and that this regulation may occur through changes in channel gene expression. Because artemin mRNA expression is up-regulated in inflamed tissue and following nerve injury, it may have a significant role in cellular changes that underlie pain associated with pathological conditions. Manipulation of artemin expression may therefore offer a new pain treatment strategy.

  13. Gender differences in platelet brain derived neurotrophic factor in patients with cardiovascular disease and depression.

    Science.gov (United States)

    Williams, Marlene S; Ngongang, Chelsea K; Ouyang, Pam; Betoudji, Fabrice; Harrer, Christine; Wang, Nae-Yuh; Ziegelstein, Roy C

    2016-07-01

    Women have a higher prevalence of depression compared to men. Serum levels of Brain-derived neurotrophic factor (BDNF) are decreased in depression. BDNF may also have a protective role in the pathogenesis of coronary artery disease (CAD) or events. We examined whether there are gender differences in BDNF levels in patients with stable CAD and comorbid depression. We enrolled 37 patients (17 women) with stable CAD with and without depression from a single medical center. All patients had depression assessment with the Beck Depression Inventory-II questionnaire. Both plasma and platelet BDNF were measured in all patients using a standard ELISA method. Platelet BDNF levels were higher than plasma BDNF levels in the entire group (5903.9 ± 1915.6 vs 848.5 ± 460.5 pg/ml, p depression (BDI-II depression (n = 8, 7382.8 ± 1633.1 vs 4811.7 ± 1642.3 pg/ml, p = 0.007). Women with no or minimal depression (BDI depression (n = 18, 6900.2 ± 1486.6 vs 4972.9 ± 1568.9 pg/ml, p = 0.001). The plasma BDNF levels were similar between men and women in all categories of depression. In conclusion, women with stable CAD have increased platelet BDNF levels when compared to men with stable CAD regardless of their level of depression. Sex specific differences in BDNF could possibly indicate differences in factors linking platelet activation and depression in men and women. PMID:27082490

  14. Brain-derived neurotrophic factor acutely inhibits AMPA-mediated currents in developing sensory relay neurons.

    Science.gov (United States)

    Balkowiec, A; Kunze, D L; Katz, D M

    2000-03-01

    Brain-derived neurotrophic factor (BDNF) is expressed by many primary sensory neurons that no longer require neurotrophins for survival, indicating that BDNF may be used as a signaling molecule by the afferents themselves. Because many primary afferents also express glutamate, we investigated the possibility that BDNF modulates glutamatergic AMPA responses of newborn second-order sensory relay neurons. Perforated-patch, voltage-clamp recordings were made from dissociated neurons of the brainstem nucleus tractus solitarius (nTS), a region that receives massive primary afferent input from BDNF-containing neurons in the nodose and petrosal cranial sensory ganglia. Electrophysiological analysis was combined in some experiments with anterograde labeling of primary afferent terminals to specifically analyze responses of identified second-order neurons. Our data demonstrate that BDNF strongly inhibits AMPA-mediated currents in a large subset of nTS cells. Specifically, AMPA responses were either completely abolished or markedly inhibited by BDNF in 73% of postnatal day (P0) cells and in 82% of identified P5 second-order sensory relay neurons. This effect of BDNF is mimicked by NT-4, but not NGF, and blocked by the Trk tyrosine kinase inhibitor K252a, consistent with a requirement for TrkB receptor activation. Moreover, analysis of TrkB expression in culture revealed a close correlation between the percentage of nTS neurons in which BDNF inhibits AMPA currents and the percentage of neurons that exhibit TrkB immunoreactivity. These data document a previously undefined mechanism of acute modulation of AMPA responses by BDNF and indicate that BDNF may regulate glutamatergic transmission at primary afferent synapses. PMID:10684891

  15. Something old, something new: a successful case of meprobamate withdrawal.

    Science.gov (United States)

    James, Alexander Owen; Nicholson, Timothy R; Hill, Robert; Bearn, Jennifer

    2016-01-01

    Meprobamate, a benzodiazepine-like drug, was commonly prescribed for anxiety in the 1960s and 1970s, but fell out of favour, at least in part, due to the risk of dependence, for which there is little published evidence to guide clinical management. We discuss a 70-year-old man with a 45-year history of meprobamate dependency and multiple failed previous withdrawal attempts who was successfully withdrawn from meprobamate using diazepam during a 2-week inpatient stay on a specialist Addictions ward. An appropriate diazepam dose was established using the Clinical Institute Withdrawal Assessment scale for benzodiazepines (CIWA-B). This dose was then slowly reduced over 12 days. Multidisciplinary input, especially psychological therapy tackling his underlying anxiety disorder during his admission, was thought to be particularly helpful. PMID:26929223

  16. Methyl Parathion Masks Withdrawal from Physical Dependence on Morphine

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    Robin W. Rockhold

    2002-10-01

    Full Text Available Abstract: The cholinergic system has been proposed to participate in the development of dependence on opioids. The present study examined effects of dermal pretreatment with methyl parathion (MP, an acetylcholinesterase inhibitor, on the development of physical dependence on morphine. Opioid dependence was induced by continuous intracerebroventricular (i.c.v. infusion of morphine (26 nmol/μl/h for 3 days in adult male Sprague-Dawley rats. Each rat received two doses of MP, 12.5 mg/kg, dermally, initially, 3 days prior to initiation of i.c.v. morphine infusion and again on the first day of infusion. Withdrawal was precipitated after 3 days of infusion by administering an opioid antagonist, naloxone (48 nmol/5 μl, i.c.v.. Twelve of 23 MP-treated rats exhibited signs of acetylcholinesterase inhibitor intoxication (mild tremors and showed reduced spontaneous locomotor activity (tested by an open field test, prior to naloxone. The brain cholinesterase activity in these 12 rats was 13% of levels in control rats. Eleven rats that did not show toxic signs, exhibited cholinesterase activities that were 20% of control (not significant versus toxic group. The group that showed signs of MP intoxication exhibited a significantly lower incidence of opioid withdrawal jumping, rearing and wet dog shakes compared with the non-toxic group. No differences between quantal withdrawal signs (ptosis, penis-licking, and vocalization were noted between the two groups. The results suggest that toxic inhibition of acetylcholinesterase non-specifically reduces locomotor activity and may obscure certain behavioral signs of withdrawal from opioid dependence. This indicates that caution should be used in interpreting a direct involvement of acetylcholinesterase inhibition in preventing opioid dependence.

  17. 45 CFR 400.301 - Withdrawal from the refugee program.

    Science.gov (United States)

    2010-10-01

    ... exception of the following provisions: 45 CFR 400.5(d), 400.7, 400.51(b)(2)(i), 400.58(c), 400.94(a), 400.94... 45 Public Welfare 2 2010-10-01 2010-10-01 false Withdrawal from the refugee program. 400.301 Section 400.301 Public Welfare Regulations Relating to Public Welfare OFFICE OF REFUGEE...

  18. The dopamine withdrawal test following surgery for intracranial aneurysms.

    OpenAIRE

    Mendelow, A D; Dharker, S; J. Patterson; Nath, F; Teasdale, G M

    1986-01-01

    Cerebral blood flow was measured in eight patients who were being treated with dopamine in order to maintain cerebral perfusion after the onset of delayed postoperative ischaemia following intracranial aneurysm surgery. Measurements were made whilst on treatment and repeated either during a reduction in the dosage or withdrawal of dopamine. There was a significant fall in cerebral blood flow in both hemispheres in all eight patients. Clinical deterioration was observed in seven of nine instan...

  19. A study of family functioning in Hikikomori (Social withdrawal)

    OpenAIRE

    Koshiba, Yoriko

    2007-01-01

    Hikikomori (Social withdrawal) has recently been examined as a problem facing Japanese society. Despite the issuance of guidelines by the Japanese government, the creation of parent groups and the availability of support from various government agencies and private organizations, no countermeasure policy has been established. Research on Hikikomori as a problem for the entire family and analysis of functioning in cases of Hikikomori has not been carried out. Hikikomori is seen in the same...

  20. Numerical simulation of earth fissures due to groundwater withdrawal

    OpenAIRE

    Wang, Z.; Zhang, Y.; Wu, J.; Yu, J.; Gong, X.

    2015-01-01

    Excessive groundwater withdrawal can cause land subsidence and earth fissures. The initiation and propagation of earth fissures are related to tensile failure and crack propagation in soils. Based on fracture mechanics, the crack band model (CBM), one of the smear crack models which is relatively easy to construct and convenient to be integrated into standard finite element codes is used in this paper. The calculated results of CBM are less dependent on the sizes of finite e...

  1. Caffeine withdrawal and high-intensity endurance cycling performance.

    Science.gov (United States)

    Irwin, Christopher; Desbrow, Ben; Ellis, Aleisha; O'Keeffe, Brooke; Grant, Gary; Leveritt, Michael

    2011-03-01

    In this study, we investigated the impact of a controlled 4-day caffeine withdrawal period on the effect of an acute caffeine dose on endurance exercise performance. Twelve well-trained and familiarized male cyclists, who were caffeine consumers (from coffee and a range of other sources), were recruited for the study. A double-blind placebo-controlled cross-over design was employed, involving four experimental trials. Participants abstained from dietary caffeine sources for 4 days before the trials and ingested capsules (one in the morning and one in the afternoon) containing either placebo or caffeine (1.5 mg · kg(-1) body weight · day(-1)). On day 5, capsules containing placebo or caffeine (3 mg · kg(-1) body weight) were ingested 90 min before completing a time trial, equivalent to one hour of cycling at 75% peak sustainable power output. Hence the study was designed to incorporate placebo-placebo, placebo-caffeine, caffeine-placebo, and caffeine-caffeine conditions. Performance time was significantly improved after acute caffeine ingestion by 1:49 ± 1:41 min (3.0%, P = 0.021) following a withdrawal period (placebo-placebo vs. placebo-caffeine), and by 2:07 ± 1:28 min (3.6%, P = 0.002) following the non-withdrawal period (caffeine-placebo vs. caffeine-caffeine). No significant difference was detected between the two acute caffeine trials (placebo-caffeine vs. caffeine-caffeine). Average heart rate throughout exercise was significantly higher following acute caffeine administration compared with placebo. No differences were observed in ratings of perceived exertion between trials. A 3 mg · kg(-1) dose of caffeine significantly improves exercise performance irrespective of whether a 4-day withdrawal period is imposed on habitual caffeine users. PMID:21279864

  2. Intraoperative Alcohol Withdrawal Syndrome: A Coincidence or Precipitation?

    OpenAIRE

    Asish Subedi; Balkrishna Bhattarai

    2013-01-01

    As the prevalence of alcohol dependence is approximately half in surgical patients with an alcohol use disorder, anesthetist often encounters such patients in the perioperative settings. Alcohol withdrawal syndrome (AWS) is one of the most feared complications of alcohol dependence and can be fatal if not managed actively. A 61-year-old man, alcoholic with 50 h of abstinence before surgery, received spinal anesthesia for surgery for femoral neck fracture. To facilitate positioning for spinal ...

  3. Coupled code calculation of rod withdrawal at power accident

    Energy Technology Data Exchange (ETDEWEB)

    Grgić, Davor, E-mail: davor.grgic@fer.hr [Faculty of Electrical Engineering and Computing, University of Zagreb, Unska 3, 10000 Zagreb (Croatia); Benčik, Vesna, E-mail: vesna.bencik@fer.hr [Faculty of Electrical Engineering and Computing, University of Zagreb, Unska 3, 10000 Zagreb (Croatia); Šadek, Siniša, E-mail: sinisa.sadek@fer.hr [Faculty of Electrical Engineering and Computing, University of Zagreb, Unska 3, 10000 Zagreb (Croatia)

    2013-08-15

    Highlights: ► Sensitivity calculations (withdrawal speed, initial power, secondary side influence) were performed for the rod withdrawal at power accident in PWR. ► Best estimate coupled RELAP5-PARCS code calculation was done, using COBRA code to model the core thermal-hydraulics. ► Specific modelling features included reactor vessel split model, explicit model of the RTD bypass and the overtemperature ΔT setpoint function. ► Average whole core values and the local hot spots were predicted. ► Local fuel centerline temperature and local DNBR were calculated using a COBRA-like model. ► Influence of the burnup on the fuel centerline temperature was studied. -- Abstract: The rod withdrawal at power (RWAP) accident is analyzed for NPP Krško as part of activity related to possible resistance temperature detectors (RTDs) bypass removal. The RWAP accident can be departure from nucleate boiling (DNB) or overpower limiting accident depending on initial power level and rate and amount of reactivity addition. In this paper we have analyzed the response of the plant in current configuration to RWAP for different withdrawal speeds and different initial power levels. By demonstrating adequacy of current protection system we can, in the next step, quantify the influence of change in narrow range coolant temperature measurement to available safety margins. The overtemperature ΔT setpoint and its relation to local DNBR values are in center of attention. The coupled RELAP5–PARCS code was used as the calculation tool with the provision to extend the calculation to local pin-by-pin COBRA subchannel calculation for selected state points derived from main coupled code results. In the first part of the calculation methodology, point kinetics calculation is performed using standalone RELAP5 to reproduce USAR results, and in the second part, more demanding coupled code calculation is introduced.

  4. Randomised controlled trial of azathioprine withdrawal in ulcerative colitis.

    OpenAIRE

    Hawthorne, A. B.; Logan, R. F.; Hawkey, C. J.; Foster, P. N.; Axon, A T; Swarbrick, E T; Scott, B B; Lennard-Jones, J E

    1992-01-01

    OBJECTIVE--To determine whether azathioprine can prevent relapse in ulcerative colitis. DESIGN--One year placebo controlled double blind trial of withdrawal or continuation of azathioprine. SETTING--Outpatient clinics of five hospitals. SUBJECTS--79 patients with ulcerative colitis who had been taking azathioprine for six months or more. Patients in full remission for two months or more (67), and patients with chronic low grade or corticosteroid dependent disease (12) were randomised separate...

  5. Dopamine agonist withdrawal syndrome: implications for patient care.

    Science.gov (United States)

    Nirenberg, Melissa J

    2013-08-01

    Dopamine agonists are effective treatments for a variety of indications, including Parkinson's disease and restless legs syndrome, but may have serious side effects, such as orthostatic hypotension, hallucinations, and impulse control disorders (including pathological gambling, compulsive eating, compulsive shopping/buying, and hypersexuality). The most effective way to alleviate these side effects is to taper or discontinue dopamine agonist therapy. A subset of patients who taper a dopamine agonist, however, develop dopamine agonist withdrawal syndrome (DAWS), which has been defined as a severe, stereotyped cluster of physical and psychological symptoms that correlate with dopamine agonist withdrawal in a dose-dependent manner, cause clinically significant distress or social/occupational dysfunction, are refractory to levodopa and other dopaminergic medications, and cannot be accounted for by other clinical factors. The symptoms of DAWS include anxiety, panic attacks, dysphoria, depression, agitation, irritability, suicidal ideation, fatigue, orthostatic hypotension, nausea, vomiting, diaphoresis, generalized pain, and drug cravings. The severity and prognosis of DAWS is highly variable. While some patients have transient symptoms and make a full recovery, others have a protracted withdrawal syndrome lasting for months to years, and therefore may be unwilling or unable to discontinue DA therapy. Impulse control disorders appear to be a major risk factor for DAWS, and are present in virtually all affected patients. Thus, patients who are unable to discontinue dopamine agonist therapy may experience chronic impulse control disorders. At the current time, there are no known effective treatments for DAWS. For this reason, providers are urged to use dopamine agonists judiciously, warn patients about the risks of DAWS prior to the initiation of dopamine agonist therapy, and follow patients closely for withdrawal symptoms during dopamine agonist taper. PMID:23686524

  6. Coupled code calculation of rod withdrawal at power accident

    International Nuclear Information System (INIS)

    Highlights: ► Sensitivity calculations (withdrawal speed, initial power, secondary side influence) were performed for the rod withdrawal at power accident in PWR. ► Best estimate coupled RELAP5-PARCS code calculation was done, using COBRA code to model the core thermal-hydraulics. ► Specific modelling features included reactor vessel split model, explicit model of the RTD bypass and the overtemperature ΔT setpoint function. ► Average whole core values and the local hot spots were predicted. ► Local fuel centerline temperature and local DNBR were calculated using a COBRA-like model. ► Influence of the burnup on the fuel centerline temperature was studied. -- Abstract: The rod withdrawal at power (RWAP) accident is analyzed for NPP Krško as part of activity related to possible resistance temperature detectors (RTDs) bypass removal. The RWAP accident can be departure from nucleate boiling (DNB) or overpower limiting accident depending on initial power level and rate and amount of reactivity addition. In this paper we have analyzed the response of the plant in current configuration to RWAP for different withdrawal speeds and different initial power levels. By demonstrating adequacy of current protection system we can, in the next step, quantify the influence of change in narrow range coolant temperature measurement to available safety margins. The overtemperature ΔT setpoint and its relation to local DNBR values are in center of attention. The coupled RELAP5–PARCS code was used as the calculation tool with the provision to extend the calculation to local pin-by-pin COBRA subchannel calculation for selected state points derived from main coupled code results. In the first part of the calculation methodology, point kinetics calculation is performed using standalone RELAP5 to reproduce USAR results, and in the second part, more demanding coupled code calculation is introduced

  7. An Engineered Endomorphin-2 Gene for Morphine Withdrawal Syndrome

    Science.gov (United States)

    Wu, Fei-xiang; He, Yan; Di, Hui-ting; Sun, Yu-ming; Pan, Rui-rui; Yu, Wei-feng; Liu, Renyu

    2016-01-01

    An optimal therapeutics to manage opioid withdrawal syndrome is desired for opioid addiction treatment. Down-regulation of endogenous endomorphin-2 (EM2) level in the central nervous system after continuous morphine exposure was observed, which suggested that increase of EM2 could be an alternative novel method for opioid dependence. As a short peptide, the short half-life of EM2 limits its clinical usage through conventional administration. In the present study, we engineered an EM2 gene using a signal peptide of mouse growth factor for an out-secretory expression of EM2 and an adenovirus as a vector, which ultimately sustained the release of EM-2. After administration of the adenovirus in central nervous system, a sustained increase of EM2 level in the cerebral spinal fluid (CSF) was observed along with a reduction of morphine withdrawal syndrome. These findings suggest that the engineered EM2 gene delivered to the central nervous system could be a novel therapeutics for withdrawal syndrome in opioid dependent subjects. PMID:27003293

  8. [Treatment in the Intensive Care Unit: continue or withdraw?].

    Science.gov (United States)

    Savelkoul, Claudia; de Graeff, Nienke; Kompanje, Erwin J O; Tjan, Dave H T

    2016-01-01

    End-of-life decision-making in the Intensive Care Unit is a common and complex process. The step-by-step process of decision-making leading to withdrawal of life-sustaining treatment is illustrated in this paper by a clinical case. A variety of factors influences the decision to adjust the initial curative treatment policy towards withdrawal of life-sustaining therapy and the pursuit of comfort care. For a smooth decision-making process, it is necessary to make a prognosis and obtain consensus amongst the healthcare team. Withdrawal of life-sustaining treatment is ultimately a medical decision and a consensual decision should be reached by all medical staff and nurses, and preferably also by the patient and family. Timely involvement of a legal representative of the patient is essential for an uncomplicated decision-making process. Advance care planning and advance directives provide opportunities for patients to express their preferences beforehand. It is important to realise that end-of-life decisions are significantly influenced by personal and cultural values. PMID:27050494

  9. In utero oxcarbazepine and a withdrawal syndrome, anomalies, and hyponatremia.

    Science.gov (United States)

    Rolnitsky, Asaph; Merlob, Paul; Klinger, Gil

    2013-06-01

    Oxcarbazepine is an antiepileptic agent that has been used during pregnancy, although its safety during pregnancy has not been sufficiently established. This article presents an infant born with renal and cardiac malformations who developed a withdrawal syndrome and hyponatremia following in utero exposure to oxcarbazepine. The infant was born at 35 weeks' gestation by urgent cesarean section to a mother in status epilepticus who had been treated with oxcarbazepine throughout her pregnancy. Evaluation for congenital anomalies identified mild aortic stenosis, a bicuspid aortic valve, patent foramen ovale, patent ductus arteriosus, and severe left hydronephrosis due to left ureteropelvic junction stenosis. On the third day of life the infant developed clinical signs of a withdrawal syndrome, which peaked on day 7 and resolved by day 12. Transient hyponatremia resolved by day 8 of life. Follow-up showed normal development at 15 months. The association of a withdrawal syndrome with oxcarbazepine exposure has not been previously reported. The hyponatremia is consistent with adult reports. The possible association of oxcarbazepine with renal and cardiac malformations requires further confirmation. PMID:23668873

  10. The pharmacology of neurotrophic treatment with Cerebrolysin: brain protection and repair to counteract pathologies of acute and chronic neurological disorders.

    Science.gov (United States)

    Masliah, E; Díez-Tejedor, E

    2012-04-01

    Neurotrophic factors are considered as part of the therapeutic strategy for neurological disorders like dementia, stroke and traumatic brain injury. Cerebrolysin is a neuropeptide preparation which mimics the action of endogenous neurotrophic factors on brain protection and repair. In dementia models, Cerebrolysin decreases β-amyloid deposition and microtubule-associated protein tau phosphorylation by regulating glycogen synthase kinase-3β and cyclin-dependent kinase 5 activity, increases synaptic density and restores neuronal cytoarchitecture. These effects protect integrity of the neuronal circuits and thus result in improved cognitive and behavioral performance. Furthermore, Cerebrolysin enhances neurogenesis in the dentate gyrus, the basis for neuronal replacement therapy in neurodegenerative diseases. Experimental studies in stroke animal models have shown that Cerebrolysin stabilizes the structural integrity of cells by inhibition of calpain and reduces the number of apoptotic cells after ischemic lesion. Cerebrolysin induces restorative processes, decreases infarct volume and edema formation and promotes functional recovery. Stroke-induced neurogenesis in the subventricular zone was also promoted by Cerebrolysin, thus supporting the brain's self-repair after stroke. Both, traumatic brain and spinal cord injury conditions stimulate the expression of natural neurotrophic factors to promote repair and regeneration processes -axonal regeneration, neuronal plasticity and neurogenesis- that is considered to be crucial for the future recovery. Neuroprotective effects of Cerebrolysin on experimentally induced traumatic spinal cord injury have shown that Cerebrolysin prevents apoptosis of lesioned motoneurons and promotes functional recovery. This section summarizes the most relevant data on the pharmacology of Cerebrolysin obtained from in vitro assays (biochemical and cell cultures) and in vivo animal models of acute and chronic neurological disorders. PMID

  11. Upregulation of mesencephalic astrocyte-derived neurotrophic factor in glial cells is associated with ischemia-induced glial activation

    Directory of Open Access Journals (Sweden)

    Shen Yujun

    2012-11-01

    Full Text Available Abstract Background Mesencephalic astrocyte-derived neurotrophic factor (MANF, a 20 kDa secreted protein, was originally derived from a rat mesencephalic type-1 astrocyte cell line. MANF belongs to a novel evolutionally conserved family of neurotrophic factors along with conserved dopamine neurotrophic factor. In recent years, ever-increasing evidence has shown that both of them play a remarkable protective role against various injuries to neurons in vivo or in vitro. However, the characteristics of MANF expression in the different types of glial cells, especially in astrocytes, remain unclear. Methods The model of focal cerebral ischemia was induced by rat middle cerebral artery occlusion. Double-labeled immunofluorescent staining was used to identify the types of neural cells expressing MANF. Primarily cultured glial cells were used to detect the response of glial cells to endoplasmic reticulum stress stimulation. Propidium iodide staining was used to determine dead cells. Reverse transcription PCR and western blotting were used to detect the levels of mRNA and proteins. Results We found that MANF was predominantly expressed in neurons in both normal and ischemic cortex. Despite its name, MANF was poorly expressed in glial cells, including astrocytes, in normal brain tissue. However, the expression of MANF was upregulated in the glial cells under focal cerebral ischemia, including the astrocytes. This expression was also induced by several endoplasmic reticulum stress inducers and nutrient deprivation in cultured primary glial cells. The most interesting phenomenon observed in this study was the pattern of MANF expression in the microglia. The expression of MANF was closely associated with the morphology and state of microglia, accompanied by the upregulation of BIP/Grp78. Conclusions These results indicate that MANF expression was upregulated in the activated glial cells, which may contribute to the mechanism of ischemia-induced neural injury.

  12. Brain-derived neurotrophic factor promotes cochlear spiral ganglion cell survival and function in deafened, developing cats.

    Science.gov (United States)

    Leake, Patricia A; Hradek, Gary T; Hetherington, Alexander M; Stakhovskaya, Olga

    2011-06-01

    Postnatal development and survival of spiral ganglion (SG) neurons depend on both neural activity and neurotrophic support. Our previous studies showed that electrical stimulation from a cochlear implant only partially prevents SG degeneration after early deafness. Thus, neurotrophic agents that might be combined with an implant to improve neural survival are of interest. Recent studies reporting that brain-derived neurotrophic factor (BDNF) promotes SG survival after deafness have been conducted in rodents and limited to relatively short durations. Our study examined longer duration BDNF treatment in deafened cats that may better model the slow progression of SG degeneration in human cochleae, and this is the first study of BDNF in the developing auditory system. Kittens were deafened neonatally, implanted at 4-5 weeks with intracochlear electrodes containing a drug-delivery cannula, and BDNF or artificial perilymph was infused for 10 weeks from a miniosmotic pump. In BDNF-treated cochleae, SG cells grew to normal size and were significantly larger than cells on the contralateral side. However, their morphology was not completely normal, and many neurons lacked or had thinned perikaryl myelin. Unbiased stereology was employed to estimate SG cell density, independent of cell size. BDNF was effective in promoting significantly improved survival of SG neurons in these developing animals. BDNF treatment also resulted in higher density and larger size of myelinated radial nerve fibers, sprouting of fibers into the scala tympani, and improvement of electrically evoked auditory brainstem response thresholds. BDNF may have potential therapeutic value in the developing auditory system, but many serious obstacles currently preclude clinical application. PMID:21452221

  13. Ciliary neurotrophic factor-treated astrocyte-conditioned medium increases the intracellular free calcium concentration in rat cortical neurons

    OpenAIRE

    SUN, MEIQUN; Liu, Hongli; MIN, SHENGPING; Wang, Hongtao; Wang, Xiaojing

    2016-01-01

    Ciliary neurotrophic factor (CNTF) is involved in the activation of astrocytes. A previous study showed that CNTF-treated astrocyte-conditioned medium (CNTF-ACM) contributed to the increase of the calcium current and the elevation of corresponding ion channels in cortical neurons. On this basis, it is reasonable to assume that CNTF-ACM may increase the intracellular free calcium concentration ([Ca2+]i) in neurons. In the present study, the effects of CNTF-ACM on [Ca2+]i in rat cortical neuron...

  14. Neurotrophic factors in women with crack cocaine dependence during early abstinence: the role of early life stress

    Science.gov (United States)

    Viola, Thiago Wendt; Tractenberg, Saulo Gantes; Levandowski, Mateus Luz; Pezzi, Júlio Carlos; Bauer, Moisés Evandro; Teixeira, Antonio Lúcio; Grassi-Oliveira, Rodrigo

    2014-01-01

    Background Neurotrophic factors have been investigated in the pathophysiology of alcohol and drug dependence and have been related to early life stress driving developmental programming of neuroendocrine systems. Methods We conducted a follow-up study that aimed to assess the plasma levels of glial cell line–derived neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), neurotrophin-3 (NT3) and neurotrophin-4/5 (NT4/5) in crack users during 3 weeks of early abstinence in comparison with healthy controls. We performed a comprehensive clinical assessment in female inpatients with crack cocaine dependence (separated into 2 groups: participants with (CSA+) and without (CSA−) a history of childhood sexual abuse) and a group of nonuser control participants. Results Our sample included 104 women with crack cocaine dependence and 22 controls; of the women who used crack cocaine, 22 had a history of childhood sexual abuse and 82 did not. The GDNF plasma levels in the CSA+ group increased dramatically during 3 weeks of detoxification. In contrast, those in the CSA− group showed lower and stable levels of GDNF under the same conditions. Compared with the control group, BDNF plasma levels remained elevated and NGF levels were reduced during early abstinence. We found no differences in NT3 and NT4/5 between the patients and controls. However, within-group analyses showed that the CSA+ group exhibited higher levels of NT4/5 than the CSA− group at the end of detoxification. Limitations Some of the participants were using neuroleptics, mood stabilizers or antidepressants; our sample included only women; memory bias could not be controlled; and we did not investigate the possible confounding effects of other forms of stress during childhood. Conclusion This study supports the association between early life stress and peripheral neurotrophic factor levels in crack cocaine users. During early abstinence, plasmastic GDNF and NT4/5 were

  15. LncRNA analysis of mouse spermatogonial stem cells following glial cell-derived neurotrophic factor treatment

    OpenAIRE

    Lufan Li; Min Wang; Mei Wang; Xiaoxi Wu; Lei Geng; Yuanyuan Xue; Xiang Wei; Yuanyuan Jia; Xin Wu

    2015-01-01

    Spermatonial stem cells (SSCs) are the foundation of spermatogenesis. Long non-coding RNAs (lncRNAs) are a class of non-coding RNAs with at least 200 bp in length, which play important roles in various biological processes. Growth factor glial cell line-derived neurotrophic factor (GDNF), secreted from testis niches, is critical for self-renewal of SSCs in vitro and in vivo. Using Illumina HiSeq™ 2000 high throughput sequencing, we found 55924 lncRNAs which were regulated by GDNF in SSCs in v...

  16. Lipid-mediated glial cell line-derived neurotrophic factor gene transfer to cultured porcine ventral mesencephalic tissue

    DEFF Research Database (Denmark)

    Bauer, Matthias; Meyer, Morten; Brevig, Thomas;

    2002-01-01

    -mediated transfer of the gene for human glial cell line-derived neurotrophic factor (GDNF) to embryonic (E27/28) porcine VM tissue kept as organotypic explant cultures. Treatment of the developing VM with two mitogens, basic fibroblast growth factor and epidermal growth factor, prior to transfection significantly...... increased transfection yields. Expression of human GDNF via an episomal vector could be detected by in situ hybridization and by the measuring of GDNF protein secreted into the culture medium. When compared to mock-transfected controls, VM tissue expressing recombinant GDNF contained significantly higher...

  17. New insight in expression, transport, and secretion of brain-derived neurotrophic factor: Implications in brainrelated diseases

    Institute of Scientific and Technical Information of China (English)

    Naoki; Adachi; Tadahiro; Numakawa; Misty; Richards; Shingo; Nakajima; Hiroshi; Kunugi

    2014-01-01

    Brain-derived neurotrophic factor(BDNF) attracts increasing attention from both research and clinical fields because of its important functions in the central nervous system. An adequate amount of BDNF is critical to develop and maintain normal neuronal circuits in the brain. Given that loss of BDNF function has beenreported in the brains of patients with neurodegenerative or psychiatric diseases, understanding basic properties of BDNF and associated intracellular processes is imperative. In this review, we revisit the gene structure, transcription, translation, transport and secretion mechanisms of BDNF. We also introduce implications of BDNF in several brain-related diseases including Alzheimer’s disease, Huntington’s disease, depression and schizophrenia.

  18. Effects of maternal smoking and exposure to methylmercury on brain-derived neurotrophic factor concentrations in umbilical cord serum

    DEFF Research Database (Denmark)

    Spulber, Stefan; Rantamäki, Tomi; Nikkilä, Outi;

    2010-01-01

    Brain-derived neurotrophic factor (BDNF) is a neurotrophin essential for neuronal survival and differentiation. We examined the concentration of BDNF in cord serum from newborns exposed to methylmercury (MeHg) and polychlorinated biphenyls (PCB) in utero by maternal consumption of whale meat. The...... decrease in serum BDNF induced by MeHg exposure. Cord blood BDNF has been reported to increase in association with perinatal brain injuries and has been proposed as a possible predictive marker of neurodevelopmental outcomes. The negative effect that MeHg seems to exert on cord blood BDNF concentration...

  19. The effect of recombinant erythropoietin on plasma brain derived neurotrophic factor levels in patients with affective disorders

    DEFF Research Database (Denmark)

    Vinberg, Maj; Miskowiak, Kamilla; Hoejman, Pernille;

    2015-01-01

    UNLABELLED: The study aims to investigate the effect of repeated infusions of recombinant erythropoietin (EPO) on plasma brain derived neurotrophic factor (BDNF) levels in patients with affective disorders. In total, 83 patients were recruited: 40 currently depressed patients with treatment-resistant...... depression (TRD) (Hamilton Depression Rating Scale-17 items (HDRS-17) score >17) (study 1) and 43 patients with bipolar disorder (BD) in partial remission (HDRS-17 and Young Mania Rating Scale (YMRS) ≤ 14) (study 2). In both studies, patients were randomised to receive eight weekly EPO (Eprex; 40,000 IU) or...

  20. Mechanisms of extracellular signal-regulated kinase/cAMP response element-binding protein/brain-derived neurotrophic factor signaltransduction pathway in depressive disorder

    Institute of Scientific and Technical Information of China (English)

    Hongyan Wang; Yingquan Zhang; Mingqi Qiao

    2013-01-01

    The extracellular signal-regulated kinase/cAMP response element-binding protein/brain-derived neurotrophic factor signal transduction pathway plays an important role in the mechanism of action of antidepressant drugs and has dominated recent studies on the pathogenesis of depression. In the present review we summarize the known roles of extracellular signal-regulated kinase, cAMP response element-binding protein and brain-derived neurotrophic factor in the pathogenesis of depression and in the mechanism of action of antidepressant medicines. The extracellular signal-regulated kinase/cAMP response element-binding protein/brain-derived neurotrophic factor pathway has potential to be used as a biological index to help diagnose depression, and as such it is considered as an important new target in the treatment of depression.

  1. Withdrawing Empire: A Test of Structural Realism and Neoclassical Realism to Explain the Withdrawal of US Military Presence

    OpenAIRE

    Magnús Fannar Eggertsson 1987

    2016-01-01

    Little work has been done to explain why the United States, a great power, would willingly withdraw its military presence from a much smaller country. In this thesis I attempt to explain why this happens in three cases by testing two major International Relations theories, Structural Realism and Neoclassical Realism. I provide two hypotheses based on each theory in the cases of Vietnam, Panama and Uzbekistan. Structural Realism is heavily based on behavior being influenced by capabilities and...

  2. Alcohol Withdrawal Syndrome in Critically Ill Patients: Identification, Assessment, and Management.

    Science.gov (United States)

    Sutton, Lynsey J; Jutel, Annemarie

    2016-02-01

    Management of alcohol withdrawal in critically ill patients is a challenge. The alcohol consumption histories of intensive care patients are often incomplete, limiting identification of patients with alcohol use disorders. Abrupt cessation of alcohol places these patients at risk for alcohol withdrawal syndrome. Typically benzodiazepines are used as first-line therapy to manage alcohol withdrawal. However, if patients progress to more severe withdrawal or delirium tremens, extra adjunctive medications in addition to benzodiazepines may be required. Sedation and mechanical ventilation may also be necessary. Withdrawal assessment scales such as the Clinical Institute of Withdrawal Assessment are of limited use in these patients. Instead, general sedation-agitation scales and delirium detection tools have been used. The important facets of care are the rapid identification of at-risk patients through histories of alcohol consumption, management with combination therapies, and ongoing diligent assessment and evaluation. (Critical Care Nurse. 2016;36[1]:28-39). PMID:26830178

  3. Decreased serum levels of brain-derived neurotrophic factor in schizophrenic patients with deficit syndrome

    Directory of Open Access Journals (Sweden)

    Akyol ES

    2015-03-01

    Full Text Available Esra Soydas Akyol,1 Yakup Albayrak,2 Murat Beyazyüz,3 Nurkan Aksoy,4 Murat Kuloglu,5 Kenji Hashimoto6 1Deparment of Psychiatry, Yenimahalle Education and Research Hospital, Ankara, Turkey; 2Department of Psychiatry, Faculty of Medicine, Namik Kemal University, Tekirdag, Turkey; 3Department of Psychiatry, Biga State Hospital, Çanakkale, Turkey; 4Department of Biochemistry, Yenimahalle Education and Research Hospital, Ankara, Turkey; 5Department of Psychiatry, Faculty of Medicine, Akdeniz University, Antalya, Turkey; 6Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan Background: Brain-derived neurotrophic factor (BDNF is a well-established neurotrophin that plays a role in the pathophysiology of numerous psychiatric disorders. Many studies have investigated the serum BDNF levels in patients with schizophrenia. However, there are restricted data in the literature that compare the serum BDNF levels in patients with deficit and nondeficit syndromes. In this study, we aimed to compare the serum BDNF levels between schizophrenic patients with deficit or nondeficit syndrome and healthy controls.Methods: After fulfilling the inclusion and exclusion criteria, 58 patients with schizophrenia and 36 healthy controls were included in the study. The patients were grouped as deficit syndrome (N=23 and nondeficit syndrome (N=35 according to the Schedule for the Deficit Syndrome. Three groups were compared in terms of the sociodemographic and clinical variants and serum BDNF levels.Results: The groups were similar in terms of age, sex, body mass index, and smoking status. The serum BDNF levels in patients with deficit syndrome were significantly lower than those in healthy controls. In contrast, the serum BDNF levels in patients with nondeficit syndrome were similar to those in healthy controls.Conclusion: This study suggests that decreased BDNF levels may play a role in the pathophysio­logy of schizophrenic

  4. Brain-derived neurotrophic factor inducing angiogenesis through modulation of matrix-degrading proteases

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Background Recent studies have proved that brain-derived neurotrophic factor (BDNF) possesses angiogenic activity in vitro and in vivo. However, the proangiogenic mechanism of BDNF has not yet been provided with enough information. To explore the proangiogenic mechanism of BDNF, we investigated the effects of BDNF on extracellular proteolytic enzymes, including matrix metalloproteinases (MMPs) and serine proteases, particularly the urokinase-type plasminogen activator (uPA)-plasmin system in human umbilical vein endothelial cells (HUVECs) model. Methods Tube formation assay was performed in vitro to evaluate the effects of BDNF on angiogenesis. The HUVECs were treated with various concentrations of BDNF (25-400 ng/ml) for different (6-48 hours), reverse transcriptase-polymerase chain reaction (RT-PCR) was used to assay MMP-2, MMP-9, TIMP-1, and TIMP-2 mRNA in HUVECs, and the conditioned medium was analyzed for MMP and uPA activity by gelatin zymography and fibrin zymography, respectively. uPA, plasminogen activator inhibitor (PAI)-1, tissue inhibitors of metalloproteinase (TIMP)-1, and TIMP-2 were quantified by western blotting analysis. Results BDNF elicited robust and elongated angiogeneis in two-dimensional cultures of HUVECs in comparison with control. The stimulation of serum-starved HUVECs with BDNF caused obvious increase in MMP-2 and MMP-9 mRNA expression and induced the pro-MMP-2 and pro-MMP-9 activation without significant differences in proliferation. However, BDNF had no effect on TIMP-1 and TIMP-2 production. BDNF increased uPA and PAI-1 production in a dose-dependent manner. Maximal activation of uPA and PAI-1 expression in HUVECs was induced by 100 ng/ml BDNF, while effects of 200 ng/ml and 400 ng/ml BDNF were slightly reduced in comparison with with those of 100 ng/ml. Protease activity for uPA was also increased by BDNF in a dose-dependent manner. BDNF also stimulated uPA and PAI-1 production beyond that in control cultures in a time

  5. Brain-derived neurotrophic factor ameliorates brain stem cardiovascular dysregulation during experimental temporal lobe status epilepticus.

    Directory of Open Access Journals (Sweden)

    Ching-Yi Tsai

    Full Text Available BACKGROUND: Status epilepticus (SE is an acute, prolonged epileptic crisis with a mortality rate of 20-30%; the underlying mechanism is not completely understood. We assessed the hypothesis that brain stem cardiovascular dysregulation occurs during SE because of oxidative stress in rostral ventrolateral medulla (RVLM, a key nucleus of the baroreflex loop; to be ameliorated by brain-derived neurotrophic factor (BDNF via an antioxidant action. METHODOLOGY/PRINCIPAL FINDINGS: In a clinically relevant experimental model of temporal lobe SE (TLSE using Sprague-Dawley rats, sustained hippocampal seizure activity was accompanied by progressive hypotension that was preceded by a reduction in baroreflex-mediated sympathetic vasomotor tone; heart rate and baroreflex-mediated cardiac responses remained unaltered. Biochemical experiments further showed concurrent augmentation of superoxide anion, phosphorylated p47(phox subunit of NADPH oxidase and mRNA or protein levels of BDNF, tropomyosin receptor kinase B (TrkB, angiotensin AT1 receptor subtype (AT1R, nitric oxide synthase II (NOS II or peroxynitrite in RVLM. Whereas pretreatment by microinjection bilaterally into RVLM of a superoxide dismutase mimetic (tempol, a specific antagonist of NADPH oxidase (apocynin or an AT1R antagonist (losartan blunted significantly the augmented superoxide anion or phosphorylated p47(phox subunit in RVLM, hypotension and the reduced baroreflex-mediated sympathetic vasomotor tone during experimental TLSE, pretreatment with a recombinant human TrkB-Fc fusion protein or an antisense bdnf oligonucleotide significantly potentiated all those events, alongside peroxynitrite. However, none of the pretreatments affected the insignificant changes in heart rate and baroreflex-mediated cardiac responses. CONCLUSIONS/SIGNIFICANCE: We conclude that formation of peroxynitrite by a reaction between superoxide anion generated by NADPH oxidase in RVLM on activation by AT1R and NOS II

  6. Action of Administered Ciliary Neurotrophic Factor on the Mouse Dorsal Vagal Complex

    Science.gov (United States)

    Senzacqua, Martina; Severi, Ilenia; Perugini, Jessica; Acciarini, Samantha; Cinti, Saverio; Giordano, Antonio

    2016-01-01

    Ciliary neurotrophic factor (CNTF) induces weight loss in obese rodents and humans through activation of the hypothalamic Jak-STAT (Janus kinase-signal transducer and activator of transcription) signaling pathway. Here, we tested the hypothesis that CNTF also affects the brainstem centers involved in feeding and energy balance regulation. To this end, wild-type and leptin-deficient (ob/ob and db/db) obese mice were acutely treated with intraperitoneal recombinant CNTF. Coronal brainstem sections were processed for immunohistochemical detection of STAT3, STAT1, STAT5 phosphorylation and c-Fos. In wild-type mice, CNTF treatment for 45 min induced STAT3, STAT1, and STAT5 phosphorylation in neurons as well as glial cells of the area postrema; here, the majority of CNTF-responsive cells activated multiple STAT isoforms, and a significant proportion of CNTF-responsive glial cells bore the immaturity and plasticity markers nestin and vimentin. After 120 min CNTF treatment, c-Fos expression was intense in glial cells and weak in neurons of the area postrema, it was intense in several neurons of the rostral and caudal solitary tract nucleus (NTS), and weak in some cholinergic neurons of the dorsal motor nucleus of the vagus. In the ob/ob and db/db mice, Jak-STAT activation and c-Fos expression were similar to those induced in wild-type mouse brainstem. Treatment with CNTF (120 min, to induce c-Fos expression) and leptin (25 min, to induce STAT3 phosphorylation) demonstrated the co-localization of the two transcription factors in a small neuron population in the caudal NTS portion. Finally, weak immunohistochemical CNTF staining, detected in funiculus separans, and meningeal glial cells, matched the modest amount of CNTF found by RT-qPCR in micropunched area postrema tissue, which in contrast exhibited a very high amount of CNTF receptor. Collectively, the present findings show that the area postrema and the NTS exhibit high, distinctive responsiveness to circulating

  7. Glial cell line-derived neurotrophic factor gene delivery via a polyethylene imine grafted chitosan carrier

    Directory of Open Access Journals (Sweden)

    Peng YS

    2014-06-01

    Full Text Available Yu-Shiang Peng,1,* Po-Liang Lai,2,* Sydney Peng,1 His-Chin Wu,3 Siang Yu,1 Tsan-Yun Tseng,4 Li-Fang Wang,5 I-Ming Chu1 1Department of Chemical Engineering, National Tsing Hua University, Hsinchu, 2Department of Orthopedic Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, 3Department of Materials Engineering, Tatung University, Taipei, 4Graduate School of Biotechnology and Bioengineering, College of Engineering, Yuan Ze University, Chung-Li, 5Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung, Taiwan *Yu-Shiang Peng and Po-Liang Lai contributed equally to this work Abstract: Parkinson’s disease is known to result from the loss of dopaminergic neurons. Direct intracerebral injections of high doses of recombinant glial cell line-derived neurotrophic factor (GDNF have been shown to protect adult nigral dopaminergic neurons. Because GDNF does not cross the blood–brain barrier, intracerebral gene transfer is an ideal option. Chitosan (CHI is a naturally derived material that has been used for gene transfer. However, the low water solubility often leads to decreased transfection efficiency. Grafting of highly water-soluble polyethylene imines (PEI and polyethylene glycol onto polymers can increase their solubility. The purpose of this study was to design a non-viral gene carrier with improved water solubility as well as enhanced transfection efficiency for treating Parkinsonism. Two molecular weights (Mw =600 and 1,800 g/mol of PEI were grafted onto CHI (PEI600-g-CHI and PEI1800-g-CHI, respectively by opening the epoxide ring of ethylene glycol diglycidyl ether (EX-810. This modification resulted in a non-viral gene carrier with less cytotoxicity. The transfection efficiency of PEI600-g-CHI/deoxyribonucleic acid (DNA polyplexes was significantly higher than either PEI1800-g-CHI/DNA or CHI/DNA polyplexes. The maximal GDNF expression of PEI600-g-CHI/DNA was at the

  8. Action of Administered Ciliary Neurotrophic Factor on the Mouse Dorsal Vagal Complex.

    Science.gov (United States)

    Senzacqua, Martina; Severi, Ilenia; Perugini, Jessica; Acciarini, Samantha; Cinti, Saverio; Giordano, Antonio

    2016-01-01

    Ciliary neurotrophic factor (CNTF) induces weight loss in obese rodents and humans through activation of the hypothalamic Jak-STAT (Janus kinase-signal transducer and activator of transcription) signaling pathway. Here, we tested the hypothesis that CNTF also affects the brainstem centers involved in feeding and energy balance regulation. To this end, wild-type and leptin-deficient (ob/ob and db/db) obese mice were acutely treated with intraperitoneal recombinant CNTF. Coronal brainstem sections were processed for immunohistochemical detection of STAT3, STAT1, STAT5 phosphorylation and c-Fos. In wild-type mice, CNTF treatment for 45 min induced STAT3, STAT1, and STAT5 phosphorylation in neurons as well as glial cells of the area postrema; here, the majority of CNTF-responsive cells activated multiple STAT isoforms, and a significant proportion of CNTF-responsive glial cells bore the immaturity and plasticity markers nestin and vimentin. After 120 min CNTF treatment, c-Fos expression was intense in glial cells and weak in neurons of the area postrema, it was intense in several neurons of the rostral and caudal solitary tract nucleus (NTS), and weak in some cholinergic neurons of the dorsal motor nucleus of the vagus. In the ob/ob and db/db mice, Jak-STAT activation and c-Fos expression were similar to those induced in wild-type mouse brainstem. Treatment with CNTF (120 min, to induce c-Fos expression) and leptin (25 min, to induce STAT3 phosphorylation) demonstrated the co-localization of the two transcription factors in a small neuron population in the caudal NTS portion. Finally, weak immunohistochemical CNTF staining, detected in funiculus separans, and meningeal glial cells, matched the modest amount of CNTF found by RT-qPCR in micropunched area postrema tissue, which in contrast exhibited a very high amount of CNTF receptor. Collectively, the present findings show that the area postrema and the NTS exhibit high, distinctive responsiveness to circulating

  9. Tooth pulp inflammation increases brain-derived neurotrophic factor expression in rodent trigeminal ganglion neurons.

    Science.gov (United States)

    Tarsa, L; Bałkowiec-Iskra, E; Kratochvil, F J; Jenkins, V K; McLean, A; Brown, A L; Smith, J A; Baumgartner, J C; Balkowiec, A

    2010-06-01

    Nociceptive pathways with first-order neurons located in the trigeminal ganglion (TG) provide sensory innervation to the head, and are responsible for a number of common chronic pain conditions, including migraines, temporomandibular disorders and trigeminal neuralgias. Many of those conditions are associated with inflammation. Yet, the mechanisms of chronic inflammatory pain remain poorly understood. Our previous studies show that the neurotrophin brain-derived neurotrophic factor (BDNF) is expressed by adult rat TG neurons, and released from cultured newborn rat TG neurons by electrical stimulation and calcitonin gene-related peptide (CGRP), a well-established mediator of trigeminal inflammatory pain. These data suggest that BDNF plays a role in activity-dependent plasticity at first-order trigeminal synapses, including functional changes that take place in trigeminal nociceptive pathways during chronic inflammation. The present study was designed to determine the effects of peripheral inflammation, using tooth pulp inflammation as a model, on regulation of BDNF expression in TG neurons of juvenile rats and mice. Cavities were prepared in right-side maxillary first and second molars of 4-week-old animals, and left open to oral microflora. BDNF expression in right TG was compared with contralateral TG of the same animal, and with right TG of sham-operated controls, 7 and 28 days after cavity preparation. Our ELISA data indicate that exposing the tooth pulp for 28 days, with confirmed inflammation, leads to a significant upregulation of BDNF in the TG ipsilateral to the affected teeth. Double-immunohistochemistry with antibodies against BDNF combined with one of nociceptor markers, CGRP or transient receptor potential vanilloid type 1 (TRPV1), revealed that BDNF is significantly upregulated in TRPV1-immunoreactive (IR) neurons in both rats and mice, and CGRP-IR neurons in mice, but not rats. Overall, the inflammation-induced upregulation of BDNF is stronger in mice

  10. Brain-derived neurotrophic factor expression predicts adverse pathological & clinical outcomes in human breast cancer

    Directory of Open Access Journals (Sweden)

    Mokbel Kefah

    2011-07-01

    Full Text Available Abstract Introduction Brain-derived neurotrophic factor (BDNF has established physiological roles in the development and function of the vertebrate nervous system. BDNF has also been implicated in several human malignancies, including breast cancer (BC. However, the precise biological role of BDNF and its utility as a novel biomarker have yet to be determined. The objective of this study was to determine the mRNA and protein expression of BDNF in a cohort of women with BC. Expression levels were compared with normal background tissues and evaluated against established pathological parameters and clinical outcome over a 10 year follow-up period. Methods BC tissues (n = 127 and normal tissues (n = 33 underwent RNA extraction and reverse transcription, BDNF transcript levels were determined using real-time quantitative PCR. BDNF protein expression in mammary tissues was assessed with standard immuno-histochemical methodology. Expression levels were analyzed against tumour size, grade, nodal involvement, TNM stage, Nottingham Prognostic Index (NPI and clinical outcome over a 10 year follow-up period. Results Immuno-histochemical staining revealed substantially greater BDNF expression within neoplastic cells, compared to normal mammary epithelial cells. Significantly higher mRNA transcript levels were found in the BC specimens compared to background tissues (p = 0.007. The expression of BDNF mRNA was demonstrated to increase with increasing NPI; NPI-1 vs. NPI-2 (p = 0.009. Increased BDNF transcript levels were found to be significantly associated with nodal positivity (p = 0.047. Compared to patients who remained disease free, higher BDNF expression was significantly associated with local recurrence (LR (p = 0.0014, death from BC (p = 0.018 and poor prognosis overall (p = 0.013. After a median follow up of 10 years, higher BDNF expression levels were significantly associated with reduced overall survival (OS (106 vs. 136 months, p = 0.006. BDNF

  11. Alcohol withdrawal – therapeutical management in surgical patients with upper intestinal bleeding

    OpenAIRE

    Bălălău Cristian; Cobani Oana Denisa; Trambitasu Gloria; Popescu Bogdan; Carolina Negrei; Scăunașu Răzvan Valentin

    2015-01-01

    Psychological dependence involves a desire to use a drug to avoid the unpleasant withdrawal syndrome that results from cessation of exposure to it. Alcohol withdrawal syndrome is one of the most feared complications of alcohol addiction and sometimes can be fatal if not treated properly. Withdrawal syndrome is characterized by neurological hyperexcitability, which can lead to severe psychological and neurological symptoms. A survey was conceived in order to monitor the efficiency of several d...

  12. Brain reward deficits accompany withdrawal (hangover) from acute ethanol in rats

    OpenAIRE

    Schulteis, Gery; Liu, Jian

    2006-01-01

    Withdrawal from an acute bolus injection of ethanol produces affective or emotional signs that include anxiogenic-like behavior (Gauvin et al., 1992) and conditioned place aversion (Morse et al., 2000). The current study assessed whether brain reward deficits that accompany withdrawal from chronic ethanol dependence (Schulteis et al., 1995) are also observed upon withdrawal from acute intoxication. Rats were implanted with stimulating electrodes aimed at the medial forebrain bundle in the lat...

  13. Attention biases to threat and behavioral inhibition in early childhood shape adolescent social withdrawal

    OpenAIRE

    Pérez-Edgar, Koraly; Bar-Haim, Yair; McDermott, Jennifer Martin; Chronis-Tuscano, Andrea; Pine, Daniel S.; Fox, Nathan A.

    2010-01-01

    Behavioral inhibition (BI) is a temperament characterized in young children by a heightened sensitivity to novelty, social withdrawal, and anxious behaviors. For many children, these social difficulties dissipate over time. For others, patterns of social withdrawal continue into adolescence. Over time, attention biases to threat may influence the stability of behavioral inhibition and its association with social withdrawal, ultimately modulating the risk for anxiety disorders in BI children. ...

  14. The cytokine ciliary neurotrophic factor (CNTF activates hypothalamic urocortin-expressing neurons both in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Matthew J Purser

    Full Text Available Ciliary neurotrophic factor (CNTF induces neurogenesis, reduces feeding, and induces weight loss. However, the central mechanisms by which CNTF acts are vague. We employed the mHypoE-20/2 line that endogenously expresses the CNTF receptor to examine the direct effects of CNTF on mRNA levels of urocortin-1, urocortin-2, agouti-related peptide, brain-derived neurotrophic factor, and neurotensin. We found that treatment of 10 ng/ml CNTF significantly increased only urocortin-1 mRNA by 1.84-fold at 48 h. We then performed intracerebroventricular injections of 0.5 mg/mL CNTF into mice, and examined its effects on urocortin-1 neurons post-exposure. Through double-label immunohistochemistry using specific antibodies against c-Fos and urocortin-1, we showed that central CNTF administration significantly activated urocortin-1 neurons in specific areas of the hypothalamus. Taken together, our studies point to a potential role for CNTF in regulating hypothalamic urocortin-1-expressing neurons to mediate its recognized effects on energy homeostasis, neuronal proliferaton/survival, and/or neurogenesis.

  15. Assessment of oxidative stress parameters of brain-derived neurotrophic factor heterozygous mice in acute stress model

    Directory of Open Access Journals (Sweden)

    Gulay Hacioglu

    2016-04-01

    Full Text Available Objective(s: Exposing to stress may be associated with increased production of reactive oxygen species (ROS. Therefore, high level of oxidative stress may eventually give rise to accumulation of oxidative damage and development of numerous neurodegenerative diseases. It has been presented that brain-derived neurotrophic factor (BDNF supports neurons against various neurodegenerative conditions. Lately, there has been growing evidence that changes in the cerebral neurotrophic support and especially in the BDNF expression and its engagement with ROS might be important in various disorders and neurodegenerative diseases. Hence, we aimed to investigate protective effects of BDNF against stress-induced oxidative damage. Materials and Methods: Five- to six-month-old male wild-type and BDNF knock-down mice were used in this study. Activities of catalase (CAT and superoxide dismutase (SOD enzymes, and the amount of malondialdehyde (MDA were assessed in the cerebral homogenates of studied groups in response to acute restraint stress. Results: Exposing to acute physiological stress led to significant elevation in the markers of oxidative stress in the cerebral cortexes of experimental groups. Conclusion: As BDNF-deficient mice were observed to be more susceptible to stress-induced oxidative damage, it can be suggested that there is a direct interplay between oxidative stress indicators and BDNF levels in the brain.

  16. A putative model of overeating and obesity based on brain-derived neurotrophic factor: direct and indirect effects.

    Science.gov (United States)

    Ooi, Cara L; Kennedy, James L; Levitan, Robert D

    2012-08-01

    Increased food intake is a major contributor to the obesity epidemic in all age groups. Elucidating brain systems that drive overeating and that might serve as targets for novel prevention and treatment interventions is thus a high priority for obesity research. The authors consider 2 major pathways by which decreased activity of brain-derived neurotrophic factor (BDNF) may confer vulnerability to overeating and weight gain in an obesogenic environment. The first "direct" pathway focuses on the specific role of BDNF as a mediator of food intake control at brain areas rich in BDNF receptors, including the hypothalamus and hindbrain. It is proposed that low BDNF activity limited to this direct pathway may best explain overeating and obesity outside the context of major neuropsychiatric disturbance. A second "indirect" pathway considers the broad neurotrophic effects of BDNF on key monoamine systems that mediate mood dysregulation, impulsivity, and executive dysfunction as well as feeding behavior per se. Disruption in this pathway may best explain overeating and obesity in the context of various neuropsychiatric disturbances including mood disorders, attention-deficit disorder, and/or binge eating disorders. An integrative model that considers these potential roles of BDNF in promoting obesity is presented. The implications of this model for the early prevention and treatment of obesity are also considered. PMID:22687148

  17. The brain-derived neurotrophic factor Val66Met polymorphism moderates early deprivation effects on attention problems.

    Science.gov (United States)

    Gunnar, Megan R; Wenner, Jennifer A; Thomas, Kathleen M; Glatt, Charles E; McKenna, Morgan C; Clark, Andrew G

    2012-11-01

    Adverse early care is associated with attention regulatory problems, but not all so exposed develop attention problems. In a sample of 612 youth (girls = 432, M = 11.82 years, SD = 1.5) adopted from institutions (e.g., orphanages) in 25 countries, we examined whether the Val66Met polymorphism of the brain-derived neurotrophic factor gene moderates attention problems associated with the duration of institutional care. Parent-reported attention problem symptoms were collected using the MacArthur Health and Behavior Questionnaire. DNA was genotyped for the brain-derived neurotrophic factor Val66Met (rs6265) single nucleotide polymorphism. Among youth from Southeast (SE) Asia, the predominant genotype was valine/methionine (Val/Met), whereas among youth from Russia/Europe and Caribbean/South America, the predominant genotype was Val/Val. For analysis, youth were grouped as carrying Val/Val or Met/Met alleles. Being female, being from SE Asia, and being younger when adopted were associated with fewer attention regulatory problem symptoms. Youth carrying at least one copy of the Met allele were more sensitive to the duration of deprivation, yielding an interaction that followed a differential susceptibility pattern. Thus, youth with Val/Met or Met/Met genotypes exhibited fewer symptoms than Val/Val genotypes when adoption was very early and more symptoms when adoption occurred later in development. Similar patterns were observed when SE Asian youth and youth from other parts of the world were analyzed separately. PMID:23062292

  18. Clonidine attenuates morphine withdrawal and subsequent drug sensitization in rhesus monkeys1

    Institute of Scientific and Technical Information of China (English)

    Su-qing CHEN; Hai-feng ZHAI; Yan-ying CUI; Jie SHI; Bernard LE FOLL; Lin LU

    2007-01-01

    Aim: Clonidine is an α2 adrenoceptor agonist that is frequently used to reduce withdrawal symptoms during opioid detoxification in humans. The long-term effects of clonidine on withdrawal symptoms and its effects on subsequent drug exposure have not been thoroughly documented. The aim of the study was to determine if clonidine administered during morphine withdrawal in rhesus mon-keys produces long-lasting effects on withdrawal symptoms and alters the effects of subsequently taken drugs of abuse. Methods: Adult male rhesus monkeys were treated with increasing doses of morphine for 90 d to induce opiate (narcotic)dependence. The immediate and long-lasting effects of 1 week's administration of clonidine were measured via the recording of morphine withdrawal signs and the subsequent effects of challenge injections of morphine or cocaine. Results:Monkeys chronically treated with morphine displayed withdrawal signs that lasted 2 weeks after cessation of morphine administration and displayed sensitized re-sponses to subsequent morphine and cocaine injections. Clonidine significantly reduced certain morphine withdrawal signs and overall withdrawal score, but these effects did not persist upon cessation of clonidine treatment. Sensitization to the effects of morphine and cocaine were significantly reduced in monkeys previ-ously treated with clonidine. Conclusion: Our results suggest that in addition to its short-term alleviating effect on morphine withdrawal signs, clonidine may re-duce subsequent effects of drugs of abuse after prolonged abstinence.

  19. Early steroid withdrawal after liver transplantation for hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To evaluate the impact of early steroid withdrawal on the incidence of rejection, tumor recurrence and complications after liver transplantation for advancedstage hepatocellular carcinoma.METHODS: Fifty-four patients underwent liver transplantation for advanced-stage hepatocellular carcinoma from April 2003 to June 2005. These cases were divided into a steroid-withdrawal group (group A, n = 28) and a steroid-maintenance group (group B,n = 26). In group A, steroid was withdrawn 3 mo after transplantation. In group B, steroid was continuously used postoperatively. The incidence of rejection, 6-mo and 1-year recurrence rate of carcinoma, 1-year survival rate, mean serum tacrolimus trough level, and liver and kidney function were compared between the two groups.RESULTS: In the two groups, no statistical difference was observed in the incidence of rejection (14.3 vs 11.5%, P > 0.05), mean serum tacrolimus trough levels (6.9 ± 1.4 vs 7.1 ± 1.1 μg/L, P > 0.05), liver and kidney function after 6 mo [alanine aminotransferase (ALT):533 ± 183 vs 617 ± 217 nka/L, P > 0.05; creatinine:66 ± 18 vs 71 ± 19 μmol/L, P > 0.05], 6-mo recurrence rate of carcinoma (25.0 vs 42.3%, P > 0.05), and 1-year survival rate (64.2 vs 46.1%, P > 0.05). The 1-year tumor recurrence rate (39.2 vs 69.2%, P < 0.05), serum cholesterol level (3.9 ± 1.8 vs 5.9 ± 2.6 mmol/L, P < 0.01)and fasting blood sugar (5.1 ± 2.1 vs 8.9 ± 3.6 mmol/L,P < 0.01) were significantly different. These were lower in the steroid-withdrawal group than in the steroidmaintenance group.CONCLUSION: Early steroid withdrawal was safe after liver transprantation in patients with advanced-stage hepatocellular carcinoma. When steroids were withdrawn 3 mo post-operation, the incidence of rejection did not increase, and there was no demand to maintain tacrolimus at a high level. In contrast, the tumor recurrence rate and the potential of adverse effects decreased significantly. This may have led to an

  20. Radiohippuran renography in chronic alcoholics with acute alcohol withdrawal syndromes

    International Nuclear Information System (INIS)

    Functional changes found in radiohippuran renography in chronic alcoholics with acute alcohol withdrawal syndromes (n=82; AAWS) regressed to normal values with recovery from AAWS (during 4 days on the average) with the exception of the secretory value which increased to a maximum on the 7th day of observation, remaining approximately unchanged for the following 3 days and decreasing more gradually to a normal value on the 23rd day of observation. In various forms of AAWS the same functional changes in the radiohippuran renogram were observed. (author)

  1. Gamma-hydroxybutyrate Withdrawal in Jamaica – A Case Report

    Directory of Open Access Journals (Sweden)

    CA Sewell

    2015-03-01

    Full Text Available Gamma-hydroxybutyrate (GHB use became more prominent during the 1990s in various parts of the developed world. To date, no case of GHB use has been identified in Jamaica, though this drug is frequently used in other parts of the world at “raves” and other parties characterized by elaborate lights and fast-paced music. Here, a case of a 30-year old visitor to Jamaica is presented, highlighting the typical features of GHB withdrawal and the ease with which this party drug can be imported into the country.

  2. Increasing withdrawal rates add oil reserves in Java Sea area

    International Nuclear Information System (INIS)

    This paper reports on an offshore Southeast Sumatra contract area, resizing downhole pumps which increased withdrawal rates from 36 to 37 worked-over wells. These greater fluid producing rates, according to decline curve analysis, will substantially add to the recoverable oil reserves. The work increased an average well's oil production rate by 183 bo/d and added 183,000 bbl/well to recoverable oil reserves without materially affecting water cut. The cost of the reserve additions was $0.37/bbl. No loss in ultimate recovery was indicated for any of the wells

  3. Increasing withdrawal rates add oil reserves in Java Sea area

    Energy Technology Data Exchange (ETDEWEB)

    Ventura, J. (Maxis Energy Corp., Dallas, TX (US)); Temansja, A.D. (Maxus Southeast, Sumatra Inc., Jakarta (ID))

    1991-11-18

    This paper reports on an offshore Southeast Sumatra contract area, resizing downhole pumps which increased withdrawal rates from 36 to 37 worked-over wells. These greater fluid producing rates, according to decline curve analysis, will substantially add to the recoverable oil reserves. The work increased an average well's oil production rate by 183 bo/d and added 183,000 bbl/well to recoverable oil reserves without materially affecting water cut. The cost of the reserve additions was $0.37/bbl. No loss in ultimate recovery was indicated for any of the wells.

  4. Alcohol Withdrawal and Brain Injuries: Beyond Classical Mechanisms

    Directory of Open Access Journals (Sweden)

    Marianna E. Jung

    2010-07-01

    Full Text Available Unmanaged sudden withdrawal from the excessive consumption of alcohol (ethanol adversely alters neuronal integrity in vulnerable brain regions such as the cerebellum, hippocampus, or cortex. In addition to well known hyperexcitatory neurotransmissions, ethanol withdrawal (EW provokes the intense generation of reactive oxygen species (ROS and the activation of stress-responding protein kinases, which are the focus of this review article. EW also inflicts mitochondrial membranes/membrane potential, perturbs redox balance, and suppresses mitochondrial enzymes, all of which impair a fundamental function of mitochondria. Moreover, EW acts as an age-provoking stressor. The vulnerable age to EW stress is not necessarily the oldest age and varies depending upon the target molecule of EW. A major female sex steroid, 17β-estradiol (E2, interferes with the EW-induced alteration of oxidative signaling pathways and thereby protects neurons, mitochondria, and behaviors. The current review attempts to provide integrated information at the levels of oxidative signaling mechanisms by which EW provokes brain injuries and E2 protects against it. Unmanaged sudden withdrawal from the excessive consumption of alcohol (ethanol adversely alters neuronal integrity in vulnerable brain regions such as the cerebellum, hippocampus, or cortex. In addition to well known hyperexcitatory neurotransmissions, ethanol withdrawal (EW provokes the intense generation of reactive oxygen species (ROS and the activation of stress-responding protein kinases, which are the focus of this review article. EW also inflicts mitochondrial membranes/membrane potential, perturbs redox balance, and suppresses mitochondrial enzymes, all of which impair a fundamental function of mitochondria. Moreover, EW acts as an age-provoking stressor. The vulnerable age to EW stress is not necessarily the oldest age and varies depending upon the target molecule of EW. A major female sex steroid, 17

  5. Activation of signaling pathways following localized delivery of systemically administered neurotrophic factors across the blood-brain barrier using focused ultrasound and microbubbles

    Science.gov (United States)

    Baseri, Babak; Choi, James J.; Deffieux, Thomas; Samiotaki, Gesthimani; Tung, Yao-Sheng; Olumolade, Oluyemi; Small, Scott A.; Morrison, Barclay, III; Konofagou, Elisa E.

    2012-04-01

    The brain-derived neurotrophic factor (BDNF) has been shown to have broad neuroprotective effects in addition to its therapeutic role in neurodegenerative disease. In this study, the efficacy of delivering exogenous BDNF to the left hippocampus is demonstrated in wild-type mice (n = 7) through the noninvasively disrupted blood-brain barrier (BBB) using focused ultrasound (FUS). The BDNF bioactivity was found to be preserved following delivery as assessed quantitatively by immunohistochemical detection of the pTrkB receptor and activated pAkt, pMAPK, and pCREB in the hippocampal neurons. It was therefore shown for the first time that systemically administered neurotrophic factors can cross the noninvasively disrupted BBB and trigger neuronal downstream signaling effects in a highly localized region in the brain. This is the first time that the administered molecule is tracked through the BBB and localized in the neuron triggering molecular effects. Additional preliminary findings are shown in wild-type mice with two additional neurotrophic factors such as the glia-derived neurotrophic factor (n = 12) and neurturin (n = 2). This further demonstrates the impact of FUS for the early treatment of CNS diseases at the cellular and molecular level and strengthens its premise for FUS-assisted drug delivery and efficacy.

  6. Ciliary neurotrophic factor activates NF-κB to enhance mitochondrial bioenergetics and prevent neuropathy in sensory neurons of streptozotocin-induced diabetic rodents

    OpenAIRE

    Saleh, Ali; Roy Chowdhury, Subir K.; Smith, Darrel R.; Balakrishnan, Savitha; Tessler, Lori; Martens, Corina; Morrow, Dwane; Schartner, Emily; Frizzi, Katie E.; Calcutt, Nigel A.; Fernyhough, Paul

    2012-01-01

    Diabetes causes mitochondrial dysfunction in sensory neurons that may contribute to peripheral neuropathy. Ciliary neurotrophic factor (CNTF) promotes sensory neuron survival and axon regeneration and prevents axonal dwindling, nerve conduction deficits and thermal hypoalgesia in diabetic rats. In this study, we tested the hypothesis that CNTF protects sensory neuron function during diabetes through normalization of impaired mitochondrial bioenergetics. In addition, we investigated whether th...

  7. Intravitreal injection of ciliary neurotrophic factor (CNTF) causes peripheral remodeling and does not prevent photoreceptor loss in canine RPGR mutant retina

    OpenAIRE

    Beltran, William A.; Wen, Rong; Acland, Gregory M.; Aguirre, Gustavo D.

    2007-01-01

    Ciliary neurotrophic factor (CNTF) rescues photoreceptors in several animal models of retinal degeneration and is currently being evaluated as a potential treatment for retinitis pigmentosa in humans. This study was conducted to test whether CNTF prevents photoreceptor cell loss in XLPRA2, an early onset canine model of X-linked retinitis pigmentosa caused by a frameshift mutation in RPGR exon ORF15.

  8. Interaction Between Childhood Adversity, Brain-Derived Neurotrophic Factor val/met and Serotonin Transporter Promoter Polymorphism on Depression : The TRAILS Study

    NARCIS (Netherlands)

    Nederhof, E; Bouma, Esther; Oldehinkel, A.J.; Ormel, J.

    2010-01-01

    Background: The three-way interaction between the functional polymorphism in the serotonin transporter gene linked promoter region, the val66met polymorphism in the brain-derived neurotrophic factor gene, and childhood adversity in the prediction of depression in children, reported by Kaufman and co

  9. Promoting Neuroplasticity for Motor Rehabilitation After Stroke: Considering the Effects of Aerobic Exercise and Genetic Variation on Brain-Derived Neurotrophic Factor

    OpenAIRE

    Mang, Cameron S.; Campbell, Kristin L.; Ross, Colin J.D.; Boyd, Lara A

    2013-01-01

    Recovery of motor function after stroke involves relearning motor skills and is mediated by neuroplasticity. Recent research has focused on developing rehabilitation strategies that facilitate such neuroplasticity to maximize functional outcome poststroke. Although many molecular signaling pathways are involved, brain-derived neurotrophic factor (BDNF) has emerged as a key facilitator of neuroplasticity involved in motor learning and rehabilitation after stroke. Thus, rehabilitation strategie...

  10. Cometin is a novel neurotrophic factor that promotes neurite outgrowth and neuroblast migration in vitro and supports survival of spiral ganglion neurons in vivo

    DEFF Research Database (Denmark)

    Jørgensen, Jesper Roland; Fransson, Anette; Fjord-Larsen, Lone;

    2012-01-01

    Neurotrophic factors are secreted proteins responsible for migration, growth and survival of neurons during development, and for maintenance and plasticity of adult neurons. Here we present a novel secreted protein named Cometin which together with Meteorin defines a new evolutionary conserved pr...

  11. Brain Derived Neurotrophic Factor (BDNF) levels as a possible predictor of psychopathology in healthy twins at high and low risk for affective disorder

    DEFF Research Database (Denmark)

    Vinberg, Maj; Miskowiak, Kamilla; Kessing, Lars Vedel

    2014-01-01

    Brain Derived Neurotrophic Factor (BDNF) is a potential biomarker of affective disorder. However, longitudinal studies evaluating a potential predictive role of BDNF on subsequent psychopathology are lacking. The aim of this study was to investigate whether BDNF alone or in interaction with the...

  12. Intraspinal Rewiring of the Corticospinal Tract Requires Target-Derived Brain-Derived Neurotrophic Factor and Compensates Lost Function after Brain Injury

    Science.gov (United States)

    Ueno, Masaki; Hayano, Yasufumi; Nakagawa, Hiroshi; Yamashita, Toshihide

    2012-01-01

    Brain injury that results in an initial behavioural deficit is frequently followed by spontaneous recovery. The intrinsic mechanism of this functional recovery has never been fully understood. Here, we show that reorganization of the corticospinal tract induced by target-derived brain-derived neurotrophic factor is crucial for spontaneous recovery…

  13. Brain-derived neurotrophic factor expression in dorsal root ganglion neurons in response to reanastomosis of the distal stoma after nerve grafting

    Institute of Scientific and Technical Information of China (English)

    Wei Yu; Jian Wang; Mingzhu Xu; Hanjiao Qin; Shusen Cui

    2012-01-01

    Studies have shown that retreatment of the distal stoma after nerve grafting can stimulate nerve regeneration. The present study attempted to verify the effects of reanastomosis of the distal stoma, after nerve grafting, on nerve regeneration by assessing brain-derived neurotrophic factor expression in 2-month-old rats. Results showed that brain-derived neurotrophic factor expression in L2-4 dorsal root ganglia began to increase 3 days after autologous nerve grafting post sciatic nerve injury, peaked at 14 days, decreased at 28 days, and reached similar levels to the sham-surgery group at 56 days. Brain-derived neurotrophic factor expression in L2-4 dorsal root ganglia began to increase 3 days after reanastomosis of the distal stoma, 59 days after autologous nerve grafting post sciatic nerve injury, significantly increased at 63 days, peaked at 70 days, and gradually decreased thereafter, but remained higher compared with the sham-surgery group up to 112 days. The results of this study indicate that reanastomosis of the distal stoma after orthotopic nerve grafting stimulated brain-derived neurotrophic factor expression in L2-4 dorsal root ganglia.

  14. Anti-Estrogen Withdrawal Effect With Raloxifene? A Case Report.

    Science.gov (United States)

    Lemmo, Walter

    2016-09-01

    A 66-year-old patient presented with acute recurrent metastatic estrogen and progesterone receptor-positive, Her-2/neu-negative breast cancer, bone lesions (lumbar spine, pelvis), pulmonary nodules, hepatic metastasis, elevated cancer antigen 15 and liver enzymes, dyspepsia, and diarrhea. The patient had been taking raloxifene for approximately 8 years. After discontinuation, clinical parameters and symptoms improved rapidly without oncological therapy or other forms of treatment. Three months after raloxifene discontinuation, capecitabine was initiated by the treating oncologist who deemed an anti-estrogen withdrawal effect (AEWE) implausible. However, the lasting regression was more indicative of a raloxifene rebound effect than chemotherapy or other interventions. Today, the patient is asymptomatic with a good performance status. Hepatic metastatic regression has been confirmed, without any oncological treatment administered in the past 16 months and approximately 23 months following the withdrawal of raloxifene. This case highlights the need to screen breast cancer patients for the possibility of an AEWE if they are using raloxifene and possibly similar selective estrogen receptor modulators (SERMs) which includes tamoxifen, when diagnosed with advanced breast cancer, especially in the recurrent disease setting. PMID:27411856

  15. Crop Insurance Increases Water Withdrawals for Irrigation in Agriculture

    Science.gov (United States)

    Konar, M.; Deryugina, T.; Lin, X.

    2015-12-01

    Agricultural production remains particularly vulnerable to weather fluctuations and extreme events, such as droughts, floods, and heat waves. Crop insurance is a risk management tool that has been developed to mitigate some of this weather risk and protect farmer income in times of poor production. However, it is not clear what the implications of crop insurance are for crop irrigation. By providing a guaranteed level of income in case of crop failure, crop insurance can reduce the farmer's incentive to irrigate. Thus, crop insurance can decrease water use in times of drought and promote water sustainability. However, to minimize this "moral hazard", the insurer may require farmers to irrigate crops more than necessary. Further, by shifting crop production, crop insurance may increase demand for water. Thus, it is unclear whether crop insurance increases or decreases crop water use. Here, we determine the empirical relationship between crop insurance and irrigation withdrawals in the United States. To establish causality, we exploit variation in crop insurance policies over time, using an instrumental variables approach. We find that a 1% increase in insured crop acreage leads to a 0.223% increase in irrigation withdrawals, primarily from groundwater aquifers.

  16. Causes for Withdrawal in an Urban Peritoneal Dialysis Program

    Directory of Open Access Journals (Sweden)

    Biruh Workeneh

    2015-01-01

    Full Text Available Background. Peritoneal dialysis (PD is an underutilized dialysis modality in the United States, especially in urban areas with diverse patient populations. Technique retention is a major concern of dialysis providers and might influence their approach to patients ready to begin dialysis therapy. Methods. Records from January 2009 to March 2014 were abstracted for demographic information, technique duration, and the reasons for withdrawal. Results. The median technique survival of the 128 incident patients during the study window was 781 days (2.1 years. The principle reasons for PD withdrawal were repeated peritonitis (30%; catheter dysfunction (18%; ultrafiltration failure (16%; patient choice or lack of support (16%; or hernia, leak, or other surgical complications (6%; and a total of 6 patients died during this period. Of the patients who did not expire and were not transplanted, most transferred to in-center hemodialysis and 8% transitioned to home-hemodialysis. Conclusions. Our findings suggest measures to ensure proper catheter placement and limiting infectious complications should be primary areas of focus in order to promote technique retention. Lastly, more focused education about home-hemodialysis as an option may allow those on PD who are beginning to demonstrate signs of technique failure to stay on home therapy.

  17. Streptococcus pneumoniae infection regulates expression of neurotrophic factors in the olfactory bulb and cultured olfactory ensheathing cells.

    Science.gov (United States)

    Ruiz-Mendoza, S; Macedo-Ramos, H; Santos, F A; Quadros-de-Souza, L C; Paiva, M M; Pinto, T C A; Teixeira, L M; Baetas-da-Cruz, W

    2016-03-11

    Streptococcus pneumoniae is the causative agent of numerous diseases including severe invasive infections such as bacteremia and meningitis. It has been previously shown that strains of S. pneumoniae that are unable to survive in the bloodstream may colonize the CNS. However, information on cellular components and pathways involved in the neurotropism of these strains is still scarce. The olfactory system is a specialized tissue in which olfactory receptor neurons (ORNs) are interfacing with the external environment through several microvilli. Olfactory ensheathing cells (OECs) which also form the glial limiting membrane at the surface of the olfactory bulb (OB) are the only cells that ensheathe the ORNs axons. Since previous data from our group showed that OECs may harbor S. pneumoniae, we decided to test whether infection of the OB or OEC cultures modulates the expression levels of neurotrophic factor's mRNA and its putative effects on the activation and viability of microglia. We observed that neurotrophin-3 (NT-3) and glial cell-line-derived neurotrophic factor (GDNF) expression was significantly higher in the OB from uninfected mice than in infected mice. A similar result was observed when we infected OEC cultures. Brain-derived neurotrophic factor (BNDF) expression was significantly lower in the OB from infected mice than in uninfected mice. In contrast, in vitro infection of OECs resulted in a significant increase of BDNF mRNA expression. An upregulation of high-mobility group box 1 (HMGB1) expression was observed in both OB and OEC cultures infected with S. pneumoniae. Moreover, we found that conditioned medium from infected OEC cultures induced the expression of the pro-apoptotic protein cleaved-caspase-3 and an apparently continuous nuclear factor-kappa B (NF-κB) p65 activation in the N13 microglia. Altogether, our data suggest the possible existence of an OEC-pathogen molecular interface, through which the OECs could interfere on the activation and

  18. 40 CFR 96.86 - Withdrawal from NOX Budget Trading Program.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Withdrawal from NOX Budget Trading... PROGRAMS (CONTINUED) NOX BUDGET TRADING PROGRAM AND CAIR NOX AND SO2 TRADING PROGRAMS FOR STATE IMPLEMENTATION PLANS Individual Unit Opt-ins § 96.86 Withdrawal from NOX Budget Trading Program. (a)...

  19. 40 CFR 97.286 - Withdrawal from CAIR SO2 Trading Program.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Withdrawal from CAIR SO2 Trading... PROGRAMS (CONTINUED) FEDERAL NOX BUDGET TRADING PROGRAM AND CAIR NOX AND SO2 TRADING PROGRAMS CAIR SO2 Opt-in Units § 97.286 Withdrawal from CAIR SO2 Trading Program. Except as provided under paragraph (g)...

  20. 40 CFR 96.286 - Withdrawal from CAIR SO2 Trading Program.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Withdrawal from CAIR SO2 Trading... PROGRAMS (CONTINUED) NOX BUDGET TRADING PROGRAM AND CAIR NOX AND SO2 TRADING PROGRAMS FOR STATE IMPLEMENTATION PLANS CAIR SO2 Opt-in Units § 96.286 Withdrawal from CAIR SO2 Trading Program. Except as...

  1. Time-course of the DSM-5 cannabis withdrawal symptoms in poly-substance abusers

    DEFF Research Database (Denmark)

    Hesse, Morten; Thylstrup, Birgitte

    2013-01-01

    Background Evidence is accumulating that a cannabis withdrawal syndrome is common, of clinical significance, and has a clear time course. Up till now, very limited data exist on the cannabis withdrawal symptoms in patients with co-morbid substance use disorders, other than cannabis use and tobacc...

  2. 78 FR 64531 - Notice of Proposed Withdrawal Extension, Sacramento Pass Recreation Area; Nevada

    Science.gov (United States)

    2013-10-29

    ... withdrawal established by PLO No. 7060 (59 FR 28790 (1994)), for an additional 20-year term. PLO No. 7060... Bureau of Land Management Notice of Proposed Withdrawal Extension, Sacramento Pass Recreation Area..., but not from leasing under the mineral leasing laws, to protect the Sacramento Pass Recreation...

  3. What Are They Thinking? Students' Affective Reasoning and Attitudes about Course Withdrawal

    Science.gov (United States)

    Wheland, Ethel R.; Butler, Kevin A.; Qammar, Helen; Katz, Karyn Bobkoff; Harris, Rose

    2012-01-01

    In this mixed-methods study we identify situations that impact students' decisions to withdraw from a course and examine their affective reasoning and attitudes toward course withdrawal. Exploring students' decision-making processes through the lens of self-authorship, we show that students frequently seek information from people with whom they…

  4. Complementing the Numbers: A Text Mining Analysis of College Course Withdrawals

    Science.gov (United States)

    Michalski, Greg V.

    2011-01-01

    Excessive college course withdrawals are costly to the student and the institution in terms of time to degree completion, available classroom space, and other resources. Although generally well quantified, detailed analysis of the reasons given by students for course withdrawal is less common. To address this, a text mining analysis was performed…

  5. Neuroleptic malignant syndrome and subsequent clozapine-withdrawal effects in a patient with refractory schizophrenia

    Science.gov (United States)

    Cheng, Minfeng; Gu, Huaying; Zheng, Liangrong; Wang, Houliang; Zhong, Zhiyong; Wen, Shenglin

    2016-01-01

    Here, we report a female patient developing neuroleptic malignant syndrome following the use of a combination of clozapine and haloperidol. Subsequently, the patient presented withdrawal effects after an abrupt discontinuation of clozapine. Psychiatrists not aware of possible clozapine-withdrawal effects may misdiagnose as a part of the primary mental illness or as the initial symptoms worsening, if unrecognized. PMID:27099499

  6. 27 CFR 19.502 - Withdrawal of spirits on production or filling gauge.

    Science.gov (United States)

    2010-04-01

    ... production or filling gauge. 19.502 Section 19.502 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS DISTILLED SPIRITS PLANTS Transfer and Withdrawals General § 19.502 Withdrawal of spirits on production or filling gauge. When the production...

  7. A genetic perspective on the proposed inclusion of cannabis withdrawal in DSM-5

    NARCIS (Netherlands)

    Verweij, K.J.H.; Agrawal, A.; Nat, N.O.; Creemers, H.E.; Huizink, A.C.; Martin, N.G.; Lynskey, M.T.

    2013-01-01

    Background Various studies support the inclusion of cannabis withdrawal in the diagnosis of cannabis use disorder (CUD) in the upcoming DSM-5. The aims of the current study were to (1) estimate the prevalence of DSM-5 cannabis withdrawal (criterion B), (2) estimate the role of genetic and environmen

  8. 76 FR 44376 - Vermont Yankee Nuclear Power Station; Notice of Withdrawal of Application for Amendment to...

    Science.gov (United States)

    2011-07-25

    ... COMMISSION Vermont Yankee Nuclear Power Station; Notice of Withdrawal of Application for Amendment to... request of Vermont Yankee Nuclear Power Station (the licensee) to withdraw its August 19, 2010, application for proposed amendment to Facility Operating License No. DPR-28 for the Vermont Yankee...

  9. Childhood Social Withdrawal, Interpersonal Impairment, and Young Adult Depression: A Mediational Model

    Science.gov (United States)

    Katz, Shaina J.; Conway, Christopher C.; Hammen, Constance L.; Brennan, Patricia A.; Najmanm, Jake M.

    2011-01-01

    Building on interpersonal theories of depression, the current study sought to explore whether early childhood social withdrawal serves as a risk factor for depressive symptoms and diagnoses in young adulthood. The researchers hypothesized that social impairment at age 15 would mediate the association between social withdrawal at age 5 and…

  10. Delay and probability discounting: Examining the relationship between caffeine withdrawal and impulsivity

    Directory of Open Access Journals (Sweden)

    2015-09-01

    Conclusions: Validating previous research for other stimulants, conditional support was found for a correlation between caffeine withdrawal and impulsivity. However, these results could also be explained by other well-documented symptoms of stimulant withdrawal such as confusion or anxiety. Further efforts should be devoted to determining the effect anxiety has on impulsivity as measured by the delay discounting procedure.

  11. 29 CFR 4211.34 - Rolling-5 method for withdrawals after the initial plan year.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 9 2010-07-01 2010-07-01 false Rolling-5 method for withdrawals after the initial plan year. 4211.34 Section 4211.34 Labor Regulations Relating to Labor (Continued) PENSION BENEFIT GUARANTY... EMPLOYERS Allocation Methods for Merged Multiemployer Plans § 4211.34 Rolling-5 method for withdrawals...

  12. 19 CFR 159.52 - Warehouse entry not liquidated until final withdrawal.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Warehouse entry not liquidated until final withdrawal. 159.52 Section 159.52 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND... Warehouse entry not liquidated until final withdrawal. Liquidation of a warehouse or rewarehouse entry...

  13. 29 CFR 102.9 - Who may file; withdrawal and dismissal.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 2 2010-07-01 2010-07-01 false Who may file; withdrawal and dismissal. 102.9 Section 102.9....9 Who may file; withdrawal and dismissal. A charge that any person has engaged in or is engaging in... motion, with the consent of the administrative law judge designated to conduct the hearing; and after...

  14. 8 CFR 246.4 - Immigration judge's authority; withdrawal and substitution.

    Science.gov (United States)

    2010-01-01

    ... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Immigration judge's authority; withdrawal... IMMIGRATION REGULATIONS RESCISSION OF ADJUSTMENT OF STATUS § 246.4 Immigration judge's authority; withdrawal and substitution. In any proceeding conducted under this part, the immigration judge shall...

  15. 19 CFR 144.42 - Combined entry for rewarehouse and withdrawal for consumption.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Combined entry for rewarehouse and withdrawal for... Rewarehouse Entries § 144.42 Combined entry for rewarehouse and withdrawal for consumption. (a) Applicability... of the merchandise immediately upon arrival at destination, he may make a combined entry...

  16. 78 FR 52429 - New Animal Drugs; Withdrawal of Approval of New Animal Drug Applications; Diethylcarbamazine...

    Science.gov (United States)

    2013-08-23

    ... HUMAN SERVICES Food and Drug Administration 21 CFR Parts 510, 520, and 558 New Animal Drugs; Withdrawal of Approval of New Animal Drug Applications; Diethylcarbamazine; Nicarbazin; Penicillin AGENCY: Food... amending the animal drug regulations to reflect the withdrawal of approval of three new animal...

  17. 14 CFR 205.7 - Cancellation, withdrawal, modification, expiration, or replacement of insurance coverage.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Cancellation, withdrawal, modification, expiration, or replacement of insurance coverage. 205.7 Section 205.7 Aeronautics and Space OFFICE OF THE... LIABILITY INSURANCE § 205.7 Cancellation, withdrawal, modification, expiration, or replacement of...

  18. 48 CFR 2819.506 - Withdrawing or modifying set-asides.

    Science.gov (United States)

    2010-10-01

    ... set-asides. 2819.506 Section 2819.506 Federal Acquisition Regulations System DEPARTMENT OF JUSTICE Socioeconomic Programs SMALL BUSINESS PROGRAMS Set-Asides for Small Business 2819.506 Withdrawing or modifying set-asides. (a) Before a contracting officer may withdraw or modify a small business set-aside,...

  19. The role of spiritual intelligence in employees’ withdrawal behaviors in physical education organization

    Directory of Open Access Journals (Sweden)

    Davoud Noroozi

    2015-03-01

    Full Text Available Spiritual intelligence is the mind’s capacity to handle substantial and spiritual aspects of life. According to previous studies, spiritual intelligence can be effective in reducing the withdrawal behavior of employees. This study investigated the effect of spiritual intelligence on employees’ withdrawal behavior in Ardabil Physical Education organization. The statistical population of this study included all the employees of Physical Education organization of Ardabil (N=60. Descriptive Statistics, Pearson Correlation, and Linear Regression Analyses were used to assess the association between spiritual intelligence and withdrawal behaviors. The results of the study revealed that spiritual intelligence had positive and significant effect on reducing employees’ withdrawal behavior. The findings supported that spiritual intelligence training as a new psychological and religious construction may reduce psychological and physical withdrawal behaviors and improve the employees’ perception of themselves.

  20. Cytokines, brain-derived neurotrophic factor and C-reactive protein in bipolar I disorder - Results from a prospective study

    DEFF Research Database (Denmark)

    Jacoby, Anne Sophie; Munkholm, Klaus; Vinberg, Maj;

    2016-01-01

    . Further, 69 blood samples were drawn from 35 healthy control subjects with three months apart. In unadjusted mixed-model analysis, levels of IL-6 and IL-8 were increased 64% (b=1.64, 95% CI: 1.31-2.05, p=<0.0001) and 24% (b=1.24, 95% CI: 1.05-1.47, p=0.013), respectively in patients with bipolar disorder......BACKGROUND: Peripheral blood brain-derived neurotrophic factor (BDNF) and inflammatory markers may reflect key pathophysiological mechanisms in bipolar disorder in relation to disease activity and neuroprogression. AIMS: To investigate whether neutrophins and inflammatory marker vary with mood...... states and are increased in patients with bipolar disorder type I during euthymia as well as in all affective states as a group, compared to levels in healthy control subjects. METHODS: In a prospective 6-12 months follow-up study, we investigated state specific, intra-individual alterations in levels of...

  1. Coping with unpredictability: Dopaminergic and neurotrophic responses to omission of expected reward in Atlantic salmon (Salmo salar L.)

    DEFF Research Database (Denmark)

    Vindas, Marco A; Sørensen, Christina; Johansen, Ida;

    2014-01-01

    abundance and plasma cortisol concentration. These observations indicate a conserved link between DA, neurotrophin regulation, and corticosteroid-signaling pathways. The results also emphasize how fish models can be important tools in the study of neural plasticity and responsiveness to environmental......Comparative studies are imperative for understanding the evolution of adaptive neurobiological processes such as neural plasticity, cognition, and emotion. Previously we have reported that prolonged omission of expected rewards (OER, or 'frustrative nonreward') causes increased aggression in...... Atlantic salmon (Salmo salar). Here we report changes in brain monoaminergic activity and relative abundance of brain derived neurotrophic factor (BDNF) and dopamine receptor mRNA transcripts in the same paradigm. Groups of fish were initially conditioned to associate a flashing light with feeding...

  2. Gender and brain regions specific differences in brain derived neurotrophic factor protein levels of depressed individuals who died through suicide.

    Science.gov (United States)

    Hayley, Shawn; Du, Lisheng; Litteljohn, Darcy; Palkovits, Miklós; Faludi, Gábor; Merali, Zul; Poulter, Michael O; Anisman, Hymie

    2015-07-23

    Considerable evidence supports the view that depressive illness and suicidal behaviour stem from perturbations of neuroplasticity. Presently, we assessed whether depressed individuals who died by suicide displayed brain region-specific changes in brain derived neurotrophic factor (BDNF) and whether such effects varied by gender. Using postmortem samples from non-psychiatric controls and depressed individuals who died by suicide, BDNF protein levels were assessed within the hippocampus and frontopolar prefrontal cortex using Western blot. As expected, BDNF levels were reduced within the frontopolar prefrontal cortex among female depressed suicides; however, males showed no such effect. Contrastingly, within the hippocampus, depressed male but not female suicides displayed significant reductions of BDNF protein levels. Although the mechanisms driving the gender and brain region specific BDNF changes are unclear, our data do support the notion that complex alterations of neuroplasticity may be fundamentally involved in the illness. PMID:26033186

  3. Reg-2, A Downstream Signaling Protein in the Ciliary Neurotrophic Factor Survival Pathway, Alleviates Experimental Autoimmune Encephalomyelitis.

    Science.gov (United States)

    Jiang, Hong; Tian, Ke-Wei; Zhang, Fan; Wang, Beibei; Han, Shu

    2016-01-01

    Ciliary neurotrophic factor (CNTF), originally described as a neurocytokine that could support the survival of neurons, has been recently found to alleviate demyelination, prevent axon loss, and improve functional recovery in a rat model of acute experimental autoimmune encephalomyelitis (EAE). However, poor penetration into the brain parenchyma and unfavorable side effects limit the utility of CNTF. Here, we evaluated the therapeutic potential of a protein downstream of CNTF, regeneration gene protein 2 (Reg-2). Using multiple morphological, molecular biology, and electrophysiological methods to assess neuroinflammation, axonal loss, demyelination, and functional impairment, we observed that Reg-2 and CNTF exert similar effects in the acute phase of EAE. Both treatments attenuated axonal loss and demyelination, improved neuronal survival, and produced functional improvement. With a smaller molecular weight and improved penetration into the brain parenchyma, Reg-2 may be a useful substitute for CNTF therapy in EAE and multiple sclerosis (MS). PMID:27242448

  4. Enhanced brain-derived neurotrophic factor delivery by ultrasound and microbubbles promotes white matter repair after stroke.

    Science.gov (United States)

    Rodríguez-Frutos, Berta; Otero-Ortega, Laura; Ramos-Cejudo, Jaime; Martínez-Sánchez, Patricia; Barahona-Sanz, Inés; Navarro-Hernanz, Teresa; Gómez-de Frutos, María Del Carmen; Díez-Tejedor, Exuperio; Gutiérrez-Fernández, María

    2016-09-01

    Ultrasound-targeted microbubble destruction (UTMD) has been shown to be a promising tool to deliver proteins to select body areas. This study aimed to analyze whether UTMD was able to deliver brain-derived neurotrophic factor (BDNF) to the brain, enhancing functional recovery and white matter repair, in an animal model of subcortical stroke induced by endothelin (ET)-1. UTMD was used to deliver BDNF to the brain 24 h after stroke. This technique was shown to be safe, given there were no cases of hemorrhagic transformation or blood brain barrier (BBB) leakage. UTMD treatment was associated with increased brain BDNF levels at 4 h after administration. Targeted ultrasound delivery of BDNF improved functional recovery associated with fiber tract connectivity restoration, increasing oligodendrocyte markers and remyelination compared to BDNF alone administration in an experimental animal model of white matter injury. PMID:27240161

  5. LncRNA analysis of mouse spermatogonial stem cells following glial cell-derived neurotrophic factor treatment

    Directory of Open Access Journals (Sweden)

    Lufan Li

    2015-09-01

    Full Text Available Spermatonial stem cells (SSCs are the foundation of spermatogenesis. Long non-coding RNAs (lncRNAs are a class of non-coding RNAs with at least 200 bp in length, which play important roles in various biological processes. Growth factor glial cell line-derived neurotrophic factor (GDNF, secreted from testis niches, is critical for self-renewal of SSCs in vitro and in vivo. Using Illumina HiSeq™ 2000 high throughput sequencing, we found 55924 lncRNAs which were regulated by GDNF in SSCs in vitro; these included 21,929 known lncRNAs from NONCODE library (version 3.0 and 33,975 predicted lncRNAs which were identified using Coding Potential Calculator. Analyses of these data should provide new insights into regulated mechanism in SSC self-renewal and proliferation. The data have been deposited in the Gene Expression Omnibus (series GSE66998.

  6. LncRNA analysis of mouse spermatogonial stem cells following glial cell-derived neurotrophic factor treatment

    Science.gov (United States)

    Li, Lufan; Wang, Min; Wang, Mei; Wu, Xiaoxi; Geng, Lei; Xue, Yuanyuan; Wei, Xiang; Jia, Yuanyuan; Wu, Xin

    2015-01-01

    Spermatonial stem cells (SSCs) are the foundation of spermatogenesis. Long non-coding RNAs (lncRNAs) are a class of non-coding RNAs with at least 200 bp in length, which play important roles in various biological processes. Growth factor glial cell line-derived neurotrophic factor (GDNF), secreted from testis niches, is critical for self-renewal of SSCs in vitro and in vivo. Using Illumina HiSeq™ 2000 high throughput sequencing, we found 55924 lncRNAs which were regulated by GDNF in SSCs in vitro; these included 21,929 known lncRNAs from NONCODE library (version 3.0) and 33,975 predicted lncRNAs which were identified using Coding Potential Calculator. Analyses of these data should provide new insights into regulated mechanism in SSC self-renewal and proliferation. The data have been deposited in the Gene Expression Omnibus (series GSE66998). PMID:26484267

  7. Chronic intermittent hypoxia-induced deficits in synaptic plasticity and neurocognitive functions: a role for brain-derived neurotrophic factor

    Institute of Scientific and Technical Information of China (English)

    Hui XIE; Wing-ho YUNG

    2012-01-01

    Obstructive sleep apnea (OSA) is well known for its metabolic as well as neurobehavioral consequences.Chronic intermittent hypoxia (IH) is a major component of OSA.In recent years,substantial advances have been made in elucidating the cellular and molecular mechanisms underlying the effect of chronic IH on neurocognitive functions,many of which are based on studies in animal models.A number of hypotheses have been put forward to explain chronic IH-induced neurological dysfunctions.Among these,the roles of oxidative stress and apoptosis-related neural injury are widely accepted.Here,focusing on results derived from animal studies,we highlight a possible role of reduced expression of brain-derived neurotrophic factor (BDNF) in causing impairment in long-term synaptic plasticity and neurocognitive functions during chronic IH.The possible relationship between BDNF and previous findings on this subject will be elucidated.

  8. Reg-2, A Downstream Signaling Protein in the Ciliary Neurotrophic Factor Survival Pathway, Alleviates Experimental Autoimmune Encephalomyelitis

    Science.gov (United States)

    Jiang, Hong; Tian, Ke-Wei; Zhang, Fan; Wang, Beibei; Han, Shu

    2016-01-01

    Ciliary neurotrophic factor (CNTF), originally described as a neurocytokine that could support the survival of neurons, has been recently found to alleviate demyelination, prevent axon loss, and improve functional recovery in a rat model of acute experimental autoimmune encephalomyelitis (EAE). However, poor penetration into the brain parenchyma and unfavorable side effects limit the utility of CNTF. Here, we evaluated the therapeutic potential of a protein downstream of CNTF, regeneration gene protein 2 (Reg-2). Using multiple morphological, molecular biology, and electrophysiological methods to assess neuroinflammation, axonal loss, demyelination, and functional impairment, we observed that Reg-2 and CNTF exert similar effects in the acute phase of EAE. Both treatments attenuated axonal loss and demyelination, improved neuronal survival, and produced functional improvement. With a smaller molecular weight and improved penetration into the brain parenchyma, Reg-2 may be a useful substitute for CNTF therapy in EAE and multiple sclerosis (MS). PMID:27242448

  9. Sequence analysis and functional study of the Han Nationality glial cell line-derived neurotrophic factor transcript

    Institute of Scientific and Technical Information of China (English)

    CHEN Zhe-yu; HUANG Ai-jun; LU Chang-lin; WU Xiang-fu; HE Cheng

    2001-01-01

    To study the sequence and function of the glial cell line-derived neurotrophic factor (GDNF) transcript in subjects of Han nationality. Methods: The Han nationality GDNF transcript was amplified by RT-PCR and expressed by baculovirus expression system. Biological activity of the expressed product was measured by the primary culture of midbrain dopaminergic neurons. Results: There only existed the shorter GDNF transcript of 555 bp in the Han nationality. The secretory expression product of the shorter transcript in insect cells promoted the survival and differentiation of dopaminergic neurons. Conclusion: It is found that there is a 78 bp deletion in the Han nationality GDNF transcript compared with the reported 633 bp GDNF transcript. The 78 bp deletion does not affect the secretory expression and biological activity of GDNF mature protein.

  10. The effects of acute levodopa withdrawal on motor performance and dopaminergic receptor sensitivity in patients with Parkinson's disease.

    OpenAIRE

    Turjanski, N; Fernandez, W; Lees, A J

    1993-01-01

    The effects of acute levodopa withdrawal were studied in nine patients with levodopa related on-off oscillations. One patient withdrew from the study due to off period confusion and hallucinations. A marked deterioration in motor disability occurred in all patients following overnight withdrawal of levodopa and a further mild delayed deterioration was present over a mean withdrawal period of 44 hours. Patients with more severe disease were able to tolerate levodopa withdrawal for a shorter pe...

  11. Association study of a brain-derived neurotrophic factor polymorphism and short-term antidepressant response in major depressive disorders

    Directory of Open Access Journals (Sweden)

    Lung-Cheng Huang

    2008-10-01

    Full Text Available Eugene Lin1,7, Po See Chen2,6,7, Lung-Cheng Huang3,4, Sen-Yen Hsu51Vita Genomics, Inc., Wugu Shiang, Taipei, Taiwan; 2Department of Psychiatry, Hospital and College of Medicine, National Cheng Kung University, Tainan, Taiwan; 3Department of Psychiatry, National Taiwan University Hospital Yun-Lin Branch, Taiwan; 4Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 5Department of Psychiatry, Chi Mei Medical Center, Liouying, Tainan, Taiwan; 6Department of Psychiatry, National Cheng Kung University Hospital, Dou-liou Branch, Yunlin, Taiwan; 7These authors contributed equally to this workAbstract: Major depressive disorder (MDD is one of the most common mental disorders worldwide. Single nucleotide polymorphisms (SNPs can be used in clinical association studies to determine the contribution of genes to drug efficacy. A common SNP in the brain-derived neurotrophic factor (BDNF gene, a methionine (Met substitution for valine (Val at codon 66 (Val66Met, is a candidate SNP for influencing antidepressant treatment outcome. In this study, our goal was to determine the relationship between the Val66Met polymorphism in the BDNF gene and the rapid antidepressant response to venlafaxine in a Taiwanese population with MDD. Overall, the BDNF Val66Met polymorphism was found not to be associated with short-term venlafaxine treatment outcome. However, the BDNF Val66Met polymorphism showed a trend to be associated with rapid venlafaxine treatment response in female patients. Future research with independent replication in large sample sizes is needed to confirm the role of the BDNF Val66Met polymorphism identified in this study.Keywords: antidepressant response, brain-derived neurotrophic factor, major depressive disorder, serotonin and norepinephrine reuptake inhibitor, single nucleotide polymorphisms

  12. Bone marrow-derived mesenchymal stem cells in three-dimensional culture promote neuronal regeneration by neurotrophic protection and immunomodulation.

    Science.gov (United States)

    Han, Sufang; Wang, Bin; Li, Xing; Xiao, Zhifeng; Han, Jin; Zhao, Yannan; Fang, Yongxiang; Yin, Yanyun; Chen, Bing; Dai, Jianwu

    2016-07-01

    Accumulating evidence has revealed three-dimensional (3D) culture could better mimic the stem cell niche in vivo in comparison with conventional two-dimensional (2D) culture. In this study, we found that bone marrow derived mesenchymal stem cells (BMSCs) cultured in 3D collagen scaffold (3D BMSCs) exhibited distinctive features including significantly enhancing neurotrophic factor secretions and reducing macrophage activations challenged by lipopolysaccharide (LPS) in vitro. To further evaluate 3D BMSCs' potential benefits to the regeneration of spinal cord injury (SCI), the 3D and 2D BMSCs were respectively implanted in rat hemisected SCI. Compared with 2D cohort, 3D BMSCs transplantation significantly reduced the expressions of inflammatory cytokines such as TNF-α, IL-1β, and IL-6 at 5 days after transplantation, markedly enhanced axonal regeneration, and promoted motor functional recovery during 8 weeks of observation. When Nocodazole was used to depolymerize the cytoskeleton of 3D BMSCs, the changed expressions of neurotrophic factors and inflammatory cytokines were blunted, at least partially. Thus synergistic effects of neuronal protection and immunomodulation of 3D BMSCs may lead to a better functional recovery of SCI and the underlying mechanism may involve the alteration of their cellular morphology because of 3D culture. This study contributes to a better understanding of the cellular characteristics of 3D BMSCs and provides a novel strategy to promote the repair of the injured spinal cord. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1759-1769, 2016. PMID:26990583

  13. Antimanic-like activity of candesartan in mice: Possible involvement of antioxidant, anti-inflammatory and neurotrophic mechanisms.

    Science.gov (United States)

    de Souza Gomes, Júlia Ariana; de Souza, Greicy Coelho; Berk, Michael; Cavalcante, Lígia Menezes; de Sousa, Francisca Cléa F; Budni, Josiane; de Lucena, David Freitas; Quevedo, João; Carvalho, André F; Macêdo, Danielle

    2015-11-01

    Activation of the brain angiotensin II type 1 receptor (AT1R) triggers pro-oxidant and pro-inflammatory mechanisms which are involved in the neurobiology of bipolar disorder (BD). Candesartan (CDS) is an AT1 receptor antagonist with potential neuroprotective properties. Herein we investigated CDS effects against oxidative, neurotrophic inflammatory and cognitive effects of amphetamine (AMPH)-induced mania. In the reversal protocol adult mice were given AMPH 2 mg/kg i.p. or saline and between days 8 and 14 received CDS 0.1, 0.3 or 1 mg/kg orally, lithium (Li) 47.5 mg/kg i.p., or saline. In the prevention treatment, mice were pretreated with CDS, Li or saline prior to AMPH. Locomotor activity and working memory performance were assessed. Glutathione (GSH), thiobarbituric acid-reactive substance (TBARS) and TNF-α levels were evaluated in the hippocampus (HC) and cerebellar vermis (CV). Brain-derived neurotrophic factor (BDNF) and glycogen synthase kinase 3-beta (GSK-3beta) levels were measured in the HC. CDS and Li prevented and reversed the AMPH-induced increases in locomotor activity. Only CDS prevented and reversed AMPH-induced working memory deficits. CDS prevented AMPH-induced alterations in GSH (HC and CV), TBARS (HC and CV), TNF-α (HC and CV) and BDNF (HC) levels. Li prevented alterations in BDNF and phospho-Ser9-GSK3beta. CDS reversed AMPH-induced alterations in GSH (HC and CV), TBARS (HC), TNF-α (CV) and BDNF levels. Li reversed AMPH-induced alterations in TNF-α (HC and CV) and BDNF (HC) levels. CDS is effective in reversing and preventing AMPH-induced behavioral and biochemical alterations, providing a rationale for the design of clinical trials investigating CDS׳s possible therapeutic effects. PMID:26321203

  14. Peripheral brain-derived neurotrophic factor is related to cardiovascular risk factors in active and inactive elderly men.

    Science.gov (United States)

    Zembron-Lacny, A; Dziubek, W; Rynkiewicz, M; Morawin, B; Woźniewski, M

    2016-06-20

    Regular exercise plays an important preventive and therapeutic role in heart and vascular diseases, and beneficially affects brain function. In blood, the effects of exercise appear to be very complex and could include protection of vascular endothelial cells via neurotrophic factors and decreased oxidative stress. The purpose of this study was to identify the age-related changes in peripheral brain-derived neurotrophic factor (BDNF) and its relationship to oxidative damage and conventional cardiovascular disease (CVD) biomarkers, such as atherogenic index, C-reactive protein (hsCRP) and oxidized LDL (oxLDL), in active and inactive men. Seventeen elderly males (61-80 years) and 17 young males (20-24 years) participated in this study. According to the 6-min Åstrand-Rhyming bike test, the subjects were classified into active and inactive groups. The young and elderly active men had a significantly better lipoprotein profile and antioxidant status, as well as reduced oxidative damage and inflammatory state. The active young and elderly men had significantly higher plasma BDNF levels compared to their inactive peers. BDNF was correlated with VO2max (r=0.765, P<0.001). In addition, we observed a significant inverse correlation of BDNF with atherogenic index (TC/HDL), hsCRP and oxLDL. The findings demonstrate that a high level of cardiorespiratory fitness reflected in VO2max was associated with a higher level of circulating BDNF, which in turn was related to common CVD risk factors and oxidative damage markers in young and elderly men. PMID:27332774

  15. Peripheral brain-derived neurotrophic factor is related to cardiovascular risk factors in active and inactive elderly men

    Directory of Open Access Journals (Sweden)

    A. Zembron-Lacny

    2016-01-01

    Full Text Available Regular exercise plays an important preventive and therapeutic role in heart and vascular diseases, and beneficially affects brain function. In blood, the effects of exercise appear to be very complex and could include protection of vascular endothelial cells via neurotrophic factors and decreased oxidative stress. The purpose of this study was to identify the age-related changes in peripheral brain-derived neurotrophic factor (BDNF and its relationship to oxidative damage and conventional cardiovascular disease (CVD biomarkers, such as atherogenic index, C-reactive protein (hsCRP and oxidized LDL (oxLDL, in active and inactive men. Seventeen elderly males (61-80 years and 17 young males (20-24 years participated in this study. According to the 6-min Åstrand-Rhyming bike test, the subjects were classified into active and inactive groups. The young and elderly active men had a significantly better lipoprotein profile and antioxidant status, as well as reduced oxidative damage and inflammatory state. The active young and elderly men had significantly higher plasma BDNF levels compared to their inactive peers. BDNF was correlated with VO2max (r=0.765, P<0.001. In addition, we observed a significant inverse correlation of BDNF with atherogenic index (TC/HDL, hsCRP and oxLDL. The findings demonstrate that a high level of cardiorespiratory fitness reflected in VO2max was associated with a higher level of circulating BDNF, which in turn was related to common CVD risk factors and oxidative damage markers in young and elderly men.

  16. Effect of intensive epilimnetic withdrawal on phytoplankton community in a (subtropical deep reservoir

    Directory of Open Access Journals (Sweden)

    Man Zhang

    2013-10-01

    Full Text Available Withdrawal is an important process in reservoir hydrodynamics, removing phytoplankton with flushed water. Zooplankton,the grazers of phytoplankton, having longer generation times, are even more susceptible than phytoplankton to flushing loss. Therefore phytoplankton are affected not only by abiotic conditions linked to hydrodynamics but also by zooplankton due to weakened grazing pressure. During the Asian Games (November 12-27, 2010 in Guangzhou, China, two intensive epilimnetic withdrawals were conducted in Liuxihe, a deep canyon-shaped reservoir. To examine the influence of the intensive epilimnetic withdrawals on the phytoplankton community, a seven-week field observation and a hydrodynamic simulation were carried out. The observation was divided in two stages: stage 1 represented partial surface vertical mixing period, and stage 2 represented intensive epilimnetic withdrawal period. It was found that phytoplankton abundance and biomass declined with water temperature and partial surface vertical mixing in stage 1. However, the intensive epilimnetic withdrawal reversed this decreasing trend and increased phytoplankton biomass and abundance in stage 2. Phytoplankton showed a higher rate of composition change in stage 2. A numerical model (DYRESM-CAEDYM simulated scenarios with and without epilimnetic withdrawal to test their effects on abiotic factors (water temperature, suspended sediment and soluble reactive phosphorus for phytoplankton. The results showed no obvious difference in the abiotic factors between the two scenarios during stage 2. We therefore suggested that the abiotic factors in the water column were probably driven by a seasonal pattern, not by epilimnetic withdrawal. It is likely that the intensive epilimnetic withdrawal could remove large crustaceans. The reduced grazing pressure probably explained the increase of phytoplankton biomass and abundance after the withdrawal. Thus, we suggest that reservoir operation should pay

  17. A human laboratory study investigating the effects of quetiapine on marijuana withdrawal and relapse in daily marijuana smokers

    OpenAIRE

    Cooper, Ziva D.; Foltin, Richard W.; Hart, Carl L.; Vosburg, Suzanne K; Comer, Sandra D.; Haney, Margaret

    2012-01-01

    Marijuana withdrawal contributes to the high relapse rates in individuals seeking treatment for marijuana-use disorders. Quetiapine, an atypical antipsychotic, reduces characteristic symptoms of marijuana withdrawal in a variety of psychiatric conditions including mood lability, sleep disruption, and anorexia. This human laboratory study investigated the effectiveness of quetiapine to decrease marijuana withdrawal and relapse to marijuana use in nontreatment seeking marijuana smokers. Volunte...

  18. Ecuador to withdraw from OPEC; group to maintain present flow

    International Nuclear Information System (INIS)

    This paper reports that the Organization of Petroleum Exporting Countries, which has agreed to maintain its present combined production of 24.2 million b/d of oil in the fourth quarter, will soon see the first pullout of a member. The 13 member group will shrink to 12, probably in November, when Ecuador withdraws. Ecuador President Sixto Duran Ballen issued notice of the pullout Sept. 17, a little more than 1 month after he took office. Ecuador, strapped for cash, wants to save OPEC membership dues reported to be $2-3 million/year. It plans to remain an associate member, although it wasn't immediately clear what that means. No other countries are regarded as associate members

  19. The Director General withdraws its proposal to Council

    CERN Document Server

    Staff Association

    2015-01-01

    Dear Colleagues, The Staff Association and the CERN-ESO Pensioners’ Association want to let you know that they are deeply worried. Decisions taken by CERN Council at its latest closed sessions attracted our attention.  Since these sessions took place behind closed doors, without the presence of the Association, we had to investigate, crossing several sources of information. Result: The attitude of some delegations shocked us and fills us with indignation. Let us recall the facts: the Management's action plan to compensate for the soaring Swiss franc against the euro, did not reach a consensus among the Member States, forcing Management to withdraw it. Strange, when one considers that CERN was the only international organization based in Switzerland to come forward with such an initiative. On the contrary, Council is once again using the Pension Fund as a “scape goat”. It should be recalled here, that past decisions by CERN Council on the Fund's manag...

  20. Binge ethanol withdrawal: Effects on post-withdrawal ethanol intake, glutamate-glutamine cycle and monoamine tissue content in P rat model.

    Science.gov (United States)

    Das, Sujan C; Althobaiti, Yusuf S; Alshehri, Fahad S; Sari, Youssef

    2016-04-15

    Alcohol withdrawal syndrome (AWS) is a medical emergency situation which appears after abrupt cessation of ethanol intake. Decreased GABA-A function and increased glutamate function are known to exist in the AWS. However, the involvement of glutamate transporters in the context of AWS requires further investigation. In this study, we used a model of ethanol withdrawal involving abrupt cessation of binge ethanol administration (4g/kg/gavage three times a day for three days) using male alcohol-preferring (P) rats. After 48h of withdrawal, P rats were re-exposed to voluntary ethanol intake. The amount of ethanol consumed was measured during post-withdrawal phase. In addition, the expression of GLT-1, GLAST and xCT were determined in both medial prefrontal cortex (mPFC) and nucleus accumbens (NAc). We also measured glutamine synthetase (GS) activity, and the tissue content of glutamate, glutamine, dopamine and serotonin in both mPFC and NAc. We found that binge ethanol withdrawal escalated post-withdrawal ethanol intake, which was associated with downregulation of GLT-1 expression in both mPFC and NAc. The expression of GLAST and xCT were unchanged in the ethanol-withdrawal (EW) group compared to control group. Tissue content of glutamate was significantly lower in both mPFC and NAc, whereas tissue content of glutamine was higher in mPFC but unchanged in NAc in the EW group compared to control group. The GS activity was unchanged in both mPFC and NAc. The tissue content of DA was significantly lower in both mPFC and NAc, whereas tissue content of serotonin was unchanged in both mPFC and NAc. These findings provide important information of the critical role of GLT-1 in context of AWS. PMID:26821293