Inestrosa Nibaldo C
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.
Clatterbuck, R E; Price, D L; Koliatsos, V E
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...
Gian David Greenberg
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.
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
Sun, Wei-Lun; Eisenstein, Sarah A.; Zelek-Molik, Agnieszka; McGinty, Jacqueline F.
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...
Mitchelmore, Cathy; Gede, Lene
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...
Mitchelmore, Cathy; Gede, Lene
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...
El-Daly, Ahmed; Snyderman, Carl H.
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.
... 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 ...
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 ...
... 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 ...
Carroll, P.; Sendtner, M.; Meyer, Michael; Thoenen, Hans
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...
... 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...
Deister, C.; Schmidt, C. E.
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.
Trajkovska, Viktorija; Klein, Anders Bue; Vinberg, Maj;
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...
Alele, Paul E.; Devaud, Leslie L.
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...
ANCA NICOLETA GHEORGHE; CAMELIA SPASICI
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...
Shapiro, L; Zhang, X. X.; Rupp, R G; Wolff, S. M.; Dinarello, C A
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...
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.
Kimura, Ikuo; Nakayama, Yoshiaki; Zhao, Ying; Konishi, Morichika; Itoh, Nobuyuki
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...
Monte-Secades, R; Rabuñal-Rey, R; Guerrero-Sande, H
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
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.
Christopher R.Hansebout; Caixin Su; Kiran Reddy; Donald Zhang; Cai Jiang; Michel P.Rathbone; Shucui Jiang
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.
Renan B. Domingues
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.
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.
Xu, Baoji; Xie, Xiangyang
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
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
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.
ANCA NICOLETA GHEORGHE
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.
O. A. Gromova
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.
O. A. Gromova; A. V. Pronin; I. Yu. Torshin; A. G. Kalacheva; T. R. Grishina
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.
Sendtner, Michael; Arakawa, Yoshihiro; Stöckli, Kurt A.; Kreutzberg, Georg W.; Thoenen, Hans
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...
Howard C Becker
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...
O. A. Gromova
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.
Peregud, Danil I; Yakovlev, Alexander A; Stepanichev, Mikhail Yu; Onufriev, Mikhail V; Panchenko, Leonid F; Gulyaeva, Natalia V
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
Jared E Knickelbein
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
Serafini, Gianluca; Hayley, Shawn; Pompili, Maurizio; Dwivedi, Yogesh; Brahmachari, Goutam; Girardi, Paolo; Amore, Mario
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
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.
... 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....
Piper, Megan E
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
Nakamura, Masaya; Tsuji, Osahiko; BREGMAN, BARBARA S.; Toyama, Yoshiaki; Okano, Hideyuki
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...
Zimmerman, Ryan D; Swider, Brian W; Woo, Sang Eun; Allen, David G
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
Nezihat Rana Disel
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.
Henderson, J T; Seniuk, N A; Richardson, P.M.; Gauldie, J; Roder, J. C.
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...
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
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...
Y S Prakash; Richard J Martin
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...
McGinty, Jacqueline F.; Whitfield, Timothy W.; Berglind, William J.
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...
Mikhail Stepanichev; Nikolay N Dygalo; Grigory Grigoryan; Shishkina, Galina T.; Natalia Gulyaeva
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...
Berl, Kimberly; Collins, Michelle L.; Melson, Jo; Mooney, Ruth; Muffley, Cheryl; Wright-Glover, Angela
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...
Shu, Xiaoliang; Zhang, Yongsheng; Xu, Han; Kang, Kai; Cai, Donglian
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 ...
Kuralay, Filiz; ÇAKIRLI, Başak BİNGOL; GENÇ, Şermin
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 _...
Amitai, Nurith; Liu, Jian; Schulteis, Gery
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...
Jung, Marianna E
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
Nedic, Gordana; Perkovic, Matea Nikolac; Sviglin, Korona Nenadic; Muck-Seler, Dorotea; Borovecki, Fran; Pivac, Nela
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
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.)
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
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.
Kuhlmann, Tanja; Remington, Leah; Cognet, Isabelle;
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...
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
Jôice Dias Corrêa
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.
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
Carlos Garriga; Chao Gu
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...
Vandrey, Ryan; Budney, Alan J.; Kamon, Jody L.; Stanger, Catherine
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...
... 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...
Dagø, Lone; Peters, Dan; Meyer, Morten;
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...
Berl, Kimberly; Collins, Michelle L.; Melson, Jo; Mooney, Ruth; Muffley, Cheryl; Wright-Glover, Angela
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
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.
Shu, Xiaoliang; Zhang, Yongsheng; Xu, Han; Kang, Kai; Cai, Donglian
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
Xiaoliang Shu; Yongsheng Zhang; Han Xu; Kai Kang; Donglian Cai
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.
Brust, John C M
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
... 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...
..., 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....
Munkholm, K; Vinberg, M; Kessing, L V
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...
Krabbe, K. S.; Nielsen, A. R.; Krogh-Madsen, R.;
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...
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.
Alper, K R; Lotsof, H S; Frenken, G M; Luciano, D J; Bastiaans, J
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
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
Sanjiang Feng; Minghua Zhuang; Rui Wu
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.
Haixia Ding; Meijiang Feng; Xinsheng Ding
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.
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
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.
Kim, Daniel H.; Jahng, Tae-Ahn
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...
Feng Zhang; Yan-Ying Wang; Hang Liu; Yuan-Fu Lu; Qin Wu; Jie Liu; Jing-Shan Shi
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...
Du, Jie; Gao, Xiaoqing; Deng, Li; Chang, Nengbin; Xiong, Huailin; Zheng, Yu
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...
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
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...
Ito, Yasuhiro; Wiese, Stefan; Funk, Natalja; Chittka, Alexandra; Rossoll, Wilfried; Bömmel, Heike; Watabe, Kazuhiko; Wegner, Michael; Sendtner, Michael
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...
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
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...
Hayakawa, Kazhuhide; Navaratna, Deepti; Guo, Shu-Zhen; WANG, XIAOYING; Gerhardinger, Chiara; Lo, Eng H.
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...
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...
Hernandez-Morato, Ignacio; Sharma, Sansar; Pitman, Michael J
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
Philibin, Scott D.; Cameron, Andy J.; Metten, Pamela; Crabbe, John C.
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...
... 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...
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...
Rothwell, Patrick E.; Gewirtz, Jonathan C.; Thomas, Mark J
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....
Michael H. Rothkopf
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...
Sieving, Paul A.; Caruso, Rafael C.; Tao, Weng; Coleman, Hanna R.; Thompson, Darby J. S.; Fullmer, Keri R.; Bush, Ronald A.
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...
Sachdeva, Ankur; Choudhary, Mona; Chandra, Mina
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
Rosas-Vargas, Haydeé; Martínez-Ezquerro, José Darío; Bienvenu, Thierry
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
McGinty, Jacqueline F.; Whitfield, Timothy W.; Berglind, William J.
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
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
Reeves, Roy R; Burke, Randy S
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
McDonald, Robert V; Siegel, Shepard
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
Du, Fang; Li, Rui; Huang, Yuangui; Li, Xuping; Le, Weidong
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
Jurič, Damijana M; Šuput, Dušan; Brvar, Miran
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
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.
Valk, G D; Kappelle, A C; Tjon-A-Tsien, A M; Bravenboer, B; Bakker, K; Michels, R P; Groenhout, C M; Bertelsmann, F W
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
Perry, Elizabeth C
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
Dafny, N; Wagle, V G; Drath, D B
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
Itkonen, Jaakko M; Urtti, Arto; Bird, Louise E.; Sarkhel, Sanjay
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...
Sherry L. Xu
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.
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
Hellman, M.; Arumae, U.; Yu, L.-y.; Lindholm, P.; Peranen, J.; Saarma, M.; Permi, P. (Perttu)
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...
... 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...
... 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...
Liu, Wei; Han, Xueyao; Zhou, Xianghai; Zhang, Simin; Cai, Xiaoling; Zhang, Lihua; Li, Yufeng; Li, Meng; Gong, Siqian; Ji, Linong
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
Aguirre, Claudia; Madrid, Jillian; Leventhal, Adam M.
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...
Berl, Kimberly; Collins, Michelle L; Melson, Jo; Mooney, Ruth; Muffley, Cheryl; Wright-Glover, Angela
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
... 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...
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…
Pritchard, Duncan; Hoerger, Marguerite; Dyer, Tim; Graham, Nicola; Penney, Heather; Mace, F. Charles
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…
Lee, Youngjin; Lee, Seunghee; Roh, Yongrae
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
... 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...
Chen, X; Li, Y; Kline, A E; Dixon, C E; Zafonte, R D; Wagner, A K
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
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
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
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
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
Hasselbalch, Jacob; Knorr, U; Bennike, B;
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....
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...
Zhang, Yanru; Zhang, Hui; Katiella, Kaka; Huang, Wenhua
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
Yanru Zhang; Hui Zhang; Kaka Katiella; Wenhua Huang
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.
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
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 ...
Qun Zhao; Zhi-yue Li; Ze-peng Zhang; Zhou-yun Mo; Shi-jie Chen; Si-yu Xiang; Qing-shan Zhang; Min Xue
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.
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.
Yudan Lv; Jiqing Qiu; Zan Wang; Li Cui; Hongmei Meng; Weihong Lin
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.
Williams, D A; Thorn, B E
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
Mirijello, Antonio; D'Angelo, Cristina; Ferrulli, Anna; Vassallo, Gabriele; Antonelli, Mariangela; Caputo, Fabio; Leggio, Lorenzo; Gasbarrini, Antonio; Addolorato, Giovanni
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
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
Ozog, Mark A.; Bernier, Suzanne M; Bates, Dave C.; Chatterjee, Bishwanath; Lo, Cecilia W.; Naus, Christian C.G.
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...
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.
Kattimani, Shivanand; Bharadwaj, Balaji
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
Wang, Shuju; Fang, Jianqiao; Ma, Jun; Wang, Yanchun; Liang, Shaorong; Zhou, Dan; Sun, Guojie
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
Leake, Patricia A.; Hradek, Gary T.; Hetherington, Alexander M.; Stakhovskaya, Olga
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...
Wang, Shuju; Fang, Jianqiao; Ma, Jun; Wang, Yanchun; Liang, Shaorong; Zhou, Dan; Sun, Guojie
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...
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...
Ejstrup, Rasmus; Dornonville de la Cour, Morten; Kyhn, Maria Voss;
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....
Paulo Roberto Correia; Aline Pansani; Felipe Machado; Marilia Andrade; Antonio Carlos da Silva; Fulvio Alexandre Scorza; Esper Abrão Cavalheiro; Ricardo Mario Arida
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...
Pei Jiang; Rui-Li Dang; Huan-De Li; Li-Hong Zhang; Wen-Ye Zhu; Ying Xue; Mi-Mi Tang
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...
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.
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.
Paulo Roberto Correia
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.
Changwei Song; Shiqiang Fang; Gang Lv; Xifan Mei
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.
Jinhua Fu; Yingjin Zhang; Renrong Wu; Yingjun Zheng; Xianghui Zhang; Mei Yang; Jingping Zhao; Yong Liu
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.
Paik, Ahyoung; Oh, Daeyoung; Kim, Daeho
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...
Sulmasy, D P; Sugarman, J
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...
Martinowich Keri; Schloesser Robert J; Jimenez Dennisse V; Weinberger Daniel R; Lu Bai
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...
Suzuki, Go; Tokuno, Shinichi; Nibuya, Masashi; Ishida, Toru; Yamamoto, Tetsuo; Mukai, Yasuo; Mitani, Keiji; Tsumatori, Gentaro; Scott, Daniel; Shimizu, Kunio
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...
Doppler, Edith; Rockenstein, Edward; Ubhi, Kiren; Inglis, Chandra; Mante, Michael; Adame, Anthony; Crews, Leslie; Hitzl, Monika; Moessler, Herbert; Masliah, Eliezer
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...
Bartels, Jess; Andreasen, Dinal; Ehirim, Princewill; Mao, Hui; Seibert, Steven; Wright, E. Joe; Kennedy, Philip
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...
Greenwood, Benjamin N.; Strong, Paul V; Foley, Teresa E.; Thompson, Robert; Fleshner, Monika
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...
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
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...
Hartman, William; Helan, Martin; Smelter, Dan; Sathish, Venkatachalem; Thompson, Michael; Pabelick, Christina M.; Johnson, Bruce; Y S Prakash
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...
Wang, Qiong; Shao, Feng; Wang, Weiwen
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...
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
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]...
Akahori, Yoichiro; Takamoto, Norio; Masumoto,Akio; Inoue,Seiji; Nakatsukasa, Hideki; MASUYAMA, HISASHI; Hiramatsu,Yuji
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...
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.
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...
Lee, Byoung-Seung; Choi, Jae-Youn; Cha, Jung-Ho
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 ...
Lo, David; SunRhodes, Neil; Watt, John A.
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...
Koh, Shay-Whey M.; Guo, Yan; Bernstein, Steve L.; Waschek, James A.; Liu, Xiuhuai; Symes, Aviva J
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...
McDonald, N. Q.; Panayotatos, N; Hendrickson, W A
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...
Beurrier, Corinne; Faideau, Mathilde; Bennouar, Khaled-Ezaheir; Escartin, Carole; Kerkerian-Le Goff, Lydia; Bonvento, Gilles; Gubellini, Paolo
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...
Sendtner, Michael; Stöckli, Kurt A.; Thoenen, Hans; Schmalbruch, H.; Carroll, P.; Kreutzberg, Georg W.
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...
Ferrell Robert; Hurley Ben; Roth Stephen; Stashuk Daniel; Ling Shari; Conwit Robin A; Metter E Jeffrey
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...
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
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 ...
Li, Rong; Wen, Rong; Banzon, Tina; Maminishkis, Arvydas; Miller, Sheldon S.
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...
T. Hagg; Varon, S
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...
L. Esakowit; M. Gupta; Lascaratos, G.; A. Syrogiannis
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...
Xinfeng Liu; Gelin Xu; Zhaoyao Chen; Tingting Lu; Ning Wei; Juehua Zhu; Yongjun Jiang
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...
Clark, Catharine G.; Hasser, Eileen M.; Kunze, Diana L.; Katz, David M.; Kline, David D.
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...
Zhang, Yanru; Zhang, Hui; Katiella, Kaka; Huang, Wenhua
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...
Rini Rossanti; Dida Akhmad Gurnida; Eddy Fadlyana
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,...
Rini Rossanti; Dida Akhmad Gurnida; Eddy Fadlyana
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...
Altar, C A; Boylan, C B; Jackson, C; Hershenson, S; Miller, J.; Wiegand, S. J.; Lindsay, R M; Hyman, C.
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...
Yunita Fediani; Masayu Rita Dewi; Muhammad Irfannuddin; Masagus Irsan Saleh; Safri Dhaini
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...
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
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)...
Song, Changwei; Fang, Shiqiang; Gang LV; Mei, Xifan
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...
Xiao-dong Wang; Heng-zhu Zhang; Zhi-gang Gong; Xi-gang Yan; Qing Lan; Qiang Huang
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...
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...
Morel, Gustavo R.; Sosa, Yolanda E.; Bellini, Maria J.; Carri, Nestor G.; Rodriguez, Silvia S.; Bohn, Martha C.; Goya, Rodolfo G.
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...
Farshid Saadat; Maryam Kosha; Ali Amiry; Gholamreza Torabi
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 ...
Naftali Raz; Dahle, Cheryl L.; Rodrigue, Karen M.; Kennedy, Kristen M.; Land, Susan J.; Jacobs, Bradley S.
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...
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.
Glat, Micaela Johanna; Benninger, Felix; Barhum, Yael; Ben-Zur, Tali; Kogan, Elena; Steiner, Israel; Yaffe, David; Offen, Daniel
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
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.
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
J. Karzis; E.F. Donkin; I.M. Petzer
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...
... 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,...
Sampath Kumar Venkatesh
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.
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.
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...
Greenberg, Gian D.; Laman-Maharg, Abigail; Campi, Katharine L.; Voigt, Heather; Orr, Veronica N.; Schaal, Leslie; Trainor, Brian C.
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....
Gian David Greenberg; Campi, Katharine L.
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....
Greenberg, GD; Laman-Maharg, A; Campi, KL; Voigt, H; Orr, VN; Schaal, L; Trainor, BC
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....
Changsheng Wang; Jianhua Lin; Chaoyang Wu; Rongsheng Chen
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.
Hashikawa, Naoya; Ogawa, Takumi; Sakamoto, Yusuke; Ogawa, Mami; Matsuo, Yumi; Zamami, Yoshito; Hashikawa-Hobara, Narumi
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
Jana, Arundhati; Modi, Khushbu K; Roy, Avik; Anderson, John A; van Breemen, Richard B; Pahan, Kalipada
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
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
... 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...
... 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...
... 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...
Etherington, J. M.
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.
... 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...
... 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...
... 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...
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.
Irfanali R. Kugasia
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.
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.
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.
Chohan, Muhammad Omar; Bragina, Olga; Kazim, Syed Faraz; Statom, Gloria; Baazaoui, Narjes; Bragin, Denis; Iqbal, Khalid; Nemoto, Edwin; Yonas, Howard
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
Mueller, Karsten; Möller, Harald E.; Horstmann, Annette; Busse, Franziska; Lepsien, Jöran; Blüher, Matthias; Stumvoll, Michael; Villringer, Arno; Pleger, Burkhard
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
Pinheiro, Vera Lúcia Margarido
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...
Heymanns, J.; Unsicker, K
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...
S. Saadat; Sendtner, Michael; H. Rohrer(Universität Mainz, Germany)
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....
Sendtner, Michael; Kreutzberg, Georg W.; Thoenen, Hans
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...
Klein, Anders B; Jennum, Poul; Knudsen, Stine;
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...
Foldvari, Marianna; Chen, Ding Wen
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.
Khor, Beng-Siang; Jamil, Mohd Fadzly Amar; Adenan, Mohamad Ilham; Shu-Chien, Alexander Chong
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
Aguirre, Claudia G; Madrid, Jillian; Leventhal, Adam M
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
Purser, Matthew J.; Dalvi, Prasad S.; Wang, Zi C.; Belsham, Denise D.
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...
... 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...
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.
Munkholm, Klaus; Pedersen, Bente Klarlund; Kessing, Lars Vedel;
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...
Lippoldt, Erika K; Ongun, Serra; Kusaka, Geoffrey K; McKemy, David D
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
Vega, Sandra Rojas; Kleinert, Jens; Sulprizio, Marion; Hollmann, Wildor; Bloch, Wilhelm; Strüder, Heiko K
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
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.
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.
Martin, Jean Luc
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.
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.
Phelan, P J
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.
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...
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...
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
Sriram Ganeshalingam; Epa Dhanesha; Rodrigo Chaturaka; Jayasinghe Saroj
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...
Berigan, Timothy R.; Harazin, Jeffrey S.
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...
Jensen, Hanne Irene; Ammentorp, Jette; Erlandsen, Mogens; Ording, Helle
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)....
Shekarchizadeh Hajar; Khami Mohammad R; Mohebbi Simin Z; Virtanen Jorma I
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...
Pizon, Anthony F.; LoVecchio, Frank
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...
Khor, Beng-Siang; Amar Jamil, Mohd Fadzly; Adenan, Mohamad Ilham; Chong Shu-Chien, Alexander
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...
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 ...
Lounis, Yacine; Bonnet-Zamponi, Dominique; Pautas, Éric; Gaubert-Dahan, Marie-Line
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
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. ...
Cook, Jessica W; Piper, Megan E; Leventhal, Adam M; Schlam, Tanya R; Fiore, Michael C; Baker, Timothy B
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
Piñeiro, Bárbara; López-Durán, Ana; Fernández del Río, Elena; Martínez, Úrsula; Brandon, Thomas H; Becoña, Elisardo
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
Gambolati, Giuseppe; Teatini, Pietro
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.