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Sample records for excitotoxicity inflicts paranodal

  1. Molecular architecture of myelinated nerve fibers: leaky paranodal junctions and paranodal dysmyelination.

    Science.gov (United States)

    Rosenbluth, Jack; Mierzwa, Amanda; Shroff, Seema

    2013-12-01

    Myelinated nerve fibers have evolved to optimize signal propagation. Each myelin segment is attached to the axon by the unique paranodal axoglial junction (PNJ), a highly complex structure that serves to define axonal ion channel domains and to direct nodal action currents through adjacent nodes. Surprisingly, this junction does not entirely seal the paranodal myelin sheath to the axon and thus does not entirely isolate the perinodal space from the internodal periaxonal space. Rather the paranode is penetrated by extracellular pathways between the myelin sheath and the axolemma for movement of molecules and the flow of current to and from the internodal axon. This review summarizes past and current studies demonstrating these pathways and considers what functional roles they subserve. In addition, modern genetic engineering methods permit modification of individual PNJ constituents, which provides an opportunity to define their specific functions. One component in particular, the transverse bands, plays a key role in maintaining the structure and function of the PNJ. Loss of transverse bands results not in frank demyelination but rather in subtle dysmyelination, which causes significant functional impairment. The consequences of such subtle defects in the PNJ are considered along with the relevance of these studies to human diseases of myelin.

  2. Paranodal reorganization results in the depletion of transverse bands in the aged central nervous system

    Science.gov (United States)

    Shepherd, Mark N.; Pomicter, Anthony D.; Velazco, Cristine S.; Henderson, Scott C.; Dupree, Jeffrey L.

    2012-01-01

    Paranodal axo-glial junctional complexes anchor the myelin sheath to the axon and breakdown of these complexes presumably facilitates demyelination. Myelin deterioration is also prominent in the aging central nervous system (CNS); however, the stability of the paranodal complexes in the aged CNS has not been examined. Here, we show that transverse bands, prominent components of paranodal junctions, are significantly reduced in the aged CNS; however, the number of paired clusters of both myelin and axonal paranodal proteins is not altered. Ultrastructural analyses also reveal that thicker myelin sheaths display a “piling” of paranodal loops, the cytoplasm-containing sacs that demarcate the paranode. Loops involved in piling are observed throughout the paranode and are not limited to loops positioned in either the nodal- or juxtanodal-most regions. Here, we propose that as myelination continues, previously anchored loops lose their transverse bands and recede away from the axolemma. Newly juxtaposed loops then lose their transverse bands, move laterally to fill in the gap left by the receded loops and finally reform their transverse bands. This paranodal reorganization results in conservation of paranodal length, which may be important in maintaining ion channel spacing and axonal function. Furthermore, we propose that transverse band reformation is less efficient in the aged CNS, resulting in the significant reduction of these junctional components. Although demyelination was not observed, we propose that loss of transverse bands facilitates myelin degeneration and may predispose the aged CNS to a poorer prognosis following a secondary insult. PMID:20888080

  3. Subtle paranodal injury slows impulse conduction in a mathematical model of myelinated axons.

    Directory of Open Access Journals (Sweden)

    Charles F Babbs

    Full Text Available This study explores in detail the functional consequences of subtle retraction and detachment of myelin around the nodes of Ranvier following mild-to-moderate crush or stretch mediated injury. An equivalent electrical circuit model for a series of equally spaced nodes of Ranvier was created incorporating extracellular and axonal resistances, paranodal resistances, nodal capacitances, time varying sodium and potassium currents, and realistic resting and threshold membrane potentials in a myelinated axon segment of 21 successive nodes. Differential equations describing membrane potentials at each nodal region were solved numerically. Subtle injury was simulated by increasing the width of exposed nodal membrane in nodes 8 through 20 of the model. Such injury diminishes action potential amplitude and slows conduction velocity from 19.1 m/sec in the normal region to 7.8 m/sec in the crushed region. Detachment of paranodal myelin, exposing juxtaparanodal potassium channels, decreases conduction velocity further to 6.6 m/sec, an effect that is partially reversible with potassium ion channel blockade. Conduction velocity decreases as node width increases or as paranodal resistance falls. The calculated changes in conduction velocity with subtle paranodal injury agree with experimental observations. Nodes of Ranvier are highly effective but somewhat fragile devices for increasing nerve conduction velocity and decreasing reaction time in vertebrate animals. Their fundamental design limitation is that even small mechanical retractions of myelin from very narrow nodes or slight loosening of paranodal myelin, which are difficult to notice at the light microscopic level of observation, can cause large changes in myelinated nerve conduction velocity.

  4. Pregabalin attenuates excitotoxicity in diabetes.

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    Chin-Wei Huang

    Full Text Available Diabetes can exacerbate seizures and worsen seizure-related brain damage. In the present study, we aimed to determine whether the standard antiepileptic drug pregabalin (PGB protects against pilocarpine-induced seizures and excitotoxicity in diabetes. Adult male Sprague-Dawley rats were divided into either a streptozotocin (STZ-induced diabetes group or a normal saline (NS group. Both groups were further divided into subgroups that were treated intravenously with either PGB (15 mg/kg or a vehicle; all groups were treated with subcutaneous pilocarpine (60 mg/kg to induce seizures. To evaluate spontaneous recurrent seizures (SRS, PGB-pretreated rats were fed rat chow containing oral PGB (450 mg for 28 consecutive days; vehicle-pretreated rats were fed regular chow. SRS frequency was monitored for 2 weeks from post-status epilepticus day 15. We evaluated both acute neuronal loss and chronic mossy fiber sprouting in the CA3 area. In addition, we performed patch clamp recordings to study evoked excitatory postsynaptic currents (eEPSCs in hippocampal CA1 neurons for both vehicle-treated rats with SRS. Finally, we used an RNA interference knockdown method for Kir6.2 in a hippocampal cell line to evaluate PGB's effects in the presence of high-dose ATP. We found that compared to vehicle-treated rats, PGB-treated rats showed less severe acute seizure activity, reduced acute neuronal loss, and chronic mossy fiber sprouting. In the vehicle-treated STZ rats, eEPSC amplitude was significantly lower after PGB administration, but glibenclamide reversed this effect. The RNA interference study confirmed that PGB could counteract the ATP-sensitive potassium channel (KATP-closing effect of high-dose ATP. By opening KATP, PGB protects against neuronal excitotoxicity, and is therefore a potential antiepileptogenic in diabetes. These findings might help develop a clinical algorithm for treating patients with epilepsy and comorbid metabolic disorders.

  5. Paranode Abnormalities and Oxidative Stress in Optic Nerve Vulnerable to Secondary Degeneration: Modulation by 670 nm Light Treatment.

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    Charis R Szymanski

    Full Text Available Secondary degeneration of nerve tissue adjacent to a traumatic injury results in further loss of neurons, glia and function, via mechanisms that may involve oxidative stress. However, changes in indicators of oxidative stress have not yet been demonstrated in oligodendrocytes vulnerable to secondary degeneration in vivo. We show increases in the oxidative stress indicator carboxymethyl lysine at days 1 and 3 after injury in oligodendrocytes vulnerable to secondary degeneration. Dihydroethidium staining for superoxide is reduced, indicating endogenous control of this particular reactive species after injury. Concurrently, node of Ranvier/paranode complexes are altered, with significant lengthening of the paranodal gap and paranode as well as paranode disorganisation. Therapeutic administration of 670 nm light is thought to improve oxidative metabolism via mechanisms that may include increased activity of cytochrome c oxidase. Here, we show that light at 670 nm, delivered for 30 minutes per day, results in in vivo increases in cytochrome c oxidase activity co-localised with oligodendrocytes. Short term (1 day 670 nm light treatment is associated with reductions in reactive species at the injury site. In optic nerve vulnerable to secondary degeneration superoxide in oligodendrocytes is reduced relative to handling controls, and is associated with reduced paranode abnormalities. Long term (3 month administration of 670 nm light preserves retinal ganglion cells vulnerable to secondary degeneration and maintains visual function, as assessed by the optokinetic nystagmus visual reflex. Light at a wavelength of 670 nm may serve as a therapeutic intervention for treatment of secondary degeneration following neurotrauma.

  6. Protective effect of parvalbumin on excitotoxic motor neuron death

    DEFF Research Database (Denmark)

    Van den Bosch, L.; Schwaller, B.; Vleminckx, V.

    2002-01-01

    Amyotrophic lateral sclerosis, ALS, AMPA receptor, calcium-binding proteins, calcium buffering, excitotoxity, kainic acid, motor neuron, parvalbumin......Amyotrophic lateral sclerosis, ALS, AMPA receptor, calcium-binding proteins, calcium buffering, excitotoxity, kainic acid, motor neuron, parvalbumin...

  7. A role for myelin-associated peroxisomes in maintaining paranodal loops and axonal integrity.

    Science.gov (United States)

    Kassmann, Celia M; Quintes, Susanne; Rietdorf, Jens; Möbius, Wiebke; Sereda, Michael Werner; Nientiedt, Tobias; Saher, Gesine; Baes, Myriam; Nave, Klaus-Armin

    2011-07-21

    Demyelinating diseases of the nervous system cause axon loss but the underlying mechanisms are not well understood. Here we show by confocal and electron microscopy that in myelin-forming glia peroxisomes are associated with myelin membranes. When peroxisome biogenesis is experimentally perturbed in Pex5 conditional mouse mutants, myelination by Schwann cells appears initially normal. However, in nerves of older mice paranodal loops become physically unstable and develop swellings filled with vesicles and electron-dense material. This novel model of a demyelinating neuropathy demonstrates that peroxisomes serve an important function in the peripheral myelin compartment, required for long-term axonal integrity. Copyright © 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  8. Self-Inflicted Lesions in Dermatology

    DEFF Research Database (Denmark)

    Tomas-Aragones, Lucía; Consoli, Silla M; Consoli, Sylvie G

    2017-01-01

    The classification of self-inflicted skin lesions proposed by the European Society for Dermatology and Psychiatry (ESDaP) group generated questions with regard to specific treatments that could be recommended for such cases. The therapeutic guidelines in the current paper integrate new psychother......The classification of self-inflicted skin lesions proposed by the European Society for Dermatology and Psychiatry (ESDaP) group generated questions with regard to specific treatments that could be recommended for such cases. The therapeutic guidelines in the current paper integrate new...

  9. Excitotoxicity and neuronal death in epilepsy

    OpenAIRE

    Lorigados, Lourdes; Orozco, Sandra; Morales, Lilia; Estupiñán, Bárbara; García, Iván; Rocha, Luisa

    2013-01-01

    Epilepsy is a recurrent, often progressive neurological disorder with a chronic evolution, affecting 1 to 2 % of the world population. Research with experimental models and imaging analysis of diseased patients have been used to show that recurrent episodes produce oxidative stress, most of which is related to neuronal excitability phenomena. It is known that the excessive stimulation of glutamate receptors results in neurotoxicity; a process that, under the denomination of excitotoxicity, is...

  10. Self-inflicted lesions in dermatology

    DEFF Research Database (Denmark)

    Gieler, Uwe; Consoli, Sylvie G; Tomás-Aragones, Lucía

    2013-01-01

    The terminology, classification, diagnosis and treatment of self-inflicted dermatological lesions are subjects of open debate. The present study is the result of various meetings of a task force of dermatologists, psychiatrists and psychologists, all active in the field of psychodermatology, aimed...

  11. Self-inflicted serious injuries among adolescents in Zambia | Muula ...

    African Journals Online (AJOL)

    The following variables were associated with history of self inflicted injury: worry; sadness; suicidal behavior; history of ever having been drunk and marijuana use. Reported history of injury and self-inflicted injury among in-school adolescents in Zambia are common. History of self-inflicted injury was associated with other ...

  12. Real-time CARS imaging reveals a calpain-dependent pathway for paranodal myelin retraction during high-frequency stimulation.

    Directory of Open Access Journals (Sweden)

    Terry B Huff

    2011-03-01

    Full Text Available High-frequency electrical stimulation is becoming a promising therapy for neurological disorders, however the response of the central nervous system to stimulation remains poorly understood. The current work investigates the response of myelin to electrical stimulation by laser-scanning coherent anti-Stokes Raman scattering (CARS imaging of myelin in live spinal tissues in real time. Paranodal myelin retraction at the nodes of Ranvier was observed during 200 Hz electrical stimulation. Retraction was seen to begin minutes after the onset of stimulation and continue for up to 10 min after stimulation was ceased, but was found to reverse after a 2 h recovery period. The myelin retraction resulted in exposure of Kv 1.2 potassium channels visualized by immunofluorescence. Accordingly, treating the stimulated tissue with a potassium channel blocker, 4-aminopyridine, led to the appearance of a shoulder peak in the compound action potential curve. Label-free CARS imaging of myelin coupled with multiphoton fluorescence imaging of immuno-labeled proteins at the nodes of Ranvier revealed that high-frequency stimulation induced paranodal myelin retraction via pathologic calcium influx into axons, calpain activation, and cytoskeleton degradation through spectrin break-down.

  13. Cyclooxygenase-2 expression in oligodendrocytes increases sensitivity to excitotoxic death

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    Rojas Monica A

    2010-04-01

    Full Text Available Abstract Background We previously found that cyclooxygenase 2 (COX-2 was expressed in dying oligodendrocytes at the onset of demyelination in the Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD model of multiple sclerosis (MS (Carlson et al. J.Neuroimmunology 2006, 149:40. This suggests that COX-2 may contribute to death of oligodendrocytes. Objective The goal of this study was to examine whether COX-2 contributes to excitotoxic death of oligodendrocytes and potentially contributes to demyelination. Methods The potential link between COX-2 and oligodendrocyte death was approached using histopathology of MS lesions to examine whether COX-2 was expressed in dying oligodendrocytes. COX-2 inhibitors were examined for their ability to limit demyelination in the TMEV-IDD model of MS and to limit excitotoxic death of oligodendrocytes in vitro. Genetic manipulation of COX-2 expression was used to determine whether COX-2 contributes to excitotoxic death of oligodendrocytes. A transgenic mouse line was generated that overexpressed COX-2 in oligodendrocytes. Oligodendrocyte cultures derived from these transgenic mice were used to examine whether increased expression of COX-2 enhanced the vulnerability of oligodendrocytes to excitotoxic death. Oligodendrocytes derived from COX-2 knockout mice were evaluated to determine if decreased COX-2 expression promotes a greater resistance to excitotoxic death. Results COX-2 was expressed in dying oligodendrocytes in MS lesions. COX-2 inhibitors limited demyelination in the TMEV-IDD model of MS and protected oligodendrocytes against excitotoxic death in vitro. COX-2 expression was increased in wild-type oligodendrocytes following treatment with Kainic acid (KA. Overexpression of COX-2 in oligodendrocytes increased the sensitivity of oligodendrocytes to KA-induced excitotoxic death eight-fold compared to wild-type. Conversely, oligodendrocytes prepared from COX-2 knockout mice showed a

  14. Scientific Letter: Self-inflicted bilateral orchidectomy precipitated by ...

    African Journals Online (AJOL)

    Scientific Letter: Self-inflicted bilateral orchidectomy precipitated by erotic bizarre delusions: a case report. ... African Journal of Psychiatry. Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue · Archives · Journal Home ...

  15. FastStats: Self-Inflicted Injury/Suicide

    Science.gov (United States)

    ... this? Submit What's this? Submit Button NCHS Home Suicide and Self-Inflicted Injury Recommend on Facebook Tweet ... Tables, table 17 [PDF – 676 KB] Mortality All suicides Number of deaths: 44,193 Deaths per 100, ...

  16. Neuroprotective function for ramified microglia in hippocampal excitotoxicity

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    Vinet Jonathan

    2012-01-01

    Full Text Available Abstract Background Most of the known functions of microglia, including neurotoxic and neuroprotective properties, are attributed to morphologically-activated microglia. Resting, ramified microglia are suggested to primarily monitor their environment including synapses. Here, we show an active protective role of ramified microglia in excitotoxicity-induced neurodegeneration. Methods Mouse organotypic hippocampal slice cultures were treated with N-methyl-D-aspartic acid (NMDA to induce excitotoxic neuronal cell death. This procedure was performed in slices containing resting microglia or slices that were chemically or genetically depleted of their endogenous microglia. Results Treatment of mouse organotypic hippocampal slice cultures with 10-50 μM N-methyl-D-aspartic acid (NMDA induced region-specific excitotoxic neuronal cell death with CA1 neurons being most vulnerable, whereas CA3 and DG neurons were affected less. Ablation of ramified microglia severely enhanced NMDA-induced neuronal cell death in the CA3 and DG region rendering them almost as sensitive as CA1 neurons. Replenishment of microglia-free slices with microglia restored the original resistance of CA3 and DG neurons towards NMDA. Conclusions Our data strongly suggest that ramified microglia not only screen their microenvironment but additionally protect hippocampal neurons under pathological conditions. Morphological activation of ramified microglia is thus not required to influence neuronal survival.

  17. Distinct subsets of nucleus basalis neurons exhibit similar sensitivity to excitotoxicity

    NARCIS (Netherlands)

    Harkany, Tibor; Varga, Csaba; Grosche, Jens; Mulder, Jan; Luiten, Paul G.M.; Hortobágyi, Tibor; Penke, Botond; Härtig, Wolfgang

    2002-01-01

    Excitotoxic lesions in the magnocellular nucleus basalis (MBN) lead to a significant damage of cholinergic neurons concomitant with increased amyloid precursor protein (APP) expression in the cerebral cortex. However, the sensitivity of non-cholinergic neurons to excitotoxicity, and changes of APP

  18. Feminist therapy with people who self-inflict violence.

    Science.gov (United States)

    Brown, Laura S; Bryan, Tracy C

    2007-11-01

    In this article, the authors describe how a feminist therapist approaches work with clients who practice self-inflicted violence (SIV). They begin by discussing feminist therapy, with its focus on empowerment of clients and the use of noncoercive strategies. The feminist perspective on understanding SIV behaviors is described, with SIV being defined as a coping strategy used by survivors of complex trauma as a means of self-care. Feminist therapy is illustrated with a case example of a woman who used SIV, and the challenges to a therapist wishing to promote client safety while empowering the client. Practice recommendations and cautions are advanced.

  19. Rogue-Elephant-Inflicted Panfacial Injuries: A Rare Case Report

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    Santosh Kumar Yadav

    2012-01-01

    Full Text Available Attacks by elephants, the largest of the “large animals,” produce many fatalities a year. Most attacks are provoked, although rogue elephants are occasionally responsible. Trampling, goring, tossing the individual with the trunk, or crushing with the knees produces the injuries. Injuries from encounters with large animals represent a significant health risk for rural communities. Wild-animal-inflicted maxillofacial injuries are rare, and limited literature is available describing their management. We present a case of severe maxillofacial injuries caused by the attack of a rogue elephant.

  20. BDNF heightens the sensitivity of motor neurons to excitotoxic insults through activation of TrkB

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    Hu, Peter; Kalb, Robert G.; Walton, K. D. (Principal Investigator)

    2003-01-01

    The survival promoting and neuroprotective actions of brain-derived neurotrophic factor (BDNF) are well known but under certain circumstances this growth factor can also exacerbate excitotoxic insults to neurons. Prior exploration of the receptor through which BDNF exerts this action on motor neurons deflects attention away from p75. Here we investigated the possibility that BDNF acts through the receptor tyrosine kinase, TrkB, to confer on motor neurons sensitivity to excitotoxic challenge. We blocked BDNF activation of TrkB using a dominant negative TrkB mutant or a TrkB function blocking antibody, and found that this protected motor neurons against excitotoxic insult in cultures of mixed spinal cord neurons. Addition of a function blocking antibody to BDNF to mixed spinal cord neuron cultures is also neuroprotective indicating that endogenously produced BDNF participates in vulnerability to excitotoxicity. We next examined the intracellular signaling cascades that are engaged upon TrkB activation. Previously we found that inhibition of the phosphatidylinositide-3'-kinase (PI3'K) pathway blocks BDNF-induced excitotoxic sensitivity. Here we show that expression of a constitutively active catalytic subunit of PI3'K, p110, confers excitotoxic sensitivity (ES) upon motor neurons not incubated with BDNF. Parallel studies with purified motor neurons confirm that these events are likely to be occuring specifically within motor neurons. The abrogation of BDNF's capacity to accentuate excitotoxic insults may make it a more attractive neuroprotective agent.

  1. Kainic Acid-Induced Excitotoxicity Experimental Model: Protective Merits of Natural Products and Plant Extracts

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    Nur Shafika Mohd Sairazi

    2015-01-01

    Full Text Available Excitotoxicity is well recognized as a major pathological process of neuronal death in neurodegenerative diseases involving the central nervous system (CNS. In the animal models of neurodegeneration, excitotoxicity is commonly induced experimentally by chemical convulsants, particularly kainic acid (KA. KA-induced excitotoxicity in rodent models has been shown to result in seizures, behavioral changes, oxidative stress, glial activation, inflammatory mediator production, endoplasmic reticulum stress, mitochondrial dysfunction, and selective neurodegeneration in the brain upon KA administration. Recently, there is an emerging trend to search for natural sources to combat against excitotoxicity-associated neurodegenerative diseases. Natural products and plant extracts had attracted a considerable amount of attention because of their reported beneficial effects on the CNS, particularly their neuroprotective effect against excitotoxicity. They provide significant reduction and/or protection against the development and progression of acute and chronic neurodegeneration. This indicates that natural products and plants extracts may be useful in protecting against excitotoxicity-associated neurodegeneration. Thus, targeting of multiple pathways simultaneously may be the strategy to maximize the neuroprotection effect. This review summarizes the mechanisms involved in KA-induced excitotoxicity and attempts to collate the various researches related to the protective effect of natural products and plant extracts in the KA model of neurodegeneration.

  2. Bear-inflicted injuries - a report from Nepal.

    Science.gov (United States)

    Atreya, Alok; Kanchan, Tanuj; Nepal, Samata; Acharya, Jenash

    2016-06-01

    Upper Mustang in the Northern Himalayan range of Nepal is the home of brown bears (Ursusarctos). Low-plant biomass as a result of scanty rainfall in Upper Mustang is a reason for habitat overlap of humans and wild animals. Humans who enter into the wild to collect firewood and graze cattle are liable to wild animal attacks. Such attacks, especially by brown bears, are readily identified by the type of injuries. These are more commonly confined to head and neck regions. Cutting, gnawing and tearing by sharp teeth and claws produces specific pattern of injuries, which are devastating but seldom fatal. This article reports a rare case of brown bear injury inflicted upon a man from the Upper Mustang region in Nepal. © The Author(s) 2016.

  3. Investigation of elemental changes in brain tissues following excitotoxic injury

    International Nuclear Information System (INIS)

    Siegele, Rainer; Howell, Nicholas R.; Callaghan, Paul D.; Pastuovic, Zeljko

    2013-01-01

    Recently the ANSTO heavy ion microprobe has been used for elemental mapping of thin brain tissue sections. The fact that a very small portion of the proton energy is used for X-ray excitation combined with small variations of the major element concentrations makes μ-PIXE imaging and GeoPIXE analysis a challenging task. Excitotoxic brain injury underlies the pathology of stroke and various neurodegenerative disorders. Large fluxes in Ca +2 cytosolic concentrations are a key feature of the initiation of this pathophysiological process. In order to understand if these modifications are associated with changes in the elemental composition, several brain sections have been mapped with μ-PIXE. Increases in Ca +2 cytosolic concentrations were indicative of the pathophysiological process continuing 1 week after an initiating neural insult. We were able to measure significant variations in K and Ca concentration distribution across investigated brain tissue. These variations correlate very well with physiological changes visible in the brain tissue. Moreover, the obtained μ-PIXE results clearly demonstrate that the elemental composition changes significantly correlate with brain drauma

  4. Investigation of elemental changes in brain tissues following excitotoxic injury

    Energy Technology Data Exchange (ETDEWEB)

    Siegele, Rainer, E-mail: rns@ansto.gov.au [Institute for Environmental Research, ANSTO, Locked Bag 2001, Kirrawee DC, NSW 2232 (Australia); Howell, Nicholas R.; Callaghan, Paul D. [Life Sciences, ANSTO, Locked Bag 2001, Kirrawee DC, NSW 2232 (Australia); Pastuovic, Zeljko [Institute for Environmental Research, ANSTO, Locked Bag 2001, Kirrawee DC, NSW 2232 (Australia)

    2013-07-01

    Recently the ANSTO heavy ion microprobe has been used for elemental mapping of thin brain tissue sections. The fact that a very small portion of the proton energy is used for X-ray excitation combined with small variations of the major element concentrations makes μ-PIXE imaging and GeoPIXE analysis a challenging task. Excitotoxic brain injury underlies the pathology of stroke and various neurodegenerative disorders. Large fluxes in Ca{sup +2} cytosolic concentrations are a key feature of the initiation of this pathophysiological process. In order to understand if these modifications are associated with changes in the elemental composition, several brain sections have been mapped with μ-PIXE. Increases in Ca{sup +2} cytosolic concentrations were indicative of the pathophysiological process continuing 1 week after an initiating neural insult. We were able to measure significant variations in K and Ca concentration distribution across investigated brain tissue. These variations correlate very well with physiological changes visible in the brain tissue. Moreover, the obtained μ-PIXE results clearly demonstrate that the elemental composition changes significantly correlate with brain drauma.

  5. Gross and histopathological evaluation of human inflicted bruises in Danish slaughter pigs

    DEFF Research Database (Denmark)

    Barington, Kristiane; Agger, Jens Frederik Gramstrup; Nielsen, Søren Saxmose

    2016-01-01

    Background: Human inflicted bruises in slaughter pigs are hampering animal welfare, are an infringement of the animal protection act, and are a focus of public attention. The aim of the present study was to evaluate the gross appearance of human inflicted bruises in slaughter pigs and to compare ...

  6. Elevated lactate as an early marker of brain injury in inflicted traumatic brain injury

    International Nuclear Information System (INIS)

    Makoroff, Kathi L.; Cecil, Kim M.; Ball, William S.; Care, Marguerite

    2005-01-01

    Patients with inflicted traumatic brain injury and evidence of hypoxic-ischemic injury as indicated by elevated lactate on MRS tend to have worse early neurological status and early outcome scores. Lactate levels as sampled by MRS might predict early clinical outcome in inflicted traumatic brain injury. (orig.)

  7. MRI Overestimates Excitotoxic Amygdala Lesion Damage in Rhesus Monkeys

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    Benjamin M. Basile

    2017-06-01

    Full Text Available Selective, fiber-sparing excitotoxic lesions are a state-of-the-art tool for determining the causal contributions of different brain areas to behavior. For nonhuman primates especially, it is advantageous to keep subjects with high-quality lesions alive and contributing to science for many years. However, this requires the ability to estimate lesion extent accurately. Previous research has shown that in vivo T2-weighted magnetic resonance imaging (MRI accurately estimates damage following selective ibotenic acid lesions of the hippocampus. Here, we show that the same does not apply to lesions of the amygdala. Across 19 hemispheres from 13 rhesus monkeys, MRI assessment consistently overestimated amygdala damage as assessed by microscopic examination of Nissl-stained histological material. Two outliers suggested a linear relation for lower damage levels, and values of unintended amygdala damage from a previous study fell directly on that regression line, demonstrating that T2 hypersignal accurately predicts damage levels below 50%. For unintended damage, MRI estimates correlated with histological assessment for entorhinal cortex, perirhinal cortex and hippocampus, though MRI significantly overestimated the extent of that damage in all structures. Nevertheless, ibotenic acid injections routinely produced extensive intentional amygdala damage with minimal unintended damage to surrounding structures, validating the general success of the technique. The field will benefit from more research into in vivo lesion assessment techniques, and additional evaluation of the accuracy of MRI assessment in different brain areas. For now, in vivo MRI assessment of ibotenic acid lesions of the amygdala can be used to confirm successful injections, but MRI estimates of lesion extent should be interpreted with caution.

  8. Calpain-Mediated Degradation of Drebrin by Excitotoxicity In vitro and In vivo.

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    Takahiko Chimura

    Full Text Available The level of drebrin, an evolutionarily conserved f-actin-binding protein that regulates synaptic structure and function, is reduced in the brains of patients with chronic neurodegenerative diseases such as Alzheimer's disease (AD and Down's syndrome (DS. It was suggested that excitotoxic neuronal death caused by overactivation of NMDA-type glutamate receptors (NMDARs occurs in AD and DS; however, the relationship between excitotoxicity and drebrin loss is unknown. Here, we show that drebrin is a novel target of calpain-mediated proteolysis under excitotoxic conditions induced by the overactivation of NMDARs. In cultured rodent neurons, degradation of drebrin was confirmed by the detection of proteolytic fragments, as well as a reduction in the amount of full-length drebrin. Notably, the NMDA-induced degradation of drebrin in mature neurons occurred concomitantly with a loss of f-actin. Furthermore, pharmacological inhibition of f-actin loss facilitated the drebrin degradation, suggesting a functional linkage between f-actin and drebrin degradation. Biochemical analyses using purified drebrin and calpain revealed that calpain degraded drebrin directly in vitro. Furthermore, cerebral ischemia also induced the degradation of drebrin in vivo. These findings suggest that calpain-mediated degradation of drebrin is a fundamental pathology of neurodegenerative diseases mediated by excitotoxicity, regardless of whether they are acute or chronic. Drebrin regulates the synaptic clustering of NMDARs; therefore, degradation of drebrin under excitotoxic conditions may modulate NMDAR-mediated signal transductions, including pro-survival signaling. Overall, the results presented here provide novel insights into the molecular basis of cellular responses to excitotoxicity in vitro and in vivo.

  9. Clinical outcome of patients with self-inflicted burns.

    Science.gov (United States)

    Cornet, P A; Niemeijer, A S; Figaroa, G D; van Daalen, M A; Broersma, T W; van Baar, M E; Beerthuizen, G I J M; Nieuwenhuis, M K

    2017-06-01

    Patients with self-inflicted burns (SIB) are thought to have a longer length of stay compared to patients with accidental burns. However, other predictors for a longer length of stay are often not taken into account, e.g. percentage of the body surface area burned, age or comorbidities. Therefore, we wanted to study the outcome of patients with SIB at our burn center. A retrospective, observational study was conducted. All adult patients with acute burns admitted to the burn center of the Martini Hospital Groningen, between January 1, 2009 and December 31, 2013 were included. Data on characteristics of the patient, injury, and outcome (LOS, mortality, discharge destination) were collected. In patients with SIB, suicide attempts (SA) were distinguished from self-harm without the intention to die (non-suicidal self-injury, NSSI). To evaluate differences in outcome, each patient with SIB was matched on variables and total score of the Abbreviated Burn Severity Index (ABSI) to a patient with accidental burns (AB). In total 29 admissions (21 SA and 8 NSSI) were due to SIB and 528 due to accidents. Overall, when compared to AB, there were significant differences with respect to mortality and LOS for SA and/or NSSI. Mortality was higher in the SA group, while the LOS was higher in both the SA and NSSI groups compared to the AB group. However, after matching on ABSI, no statistical significant differences between the SA and SA-match or the NSSI and NSSI-match group were found. With the right and timely treatment, differences in mortality rate or length of stay in hospital could all be explained by the severity of the burn and the intention of the patient. Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved.

  10. Hypopituitarism in pediatric survivors of inflicted traumatic brain injury.

    Science.gov (United States)

    Auble, Bethany A; Bollepalli, Sureka; Makoroff, Kathi; Weis, Tammy; Khoury, Jane; Colliers, Tracy; Rose, Susan R

    2014-02-15

    Endocrine dysfunction is common after accidental traumatic brain injury (TBI). Prevalence of endocrine dysfunction after inflicted traumatic brain injury (iTBI) is not known. The aim of this study was to examine endocrinopathy in children after moderate-to-severe iTBI. Children with previous iTBI (n=14) were evaluated for growth/endocrine dysfunction, including anthropometric measurements and hormonal evaluation (nocturnal growth hormone [GH], thyrotropin surge, morning and low-dose adrenocorticotropin stimulated cortisol, insulin-like growth factor 1, IGF-binding protein 3, free thyroxine, prolactin [PRL], and serum/urine osmolality). Analysis used Fisher's exact test and Wilcoxon's rank-sum test, as appropriate. Eighty-six percent of subjects had endocrine dysfunction with at least one abnormality, whereas 50% had two or more abnormalities, significantly increased compared to an estimated 2.5% with endocrine abnormality in the general population (p<0.001). Elevated prolactin was common (64%), followed by abnormal thyroid function (33%), short stature (29%), and low GH peak (17%). High prolactin was common in subjects with other endocrine abnormalities. Two were treated with thyroid hormone and 2 may require GH therapy. In conclusion, children with a history of iTBI show high risk for endocrine dysfunction, including elevated PRL and growth abnormalities. This effect of iTBI has not been well described in the literature. Larger, multi-center, prospective studies would provide more data to determine the extent of endocrine dysfunction in iTBI. We recommend that any child with a history of iTBI be followed closely for growth velocity and pubertal changes. If growth velocity is slow, PRL level and a full endocrine evaluation should be performed.

  11. [The death of Kaspar Hauser (17 Dec 1833)--assassination, suicide or self-inflicted injury?].

    Science.gov (United States)

    Risse, Manfred; Bartsch, Christine; Dreyer, Thomas; Weiler, Günter

    2005-01-01

    The death of Kaspar Hauser is described taking present medicolegal and criminological knowledge into account, the main question being whether the injury was self-inflicted, homicidal or suicidal. In spite of a critical retrospective analysis this question cannot be answered with sufficient certainty even from our modern perspective. It seems unlikely that the stab to the chest was inflicted exclusively for the purpose of self-damage, but both a suicidal stab and a homicidal act (assassination) cannot be definitely ruled out.

  12. Self-Inflicted Orbito-Cranial Injury Secondary to Gunshot: Case Report

    Directory of Open Access Journals (Sweden)

    Yam Bahadur Roka

    2017-10-01

    Full Text Available The eye may be injured by various penetrating and non-penetrating injuries like sticks, pencils, rods, gunshot and chopsticks. Self-inflicted gunshot injuries have been rarely reported in literature. This case is interesting in multiple aspects which include poverty, lack of education and the failure of government to ensure control of the use of firearms in Nepal. We report a case of self-inflicted gun injury which was managed successfully.

  13. The Effects of NAD+ on Apoptotic Neuronal Death and Mitochondrial Biogenesis and Function after Glutamate Excitotoxicity

    Science.gov (United States)

    Wang, Xiaowan; Li, Hailong; Ding, Shinghua

    2014-01-01

    NAD+ is an essential co-enzyme for cellular energy metabolism and is also involved as a substrate for many cellular enzymatic reactions. It has been shown that NAD+ has a beneficial effect on neuronal survival and brain injury in in vitro and in vivo ischemic models. However, the effect of NAD+ on mitochondrial biogenesis and function in ischemia has not been well investigated. In the present study, we used an in vitro glutamate excitotoxicity model of primary cultured cortical neurons to study the effect of NAD+ on apoptotic neuronal death and mitochondrial biogenesis and function. Our results show that supplementation of NAD+ could effectively reduce apoptotic neuronal death, and apoptotic inducing factor translocation after neurons were challenged with excitotoxic glutamate stimulation. Using different approaches including confocal imaging, mitochondrial DNA measurement and Western blot analysis of PGC-1 and NRF-1, we also found that NAD+ could significantly attenuate glutamate-induced mitochondrial fragmentation and the impairment of mitochondrial biogenesis. Furthermore, NAD+ treatment effectively inhibited mitochondrial membrane potential depolarization and NADH redistribution after excitotoxic glutamate stimulation. Taken together, our results demonstrated that NAD+ is capable of inhibiting apoptotic neuronal death after glutamate excitotoxicity via preserving mitochondrial biogenesis and integrity. Our findings provide insights into potential neuroprotective strategies in ischemic stroke. PMID:25387075

  14. Single-cell imaging of bioenergetic responses to neuronal excitotoxicity and oxygen and glucose deprivation.

    Science.gov (United States)

    Connolly, Niamh M C; Düssmann, Heiko; Anilkumar, Ujval; Huber, Heinrich J; Prehn, Jochen H M

    2014-07-30

    Excitotoxicity is a condition occurring during cerebral ischemia, seizures, and chronic neurodegeneration. It is characterized by overactivation of glutamate receptors, leading to excessive Ca(2+)/Na(+) influx into neurons, energetic stress, and subsequent neuronal injury. We and others have previously investigated neuronal populations to study how bioenergetic parameters determine neuronal injury; however, such experiments are often confounded by population-based heterogeneity and the contribution of effects of non-neuronal cells. Hence, we here characterized bioenergetics during transient excitotoxicity in rat and mouse primary neurons at the single-cell level using fluorescent sensors for intracellular glucose, ATP, and activation of the energy sensor AMP-activated protein kinase (AMPK). We identified ATP depletion and recovery to energetic homeostasis, along with AMPK activation, as surprisingly rapid and plastic responses in two excitotoxic injury paradigms. We observed rapid recovery of neuronal ATP levels also in the absence of extracellular glucose, or when glycolytic ATP production was inhibited, but found mitochondria to be critical for fast and complete energetic recovery. Using an injury model of oxygen and glucose deprivation, we identified a similarly rapid bioenergetics response, yet with incomplete ATP recovery and decreased AMPK activity. Interestingly, excitotoxicity also induced an accumulation of intracellular glucose, providing an additional source of energy during and after excitotoxicity-induced energy depletion. We identified this to originate from extracellular, AMPK-dependent glucose uptake and from intracellular glucose mobilization. Surprisingly, cells recovering their elevated glucose levels faster to baseline survived longer, indicating that the plasticity of neurons to adapt to bioenergetic challenges is a key indicator of neuronal viability. Copyright © 2014 the authors 0270-6474/14/3410192-14$15.00/0.

  15. [Alleged assault in a forest: An unusual case of self-inflicted blunt injury].

    Science.gov (United States)

    Kunz, Sebastian Niko; Tutsch-Bauer, Edith

    2014-01-01

    The medico-legal assessment of potentially self-inflicted injuries is an important field of clinical forensic medicine. Compared with sharp force injuries, it is much more difficult to distinguish blunt injuries caused by another party from self-inflicted lesions. We present a case of a young female doctor, who was allegedly attacked by an unknown stranger during her evening walk in the woods. She claimed to have been hit repeatedly on the head and arms with a stone. During the forensic investigation, blunt injuries could be confirmed on her head and forearms. Based on the arrangement and intensity of the injuries, together with the result of a bloodstain pattern analysis of the weapon, the victim's statement could be disproved. After being confronted with the results of the investigation, the woman admitted to have inflicted the injuries herself. This case is an unusual and rare example of self-inflicted blunt injury. It shows that the criteria of self-inflicted injuries can also be applied to blunt trauma. However, due to the small number of cases, a high degree of caution is required from the forensic expert.

  16. Self Inflicted Injuries among Children in United States - estimates from a nationwide emergency department sample.

    Directory of Open Access Journals (Sweden)

    Naseem Sulyman

    Full Text Available OBJECTIVE: The objectives of the current study are to provide nationally representative estimates of hospital based emergency department visits (ED attributed to self inflicted injuries and attempted suicides among children in United States; and to identify potential methods of such intentional self inflicted injuries and attempted suicides. METHODS: The Nationwide Emergency Department Sample (year 2007 was used. All ED visits occurring among children (aged ≤18 years with an External Cause of Injury for any of self inflicted injuries were selected. Outcomes examined include hospital ED charges and hospitalization charges. All estimates were projected to national levels. RESULTS: 77,420 visits to hospital based emergency departments were attributed to self inflicted injuries among children (26,045 males and 51,370 females. The average age of the ED visits was 15.7 years. 134 patients died in ED's (106 males and 28 females and 93 died in hospitals following in-patient admission (75 males and 18 females. A greater proportion of male ED visits were discharged routinely as opposed to female ED visits (51.1% versus 44%. A greater proportion of male ED visits also died in the emergency departments compared to female visits (0.4% versus 0.05%. 17,965 ED visits necessitated admission into same hospital. The mean charge for each ED visit was $1,874. Self inflicted injuries by poisoning were the most frequently reported sources accounting for close to 70% of all ED visits. CONCLUSIONS: Females comprise a greater proportion of ED visits attributed to self inflicted injuries. 227 children died either in the ED's or in hospitals. The current study results highlight the burden associated with such injuries among children.

  17. Excitotoxic effects of non-NMDA receptor agonists in organotypic corticostriatal slice cultures

    DEFF Research Database (Denmark)

    Kristensen, B W; Noraberg, J; Jakobsen, B

    1999-01-01

    of the cytosolic enzyme lactate dehydrogenase (LDH) into the culture medium and loss of glutamic acid decarboxylase (GAD) activity in the tissue. Histological sections were also stained by the fluorescent dye Fluoro-Jade (FJ), for degenerating neurons and by immunocytochemical staining for gamma-aminobutyric acid...... density of Fluoro-Jade staining, (3) loss of GAD-activity in tissue homogenates, and (4) loss of GABA-immunostained neurons. We conclude that both differences between compounds (AMPA vs. KA) and brain areas (striatum vs. cortex) can be demonstrated in corticostriatal slice cultures, which in conjunction...... in corticostriatal slice cultures. The purpose was to examine the feasibility of these cultures for excitotoxic studies, and to demonstrate possible differential excitotoxic effects of KA and AMPA on striatal and cortical neurons. Slices of dorsolateral striatum with overlying neocortex were obtained from neonatal...

  18. Pilocarpine-induced status epilepticus in rats involves ischemic and excitotoxic mechanisms.

    Directory of Open Access Journals (Sweden)

    Paolo Francesco Fabene

    Full Text Available The neuron loss characteristic of hippocampal sclerosis in temporal lobe epilepsy patients is thought to be the result of excitotoxic, rather than ischemic, injury. In this study, we assessed changes in vascular structure, gene expression, and the time course of neuronal degeneration in the cerebral cortex during the acute period after onset of pilocarpine-induced status epilepticus (SE. Immediately after 2 hr SE, the subgranular layers of somatosensory cortex exhibited a reduced vascular perfusion indicative of ischemia, whereas the immediately adjacent supragranular layers exhibited increased perfusion. Subgranular layers exhibited necrotic pathology, whereas the supergranular layers were characterized by a delayed (24 h after SE degeneration apparently via programmed cell death. These results indicate that both excitotoxic and ischemic injuries occur during pilocarpine-induced SE. Both of these degenerative pathways, as well as the widespread and severe brain damage observed, should be considered when animal model-based data are compared to human pathology.

  19. Single-Cell Imaging of Bioenergetic Responses to Neuronal Excitotoxicity and Oxygen and Glucose Deprivation

    OpenAIRE

    Connolly, Niamh M; Düssmann, Heiko; Anilkumar, Ujval; Huber, Heinrich J; Prehn, Jochen HM

    2014-01-01

    Excitotoxicity is a condition occurring during cerebral ischemia, seizures, and chronic neurodegeneration. It is characterized by overactivation of glutamate receptors, leading to excessive Ca2+/Na+ influx into neurons, energetic stress, and subsequent neuronal injury.We and others have previously investigated neuronal populations to study how bioenergetic parameters determine neuronal injury; however, such experiments are often confounded by population-based heterogeneity and the contributio...

  20. A new infectious encephalopathy syndrome, clinically mild encephalopathy associated with excitotoxicity (MEEX).

    Science.gov (United States)

    Hirai, Nozomi; Yoshimaru, Daisuke; Moriyama, Yoko; Yasukawa, Kumi; Takanashi, Jun-Ichi

    2017-09-15

    Acute infectious encephalopathy is often observed in children in East Asia including Japan. More than 40% of the patients remain unclassified into specific syndromes. To investigate the underlying pathomechanisms in those with unclassified encephalopathy, we evaluated brain metabolism by MR spectroscopy. Among seven patients with acute encephalopathy admitted to our hospital from June 2016 to May 2017, three were classified into acute encephalopathy with biphasic seizures and late reduced diffusion (AESD). The other four showed consciousness disturbance lasting more than three days with no parenchymal lesion visible on MRI, which led to a diagnosis of unclassified encephalopathy. MR spectroscopy in these four patients, however, revealed an increase of glutamine with a normal N-acetyl aspartate level on days 5 to 8, which had normalized by follow-up studies on days 11 to 16. The four patients clinically recovered completely. Among 27 patients with encephalopathy, including the present seven patients, admitted to our hospital from January 2015 to March 2017, seven (26%) were classified into this type, which we propose is a new encephalopathy syndrome, clinically mild encephalopathy associated with excitotoxicity (MEEX). MEEX is the second most common subtype, following AESD (30%). This study suggests that excitotoxicity may be a common underlying pathomechanism of acute infectious encephalopathy, and prompt astrocytic neuroprotection from excitotoxicity may prevent progression of MEEX into AESD. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Neuroprotective effects of NAP against excitotoxic brain damage in the newborn mice: implications for cerebral palsy.

    Science.gov (United States)

    Sokolowska, P; Passemard, S; Mok, A; Schwendimann, L; Gozes, I; Gressens, P

    2011-01-26

    Activity-dependent neuroprotective protein (ADNP) was shown to be essential for embryogenesis and brain development while NAP, an active motif of ADNP, is neuroprotective in a broad range of neurodegenerative disorders. In the present study, we examined the protective potential of ADNP/NAP in a mouse model of excitotoxic brain lesion mimicking brain damage associated with cerebral palsy. We demonstrated that NAP had a potent neuroprotective effect against ibotenate-induced excitotoxic damage in the cortical plate and the white matter of P5 mice, and moderate against brain lesions of P0 mice. In contrast, endogenous ADNP appears not to be involved in the response to excitotoxic challenge in the studied model. Our findings further show that NAP reduced the number of apoptotic neurons through activation of PI-3K/Akt pathway in the cortical plate or both PI-3K/Akt and MAPK/MEK1 kinases in the white matter. In addition, NAP prevented ibotenate-induced loss of pre-oligodendrocytes without affecting the number of astrocytes or activated microglia around the site of injection. These findings indicate that protective actions of NAP are mediated by triggering transduction pathways that are crucial for neuronal and oligodendroglial survival, thus, NAP might be a promising therapeutic agent for treating developing brain damage. © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

  2. The burden and management of self-inflicted injuries at a tertiary ...

    African Journals Online (AJOL)

    The mortality rate was 22.8%. Late presentation (>24 hour), severe injuries (KTS II ≤ 6) and presence of surgical site infections were the main predictors of mortality (p<0.001). Conclusion: Self-inflicted injuries are an emerging but neglected public health problem in Mwanza, Tanzania and contribute to unacceptably high ...

  3. Income inequality, social capital and self-inflicted injury and violence-related mortality

    NARCIS (Netherlands)

    Huisman, M.; Oldehinkel, A. J.

    Background: The objective of the study was to investigate the relation of income inequality and indicators of social capital to self-inflicted injury mortality (suicide) and violence-related mortality, and to the share of total mortality that is due to these two causes of death in 35 developed

  4. [The morphological characteristic of the skin lesions inflicted by plastic knives with four cutting edges].

    Science.gov (United States)

    Leonov, S V; Finkel'shtein, V T

    2015-01-01

    The objective of the present work was to study the morphological features of the skin lesions inflicted by the blades of the Fgx Boot Blade I knives having four cutting edges. The study revealed the signs that can be used to distinguish between morphological characteristics of the stab and lacerated wounds having the primary and secondary incisions made by the four-edge blade.

  5. Parent-Child Interactions, Peripheral Serotonin, and Self-Inflicted Injury in Adolescents

    Science.gov (United States)

    Crowell, Sheila E.; Beauchaine, Theodore P.; McCauley, Elizabeth; Smith, Cindy J.; Vasilev, Christina A.; Stevens, Adrianne L.

    2008-01-01

    Self-inflicted injury in adolescence indicates significant emotional and psychological suffering. Although data on the etiology of self-injury are limited, current theories suggest that the emotional lability observed among self-injuring adolescents results from complex interactions between individual biological vulnerabilities and environmental…

  6. [Child-pedestrian injuries inflicted in the road traffic accidents as a forensic medical problem].

    Science.gov (United States)

    Savenkova, E N; Efimov, A A

    The road traffic accidents are known to make the greatest contribution to the overall structure of pediatric traumatism with the fatal outcome. The problem of pediatric traumatism remains on top of its relevancy despite numerous administrative, legal, technical, and financial measures taken at the government level in an attempt to reduce the mortality rate associated with the child-pedestrian injuries inflicted in the road traffic accidents. The objective of the present study was to summarize and interpret the results published in the scientific literature concerning child-pedestrian injuries inflicted in the road traffic accidents with special reference to the age of the victims and the type of the injury. The analysis of the publications of the domestic and foreign authors has demonstrated that the available data of interest remain to be systematized and that the forensic medical aspects of the problem in question are poorly represented in these materials. It was shown that forensic medical expertises of child-pedestrian injuries inflicted in the road traffic accidents are frequently carried out without taking into consideration the peculiar anatomical and physiological features of the child's organism. The available data concerning the mechanisms and evaluation of severe injuries inflicted to the children in the road traffic accidents are insufficient for the development of the algorithms for the relevant adequate forensic medical expertise. In the light of these findings, the problem of the child-pedestrian injuries inflicted in the road traffic accidents takes on new significance when considered in the context of pediatric traumatism. There is evidently the growing necessity to formulate the universal database containing systematized objective information for the development of new methods of forensic medical expertise for the elucidation of the mechanisms of road traffic injuries inflicted to the children of different age groups depending on the type of the

  7. ASIC channel inhibition enhances excitotoxic neuronal death in an in vitro model of spinal cord injury.

    Science.gov (United States)

    Mazzone, Graciela L; Veeraraghavan, Priyadharishini; Gonzalez-Inchauspe, Carlota; Nistri, Andrea; Uchitel, Osvaldo D

    2017-02-20

    In the spinal cord high extracellular glutamate evokes excitotoxic damage with neuronal loss and severe locomotor impairment. During the cell dysfunction process, extracellular pH becomes acid and may activate acid-sensing ion channels (ASICs) which could be important contributors to neurodegenerative pathologies. Our previous studies have shown that transient application of the glutamate analog kainate (KA) evokes delayed excitotoxic death of spinal neurons, while white matter is mainly spared. The present goal was to enquire if ASIC channels modulated KA damage in relation to locomotor network function and cell death. Mouse spinal cord slices were treated with KA (0.01 or 0.1mM) for 1h, and then washed out for 24h prior to analysis. RT-PCR results showed that KA (at 0.01mM concentration that is near-threshold for damage) increased mRNA expression of ASIC1a, ASIC1b, ASIC2 and ASIC3, an effect reversed by the ASIC inhibitor 4',6-diamidino-2-phenylindole (DAPI). A KA neurotoxic dose (0.1mM) reduced ASIC1a and ASIC2 expression. Cell viability assays demonstrated KA-induced large damage in spinal slices from mice with ASIC1a gene ablation. Likewise, immunohistochemistry indicated significant neuronal loss when KA was followed by the ASIC inhibitors DAPI or amiloride. Electrophysiological recording from ventral roots of isolated spinal cords showed that alternating oscillatory cycles were slowed down by 0.01mMKA, and intensely inhibited by subsequently applied DAPI or amiloride. Our data suggest that early rise in ASIC expression and function counteracted deleterious effects on spinal networks by raising the excitotoxicity threshold, a result with potential implications for improving neuroprotection. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  8. Red Ginseng Extract Attenuates Kainate-Induced Excitotoxicity by Antioxidative Effects

    Directory of Open Access Journals (Sweden)

    Jin-Yi Han

    2012-01-01

    Full Text Available This study investigated the neuroprotective activity of red ginseng extract (RGE, Panax ginseng, C. A. Meyer against kainic acid- (KA- induced excitotoxicity in vitro and in vivo. In hippocampal cells, RGE inhibited KA-induced excitotoxicity in a dose-dependent manner as measured by the MTT assay. To study the possible mechanisms of the RGE-mediated neuroprotective effect against KA-induced cytotoxicity, we examined the levels of intracellular reactive oxygen species (ROS and [Ca2+]i in cultured hippocampal neurons and found that RGE treatment dose-dependently inhibited intracellular ROS and [Ca2+]i elevation. Oral administration of RGE (30 and 200 mg/kg in mice decreased the malondialdehyde (MDA level induced by KA injection (30 mg/kg, i.p.. In addition, similar results were obtained after pretreatment with the radical scavengers Trolox and N, N′-dimethylthiourea (DMTU. Finally, after confirming the protective effect of RGE on hippocampal brain-derived neurotropic factor (BDNF protein levels, we found that RGE is active compounds mixture in KA-induced hippocampal mossy-fiber function improvement. Furthermore, RGE eliminated 1,1-diphenyl-2-picrylhydrazyl (DPPH radicals, and the IC50 was approximately 10 mg/ml. The reductive activity of RGE, as measured by reaction with hydroxyl radical (•OH, was similar to trolox. The second-order rate constant of RGE for •OH was 3.5–4.5×109 M−1·S−1. Therefore, these results indicate that RGE possesses radical reduction activity and alleviates KA-induced excitotoxicity by quenching ROS in hippocampal neurons.

  9. Excitatory and inhibitory pathways modulate kainate excitotoxicity in hippocampal slice cultures

    DEFF Research Database (Denmark)

    Casaccia-Bonnefil, P; Benedikz, Eirikur; Rai, R

    1993-01-01

    In organotypic hippocampal slice cultures, kainate (KA) specifically induces cell loss in the CA3 region while N-methyl-D-aspartate induces cell loss in the CA1 region. The sensitivity of slice cultures to KA toxicity appears only after 2 weeks in vitro which parallels the appearance of mossy...... fibers. KA toxicity is potentiated by co-application with the GABA-A antagonist, picrotoxin. These data suggest that the excitotoxicity of KA in slice cultures is modulated by both excitatory and inhibitory synapses....

  10. GDNF and neublastin protect against NMDA-induced excitotoxicity in hippocampal slice cultures

    DEFF Research Database (Denmark)

    Bonde, C; Kristensen, B W; Blaabjerg, M

    2000-01-01

    -producing HiB5 cells, were added to slice cultures I h before exposure to 10 microM NMDA for 48h. Neuronal cell death was monitored, before and during the NMDA exposure, by densitometric measurements of propidium iodide (PI) uptake and loss of Nissl staining. Both the addition of rhGDNF and NBN......The potential neuroprotective effects of glial cell line-derived neurotrophic factor (GDNF) and neublastin (NBN) against NMDA-induced excitotoxicity were examined in hippocampal brain slice cultures. Recombinant human GDNF (25-100 ng/ ml) or NBN, in medium conditioned by growth of transfected, NBN...

  11. AMPA receptor mediated excitotoxicity in neocortical neurons is developmentally regulated and dependent upon receptor desensitization

    DEFF Research Database (Denmark)

    Jensen, J B; Schousboe, A; Pickering, D S

    1998-01-01

    with a fast and rapidly desensitizing response, this could explain the relatively low toxicity produced by 500 microM AMPA. This was investigated by blocking AMPA receptor desensitization with cyclothiazide. Using a lower concentration (25 microM) of AMPA, addition of 50 microM cyclothiazide increased...... the AMPA induced excitotoxicity in cultured cortical neurons at all DIV except for DIV 2. This combination of AMPA + cyclothiazide yielded 77% cell death for DIV 12 cultures. In contrast to the results observed with 500 microM AMPA, the neurotoxicity mediated directly by AMPA receptors when desensitization...

  12. Comparison of the General Health, Self-Esteem and Social Support in Self-Inflicted Burn Patients and Non Self Inflicted Burn Patients of the Choromy Accidental and Burning Hospital of Ganaveh

    Directory of Open Access Journals (Sweden)

    MS Enayati

    2006-04-01

    Full Text Available ABSTRACT: Introduction & Objective: Self-inflicted burn is a violent method of suicide. Since our society faces lots of psychological, social, personal and economical problems due to self-inflicted burn, more survey for this event can assist us to know its causes and prevent from its occurrence. This research was carried out to compare general health, self- esteem and social support in patient's self-inflicted burn and non-self-inflicted burn of the Choromy accidental and burning hospital in Ganaveh. Materials & Methods: This is a descriptive – analytic study. The sample consisted of 60 inpatients burnt (males & females of the Choromy accidental and burning hospital (Ganaveh. The method of sampling was simple random. Participants completed the General Health Questionnaire (G.H.Q- 28 of Goldberg, Cooper Smith’s questionnaire of self–esteem and Philip’s social support scale. Multivariate analysis of variance (MANOVA and T-test were the major statistical analysis in this research. Results: The mean and standard deviation of the general health were 44.57 ± 14.65 for self-inflicted burn persons and for non - self inflicted burn they were 10.83 ± 6.27. In the self–esteem variable, the mean and the standard deviation were 57.90 ± 4.94 for self-inflicted burn persons and 55.47 ± 6.04 for non-self inflicted burn ones. Mean and standard deviation of whole social supporting were 20.40 ± 4.94 for self-inflicted burn persons and 23.73 ± 1.17 for non-self inflicted burn group. The findings showed significant differences between the two groups from viewpoint of general health and social supporting while there were no significant differences between two groups in case of self–esteem. Conclusion: There are a significant relationship between general health, social supporting and self-inflicted burn.Therefore, in order to prevent self inflicted burn it is suggested that we make a relationship between persons and societies, families, groups and

  13. Blockade of cannabinoid CB receptor function protects against in vivo disseminating brain damage following NMDA-induced excitotoxicity

    DEFF Research Database (Denmark)

    Hansen, H.H.; Ramos, J.A.; Fernández-Ruiz, J.

    2002-01-01

    -induced excitotoxic damage in the ipsilateral forebrain was not influenced by agonist-stimulated CB receptor function. In contrast, blockade of CB, but not CB, receptor activity evoked a robust neuroprotective response by reducing the infarct area and the number of cortical degenerating neurons. These results suggest...... receptor function on NMDA-induced excitotoxicity. Neonatal (6-day-old) rat pups received a systemic injection of a mixed CB/CB receptor agonist (WIN55,212-2) or their respective antagonists (SR141716A for CB and SR144528 for CB) prior to an unilateral intrastriatal microinjection of NMDA. The NMDA...... a critical involvement of CB receptor tonus on neuronal survival following NMDA receptor-induced excitotoxicity in vivo....

  14. Self-inflicted skin lesions: the importance of a proper diagnostic and therapeutic approach

    OpenAIRE

    Dimitre Dimitrov; Radomir Reszke; Jacek Szepietowski

    2016-01-01

    Introduction . Patients with self-inflicted skin lesions (SISL) are most often referred to dermatologists. Since psychological and psychiatric conditions might be the underlying reasons for the behavior of these patients, the psychology-associated component should always be kept in mind when approaching such individuals. Objective. To discuss distinctive aspects of the approach towards patients with SISL and emphasize the most relevant issues concerning the management of psychodermatose...

  15. An unusual case of self-inflicted multiple needles injuries to eye

    Directory of Open Access Journals (Sweden)

    Shweta Gaur

    2013-01-01

    Full Text Available Self-inflicted eye injuries among psychiatric patients are rare but important group of ophthalmic conditions that require close cooperation between different medical specialties to ensure optimum care of the severely disturbed patient. They have been associated with a variety of disorders, including paranoid schizophrenia, drug-induced psychosis, obsessive-compulsive disorder, depression, mental retardation, and ritualistic behavior. It has been described in both adults and children, but occurs most commonly in young adults with acute or chronic psychoses.

  16. Pharmacologic modulation of cerebral metabolic derangement and excitotoxicity in a porcine model of traumatic brain injury and hemorrhagic shock

    DEFF Research Database (Denmark)

    Hwabejire, John O; Jin, Guang; Imam, Ayesha M

    2013-01-01

    Cerebral metabolic derangement and excitotoxicity play critical roles in the evolution of traumatic brain injury (TBI). We have shown previously that treatment with large doses of valproic acid (VPA) decreases the size of brain lesion. The goal of this experiment was to determine whether...

  17. Levodopa-Induced Dyskinesia Is Related to Indirect Pathway Medium Spiny Neuron Excitotoxicity: A Hypothesis Based on an Unexpected Finding

    Directory of Open Access Journals (Sweden)

    Svetlana A. Ivanova

    2016-01-01

    Full Text Available A serendipitous pharmacogenetic finding links the vulnerability to developing levodopa-induced dyskinesia to the age of onset of Huntington’s disease. Huntington’s disease is caused by a polyglutamate expansion of the protein huntingtin. Aberrant huntingtin is less capable of binding to a member of membrane-associated guanylate kinase family (MAGUKs: postsynaptic density- (PSD- 95. This leaves more PSD-95 available to stabilize NR2B subunit carrying NMDA receptors in the synaptic membrane. This results in increased excitotoxicity for which particularly striatal medium spiny neurons from the indirect extrapyramidal pathway are sensitive. In Parkinson’s disease the sensitivity for excitotoxicity is related to increased oxidative stress due to genetically determined abnormal metabolism of dopamine or related products. This probably also increases the sensitivity of medium spiny neurons for exogenous levodopa. Particularly the combination of increased oxidative stress due to aberrant dopamine metabolism, increased vulnerability to NMDA induced excitotoxicity, and the particular sensitivity of indirect pathway medium spiny neurons for this excitotoxicity may explain the observed increased prevalence of levodopa-induced dyskinesia.

  18. Neuroprotection by delta9-tetrahydrocannabinol, the main active compound in marijuana, against ouabain-induced in vivo excitotoxicity

    NARCIS (Netherlands)

    Vliegenthart, J.F.G.; Stelt, M. van der; Veldhuis, W.B.; Bär, P.R; Veldink, G.A.; Nicolay, K.

    2001-01-01

    Excitotoxicity is a paradigm used to explain the biochemical events in both acute neuronal damage and in slowly progressive, neurodegenerative diseases. Here, we show in a longitudinal magnetic resonance imaging study that delta9-tetrahydrocannabinol (delta9-THC), the main active compound in

  19. Neuroprotection by Δ9-Tetrahydrocannabinol, the main active compound in marijuana, against ouabain-induced in vivo excitotoxicity

    NARCIS (Netherlands)

    Stelt, van der M.; Veldhuis, W.B.; Bär, P.R.; Veldink, G.A.; Vliegenthart, J.F.G.; Nicolaij, K.

    2001-01-01

    Excitotoxicity is a paradigm used to explain the biochemical events in both acute neuronal damage and in slowly progressive, neurodegenerative diseases. Here, we show in a longitudinal magnetic resonance imaging study that ¿9-tetrahydrocannabinol (¿9-THC), the main active compound in marijuana,

  20. Dynamics of Trace Element Concentration During Development and Excitotoxic Cell Death in the Cerebellum of Lurcher Mutant Mice

    Czech Academy of Sciences Publication Activity Database

    Bäurle, J.; Kučera, Jan; Frischmuth, S.; Lambertz, M.; Kranda, Karel

    2009-01-01

    Roč. 19, č. 4 (2009), s. 586-595 ISSN 1015-6305 R&D Projects: GA ČR GA309/09/1189 Institutional research plan: CEZ:AV0Z10480505 Keywords : apoptosis * copper * excitotoxicity Subject RIV: BG - Nuclear, Atomic and Molecular Physics, Colliders Impact factor: 5.903, year: 2009

  1. Antidepressant treatment and suicide attempts and self-inflicted injury in children and adolescents.

    Science.gov (United States)

    Gibbons, Robert D; Coca Perraillon, Marcelo; Hur, Kwan; Conti, Rena M; Valuck, Robert J; Brent, David A

    2015-02-01

    In the 2004, FDA placed a black box warning on antidepressants for risk of suicidal thoughts and behavior in children and adolescents. The purpose of this paper is to examine the risk of suicide attempt and self-inflicted injury in depressed children ages 5-17 treated with antidepressants in two large observational datasets taking account time-varying confounding. We analyzed two large US medical claims databases (MarketScan and LifeLink) containing 221,028 youth (ages 5-17) with new episodes of depression, with and without antidepressant treatment during the period of 2004-2009. Subjects were followed for up to 180 days. Marginal structural models were used to adjust for time-dependent confounding. For both datasets, significantly increased risk of suicide attempts and self-inflicted injury were seen during antidepressant treatment episodes in the unadjusted and simple covariate adjusted analyses. Marginal structural models revealed that the majority of the association is produced by dynamic confounding in the treatment selection process; estimated odds ratios were close to 1.0 consistent with the unadjusted and simple covariate adjusted association being a product of chance alone. Our analysis suggests antidepressant treatment selection is a product of both static and dynamic patient characteristics. Lack of adjustment for treatment selection based on dynamic patient characteristics can lead to the appearance of an association between antidepressant treatment and suicide attempts and self-inflicted injury among youths in unadjusted and simple covariate adjusted analyses. Marginal structural models can be used to adjust for static and dynamic treatment selection processes such as that likely encountered in observational studies of associations between antidepressant treatment selection, suicide and related behaviors in youth. Copyright © 2014 John Wiley & Sons, Ltd.

  2. Comparison of excitotoxic profiles of ATPA, AMPA, KA and NMDA in organotypic hippocampal slice cultures

    DEFF Research Database (Denmark)

    Kristensen, Bjarne Winther; Noraberg, J; Zimmer, J

    2001-01-01

    ) values was found after 2 days of exposure: AMPA (3.7 mM)>NMDA (11 mM)=KA (13 mM)>ATPA (33 mM). Exposed to 30 microM ATPA, 3 microM AMPA and 10 microM NMDA, CA1 was the most susceptible subfield followed by fascia dentata and CA3. Using 8 microM KA, CA3 was the most susceptible subfield, followed...... by fascia dentata and CA1. In 100 microM concentrations, all four agonists induced the same, maximal PI uptake in all hippocampal subfields, corresponding to total neuronal degeneration. Using glutamate receptor antagonists, like GYKI 52466, NBQX and MK-801, inhibition data revealed that AMPA excitotoxicity...

  3. IGF-1-Involved Negative Feedback of NR2B NMDA Subunits Protects Cultured Hippocampal Neurons Against NMDA-Induced Excitotoxicity.

    Science.gov (United States)

    Li, Yun; Sun, Wei; Han, Song; Li, Jianing; Ding, Shu; Wang, Wei; Yin, Yanling

    2017-01-01

    Insulin-like growth factor 1 (IGF-1) is a multifunctional protein involved in neuronal polarity and axonal guidance. In our previous study, it was discovered that IGF-1 alleviated 50-μM NMDA-induced excitotoxicity against neuronal autophagy via depression of NR2B p-Ser1303 activation. However, it was found that NMDA at a higher dose did not cause neuronal autophagy. And, the performance of IGF-1 under severe excitotoxicity still needs to be clarified. In this study, we observed that IGF-1 can salvage the hippocampal neurons in an autophagy-independent manner after 150-μM NMDA exposure using thiazolyl blue tetrazolium bromide (MTT), lactate dehydrogenase (LDH), Western blot assay, and transmission electron microscopy. In addition, over-activation of post-synaptic NMDARs was found with the whole-cell patch clamp recording method. In order to explore whether there is a positive feedback way for post-synaptic NMDARs and the different pathway caused by 150 μM NMDA, the phosphorylation level of Fyn and the phosphorylation site of NR2B were investigated. It was observed that NR2B p-Tyr1472 was increased by the activation of Fyn after 150-μM NMDA exposure. When the neutralizing antibody against NR2B p-Ser1303 was added into the medium, both the activations of Fyn and NR2B p-Tyr1472 were blocked, suggesting NR2B p-Ser1303 may be the initial step of NMDA-induced excitotoxicity. In addition, since IGF-1 can block the initial step of NR2B activation, its effect is concluded to continue with the development of excitotoxicity. Overall, this study strongly indicates that the relationship between different phosphorylation sites of NR2B should be laid more emphasis on, which may be a vital target for the NR2B-involved excitotoxicity.

  4. SIRT1-mediated deacetylation of PGC1α attributes to the protection of curcumin against glutamate excitotoxicity in cortical neurons

    International Nuclear Information System (INIS)

    Jia, Ning; Sun, Qinru; Su, Qian; Chen, Guomin

    2016-01-01

    It is widely accepted that accumulation of extracellular glutamate mediates neuronal injuries in a number of neurological disorders via binding glutamate receptors. However, usage of the glutamate receptor antagonists aimed to prevent glutamate excitotoxicity is still controversial. As a polyphenol natural product, curcumin, has been implied multiple bioactivities. In this study, we explored whether the silent information regulator 1 (SIRT1)-peroxisome proliferator-activated receptor-coactivator 1α (PGC1α) pathway participated in the protection of curcumin against glutamate excitotoxicity. The cultured primary cortical neurons were treated with glutamate to set up a neuronal excitotoxicity model. The MTT and TUNEL methods were employed to measure cell viability and apoptosis, respectively. The mitochondrial function, the expression levels of SIRT1, PGC1α and acetylated PGC1α (ac-PGC1α) were measured to explore the mechanism of curcumin against glutamate excitotoxicity. The results showed that glutamate significantly induced cell death and apoptosis, which was blocked by pretreatment with curcumin. Meanwhile, curcumin preserved mitochondrial function, increased the expression level of SIRT1 and reduced the level of ac-PGC1α in the presence of glutamate. These results suggest that SIRT1-mediated deacetylation of PGC1α attributes to the neuroprotection of curcumin against glutamate excitotoxicity. - Highlights: • Curcumin attenuates glutamate induced cell death and apoptosis in cultured neurons. • Curcumin preserves mitochondrial function in the presence of glutamate. • Curcumin enhanced the expression of SIRT1 in the glutamate rich environment. • SIRT1-mediated deacetylation of PGC1α attributes to the neuroprotection of curcumin.

  5. Force spectroscopy measurements show that cortical neurons exposed to excitotoxic agonists stiffen before showing evidence of bleb damage.

    Directory of Open Access Journals (Sweden)

    Shan Zou

    Full Text Available In ischemic and traumatic brain injury, hyperactivated glutamate (N-methyl-D-aspartic acid, NMDA and sodium (Nav channels trigger excitotoxic neuron death. Na(+, Ca(++ and H2O influx into affected neurons elicits swelling (increased cell volume and pathological blebbing (disassociation of the plasma membrane's bilayer from its spectrin-actomyosin matrix. Though usually conflated in injured tissue, cell swelling and blebbing are distinct processes. Around an injury core, salvageable neurons could be mildly swollen without yet having suffered the bleb-type membrane damage that, by rendering channels leaky and pumps dysfunctional, exacerbates the excitotoxic positive feedback spiral. Recognizing when neuronal inflation signifies non-lethal osmotic swelling versus blebbing should further efforts to salvage injury-penumbra neurons. To assess whether the mechanical properties of osmotically-swollen versus excitotoxically-blebbing neurons might be cytomechanically distinguishable, we measured cortical neuron elasticity (gauged via atomic force microscopy (AFM-based force spectroscopy upon brief exposure to hypotonicity or to excitotoxic agonists (glutamate and Nav channel activators, NMDA and veratridine. Though unperturbed by solution exchange per se, elasticity increased abruptly with hypotonicity, with NMDA and with veratridine. Neurons then invariably softened towards or below the pre-treatment level, sometimes starting before the washout. The initial channel-mediated stiffening bespeaks an abrupt elevation of hydrostatic pressure linked to NMDA or Nav channel-mediated ion/H2O fluxes, together with increased [Ca(++]int-mediated submembrane actomyosin contractility. The subsequent softening to below-control levels is consistent with the onset of a lethal level of bleb damage. These findings indicate that dissection/identification of molecular events during the excitotoxic transition from stiff/swollen to soft/blebbing is warranted and should be

  6. Retroperitoneal migration of a self-inflicted ballpoint pen via the urethra

    Directory of Open Access Journals (Sweden)

    Jose Cury

    2006-04-01

    Full Text Available Numerous accounts documenting the introduction of foreign bodies into the urinary bladder have been reported. These foreign bodies are typically self-inserted via urethral but migration from adjacent organs by an ulcerative process and penetrating injuries are also reported. However, "contrary" migration of a self-inflicted vesical foreign body to the retroperitoneum was not previously reported in literature. We report here a case of a ballpoint pen self-inserted via urethral by a female patient, which was identified in retroperitoneal position years later.

  7. Suicide and self-inflicted injury hospitalizations in Canada (1979 to 2014/15

    Directory of Open Access Journals (Sweden)

    R. Skinner

    2016-11-01

    Full Text Available Introduction: The purpose of this paper is to describe the trends and patterns of self-inflicted injuries, available from Canadian administrative data between 1979 and 2014/15, in order to inform and improve suicide prevention efforts. Methods: Suicide mortality and hospital separation data were retrieved from the Public Health Agency of Canada (PHAC holdings of Statistics Canada's Canadian Vital Statistics: Death Database (CVS:D (1979 to 2012; Canadian Socio-Economic Information Management System (CANSIM 2011, 2012; the Hospital Morbidity Database (HMDB (1994/95 to 2010/11; and the Discharge Abstract Database (2011/12 to 2014/15. Mortality and hospitalization counts and rates were reported by sex, 5-year age groups and method. Results: The Canadian suicide rate (males and fe­males combined, all ages, age-sex standardized rate has decreased from 14.4/100 000 (n = 3355 in 1979 to 10.4/100 000 (n = 3926 in 2012, with an annual percent change (APC of ­ 1.2% (95% CI: ­1.3 to ­1.0. However, this trend was not observed in both sexes: female suicide rates stabilized around 1990, while male rates continued declining over time—yet males still accounted for 75.7% of all suicides in 2012. Suffocation (hanging and strangulation was the primary method of suicide (46.9% among Canadians of all ages in 2012, followed by poisoning at 23.3%. In the 2014/15 fiscal year, there were 13 438 hospitalizations in Canada (excluding Quebec associated with self-in­flicted injuries—over 3 times the number of suicides. Over time females have displayed con­sistently higher rates of hospitalization for self-inflicted injury than males, with 63% of the total. Poisoning was reported as the most frequent means of self-inflicted harm in the fiscal year 2014/15, at 86% of all hospitalizations. Conclusion: Suicides and self-inflicted injuries continue to be a serious—but preventable—public health problem that requires ongoing surveillance.

  8. Self-Inflicted Needle Injuries to the Eye: A Curing Pain

    Directory of Open Access Journals (Sweden)

    Shahrokh Amiri

    2015-01-01

    Full Text Available There are few reports of severe self-injury to eyes in patients with schizophrenia. We report on a 41-year-old woman, primarily visiting for symptoms of endophthalmitis resulting from self-inflicted needles. Further evaluations established the diagnosis of schizophrenia because of arguing and commenting on auditory hallucinations and negative symptoms including social isolation, decreased self-care, blunt affect, and a monotone voice. The patient had been suffering from auditory hallucinations for several years and found relief in bodily pain caused by needles. The patient received 6 mg of risperidone. Hallucinations were resolved and self-injury behaviour was not repeated.

  9. Proposed diagnosis criteria for inflicted head injury of children younger than two years of age

    International Nuclear Information System (INIS)

    Fujiwara, Takeo; Okuyama, Makiko; Matsumoto, Tsutomu; Aritaki, Kentarou; Yotani, Nobuyuki; Miyasaka, Mikiko; Nishina, Sachiko

    2008-01-01

    It is difficult to distinguish whether children's head injuries are due to physical abuse or unintentional accidents. However, in the literature, medical findings specific to infant physical abuse were identified. Thus, we developed diagnostic criteria for inflicted head injury (IHI) and assessed its validity. Subjects were collected from all patients who were less than two years old when they visited National Center for Child Health (NCCHD) and Development and underwent head CT scan to assess head trauma from March 1, 2002 to December 31, 2005. Diagnostic criteria for IHI were developed based on definitions of Duhaime et al (1992) and Reece et al (2001). Validity of diagnosis criteria was assessed by comparing the official report to the Child Guidance Center (CGC) from NCCHD to the disposition decided by the CGC. Two-hundred and sixty cases were collected and diagnosed. There was a 86.5% match of the number of cases which were diagnosed as IHI or non-IHI using the IHI diagnostic criteria with official reports to CGC from NCCHD. Among the cases which were diagnosed as presumptive IHI and also reported to the CGC, 20 cases (83.3%) were regarded as abused cases by the CGC. The diagnostic criteria for IHI were valid and would be useful for pediatricians not to condone inflicted head injury. (author)

  10. [The peculiar features of conducting comprehensive expertises of the injuries inflicted inside the passenger car compartment].

    Science.gov (United States)

    Fetisov, V A; Gusarov, A A; Smirenin, S A

    2016-01-01

    The present article deals with the problem of forensic medical diagnostics of the injuries inflicted inside the passenger car compartment during motor vehicle accidents. The authors place special emphasis on the fact of a significant increase in the number of road traffic accidents (RTA) with such consequences throughout the world. The modern automobile industry pays much attention to the enhancement of the car safety features by significantly improving the design of passenger compartments. It accounts for a change in the traditional character of the injuries to both the driver and the passengers resulting from motor vehicle accidents. This, in turn, creates difficulties for the forensic medical experts as regards personality identification of the subjects who happened to be inside the car at the moment of the collision especially in the case of unascertainable circumstances of the accident and/or the involvement of several victims. The authors describe peculiarities of the injuries inflicted inside the passenger car compartment during road traffic accidents including such that result from bringing the driver and the passengers closer to the construction elements of the car (stage I), their direct contact with these elements (stage II), and subsequent displacement (stage III).

  11. Post-dexamethasone Cortisol, Self-inflicted Injury, and Suicidal Ideation among Depressed Adolescent Girls

    Science.gov (United States)

    Beauchaine, Theodore P.; Crowell, Sheila E.; Hsiao, Ray C.

    2014-01-01

    Although the dexamethasone suppression test (DST) has limited use as a marker of depression given inadequate sensitivity and specificity, it marks prospective risk for suicide among adults. However, few studies have examined associations between the DST, suicidal ideation, and self-inflicted injury (SII) among adolescents, even though SII is the single best predictor of eventual suicide. We evaluated the DST as a correlate of suicidal ideation and retrospective reports of self-inflicted injury (SII) among adolescent girls, ages 13–17, with histories of depression (n=28) or depression/self-harm (n=29). Lower post-DST cortisol was associated with suicidal ideation and SII, over-and-above parent-reports and combined parent-/self-reports of internalizing and externalizing behavior. These findings are consistent with recent acquired capacity models of stress-related psychopathology in which hypothalamic-pituitary adrenal (HPA) axis function is altered through epigenetic/allostatic mechanisms among vulnerable individuals who incur adversity early in life. PMID:25208812

  12. Late neurologic and cognitive sequelae of inflicted traumatic brain injury in infancy.

    Science.gov (United States)

    Barlow, Karen M; Thomson, Elaine; Johnson, David; Minns, Robert A

    2005-08-01

    There is limited information regarding the long-term outcome of inflicted traumatic brain injury (TBI), including shaken infant syndrome. The purpose of this study was to describe the long-term neurologic, behavioral, and cognitive sequelae seen in this population. A cross-sectional and prospective longitudinal study was conducted of 25 children with inflicted TBI in Scotland between 1980 and 1999. After consent was obtained, neurologic and cognitive examinations were performed on all participants and sequentially in the prospective cohort. Two global outcome measures were used: Glasgow Outcome Score (GOS) and Seshia's outcome score. Cognitive outcome was assessed using the Bayley Scales of Infant Development, British Ability Scales, and the Vineland Adaptive Behavior Scales. The mean length of follow-up was 59 months. A total of 68% of survivors were abnormal on follow-up, 36% had severe difficulties and were totally dependant, 16% had moderate difficulties, and 16% had mild difficulties on follow-up. A wide range of neurologic sequelae were seen, including motor deficits (60%), visual deficits (48%), epilepsy (20%), speech and language abnormalities (64%), and behavioral problems (52%). There was a wide range of cognitive abilities: the mean psychomotor index, 69.9 (SD: +/-25.73); and mean mental development index, 74.53 (SD: +/-28.55). Adaptive functioning showed a wide range of difficulties across all domains: communication domain (mean: 76.1; SD: +/-25.4), Daily living skills domain (mean: 76.9; SD: +/-24.3), and socialization domain (mean: 79.1; SD: +/-23.1). Outcome was found to correlate with the Pediatric Trauma Score and the Glasgow Coma Score but did not correlate with age at injury or mechanism of injury. Inflicted TBI has a very poor prognosis and correlates with severity of injury. Extended follow-up is necessary so as not to underestimate problems such as specific learning difficulties and attentional and memory problems that may become apparent only

  13. Assessment of R18, COG1410, and APP96-110 in excitotoxicity and traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Chiu Li Shan

    2017-11-01

    Full Text Available Cationic arginine-rich and poly-arginine peptides (referred to as CARPs have potent neuroprotective properties in in vitro excitotoxicity and in vivo models of stroke. Traumatic brain injury (TBI shares many pathophysiological processes as stroke, including excitotoxicity. Therefore, we evaluated our lead peptide, poly-arginine R18, with the COG1410 and APP96-110 peptides, which have neuroprotective actions following TBI. In an in vitro cortical neuronal glutamic acid excitotoxicity injury model, R18 was highly neuroprotective and reduced neuronal calcium influx, while COG1410 and APP96-110 displayed modest neuroprotection and were less effective at reducing calcium influx. In an impact-acceleration closed-head injury model (Marmarou model, R18, COG1410, and APP96-110 were administered intravenously (300 nmol/kg at 30 minutes after injury in male Sprague-Dawley rats. When compared to vehicle, no peptide significantly improved functional outcomes, however the R18 and COG1410 treatment groups displayed positive trends in the adhesive tape test and rotarod assessments. Similarly, no peptide had a significant effect on hippocampal neuronal loss, however a significant reduction in axonal injury was observed for R18 and COG1410. In conclusion, this study has demonstrated that R18 is significantly more effective than COG1410 and APP96-110 at reducing neuronal injury and calcium influx following excitotoxicity, and that both R18 and COG1410 reduce axonal injury following TBI. Additional dose response and treatment time course studies are required to further assess the efficacy of R18 in TBI.

  14. Transgenic mice expressing a Huntington s disease mutation are resistant to quinolinic acid-induced striatal excitotoxicity

    OpenAIRE

    Hansson, Oskar; Petersén, Åsa; Leist, Marcel; Nicotera, Pierluigi; Castilho, Roger F.; Brundin, Patrik

    1999-01-01

    Huntington’s disease (HD) is a hereditary neurodegenerative disorder presenting with chorea, dementia, and extensive striatal neuronal death. The mechanism through which the widely expressed mutant HD gene mediates a slowly progressing striatal neurotoxicity is unknown. Glutamate receptor-mediated excitotoxicity has been hypothesized to contribute to the pathogenesis of HD. Here we show that transgenic HD mice expressing exon 1 of a human HD gene with an expanded number of CAG repeats (line R...

  15. Repetitive urges to inflict burns: An unusual presentation of impulse control disorder.

    Science.gov (United States)

    Pal, Arghya; Parmar, Arpit; Pattanayak, Raman Deep

    2016-01-01

    Impulse control disorders (ICDs) are characterized by an inability to resist an intense impulse or drive to perform a particular act that is excessive and/or harmful to self/others. Till date, there is no published report of an ICD presenting with repetitive urges to inflict burns. We describe the case of an adult male in regular follow-up for 6 months who presented with intense, irresistible, and repetitive urges and acts of causing burns on his skin for past 1 year. The phenomenology shared the core qualities described for ICDs and patient showed adequate response to treatment. The case report describes an unusual type of ICD classifiable as not otherwise specified. More clinical and research attention is warranted toward ICDs in general, with implications for ICD-11.

  16. Repetitive urges to inflict burns: An unusual presentation of impulse control disorder

    Directory of Open Access Journals (Sweden)

    Arghya Pal

    2016-01-01

    Full Text Available Impulse control disorders (ICDs are characterized by an inability to resist an intense impulse or drive to perform a particular act that is excessive and/or harmful to self/others. Till date, there is no published report of an ICD presenting with repetitive urges to inflict burns. We describe the case of an adult male in regular follow-up for 6 months who presented with intense, irresistible, and repetitive urges and acts of causing burns on his skin for past 1 year. The phenomenology shared the core qualities described for ICDs and patient showed adequate response to treatment. The case report describes an unusual type of ICD classifiable as not otherwise specified. More clinical and research attention is warranted toward ICDs in general, with implications for ICD-11.

  17. Self-inflicted skin lesions: the importance of a proper diagnostic and therapeutic approach

    Directory of Open Access Journals (Sweden)

    Dimitre Dimitrov

    2016-12-01

    Full Text Available Introduction . Patients with self-inflicted skin lesions (SISL are most often referred to dermatologists. Since psychological and psychiatric conditions might be the underlying reasons for the behavior of these patients, the psychology-associated component should always be kept in mind when approaching such individuals. Objective. To discuss distinctive aspects of the approach towards patients with SISL and emphasize the most relevant issues concerning the management of psychodermatoses. Case report. We present a case of a 13-year-old girl with a 6-month history of skin lesions misdiagnosed as allergic contact dermatitis. Conscientious history taking and physical examination enabled the diagnosis of SISL. Conclusions. The proper approach to patients presenting with psychodermatoses differs from that for other dermatological patients and requires considering several additional aspects. We would like to emphasize the distinguishing aspects and importance of the proper approach to patients with SISL that might aid clinicians in diagnosing and treating these individuals in the future.

  18. Are There Ways out of the Self-inflicted Irrelevance of the Qualitative Off-stream?

    Directory of Open Access Journals (Sweden)

    Norbert Groeben

    2006-09-01

    Full Text Available The qualitative paradigm is relatively irrelevant in psychological research and teaching, which is not only due to the hegemony of the quantitative paradigm. This irrelevance also arises from the fragmentation within the qualitative research paradigm, which is a result of the principle of a close interdependence of research object and method; this fragmentation is evident in the lack of a systematic approach to the concept of method. The conviction to conduct a superior psychological approach leads to destructive competition both within the qualitative paradigm and in relation to the quantitative paradigm. Instead, I recommend the pursuit of approaches that attempt to integrate qualitative and quantitative research methods on the basis of the idea of ontological layers, clearly distinct from esoteric approaches. Above all, the development of sophisticated and complex methods of statistical analysis appears a promising way to overcome the self-inflicted irrelevance of the qualitative research paradigm. URN: urn:nbn:de:0114-fqs0604347

  19. Investigation of inflicted injury in a young girl reveals mild haemophilia A and Turner's syndrome.

    Science.gov (United States)

    Williams, V K; Suppiah, R; Coppin, B; Nicholls, C M; Simsek, A; McGregor, L K

    2012-02-01

    A 2-year-old girl presented to casualty with a right knee effusion after apparently minor trauma. Inflicted injury was suspected and full forensic coagulation studies were performed which revealed a mild deficiency of factor VIII. Screening of the exons and intron/exon boundaries of F8 gene indicated that the child appeared to be homozygous for the missense mutation c.5123G>A (p.Arg1708His) in exon 14 of the F8 gene. This mutation has been reported to be associated with mild haemophilia A. The possibility of hemizygosity had been masked by the test kit employed but referral to the genetics service and subsequent array CGH resulted in a diagnosis of Turner syndrome. © 2011 Blackwell Publishing Ltd.

  20. Green Tea Polyphenols Attenuated Glutamate Excitotoxicity via Antioxidative and Antiapoptotic Pathway in the Primary Cultured Cortical Neurons

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    Lin Cong

    2016-01-01

    Full Text Available Green tea polyphenols are a natural product which has antioxidative and antiapoptotic effects. It has been shown that glutamate excitotoxicity induced oxidative stress is linked to neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. In this study we explored the neuroprotective effect of green teen polyphenols against glutamate excitotoxicity in the primary cultured cortical neurons. We found that green tea polyphenols protected against glutamate induced neurotoxicity in the cortical neurons as measured by MTT and TUNEL assays. Green tea polyphenols were then showed to inhibit the glutamate induced ROS release and SOD activity reduction in the neurons. Furthermore, our results demonstrated that green tea polyphenols restored the dysfunction of mitochondrial pro- or antiapoptotic proteins Bax, Bcl-2, and caspase-3 caused by glutamate. Interestingly, the neuroprotective effect of green tea polyphenols was abrogated when the neurons were incubated with siBcl-2. Taken together, these results demonstrated that green tea polyphenols protected against glutamate excitotoxicity through antioxidative and antiapoptotic pathways.

  1. Pharmacological activation/inhibition of the cannabinoid system affects alcohol withdrawal-induced neuronal hypersensitivity to excitotoxic insults.

    Directory of Open Access Journals (Sweden)

    Marina Rubio

    Full Text Available Cessation of chronic ethanol consumption can increase the sensitivity of the brain to excitotoxic damages. Cannabinoids have been proposed as neuroprotectants in different models of neuronal injury, but their effect have never been investigated in a context of excitotoxicity after alcohol cessation. Here we examined the effects of the pharmacological activation/inhibition of the endocannabinoid system in an in vitro model of chronic ethanol exposure and withdrawal followed by an excitotoxic challenge. Ethanol withdrawal increased N-methyl-D-aspartate (NMDA-evoked neuronal death, probably by altering the ratio between GluN2A and GluN2B NMDA receptor subunits. The stimulation of the endocannabinoid system with the cannabinoid agonist HU-210 decreased NMDA-induced neuronal death exclusively in ethanol-withdrawn neurons. This neuroprotection could be explained by a decrease in NMDA-stimulated calcium influx after the administration of HU-210, found exclusively in ethanol-withdrawn neurons. By contrast, the inhibition of the cannabinoid system with the CB1 receptor antagonist rimonabant (SR141716 during ethanol withdrawal increased death of ethanol-withdrawn neurons without any modification of NMDA-stimulated calcium influx. Moreover, chronic administration of rimonabant increased NMDA-stimulated toxicity not only in withdrawn neurons, but also in control neurons. In summary, we show for the first time that the stimulation of the endocannabinoid system is protective against the hyperexcitability developed during alcohol withdrawal. By contrast, the blockade of the endocannabinoid system is highly counterproductive during alcohol withdrawal.

  2. A Comparison of Self-Inflicted Stab Wounds Versus Assault-Induced Stab Wounds

    Science.gov (United States)

    Ahn, Sanghyun; Kim, Dong Jin; Paik, Kwang Yeol; Chung, Jae Hee; Park, Woo-Chan; Kim, Wook; Lee, In Kyu

    2016-01-01

    Background Although self-inflicted and assault-induced knife injuries might have different mortality and morbidity rates, no studies have actually evaluated the importance of the cause of knife injuries in terms of patient outcomes and treatment strategies. Objectives The aims of this study were to assess the difference between the outcomes of patients presenting with self-inflicted stab wounds (SISW) versus assault-induced stab wounds (AISW). Patients and Methods A retrospective review of the relevant electronic medical records was performed for the period between January 2000 and December 2012 for patients who were referred to the department of surgery for stab wounds by the trauma team. The patients were divided into either SISW (n = 10) or AISW groups (n = 11), depending on the cause of the injury. Results A total of 19 patients had undergone exploratory laparotomy. Of the nine patients with SISW undergoing this procedure, no injury was found in seven of the patients. In the AISW group, eight of the ten laparotomies were therapeutic. Three patients in the AISW group died during hospital admission. The average number of stab wounds was 1.2 for the SISW group and 3.5 for the AISW group. Organ injuries were more frequent in the AISW group, affecting the lung (2), diaphragm (3), liver (5), small bowel (2), colon (2), and kidney (1). Conclusions Although evaluations of the initial vital signs and physical examinations are still important, the history regarding the source of the stab wounds (AISW vs. SISW) may be helpful in determining the appropriate treatment methods and predicting patient outcomes. PMID:28184363

  3. L-Lactate protects neurons against excitotoxicity: implication of an ATP-mediated signaling cascade

    KAUST Repository

    Jourdain, P.

    2016-02-19

    Converging experimental data indicate a neuroprotective action of L-Lactate. Using Digital Holographic Microscopy, we observe that transient application of glutamate (100 μM; 2 min) elicits a NMDA-dependent death in 65% of mouse cortical neurons in culture. In the presence of L-Lactate (or Pyruvate), the percentage of neuronal death decreases to 32%. UK5099, a blocker of the Mitochondrial Pyruvate Carrier, fully prevents L-Lactate-mediated neuroprotection. In addition, L-Lactate-induced neuroprotection is not only inhibited by probenicid and carbenoxolone, two blockers of ATP channel pannexins, but also abolished by apyrase, an enzyme degrading ATP, suggesting that ATP produced by the Lactate/Pyruvate pathway is released to act on purinergic receptors in an autocrine/paracrine manner. Finally, pharmacological approaches support the involvement of the P2Y receptors associated to the PI3-kinase pathway, leading to activation of KATP channels. This set of results indicates that L-Lactate acts as a signalling molecule for neuroprotection against excitotoxicity through coordinated cellular pathways involving ATP production, release and activation of a P2Y/KATP cascade.

  4. The Role of Canonical Transient Receptor Potential Channels in Seizure and Excitotoxicity

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    Fang Zheng

    2014-04-01

    Full Text Available Canonical transient receptor potential (TRPC channels are a family of polymodal cation channels with some degree of Ca2+ permeability. Although initially thought to be channels mediating store-operated Ca2+ influx, TRPC channels can be activated by stimulation of Gq-coupled G-protein coupled receptors, or by an increase in intracellular free Ca2+ concentration. Thus, activation of TRPC channels could be a common downstream event of many signaling pathways that contribute to seizure and excitotoxicity, such as N-methyl-D-aspartate (NMDA receptor-mediated Ca2+ influx, or metabotropic glutamate receptor activation. Recent studies with genetic ablation of various TRPC family members have demonstrated that TRPC channels, in particular heteromeric TRPC1/4 channels and homomeric TRPC5 channels, play a critical role in both pilocarpine-induced acute seizures and neuronal cell death. However, exact underlying mechanisms remain to be fully elucidated, and selective TRPC modulators and antibodies with better specificity are urgently needed for future research.

  5. Effects of neonatal excitotoxic lesions in ventral thalamus on social interaction in the rat.

    Science.gov (United States)

    Wolf, Rainer; Dobrowolny, Henrik; Nullmeier, Sven; Bogerts, Bernhard; Schwegler, Herbert

    2017-03-30

    The role of the thalamus in schizophrenia has increasingly been studied in recent years. Deficits in the ventral thalamus have been described in only few postmortem and neuroimaging studies. We utilised our previously introduced neurodevelopmental animal model, the neonatal excitotoxic lesion of the ventral thalamus of Sprague-Dawley rats (Wolf et al., Pharmacopsychiatry 43:99-109, 22). At postnatal day (PD7), male pubs received bilateral thalamic infusions with ibotenic acid (IBA) or artificial cerebrospinal fluid (control). In adulthood, social interaction of two animals not familiar to each other was studied by a computerised video tracking system. This study displays clear lesion effects on social interaction of adult male rats. The significant reduction of total contact time and the significant increase in distance between the animals in the IBA group compared to controls can be interpreted as social withdrawal modelling a negative symptom of schizophrenia. The significant increase of total distance travelled in the IBA group can be hypothesised as agitation modelling a positive symptom of schizophrenia. Using a triple concept of social interaction, the percentage of no social interaction (Non-SI%) was significantly larger, and inversely, the percentage of passive social interaction (SI-passive%) was significantly smaller in the IBA group when compared to controls. In conclusion, on the background of findings in schizophrenic patients, the effects of neonatal ventral thalamic IBA lesions in adult male rats support the hypothesis of face and construct validity as animal model of schizophrenia.

  6. Quinolinic Acid, an Endogenous Molecule Combining Excitotoxicity, Oxidative Stress and Other Toxic Mechanisms

    Directory of Open Access Journals (Sweden)

    Verónica Pérez-De La Cruz

    2012-01-01

    Full Text Available Quinolinic acid (QUIN, an endogenous metabolite of the kynurenine pathway, is involved in several neurological disorders, including Huntington's disease, Alzheimer's disease, schizophrenia, HIV associated dementia (HAD etc. QUIN toxicity involves several mechanisms which trigger various metabolic pathways and transcription factors. The primary mechanism exerted by this excitotoxin in the central nervous system (CNS has been largely related with the overactivation of N-methyl-D-aspartate receptors and increased cytosolic Ca 2+ concentrations, followed by mitochondrial dysfunction, cytochrome c release, ATP exhaustion, free radical formation and oxidative damage. As a result, this toxic pattern is responsible for selective loss of middle size striatal spiny GABAergic neurons and motor alterations in lesioned animals. This toxin has recently gained attention in biomedical research as, in addition to its proven excitotoxic profile, a considerable amount of evidence suggests that oxidative stress and energetic disturbances are major constituents of its toxic pattern in the CNS. Hence, this profile has changed our perception of how QUIN-related disorders combine different toxic mechanisms resulting in brain damage. This review will focus on the description and integration of recent evidence supporting old and suggesting new mechanisms to explain QUIN toxicity.

  7. L-Lactate protects neurons against excitotoxicity: implication of an ATP-mediated signaling cascade

    KAUST Repository

    Jourdain, P.; Allaman, I.; Rothenfusser, K.; Fiumelli, Hubert; Marquet, P.; Magistretti, Pierre J.

    2016-01-01

    Converging experimental data indicate a neuroprotective action of L-Lactate. Using Digital Holographic Microscopy, we observe that transient application of glutamate (100 μM; 2 min) elicits a NMDA-dependent death in 65% of mouse cortical neurons in culture. In the presence of L-Lactate (or Pyruvate), the percentage of neuronal death decreases to 32%. UK5099, a blocker of the Mitochondrial Pyruvate Carrier, fully prevents L-Lactate-mediated neuroprotection. In addition, L-Lactate-induced neuroprotection is not only inhibited by probenicid and carbenoxolone, two blockers of ATP channel pannexins, but also abolished by apyrase, an enzyme degrading ATP, suggesting that ATP produced by the Lactate/Pyruvate pathway is released to act on purinergic receptors in an autocrine/paracrine manner. Finally, pharmacological approaches support the involvement of the P2Y receptors associated to the PI3-kinase pathway, leading to activation of KATP channels. This set of results indicates that L-Lactate acts as a signalling molecule for neuroprotection against excitotoxicity through coordinated cellular pathways involving ATP production, release and activation of a P2Y/KATP cascade.

  8. The insulin/IGF signaling regulators cytohesin/GRP-1 and PIP5K/PPK-1 modulate susceptibility to excitotoxicity in C. elegans.

    Directory of Open Access Journals (Sweden)

    Nazila Tehrani

    Full Text Available During ischemic stroke, malfunction of excitatory amino acid transporters and reduced synaptic clearance causes accumulation of Glutamate (Glu and excessive stimulation of postsynaptic neurons, which can lead to their degeneration by excitotoxicity. The balance between cell death-promoting (neurotoxic and survival-promoting (neuroprotective signaling cascades determines the fate of neurons exposed to the excitotoxic insult. The evolutionary conserved Insulin/IGF Signaling (IIS cascade can participate in this balance, as it controls cell stress resistance in nematodes and mammals. Blocking the IIS cascade allows the transcription factor FoxO3/DAF-16 to accumulate in the nucleus and activate a transcriptional program that protects cells from a range of insults. We study the effect of IIS cascade on neurodegeneration in a C. elegans model of excitotoxicity, where a mutation in a central Glu transporter (glt-3 in a sensitizing background causes Glu-Receptor -dependent neuronal necrosis. We expand our studies on the role of the IIS cascade in determining susceptibility to excitotoxic necrosis by either blocking IIS at the level of PI3K/AGE-1 or stimulating it by removing the inhibitory effect of ZFP-1 on the expression of PDK-1. We further show that the components of the Cytohesin/GRP-1, Arf, and PIP5K/PPK-1 complex, known to regulate PIP2 production and the IIS cascade, modulate nematode excitotoxicity: mutations that are expected to reduce the complex's ability to produce PIP2 and inhibit the IIS cascade protect from excitotoxicity, while overstimulation of PIP2 production enhances neurodegeneration. Our observations therefore affirm the importance of the IIS cascade in determining the susceptibility to necrotic neurodegeneration in nematode excitotoxicity, and demonstrate the ability of Cytohesin/GRP-1, Arf, and PIP5K/PPK-1 complex to modulate neuroprotection.

  9. Glial activation in nitrous oxide toxicity is related to oxidative stress and glutamate excitotoxicity

    Directory of Open Access Journals (Sweden)

    Sandeep Kumar Singh

    2017-12-01

    Full Text Available Myelin disorders can be due to diverse mechanisms such as autoimmune, parainfectious, metabolic or toxic. The prototype of immune mediated demyelination is multiple sclerosis. To understand the underlying mechanism of cell damage in vitamin b12 deficiency, a number of animal models have been used which include total gastrectomy (TGX, cobalamine deficient diet and N2O exposure (Tredici G, et al., 1998;Scalabrino G, 2001. Six adult wistar male rats were exposed to N2O oxygen mixture in 1:1 ratio at a rate of 2 L/min for 120 min for 60 days. The control rats received only oxygen and room air. At the end of exposure, spontaneous locomotor activity (total distance travelled, time resting, time moving, number of rearing, stereotypic count and grip strength. Plasma glutathione (GSH, total antioxidant capacity (TAC and serum malonodialdehyde (MDA and serum homocysteine (Hcy were measured by spectrophotometer. Glutamate in the cerebral cortex and cerebellum was measured by colorimetry. Immunohistochemistry for GFAP expression in brain and spinal cord was done and quantified using image J software. The N2O exposed rats had significant reduction in total distance travelled, time moving, number of rearing and increased time resting compared to the controls. Hcy, glutamate and MDA levels were increased, and GSH and TAC decreased in N2O exposed group compared to the controls. GFAP was more expressed in N2O exposed group, and its expression was higher in spinal cord compared to brain. The GFAP expression correlated with neurobehavioral changes, oxidative stress and glutamate level.N2O toxicity results in GFAP expression suggesting astrocytic reaction, which is mediated by oxidative stress and excitotoxicity.

  10. Human immunodeficiency virus-1 protein Tat induces excitotoxic loss of presynaptic terminals in hippocampal cultures.

    Science.gov (United States)

    Shin, Angela H; Thayer, Stanley A

    2013-05-01

    Human immunodeficiency virus (HIV) infection of the CNS produces dendritic damage that correlates with cognitive decline in patients with HIV-associated neurocognitive disorders (HAND). HIV-induced neurotoxicity results in part from viral proteins shed from infected cells, including the HIV transactivator of transcription (Tat). We previously showed that Tat binds to the low density lipoprotein receptor-related protein (LRP), resulting in overactivation of NMDA receptors, activation of the ubiquitin-proteasome pathway, and subsequent loss of postsynaptic densities. Here, we show that Tat also induces a loss of presynaptic terminals. The number of presynaptic terminals was quantified using confocal imaging of synaptophysin fused to green fluorescent protein (Syn-GFP). Tat-induced loss of presynaptic terminals was secondary to excitatory postsynaptic mechanisms because treatment with an LRP antagonist or an NMDA receptor antagonist inhibited this loss. Treatment with nutlin-3, an E3 ligase inhibitor, prevented Tat-induced loss of presynaptic terminals. These data suggest that Tat-induced loss of presynaptic terminals is a consequence of excitotoxic postsynaptic activity. We previously found that ifenprodil, an NR2B subunit-selective NMDA receptor antagonist, induced recovery of postsynaptic densities. Here we show that Tat-induced loss of presynaptic terminals was reversed by ifenprodil treatment. Thus, Tat-induced loss of presynaptic terminals is reversible, and this recovery can be initiated by inhibiting a subset of postsynaptic NMDA receptors. Understanding the dynamics of synaptic changes in response to HIV infection of the CNS may lead to the design of improved pharmacotherapies for HAND patients. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. Correlation between incidences of self-inflicted burns and means of inbreeding coefficients, an ecologic study.

    Science.gov (United States)

    Saadat, Mostafa; Zendeh-Boodi, Zahra

    2006-09-01

    The aim of the study is to obtain more insight into the possible association between consanguinity and the incidence of deliberate self-burning. Data were obtained by analysis of medical records of patients hospitalized in two referral burn centers: Chormy Burn Center (Bushehr Province, south of Iran) from March 21, 1998, through March 20, 2004, and Shahid Sadoqi Center of Burns and Injuries (Yazd Province, center of Iran) from March 21, 2000, through March 20, 2004. The incidence of suicidal burns was 6.51 and 2.32/100,000 person-years for Bushehr and Yazd Provinces, respectively. The observed sex ratio of patients in both centers indicated there was a female predominance in patients with self-inflicted burns. Using patients' home addresses, patients were sorted into 16 cities. The incidence of suicide by self-burning ranged from 0.80 (for Tabas, located in Yazd Province) to 12.60/100,000 person-years (for Dilam, located in Bushehr Province). The coefficient of inbreeding defines the probability that an individual received both alleles of a pair from an identical ancestral source. There was a significant correlation between incidences of suicidal burns and mean coefficient of inbreeding (r = 0.782, df = 14, p < 0.001). In addition to other factors, consanguineous marriage may be a risk factor that influences the incidence of suicidal burns in a population.

  12. Increasing incidence of injuries and fatalities inflicted by wild animals in Kashmir.

    Science.gov (United States)

    Nabi, Dar G; Tak, Shafaat Rashid; Kangoo, K A; Halwai, Manzoor A

    2009-01-01

    To clarify the causes of the increased incidence of injuries inflicted by wild animals in Kashmir, and to suggest preventive measures. A retrospective study reviewed records of these injuries. Data were collected from the hospital in Srinagar and from the Wildlife Protection Department of Kashmir. A total of 203 attacks (26 deaths and 177 near-fatal injuries) were recorded from January 2005 to October 2007, involving 145 (71.5%) male and 58 (28.5%) female victims. The attacking animal was a black bear in 104 (51.2%), a leopard in 18 (8.8%), a wolf in 7 (3.4%) and unidentified in 74 (36.4%) cases; 130 (64%) of these attacks occurred in southern Kashmir. The steady increase in human population in areas close to jungle results in deforestation and destruction of wildlife habitat. The reduction in monkeys and deer (the staple food of leopards) causes these dangerous predators to search for food in the areas occupied by humans, who may then be attacked. Treatment of these cases requires a multidisciplinary approach, including an orthopaedic surgeon, plastic surgeon, microbiologist and psychiatrist, to achieve best cosmetic and functional results.

  13. Parent–Child Interactions, Peripheral Serotonin, and Self-Inflicted Injury in Adolescents

    Science.gov (United States)

    Crowell, Sheila E.; Beauchaine, Theodore P.; McCauley, Elizabeth; Smith, Cindy J.; Vasilev, Christina A.; Stevens, Adrianne L.

    2009-01-01

    Self-inflicted injury in adolescence indicates significant emotional and psychological suffering. Although data on the etiology of self-injury are limited, current theories suggest that the emotional lability observed among self-injuring adolescents results from complex interactions between individual biological vulnerabilities and environmental risk. For example, deficiencies in serotonergic functioning, in conjunction with certain family interaction patterns, may contribute to the development of emotional lability and risk for self-injury. The authors explored the relation between peripheral serotonin levels and mother–child interaction patterns among typical (n = 21) and self-injuring (n = 20) adolescents. Findings revealed higher levels of negative affect and lower levels of both positive affect and cohesiveness among families of self-injuring participants. Peripheral serotonin was also correlated with the expression of positive affect within dyads. Furthermore, adolescents’ serotonin levels interacted with negativity and conflict within dyads to explain 64% of the variance in self-injury. These findings underscore the importance of considering both biological and environmental risk factors in understanding and treating self-injuring adolescents. PMID:18229978

  14. Development of self-inflicted injury: Comorbidities and continuities with borderline and antisocial personality traits.

    Science.gov (United States)

    Crowell, Sheila E; Kaufman, Erin A

    2016-11-01

    Self-inflicted injury (SII) is a continuum of intentionally self-destructive behaviors, including nonsuicidal self-injuries, suicide attempts, and death by suicide. These behaviors are among the most pressing yet perplexing clinical problems, affecting males and females of every race, ethnicity, culture, socioeconomic status, and nearly every age. The complexity of these behaviors has spurred an immense literature documenting risk and vulnerability factors ranging from individual to societal levels of analysis. However, there have been relatively few attempts to articulate a life span developmental model that integrates ontogenenic processes across these diverse systems. The objective of this review is to outline such a model with a focus on how observed patterns of comorbidity and continuity can inform developmental theories, early prevention efforts, and intervention across traditional diagnostic boundaries. Specifically, when SII is viewed through the developmental psychopathology lens, it becomes apparent that early temperamental risk factors are associated with risk for SII and a range of highly comorbid conditions, such as borderline and antisocial personality disorders. Prevention efforts focused on early-emerging biological and temperamental contributors to psychopathology have great potential to reduce risk for many presumably distinct clinical problems. Such work requires identification of early biological vulnerabilities, behaviorally conditioned social mechanisms, as well as societal inequities that contribute to self-injury and underlie intergenerational transmission of risk.

  15. [The morphological features of skin wounds inflicted by joinery hand saws designed for different types of sawing].

    Science.gov (United States)

    Sarkisian, B A; Azarov, P A

    2014-01-01

    The objective of the present work was to study the morphological features of skin wounds inflicted by joinery hand saws designed for longitudinal, transverse, and mixed sawing. A total of 60 injuries to the thigh skin inflicted by the recurring and reciprocating saw movements were simulated. The hand saws had 5 mm high "sharp" and "blunt"-tipped teeth. The analysis of the morphological features of the wounds revealed differences in their length and depth, shape of edge cuts and defects, and the relief of the walls depending on the sawtooth sharpness and the mode of sawing. It is concluded that morphological features of the wounds may be used to determine the type of the saw, the sharpness of its teeth, the direction and frequency of its movements.

  16. “It's Just a Matter of Time:” Lessons from Agency and Community Responses to Polar Bear-inflicted Human Injury

    OpenAIRE

    Aimee L Schmidt; Douglas A Clark

    2018-01-01

    Bear-inflicted human injuries or deaths are often widely publicised, controversial, and evoke substantial social responses that articulate public expectations about bear management. In this paper, we examine how local people and management agencies (i.e. Manitoba Conservation, Parks Canada, and the Town of Churchill) responded to a polar bear-inflicted human injury in Churchill, Manitoba, Canada. On November 1st, 2013, two people in Churchill were badly mauled by a polar bear. The incident sh...

  17. Growth hormone reverses excitotoxic damage induced by kainic acid in the green iguana neuroretina.

    Science.gov (United States)

    Ávila-Mendoza, José; Mora, Janeth; Carranza, Martha; Luna, Maricela; Arámburo, Carlos

    2016-08-01

    It is known that growth hormone (GH) is expressed in extrapituitary tissues, including the nervous system and ocular tissues, where it is involved in autocrine/paracrine actions related to cell survival and anti-apoptosis in several vertebrates. Little is known, however, in reptiles, so we analyzed the expression and distribution of GH in the eye of green iguana and its potential neuroprotective role in retinas that were damaged by the intraocular administration of kainic acid (KA). It was found, by Western blotting, that GH-immunoreactivity (GH-IR) was expressed as two isoforms (15 and 26kDa, under reducing conditions) in cornea, vitreous, retina, crystalline, iris and sclera, in varying proportions. Also, two bands for the growth hormone receptor (GHR)-IR were observed (70 and 44kDa, respectively) in the same tissues. By immunofluorescence, GH-IR was found in neurons present in several layers of the neuroretina (inner nuclear [INL], outer nuclear [ONL] and ganglion cell [GCL] layers) as determined by its co-existence with NeuN, but not in glial cells. In addition, GH and GHR co-expression was found in the same cells, suggesting paracrine/autocrine interactions. KA administration induced retinal excitotoxic damage, as determined by a significant reduction of the cell density and an increase in the appearance of apoptotic cells in the INL and GCL. In response to KA injury, both endogenous GH and Insulin-like Growth Factor I (IGF-I) expression were increased by 70±1.8% and 33.3±16%, respectively. The addition of exogenous GH significantly prevented the retinal damage produced by the loss of cytoarchitecture and cell density in the GCL (from 4.9±0.79 in the control, to 1.45±0.2 with KA, to 6.35±0.49cell/mm(2) with KA+GH) and in the INL (19.12±1.6, 10.05±1.9, 21.0±0.8cell/mm(2), respectively) generated by the long-term effect of 1mM KA intraocular administration. The co-incubation with a specific anti-GH antibody, however, blocked the protective effect of GH

  18. Mechanisms underlying the neurotoxicity induced by glyphosate-based herbicide in immature rat hippocampus: Involvement of glutamate excitotoxicity

    International Nuclear Information System (INIS)

    Cattani, Daiane; Oliveira Cavalli, Liz Vera Lúcia de; Heinz Rieg, Carla Elise; Domingues, Juliana Tonietto; Dal-Cim, Tharine; Tasca, Carla Inês; Mena Barreto Silva, Fátima Regina; Zamoner, Ariane

    2014-01-01

    Graphical abstract: - Highlights: • Roundup ® induces Ca 2+ influx through L-VDCC and NMDA receptor activation. • The mechanisms underlying Roundup ® neurotoxicity involve glutamatergic excitotoxicity. • Kinase pathways participate in Roundup ® -induced neural toxicity. • Roundup ® alters glutamate uptake, release and metabolism in hippocampal cells. - Abstract: Previous studies demonstrate that glyphosate exposure is associated with oxidative damage and neurotoxicity. Therefore, the mechanism of glyphosate-induced neurotoxic effects needs to be determined. The aim of this study was to investigate whether Roundup ® (a glyphosate-based herbicide) leads to neurotoxicity in hippocampus of immature rats following acute (30 min) and chronic (pregnancy and lactation) pesticide exposure. Maternal exposure to pesticide was undertaken by treating dams orally with 1% Roundup ® (0.38% glyphosate) during pregnancy and lactation (till 15-day-old). Hippocampal slices from 15 day old rats were acutely exposed to Roundup ® (0.00005–0.1%) during 30 min and experiments were carried out to determine whether glyphosate affects 45 Ca 2+ influx and cell viability. Moreover, we investigated the pesticide effects on oxidative stress parameters, 14 C-α-methyl-amino-isobutyric acid ( 14 C-MeAIB) accumulation, as well as glutamate uptake, release and metabolism. Results showed that acute exposure to Roundup ® (30 min) increases 45 Ca 2+ influx by activating NMDA receptors and voltage-dependent Ca 2+ channels, leading to oxidative stress and neural cell death. The mechanisms underlying Roundup ® -induced neurotoxicity also involve the activation of CaMKII and ERK. Moreover, acute exposure to Roundup ® increased 3 H-glutamate released into the synaptic cleft, decreased GSH content and increased the lipoperoxidation, characterizing excitotoxicity and oxidative damage. We also observed that both acute and chronic exposure to Roundup ® decreased 3 H-glutamate uptake and

  19. Novel application of stem cell-derived neurons to evaluate the time- and dose-dependent progression of excitotoxic injury.

    Directory of Open Access Journals (Sweden)

    Ian M Gut

    Full Text Available Glutamate receptor (GluR-mediated neurotoxicity is implicated in a variety of disorders ranging from ischemia to neural degeneration. Under conditions of elevated glutamate, the excessive activation of GluRs causes internalization of pathologic levels of Ca(2+, culminating in bioenergetic failure, organelle degradation, and cell death. Efforts to characterize cellular and molecular aspects of excitotoxicity and conduct therapeutic screening for pharmacologic inhibitors of excitogenic progression have been hindered by limitations associated with primary neuron culture. To address this, we evaluated glutamate-induced neurotoxicity in highly enriched glutamatergic neurons (ESNs derived from murine embryonic stem cells. As of 18 days in vitro (DIV 18, ESNs were synaptically coupled, exhibited spontaneous network activity with neurotypic mEPSCs and expressed NMDARs and AMPARs with physiological current:voltage behaviors. Addition of 0.78-200 μM glutamate evoked reproducible time- and dose-dependent metabolic failure in 6 h, with a calculated EC50 value of 0.44 μM at 24 h. Using a combination of cell viability assays and electrophysiology, we determined that glutamate-induced toxicity was specifically mediated by NMDARs and could be inhibited by addition of NMDAR antagonists, increased extracellular Mg(2+ or substitution of Ba(2+ for Ca(2+. Glutamate treatment evoked neurite fragmentation and focal swelling by both immunocytochemistry and scanning electron microscopy. Presentation of morphological markers of cell death was dose-dependent, with 0.78-200 μM glutamate resulting in apoptosis and 3000 μM glutamate generating a mixture of necrosis and apoptosis. Addition of neuroprotective small molecules reduced glutamate-induced neurotoxicity in a dose-dependent fashion. These data indicate that ESNs replicate many of the excitogenic mechanisms observed in primary neuron culture, offering a moderate-throughput model of excitotoxicity that combines the

  20. Low dose of L-glutamic acid attenuated the neurological dysfunctions and excitotoxicity in bilateral common carotid artery occluded mice.

    Science.gov (United States)

    Ramanathan, Muthiah; Abdul, Khadar K; Justin, Antony

    2016-10-01

    Glutamate, an excitatory neurotransmitter in the brain, produces excitotoxicity through its agonistic action on postsynaptic N-methyl-D-aspartate receptor, resulting in neurodegeneration. We hypothesized that the administration of low doses of glutamate in cerebral ischemia could attenuate the excitotoxicity in neurons through its autoreceptor regulatory mechanism, and thereby control neurodegeneration. To test the hypothesis, the effect of L-glutamic acid (L-GA) 400 μmol/l/kg was evaluated in a bilateral common carotid artery occlusion-induced global ischemic mouse model. Memantine was used as a positive control. Global ischemia in mice was induced by occlusion of both the common carotid artery (bilateral common carotid artery occlusion) for 20 min, followed by reperfusion injury. L-GA was infused slowly through the tail vein 30 min before the surgery and every 24 h thereafter until the end of the experiment. The time-dependent change in cerebral blood flow was monitored using a laser Doppler image analyzer. The neurotransmitters glutamate and γ-aminobutyric acid (GABA) and the neurobiochemicals ATP, glutathione, and nitric oxide were measured in the different regions of brain at 0, 24, 48, and 72 h after reperfusion injury. L-GA increased locomotor activity, muscle coordination, and cerebral blood flow in ischemic mice at 72 h after ischemic insult. L-GA reduced glutamate levels in the cortex, striatum, and hippocampus at 72 h, whereas GABA levels were elevated in all three brain regions studied. Further, L-GA elevated glutathione levels and attenuated nitric oxide levels, but failed to restore ATP levels 72 h after ischemia-reperfusion. We conclude that the gradual reduction of glutamate along with elevation of GABA in different brain regions could have contributed toward the neuroprotective effect of L-GA. Hence, a slow infusion of a low dose of L-GA could be beneficial in controlling excitotoxicity-induced neurodegeneration following ischemia.

  1. Protection of cortical cells by equine estrogens against glutamate-induced excitotoxicity is mediated through a calcium independent mechanism

    Directory of Open Access Journals (Sweden)

    Perrella Joel

    2005-05-01

    Full Text Available Abstract Background High concentrations of glutamate can accumulate in the brain and may be involved in the pathogenesis of neurodegenerative disorders such as Alzheimer's disease. This form of neurotoxicity involves changes in the regulation of cellular calcium (Ca2+ and generation of free radicals such as peroxynitrite (ONOO-. Estrogen may protect against glutamate-induced cell death by reducing the excitotoxic Ca2+ influx associated with glutamate excitotoxicity. In this study, the inhibition of N-methyl-D-aspartate (NMDA receptor and nitric oxide synthase (NOS along with the effect of 17β-estradiol (17β-E2 and a more potent antioxidant Δ8, 17β-estradiol (Δ8, 17β-E2 on cell viability and intracellular Ca2+ ([Ca2+]i, following treatment of rat cortical cells with glutamate, was investigated. Results Primary rat cortical cells were cultured for 7–12 days in Neurobasal medium containing B27 supplements. Addition of glutamate (200 μM decreased cell viability to 51.3 ± 0.7% compared to control. Treatment with the noncompetitive NMDAR antagonist, MK-801, and the NOS inhibitor, L-NAME, completely prevented cell death. Pretreatment (24 hrs with 17β-E2 and Δ8, 17β-E2 (0.01 to 10 μM significantly reduced cell death. 17β-E2 was more potent than Δ8, 17β-E2. Glutamate caused a rapid 2.5 fold increase in [Ca2+]i. Treatment with 0.001 to 10 μM MK-801 reduced the initial Ca2+ influx by 14–41% and increased cell viability significantly. Pretreatment with 17β-E2 and Δ8, 17β-E2 had no effect on Ca2+ influx but protected the cortical cells against glutamate-induced cell death. Conclusion Glutamate-induced cell death in cortical cultures can occur through NMDAR and NOS-linked mechanisms by increasing nitric oxide and ONOO-. Equine estrogens: 17β-E2 and Δ8, 17β-E2, significantly protected cortical cells against glutamate-induced excitotoxicity by a mechanism that appears to be independent of Ca2+ influx. To our knowledge, this is a first

  2. Effects of dimeric PSD-95 inhibition on excitotoxic cell death and outcome after controlled cortical impact in rats

    DEFF Research Database (Denmark)

    Sommer, Jens Bak; Bach, Anders; Rytter, Hana Malá

    2017-01-01

    Therapeutic effects of PSD-95 inhibition have been demonstrated in numerous studies of stroke; however only few studies have assessed the effects of PSD-95 inhibitors in traumatic brain injury (TBI). As the pathophysiology of TBI partially overlaps with that of stroke, PSD-95 inhibition may also...... assessed in a water maze at two weeks post-trauma, and at four weeks lesion volumes were estimated. Overall, UCCB01-144 did not protect against NMDA-toxicity in neuronal cultures or experimental TBI in rats. Important factors that should be investigated further in future studies assessing the effects...... be an effective therapeutic strategy in TBI. The objectives of the present study were to assess the effects of a dimeric inhibitor of PSD-95, UCCB01-144, on excitotoxic cell death in vitro and outcome after experimental TBI in rats in vivo. In addition, the pharmacokinetic parameters of UCCB01-144 were...

  3. Protective effect of methanol extract of Uncaria rhynchophylla against excitotoxicity induced by N-methyl-D-aspartate in rat hippocampus.

    Science.gov (United States)

    Lee, Jongseok; Son, Dongwook; Lee, Pyeongjae; Kim, Dae-Keun; Shin, Min-Chul; Jang, Mi-Hyeon; Kim, Chang-Ju; Kim, Yong-Sik; Kim, Sun-Yeou; Kim, Hocheol

    2003-05-01

    Uncaria rhynchophylla is a medicinal herb used for convulsive disorders in Oriental medicine. In this study, the effect of the methanol extract of Uncaria rhynchophylla against N-methyl-D-aspartate (NMDA)-induced excitotoxicity was investigated. Pretreatment with the extract of Uncaria rhynchopylla reduced the degree of neuronal damage induced by NMDA exposure in cultured hippocampal slices. In the patch clamp study, Uncaria rhynchophylla significantly inhibited NMDA receptor-activated ion current in acutely dissociated hippocampal CA1 neurons. These results indicate that Uncaria rhynchophylla offers protection against NMDA-induced neuronal injury and inhibitory action on NMDA receptor-mediated ion current may be a mechanism behind the neuroprotective effect of Uncaria rhynchophylla.

  4. Prolactin-induced neuroprotection against glutamate excitotoxicity is mediated by the reduction of [Ca2+]i overload and NF-κB activation

    Science.gov (United States)

    Rivero-Segura, Nadia A.; Flores-Soto, Edgar; García de la Cadena, Selene; Coronado-Mares, Isabel; Gomez-Verjan, Juan C.; Ferreira, Diana G.; Cabrera-Reyes, Erika Alejandra; Lopes, Luísa V.; Massieu, Lourdes

    2017-01-01

    Prolactin (PRL) is a peptidic hormone that displays pleiotropic functions in the organism including different actions in the brain. PRL exerts a neuroprotective effect against excitotoxicity produced by glutamate (Glu) or kainic acid in both in vitro and in vivo models. It is well known that Glu excitotoxicity causes cell death through apoptotic or necrotic pathways due to intracellular calcium ([Ca2+] i) overload. Therefore, the aim of the present study was to assess the molecular mechanisms by which PRL maintains cellular viability of primary cultures of rat hippocampal neurons exposed to Glu excitotoxicity. We determined cell viability by monitoring mitochondrial activity and using fluorescent markers for viable and dead cells. The intracellular calcium level was determined by a fluorometric assay and proteins involved in the apoptotic pathway were determined by immunoblot. Our results demonstrated that PRL afforded neuroprotection against Glu excitotoxicity, as evidenced by a decrease in propidium iodide staining and by the decrease of the LDH activity. In addition, the MTT assay shows that PRL maintains normal mitochondrial activity even in neurons exposed to Glu. Furthermore, the Glu-induced intracellular [Ca2+]i overload was attenuated by PRL. These data correlate with the reduction found in the level of active caspase-3 and the pro-apoptotic ratio (Bax/Bcl-2). Concomitantly, PRL elicited the nuclear translocation of the transcriptional factor NF-κB, which was detected by immunofluorescence and confocal microscopy. To our knowledge, this is the first report demonstrating that PRL prevents Glu excitotoxicity by a mechanism involving the restoration of the intracellular calcium homeostasis and mitochondrial activity, as well as an anti-apoptotic action possibly mediated by the activity of NF-κB. Overall, the current results suggest that PRL could be of potential therapeutic advantage in the treatment of neurodegenerative diseases. PMID:28475602

  5. Protection of neurons in the retinal ganglion cell layer against excitotoxicity by the N-acylethanolamine, N-linoleoylethanolamine

    Directory of Open Access Journals (Sweden)

    Duncan RS

    2011-04-01

    Full Text Available R. Scott Duncan1,*, Hua Xin1,*, Daryl L Goad1, Kent D Chapman2,3, Peter Koulen1,31Vision Research Center and Departments of Ophthalmology and Basic Medical Science, School of Medicine, University of Missouri, Kansas City, MO, USA; 2Department of Biological Sciences, University of North Texas, Denton, TX, USA; 3Center for Plant Lipid Research, University of North Texas, Denton, TX, USA *Authors contributed equallyAbstract: Retinal ganglion cell (RGC death is a hallmark of neurodegenerative diseases and disease processes of the eye, including glaucoma. The protection of RGCs has been an important strategy for combating glaucoma, but little clinical success has been reported to date. One pathophysiological consequence of glaucoma is excessive extracellular glutamate subsequently leading to excitotoxicity in the retina. Endocannabinoids, such as the N-acylethanolamine (NAE, arachidonylethanolamine (NAE 20:4, exhibit neuroprotective properties in some models of neurodegenerative disease. The majority of NAEs, however, are not cannabinoids, and their physiological function is not clear. Here, we determined whether the noncannabinoid NAE, linoleoylethanolamine (NAE18:2, protects neurons in the RGC layer against glutamate excitotoxicity in ex-vivo retina cultures. Using a terminal deoxynucleotidyl transferase-mediated dUTP (2´-deoxyuridine 5´-triphosphate nick-end labeling (TUNEL assay, we determined that NAE18:2 reduces the number of apoptotic RGC layer neurons in response to glutamate and conclude that NAE18:2 is a neuroprotective compound with potential for treating glaucomatous retinopathy.Keywords: neuroprotection, glutamate, calcium signaling, immunocytochemistry, eye, vision, glaucoma.

  6. Hydrogen-rich saline protects retina against glutamate-induced excitotoxic injury in guinea pig.

    Science.gov (United States)

    Wei, Lihua; Ge, Li; Qin, Shucun; Shi, Yunzhi; Du, Changqing; Du, Hui; Liu, Liwei; Yu, Yang; Sun, Xuejun

    2012-01-01

    Molecular hydrogen (H(2)) is an efficient antioxidant that can selectively reduce hydroxyl radicals and inhibit oxidative stress-induced injuries. We investigated the protective effects and mechanism of hydrogen-rich saline in a glutamate-induced retinal injury model. Retinal excitotoxicity was induced in healthy guinea pigs by injecting glutamate into the vitreous cavity. After 30 min, hydrogen-rich saline was injected into the vitreous cavity, the peritoneal cavity or both. Seven days later, the retinal stress response was evaluated by examining the stress biomarkers, inducible nitric-oxide synthase (iNOS) and glucose-regulated protein 78 (GRP78). The impaired glutamate uptake was assessed by the expression of the excitatory amino acid transporter 1(EAAT-1). The retinal histopathological changes were investigated, focusing on the thicknesses of the entire retina and its inner layer, the number of cells in the retinal ganglion cell layer (GCL) and the ultrastructure of the retinal ganglion cells (RGCs) and glial cells. Compared with the glutamate-induced injury group, the hydrogen-rich saline treatment reduced the loss of cells in the GCL and thinning of the retina and attenuated cellular morphological damage. These improvements were greatest in animals that received H(2) injections into both the vitreous and the peritoneal cavities. The hydrogen-rich saline also inhibited the expression of glial fibrillary acidic protein (GFAP) in Müller cells, CD11b in microglia, and iNOS and GRP78 in glial cells. Moreover, the hydrogen-rich saline increased the expression of EAAT-1. In conclusion, the administration of hydrogen-rich saline through the intravitreal or/and intraperitoneal routes could reduce the retinal excitotoxic injury and promote retinal recovery. This result likely occurs by inhibiting the activation of glial cells, decreasing the production of the iNOS and GRP78 and promoting glutamate clearance. Copyright © 2011 Elsevier Ltd. All rights reserved.

  7. Neuroprotection from NMDA excitotoxic lesion by Cu/Zn superoxide dismutase gene delivery to the postnatal rat brain by a modular protein vector

    OpenAIRE

    Peluffo, Hugo; Acarin, Laia; Arís, Anna; González, Pau; Villaverde, Antoni; Castellano, Bernardo; González, Berta

    2006-01-01

    Abstract Background Superoxide mediated oxidative stress is a key neuropathologic mechanism in acute central nervous system injuries. We have analyzed the neuroprotective efficacy of the transient overexpression of antioxidant enzyme Cu/Zn Superoxide dismutase (SOD) after excitotoxic injury to the immature rat brain by using a recently constructed modular protein vector for non-viral gene delivery termed NLSCt. For this purpose, animals were injected with the NLSCt vector carrying the Cu/Zn S...

  8. The hippocampus and appetitive Pavlovian conditioning: effects of excitotoxic hippocampal lesions on conditioned locomotor activity and autoshaping.

    Science.gov (United States)

    Ito, Rutsuko; Everitt, Barry J; Robbins, Trevor W

    2005-01-01

    The hippocampus (HPC) is known to be critically involved in the formation of associations between contextual/spatial stimuli and behaviorally significant events, playing a pivotal role in learning and memory. However, increasing evidence indicates that the HPC is also essential for more basic motivational processes. The amygdala, by contrast, is important for learning about the motivational significance of discrete cues. This study investigated the effects of excitotoxic lesions of the rat HPC and the basolateral amygdala (BLA) on the acquisition of a number of appetitive behaviors known to be dependent on the formation of Pavlovian associations between a reward (food) and discrete stimuli or contexts: (1) conditioned/anticipatory locomotor activity to food delivered in a specific context and (2) autoshaping, where rats learn to show conditioned discriminated approach to a discrete visual CS+. While BLA lesions had minimal effects on conditioned locomotor activity, hippocampal lesions facilitated the development of both conditioned activity to food and autoshaping behavior, suggesting that hippocampal lesions may have increased the incentive motivational properties of food and associated conditioned stimuli, consistent with the hypothesis that the HPC is involved in inhibitory processes in appetitive conditioning. (c) 2005 Wiley-Liss, Inc.

  9. Pacific Ciguatoxin Induces Excitotoxicity and Neurodegeneration in the Motor Cortex Via Caspase 3 Activation: Implication for Irreversible Motor Deficit.

    Science.gov (United States)

    Asthana, Pallavi; Zhang, Ni; Kumar, Gajendra; Chine, Virendra Bhagawan; Singh, Kunal Kumar; Mak, Yim Ling; Chan, Leo Lai; Lam, Paul Kwan Sing; Ma, Chi Him Eddie

    2018-01-18

    Consumption of fish containing ciguatera toxins or ciguatoxins (CTXs) causes ciguatera fish poisoning (CFP). In some patients, CFP recurrence occurs even years after exposure related to CTXs accumulation. Pacific CTX-1 (P-CTX-1) is one of the most potent natural substances known that causes predominantly neurological symptoms in patients; however, the underlying pathogenies of CFP remain unknown. Using clinically relevant neurobehavioral tests and electromyography (EMG) to assess effects of P-CTX-1 during the 4 months after exposure, recurrent motor strength deficit occurred in mice exposed to P-CTX-1. We detected irreversible motor strength deficits accompanied by reduced EMG activity, demyelination, and slowing of motor nerve conduction, whereas control unexposed mice fully recovered in 1 month after peripheral nerve injury. Finally, to uncover the mechanism underlying CFP, we detected reduction of spontaneous firing rate of motor cortical neurons even 6 months after exposure and increased number of glial fibrillary acidic protein (GFAP)-immunoreactive astrocytes. Increased numbers of motor cortical neuron apoptosis were detected by dUTP-digoxigenin nick end labeling assay along with activation of caspase 3. Taken together, our study demonstrates that persistence of P-CTX-1 in the nervous system induces irreversible motor deficit that correlates well with excitotoxicity and neurodegeneration detected in the motor cortical neurons.

  10. Self-Inflicted Lesions in Dermatology: A Management and Therapeutic Approach - A Position Paper From the European Society for Dermatology and Psychiatry

    NARCIS (Netherlands)

    Tomas-Aragones, Lucia; Consoli, Silla M.; Consoli, Sylvie G.; Poot, Francoise; Taube, Klaus-Michael; Linder, M. Dennis; Jemec, Gregor B. E.; Szepietowski, Jacek C.; de Korte, John; Lvov, Andrey; Gieler, Uwe

    2017-01-01

    The classification of self-inflicted skin lesions proposed by the European Society for Dermatology and Psychiatry (ESDaP) group generated questions with regard to specific treatments that could be recommended for such cases. The therapeutic guidelines in the current paper integrate new

  11. Self-inflicted lesions in dermatology: terminology and classification--a position paper from the European Society for Dermatology and Psychiatry (ESDaP)

    NARCIS (Netherlands)

    Gieler, Uwe; Consoli, Sylvie G.; Tomás-Aragones, Lucía; Linder, Dennis M.; Jemec, Gregor B. E.; Poot, Francoise; Szepietowski, Jacek C.; de Korte, John; Taube, Klaus-Michael; Lvov, Andrey; Consoli, Silla M.

    2013-01-01

    The terminology, classification, diagnosis and treatment of self-inflicted dermatological lesions are subjects of open debate. The present study is the result of various meetings of a task force of dermatologists, psychiatrists and psychologists, all active in the field of psychodermatology, aimed

  12. Survivors of self-inflicted gunshot wounds to the head: characterization of ocular injuries and health care costs.

    Science.gov (United States)

    Reddy, Amit K; Baker, Meredith S; Sobel, Rachel K; Whelan, David A; Carter, Keith D; Allen, Richard C

    2014-06-01

    Suicides and attempted suicides are major public health issues in the United States and around the world. Self-inflicted gunshot wounds (SIGSWs) are a common method of attempting suicide, the head being the most commonly injured body region; however, the literature lacks an overview of the orbital and ocular injuries as well as outcomes associated with SIGSWs. To characterize the ocular and orbital injuries and outcomes of patients presenting with SIGSWs and to examine the cost associated with these injuries. Retrospective medical record review was performed of all patients who presented to the University of Iowa Hospitals and Clinics between 2003 to 2013 with the admitting diagnosis of self-inflicted injuries via firearms. Patients with no periorbital or ocular injuries and/or those who did not survive for at least 2 months following the incident were excluded. Ocular injuries and outcomes and health care costs and reimbursements, which were generated by a financial report obtained from the hospital finance department that included data from both the hospital billing and cost accounting systems. All patients in this study (n = 18) were men with a mean age of 47.2 years. Eight patients (44.4%) displayed submental missile entry points, 7 (38.9%) displayed intraoral entry points, and 3 (16.7%) displayed pericranial entry points. Patients with pericranial entries sustained more severe ocular injuries and had poorer ocular outcomes. Seven patients (38.9%) were found at final follow-up to have visual acuity of 20/40 or better in each eye and all showed missile trajectories in the sagittal plane. The mean cost of treatment of these patients totaled $117,338 while the mean reimbursement amount was $124,388. Data regarding ocular injuries and outcomes may assist ophthalmologists in the treatment of patients with SIGSWs in the future. Many patients had extremely functional vision at final follow-ups, which highlights the importance of specialists conducting examinations

  13. Characterisation of neuroprotective efficacy of modified poly-arginine-9 (R9) peptides using a neuronal glutamic acid excitotoxicity model.

    Science.gov (United States)

    Edwards, Adam B; Anderton, Ryan S; Knuckey, Neville W; Meloni, Bruno P

    2017-02-01

    In a recent study, we highlighted the importance of cationic charge and arginine residues for the neuroprotective properties of poly-arginine and arginine-rich peptides. In this study, using cortical neuronal cultures and an in vitro glutamic acid excitotoxicity model, we examined the neuroprotective efficacy of different modifications to the poly-arginine-9 peptide (R9). We compared an unmodified R9 peptide with R9 peptides containing the following modifications: (i) C-terminal amidation (R9-NH2); (ii) N-terminal acetylation (Ac-R9); (iii) C-terminal amidation with N-terminal acetylation (Ac-R9-NH2); and (iv) C-terminal amidation with D-amino acids (R9D-NH2). The three C-terminal amidated peptides (R9-NH2, Ac-R9-NH2, and R9D-NH2) displayed neuroprotective effects greater than the unmodified R9 peptide, while the N-terminal acetylated peptide (Ac-R9) had reduced efficacy. Using the R9-NH2 peptide, neuroprotection could be induced with a 10 min peptide pre-treatment, 1-6 h before glutamic acid insult, or when added to neuronal cultures up to 45 min post-insult. In addition, all peptides were capable of reducing glutamic acid-mediated neuronal intracellular calcium influx, in a manner that reflected their neuroprotective efficacy. This study further highlights the neuroprotective properties of poly-arginine peptides and provides insight into peptide modifications that affect efficacy.

  14. Berberine induces p53-dependent cell cycle arrest and apoptosis of human osteosarcoma cells by inflicting DNA damage

    International Nuclear Information System (INIS)

    Liu Zhaojian; Liu Qiao; Xu Bing; Wu Jingjing; Guo Chun; Zhu Faliang; Yang Qiaozi; Gao Guimin; Gong Yaoqin; Shao Changshun

    2009-01-01

    Alkaloid berberine is widely used for the treatment of diarrhea and other diseases. Many laboratory studies showed that it exhibits anti-proliferative activity against a wide spectrum of cancer cells in culture. In this report we studied the mechanisms underlying the inhibitory effects of berberine on human osteosarcoma cells and on normal osteoblasts. The inhibition was largely attributed to cell cycle arrest at G1 and G2/M, and to a less extent, to apoptosis. The G1 arrest was dependent on p53, as G1 arrest was abolished in p53-deficient osteosarcoma cells. The induction of G1 arrest and apoptosis was accompanied by a p53-dependent up-regulation of p21 and pro-apoptotic genes. However, the G2/M arrest could be induced by berberine regardless of the status of p53. Interestingly, DNA double-strand breaks, as measured by the phosphorylation of H2AX, were remarkably accumulated in berberine-treated cells in a dose-dependent manner. Thus, one major mechanism by which berberine exerts its growth-inhibitory effect is to inflict genomic lesions on cells, which in turn trigger the activation of p53 and the p53-dependent cellular responses including cell cycle arrest and apoptosis

  15. Berberine induces p53-dependent cell cycle arrest and apoptosis of human osteosarcoma cells by inflicting DNA damage

    Energy Technology Data Exchange (ETDEWEB)

    Liu Zhaojian; Liu Qiao; Xu Bing; Wu Jingjing [Key Laboratory of Experimental Teratology of Ministry of Education and Institute of Molecular Medicine and Genetics, Shandong University School of Medicine, Jinan, Shandong 250012 (China); Guo Chun; Zhu Faliang [Institute of Immunology, Shandong University School of Medicine, Jinan, Shandong 250012 (China); Yang Qiaozi [Department of Genetics, Rutgers University, Piscataway, NJ 08854 (United States); Gao Guimin [Key Laboratory of Experimental Teratology of Ministry of Education and Institute of Molecular Medicine and Genetics, Shandong University School of Medicine, Jinan, Shandong 250012 (China); Gong Yaoqin [Key Laboratory of Experimental Teratology of Ministry of Education and Institute of Molecular Medicine and Genetics, Shandong University School of Medicine, Jinan, Shandong 250012 (China)], E-mail: yxg8@sdu.edu.cn; Shao Changshun [Key Laboratory of Experimental Teratology of Ministry of Education and Institute of Molecular Medicine and Genetics, Shandong University School of Medicine, Jinan, Shandong 250012 (China); Department of Genetics, Rutgers University, Piscataway, NJ 08854 (United States)], E-mail: shao@biology.rutgers.edu

    2009-03-09

    Alkaloid berberine is widely used for the treatment of diarrhea and other diseases. Many laboratory studies showed that it exhibits anti-proliferative activity against a wide spectrum of cancer cells in culture. In this report we studied the mechanisms underlying the inhibitory effects of berberine on human osteosarcoma cells and on normal osteoblasts. The inhibition was largely attributed to cell cycle arrest at G1 and G2/M, and to a less extent, to apoptosis. The G1 arrest was dependent on p53, as G1 arrest was abolished in p53-deficient osteosarcoma cells. The induction of G1 arrest and apoptosis was accompanied by a p53-dependent up-regulation of p21 and pro-apoptotic genes. However, the G2/M arrest could be induced by berberine regardless of the status of p53. Interestingly, DNA double-strand breaks, as measured by the phosphorylation of H2AX, were remarkably accumulated in berberine-treated cells in a dose-dependent manner. Thus, one major mechanism by which berberine exerts its growth-inhibitory effect is to inflict genomic lesions on cells, which in turn trigger the activation of p53 and the p53-dependent cellular responses including cell cycle arrest and apoptosis.

  16. Made up by makeup--A case report about an exceptional kind of self-inflicted "injuries".

    Science.gov (United States)

    Mauf, Sabrina; Martinez, Rosa M; Thali, Michael J; Bartsch, Christine

    2015-12-01

    Self-inflicted injuries are a known, but challenging topic in the healthcare sector and the judicial system. Therefore, differentiation of these injuries from a third-party-interference is crucial in the field of forensic medicine. However, self-painted injuries with makeup, which entail misleading of medical staff and the administration of justice, have apparently not been described in the literature so far. A case of a rare kind of victim role staging in a 26-year-old Caucasian woman in the field of forensic medicine is presented. She supposedly had been robbed and harmed by two unknown men. The forensic examination revealed subjective symptoms and objective findings, such as skin discolorations appearing as fresh bruises. However, a closer look revealed makeup. After removal, no injuries were seen. Awareness of the existence of exceptional cases of victim role staging is essential in the daily routine of healthcare, judicial and forensic professionals. Therefore, a questioning attitude within the physical examination as well as proper assessment of objective findings is crucial. Furthermore, the importance of an interdisciplinary approach of possible factitious disorders is demonstrated. The sensitization may exclude a third-party-interference, prevent damages to the health care system, avoid misleading of the administration of justice, and, therefore, reduce socioeconomic costs. Moreover, the recognition may enable adequate interventions and provide patients with professional help. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  17. An alarming presentation of Creutzfeldt-Jakob disease following a self-inflicted gunshot wound to the head.

    Science.gov (United States)

    Harnish, Carissa; Gross, Brian; Rittenhouse, Katelyn; Bupp, Katherine; Vellucci, Ashley; Anderson, Jeffrey; Riley, Deborah; Rogers, Frederick B

    2015-05-01

    Transmissible spongiform encephalopathies (TSE), also known as prion diseases, are characterized by rapid and fatal neurological decline. They not only detrimentally affect the patient, but also present additional challenges to healthcare systems due to the infectivity of the tissues and the difficulty of inactivating the prion. The most common TSE is Creutzfeldt-Jakob disease (CJD), which can occur after familial, spontaneous or acquired transmission. TSEs received more attention after the development of variant CJD (vCJD), also known as Mad Cow Disease, in the UK during the mid-1990s. Unlike familial or spontaneous CJD, this variant was connected to consumption of cattle contaminated with the prion disease, bovine spongiform encephalopathy.This development increased interest in the etiology of CJD and other TSEs and the risk it presents as an infectious disease. The following details the case of a 59-year-old male infected with CJD presented to our level II trauma center for treatment following a self-inflicted gunshot wound to the head. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Effect of auto-skin grafting on bacterial infection of wound in rats inflicted with combined radiation-burn injury

    International Nuclear Information System (INIS)

    Ran Xinze; Yan Yongtang; Wei Shuqing

    1992-01-01

    Rats were exposed to 6 Gy whole body γ-ray irradiation from a 60 Co source followed by light radiation burn (15% TBSA, full thickness burn) from a 5 kw bromo-tungsten lamp. The effect of auto-skin grafting on invasive bacterial infection of wound in the rats with combined radiation-burn injury was studied, In the control group inflicted with combined radiation-burn injury but without skin grafting, bacteria were found on and in the eschars at 24th hour after injury, and in the subeschar tissue on 3rd day. Tremendous bacterial multiplication occurred from 7th to 15th day, and the amount of bacteria in the internal organs increased along with the increase of subeschar infection. At the same time, no bacterial infection was found in internal organs in auto-skin grafted group at 24th hour after injury. The results show that skin grafting can decrease or prevent bacterial infection in both subeschar tissue and internal organs

  19. Pathological changes after bone marrow and skin allograft transplantation in rats inflicted with severe combined radiation-burn injury

    International Nuclear Information System (INIS)

    Zheng Huaien; Cheng Tianmin; Yan Yongtang

    1994-01-01

    Bone marrow and skin allografts from the same donor were transplanted to rats inflicted with 8 Gy γ-radiation combined with third degree burns of 15% body surface area within 6 hr post injury. Pathological changes of hematopoietic tissues and skin allografts were studied. All injured controls died within 7 days post injury without bone marrow regeneration; 50% of treated rats survived with living skin allografts on 50th day post injury. On days 100 and 480 post operation, grafted skin still survived well on recipients with normal ultrastructure. Epidermic cells of skin allografts proliferated on day 5, developed and repaired on day 10. Histological structure of the skin returned to normal on day 30 post operation. The regeneration of bone marrow appeared on 5th day, increased markedly on day 10, and almost completed on day 15 after bone marrow transplantation. However, the regeneration of lymphocytes in cortex of spleen and lymph nodes did not appear until day 15 of BMT. The results show that bone marrow and skin allograft transplantation at early time post injury in most severe combined radiation-burn injury have tremendous beneficial effects, and the skin allograft can survive for a long time

  20. What neuroimaging should be performed in children in whom inflicted brain injury (iBI) is suspected? A systematic review

    International Nuclear Information System (INIS)

    Kemp, A.M.; Rajaram, S.; Mann, M.; Tempest, V.; Farewell, D.; Gawne-Cain, M.L.; Jaspan, T.; Maguire, S.

    2009-01-01

    Aims: To investigate the optimal neuroradiological investigation strategy to identify inflicted brain injury (iBI). Materials and methods: A systematic review of studies published between 1970-2008 in any language was conducted, searching 20 databases and four websites, using over 100 keywords/phrases, supplemented by hand-searching of references. All studies underwent two independent reviews (with disagreements adjudicated by a third reviewer) by trained reviewers from paediatrics, paediatric neuroradiology and related disciplines, using standardized critical appraisal tools, and strict inclusion/exclusion criteria. We included primary studies that evaluated the diagnostic yield of magnetic resonance imaging (MRI), in addition to initial computed tomography (CT), or follow-up CT or ultrasound in children with suspected iBI. Results: Of the 320 studies reviewed, 18 met the inclusion criteria, reflecting data on 367 children with iBI and 12 were published since 1998. When an MRI was conducted in addition to an abnormal early CT examination, additional information was found in 25% (95% CI: 18.3-33.16%) of children. The additional findings included further subdural haematoma, subarachnoid haemorrhage, shearing injury, ischaemia, and infarction; it also contributed to dating of injuries. Diffusion-weighted imaging (DWI) further enhanced the delineation of ischaemic changes, and assisted in prognosis. Repeat CT studies varied in timing and quality, and none were compared to the addition of an early MRI/DWI. Conclusions: In an acutely ill child, the optimal imaging strategy involves initial CT, followed by early MRI and DWI if early CT examination is abnormal, or there are ongoing clinical concerns. The role of repeat CT imaging, if early MRI is performed, is unclear, as is the place for MRI/DWI if initial CT examination is normal in an otherwise well child.

  1. What neuroimaging should be performed in children in whom inflicted brain injury (iBI) is suspected? A systematic review

    Energy Technology Data Exchange (ETDEWEB)

    Kemp, A.M. [Department of Child Health, Wales School of Medicine, Cardiff University, Cardiff (United Kingdom); Rajaram, S. [Department of Child Health, Sue Nicholls Centre, Aylesbury (United Kingdom); Mann, M. [Support Unit for Research Evidence, Cardiff University, Cardiff (United Kingdom); Tempest, V. [Department of Child Health, Wales School of Medicine, Cardiff University, Cardiff (United Kingdom); Farewell, D. [Department of Primary Care and Public Health, Cardiff University, Cardiff (United Kingdom); Gawne-Cain, M.L. [Department of Neuroradiology, Wessex Neurological Centre, Southampton University Hospitals Trust (United Kingdom); Jaspan, T. [Imaging Centre, University Hospital, Nottingham (United Kingdom); Maguire, S. [Department of Child Health, Wales School of Medicine, Cardiff University, Cardiff (United Kingdom)], E-mail: sabinemaguire@yahoo.co.uk

    2009-05-15

    Aims: To investigate the optimal neuroradiological investigation strategy to identify inflicted brain injury (iBI). Materials and methods: A systematic review of studies published between 1970-2008 in any language was conducted, searching 20 databases and four websites, using over 100 keywords/phrases, supplemented by hand-searching of references. All studies underwent two independent reviews (with disagreements adjudicated by a third reviewer) by trained reviewers from paediatrics, paediatric neuroradiology and related disciplines, using standardized critical appraisal tools, and strict inclusion/exclusion criteria. We included primary studies that evaluated the diagnostic yield of magnetic resonance imaging (MRI), in addition to initial computed tomography (CT), or follow-up CT or ultrasound in children with suspected iBI. Results: Of the 320 studies reviewed, 18 met the inclusion criteria, reflecting data on 367 children with iBI and 12 were published since 1998. When an MRI was conducted in addition to an abnormal early CT examination, additional information was found in 25% (95% CI: 18.3-33.16%) of children. The additional findings included further subdural haematoma, subarachnoid haemorrhage, shearing injury, ischaemia, and infarction; it also contributed to dating of injuries. Diffusion-weighted imaging (DWI) further enhanced the delineation of ischaemic changes, and assisted in prognosis. Repeat CT studies varied in timing and quality, and none were compared to the addition of an early MRI/DWI. Conclusions: In an acutely ill child, the optimal imaging strategy involves initial CT, followed by early MRI and DWI if early CT examination is abnormal, or there are ongoing clinical concerns. The role of repeat CT imaging, if early MRI is performed, is unclear, as is the place for MRI/DWI if initial CT examination is normal in an otherwise well child.

  2. [Association between violence against women inflicted by the partner and chronic malnutrition in their children under five years old in Peru].

    Science.gov (United States)

    Ruiz-Grosso, Paulo; Loret de Mola, Christian; Miranda, J Jaime

    2014-01-01

    To assess the association between violence against women inflicted by their partner and the prevalence of chronic malnutrition in their children less than five years old. A secondary cross-sectional analysis of the 2001 Peru Demographic and Health Survey performed in Peru, with national representativeness. The dependent variable was chronic malnutrition in the youngest child under five years old. The independent variables were emotional violence, physical violence (mild or severe) and sexual violence self-report; the violence was inflicted by the mother's last partner or spouse in the last 12 months. Univariate and multivariate analysis was performed, generalized linear models (log-binomial regression) were used, and the nature of the sample was taken into account. Models for socio-demographic and mother-son health variables were adjusted. Prevalence ratios (PR) and confidence intervals were calculated. Data from 5,154 mothers and children were analyzed. The prevalence of chronic malnutrition was 19.8% (CI 95%: 18.1-21.6). In the multivariate analysis, a higher prevalence of chronic malnutrition was found in the children whose mothers had a history of severe physical violence history: PR=1.27% (IC 95%: 1.09-1.48). There was no evidence of association between the prevalence of chronic malnutrition and other kinds of violence inflicted by a partner. The mothers' report of physical violence in the last year was associated with an increased prevalence of chronic malnutrition in children under five years old.

  3. Socio-Demographic and Mental Health Profile of Admitted Cases of Self-Inflicted Harm in the US Population

    Directory of Open Access Journals (Sweden)

    Chris Hanuscin

    2018-01-01

    Full Text Available Self-inflicted harm (SIH has a substantial lifetime prevalence, it is associated with tremendous costs, and its rate is increasing on a national scale. To examine the characteristics of those admitted for SIH in the US and to investigate the factors that potentially modify the methods used for SIH. This was a retrospective analysis of admitted cases of SIH including suicide attempts between 2007 and 2012 using the National Trauma Data Bank. We included a total of 204,633 cases admitted for SIH. Our participants were 75.1% males. Those aged 15–24 (21%, 25–34 (22%, 35–44 (19%, 45–54 (19%, and 55–64 (10% years comprised the largest age groups among our cases—70.8%, 11.5%, 11.1%, and 6.6% were, respectively, Caucasians, Hispanics, Blacks, and Asian/Others. Analyses of the SIH methods revealed that Blacks were less likely to self-poison [Odds Ratio (OR: 0.78] compared to Whites, whereas individuals with psychiatric disorders or substance abuse carried 2.5 and 2.0-fold higher risk, respectively. Blacks were also less likely to use anoxic methods (OR: 0.69, whereas patients with psychiatric disorders or substance abuse carried 1.5-fold higher risk. Being Black, Hispanic, and Asian (OR: 0.58, 0.55, and 0.55, respectively as well as having psychiatric disorders (OR: 0.80 were associated with lower risks of using firearms, whereas its risk was increased with increasing age. Blacks (OR: 0.77 were less likely to cut or pierce in contrast to Hispanics (OR: 1.4, Asians/Others (OR: 1.29, and those with psychiatric disorders (2.5-fold higher risk or drug abuse (2-fold higher risk. Blacks (OR: 1.11, Hispanics (OR: 1.13, and Asians/Others (OR: 1.57 were more likely to jump from high places, whereas those with substance abuse were less likely (OR: 0.77. Among patients admitted for SIH, males, those aged 15–64 years, and Whites comprised the largest sex, age, and racial/ethnic groups, respectively. We also found that several factors including race

  4. Characteristics of Firearm Brain Injury Survivors in the Traumatic Brain Injury Model Systems (TBIMS) National Database: A Comparison of Assault and Self-Inflicted Injury Survivors.

    Science.gov (United States)

    Bertisch, Hilary; Krellman, Jason W; Bergquist, Thomas F; Dreer, Laura E; Ellois, Valerie; Bushnik, Tamara

    2017-11-01

    To characterize and compare subgroups of survivors with assault-related versus self-inflicted traumatic brain injuries (TBIs) via firearms at the time of inpatient rehabilitation and at 1-, 2-, and 5-year follow-up. Secondary analysis of data from the Traumatic Brain Injury Model Systems National Database (TBIMS NDB), a multicenter, longitudinal cohort study. Retrospective analyses of a subset of individuals enrolled in the TBIMS NDB. Individuals 16 years and older (N=399; 310 via assault, 89 via self-inflicted injury) with a primary diagnosis of TBI caused by firearm injury enrolled in the TBIMS NDB. Not applicable. Disability Rating Scale, Glasgow Outcome Scale-Extended, sociodemographic variables (sex, age, race, marital status), injury-related/acute care information (posttraumatic amnesia, loss of consciousness, time from injury to acute hospital discharge), and mental health variables (substance use history, psychiatric hospitalizations, suicide history, incarcerations). Individuals who survived TBI secondary to a firearm injury differed by injury mechanism (assault vs self-inflicted) on critical demographic, injury-related/acute care, and mental health variables at inpatient rehabilitation and across long-term recovery. Groups differed in terms of geographic area, age, ethnicity, education, marital status, admission Glasgow Coma Scale score, and alcohol abuse, suicide attempts, and psychiatric hospitalizations at various time points. These findings have implications for prevention (eg, mental health programming and access to firearms in targeted areas) and for rehabilitation planning (eg, by incorporating training with coping strategies and implementation of addictions-related services) for firearm-related TBI, based on subtype of injury. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  5. Modulator effects of interleukin-1beta and tumor necrosis factor-alpha on AMPA-induced excitotoxicity in mouse organotypic hippocampal slice cultures

    DEFF Research Database (Denmark)

    Bernardino, Liliana; Xapelli, Sara; Silva, Ana P

    2005-01-01

    The inflammatory cytokines interleukin-1beta and tumor necrosis factor-alpha (TNF-alpha) have been identified as mediators of several forms of neurodegeneration in the brain. However, they can produce either deleterious or beneficial effects on neuronal function. We investigated the effects...... of mouse recombinant TNF-alpha (10 ng/ml) enhanced excitotoxicity when the cultures were simultaneously exposed to AMPA and to this cytokine. Decreasing the concentration of TNF-alpha to 1 ng/ml resulted in neuroprotection against AMPA-induced neuronal death independently on the application protocol....... By using TNF-alpha receptor (TNFR) knock-out mice, we demonstrated that the potentiation of AMPA-induced toxicity by TNF-alpha involves TNF receptor-1, whereas the neuroprotective effect is mediated by TNF receptor-2. AMPA exposure was associated with activation and proliferation of microglia as assessed...

  6. “It's Just a Matter of Time:” Lessons from Agency and Community Responses to Polar Bear-inflicted Human Injury

    Directory of Open Access Journals (Sweden)

    Aimee L Schmidt

    2018-01-01

    Full Text Available Bear-inflicted human injuries or deaths are often widely publicised, controversial, and evoke substantial social responses that articulate public expectations about bear management. In this paper, we examine how local people and management agencies (i.e. Manitoba Conservation, Parks Canada, and the Town of Churchill responded to a polar bear-inflicted human injury in Churchill, Manitoba, Canada. On November 1st, 2013, two people in Churchill were badly mauled by a polar bear. The incident shocked the community, highlighted problems such as a lack of bear safety education, and led to reviews of institutional policies for preventing polar bear-human conflicts. We used qualitative analysis methods to describe what is said (about polar bears, about people, and about management and what is done (changes in behaviours and changes in policies/practices when someone is attacked by a polar bear in Churchill. Results show that polar bear management agencies in Churchill respond remarkably well to errors in procedure, but are often unable to address the many underlying systematic drivers of polar bear-human conflict. Hence, managerial reactions to bear-human conflicts are successful at addressing the proximate cause of the problem, but offer few long-term solutions.

  7. Alterations in mGluR5 expression and signaling in Lewy body disease and in transgenic models of alpha-synucleinopathy--implications for excitotoxicity.

    Directory of Open Access Journals (Sweden)

    Diana L Price

    2010-11-01

    Full Text Available Dementia with Lewy bodies (DLB and Parkinson's Disease (PD are neurodegenerative disorders of the aging population characterized by the abnormal accumulation of alpha-synuclein (alpha-syn. Previous studies have suggested that excitotoxicity may contribute to neurodegeneration in these disorders, however the underlying mechanisms and their relationship to alpha-syn remain unclear. For this study we proposed that accumulation of alpha-syn might result in alterations in metabotropic glutamate receptors (mGluR, particularly mGluR5 which has been linked to deficits in murine models of PD. In this context, levels of mGluR5 were analyzed in the brains of PD and DLB human cases and alpha-syn transgenic (tg mice and compared to age-matched, unimpaired controls, we report a 40% increase in the levels of mGluR5 and beta-arrestin immunoreactivity in the frontal cortex, hippocampus and putamen in DLB cases and in the putamen in PD cases. In the hippocampus, mGluR5 was more abundant in the CA3 region and co-localized with alpha-syn aggregates. Similarly, in the hippocampus and basal ganglia of alpha-syn tg mice, levels of mGluR5 were increased and mGluR5 and alpha-syn were co-localized and co-immunoprecipitated, suggesting that alpha-syn interferes with mGluR5 trafficking. The increased levels of mGluR5 were accompanied by a concomitant increase in the activation of downstream signaling components including ERK, Elk-1 and CREB. Consistent with the increased accumulation of alpha-syn and alterations in mGluR5 in cognitive- and motor-associated brain regions, these mice displayed impaired performance in the water maze and pole test, these behavioral alterations were reversed with the mGluR5 antagonist, MPEP. Taken together the results from study suggest that mGluR5 may directly interact with alpha-syn resulting in its over activation and that this over activation may contribute to excitotoxic cell death in select neuronal regions. These results highlight the

  8. Piroxicam inhibits NMDA receptor-mediated excitotoxicity through allosteric inhibition of the GluN2B subunit: an in silico study elucidating a novel mechanism of action of the drug.

    Science.gov (United States)

    Mazumder, Muhammed Khairujjaman; Borah, Anupom

    2014-12-01

    Hyperactivation of GluN2B subunit containing N-methyl-d-aspartate receptors (NMDARs) significantly contributes to the development of several neurodegenerative diseases through a process called excitotoxicity. NMDARs are voltage-gated Ca2+ channels which when activated lead to excessive influx of Ca2+ into neurons thereby exacerbating several calcium-dependent pathways that cause oxidative stress and apoptosis. Several drugs are presently in use to counter the NMDAR-mediated excitotoxic events among which Ifenprodil and its derivatives are GluN2B selective allosteric antagonists. Certain non-steroidal anti-inflammatory drugs (NSAIDs) have also been reported to inhibit NMDARs and the resultant pathologies. Meanwhile, Piroxicam, which is a NSAID, has been reported to be protective in cerebral ischemia-induced neurodegeneration through various pathways. Since Piroxicam has more number of interacting groups as compared to other NSAIDs and also has structural similarities with Ifenprodil, we thought it prudent that Piroxicam may inhibit NMDARs similar to Ifenprodil. By using molecular docking as a tool, we validated the hypothesis and hereby report for the first time that Piroxicam can inhibit GluN2B containing NMDARs through allosteric mode similar to the well known selective antagonist--Ifenprodil; and thus can be a therapeutic drug for the prevention of excitotoxic neurodegeneration. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Neuroprotection from NMDA excitotoxic lesion by Cu/Zn superoxide dismutase gene delivery to the postnatal rat brain by a modular protein vector

    Science.gov (United States)

    Peluffo, Hugo; Acarin, Laia; Arís, Anna; González, Pau; Villaverde, Antoni; Castellano, Bernardo; González, Berta

    2006-01-01

    Background Superoxide mediated oxidative stress is a key neuropathologic mechanism in acute central nervous system injuries. We have analyzed the neuroprotective efficacy of the transient overexpression of antioxidant enzyme Cu/Zn Superoxide dismutase (SOD) after excitotoxic injury to the immature rat brain by using a recently constructed modular protein vector for non-viral gene delivery termed NLSCt. For this purpose, animals were injected with the NLSCt vector carrying the Cu/Zn SOD or the control GFP transgenes 2 hours after intracortical N-methyl-D-aspartate (NMDA) administration, and daily functional evaluation was performed. Moreover, 3 days after, lesion volume, neuronal degeneration and nitrotyrosine immunoreactivity were evaluated. Results Overexpression of Cu/Zn SOD transgene after NMDA administration showed improved functional outcome and a reduced lesion volume at 3 days post lesion. In secondary degenerative areas, increased neuronal survival as well as decreased numbers of degenerating neurons and nitrotyrosine immunoreactivity was seen. Interestingly, injection of the NLSCt vector carrying the control GFP transgene also displayed a significant neuroprotective effect but less pronounced. Conclusion When the appropriate levels of Cu/Zn SOD are expressed transiently after injury using the non-viral modular protein vector NLSCt a neuroprotective effect is seen. Thus recombinant modular protein vectors may be suitable for in vivo gene therapy, and Cu/Zn SOD should be considered as an interesting therapeutic transgene. PMID:16638118

  10. Neuroprotection from NMDA excitotoxic lesion by Cu/Zn superoxide dismutase gene delivery to the postnatal rat brain by a modular protein vector

    Directory of Open Access Journals (Sweden)

    Castellano Bernardo

    2006-04-01

    Full Text Available Abstract Background Superoxide mediated oxidative stress is a key neuropathologic mechanism in acute central nervous system injuries. We have analyzed the neuroprotective efficacy of the transient overexpression of antioxidant enzyme Cu/Zn Superoxide dismutase (SOD after excitotoxic injury to the immature rat brain by using a recently constructed modular protein vector for non-viral gene delivery termed NLSCt. For this purpose, animals were injected with the NLSCt vector carrying the Cu/Zn SOD or the control GFP transgenes 2 hours after intracortical N-methyl-D-aspartate (NMDA administration, and daily functional evaluation was performed. Moreover, 3 days after, lesion volume, neuronal degeneration and nitrotyrosine immunoreactivity were evaluated. Results Overexpression of Cu/Zn SOD transgene after NMDA administration showed improved functional outcome and a reduced lesion volume at 3 days post lesion. In secondary degenerative areas, increased neuronal survival as well as decreased numbers of degenerating neurons and nitrotyrosine immunoreactivity was seen. Interestingly, injection of the NLSCt vector carrying the control GFP transgene also displayed a significant neuroprotective effect but less pronounced. Conclusion When the appropriate levels of Cu/Zn SOD are expressed transiently after injury using the non-viral modular protein vector NLSCt a neuroprotective effect is seen. Thus recombinant modular protein vectors may be suitable for in vivo gene therapy, and Cu/Zn SOD should be considered as an interesting therapeutic transgene.

  11. Delayed Administration of VEGF Rescues Spinal Motor Neurons from Death with a Short Effective Time Frame in Excitotoxic Experimental Models in Vivo

    Directory of Open Access Journals (Sweden)

    Luis B Tovar-y-Romo

    2012-02-01

    Full Text Available VEGF (vascular endothelial growth factor prevents neuronal death in different models of ALS (amyotrophic lateral sclerosis, but few studies have addressed the efficacy of VEGF to protect motor neurons after the onset of symptoms, a critical point when considering VEGF as a potential therapeutic target for ALS. We studied the capability of VEGF to protect motor neurons after an excitotoxic challenge in two models of spinal neurodegeneration in rats induced by AMPA (α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid administered either chronically with osmotic minipumps or acutely by microdialysis. VEGF was administered through osmotic minipumps in the chronic model or injected intracerebroventricularly in the acute model, and its effects were assessed by immunohistochemical and histological analyses and motor performance tests. In the chronic model, VEGF stopped the progression of the paralysis and protected motor neurons when administered after AMPA before the onset of the motor symptoms, whereas no protection was observed when administered after the onset. VEGF was also protective in the acute model, but with a short time window, since the protection was effective when administered 1 h but not 2 h after AMPA. Our results indicate that while VEGF has an indubitable neuroprotective effect, its therapeutic potential for halting or delaying the progression of motor neuron loss in ALS would likely have a short effective time frame.

  12. Comparison of neuroprotective effects of erythropoietin (EPO) and carbamylerythropoietin (CEPO) against ischemia-like oxygen-glucose deprivation (OGD) and NMDA excitotoxicity in mouse hippocampal slice cultures

    DEFF Research Database (Denmark)

    Montero, Maria; Rom Poulsen, Frantz; Noraberg, Jens

    2007-01-01

    of hematopoietic bioactivity, is the chemically modified, EPO-derivative carbamylerythropoietin (CEPO). For comparison of the neuroprotective effects of CEPO and EPO, we subjected organotypic hippocampal slice cultures to oxygen-glucose deprivation (OGD) or N-methyl-d-aspartate (NMDA) excitotoxicity. Hippocampal...... slice cultures were pretreated for 24 h with 100 IU/ml EPO (=26 nM) or 26 nM CEPO before OGD or NMDA lesioning. Exposure to EPO and CEPO continued during OGD and for the next 24 h until histology, as well as during the 24 h exposure to NMDA. Neuronal cell death was quantified by cellular uptake...... of propidium iodide (PI), recorded before the start of OGD and NMDA exposure and 24 h after. In cultures exposed to OGD or NMDA, CEPO reduced PI uptake by 49+/-3 or 35+/-8%, respectively, compared to lesion-only controls. EPO reduced PI uptake by 33+/-5 and 15+/-8%, respectively, in the OGD and NMDA exposed...

  13. Therapy of infections in mice irradiated in mixed neutron/photon fields and inflicted with wound trauma: a review of current work.

    Science.gov (United States)

    Ledney, G D; Madonna, G S; Elliott, T B; Moore, M M; Jackson, W E

    1991-10-01

    When host antimicrobial defenses are severely compromised by radiation or trauma in conjunction with radiation, death from sepsis results. To evaluate therapies for sepsis in radiation casualties, we developed models of acquired and induced bacterial infections in irradiated and irradiated-wounded mice. Animals were exposed to either a mixed radiation field of equal proportions of neutrons and gamma rays (n/gamma = 1) from a TRIGA reactor or pure gamma rays from 60[Co sources. Skin wounds (15% of total body surface area) were inflicted under methoxyflurane anesthesia 1 h after irradiation. In all mice, wounding after irradiation decreased resistance to infection. Treatments with the immunomodulator synthetic trehalose dicorynomycolate (S-TDCM) before or after mixed neutron-gamma irradiation or gamma irradiation increased survival. Therapy with S-TDCM for mice irradiated with either a mixed field or gamma rays increased resistance to Klebsiella pneumoniae-induced infections. Combined therapy with S-TDCM and ceftriaxone for K. pneumoniae infections in mice exposed to a mixed radiation field or to gamma rays was more effective than single-agent therapy. In all irradiated-wounded mice, single therapy of acquired infections with an antibiotic or S-TDCM did not increase survival. Survival of irradiated-wounded mice after topical application of gentamicin sulfate cream suggested that bacteria colonizing the wound disseminated systemically in untreated irradiated mice, resulting in death from sepsis. In lethal models of acquired infections in irradiated-wounded mice, significant increases in survival were achieved when systemic treatments with S-TDCM or gentamicin were combined with topical treatments of gentamicin cream. Therapies for sepsis in all mice exposed to a mixed field were less effective than in mice exposed to gamma rays. Nonetheless, the data show a principle by which successful therapy may be provided to individuals receiving tissue trauma in conjunction with

  14. Intractable Postoperative Wounds Caused by Self-Inflicted Trauma in a Patient with Cutaneous Munchausen Syndrome Presenting as a Pyoderma Gangrenosum-Like Lesion

    Directory of Open Access Journals (Sweden)

    Keiko Inui

    2016-04-01

    Full Text Available A 50-year-old Japanese woman consulted the emergency department of our hospital for bleeding due to an intractable postoperative wound on the lower abdomen; the postoperative wound was owing to a laparoscopic cholecystectomy performed 1 year previously for acute cholecystitis. She presented with a painful ulcer on her right lower abdomen. She also presented with multiple scars, skin grafts on the extremities, and a missing left lower leg, the causes for all of which were unexplained. The results of her blood test were normal, except for the hemoglobin level. Histology of the skin biopsy specimen from the ulcer did not show any specific findings. The previous surgeon who had performed the laparoscopic cholecystectomy revealed that surgical wound dehiscence had occurred during her admission. After a body restraint had been applied, the ulcer improved. Medical records indicated that she had been admitted to the department of plastic surgery at our hospital for skin grafting of a leg ulcer. During that admission, she refused to consult with the department of psychiatry, although the staff suspected mental disorders. Therefore, we diagnosed her with cutaneous Munchausen syndrome. After vacuum-assisted closure (VAC therapy had been performed to prevent her from traumatizing the ulcer again, it rapidly became granulated and reepithelialized. Munchausen syndrome is characterized by feigning physical symptoms to seek attention. Patients self-inflict numerous lesions, keep getting admitted to different hospitals, and feign acute illness, usually spectacular diseases. VAC therapy may be effective for preventing patients with cutaneous Munchausen syndrome from traumatizing their wounds.

  15. Intractable Postoperative Wounds Caused by Self-Inflicted Trauma in a Patient with Cutaneous Munchausen Syndrome Presenting as a Pyoderma Gangrenosum-Like Lesion.

    Science.gov (United States)

    Inui, Keiko; Hanafusa, Takaaki; Namiki, Takeshi; Ueno, Makiko; Igawa, Ken; Yokozeki, Hiroo

    2016-01-01

    A 50-year-old Japanese woman consulted the emergency department of our hospital for bleeding due to an intractable postoperative wound on the lower abdomen; the postoperative wound was owing to a laparoscopic cholecystectomy performed 1 year previously for acute cholecystitis. She presented with a painful ulcer on her right lower abdomen. She also presented with multiple scars, skin grafts on the extremities, and a missing left lower leg, the causes for all of which were unexplained. The results of her blood test were normal, except for the hemoglobin level. Histology of the skin biopsy specimen from the ulcer did not show any specific findings. The previous surgeon who had performed the laparoscopic cholecystectomy revealed that surgical wound dehiscence had occurred during her admission. After a body restraint had been applied, the ulcer improved. Medical records indicated that she had been admitted to the department of plastic surgery at our hospital for skin grafting of a leg ulcer. During that admission, she refused to consult with the department of psychiatry, al-though the staff suspected mental disorders. Therefore, we diagnosed her with cutaneous Munchausen syndrome. After vacuum-assisted closure (VAC) therapy had been performed to prevent her from traumatizing the ulcer again, it rapidly became granulated and reepithelialized. Munchausen syndrome is characterized by feigning physical symptoms to seek attention. Patients self-inflict numerous lesions, keep getting admitted to different hospitals, and feign acute illness, usually spectacular diseases. VAC therapy may be effective for preventing patients with cutaneous Munchausen syndrome from traumatizing their wounds.

  16. Self-inflicted skin lesions

    DEFF Research Database (Denmark)

    Ring, Hans Christian; Smith, Matthias Nybro; Jemec, Gregor B E

    2014-01-01

    professionals, the European Society for Dermatology and Psychiatry (ESDaP) recently proposed a classification of psychodermatological terms in order to establish a coherent use of terms across the medical fields involved. We reviewed current and previous psychodermatological diagnoses in order to clarify how...

  17. Simultaneous two-voxel localized 1H-observed 13C-edited spectroscopy for in vivo MRS on rat brain at 9.4 T: Application to the investigation of excitotoxic lesions

    Science.gov (United States)

    Doan, Bich-Thuy; Autret, Gwennhael; Mispelter, Joël; Méric, Philippe; Même, William; Montécot-Dubourg, Céline; Corrèze, Jean-Loup; Szeremeta, Frédéric; Gillet, Brigitte; Beloeil, Jean-Claude

    2009-05-01

    13C spectroscopy combined with the injection of 13C-labeled substrates is a powerful method for the study of brain metabolism in vivo. Since highly localized measurements are required in a heterogeneous organ such as the brain, it is of interest to augment the sensitivity of 13C spectroscopy by proton acquisition. Furthermore, as focal cerebral lesions are often encountered in animal models of disorders in which the two brain hemispheres are compared, we wished to develop a bi-voxel localized sequence for the simultaneous bilateral investigation of rat brain metabolism, with no need for external additional references. Two sequences were developed at 9.4 T: a bi-voxel 1H-( 13C) STEAM-POCE (Proton Observed Carbon Edited) sequence and a bi-voxel 1H-( 13C) PRESS-POCE adiabatically decoupled sequence with Hadamard encoding. Hadamard encoding allows both voxels to be recorded simultaneously, with the same acquisition time as that required for a single voxel. The method was validated in a biological investigation into the neuronal damage and the effect on the Tri Carboxylic Acid cycle in localized excitotoxic lesions. Following an excitotoxic quinolinate-induced localized lesion in the rat cortex and the infusion of U- 13C glucose, two 1H-( 13C) spectra of distinct (4 × 4 × 4 mm 3) voxels, one centred on the injured hemisphere and the other on the contralateral hemisphere, were recorded simultaneously. Two 1H bi-voxel spectra were also recorded and showed a significant decrease in N-acetyl aspartate, and an accumulation of lactate in the ipsilateral hemisphere. The 1H-( 13C) spectra could be recorded dynamically as a function of time, and showed a fall in the glutamate/glutamine ratio and the presence of a stable glutamine pool, with a permanent increase of lactate in the ipsilateral hemisphere. This bi-voxel 1H-( 13C) method can be used to investigate simultaneously both brain hemispheres, and to perform dynamic studies. We report here the neuronal damage and the

  18. Teenage pregnancy: A socially inflicted health hazard

    Directory of Open Access Journals (Sweden)

    Banerjee Bratati

    2009-01-01

    Full Text Available Background: Early marriage and confinement are contributing factors to high maternal and perinatal mortality and morbidity. Objective: To assess the magnitude of the problem of teenage pregnancy and its complications. Materials and Methods: A hospital-based cohort study was undertaken over 4 months among women admitted to a rural hospital in West Bengal. The study cohort comprised of teenage mothers between 15-19 years old and a control cohort of mothers between 20-24 years old. Data included demographic variables, available medical records, and complications viz. anemia, preterm delivery, and low birth weight. Anemia was defined as a hemoglobin level below 10 gm% during the last trimester of pregnancy, preterm delivery was defined as occurring within 37 weeks of gestation, and low birth weight was defined as babies weighing less than 2500 grams at birth. Result: Teenage pregnancy comprised 24.17% of total pregnancies occurring in the hospital during the study period. The study group had 58 subjects and the control group had 91 subjects. The prevalence of anemia was significantly higher ( P < 0.05 in the women in the teenage group (62.96% than in the women in the control group (43.59%. However, severe anemia with a hemoglobin level below 8 gm% was only found in the control group. Preterm delivery occurred significantly more ( P < 0.001 in the study group (51.72% than in the control group (25.88%. The incidence of low birth weight was significantly higher ( P < 0.0001 among the group of teenagers (65.52% than among the women in the control group (26.37%. Not a single newborn was above 3 kg in the study group, while none were below 1.5 kg in the control group. The mean birth weight was 2.36 kg in the study group and 2.74 kg in the control group; the difference was strongly significant ( P < 0.001. Conclusion: The study shows that anemia, preterm delivery, and low birth weight were more prevalent among teenagers than among women who were 20-24 years old. This indicates the need for enhancing family welfare measures to delay the age at first pregnancy, thereby reducing the multiple complications that may occur in the young mother and her newborn baby.

  19. Eating and inflicting pain out of boredom.

    Science.gov (United States)

    Havermans, Remco C; Vancleef, Linda; Kalamatianos, Antonis; Nederkoorn, Chantal

    2015-02-01

    In the present study it was investigated whether boredom promotes eating and if so, whether this effect likely reflects an increased drive for rewarding stimulation (positive reinforcement) or more plainly the drive to escape boredom (negative reinforcement). In the latter case, the valence of the stimulation should not matter and people might even be willing to look for negative stimulation, for instance to hurt oneself, just to escape boredom. In two parallel experiments, it was tested whether induced boredom promotes the consumption of chocolate (Experiment 1) and whether participants likewise are more inclined to self-administer electrocutaneous stimuli (Experiment 2). In both experiments, a total of 30 participants attended two separate sessions watching a documentary for 1 h (neutral condition) and a monotonous repetition of a single clip from the same documentary for 1 h (boring condition), in balanced order. During Experiment 1, participants had free access to M&Ms and during Experiment 2 participants could freely self-administer brief electrical shocks. It was found that participants ate more M&Ms when bored but also that they more readily self-administered electrical shocks when bored. It is concluded that eating when bored is not driven by an increased desire for satisfying incentive stimulation, but mainly by the drive to escape monotony. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Self-inflicted bilateral orchidectomy precipitated by erotic bizarre ...

    African Journals Online (AJOL)

    power that enabled him to make any football club of his choice have a winning streak in the English Premiership. League. He cited instances of drops in the ratings of his favourite ... drug-induced as indicated by his drug and alcohol history.

  1. genetics and inheritance of seed dormancy inflicted by seed

    African Journals Online (AJOL)

    Mgina

    ABSTRACT. The study was undertaken to investigate the genetic mode of inheritance of dormancy imposed by the hull (seed coat) in rice seeds. Freshly harvested seeds of parents, F1 and F2 populations of a cross between a dormant cultivar Kisegese and non-dormant strain K2004 were used. Germination test of the ...

  2. Specific Characteristics of Injuries Inflicted by Claw Hammer.

    Science.gov (United States)

    Buchaillet, Céline; Gaudin, Arnaud; Rougé-Maillart, Clotilde; Jousset, Nathalie

    2016-09-01

    Claw hammers have the specific characteristic of having two distinct ends: one a flat head of variable form, the other bifurcated. So the use of this tool as a blunt instrument will cause varying injuries. The authors present two clinical cases of assault with a claw hammer. Examinations revealed two types of wound. A first injury composed of integumentary lacerations and underlying bone injuries in terms of "shape" suggested the use of a blunt instrument. A second injury made up of damage showing two parallel wounds or two wounds located one in the extension of the other suggested the use of an object with a bifurcated end. The combination of both types of injury should alert examiners to the possibility of the use of a claw hammer in causing the injuries in order to help direct investigators in their investigations and in the search for the weapon used. © 2016 American Academy of Forensic Sciences.

  3. Self-inflicted transparietal intraventricular nail: case report and ...

    African Journals Online (AJOL)

    Background Deliberate self-harm with stone- or hammer-driven nail through the cranium is unusual. The need is stressed for comprehensive radiological evaluation with computed tomography (CT) scan, with or without angiography, and removal through an open cranial procedure under general anaesthesia, rather than ...

  4. Self-Inflicted Trauma Secondary to Local Anaesthesia in Children

    Directory of Open Access Journals (Sweden)

    Srikrishna Vempaty

    2017-01-01

    Full Text Available Long acting local anaesthetics and inferior alveolar nerve block in children can cause loss of sensation and proprioception in a large area supplied by that particular nerve. Similar to the maxilla in mandible also, adequate level of anaesthesia can be achieved in the desired site of treatment by using a short acting local anaesthetic. Early return of normal sensory feedback after using short acting anaesthetics can be helpful in preventing self-harm.

  5. Pharmacological Treatment of Glutamate Excitotoxicity Following Traumatic Brain Injury

    Science.gov (United States)

    2009-01-14

    schizophrenia -like psychosis. TBI patients are also a higher risk for developing psychological problem many years post-injury. Cognitive symptoms of...promoting the propagation of action potentials. On the other hand, inhibitory neurotransmission mediated by GABA , causes the hyperpolarization of the...transporter contributes to neurotransmitter GABA synthesis and epilepsy. J Neurosci. 2002 Aug 1;22(15):6372-9. Shen M, Piser TM, Seybold VS, Thayer SA

  6. Urocortin 2 treatment is protective in excitotoxic retinal degeneration.

    Science.gov (United States)

    Szabadfi, K; Kiss, P; Reglodi, D; Fekete, E M; Tamas, A; Danyadi, B; Atlasz, T; Gabriel, R

    2014-03-01

    Urocortin 2 (Ucn 2) is a corticotrop releasing factor paralog peptide with many physiological functions and it has widespread distribution. There are some data on the cytoprotective effects of Ucn 2, but less is known about its neuro- and retinoprotective actions. We have previously shown that Ucn 2 is protective in ischemia-induced retinal degeneration. The aim of the present study was to examine the protective potential of Ucn 2 in monosodium-glutamate (MSG)-induced retinal degeneration by routine histology and to investigate cell-type specific effects by immunohistochemistry. Rat pups received MSG applied on postnatal days 1, 5 and 9 and Ucn 2 was injected intravitreally into one eye. Retinas were processed for histology and immunocytochemistry after 3 weeks. Immunolabeling was determined for glial fibrillary acidic protein, vesicular glutamate transporter 1, protein kinase Cα, calbindin, parvalbumin and calretinin. Retinal tissue from animals treated with MSG showed severe degeneration compared to normal retinas, but intravitreal Ucn 2 treatment resulted in a retained retinal structure both at histological and neurochemical levels: distinct inner retinal layers and rescued inner retinal cells (different types of amacrine and rod bipolar cells) could be observed. These findings support the neuroprotective function of Ucn 2 in MSG-induced retinal degeneration.

  7. Cutaneous cut sign: A clue to self inflicted carving on the body by sharp object

    Directory of Open Access Journals (Sweden)

    Vipul Namdeorao Ambade

    2016-09-01

    Full Text Available Suicide notes are usually written with pen or marker on a paper, notebook, wall or mirror. However, suicide notes written on one’s own body is very rare, and suicide note engraved with some metallic object on the body has not been reported yet. In the present suicidal death, the victim while carving some letters on the left arm with a razor had an incidental cut on right thumb. This incidental cut on the palm may be referred as “cutaneous cut sign” which gives a clue that the carving on the body with a sharp object was written by the victim himself. It also provides an additional importance of examination of palm for the presence of supportive evidences.

  8. The effects of glycemic control on seizures and seizure-induced excitotoxic cell death

    Directory of Open Access Journals (Sweden)

    Schauwecker Paula

    2012-08-01

    Full Text Available Abstract Background Epilepsy is the most common neurological disorder after stroke, affecting more than 50 million persons worldwide. Metabolic disturbances are often associated with epileptic seizures, but the pathogenesis of this relationship is poorly understood. It is known that seizures result in altered glucose metabolism, the reduction of intracellular energy metabolites such as ATP, ADP and phosphocreatine and the accumulation of metabolic intermediates, such as lactate and adenosine. In particular, it has been suggested that the duration and extent of glucose dysregulation may be a predictor of the pathological outcome of status. However, little is known about neither the effects of glycemic control on brain metabolism nor the effects of managing systemic glucose concentrations in epilepsy. Results In this study, we examined glycemic modulation of kainate-induced seizure sensitivity and its neuropathological consequences. To investigate the relationship between glycemic modulation, seizure susceptibility and its neuropathological consequences, C57BL/6 mice (excitotoxin cell death resistant were subjected to hypoglycemia or hyperglycemia, followed by systemic administration of kainic acid to induce seizures. Glycemic modulation resulted in minimal consequences with regard to seizure severity but increased hippocampal pathology, irrespective of whether mice were hypoglycemic or hyperglycemic prior to kainate administration. Moreover, we found that exogenous administration of glucose following kainic acid seizures significantly reduced the extent of hippocampal pathology in FVB/N mice (excitotoxin cell death susceptible following systemic administration of kainic acid. Conclusion These findings demonstrate that modulation of the glycemic index can modify the outcome of brain injury in the kainate model of seizure induction. Moreover, modulation of the glycemic index through glucose rescue greatly diminishes the extent of seizure-induced cell death following kainate administration. Our data support the hypothesis that deficient insulin signaling may represent a critical contributing factor in the susceptibility to seizure-induced cell death and this may be an important therapeutic target.

  9. The Tropilaelaps mites threat: An examination of the injuries inflicted on Apis mellifera

    Science.gov (United States)

    Tropilaelaps spp. are the most serious parasites of Apis mellifera in Asia. However, much of their biology and ecology are largely unexplored (de Guzman et al., 2017 J. Econ. Entomol. 1-14). Like varroa mites, tropilaelaps mites puncture through the integuments of their bee hosts to feed on hemolymp...

  10. Subdural Hematomas in Children under 2 Years. Accidental or Inflicted? A 10-Year Experience.

    Science.gov (United States)

    Tzioumi, Dimitra; Oates, R. Kim

    1998-01-01

    Analysis of 38 children under 2 with subdural hematomas found the most common causes were nonaccidental injury (55%), accidents (39%), and nontraumatic causes (6%). Also, the frequent presence of retinal hemorrhages, bone and rib fractures, delay in presentation, and young age suggests child abuse as the most common cause of these injuries.…

  11. An unusual case of multiple self-inflicted punctures to the precordium

    LENUS (Irish Health Repository)

    Borhan, F

    2017-06-01

    Sewing needles, albeit a rare case of penetrating cardiac injury, are potentially life-threatening. We report a case of successful intra-cardiac needle removal from a 32 year old who inserted multiple needles into the chest and abdomen.

  12. Self-inflicted violence: a sociological concern and a public health problem

    Science.gov (United States)

    Minayo

    1998-04-01

    This paper has two objectives. The first is to reflect on the meaning of suicide as a sociological issue, commenting on an article by E.D. Nunes (1988) on the famous work by Durkheim. The second is to discuss the same issue within the field of public health, analyzing the contributions by the father of sociology and approaches by the fields of epidemiology, psychology, psychiatry, and psychoanalysis, highlighting the work of Brazilian authors. The paper presents information on the Brazilian epidemiological context and concludes by demonstrating that only from an analytical point of view can violent causes as a whole can be studied separately. Thus, they constantly require epistemological and epidemiological surveillance to construct indicators capable of contributing to change. This is all the more true because data on current violence need to be viewed within the context of the social crisis and changes Brazil is undergoing.

  13. Delayed Presentation of Submucosal Retained Toothbrush from Self-Inflicted Injury in Patient with Schizophrenia

    Directory of Open Access Journals (Sweden)

    Caleb H. Creswell

    2017-01-01

    Full Text Available Foreign body ingestion occurs in not only children but also adults, particularly those with history of neurologic disease, alcohol use, or psychiatric disease. We present the case of a 40-year-old male with schizophrenia who presented to the emergency room with a long history of pharyngeal foreign body sensation which had recently progressed to include trismus, odynophagia, and dyspnea. Flexible laryngoscopy demonstrated fullness of the right posterior pharyngeal wall and computed tomography (CT showed a linear opaque foreign body extending from the level of the oropharynx to the thyroid ala. Further history elicited that he stabbed himself in the pharynx two years prior with a toothbrush following a command hallucination. The toothbrush was removed uneventfully via an external approach. The patient was discharged with psychiatry follow-up. This case is unusual due to the submucosal location of the foreign body and the length of retention. It demonstrates the atypical nature which patients with comorbid psychiatric illness may present following foreign body injury and the use of an external surgical approach for the removal of a retained foreign body based on CT reconstruction.

  14. Early evolution and recovery from excitotoxic injury in the neonatal rat brain

    NARCIS (Netherlands)

    Lookeren Campagne, van M.; Verheul, H.B.; Nicolaij, K.; Balázs, R.E.

    1994-01-01

    We explored the therapeutic potentials of two N-methyl-D-aspartate (NMDA) receptor antagonists in vivo using different techniques. NMDA injected into the striatum of neonatal rats (20 nmol/0.5 microliters) induced a rapid increase in the diffusion-weighted (DW) image intensity, spreading over a

  15. Silibinin, dexamethasone, and doxycycline as potential therapeutic agents for treating vesicant-inflicted ocular injuries

    International Nuclear Information System (INIS)

    Tewari-Singh, Neera; Jain, Anil K.; Inturi, Swetha; Ammar, David A.; Agarwal, Chapla; Tyagi, Puneet; Kompella, Uday B.; Enzenauer, Robert W.; Petrash, J. Mark; Agarwal, Rajesh

    2012-01-01

    There are no effective and approved therapies against devastating ocular injuries caused by vesicating chemical agents sulfur mustard (SM) and nitrogen mustard (NM). Herein, studies were carried out in rabbit corneal cultures to establish relevant ocular injury biomarkers with NM for screening potential efficacious agents in laboratory settings. NM (100 nmol) exposure of the corneas for 2 h (cultured for 24 h), showed increases in epithelial thickness, ulceration, apoptotic cell death, epithelial detachment microbullae formation, and the levels of VEGF, cyclooxygenase-2 (COX-2) and matrix metalloproteinase-9 (MMP-9). Employing these biomarkers, efficacy studies were performed with agent treatments 2 h and every 4 h thereafter, for 24 h following NM exposure. Three agents were evaluated, including prescription drugs dexamethasone (0.1%; anti-inflammatory steroid) and doxycycline (100 nmol; antibiotic and MMP inhibitor) that have been studied earlier for treating vesicant-induced eye injuries. We also examined silibinin (100 μg), a non-toxic natural flavanone found to be effective in treating SM analog-induced skin injuries in our earlier studies. Treatments of doxycycline + dexamethasone, and silibinin were more effective than doxycycline or dexamethasone alone in reversing NM-induced epithelial thickening, microbullae formation, apoptotic cell death, and MMP-9 elevation. However, dexamethasone and silibinin alone were more effective in reversing NM-induced VEGF levels. Doxycycline, dexamethasone and silibinin were all effective in reversing NM-induced COX-2 levels. Apart from therapeutic efficacy of doxycycline and dexamethasone, these results show strong multifunctional efficacy of silibinin in reversing NM-induced ocular injuries, which could help develop effective and safe therapeutics against ocular injuries by vesicants. -- Highlights: ► Established injury biomarkers in rabbit corneal culture with nitrogen mustard (NM) ► This NM model is a cost effective system to evaluate and optimize therapeutics. ► Show that doxycycline and dexamethasone reduce NM-caused ocular injuries ► Demonstrate that silibinin effectively reverses NM-caused ocular injury endpoints ► Suggest optimization of identified agents against ocular injuries by vesicants

  16. A neuroprotective role for microRNA miR-1000 mediated by limiting glutamate excitotoxicity

    DEFF Research Database (Denmark)

    Verma, Pushpa; Augustine, George J; Ammar, Mohamed-Raafet

    2015-01-01

    Evidence has begun to emerge for microRNAs as regulators of synaptic signaling, specifically acting to control postsynaptic responsiveness during synaptic transmission. In this report, we provide evidence that Drosophila melanogaster miR-1000 acts presynaptically to regulate glutamate release at ...... a neuroprotective function in the brains of flies and mice. Drosophila miR-1000 showed activity-dependent expression, which might serve as a mechanism to allow neuronal activity to fine-tune the strength of excitatory synaptic transmission....

  17. Self-Inflicted Wounds: Debates and Divisions within al-Qa’ida and its Periphery

    Science.gov (United States)

    2010-12-16

    Genetics : The Afghan Origins  Al‐Qa’ida’s current efforts to unify disparate Islamist groups and struggles into a global  conflict against the so‐called...upon.    The Tawhed.ws site has a special page dedicated to the Shi’a under the  rubric  of “sects  and  schools,”  a  section  that  is modeled  on

  18. The Nigrostriatal Dopamine System and Methamphetamine: Roles for Excitotoxicity and Environment, Metabolic and Oxidative Stress

    National Research Council Canada - National Science Library

    Yamamoto, Bryan

    2001-01-01

    .... Similarly, the psychostimulant drug, methamphetamine also produces relatively selective damage to nigrostriatal dopamine neurons and is rapidly becoming a widespread problem and drug of abuse throughout the U.S...

  19. The Nigrostriatal Dopamine System and Methamphetamine: Roles for Excitotoxicity and Environmental, Metabolic and Oxidative Stress

    National Research Council Canada - National Science Library

    Yamamoto, Bryan

    2005-01-01

    .... Similarly, the psychostimulant drug, methamphetamine also produces relatively selective damage to nigrostriatal dopamine neurons and is a widespread problem and drug of abuse throughout the U.S...

  20. The Nigrostriatal Dopamine System and Methamphetamine: Roles for Excitotoxicity and Environment, Metabolic and Oxidative Stress

    National Research Council Canada - National Science Library

    Yamamoto, Bryan

    2000-01-01

    .... Similarly, the psycho stimulant drug, methamphetamine also produces relatively selective damage to nigrostriatal dopamine neurons and is rapidly becoming a widespread problem and drug of abuse throughout the U.S...

  1. Interviewing insights regarding the fatalities inflicted by the 2011 Great East Japan Earthquake

    Science.gov (United States)

    Ando, M.; Ishida, M.; Hayashi, Y.; Mizuki, C.; Nishikawa, Y.; Tu, Y.

    2013-09-01

    One hundred fifty survivors of the 11 March 2011 Great East Japan Earthquake (Tohoku-oki earthquake) (Mw = 9.0) were interviewed to study the causes of deaths from the associated tsunami in coastal areas of Tohoku. The first official tsunami warning underestimated the height of the tsunami and 40% of the interviewees did not obtain this warning due to immediate blackouts and a lack of communication after the earthquake. Many chose to remain in dangerous locations based on the underestimated warning and their experiences with previous smaller tsunamis and/or due to misunderstanding the mitigating effects of nearby breakwaters in blocking incoming tsunamis. Some delayed their evacuation to perform family safety checks, and in many situations, the people affected misunderstood the risks involved in tsunamis. In this area, three large tsunamis have struck in the 115 yr preceding the 2011 tsunami. These tsunamis remained in the collective memory of communities, and numerous measures against future tsunami damage, such as breakwaters and tsunami evacuation drills, had been implemented. Despite these preparedness efforts, approximately 18 500 deaths and cases of missing persons occurred. The death rate with the age of 65 and above was particularly high, four times higher than that with other age groups. These interviews indicate that deaths resulted from a variety of reasons, but if residents had taken immediate action after the major ground motion stopped, most residents might have been saved. Education about the science behind earthquakes and tsunamis could help save more lives in the future.

  2. The Nigrostriatal Dopamine System and Methamphetamine: Roles for Excitotoxicity and Environmental, Metabolic and Oxidative Stress

    Science.gov (United States)

    2005-07-01

    K. (1995) Methamphetamine -induced hyperthermia and dopaminergic neurotoxicity in mice: pharmacological profile of protective and nonprotective agents...glutamate receptors is protective against methamphetamine neurotoxicity . JNeurosci 22, 2135-2141. Beer R., Franz G., Srinivasan A., Hayes R. L., Pike B. R...1992) The neurotoxic effects of methamphetamine on 5-hydroxytryptamine and dopamine in brain: evidence for the protective effect of chlormethiazole

  3. Reducing losses inflicted by insect pests on cashew, using weaver ants as a biological control agent

    DEFF Research Database (Denmark)

    Anato, Florence; Wargui, Rosine; Sinzogan, Antonio

    2015-01-01

    BACKGROUND: Cashew (Anacardium occidentale Linnaeus) is the largest agricultural export product in Benin. However, yields and quality are lost due to inefficient pest control. Weaver ants (Oecophylla spp.) may control pests in this crop as they eat and deter pests. In Benin, cashew pest damages......, nut quality and yield were compared among: (i) trees with weaver ant (Oecophylla longinoda Latreille), (ii) trees where weaver ants were fed sugar, (iii) IPM trees with weaver ants combined with GF-120 (a natural insecticide), and (iv) control trees receiving no control measures. RESULTS: Thrips...... damages on nuts were higher than other damage symptoms and significantly lower on control trees compared to other treatments. Percentage of first quality nuts was higher in the control compared to ants treatments, but not different from the IPM-treatment. However, compared to the control treatment, ants...

  4. [Peculiarities of forensic medical expertise of gunshot wounds inflicted through a bulletproof vest].

    Science.gov (United States)

    Ozertskovskiĭ, L B; Tiurin, M V; Denisov, A V

    2013-01-01

    A series of experimental studies was conducted with the object of elucidating the mechanisms of the bullet after-penetration effect produced by a handgun shot into the armoured vest with special reference to the changes developing in the space behind the barrier. The application of the pulsed radiographic technique revealed a transient cavity the presence of which accounts for the injuries to soft tissues, bones, and internal organs in the projection of the bullet impact without damage to the armour plates.

  5. Genetic relatedness of Trichoderma isolates antagonistic against Fusarium oxysporum f.sp. dianthi inflicting carnation wilt.

    Science.gov (United States)

    Shanmugam, V; Sharma, Vivek; Ananthapadmanaban

    2008-01-01

    Twenty-eight isolates of Trichoderma belonging to four different species were screened in vitro for their antagonistic ability against Fusarium oxysporum f.sp. dianthi causing carnation wilt. Three different levels of antagonism observed in dual plate assay were further confirmed by cell-free culture filtrate experiments. Isolates showing class I level of antagonism produced maximum lytic enzymes, chitinases and beta-1,3-glucanases. Genetic variability of 25 selected isolates was assessed by random amplified polymorphic DNA technique and the amplified products were correlated for their level of antagonism. Unweighed pair-group method with arithmetical averages cluster analysis revealed prominent inter-and intraspecific genetic variation among the isolates. Based on their genetic relationship, the isolates were mainly distributed into 3 major groups representing T. atroviride, T. pseudokoningii and T. harzianum, with 20-35% interspecific dissimilarity. However, the polymorphism shown by the isolates did not correlate to their level of antagonism.

  6. The burden and management of self-inflicted injuries at a tertiary ...

    African Journals Online (AJOL)

    Praveen Sravanam

    unemployment, financial difficulties, substance abuse, a difficult childhood, poor physical ... include extremes of heat or cold, electrocution and suicidal behaviour .... Self-poisoning (mainly drug overdose and other chemical agents unknown to.

  7. The frequency and effect of shark-inflicted bite injuries to the reef ...

    African Journals Online (AJOL)

    Shark bite injuries on reef manta rays Manta alfredi off the coast of Inhambane, Mozambique, were examined over a three-year period (2003–2006). The frequency and seasonality of attacks, the rate of wound healing, and the possible identities of attackers were explored. This study presents the first examination of bite ...

  8. From an inflicted dependency to a positive co-operation in the domain of energy

    Energy Technology Data Exchange (ETDEWEB)

    Host, Jean-Paul; Darras, Marc [Gaz de France (France)

    2007-07-01

    The 20th World Energy Congress entitled, ''Energy Future in an Interdependent World'', is aimed at highlighting the main challenges and opportunities that the energy industry should face to contribute to sustainable development across the world. For we are very much in the face of a challenge: with the demand for energy likely to increase, the energy industry will have to get by with limited resources: as concerns energy, the gradual rarefaction of fossil fuels resources, combined with the lack of any convincing substitution options in the medium term; as concerns natural resources, or more accurately, the harm that the natural environment can bear sustainably; and as concerns capital, insofar as the huge investments needed in the field of energy will be competing with other types of investments that may appear more profitable or safer. Given this situation, two types of political and economic response can be envisioned. The first is to simply let the market run its course and relations between States play out as they normally would. This would, admittedly, make it possible to solve some of the issues raised but no one can guarantee that this will not heighten political tension and lead to dangerous dawdling with regard to the climate issue. Another option is to mobilise the international community so that the interdependency leads to some sort of positive cooperation. This would require that, building on the reflections carried out virtually everywhere, international consensus would emerge and make it possible to create and champion a shared vision, leading to the institution of an enabling environment for action for states and operators altogether. Above and beyond the trade relationship that binds the latter, they have an important part to play insofar as they can significantly contribute to sustainable development across the world through the investments they make abroad and the results of their 'research' when shared through technology transfers. In a second part, this document endeavours in each of the aforementioned fields, to describe Gaz de France contributions and to highlight the developments in the legal and contractual framework, which we see as likely to cut down the barriers encountered by a company as it takes action.

  9. A metallothionein mimetic peptide protects neurons against kainic acid-induced excitotoxicity

    DEFF Research Database (Denmark)

    Sonn, Katrin; Pankratova, Stanislava; Korshunova, Irina

    2010-01-01

    Metallothioneins I and II (MTI/II) are metal-binding proteins overexpressed in response to brain injury. Recently, we have designed a peptide, termed EmtinB, which is modeled after the beta-domain of MT-II and mimics the biological effects of MTI/II in vitro. Here, we demonstrate the neuroprotect...

  10. Effects of Weaver Ants on Fruitfly and Disease-inflicted Postharvest ...

    African Journals Online (AJOL)

    Orange production in Tanzania is largely conducted by small-scale farmers and ranks the third in importance with production areas of. 52,972 (National Bureau of Statistics, 2012). The crop is grown by small-scale farmers in a mixed cropping system consisting of banana, mangoes and cassava. Tanga, Morogoro and.

  11. Linguistic Factors Associated with Self-Inflicted Injury in Borderline Personality Disorder

    Science.gov (United States)

    Birdwell, Benjamin Park

    2009-01-01

    The present study builds on previous research, which demonstrated higher levels of depressive and interpersonal conflict language in first-person narrative accounts of nonsuicidal self-injury (NSSI) and suicide attempt (SA) in borderline personality disorder. The present study was designed to examine the semantic similarity of time-sequences…

  12. A Robust and Resilient Network Design Paradigm for Region-Based Faults Inflicted by WMD Attack

    Science.gov (United States)

    2016-04-01

    Infrastructure Mapping over Transport Software - Defined Networks (T- SDN )”, IEEE/OSA OFC, 2014 (invited for a special issue of OSA/IEEE JOCN) 23. L. Liu, J...Ji and C. Qiao “Survivable Virtual Infrastructure Mapping with Shared Protection in Transport Software - Defined Networks (T- SDNs )”, OECC, 2014. 25. S...483-493, 2014. 21. Z. Ye, X. Li, A. N. Patel, P. N. Ji, X. Cao, C. Qiao, “Upgrade-aware Virtual Infrastructure Mapping in Software - Defined Elastic

  13. Inflicted T12 fracture-dislocation: CT/MRI correlation and mechanistic implications

    Energy Technology Data Exchange (ETDEWEB)

    Tran, Brandon [Brigham and Women' s Hospital, Section of Neuroradiology, Department of Radiology, Boston, MA (United States); Silvera, Michelle [Children' s Hospital Boston, Division of Neuroradiology, Department of Radiology, Boston, MA (United States); Newton, Alice [Children' s Hospital Boston, Division of General Pediatrics, Boston, MA (United States); Kleinman, Paul K. [Children' s Hospital Boston, Department of Radiology, Boston, MA (United States)

    2007-11-15

    We describe the CT and MRI findings of a thoracolumbar neurocentral synchondrosis fracture-dislocation in an abused infant. The morphologic features of this classically described fracture, and the associated cervical and sacral spine injuries displayed on cross-sectional imaging, provide compelling evidence for a mechanism of massive hyperflexion and axial spinal loading. (orig.)

  14. Automation inflicted differences on operator performance in nuclear power plant control rooms

    Energy Technology Data Exchange (ETDEWEB)

    Andersson, Jonas; Osvalder, A.L. [Chalmers Univ. of Technology, Dept. of Product and Producton Development (Sweden)

    2007-03-15

    Today it is possible to automate almost any function in a human-machine system. Therefore it is important to find a balance between automation level and the prerequisites for the operator to maintain safe operation. Different human factors evaluation methods can be used to find differences between automatic and manual operations that have an effect on operator performance; e.g. Predictive Human Error Analysis (PHEA), NASA Task Load Index (NASA-TLX), Halden Questionnaire, and Human Error Assessment and Reduction Technique (HEART). Results from an empirical study concerning automation levels, made at Ringhals power plant, showed that factors as time pressure and criticality of the work situation influenced the operator's performance and mental workload more than differences in level of automation. The results indicate that the operator's attention strategies differ between the manual and automatic sequences. Independently of level of automation, it is essential that the operator retains control and situational understanding. When performing a manual task, the operator is 'closer' to the process and in control with sufficient situational understanding. When the level of automation increases, the demands on information presentation increase to ensure safe plant operation. The need for control can be met by introducing 'control gates' where the operator has to accept that the automatic procedures are continuing as expected. Situational understanding can be established by clear information about process status and by continuous feedback. A conclusion of the study was that a collaborative control room environment is important. Rather than allocating functions to either the operator or the system, a complementary strategy should be used. Key parameters to consider when planning the work in the control room are time constraints and task criticality and how they affect the performance of the joint cognitive system.However, the examined working situations were too different with respect to levels of automation and therefore it is not possible yet to propose general automation level guidelines. Further studies are still needed. (au)

  15. Violent Dynamics: Exploring Responsibility-Attribution for Harms Inflicted During Spontaneous Group Violence

    Directory of Open Access Journals (Sweden)

    Antje du Bois Pedain

    2016-12-01

    Full Text Available Violent encounters between groups of individuals often leave one or more of the participants dead, and it may be clear from the evidence that the physical cause of death was set by the single, deliberate act of one of the participants only. When this happens, the question arises whether, and how, responsibility for the fatal act and/or for its consequences can be attributed to other participants in the punch-up. Criminal law has long sought – and found – ways of holding others apart from the direct agent responsible for the harms caused in such encounters, although the legal constructions used differ between legal systems and often change significantly over time even within the same jurisdiction. This paper investigates the appropriateness of different criminal-law responses to these cases from two directions: first, by exploring the possible doctrinal grounds within the criminal law for attributing responsibility for the fatal act/outcome to all participants; and then by investigating the extent to which these responsibility-ascriptions are supported or challenged by insights from psychological studies of group action. Los encuentros violentos entre grupos de individuos a menudo acaban con la muerte de uno o más de los participantes, y las pruebas pueden demostrar que la causa física de la muerte fue el acto único deliberado de uno solo de los participantes. Cuando esto ocurre, se plantea la pregunta de si se puede atribuir a otros participantes en la pelea la responsabilidad por el acto fatal y/o sus consecuencias, y cómo hacerlo. Durante mucho tiempo, el derecho penal ha buscado, y encontrado, formas de retener a otros participantes, además del responsable directo de los daños causados, aunque las construcciones legales utilizadas difieren entre sistemas jurídicos y a menudo cambian significativamente a lo largo del tiempo, incluso dentro de la misma jurisdicción. Este artículo investiga la conveniencia de diferentes respuestas del derecho penal a estos casos, desde dos enfoques: primero, explorando los posibles fundamentos doctrinales dentro del derecho penal para atribuir la responsabilidad del acto / resultado fatal a todos los participantes; y a continuación, investigando hasta qué punto los estudios psicológicos sobre acciones grupales confirman o rechazan esta imputación de responsabilidad. DOWNLOAD THIS PAPER FROM SSRN: https://ssrn.com/abstract=2875780

  16. Curcumin Protects Neurons from Glutamate-Induced Excitotoxicity by Membrane Anchored AKAP79-PKA Interaction Network

    Directory of Open Access Journals (Sweden)

    Kui Chen

    2015-01-01

    Full Text Available Now stimulation of AMPA receptor as well as its downstream pathways is considered as potential central mediators in antidepressant mechanisms. As a signal integrator which binds to AMPA receptor, A-kinase anchoring protein 79-(AKAP79- PKA complex is regarded as a potential drug target to exert neuroprotective effects. A well-tolerated and multitarget drug curcumin has been confirmed to exert antidepressant-like effects. To explore whether AKAP79-PKA complex is involved in curcumin-mediated antiexcitotoxicity, we detected calcium signaling, subcellular location of AKAP79-PKA complex, phosphorylation of glutamate receptor, and ERK and AKT cascades. In this study, we found that curcumin protected neurons from glutamate insult by reducing Ca2+ influx and blocking the translocation of AKAP79 from cytomembrane to cytoplasm. In parallel, curcumin enhanced the phosphorylation of AMPA receptor and its downstream pathways in PKA-dependent manner. If we pretreated cells with PKA anchoring inhibitor Ht31 to disassociate PKA from AKAP79, no neuroprotective effects were observed. In conclusion, our results show that AKAP79-anchored PKA facilitated the signal relay from AMPA receptor to AKT and ERK cascades, which may be crucial for curcumin-mediated antiexcitotoxicity.

  17. Human fetuses do not register chromosome damage inflicted by radiation exposure in lymphoid precursor cells

    International Nuclear Information System (INIS)

    Nakamura, N.; Ohtaki, K.; Kodama, Y.; Nakano, M.; Itoh, M.; Awa, A.A.; Cologne, J.B.

    2003-01-01

    Human fetuses are generally thought to be highly sensitive to radiation exposure since diagnostic, low-dose X rays (5-50 mSv) have been suggested to increase the risk of childhood leukemia by about 50%. In contrast, animal studies generally did not demonstrate a high radiosensitivity of fetuses and the underlying causes for the discrepancy are not understood. Here, we examined atomic-bomb survivors exposed in utero for translocation frequency in blood lymphocytes at 40 years of age. Contrary to our expectation of higher radiosensitivity in fetuses than in adults, the frequency did not increase with dose except for a small, but statistically significant increase (<1%) at doses below 0.1 Sv. Although an upward convex, humped dose response has been observed in other instances, the peak usually lies at doses above a few Gy, and few examples are known showing the peak response at such low doses. We interpret the results as indicating that fetal lymphoid and/or their precursor cells are sensitive to elimination through apoptosis when damaged. Our results provide a biological basis to resolve the long-standing controversy that substantial risk of childhood leukemia is implicated in human fetuses exposed to low-dose diagnostic X rays whereas animal studies composed mainly of exposures to higher doses consistently fail to confirm it

  18. Chronic excitotoxic lesion of the dorsal raphe nucleus induces sodium appetite

    Directory of Open Access Journals (Sweden)

    Cavalcante-Lima H.R.

    2005-01-01

    Full Text Available We determined if the dorsal raphe nucleus (DRN exerts tonic control of basal and stimulated sodium and water intake. Male Wistar rats weighing 300-350 g were microinjected with phosphate buffer (PB-DRN, N = 11 or 1 µg/0.2 µl, in a single dose, ibotenic acid (IBO-DRN, N = 9 to 10 through a guide cannula into the DRN and were observed for 21 days in order to measure basal sodium appetite and water intake and in the following situations: furosemide-induced sodium depletion (20 mg/kg, sc, 24 h before the experiment and a low dose of dietary captopril (1 mg/g chow. From the 6th day after ibotenic acid injection IBO-DRN rats showed an increase in sodium appetite (12.0 ± 2.3 to 22.3 ± 4.6 ml 0.3 M NaCl intake whereas PB-DRN did not exceed 2 ml (P < 0.001. Water intake was comparable in both groups. In addition to a higher dipsogenic response, sodium-depleted IBO-DRN animals displayed an increase of 0.3 M NaCl intake compared to PB-DRN (37.4 ± 3.8 vs 21.6 ± 3.9 ml 300 min after fluid offer, P < 0.001. Captopril added to chow caused an increase of 0.3 M NaCl intake during the first 2 days (IBO-DRN, 33.8 ± 4.3 and 32.5 ± 3.4 ml on day 1 and day 2, respectively, vs 20.2 ± 2.8 ml on day 0, P < 0.001. These data support the view that DRN, probably via ascending serotonergic system, tonically modulates sodium appetite under basal and sodium depletion conditions and/or after an increase in peripheral or brain angiotensin II.

  19. Group I metabotropic glutamate receptors reduce excitotoxic injury and may facilitate neurogenesis

    DEFF Research Database (Denmark)

    Baskys, Andrius; Bayazitov, Ildar; Fang, Liwei

    2005-01-01

    neuroprotective activation of group I metabotropic glutamate receptors. Brain Research, Molecular Brain Research 117, 196-205.]. In the present study, we used organotypic hippocampal culture preparation to examine specific phospholipase C (PLC) inhibitor U73122 effects on DHPG-induced neuroprotection, changes......-CA1 pathway. The fEPSP depression was not affected by the PLC inhibitor U73122. In contrast, prolonged (2-h) treatment of cultures with DHPG induced a significant protective effect that was blocked by a PLC inhibitor U73122 but not by its inactive analog U73343. Voltage-clamp measurements...... a PLC involvement. Since activation of PLC is thought to be associated with cell proliferation, we investigated whether group I mGluR agonist DHPG or subtype antagonists LY367385 and MPEP have an effect on dentate granule cells expressing immature neuronal marker TOAD-64. DHPG (100 microM, 72 h...

  20. Mitochondria, Bioenergetics and Excitotoxicity: New Therapeutic Targets in Perinatal Brain Injury

    Directory of Open Access Journals (Sweden)

    Bryan Leaw

    2017-07-01

    Full Text Available Injury to the fragile immature brain is implicated in the manifestation of long-term neurological disorders, including childhood disability such as cerebral palsy, learning disability and behavioral disorders. Advancements in perinatal practice and improved care mean the majority of infants suffering from perinatal brain injury will survive, with many subtle clinical symptoms going undiagnosed until later in life. Hypoxic-ischemia is the dominant cause of perinatal brain injury, and constitutes a significant socioeconomic burden to both developed and developing countries. Therapeutic hypothermia is the sole validated clinical intervention to perinatal asphyxia; however it is not always neuroprotective and its utility is limited to developed countries. There is an urgent need to better understand the molecular pathways underlying hypoxic-ischemic injury to identify new therapeutic targets in such a small but critical therapeutic window. Mitochondria are highly implicated following ischemic injury due to their roles as the powerhouse and main energy generators of the cell, as well as cell death processes. While the link between impaired mitochondrial bioenergetics and secondary energy failure following loss of high-energy phosphates is well established after hypoxia-ischemia (HI, there is emerging evidence that the roles of mitochondria in disease extend far beyond this. Indeed, mitochondrial turnover, including processes such as mitochondrial biogenesis, fusion, fission and mitophagy, affect recovery of neurons after injury and mitochondria are involved in the regulation of the innate immune response to inflammation. This review article will explore these mitochondrial pathways, and finally will summarize past and current efforts in targeting these pathways after hypoxic-ischemic injury, as a means of identifying new avenues for clinical intervention.

  1. Self-inflicted finger injury in individuals with spinal cord injury: an analysis of 5 cases.

    Science.gov (United States)

    Frost, Frederick S; Mukkamala, Sridevi; Covington, Edward

    2008-01-01

    To describe the occurrence of finger autophagia in 5 persons with traumatic spinal cord injury and to present a discussion of putative causes and potential treatments. Minor self-mutilating actions, such as nail biting and hair pulling, are common in humans and usually benign. In some circumstances, these behaviors are associated with obsessive-compulsive personality traits. In humans, self-injurious biting behaviors are well described in the setting of mental retardation and psychosis and in persons with Lesch-Nyhan syndrome. Rare cases of human autophagia in persons with intact cognition have been reported, most commonly in the setting of acquired nervous system lesions. After spinal cord injury, it has been suggested that this behavior constitutes a human variant of animal autotomy and a response to neuropathic pain. Case presentation narrative. Photographic and radiological study, administration of Yale-Brown Obsessive-Compulsive Scale (YBOCS). In 5 patients with complete tetraplegia, pain in the hands was present in only one instance. The severity of autoamputation varied from minor to extreme. In all cases, damage was confined to analgesic body parts. In 3 cases, autophagia behavior was discovered in progress. Treatments included pharmacotherapy, counseling, and behavioral therapy, with mixed results. All patients were intelligent, willing to discuss their issues, and able to identify conditions of stress and isolation in their lives. Mild preinjury obsessive-compulsive behaviors, such as nail biting, were universal. On the YBOCS, only 1 patient scored in a range indicative of mild obsessive-compulsive symptomatology. This group exhibited heterogeneous medical, social, and cultural characteristics. A link between pain and self-injurious behavior could not be demonstrated. This behavior may be viewed as an extreme variant of nail biting, with potential ominous complications. Treatment strategies have been employed with mixed results.

  2. [Study of generational risk in deafness inflicted couples using deafness gene microarray technique].

    Science.gov (United States)

    Wang, Ping; Zhao, Jia; Yu, Shu-yuan; Jin, Peng; Zhu, Wei; DU, Bo

    2011-06-01

    To explored the significance of screening the gene mutations of deafness related in deaf-mute (deaf & dumb) family using DNA microarray. Total of 52 couples of deaf-mute were recruited from Changchun deaf-mute community. With an average age of (58.3 ± 6.7) years old (x(-) ± s). Blood samples were obtained with informed consent. Their genomic DNA was extracted from peripheral blood and PCR was performed. Nine of hot spot mutations in four most common deafness pathologic gene were examined with the DNA microarray, including GJB2, GJB3, PDS and mtDNA 12S rRNA genes. At the same time, the results were verified with the traditional methods of sequencing. Fifty of normal people served as a control group. All patients were diagnosed non-syndromic sensorineural hearing loss by subjective pure tone audiometry. Thirty-two of 104 cases appeared GJB2 gene mutation (30.7%), the mutation sites included 35delG, 176del16, 235delC and 299delAT. Eighteen of 32 cases of GJB2 mutations were 235delC (59.1%). Seven of 104 cases appeared SLC26A4 gene IVS7-2 A > G mutation. Questionnaire survey and gene diagnosis revealed that four of 52 families have deaf offspring (7.6%). When a couple carries the same gene mutation, the risk of their children deafness was 100%. The results were confirmed with the traditional methods of sequencing. There is a high risk of deafness if a deaf-mute family is planning to have a new baby. It is very important and helpful to avoid deaf newborns again in deaf-mute family by DNA microarray.

  3. Silibinin, dexamethasone, and doxycycline as potential therapeutic agents for treating vesicant-inflicted ocular injuries

    Energy Technology Data Exchange (ETDEWEB)

    Tewari-Singh, Neera, E-mail: Neera.Tewari-Singh@ucdenver.edu [Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO 80045 (United States); Jain, Anil K., E-mail: Anil.Jain@ucdenver.edu [Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO 80045 (United States); Inturi, Swetha, E-mail: Swetha.Inturi@ucdenver.edu [Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO 80045 (United States); Ammar, David A., E-mail: David.Ammar@ucdenver.edu [Department of Ophthalmology, University of Colorado School of Medicine, Aurora, CO 80045 (United States); Agarwal, Chapla, E-mail: Chapla.Agarwal@ucdenver.edu [Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO 80045 (United States); Tyagi, Puneet, E-mail: Puneet.Tyagi@ucdenver.edu [Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO 80045 (United States); Kompella, Uday B., E-mail: Uday.Kompella@ucdenver.edu [Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO 80045 (United States); Enzenauer, Robert W., E-mail: Robert.Enzenauer@ucdenver.edu [Department of Ophthalmology, University of Colorado School of Medicine, Aurora, CO 80045 (United States); Petrash, J. Mark, E-mail: Mark.Petrash@ucdenver.edu [Department of Ophthalmology, University of Colorado School of Medicine, Aurora, CO 80045 (United States); Agarwal, Rajesh, E-mail: Rajesh.Agarwal@ucdenver.edu [Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO 80045 (United States)

    2012-10-01

    There are no effective and approved therapies against devastating ocular injuries caused by vesicating chemical agents sulfur mustard (SM) and nitrogen mustard (NM). Herein, studies were carried out in rabbit corneal cultures to establish relevant ocular injury biomarkers with NM for screening potential efficacious agents in laboratory settings. NM (100 nmol) exposure of the corneas for 2 h (cultured for 24 h), showed increases in epithelial thickness, ulceration, apoptotic cell death, epithelial detachment microbullae formation, and the levels of VEGF, cyclooxygenase-2 (COX-2) and matrix metalloproteinase-9 (MMP-9). Employing these biomarkers, efficacy studies were performed with agent treatments 2 h and every 4 h thereafter, for 24 h following NM exposure. Three agents were evaluated, including prescription drugs dexamethasone (0.1%; anti-inflammatory steroid) and doxycycline (100 nmol; antibiotic and MMP inhibitor) that have been studied earlier for treating vesicant-induced eye injuries. We also examined silibinin (100 μg), a non-toxic natural flavanone found to be effective in treating SM analog-induced skin injuries in our earlier studies. Treatments of doxycycline + dexamethasone, and silibinin were more effective than doxycycline or dexamethasone alone in reversing NM-induced epithelial thickening, microbullae formation, apoptotic cell death, and MMP-9 elevation. However, dexamethasone and silibinin alone were more effective in reversing NM-induced VEGF levels. Doxycycline, dexamethasone and silibinin were all effective in reversing NM-induced COX-2 levels. Apart from therapeutic efficacy of doxycycline and dexamethasone, these results show strong multifunctional efficacy of silibinin in reversing NM-induced ocular injuries, which could help develop effective and safe therapeutics against ocular injuries by vesicants. -- Highlights: ► Established injury biomarkers in rabbit corneal culture with nitrogen mustard (NM) ► This NM model is a cost effective system to evaluate and optimize therapeutics. ► Show that doxycycline and dexamethasone reduce NM-caused ocular injuries ► Demonstrate that silibinin effectively reverses NM-caused ocular injury endpoints ► Suggest optimization of identified agents against ocular injuries by vesicants.

  4. Automation inflicted differences on operator performance in nuclear power plant control rooms

    International Nuclear Information System (INIS)

    Andersson, Jonas; Osvalder, A.L.

    2007-03-01

    Today it is possible to automate almost any function in a human-machine system. Therefore it is important to find a balance between automation level and the prerequisites for the operator to maintain safe operation. Different human factors evaluation methods can be used to find differences between automatic and manual operations that have an effect on operator performance; e.g. Predictive Human Error Analysis (PHEA), NASA Task Load Index (NASA-TLX), Halden Questionnaire, and Human Error Assessment and Reduction Technique (HEART). Results from an empirical study concerning automation levels, made at Ringhals power plant, showed that factors as time pressure and criticality of the work situation influenced the operator's performance and mental workload more than differences in level of automation. The results indicate that the operator's attention strategies differ between the manual and automatic sequences. Independently of level of automation, it is essential that the operator retains control and situational understanding. When performing a manual task, the operator is 'closer' to the process and in control with sufficient situational understanding. When the level of automation increases, the demands on information presentation increase to ensure safe plant operation. The need for control can be met by introducing 'control gates' where the operator has to accept that the automatic procedures are continuing as expected. Situational understanding can be established by clear information about process status and by continuous feedback. A conclusion of the study was that a collaborative control room environment is important. Rather than allocating functions to either the operator or the system, a complementary strategy should be used. Key parameters to consider when planning the work in the control room are time constraints and task criticality and how they affect the performance of the joint cognitive system.However, the examined working situations were too different with respect to levels of automation and therefore it is not possible yet to propose general automation level guidelines. Further studies are still needed. (au)

  5. Management of unusual case of self-inflicted penetrating craniocerebral injury by a nail

    Directory of Open Access Journals (Sweden)

    Kishore Kamal

    2010-01-01

    Full Text Available During war, sharp high-speed missiles have been driven inside the brain; however, in civilian practice it is rare to see such episodes. An approximately 10-cm long nail was driven inside the brain in an attempt to commit suicide by a schizophrenic patient. The case is being reported for its rarity in civilian practice and as a case of clinical interest. After investigating the patient by plain X-rays and a CT scan, he was operated by a neurosurgical team and the nail was successfully removed. In post-operative phase, patient was given medical and psychiatric care along with psychological counseling. The patient made good uneventful recovery in the post-operative phase.

  6. [Self-inflicted finger-amputation: insurance fraud or accidental injury?].

    Science.gov (United States)

    Hildebrand, E; Hitzer, K; Püschel, K

    2006-03-01

    A 50-year-old surgeon was working with his electrical circle saw as a do-it-yourselfer. He was alone, nobody witnessed his mishap when he amputated his left index finger. He claimed high financial compensation from two accident insurance companies because of his disability. A long series of medical expertises followed. The juridical procedures took 12 years in total. All higher authorities had to deal with the forensic medical implications. Finally, the high court (Bundesgerichtshof) decided that the complainant would receive no compensation because he gave two very different descriptions. Concerning the reconstruction of the accident, the first version was unlikely from a biomechanical point of view. The decision of the court was solely based on the violation of the obligation to give a clear presentation of the course of events (Obliegenheitsverletzung).

  7. Self-inflicted foreign bodies in lower genitourinary tract in males: Our experience and review of literature

    Directory of Open Access Journals (Sweden)

    Nagabhushana Mahadevappa

    2016-01-01

    Conclusions: Foreign body insertion to lower urinary tract was rare. A main cause for insertion of foreign bodies was autoerotism, misconceptions regarding masturbation, and underlying psychiatric illness. In addition to suitable method of surgical removal, counseling and psychiatric evaluation are necessary to prevent recurrences or for early detection of psychiatric problems.

  8. Chronic Nosema ceranae infection inflicts comprehensive and persistent immunosuppression and accelerated lipid loss in host Apis mellifera honey bees.

    Science.gov (United States)

    Li, Wenfeng; Chen, Yanping; Cook, Steven C

    2018-05-01

    Nosema ceranae is an intracellular microsporidian parasite of the Asian honey bee Apis cerana and the European honey bee Apis mellifera. Until relatively recently, A. mellifera honey bees were naïve to N. ceranae infection. Symptoms of nosemosis, or Nosema disease, in the infected hosts include immunosuppression, damage to gut epithelium, nutrient and energetic stress, precocious foraging and reduced longevity of infected bees. Links remain unclear between immunosuppression, the symptoms of nutrient and energetic stress, and precocious foraging behavior of hosts. To clarify physiological connections, we inoculated newly emerged A. mellifera adult workers with N. ceranae spores, and over 21 days post inoculation (21 days pi), gauged infection intensity and quantified expression of genes representing two innate immune pathways, Toll and Imd. Additionally, we measured each host's whole-body protein, lipids, carbohydrates and quantified respirometric and activity levels. Results show sustained suppression of genes of both humorally regulated immune response pathways after 6 days pi. At 7 days pi, elevated protein levels of infected bees may reflect synthesis of antimicrobial peptides from an initial immune response, but the lack of protein gain compared with uninfected bees at 14 days pi may represent low de novo protein synthesis. Carbohydrate data do not indicate that hosts experience severe metabolic stress related to this nutrient. At 14 days pi infected honey bees show high respirometric and activity levels, and corresponding lipid loss, suggesting lipids may be used as fuel for increased metabolic demands resulting from infection. Accelerated lipid loss during nurse honey bee behavioral development can have cascading effects on downstream physiology that may lead to precocious foraging, which is a major factor driving colony collapse. Published by Elsevier Ltd.

  9. Neuroprotective effects of Rhodiola rosea extracts against excitotoxicity and oxygen-glucose deprivation in hippocampal slice cultures

    DEFF Research Database (Denmark)

    Gramsbergen, Jan Bert; Sindberg, J.; Lundberg, L.

    .g. salidroside) and phenylpropanoid glycosides (e.g. rosavin). Many of these compounds are considered potent antioxidants, but the significance of the various substances for the beneficial effects of roseroot is still largely unknown. Here we tested the neuroprotective effects of crude methanolic extracts of R...... and quantified by propidium iodide uptake and immunohistochemical staining for MAP2 as a neuronal marker. Significant and dose-dependent protection against NMDA and OGD-induced CA1 pyramidal cell death was obtained by crude extracts using 250 µg/ml (33-50% protection) or 500 µg/ml (45-65% protection). A number...... of chemical fractions of methanolic Rhodiola extracts, as well as the purified constituents salidrosid and rosavin were tested, but - so far - none of the tested fractions or single constituents showed protection against NMDA or OGD. To study the mechanisms of action of R. rosea extracts, we are currently...

  10. Chronic Myeloid Leukemia Blood Inflicted Injury in Cord Derived Wharton's Jelly Mesenchymal Stem Cells

    International Nuclear Information System (INIS)

    Wajid, N.; Ali, M.; Javed, S.; Ali, F.; Anwar, S. S.

    2016-01-01

    Objective: To determine the effects of blood from CML patients on human umbilical cord derived Wharton's jelly mesenchymal stem cells (WJMSCs) for evaluation of their therapeutic potential. Study Design: An experimental study. Place and Duration of Study: Centre for Research in Molecular Medicine, University of Lahore, from September 2013 to December 2014. Methodology: Possible behavior of WJMSCs in CML patients was assessed by culturing these cells in their plasma. WJMSCs at passage 3 were cultured in plasma isolated from 9 CML patients as well as 9 normal subjects. Effects on cell viability, proliferation, LDH release, paracrine factors (p38 and p53) and oxidative stress were evaluated. Result: WJMSCs cultured in plasma of CML patients showed decreased viability, slow proliferation, high LDH release, high expression of p38 and p53 and a high oxidative stress compared to normal subjects. Conclusion: Stressed environment of CML patients' blood/plasma induced injury to WJMSCs as well as reduced their viability. Effectiveness of these cells for therapeutics of CML is, therefore, likely to be reduced. (author)

  11. [Forensic medical diagnostics of the extent of the thigh skin injury inflicted by motor vehicles of different weight].

    Science.gov (United States)

    Sashko, S Iu; Isakov, V D; Droblenkov, A V

    2011-01-01

    The authors report the results of an experimental study designed to characterize microstructural changes in the thigh skin caused by the impacts simulating the car wheel loads of different intensity. It was shown that histological methods can be used to discriminate between the intensities of traumatic loading on biological tissues.

  12. Interaction between neuropeptide Y (NPY) and brain-derived neurotrophic factor in NPY-mediated neuroprotection against excitotoxicity

    DEFF Research Database (Denmark)

    Xapelli, S; Bernardino, L; Ferreira, R

    2008-01-01

    The neuroprotective effect of neuropeptide Y (NPY) receptor activation was investigated in organotypic mouse hippocampal slice cultures exposed to the glutamate receptor agonist alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA). Exposure of 2-week-old slice cultures, derived from 7-...

  13. Autopsy audit of intentional burns inflicted by self or by others in north India-5 year snapshot.

    Science.gov (United States)

    Kumar, Sachil; Verma, Anoop K; Singh, Uma Shankar; Singh, Raghvendra

    2015-10-01

    The incidence of suicide and homicide is on the increase worldwide, including India. One million people die annually due to suicides and homicides alone. Thus this study had been undertaken to find out the material and social causes of burn and to assess the socio-demographic characteristics between suicide and homicide. This retrospective study was carried out on 1393 fatal burn cases (2008-2012) who were autopsied at the mortuary of King George's Medical University, Lucknow, India. Data retrieved include: age, sex, type of family, marital status, place of incidence, psychological status and burn size (TBSA). The results were presented in Mean ± SD and percentages and analyzed with SPSS 16.0. Out of the total 1369 cases of burns, 536 cases (38.5%) were homicidal deaths in comparison to 857 cases (61.5%) of suicidal deaths. Female predominance was seen in both suicidal and homicidal deaths with peak age 30-39 years in suicides in contrast to 40-49 years in homicides. At younger age ≤19 years, the victims of suicide is almost similar to the victims of homicide; but at extremes of ages below 10 years and above 60 years, homicides were relatively more common than suicides. Married victims were predominant in the homicidal group (66.6%). There is no quite difference at the place where burn occurs. Depression and anxiety disorders were the most frequent psychiatric co-morbidities associated with suicidal behaviours. Patients from suicidal group suffered significantly larger burns than from homicidal group. Hence, this study was planned with a purpose to know the magnitude and the socio-cultural factors of the problem of burns to more clearly understand the dynamics surrounding these deaths, so that a sound prevention programme could be suggested, planned and implemented for reducing the incidence of fatal burns. Copyright © 2015 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

  14. Accidental, Non-masturbatory, Non-intercourse Related, Self-Inflicted Penile Fracture: Case Report and Review of Literature

    Directory of Open Access Journals (Sweden)

    Christopher Bastianpillai

    2017-05-01

    Our case highlights the importance of maintaining a high index of suspicion to diagnose this rare condition, even in the absence of a typical mechanism of injury, in order to ensure that such an injury is not missed.

  15. Pre-differentiated GABAergic neural precursor transplants for alleviation of dysesthetic central pain following excitotoxic spinal cord injury

    Directory of Open Access Journals (Sweden)

    Jeung Woon eLee

    2012-05-01

    Full Text Available Intraspinal quisqualic acid (QUIS injury induce (i mechanical and thermal hyperalgesia, (ii progressive self-injurious overgrooming of the affected dermatome. The latter is thought to resemble painful dysesthesia observed in spinal cord injury (SCI patients. We have reported previously loss of endogenous GABA immunoreactive (IR cells in the superficial dorsal horn of QUIS rats 2 weeks post-injury. Further histological evaluation showed that GABA-, glycine-, and synaptic vesicular transporter VIAAT-IR persisted but were substantially decreased in the injured spinal cord. In this study, partially-differentiated GABA-IR embryonic neural precursor cells (NPCs were transplanted into the spinal cord of QUIS rats to reverse overgrooming by replenishing lost inhibitory circuitry. Rat E14 NPCs were predifferentiated in 0.1 ng/ml FGF-2 for 4 hrs prior to transplantation. In vitro immunocytochemistry of transplant cohort showed large population of GABA-IR NPCs that double labeled with nestin but few co-localized with NeuN, indicating partial maturation. Two weeks following QUIS lesion at T12-L1, and following the onset of overgrooming, NPCs were transplanted into the QUIS lesion sites; bovine adrenal fibroblast cells were used as control. Overgrooming was reduced in >55.5% of NPC grafted animals, with inverse relationship between the number of surviving GABA-IR cells and the size of overgrooming. Fibroblast-control animals showed a progressive worsening of overgrooming. At 3 weeks post-transplantation, numerous GABA-, nestin-, and GFAP-IR cells were present in the lesion site. Surviving grafted GABA-IR NPCs were NeuN+ and GFAP-. These results indicate that partially-differentiated NPCs survive and differentiate in vivo into neuronal cells following transplantation into an injured spinal cord. GABA-IR NPC transplants can restore lost dorsal horn inhibitory signaling and are useful in alleviating central pain following SCI.

  16. Reaching for the bottle of pesticide--a cry for help. Self-inflicted poisonings in Sri Lanka

    DEFF Research Database (Denmark)

    Konradsen, Flemming; Hoek, Wim van der; Peiris, Pushpalatha

    2005-01-01

    , as it is likely to reduce death from pesticides although unlikely to impact on the number of episodes. Support to families plagued by domestic violence and male alcohol misuse is essential to improve the quality of life for the most vulnerable and to reduce the number of self-harm episodes in the long-term....... in general, conveying misgiving, anger, sadness, hopelessness, frustration, or simply a way to manipulate a situation to one's own advantage. The effects of alcohol misuse are especially important in understanding self-harm at the community level in terms of the impact they have on the domestic environment....... Also, issues around "love affairs," arranged marriages and domestic physical, sexual or psychological abuse in the domestic environment are referred to by many self-harmers or their relatives as a reason for ingesting poison. Clearly, easy access to lethal pesticides by impulsive individuals often...

  17. The Evaluation of the Effectiveness of Counterterrorism Policies on the PKK-inflicted Violence during the Democratization Process of Turkey

    OpenAIRE

    Irfan Ciftci; Sedat Kula

    2015-01-01

    This study tries to explore the relationship between soft-line governmental policy interventions of Turkey and the responses of the PKK (The Kurdistan Workers’ Party) by using time series data from 1995 to 2010. The negative binomial specifications for two models, the number of incidents and the number casualties are used. The aggregated impact of soft-line policies on the level of violence is found to be positive and significant. In one hand, Turkey’s EU accession process had a decreasing im...

  18. Identification of Bax-Interacting Proteins in Oligodendrocyte Progenitors during Glutamate Excitotoxicity and Perinatal Hypoxia–Ischemia

    Directory of Open Access Journals (Sweden)

    Sopio Simonishvili

    2013-11-01

    Full Text Available OPC (oligodendrocyte progenitor cell death contributes significantly to the pathology and functional deficits following hypoxic-ischemic injury in the immature brain and to deficits resulting from demyelinating diseases, trauma and degenerative disorders in the adult CNS. Glutamate toxicity is a major cause of oligodendroglial death in diverse CNS disorders, and previous studies have demonstrated that AMPA/kainate receptors require the pro-apoptotic protein Bax in OPCs undergoing apoptosis. The goal of the present study was to define the pro-apoptotic and anti-apoptotic effectors that regulate Bax in healthy OPCs and after exposure to excess glutamate in vitro and following H–I (hypoxia–ischemia in the immature rat brain. We show that Bax associates with a truncated form of Bid, a BH3-only domain protein, subsequent to glutamate treatment. Furthermore, glutamate exposure reduces Bax association with the anti-apoptotic Bcl family member, Bcl-xL. Cell fractionation studies demonstrated that both Bax and Bid translocate from the cytoplasm to mitochondria during the early stages of cell death consistent with a role for Bid as an activator, whereas Bcl-xL, which normally complexes with both Bax and Bid, disassociates from these complexes when OPCs are exposed to excess glutamate. Bax remained unactivated in the presence of insulin-like growth factor-1, and the Bcl-xL complexes were protected. Our data similarly demonstrate loss of Bcl-xL–Bax association in white matter following H–I and implicate active Bad in Bax-mediated OPC death. To identify other Bax-binding partners, we used proteomics and identified cofilin as a Bax-associated protein in OPCs. Cofilin and Bax associated in healthy OPCs, whereas the Bax–cofilin association was disrupted during glutamate-induced OPC apoptosis.

  19. The Fire Challenge: A Case Report and Analysis of Self-Inflicted Flame Injury Posted on Social Media.

    Science.gov (United States)

    Avery, Andrew H; Rae, Lisa; Summitt, J Blair; Kahn, Steven Alexander

    2016-01-01

    With the advent of social media platforms such as Facebook and YouTube, online dissemination of exhibitionist videos has gained popularity. One recent disturbing trend is the "fire challenge" wherein a participant douses his or herself in a household accelerant such as isopropyl alcohol or acetone, sets him or herself ablaze, and attempts to extinguish the flames before serious burns are incurred. As expected, participants in the "fire challenge" often accidentally suffer serious burns. A 17-year-old white male was recently treated at our burn center after participating in the "fire challenge." He suffered 15% TBSA full and partial thickness burns requiring split thickness skin grafting to his abdomen. He reported lighting himself on fire because he had seen this stunt performed on the internet. A search for "fire challenge" and similar terms was conducted on YouTube (www.youtube.com). Gender and ethnicity of each participant were documented. Burn size, burn depth, and age of video participant were estimated by two attending burn surgeons evaluating YouTube videos. Results were reported with descriptive statistics. The search yielded thousands of hits, mostly home videos, compilations of stunts, and commentaries. After omitting duplicate and irrelevant videos, 50 videos were selected for the study. Of these, 13 videos included postburn footage demonstrating burn wounds of various location, size, and severity. Of these burns, the median TBSA burned was 4 ± 2.7% with a maximum size of 10%. Superficial and partial thickness burns were sustained on the torso (10/13, 77%), face (4/13, 31%), and extremities (2/13, 15%). Full thickness burns were seen in 2/13 videos. Some burn wounds were obscured by dressings. Of the 50 videos reviewed, 45/50 participants (90%) were male and 32/50 (64%) were African American with 29/50 participants (58%) estimated to be under age 20. The "fire challenge" is a popular social media phenomenon, but it can result in severe injury as seen with the patient at our institution. The lure of a challenge and potential for a shocking video to "go viral" might entice people to mimic this risky behavior. This study shows a disturbing trend, but undoubtedly only reflects a small portion of actual participants. A disproportionate number of videos featured young African American males, making this a target population for education and prevention efforts. Our patient's TBSA exceeded the maximum found on YouTube, suggesting that less severe burns may be posted online while larger burns are not, diminishing perceived risk and encouraging this behavior.

  20. Evidence for proteolytic cleavage of brevican by the ADAMTSs in the dentate gyrus after excitotoxic lesion of the mouse entorhinal cortex

    Directory of Open Access Journals (Sweden)

    Gottschall Paul E

    2005-08-01

    Full Text Available Abstract Background Brevican is a member of the lectican family of aggregating extracellular matrix (ECM proteoglycans that bear chondroitin sulfate (CS chains. It is highly expressed in the central nervous system (CNS and is thought to stabilize synapses and inhibit neural plasticity and as such, neuritic or synaptic remodeling would be less likely to occur in regions with intact and abundant, lectican-containing, ECM complexes. Neural plasticity may occur more readily when these ECM complexes are broken down by endogenous proteases, the ADAMTSs (adisintegrin and metalloproteinase with thrombospondin motifs, that selectively cleave the lecticans. The purpose of these experiments was to determine whether the production of brevican or the ADAMTS-cleaved fragments of brevican were altered after deafferentation and reinnervation of the dentate gyrus via entorhinal cortex lesion (ECL. Results In the C57Bl6J mouse, synaptic density in the molecular layer of the dentate gyrus, as measured by synaptophysin levels in ELISA, was significantly attenuated 2 days (nearly 50% of contralateral and 7 days after lesion and returned to levels not different from the contralateral region at 30 days. Immunoreactive brevican in immunoblot was elevated 2 days after lesion, whereas there was a significant increase in the proteolytic product at 7, but not 30 days post-lesion. ADAMTS activity, estimated using the ratio of the specific ADAMTS-derived brevican fragment and intact brevican levels was increased at 7 days, but was not different from the contralateral side at 2 or 30 days after deafferentation. Conclusion These findings indicate that ADAMTS activity in the dentate outer molecular layer (OML is elevated during the initial synaptic reinnervation period (7 days after lesion. Therefore, proteolytic processing of brevican appears to be a significant extracellular event in the remodeling of the dentate after EC lesion, and may modulate the process of sprouting and/or synaptogenesis.

  1. Effects of selective excitotoxic lesions of the nucleus accumbens core, anterior cingulate cortex, and central nucleus of the amygdala on autoshaping performance in rats.

    Science.gov (United States)

    Cardinal, Rudolf N; Parkinson, John A; Lachenal, Guillaume; Halkerston, Katherine M; Rudarakanchana, Nung; Hall, Jeremy; Morrison, Caroline H; Howes, Simon R; Robbins, Trevor W; Everitt, Barry J

    2002-08-01

    The nucleus accumbens core (AcbC), anterior cingulate cortex (ACC), and central nucleus of the amygdala (CeA) are required for normal acquisition of tasks based on stimulus-reward associations. However, it is not known whether they are involved purely in the learning process or are required for behavioral expression of a learned response. Rats were trained preoperatively on a Pavlovian autoshaping task in which pairing a visual conditioned stimulus (CS+) with food causes subjects to approach the CS+ while not approaching an unpaired stimulus (CS-). Subjects then received lesions of the AcbC, ACC, or CeA before being retested. AcbC lesions severely impaired performance; lesioned subjects approached the CS+ significantly less often than controls, failing to discriminate between the CS+ and CS-. ACC lesions also impaired performance but did not abolish discrimination entirely. CeA lesions had no effect on performance. Thus, the CeA is required for learning, but not expression, of a conditioned approach response, implying that it makes a specific contribution to the learning of stimulus-reward associations.

  2. Photodynamic Treatment of Cultured Human Malignant Melanoma cells and Assessment of Resultant Cell Death and Inflicted Bio molecular Damage As Determined by Synchrotron I.R. Radiations

    International Nuclear Information System (INIS)

    Mamoon, A.; Ruppel, M.; Miller, L.M.; Smith, S.; Tsang, T.; Miller, L.M.

    2008-01-01

    Malignant melanoma is a very serious skin cancer that if not discovered early and treated by surgery can become fatal. Photodynamic treatment involves the use of a photosensitive dye that is not toxic by itself and is taken up by all cells normal and tumor cells. However it is released from normal cells in a short time while it is kept inside tumor cells for a longer time. A laser light of wave length that is maximally absorbed by the used dye is then used to illuminate tumor cells, still having the dye, and a reaction takes place resulting in the liberation of s inglet oxygen , a very active form of oxygen that damages important biomolecules and results eventually in cell death. The photosensitive dye I ndocyanine green a nd a Ti - Sapphire laser (780 nm wave length ) and power density of 55 m Watt/ cm 2 were used. The percentage of cell death increased slowly with the strength of the PDT until it reached 75% death of the exposed cells at a net dye concentration of 150 u M and laser exposure dose of 60 minute duration.Synchrotron infrared imaging was carried out on control and experimental cultures at the national synchrotron light source (BNL) using FTIR spectro microscopy to reveal the I.R. absorption characteristics of protein, lipids and nucleic acids biomolecules. It was found that increasing the strength of the PDT had an increasingly damaging effect on the concentration of cellular biomolecules, the largest effect being in the protein, lipids and nucleic acid components of the cell. More experiments are planned involving changes in the strengths of the PDT treatments for eventually reaching 100% melanoma cell death

  3. Intractable Postoperative Wounds Caused by Self-Inflicted Trauma in a Patient with Cutaneous Munchausen Syndrome Presenting as a Pyoderma Gangrenosum-Like Lesion

    OpenAIRE

    Inui, Keiko; Hanafusa, Takaaki; Namiki, Takeshi; Ueno, Makiko; Igawa, Ken; Yokozeki, Hiroo

    2016-01-01

    A 50-year-old Japanese woman consulted the emergency department of our hospital for bleeding due to an intractable postoperative wound on the lower abdomen; the postoperative wound was owing to a laparoscopic cholecystectomy performed 1 year previously for acute cholecystitis. She presented with a painful ulcer on her right lower abdomen. She also presented with multiple scars, skin grafts on the extremities, and a missing left lower leg, the causes for all of which were unexplained. The resu...

  4. The use of organotypic hippocampal slice cultures to evaluate protection by non-competitive NMDA receptor antagonists against excitotoxicity

    DEFF Research Database (Denmark)

    Ring, Avi; Tanso, Rita; Noraberg, Jens

    2010-01-01

    There is a wide interest in testing neuroprotectants which inhibit the neurodegeneration that results from excessive activation of brain NMDA receptors.  As an alternative to in vivo testing in animal models we demonstrate here the use of a complex in vitro model to compare the efficacy and toxic...

  5. In vivo microdialysis studies on the effects of decortication and excitotoxic lesions on kainic acid-induced calcium fluxes, and endogenous amino acid release, in the rat striatum

    Energy Technology Data Exchange (ETDEWEB)

    Butcher, S.P.; Lazarewicz, J.W.; Hamberger, A.

    1987-11-01

    The in vivo effects of kainate (1 mM) on fluxes of /sup 45/Ca2+, and endogenous amino acids, were examined in the rat striatum using the brain microdialysis technique. Kainate evoked a rapid decrease in dialysate /sup 45/Ca2+, and an increase in the concentration of amino acids in dialysates in Ca2+-free dialysates. Taurine was elevated six- to 10-fold, glutamate two- to threefold, and aspartate 1.5- to twofold. There was also a delayed increase in phosphoethanolamine, whereas nonneuroactive amino acids were increased only slightly. The kainic acid-evoked reduction in dialysate /sup 45/Ca2+ activity was attenuated in striata lesioned previously with kainate, suggesting the involvement of intrinsic striatal neurons in this response. The increase in taurine concentration induced by kainate was slightly smaller under these conditions. Decortication did not affect the kainate-evoked alterations in either dialysate /sup 45/Ca2+ or amino acids. These data suggest that kainate does not release acidic amino acids from their transmitter pools located in corticostriatal terminals.

  6. The developmental expression of fluorescent proteins in organotypic hippocampal slice cultures from transgenic mice and its use in the determination of excitotoxic neurodegeneration

    DEFF Research Database (Denmark)

    Noraberg, Jens; Jensen, Carsten V; Bonde, Christian

    2007-01-01

    Transgenic mice, expressing fluorescent proteins in neurons and glia, provide new opportunities for real-time microscopic monitoring of degenerative and regenerative structural changes. We have previously validated and compared a number of quantifiable markers for neuronal damage and cell death...... changes, as well as the opportunity to monitor reversible changes or long-term effects in the event of minor damage. As a first step, we present: a) the developmental expression in organotypic hippocampal brain slice cultures of transgenic fluorescent proteins, useful for the visualisation of neuronal...... transgenic mouse strains which express fluorescent proteins in their neurons and/or astroglial cells. From the time of explantation, and subsequently for up to nine weeks in culture, the transgenic neuronal fluorescence displayed the expected characteristics of a developmental, in vivo-like increase...

  7. The loss of imprinted DNA methylation in mouse blastocysts is inflicted to a similar extent by in vitro follicle culture and ovulation induction.

    Science.gov (United States)

    Saenz-de-Juano, M D; Billooye, K; Smitz, J; Anckaert, E

    2016-06-01

    Does in vitro follicle culture (IFC) have an effect on maintenance of imprinted DNA methylation in preimplantation mouse embryos? We report similar alterations in the methylation pattern of H19 imprinted maternally expressed transcript (H19), small nuclear ribonucleoprotein polypeptide N (Snrpn) and mesoderm specific transcript (Mest) imprinted genes in mouse blastocysts obtained after ovulation induction and IFC. Furthermore, we observed no differences in the gene expression of maternal effect proteins related with imprinting maintenance between superovulated in vivo grown or IFC oocytes. Assisted reproductive technology is associated with adverse post-natal outcomes such as increased risk of premature birth, altered birthweight, congenital anomalies and genomic imprinting syndromes in human and in animal models. Previous studies have shown that ovulation induction allowed normal imprinting establishment in mouse oocytes, but interfered with imprinting maintenance during preimplantation . Normal imprinting establishment was also observed in mouse oocytes derived from a standardized IFC from the early pre-antral follicle stage. The methylation profiles of differentially methylated regions (DMRs) of three key imprinted genes (H19, Snrpn and Mest) were compared at hatched blastocyst stage between embryos obtained from IFC or superovulated oocytes, each subjected to IVF and preimplantation in vitro culture (IVC); in non-manipulated in vivo produced late blastocyst (control) and in in vivo produced 2-cell embryos that were in vitro cultured until the hatched blastocyst stage (to assess the effect of IVC). Two different mice strains (Mus musculus C57BL/6J X CBA/Ca and Mus musculus B6 (CAST7)) were used to discriminate between maternal and paternal alleles of imprinted genes. Additionally, a limiting-dilution bisulfite-sequencing technique was carried out on individual embryos in order to avoid amplification bias. To assess whether IFC and ovulation induction differentially affect the mRNA expression of imprinting maintenance genes in the oocyte, a comparison of DNA methyltransferase 1 (Dnmt1o), methyl-CpG binding domain protein 3 (MBD3) and developmental pluripotency-associated 3 (Dppa3) was performed by qPCR between in vivo and in vitro grown oocytes at the germinal vesicle and metaphase II (MII) stage. Results showed a loss of global imprinted DNA methylation in all in vitro manipulated embryos, due to an increase in the amount of abnormal alleles (culture induces no additional epigenetic alterations compared with conventional ovulation induction, at least for imprinted genes at the hatched blastocyst stage. The mouse IFC system can be used to test the sensitivity of the oocyte during its growth and maturation to several nutritional, metabolic and hormonal conditions possibly linked to epigenetic alterations. N/A. This study received funding by Strategic Research Programs-Groeiers (OZR/2014/97), IWT/TBM/110680 and by UZ Brussel Fonds Willy Gepts (WFWG 2013). There is no conflict of interest. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  8. Water extract from the leaves of Withania somnifera protect RA differentiated C6 and IMR-32 cells against glutamate-induced excitotoxicity.

    Directory of Open Access Journals (Sweden)

    Hardeep Kataria

    Full Text Available Glutamate neurotoxicity has been implicated in stroke, head trauma, multiple sclerosis and neurodegenerative disorders. Search for herbal remedies that may possibly act as therapeutic agents is an active area of research to combat these diseases. The present study was designed to investigate the neuroprotective role of Withania somnifera (Ashwagandha, also known as Indian ginseng, against glutamate induced toxicity in the retinoic acid differentiated rat glioma (C6 and human neuroblastoma (IMR-32 cells. The neuroprotective activity of the Ashwagandha leaves derived water extract (ASH-WEX was evaluated. Cell viability and the expression of glial and neuronal cell differentiation markers was examined in glutamate challenged differentiated cells with and without the presence of ASH-WEX. We demonstrate that RA-differentiated C6 and IMR-32 cells, when exposed to glutamate, undergo loss of neural network and cell death that was accompanied by increase in the stress protein HSP70. ASH-WEX pre-treatment inhibited glutamate-induced cell death and was able to revert glutamate-induced changes in HSP70 to a large extent. Furthermore, the analysis on the neuronal plasticity marker NCAM (Neural cell adhesion molecule and its polysialylated form, PSA-NCAM revealed that ASH-WEX has therapeutic potential for prevention of neurodegeneration associated with glutamate-induced excitotoxicty.

  9. [Violence in families and its prevention. Also a plea for abolishing the parental right to inflict physical punishment. A report of the "Violence Commission" of the federal government].

    Science.gov (United States)

    Remschmidt, H; Schmidt, M H; Strunk, P

    1990-01-01

    Violence in families is rather frequent. Different forms of violent acts can be distinguished: violence between partners, violence between parents and children, violence among siblings, and violence against elder family members. This report gives an overview--with the emphasis on violence in families--of the work of the "Violence Commission" of the Federal Government. This commission worked out proposals for intervention in the case of intrafamiliar violence as well as for prevention. Two proposals of the commission are explained in detail: (1) Rejection of violence and prohibition of corporal punishment in education and (2) punishability of conjugal violation.

  10. [{sup 18}F]DPA-714 PET imaging of translocator protein TSPO (18 kDa) in the normal and excitotoxically-lesioned nonhuman primate brain

    Energy Technology Data Exchange (ETDEWEB)

    Lavisse, S.; Inoue, K.; Jan, C.; Petit, F.; Dauguet, J.; Guillermier, M.; Rbah-Vidal, L.; Van Camp, N.; Aron-Badin, R.; Hantraye, P. [CEA, I2BM, MIRCen, Fontenay-aux-Roses (France); CEA, CNRS, URA2210, Fontenay-aux-Roses (France); Peyronneau, M.A.; Goutal, S.; Dolle, F. [CEA, I2BM, Service Hospitalier Frederic Joliot, Orsay (France); Remy, P. [CEA, I2BM, MIRCen, Fontenay-aux-Roses (France); CEA, CNRS, URA2210, Fontenay-aux-Roses (France); Service de Neurologie, CHU Henri Mondor, Creteil (France)

    2014-12-09

    We aimed to characterize pharmacologically the TSPO- radioligand [{sup 18}F]DPA-714 in the brain of healthy cynomolgus monkeys and evaluate the cellular origin of its binding in a model of neurodegeneration induced by intrastriatal injection of quinolinic acid (QA). [{sup 18}F]DPA-714 PET images were acquired before and at 2, 7, 14, 21, 49, 70, 91 days after putaminal lesioning. Blocking and displacement studies were carried out (PK11195). Different modelling approaches estimated rate constants and V{sub T} (total distribution volume) which was used to measure longitudinal changes in the lesioned putamen. Sections for immunohistochemical labelling were prepared at the same time-points to evaluate correlations between in vivo [{sup 18}F]DPA-714 binding and microglial/astrocytic activation. [{sup 18}F]DPA-714 showed a widespread distribution with a higher signal in the thalamus and occipital cortex and lower binding in the cerebellum. TSPO was expressed throughout the whole brain and about 73 % of [{sup 18}F]DPA-714 binding was specific for TSPO in vivo. The one-tissue compartment model (1-TCM) provided good and reproducible estimates of V{sub T} and rate constants, and V{sub T} values from the 1-TCM and the Logan approach were highly correlated (r {sup 2} = 0.85). QA lesioning induced an increase in V{sub T}, which was +17 %, +54 %, +157 % and +39 % higher than baseline on days 7, 14, 21 and 91 after QA injection, respectively. Immunohistochemistry revealed an early microglial and a delayed astrocytic activation after QA injection. [{sup 18}F]DPA-714 binding matched TSPO immunopositive areas and showed a stronger colocalization with CD68 microglia than with GFAP-activated astrocytes. [{sup 18}F]DPA-714 binds to TSPO with high specificity in the primate brain under normal conditions and in the QA model. This tracer provides a sensitive tool for assessing neuroinflammation in the human brain. (orig.)

  11. Cell ATP level of Saccharomyces cerevisiae sensitively responds to culture growth and drug-inflicted variations in membrane integrity and PDR pump activity

    Czech Academy of Sciences Publication Activity Database

    Krasowska, A.; Lukaszewicz, M.; Bartosiewicz, D.; Sigler, Karel

    2010-01-01

    Roč. 395, č. 1 (2010), s. 51-55 ISSN 0006-291X R&D Projects: GA MŠk 1M0570 Institutional research plan: CEZ:AV0Z50200510 Keywords : S. cerevisiae * ABC transporters * ATP level Subject RIV: EE - Microbiology, Virology Impact factor: 2.595, year: 2010

  12. The metabotropic glutamate receptor agonist 1S,3R-ACPD stimulates and modulates NMDA receptor mediated excitotoxicity in organotypic hippocampal slice cultures

    DEFF Research Database (Denmark)

    Blaabjerg, M; Kristensen, Bjarne Winther; Bonde, C

    2001-01-01

    the PI uptake in both CA1 and CA3, compared to cultures exposed to 10 microM NMDA only. Adding the 300 microM ACPD as pretreatment for 30 min followed by a 30 min wash in normal medium before the ACPD/NMDA co-exposure, eliminated the potentiation of NMDA toxicity. The potentiation was also blocked...

  13. Health Care Experiences Prior to Suicide and Self-inflicted Injury, Active Component, U.S. Armed Forces, 2001-2010

    Science.gov (United States)

    2012-02-01

    health 23 1.2 896 4.5 164 4.8 General surgery 23 1.2 247 1.2 98 2.8 Internal medicine 22 1.1 569 2.9 110 3.2 Audiology 22 1.1 290 1.5 50 1.5...90 days 91-180 days 181-360 days 361-720 days combine diagnoses thought to be predic- tive of suicide (see article on page 7) and the results of

  14. Novel Application of Stem Cell-Derived Neurons to Evaluate the Time-and Dose-Dependent Progression of Excitotoxic Injury

    Science.gov (United States)

    2013-05-14

    3. DATES COVERED (From - To) 4. TITLE AND SUBTITLE Novel Application of Stem Cell -Derived Neurons to Evaluate the Time- and Dose-Dependent 5a...01.10.RC.021). 14. ABSTRACT See reprint. 15. SUBJECT TERMS Mouse stem cell -derived neurons, NMDA receptor, AMPA receptor, Neurotoxicity, Apoptosis...area code) 410-436-8044 Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std. Z39.18 Novel Application of Stem Cell -Derived Neurons to Evaluate the

  15. In vitro and in vivo effects of a novel dimeric inhibitor of PSD-95 on excitotoxicity and functional recovery after experimental traumatic brain injury

    DEFF Research Database (Denmark)

    Sommer, Jens Bak; Bach, Anders; Rytter, Hana Malá

    2017-01-01

    weeks post-trauma, spatial learning and memory were assessed in a water maze, and at 3 months, brains were removed for estimation of lesion volumes. Overall, neither treatment with UCCB01-147 nor MK-801 resulted in significant improvements of cognition and histopathology after CCI. Although MK-801......PSD-95 inhibitors have been shown to be neuroprotective in stroke, but have only to a very limited extent been evaluated in the treatment of traumatic brain injury (TBI) that has pathophysiological mechanisms in common with stroke. The aims of the current study were to assess the effects of a novel...

  16. Excitotoxic median raphe lesions aggravate working memory storage performance deficits caused by scopolamine infusion into the dentate gyrus of the hippocampus in the inhibitory avoidance task in rats

    Directory of Open Access Journals (Sweden)

    Babar E.

    2002-01-01

    Full Text Available The interactions between the median raphe nucleus (MRN serotonergic system and the septohippocampal muscarinic cholinergic system in the modulation of immediate working memory storage performance were investigated. Rats with sham or ibotenic acid lesions of the MRN were bilaterally implanted with cannulae in the dentate gyrus of the hippocampus and tested in a light/dark step-through inhibitory avoidance task in which response latency to enter the dark compartment immediately after the shock served as a measure of immediate working memory storage. MRN lesion per se did not alter response latency. Post-training intrahippocampal scopolamine infusion (2 and 4 µg/side produced a more marked reduction in response latencies in the lesioned animals compared to the sham-lesioned rats. Results suggest that the immediate working memory storage performance is modulated by synergistic interactions between serotonergic projections of the MRN and the muscarinic cholinergic system of the hippocampus.

  17. Selective vulnerability in brain hypoxia

    DEFF Research Database (Denmark)

    Cervos-Navarro, J.; Diemer, Nils Henrik

    1991-01-01

    Neuropathology, selective vulnerability, brain hypoxia, vascular factors, excitotoxicity, ion homeostasis......Neuropathology, selective vulnerability, brain hypoxia, vascular factors, excitotoxicity, ion homeostasis...

  18. Radiation-induced apoptosis in developing rats and kainic acid-induced excitotoxicity in adult rats are associated with distinctive morphological and biochemical c-Jun/AP-1 (N) expression

    Energy Technology Data Exchange (ETDEWEB)

    Pozas, E. [Unitat de Neuropatologia, Servei d' Anatomia Patologica, Hospital Princeps d' Espanya, Universitat de Barcelona, 08907 Hospitalet de Llobregat (Spain); Planas, A.M. [Departament de Farmacologia i Toxicologia, IIBB, CSIC Barcelona (Spain); Ferrer, I. [Unitat de Neuropatologia, Servei d' Anatomia Patologica, Hospital Princeps d' Espanya, Universitat de Barcelona, 08907 Hospitalet de Llobregat (Spain)

    1997-07-14

    Ionizing radiation produces apoptosis in the developing rat brain. Strong c-Jun immunoreactivity, as revealed with the antibody c-Jun/AP-1 (N) which is raised against the amino acids 91-105 mapping with the amino terminal domain of mouse c-Jun p39, is simultaneously observed in the nucleus and cytoplasm of apoptotic cells. Western blotting of total brain homogenates, using the same antibody, shows a p39 band in control rats which is accompanied by a strong, phosphorylated p62 double-band in irradiated animals. In addition, increased c-Jun N-terminal kinase 1 expression, as found on western blots, is found in irradiated rats when compared with controls. Intraperitoneal injection of kainic acid at convulsant doses to the adult rat produces cell death with morphological features of necrosis, together with the appearance of cells with fine granular chromatin degeneration and small numbers of apoptotic-like cells, in the entorhinal and piriform cortices, basal amygdala, certain thalamic nuclei, and CA1 region of the hippocampus. c-Jun expression in kainic acid-treated rats, as revealed with the c-Jun/AP-1 (N) antibody, is found in the nuclei of a minority of cells in the same areas. The vast majority of c-Jun-immunoreactive cells have normal nuclear morphology, whereas necrotic cells are negative and only a few cells with fine granular chromatin condensation and apoptotic cells following kainic acid injection are stained with c-Jun antibodies. Western blotting, using the same antibody, shows a p39 band in control rats, which is accompanied by a band at about p26 from 6 h onwards following kainic acid injection. Decreased c-Jun N-terminal kinase 1 expression, as revealed on western blots, is observed in kainic acid-treated rats.These results show that the antibody c-Jun/AP-1 (N) recognizes three different forms of c-Jun-related immunoreactivity in normal and pathological states, which are associated with the different outcome of cells. These results stress the necessity of examining in detail the composition of c-Jun-immunoreactive bands and the metabolic state of c-Jun(s) in different paradigms of cell death and survival. (Copyright (c) 1997 Elsevier Science B.V., Amsterdam. All rights reserved.)

  19. Live Imaging of Kv7.2/7.3 Cell Surface Dynamics at the Axon Initial Segment: High Steady-State Stability and Calpain-Dependent Excitotoxic Downregulation Revealed

    DEFF Research Database (Denmark)

    Benned-Jensen, Tau; Christensen, Rasmus Kordt; Denti, Federico

    2016-01-01

    The voltage-gated K(+) channels Kv7.2 and Kv7.3 are located at the axon initial segment (AIS) and exert strong control over action potential generation. Therefore, changes in their localization or cell surface numbers are likely to influence neuronal signaling. However, nothing is known about......7.3. This seven transmembrane chimera, named super ecliptic phluorin (SEP)-TAC-7.3, functions and traffics as a wild-type (WT) channel. We expressed SEP-TAC-7.3 in dissociated rat hippocampal neurons to examine the lateral mobility, surface numbers, and localization of AIS Kv7.2/7.3 heteromers using...

  20. Cation binding at the node of Ranvier: I. Localization of binding sites during development.

    Science.gov (United States)

    Zagoren, J C; Raine, C S; Suzuki, K

    1982-06-17

    Cations are known to bind to the node of Ranvier and the paranodal regions of myelinated fibers. The integrity of these specialized structures is essential for normal conduction. Sites of cation binding can be microscopically identified by the electrondense histochemical reaction product formed by the precipitate of copper sulfate/potassium ferrocyanide. This technique was used to study the distribution of cation binding during normal development of myelinating fibers. Sciatic nerves of C57B1 mice, at 1, 3, 5, 6, 7, 8, 9, 13, 16, 18, 24 and 30 days of age, were prepared for electron microscopy following fixation in phosphate-buffered 2.5% glutaraldehyde and 1% osmic acid, microdissection and incubation in phosphate-buffered 0.1 M cupric sulfate followed by 0.1 M potassium ferrocyanide. Localization of reaction product was studied by light and electron microscopy. By light microscopy, no reaction product was observed prior to 9 days of age. At 13 days, a few nodes and paranodes exhibited reaction product. This increased in frequency and intensity up to 30 days when almost all nodes or paranodes exhibited reaction product. Ultrastructurally, diffuse reaction product was first observed at 3 days of age in the axoplasm of the node, in the paranodal extracellular space of the terminal loops, in the Schwann cell proper and in the terminal loops of Schwann cell cytoplasm. When myelinated axons fulfilled the criteria for mature nodes, reaction product was no longer observed in the Schwann cell cytoplasm, while the intensity of reaction product in the nodal axoplasm and paranodal extracellular space of the terminal loops increased. Reaction product in the latter site appeared to be interrupted by the transverse bands. These results suggest that cation binding accompanies nodal maturity and that the Schwann cell may play a role in production or storage of the cation binding substance during myelinogenesis and development.

  1. Neuroprotection of the rat’s retinal ganglion cells against glutamate-induced toxicity

    Directory of Open Access Journals (Sweden)

    Kariman M.A El-Gohari

    2016-01-01

    Conclusion Taurine protects the retina against glutamate excitotoxicity and could have clinical implications in protecting the ganglion cells from several ophthalmic diseases such as glaucoma and diabetic retinopathy.

  2. Monitoring and Counteracting Functional Deterioration in Parkinson's Disease: A Multilevel Integrative Approach in a Primate Model System

    National Research Council Canada - National Science Library

    Philippens, Ingrid H

    2006-01-01

    ...). Presumably more than one factor is responsible. There is evidence suggesting that metabolic compromise, excitotoxicity and oxidative stress are involved in the neurodegenerative process causing PD...

  3. Monitoring and Counteracting Functional Deterioration in Parkinson's Disease: A Multilevel Integrative Approach in a Primate Model System

    National Research Council Canada - National Science Library

    Philippens, Ingrid H; Verhave, Peternella S; Jongsma, Marjan J; Blezer, Erwin; Mol, Marijke A

    2007-01-01

    ...). Presumably more than one factor is responsible. There is evidence suggesting that metabolic compromise excitotoxicity and oxidative stress are involved in the neurodegenerative process causing PD...

  4. Acute Administration of Methionine Affects Performance of Swiss ...

    African Journals Online (AJOL)

    olayemitoyin

    The effect of methionine on learning and memory in mice was investigated using Morris ... neurological disorders by excitotoxicity and ... Central cholinergic system plays a major role in ... acetylcholinesterase leads to increased levels of brain.

  5. Journal of Biosciences | Indian Academy of Sciences

    Indian Academy of Sciences (India)

    Increasing evidence supports the role of excitotoxicity in neuronal cell injury. Thus ... The results showed an impairment of the hippocampus region of brain after KA ... The diet was prepared in terms of total antioxidant activity of plant extracts.

  6. Evaluation of Early and Prolonged Effects of Acute Neurotoxicity and Neuroprotection Using Novel Functional Imaging Techniques

    National Research Council Canada - National Science Library

    Brownell, Anna-Liisa

    2002-01-01

    ... glutamate receptor agonist. We have conducted studies using a superThigh resolution positron tomograph to explore acute and long-term excitotoxicity mediated mechanisms in rats exposed to 3-nitroproptiomc acid (3-NP...

  7. Comparison of Novel and Known Neuroprotectants for Treating Exposure to Different Types of Toxins

    National Research Council Canada - National Science Library

    Bahr, Ben

    2004-01-01

    Studies using cultured brain slices have found that compensatory signals are activated in response to different types of excitotoxicity/seizures related to environmental toxin or military threat agent exposure...

  8. Biokemistri

    African Journals Online (AJOL)

    Chibuike

    2011-12-31

    Dec 31, 2011 ... domain housing the nicotinamide adenine dinucleotide (NAD)- binding site and the ..... compared to wild-type animals, in experimental models of excitotoxicity .... Factor during transient focal cerebral ischemia in rat. Brain Res.

  9. Neural Responses to Injury: Prevention, Protection, and Repair. Neurochemical Protection of the Brain, Neural Plasticity and Repair

    National Research Council Canada - National Science Library

    Bazan, Nicolas

    1998-01-01

    ... neurotransmission, eventually resulting in prolonged or repeated seizures (status epilepticus). The massive amounts of excitatory amino acids released during these episodes can stimulate further neuronal loss (excitotoxic damage), the formation of more aberrant synaptic circuits, and further seizures.

  10. Swamy et al., Afr J Tradit Complement Altern Med. (2014) 11(5):48 ...

    African Journals Online (AJOL)

    cadewumi

    in rats supplemented with propolis prior to excitotoxic injury with kainic acid (KA). ... and necrotic cell death and induction of heat sensitive proteins in hippocampus and cortical regions of rodent brain (Akbar et al., ..... motor neurons in vitro.

  11. 29 CFR 500.51 - Refusal to issue or to renew, or suspension or revocation of certificate.

    Science.gov (United States)

    2010-07-01

    ..., grand larceny, burglary, arson, violation of narcotics laws, murder, rape, assault with intent to kill, assault which inflicts grievous bodily injury, prostitution, peonage, or smuggling or harboring...

  12. Inhibition of GABA transporters fails to afford significant protection following focal cerebral ischemia

    DEFF Research Database (Denmark)

    Lie, Maria Ek; Gowing, Emma K; Clausen, Rasmus P

    2017-01-01

    Brain ischemia triggers excitotoxicity and cell death, yet no neuroprotective drugs have made it to the clinic. While enhancing GABAergic signaling to counterbalance excitotoxicity has shown promise in animal models, clinical studies have failed. Blockade of GABA transporters (GATs) offers...... show that tiagabine can promote protection, our findings indicate that caution should be had when using GAT1 and GAT3 inhibitors for conditions of brain ischemia....

  13. Prevention of Noise Damage to Cochlear Synapses

    Science.gov (United States)

    2017-10-01

    Assessment of synapse regeneration : Twelve week old CBA/CaJ mice are exposed to a moderate noise that destroys synapses on inner hair cells (IHCs) but spares...result of excitotoxic trauma to cochlear synapses due to glutamate released from the hair cells . Excitotoxic trauma damages the postsynaptic cell by...components ............................................. 12 d) Quantitative analysis of effects of neurotrophic factors on synapse regeneration in vitro

  14. Proceedings of the Symposium on Psychology in the Department of Defense (13th) Held in Colorado Springs, Colorado on 15-17 April 1992

    Science.gov (United States)

    1992-04-17

    model for ef ava teem evalution . The model shown above takes advantage of fractional factorials and total quality tools to provide understanding of...exposed to the extreme stresses of war (inflicting and/or observing death, inflicting or being the victim of friendly fire, experiencing the horror of

  15. Extreme Rituals as Social Technologies

    DEFF Research Database (Denmark)

    Fischer, Ronald; Xygalatas, Dimitris

    2014-01-01

    We often think of pain as intrinsically bad, and the avoidance of pain is a fundamental evolutionary drive of all species. How can we then explain widespread cultural prac- tices like certain rituals that involve the voluntary infliction of physical pain? In this paper, we argue that inflicting...

  16. Disruption of myelination by diagnostic US

    International Nuclear Information System (INIS)

    Ellisman, M.H.; Palmer, D.E.; Andre, M.P.

    1986-01-01

    In order to test for possible effects of US on myelination, the authors exposed 20 unanesthetized rat pups to US intensities consistent with those used for imaging a human fetus in utero. The rats were 3-5 days old and at a stage of myelination similar to that of a human fetus of about 4-5 months. Then animals were exposed for 30 minutes to the beam from a 3.5-MHz transducer (ADR 2130 real-time linear array, SPTA intensity of 0.4 mW/cm/sup 2/ and SATA intensity of 0.05 mW/cm/sup 2/). Control animals were bound and placed in the tank but not exposed for 30 minutes, and taken straight from the cage. Some animals were killed and tissues were processed for electron microscopy immediately after exposure, others were killed after recovery periods of up to 24 hours. Enlargements of the periaxonal space was visible with separation of adjacent paranodal loops and disruption of Schwann cell-axonal junctions in all exposed animals. Paranodal demyelination was also noted in several nodes. Nodes exhibiting this microedematous morphology were apparent even after a 24-hour recovery period but were not found in control preparations

  17. Early myelin breakdown following sural nerve crush: a freeze-fracture study

    Directory of Open Access Journals (Sweden)

    Martinez A.M.B.

    2000-01-01

    Full Text Available In this study we describe the early changes of the myelin sheath following surgical nerve crush. We used the freeze-fracture technique to better evaluate myelin alterations during an early stage of Wallerian degeneration. Rat sural nerves were experimentally crushed and animals were sacrificed by transcardiac perfusion 30 h after surgery. Segments of the nerves were processed for routine transmission electron microscopy and freeze-fracture techniques. Our results show that 30 h after the lesion there was asynchrony in the pattern of Wallerian degeneration, with different nerve fibers exhibiting variable degrees of axon disruption. This was observed by both techniques. Careful examination of several replicas revealed early changes in myelin membranes represented by vacuolization and splitting of consecutive lamellae, rearrangement of intramembranous particles and disappearance of paranodal transverse bands associated or not with retraction of paranodal myelin terminal loops from the axolemma. These alterations are compatible with a direct injury to the myelin sheath following nerve crush. The results are discussed in terms of a similar mechanism underlying both axon and myelin breakdown.

  18. The Ly6 protein coiled is required for septate junction and blood brain barrier organisation in Drosophila.

    Directory of Open Access Journals (Sweden)

    Assia Hijazi

    Full Text Available BACKGROUND: Genetic analysis of the Drosophila septate junctions has greatly contributed to our understanding of the mechanisms controlling the assembly of these adhesion structures, which bear strong similarities with the vertebrate tight junctions and the paranodal septate junctions. These adhesion complexes share conserved molecular components and have a common function: the formation of paracellular barriers restraining the diffusion of solutes through epithelial and glial envelopes. METHODOLOGY/PRINCIPAL FINDINGS: In this work we characterise the function of the Drosophila cold gene, that codes for a protein belonging to the Ly6 superfamily of extracellular ligands. Analysis of cold mutants shows that this gene is specifically required for the organisation of the septate junctions in epithelial tissues and in the nervous system, where its contribution is essential for the maintenance of the blood-brain barrier. We show that cold acts in a cell autonomous way, and we present evidence indicating that this protein could act as a septate junction component. CONCLUSION/SIGNIFICANCE: We discuss the specific roles of cold and three other Drosophila members of the Ly6 superfamily that have been shown to participate in a non-redundant way in the process of septate junction assembly. We propose that vertebrate Ly6 proteins could fulfill analogous roles in tight junctions and/or paranodal septate junctions.

  19. The Ly6 protein coiled is required for septate junction and blood brain barrier organisation in Drosophila.

    Science.gov (United States)

    Hijazi, Assia; Haenlin, Marc; Waltzer, Lucas; Roch, Fernando

    2011-03-15

    Genetic analysis of the Drosophila septate junctions has greatly contributed to our understanding of the mechanisms controlling the assembly of these adhesion structures, which bear strong similarities with the vertebrate tight junctions and the paranodal septate junctions. These adhesion complexes share conserved molecular components and have a common function: the formation of paracellular barriers restraining the diffusion of solutes through epithelial and glial envelopes. In this work we characterise the function of the Drosophila cold gene, that codes for a protein belonging to the Ly6 superfamily of extracellular ligands. Analysis of cold mutants shows that this gene is specifically required for the organisation of the septate junctions in epithelial tissues and in the nervous system, where its contribution is essential for the maintenance of the blood-brain barrier. We show that cold acts in a cell autonomous way, and we present evidence indicating that this protein could act as a septate junction component. We discuss the specific roles of cold and three other Drosophila members of the Ly6 superfamily that have been shown to participate in a non-redundant way in the process of septate junction assembly. We propose that vertebrate Ly6 proteins could fulfill analogous roles in tight junctions and/or paranodal septate junctions.

  20. Contactin-1 and Neurofascin-155/-186 Are Not Targets of Auto-Antibodies in Multifocal Motor Neuropathy.

    Directory of Open Access Journals (Sweden)

    Kathrin Doppler

    Full Text Available Multifocal motor neuropathy is an immune mediated disease presenting with multifocal muscle weakness and conduction block. IgM auto-antibodies against the ganglioside GM1 are detectable in about 50% of the patients. Auto-antibodies against the paranodal proteins contactin-1 and neurofascin-155 and the nodal protein neurofascin-186 have been detected in subgroups of patients with chronic inflammatory demyelinating polyneuropathy. Recently, auto-antibodies against neurofascin-186 and gliomedin were described in more than 60% of patients with multifocal motor neuropathy. In the current study, we aimed to validate this finding, using a combination of different assays for auto-antibody detection. In addition we intended to detect further auto-antibodies against paranodal proteins, specifically contactin-1 and neurofascin-155 in multifocal motor neuropathy patients' sera. We analyzed sera of 33 patients with well-characterized multifocal motor neuropathy for IgM or IgG anti-contactin-1, anti-neurofascin-155 or -186 antibodies using enzyme-linked immunosorbent assay, binding assays with transfected human embryonic kidney 293 cells and murine teased fibers. We did not detect any IgM or IgG auto-antibodies against contactin-1, neurofascin-155 or -186 in any of our multifocal motor neuropathy patients. We conclude that auto-antibodies against contactin-1, neurofascin-155 and -186 do not play a relevant role in the pathogenesis in this cohort with multifocal motor neuropathy.

  1. A Role for Excitatory Amino Acids in Diabetic Eye Disease

    Directory of Open Access Journals (Sweden)

    Jose E. Pulido

    2007-01-01

    Full Text Available Diabetic retinopathy is a leading cause of vision loss. The primary clinical hallmarks are vascular changes that appear to contribute to the loss of sight. In a number of neurodegenerative disorders there is an appreciation that increased levels of excitatory amino acids are excitotoxic. The primary amino acid responsible appears to be the neurotransmitter glutamate. This review examines the nature of glutamatergic signaling at the retina and the growing evidence from clinical and animal model studies that glutamate may be playing similar excitotoxic roles at the diabetic retina.

  2. A Glio-Protective Role of mir-263a by Tuning Sensitivity to Glutamate

    DEFF Research Database (Denmark)

    Aw, Sherry Shiying; Lim, Isaac Kok Hwee; Tang, Melissa Xue Mei

    2017-01-01

    of CG5621/Grik, Nmdar1, and Nmdar2. mir-263a mutants exhibit excitotoxic death of a subset of astrocyte-like and ensheathing glia in the CNS. Glial-specific normalization of glutamate receptor levels restores cell numbers and suppresses the movement defect. Therefore, microRNA-mediated regulation...... of glutamate receptor levels protects glia from excitotoxicity, ensuring CNS health. Chronic low-level glutamate receptor overexpression due to mutations affecting microRNA (miRNA) regulation might contribute to glial dysfunction and CNS impairment....

  3. Neuroanatomy and Physiology of Brain Dysfunction in Sepsis.

    Science.gov (United States)

    Mazeraud, Aurelien; Pascal, Quentin; Verdonk, Franck; Heming, Nicholas; Chrétien, Fabrice; Sharshar, Tarek

    2016-06-01

    Sepsis-associated encephalopathy (SAE), a complication of sepsis, is often complicated by acute and long-term brain dysfunction. SAE is associated with electroencephalogram pattern changes and abnormal neuroimaging findings. The major processes involved are neuroinflammation, circulatory dysfunction, and excitotoxicity. Neuroinflammation and microcirculatory alterations are diffuse, whereas excitotoxicity might occur in more specific structures involved in the response to stress and the control of vital functions. A dysfunction of the brainstem, amygdala, and hippocampus might account for the increased mortality, psychological disorders, and cognitive impairment. This review summarizes clinical and paraclinical features of SAE and describes its mechanisms at cellular and structural levels. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Neuroprotection of rat retinal ganglion cells mediated through alpha7 nicotinic acetylcholine receptors.

    Science.gov (United States)

    Iwamoto, K; Mata, D; Linn, D M; Linn, C L

    2013-05-01

    Glutamate-induced excitotoxicity is thought to play an important role in several neurodegenerative diseases in the central nervous system (CNS). In this study, neuroprotection against glutamate-induced excitotoxicity was analyzed using acetylcholine (ACh), nicotine and the α7 specific nicotinic acetylcholine receptor (α7 nAChR) agonist, N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-4-chlorobenzamide hydrochloride (PNU-282987), in cultured adult rat retinal neurons. Adult Long Evans rat retinas were dissociated and retinal ganglion cells (RGCs) were isolated from all other retinal tissue using a two-step panning technique. Once isolated, RGCs were cultured under various pharmacological conditions to demonstrate excitotoxicity and neuroprotection against excitotoxicity. After 3 days, RGCs were immunostained with antibodies against the glycoprotein, Thy 1.1, counted and cell survival was assessed relative to control untreated conditions. 500 μM glutamate induced excitotoxicity in large and small RGCs in an adult rat dissociated culture. After 3 days in culture with glutamate, the cell survival of large RGCs decreased by an average of 48.16% while the cell survival of small RGCs decreased by an average of 42.03%. Using specific glutamate receptor agonists and antagonists, we provide evidence that the excitotoxic response was mediated through α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainic acid (KA) and N-methyl-d-aspartate (NMDA) glutamate receptors through an apoptotic mechanism. However, the excitotoxic effect of glutamate on all RGCs was eliminated if cells were cultured for an hour with 10 μM ACh, 100 μM nicotine or 100 nM of the α7 nAChR agonist, PNU-282987, before the glutamate insult. Inhibition studies using 10nM methyllycaconitine (MLA) or α-bungarotoxin (α-Bgt) supported the hypothesis that neuroprotection against glutamate-induced excitotoxicity on rat RGCs was mediated through α7 nAChRs. In immunocytochemical studies, double

  5. Global economic meltdown and the Nigerian economy | Lawrence ...

    African Journals Online (AJOL)

    International Journal of Development and Management Review ... Other identified causes are the housing bubble and predatory lending by its financial giants. The crisis has inflicted so much harm on the Nigerian economy by resulting in ...

  6. Hidradenitis Suppurativa/Acne Inversa

    DEFF Research Database (Denmark)

    Zouboulis, Christos C.; Del Marmol, Véronique; Mrowietz, Ulrich

    2015-01-01

    BACKGROUND: Hidradenitis suppurativa/acne inversa (HS) is a chronic, inflammatory, recurrent, debilitating disease, which inflicts a significant burden on patients and is associated with comorbid disorders, such as significantly reduced quality of life, depression, stigmatization, inactivity...

  7. 43 CFR 423.22 - Interference with agency functions and disorderly conduct.

    Science.gov (United States)

    2010-10-01

    ... behavior; (2) Language, utterance, gesture, display, or act that is obscene, physically threatening or menacing, or that is likely to inflict injury or incite an immediate breach of the peace; (3) Unreasonable...

  8. 32 CFR 1903.14 - Disorderly conduct.

    Science.gov (United States)

    2010-07-01

    ... manner that is likely to inflict injury or incite an immediate breach of peace. (c) Makes noises that are...) Uses obscene language, an utterance, or gesture, or engages in a display or act that is obscene. (e...

  9. Tetanus with multiple wedge vertebral collapses

    African Journals Online (AJOL)

    owner

    2012-07-06

    Jul 6, 2012 ... associated with traumatic injury, often a penetrating wound inflicted by dirty ... multiple vertebral collapses and the management chal- .... back pains and swelling as in our patient.9 There are usually no ... The cervical and.

  10. Electrophysiological responses of male and female Amyelois transitella antennae to pistachio and almond host plant volatiles

    Science.gov (United States)

    The polyphagous navel orangeworm, Amyelois transitella (Lepidoptera: Pyralidae), is a major insect pest of California tree nuts. The larvae of A. transitella feed on kernels inflicting damage and lowering nut kernel quality. Moreover, larvae vector aflatoxigenic aspergilli resulting in internationa...

  11. Fusion of phase congruency and harris algorithm for extraction of iris corner points

    CSIR Research Space (South Africa)

    Mabuza-Hocquet, G

    2015-12-01

    Full Text Available iris identification systems. Low cost devices used under uncontrolled environments acquire poor iris images with inconsistent illumination and specular reflections. These factors inflict challenges towards the accurate identification and extraction...

  12. Analgesic effects of manual therapy in patients with musculoskeletal pain: a systematic review

    NARCIS (Netherlands)

    J. Nijs; Dr. L.P. Voogt; F. Struyf; M. Meeys; D. Meuffels; J. de Vries

    2015-01-01

    BACKGROUND: Current evidence shows that manual therapy elicits analgesic effect in different populations (healthy, pain inflicted and patients with musculoskeletal pain) when carried out at the spinal column, although the clinical significance of these effects remains unclear. Also the analgesic

  13. 78 FR 27937 - Environmental Impact Statement; Feral Swine Damage Management

    Science.gov (United States)

    2013-05-13

    ....m., Monday through Friday, except holidays. To be sure someone is there to help you, please call..., U.S. Virgin Islands, the Northern Mariana Islands, and American Samoa. Feral swine can inflict...

  14. Agricultural Terrorism (Agroterror) and Escalation Theory

    National Research Council Canada - National Science Library

    Gooding, Aeneas R

    2007-01-01

    ... credibility terrorist groups must demonstrate a continued ability to conduct operations and inflict significant numbers of casualties on their enemy, maintaining a consistent, if not escalating, level of violence. This thesis uses E...

  15. Colored Contact Lens Dangers

    Medline Plus

    Full Text Available ... With Proper Contact Lens Care Apr 23, 2018 Solar Eclipse Inflicts Damage in the Shape of the ... edging closer, thanks to a wave of new technologies aiming to fix failing eye parts with human- ...

  16. Marine Attack on Towed Hydrophone Arrays

    National Research Council Canada - National Science Library

    Kalmijn, Ad

    2002-01-01

    The original objective of the SIO Marine Attack project was to identify the electric and magnetic fields causing sharks to inflict serious damage upon the towed hydrophone arrays of US Navy submarines...

  17. Shark Attack Project - Marine Attack at Towed Hydrophone Arrays

    National Research Council Canada - National Science Library

    Kalmijn, Adrianus J

    2005-01-01

    The original objective of the SIO Marine Attack project was to identify the electric and magnetic fields causing sharks to inflict serious damage upon the towed hydrophone arrays of US Navy submarines...

  18. 14 Wynchank 03.pmd

    African Journals Online (AJOL)

    Owner

    2009-03-02

    Mar 2, 2009 ... ... treatment inflicted on the natives by employees of the monopolistic ..... the concessionary company, accompanied by the Administrator, to the market once a ... came to that hotel were gamblers and they had more money that ...

  19. Bombay Hotel

    International Development Research Centre (IDRC) Digital Library (Canada)

    the development paradigm in Indian cities plays a central role in creating and perpetuating ... inequality, exclusion), direct violence (direct infliction of physical or ..... applying for documents such as property tax bills and. NOCs** in order to ...

  20. Colored Contact Lens Dangers

    Medline Plus

    Full Text Available ... contact lenses , from the U.S. Food and Drug Administration (FDA). Are the colored lenses you are considering buying approved by ... 23, 2018 Solar Eclipse Inflicts Damage in the Shape of ...

  1. Anwar Sadat's National Security Strategy in the October War: From Vision to Victory

    National Research Council Canada - National Science Library

    Bennett, Drew A; Arnold, Michael W

    2000-01-01

    ... that Israel was not invincible. His supporting military objectives were to inflict heavy casualties on the enemy, attack across the Suez to regain control of the canal, and recapture as much occupied territory as possible...

  2. Skeletal imaging of child abuse (non-accidental injury)

    NARCIS (Netherlands)

    Offiah, A.; van Rijn, R.R.; Perez-Rossello, J.M.; Kleinman, P.K.

    2009-01-01

    In recent years there has been a worldwide increased awareness that children are physically abused by their carers. Radiologists play a vital role in the detection of inflicted injuries. This article reviews the skeletal imaging findings seen in child abuse

  3. Expression analysis of the N-Myc downstream-regulated gene 1 indicates that myelinating Schwann cells are the primary disease target in hereditary motor and sensory neuropathy-Lom.

    Science.gov (United States)

    Berger, Philipp; Sirkowski, Erich E; Scherer, Steven S; Suter, Ueli

    2004-11-01

    Mutations in the gene encoding N-myc downstream-regulated gene-1 (NDRG1) lead to truncations of the encoded protein and are associated with an autosomal recessive demyelinating neuropathy--hereditary motor and sensory neuropathy-Lom. NDRG1 protein is highly expressed in peripheral nerve and is localized in the cytoplasm of myelinating Schwann cells, including the paranodes and Schmidt-Lanterman incisures. In contrast, sensory and motor neurons as well as their axons lack NDRG1. NDRG1 mRNA levels in developing and injured adult sciatic nerves parallel those of myelin-related genes, indicating that the expression of NDRG1 in myelinating Schwann cells is regulated by axonal interactions. Oligodendrocytes also express NDRG1, and the subtle CNS deficits of affected patients may result from a lack of NDRG1 in these cells. Our data predict that the loss of NDRG1 leads to a Schwann cell autonomous phenotype resulting in demyelination, with secondary axonal loss.

  4. Differential distribution of voltage-gated ion channels in cortical neurons: implications for epilepsy.

    Science.gov (United States)

    Child, Nicholas D; Benarroch, Eduardo E

    2014-03-18

    Neurons contain different functional somatodendritic and axonal domains, each with a characteristic distribution of voltage-gated ion channels, synaptic inputs, and function. The dendritic tree of a cortical pyramidal neuron has 2 distinct domains, the basal and the apical dendrites, both containing dendritic spines; the different domains of the axon are the axonal initial segment (AIS), axon proper (which in myelinated axons includes the node of Ranvier, paranodes, juxtaparanodes, and internodes), and the axon terminals. In the cerebral cortex, the dendritic spines of the pyramidal neurons receive most of the excitatory synapses; distinct populations of γ-aminobutyric acid (GABA)ergic interneurons target specific cellular domains and thus exert different influences on pyramidal neurons. The multiple synaptic inputs reaching the somatodendritic region and generating excitatory postsynaptic potentials (EPSPs) and inhibitory postsynaptic potentials (IPSPs) sum and elicit changes in membrane potential at the AIS, the site of initiation of the action potential.

  5. Lewis-Sumner syndrome and Tangier disease.

    Science.gov (United States)

    Théaudin, Marie; Couvert, Philippe; Fournier, Emmanuel; Bouige, Daniel; Bruckert, Eric; Perrotte, Paul; Vaschalde, Yvan; Maisonobe, Thierry; Bonnefont-Rousselot, Dominique; Carrié, Alain; Le Forestier, Nadine

    2008-07-01

    To report unusual electrophysiologic data in a patient with Tangier disease in an effort to better understand the pathophysiologic features of the peripheral nerve lesions in this disease. Case report. A 15-year-old girl had subacute onset of asymmetric neuropathy with persistent conduction block, resembling Lewis-Sumner syndrome. Electrophysiologic data in Tangier disease. After initially unsuccessful treatment with intravenously administered immunoglobulins, the finding of an abnormal lipid profile led to the diagnosis of Tangier disease due to the R587W mutation in the adenotriphosphate-binding cassette transporter-1 gene (ABCA1) (OMIM 9q22-q31). Conduction block, which is the electrophysiologic hallmark of focal demyelination, can be present in Tangier disease. It could be induced by focal nerve ischemia or by preferential lipid deposition in the paranodal regions of myelinated Schwann cells. The presence of a conduction block in Tangier disease may lead to a misdiagnosis of dysimmune neuropathy.

  6. Semiannual Report to the Congress. April 1, 2012 - September 30, 2012

    Science.gov (United States)

    2012-10-01

    Killeen, Texas, restaurant frequented by military members with the intent to inflict mass casualties and to shoot anyone fleeing the building after...the explosive devices inside a Killeen, Texas, restaurant frequented by military members with the intent to inflict mass casualties...” APRIL 1...compensation cap; $1.3 million of out-of-period worker’s compensation costs; and a $2.0 million upward adjustment for actual franchise taxes in excess of

  7. Habitual biting of oral mucosa: A conservative treatment approach

    Directory of Open Access Journals (Sweden)

    Sarabjot Kaur Bhatia

    2013-01-01

    Full Text Available Chronic biting of oral mucosa is an innocuous self inflicted injury, commonly seen in children suffering from developmental and psychological problems and has rarely been reported in normal unaffected individuals. The management strategies vary from counseling, prescription of sedatives to different prosthetic shields. The paper highlights the efficacy of a simple approach using soft mouth guard in the management of self inflicted lesions due to habitual biting of oral mucosa in two normal healthy children.

  8. Retheorizing Actionable Injuries in Civil Lawsuits Involving Targeted Hate Speech:Hate Speech as Degradation and Humiliation

    OpenAIRE

    Brown, Alexander

    2018-01-01

    Many legal jurisdictions permit victims of targeted hate speech to sue for damages in civil courts. In the US plaintiffs may sue for damages using the tort of intentional infliction of emotional distress. Indeed, back in 1982, Richard Delgado proposed the introduction of a new tort of racial insult to handle such cases. In South Africa, plaintiffs can use the delict of injuria. Although there have been some successful lawsuits, the tort of intentional infliction of emotional distress has been...

  9. Noscapine protects OLN-93 oligodendrocytes from ischemia-reperfusion damage: Calcium and nitric oxide involvement.

    Science.gov (United States)

    Nadjafi, S; Ebrahimi, S-A; Rahbar-Roshandel, N

    2015-12-01

    This study was carried out to evaluate the effects of noscapine, a benzylisoquinoline alkaloid from opium poppy, on oligodendrocyte during ischemia/reperfusion-induced excitotoxic injury. Changes in intracellular calcium levels due to chemical ischemia and nitric oxide (NO) production during ischemia/reperfusion were evaluated as the hallmarks of ischemia-derived excitotoxic event. OLN-93 cell line (a permanent immature rat oligodendrocyte) was used as a model of oligodendrocyte. 30- or 60-minute-oxygen-glucose deprivation/24 hours reperfusion were used to induce excitotoxicity. MTT (3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide) assay was used to evaluate cell viability. Ratiometric fluorescence microscopy using Ca(2+)-sensitive indicator Fura-2/AM was utilized to assess intracellular calcium levels. NO production was evaluated by Griess method. Noscapine (4 μM) significantly attenuated intracellular Ca(2+) elevation (P < 0.001). Also, noscapine significantly decreased NO production during a 30-minute oxygen-glucose deprivation/reperfusion (P < 0.01). The inhibitory effect of noscapine (4 μM) on intracellular Ca(2+) was greater than ionotropic glutamate receptors antagonists. Noscapine is protective against ischemia/reperfusion-induced excitotoxic injury in OLN-93 oligodendrocyte. This protective effect seems to be related to attenuation of intracellular Ca(2+) overload and NO production.

  10. Neurofarmakologická podstata působení memantinu v léčbě Alzheimerovy demence

    Czech Academy of Sciences Publication Activity Database

    Petrovič, Miloš; Sedláček, Miloslav; Horák, Martin; Vyklický ml., Ladislav

    2004-01-01

    Roč. 18, - (2004), s. 81-89 ISSN 1212-7973 R&D Projects: GA ČR GA309/04/1537; GA MŠk LN00B122 Institutional research plan: CEZ:AV0Z5011922 Keywords : NMDA receptors * excitotoxicity * gluatamate Subject RIV: FH - Neurology

  11. Age- and Sex-Dependent Laterality of Rat Hippocampal Cholinergic System in Relation to Animal Models of Neurodevelopmental and Neurodegenerative Disorders

    Czech Academy of Sciences Publication Activity Database

    Krištofíková, Z.; Šťastný, F.; Bubeníková, V.; Druga, R.; Klaschka, Jan; Španiel, F.

    2004-01-01

    Roč. 29, č. 4 (2004), s. 671-680 ISSN 0364-3190 R&D Projects: GA MZd NF6031 Institutional research plan: CEZ:AV0Z1030915 Keywords : laterality * cholinergic * excitotoxic * rat model * schizophrenia * Alzheimer disease Subject RIV: BB - Applied Statistics, Operational Research Impact factor: 2.218, year: 2004

  12. 1H-cyclopentapyrimidine-2,4(1H,3H)-dione-related ionotropic glutamate receptors ligands. Structure-activity relationships and identification of potent and selective iGluR5 modulators

    DEFF Research Database (Denmark)

    Butini, Stefania; Pickering, Darryl S; Morelli, Elena

    2008-01-01

    (S)-CPW399 ((S)-1) is a potent and excitotoxic AMPA receptor partial agonist. Modifying the cyclopentane ring of (S)-1, we developed two of the most potent and selective functional antagonists (5 and 7) for kainate receptor (KA-R) subunit iGluR5. Derivatives 5 and 7, with their unique pharmacolog...

  13. Induction of the Wnt inhibitor, Dickkopf-1, is associated with neurodegeneration related to temporal lobe epilepsy

    NARCIS (Netherlands)

    Busceti, Carla Letizia; Biagioni, Francesca; Aronica, Eleonora; Riozzi, Barbara; Storto, Marianna; Battaglia, Giuseppe; Giorgi, Filippo S.; Gradini, Roberto; Fornai, Francesco; Caricasole, Andrea; Nicoletti, Ferdinando; Bruno, Valeria

    2007-01-01

    Inhibition of the Wnt pathway by the secreted glycoprotein, Dickkopf-1 (Dkk-1) has been related to processes of excitotoxic and ischemic neuronal death. We now report that Dkk-1 is induced in neurons of the rat olfactory cortex and hippocampus degenerating in response to seizures produced by

  14. NS 1231, a novel compound with neurotrophic-like effects in vitro and in vivo

    DEFF Research Database (Denmark)

    Dagø, Lone; Bonde, Christian; Peters, Dan

    2002-01-01

    reduced NMDA-induced excitotoxicity in organotypic hippocampal slice cultures. In a gerbil model of transient global ischaemia, treatment with NS 1231 reduced the delayed loss of neurons in the hippocampal CA1 layer. Furthermore, NS 1231 treatment resulted in a 43% reduction in total infarct volume...

  15. Disease progression continues in patients with advanced Parkinson's disease and effective subthalamic nucleus stimulation

    NARCIS (Netherlands)

    Hilker, R; Portman, AT; Voges, J; Staal, MJ; Burghaus, L; van Laar, T; Koulousakis, A; Maguire, RP; Pruim, J; de Jong, BM; Herholz, K; Sturm, [No Value; Heiss, WD; Leenders, KL

    Objectives: Glutamate mediated excitotoxicity of the hyperactive subthalamic nucleus (STN) has been reported to contribute to nigral degeneration in Parkinson's disease (PD). Deep brain stimulation of the STN (STN DBS), in its role as a highly effective treatment of severe PD motor complications,

  16. Lesional-targeting of neuroprotection to the inflammatory penumbra in experimental multiple sclerosis

    NARCIS (Netherlands)

    Al-Izki, S.; Pryce, G.; Hankey, D.J.R.; Lidster, K.; von Kutzleben, S.M.; Browne, L.; Clutterbuck, L.; Posada, C.; Chan, A.W.E.; Amor, S.; Perkins, V.; Gerritsen, W.H.; Ummenthum, K.; Peferoen-Baert, R.; van der Valk, P.; Montoya, A.; Joel, S.P.; Garthwaite, J.; Giovannoni, G.; Selwood, D.L.; Baker, D.

    2014-01-01

    Progressive multiple sclerosis is associated with metabolic failure of the axon and excitotoxicity that leads to chronic neurodegeneration. Global sodium-channel blockade causes side effects that can limit its use for neuroprotection in multiple sclerosis. Through selective targeting of drugs to

  17. Intrinsic properties of lumbar motor neurones in the adult G127insTGGG superoxide dismutase-1 mutant mouse in vivo: evidence for increased persistent inward currents

    DEFF Research Database (Denmark)

    Meehan, Claire Francesca; Moldovan, Mihai; Marklund, Stefan L.

    2010-01-01

    Aim: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by a preferential loss of motoneurones. Previous publications using in vitro neonatal preparations suggest an increased excitability of motoneurones in various superoxide dismutase-1 (SOD1) mutant mice...... of an increased PIC and less spike frequency adaptation which may contribute to excitotoxity of these neurones as the disease progresses....

  18. CXCL10/CXCR3 signaling in glia cells differentially affects NMDA-induced cell death in CA and DG neurons of the mouse hippocampus

    DEFF Research Database (Denmark)

    van Weering, Hilmar R J; Boddeke, Hendrikus W G M; Vinet, Jonathan

    2011-01-01

    are far from understood. Here, we investigated the potential role for CXCL10/CXCR3 signaling in neuronal cell death and glia activation in response to N-methyl-D-aspartic acid (NMDA)-induced excitotoxicity in mouse organotypic hippocampal slice cultures (OHSCs). Our findings demonstrate that astrocytes...

  19. Tissue Plasminogen Activator (tPA) Mediates Neurotoxin-Induced Cell Death and Microglial Activation

    National Research Council Canada - National Science Library

    Tsirka, Styliani-Anna

    2001-01-01

    .... In mice lacking tPA (tPA-/1), neurons are resistant to neurotoxic death. Delivery of tPA into tpA-/- mice restores susceptibility to neuronal death, indicating that tPA is neurotoxic in the context of excitotoxic injury...

  20. Tissue Plasminogen Activator (tPA) Mediates Neurotoxin-Induced Cell Death and Microglial Activation

    National Research Council Canada - National Science Library

    Tsirka, Styliani-Anna

    2000-01-01

    .... In mice lacking tPA (tPA-/-), neurons are resistant to neurotoxic death. Delivery of tPA into tPA mice restores susceptibility to neuronal death, indicating that tPA is neurotoxic in the context of excitotoxic injury...

  1. S-Nitrosylation and uncompetitive/fast off-rate (UFO) drug therapy in neurodegenerative disorders of protein misfolding.

    Science.gov (United States)

    Nakamura, T; Lipton, S A

    2007-07-01

    Although activation of glutamate receptors is essential for normal brain function, excessive activity leads to a form of neurotoxicity known as excitotoxicity. Key mediators of excitotoxic damage include overactivation of N-methyl-D-aspartate (NMDA) receptors, resulting in excessive Ca(2+) influx with production of free radicals and other injurious pathways. Overproduction of free radical nitric oxide (NO) contributes to acute and chronic neurodegenerative disorders. NO can react with cysteine thiol groups to form S-nitrosothiols and thus change protein function. S-nitrosylation can result in neuroprotective or neurodestructive consequences depending on the protein involved. Many neurodegenerative diseases manifest conformational changes in proteins that result in misfolding and aggregation. Our recent studies have linked nitrosative stress to protein misfolding and neuronal cell death. Molecular chaperones - such as protein-disulfide isomerase, glucose-regulated protein 78, and heat-shock proteins - can provide neuroprotection by facilitating proper protein folding. Here, we review the effect of S-nitrosylation on protein function under excitotoxic conditions, and present evidence that NO contributes to degenerative conditions by S-nitrosylating-specific chaperones that would otherwise prevent accumulation of misfolded proteins and neuronal cell death. In contrast, we also review therapeutics that can abrogate excitotoxic damage by preventing excessive NMDA receptor activity, in part via S-nitrosylation of this receptor to curtail excessive activity.

  2. 3-Hydroxybutyrate regulates energy metabolism and induces BDNF expression in cerebral cortical neurons

    DEFF Research Database (Denmark)

    Marosi, Krisztina; Kim, Sang Woo; Moehl, Keelin

    2016-01-01

    During fasting and vigorous exercise, a shift of brain cell energy substrate utilization from glucose to the ketone 3-hydroxybutyrate (3OHB) occurs. Studies have shown that 3OHB can protect neurons against excitotoxicity and oxidative stress, but the underlying mechanisms remain unclear. Neurons ...... suggest cellular signaling mechanisms by which 3OHB may mediate adaptive responses of neurons to fasting, exercise, and ketogenic diets....

  3. Excitatory amino acid neurotoxicity and modulation of glutamate receptor expression in organotypic brain slice cultures

    DEFF Research Database (Denmark)

    Zimmer, J; Kristensen, Bjarne Winther; Jakobsen, B

    2000-01-01

    Using organotypic slice cultures of hippocampus and cortex-striatum from newborn to 7 day old rats, we are currently studying the excitotoxic effects of kainic acid (KA), AMPA and NMDA and the neuroprotective effects of glutamate receptor blockers, like NBQX. For detection and quantitation...

  4. Pathophysiology and Biomarkers in Acute Ischemic Stroke – A Review

    African Journals Online (AJOL)

    The pathophysiology of ischemic stroke is complex, and majorly involves excitotoxicity, oxidative stress, inflammation, blood-brain barrier dysfunction, apoptosis, etc. Several of the biomarkers are related to these pathophysiologic mechanisms and they may have applications in stroke prediction, diagnosis, assessment, ...

  5. Glutamate excitoxicity is the key molecular mechanism which is influenced by body temperature during the acute phase of brain stroke.

    Science.gov (United States)

    Campos, Francisco; Pérez-Mato, María; Agulla, Jesús; Blanco, Miguel; Barral, David; Almeida, Angeles; Brea, David; Waeber, Christian; Castillo, José; Ramos-Cabrer, Pedro

    2012-01-01

    Glutamate excitotoxicity, metabolic rate and inflammatory response have been associated to the deleterious effects of temperature during the acute phase of stroke. So far, the association of temperature with these mechanisms has been studied individually. However, the simultaneous study of the influence of temperature on these mechanisms is necessary to clarify their contributions to temperature-mediated ischemic damage. We used non-invasive Magnetic Resonance Spectroscopy to simultaneously measure temperature, glutamate excitotoxicity and metabolic rate in the brain in animal models of ischemia. The immune response to ischemia was measured through molecular serum markers in peripheral blood. We submitted groups of animals to different experimental conditions (hypothermia at 33°C, normothermia at 37°C and hyperthermia at 39°C), and combined these conditions with pharmacological modulation of glutamate levels in the brain through systemic injections of glutamate and oxaloacetate. We show that pharmacological modulation of glutamate levels can neutralize the deleterious effects of hyperthermia and the beneficial effects of hypothermia, however the analysis of the inflammatory response and metabolic rate, demonstrated that their effects on ischemic damage are less critical than glutamate excitotoxity. We conclude that glutamate excitotoxicity is the key molecular mechanism which is influenced by body temperature during the acute phase of brain stroke.

  6. Nicotinic receptor activation contrasts pathophysiological bursting and neurodegeneration evoked by glutamate uptake block on rat hypoglossal motoneurons.

    Science.gov (United States)

    Corsini, Silvia; Tortora, Maria; Nistri, Andrea

    2016-11-15

    Impaired uptake of glutamate builds up the extracellular level of this excitatory transmitter to trigger rhythmic neuronal bursting and delayed cell death in the brainstem motor nucleus hypoglossus. This process is the expression of the excitotoxicity that underlies motoneuron degeneration in diseases such as amyotrophic lateral sclerosis affecting bulbar motoneurons. In a model of motoneuron excitotoxicity produced by pharmacological block of glutamate uptake in vitro, rhythmic bursting is suppressed by activation of neuronal nicotinic receptors with their conventional agonist nicotine. Emergence of bursting is facilitated by nicotinic receptor antagonists. Following excitotoxicity, nicotinic receptor activity decreases mitochondrial energy dysfunction, endoplasmic reticulum stress and production of toxic radicals. Globally, these phenomena synergize to provide motoneuron protection. Nicotinic receptors may represent a novel target to contrast pathological overactivity of brainstem motoneurons and therefore to prevent their metabolic distress and death. Excitotoxicity is thought to be one of the early processes in the onset of amyotrophic lateral sclerosis (ALS) because high levels of glutamate have been detected in the cerebrospinal fluid of such patients due to dysfunctional uptake of this transmitter that gradually damages brainstem and spinal motoneurons. To explore potential mechanisms to arrest ALS onset, we used an established in vitro model of rat brainstem slice preparation in which excitotoxicity is induced by the glutamate uptake blocker dl-threo-β-benzyloxyaspartate (TBOA). Because certain brain neurons may be neuroprotected via activation of nicotinic acetylcholine receptors (nAChRs) by nicotine, we investigated if nicotine could arrest excitotoxic damage to highly ALS-vulnerable hypoglossal motoneurons (HMs). On 50% of patch-clamped HMs, TBOA induced intense network bursts that were inhibited by 1-10 μm nicotine, whereas nAChR antagonists

  7. Nicotinic receptors modulate the onset of reactive oxygen species production and mitochondrial dysfunction evoked by glutamate uptake block in the rat hypoglossal nucleus.

    Science.gov (United States)

    Tortora, Maria; Corsini, Silvia; Nistri, Andrea

    2017-02-03

    In several neurodegenerative diseases, glutamate-mediated excitotoxicity is considered to be a major process to initiate cell degeneration. Indeed, subsequent to excessive glutamate receptor stimulation, reactive oxygen species (ROS) generation and mitochondrial dysfunction are regarded as two major gateways leading to neuron death. These processes are mimicked in an in vitro model of rat brainstem slice when excitotoxicity is induced by DL-threo-β-benzyloxyaspartate (TBOA), a specific glutamate-uptake blocker that increases extracellular glutamate. Our recent study has demonstrated that brainstem hypoglossal motoneurons, which are very vulnerable to this damage, were neuroprotected from excitotoxicity with nicotine application through the activation of nicotinic acetylcholine receptors (nAChRs) and subsequent inhibition of ROS and mitochondrial dysfunction. The present study examined if endogenous cholinergic activity exerted any protective effect in this pathophysiological model and how ROS production (estimated with rhodamine fluorescence) and mitochondrial dysfunction (measured as methyltetrazolium reduction) were time-related during the early phase of excitotoxicity (0-4h). nAChR antagonists did not modify TBOA-evoked ROS production (that was nearly doubled over control) or mitochondrial impairment (25% decline), suggesting that intrinsic nAChR activity was insufficient to contrast excitotoxicity and needed further stimulation with nicotine to become effective. ROS production always preceded mitochondrial dysfunction by about 2h. Nicotine prevented both ROS production and mitochondrial metabolic depression with a delayed action that alluded to a complex chain of events targeting these two lesional processes. The present data indicate a relatively wide time frame during which strong nAChR activation can arrest a runaway neurotoxic process leading to cell death. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. [The comparative characteristics of sawcuts across the femoral bone].

    Science.gov (United States)

    Sarkisian, B A; Azarov, P A

    2014-01-01

    The objective of the present work was to study the differences between the morphological features of the wounds in the long tubular bones inflicted by joinery hand saws designed for longitudinal and transverse, sawing. The experimental injuries to the femoral bones were inflicted by the recurring and reciprocating saw movements. The hand saws had 5 mm high "sharp" and "blunt"-tipped teeth. A total of 40 experiments were carried out. It was shown that the sawcuts across the femoral bones and their edges have different size, shape, and morphological characteristics (defects, ledges, projections, bright spots) depending on the type of the saw, the sharpness of its teeth, and the mode of sawing. The results of the study may be used to improve diagnostics of injuries to the long tubular bones inflicted by different types of joinery saws.

  9. Amino acids as dietary excitotoxins: a contribution to understanding neurodegenerative disorders.

    Science.gov (United States)

    Meldrum, B

    1993-01-01

    The possibility that some acidic amino acids occurring naturally or as additives in the diet can act as excitotoxins producing central nervous system pathology has been the subject of extensive debate in the last 20 years and is here reviewed. High doses of glutamate, aspartate or related excitatory amino acids given in isolation to neonatal rodents produce acute degeneration organs. Neuropathology resulting from consumption of glutamate or aspartate has not been described in man. Various unusual amino acids of plant origin can produce acute excitotoxic syndromes. In man domoate (consumed in mussels that have fed on (Nitschia pungens) can produce an acute syndrome associated with limbic system lesions and anterograde amnesia. Kainate and domoate produce similar syndromes in rodents; acromelate produces spinal pathology. The mechanisms and manifestations of chronic excitotoxicity are less clearly established. A combination of impaired energy metabolism or impaired buffering of calcium and free radicals and endogenous or exogenous excitotoxins may contribute to neuronal loss in human neurodegenerative disorders.

  10. Mild hypothermia as a treatment for central nervous system injuries: Positive or negative effects.

    Science.gov (United States)

    Darwazeh, Rami; Yan, Yi

    2013-10-05

    Besides local neuronal damage caused by the primary insult, central nervous system injuries may secondarily cause a progressive cascade of related events including brain edema, ischemia, oxida-tive stress, excitotoxicity, and dysregulation of calcium homeostasis. Hypothermia is a beneficial strategy in a variety of acute central nervous system injuries. Mild hypothermia can treat high intra-cranial pressure following traumatic brain injuries in adults. It is a new treatment that increases sur-vival and quality of life for patients suffering from ischemic insults such as cardiac arrest, stroke, and neurogenic fever following brain trauma. Therapeutic hypothermia decreases free radical produc-tion, inflammation, excitotoxicity and intracranial pressure, and improves cerebral metabolism after traumatic brain injury and cerebral ischemia, thus protecting against central nervous system dam-age. Although a series of pathological and physiological changes as well as potential side effects are observed during hypothermia treatment, it remains a potential therapeutic strategy for central nervous system injuries and deserves further study.

  11. Negative modulation of NMDA receptor channel function by DREAM/calsenilin/KChIP3 provides neuroprotection?

    Science.gov (United States)

    Wang, KeWei; Wang, Yun

    2012-01-01

    N-methyl-D-aspartate receptors (NMDARs) are glutamate-gated ion channels highly permeable to calcium and essential to excitatory neurotransmission. The NMDARs have attracted much attention because of their role in synaptic plasticity and excitotoxicity. Evidence has recently accumulated that NMDARs are negatively regulated by intracellular calcium binding proteins. The calcium-dependent suppression of NMDAR function serves as a feedback mechanism capable of regulating subsequent Ca2+ entry into the postsynaptic cell, and may offer an alternative approach to treating NMDAR-mediated excitotoxic injury. This short review summarizes the recent progress made in understanding the negative modulation of NMDAR function by DREAM/calsenilin/KChIP3, a neuronal calcium sensor (NCS) protein. PMID:22518099

  12. Naphthazarin protects against glutamate-induced neuronal death via activation of the Nrf2/ARE pathway

    Energy Technology Data Exchange (ETDEWEB)

    Son, Tae Gen; Kawamoto, Elisa M.; Yu, Qian-Sheng; Greig, Nigel H. [Laboratory of Neurosciences, National Institute on Aging, Intramural Research Program, 251 Bayview Blvd., Baltimore, MD 21224 (United States); Mattson, Mark P. [Laboratory of Neurosciences, National Institute on Aging, Intramural Research Program, 251 Bayview Blvd., Baltimore, MD 21224 (United States); Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD (United States); Camandola, Simonetta, E-mail: camandolasi@mail.nih.gov [Laboratory of Neurosciences, National Institute on Aging, Intramural Research Program, 251 Bayview Blvd., Baltimore, MD 21224 (United States)

    2013-04-19

    Highlights: •Naphthazarin activates the Nrf2/ARE pathway. •Naphthazarin induces Nrf2-driven genes in neurons and astrocytes. •Naphthazarin protects neurons against excitotoxicity. -- Abstract: Nuclear factor E2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway is an important cellular stress response pathway involved in neuroprotection. We previously screened several natural phytochemicals and identified plumbagin as a novel activator of the Nrf2/ARE pathway that can protect neurons against ischemic injury. Here we extended our studies to natural and synthetic derivatives of plumbagin. We found that 5,8-dimethoxy-1,4-naphthoquinone (naphthazarin) is a potent activator of the Nrf2/ARE pathway, up-regulates the expression of Nrf2-driven genes in primary neuronal and glial cultures, and protects neurons against glutamate-induced excitotoxicity.

  13. Modulation of Antioxidant Enzymatic Activities by Certain Antiepileptic Drugs (Valproic Acid, Oxcarbazepine, and Topiramate): Evidence in Humans and Experimental Models

    Science.gov (United States)

    Cárdenas-Rodríguez, Noemí; Coballase-Urrutia, Elvia; Rivera-Espinosa, Liliana; Romero-Toledo, Arantxa; Sampieri, Aristides III; Ortega-Cuellar, Daniel; Montesinos-Correa, Hortencia; Floriano-Sánchez, Esaú; Carmona-Aparicio, Liliana

    2013-01-01

    It is estimated that at least 100 million people worldwide will suffer from epilepsy at some point in their lives. This neurological disorder induces brain death due to the excessive liberation of glutamate, which activates the postsynaptic N-methyl-D-aspartic acid (NMDA) receptors, which in turn cause the reuptake of intracellular calcium (excitotoxicity). This excitotoxicity elicits a series of events leading to nitric oxide synthase (NOS) activation and the generation of reactive oxygen species (ROS). Several studies in experimental models and in humans have demonstrated that certain antiepileptic drugs (AEDs) exhibit antioxidant effects by modulating the activity of various enzymes associated with this type of stress. Considering the above-mentioned data, we aimed to compile evidence elucidating how AEDs such as valproic acid (VPA), oxcarbazepine (OXC), and topiramate (TPM) modulate oxidative stress. PMID:24454986

  14. Modulation of Antioxidant Enzymatic Activities by Certain Antiepileptic Drugs (Valproic Acid, Oxcarbazepine, and Topiramate: Evidence in Humans and Experimental Models

    Directory of Open Access Journals (Sweden)

    Noemí Cárdenas-Rodríguez

    2013-01-01

    Full Text Available It is estimated that at least 100 million people worldwide will suffer from epilepsy at some point in their lives. This neurological disorder induces brain death due to the excessive liberation of glutamate, which activates the postsynaptic N-methyl-D-aspartic acid (NMDA receptors, which in turn cause the reuptake of intracellular calcium (excitotoxicity. This excitotoxicity elicits a series of events leading to nitric oxide synthase (NOS activation and the generation of reactive oxygen species (ROS. Several studies in experimental models and in humans have demonstrated that certain antiepileptic drugs (AEDs exhibit antioxidant effects by modulating the activity of various enzymes associated with this type of stress. Considering the above-mentioned data, we aimed to compile evidence elucidating how AEDs such as valproic acid (VPA, oxcarbazepine (OXC, and topiramate (TPM modulate oxidative stress.

  15. Glutamate Transporters in the Blood-Brain Barrier

    DEFF Research Database (Denmark)

    Helms, Hans Christian Cederberg; Nielsen, Carsten Uhd; Waagepetersen, Helle S

    2017-01-01

    concentration of L-glutamate causes excitotoxicity. A tight control of the brain interstitial fluid L-glutamate levels is therefore imperative, in order to maintain optimal neurotransmission and to avoid such excitotoxicity. The blood-brain barrier, i.e., the endothelial lining of the brain capillaries...... cells. The mechanisms underlying transendothelial L-glutamate transport are however still not well understood. The present chapter summarizes the current knowledge on blood-brain barrier L-glutamate transporters and the suggested pathways for the brain-to-blood L-glutamate efflux......., regulates the exchange of nutrients, gases, and metabolic waste products between plasma and brain interstitial fluid. It has been suggested that brain capillary endothelial cells could play an important role in L-glutamate homeostasis by mediating brain-to-blood L-glutamate efflux. Both in vitro and in vivo...

  16. Effects of cholinergic deafferentation of the rhinal cortex on visual recognition memory in monkeys.

    Science.gov (United States)

    Turchi, Janita; Saunders, Richard C; Mishkin, Mortimer

    2005-02-08

    Excitotoxic lesion studies have confirmed that the rhinal cortex is essential for visual recognition ability in monkeys. To evaluate the mnemonic role of cholinergic inputs to this cortical region, we compared the visual recognition performance of monkeys given rhinal cortex infusions of a selective cholinergic immunotoxin, ME20.4-SAP, with the performance of monkeys given control infusions into this same tissue. The immunotoxin, which leads to selective cholinergic deafferentation of the infused cortex, yielded recognition deficits of the same magnitude as those produced by excitotoxic lesions of this region, providing the most direct demonstration to date that cholinergic activation of the rhinal cortex is essential for storing the representations of new visual stimuli and thereby enabling their later recognition.

  17. Naphthazarin protects against glutamate-induced neuronal death via activation of the Nrf2/ARE pathway

    International Nuclear Information System (INIS)

    Son, Tae Gen; Kawamoto, Elisa M.; Yu, Qian-Sheng; Greig, Nigel H.; Mattson, Mark P.; Camandola, Simonetta

    2013-01-01

    Highlights: •Naphthazarin activates the Nrf2/ARE pathway. •Naphthazarin induces Nrf2-driven genes in neurons and astrocytes. •Naphthazarin protects neurons against excitotoxicity. -- Abstract: Nuclear factor E2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway is an important cellular stress response pathway involved in neuroprotection. We previously screened several natural phytochemicals and identified plumbagin as a novel activator of the Nrf2/ARE pathway that can protect neurons against ischemic injury. Here we extended our studies to natural and synthetic derivatives of plumbagin. We found that 5,8-dimethoxy-1,4-naphthoquinone (naphthazarin) is a potent activator of the Nrf2/ARE pathway, up-regulates the expression of Nrf2-driven genes in primary neuronal and glial cultures, and protects neurons against glutamate-induced excitotoxicity

  18. Equalisation of socioeconomic differences in injury risks at school age? A study of three age cohorts of Swedish children and adolescents

    DEFF Research Database (Denmark)

    Engström, K; Laflamme, L; Diderichsen, F

    2003-01-01

    Hospital Discharge and Causes of Death registers) with documented socioeconomic differences: injuries due to traffic, interpersonal violence, and self-infliction. The Relative Index of Inequality was used to measure the magnitude of relative socioeconomic differences, for each year of observation. Where...... the two older cohorts (10-14 and 15-19, in 1990). In conclusion, this study provides limited evidence of equalisation in injury risks between socioeconomic groups among Swedish adolescents. Equalisation appears to be a gender-specific phenomenon, that is, among girls, and manifests itself around the age...... culture effects-as hypothesised by West-is debatable, particularly in the case of self-inflicted injuries....

  19. Vellykket konservativ behandling efter knivtraume mod hjertet

    DEFF Research Database (Denmark)

    Wærsted, Stian; Schou-Jensen, Katrine; Jensen, Tim

    2012-01-01

    A five year-old girl was admitted to hospital following an accidental stab wound to the chest, inflicted by a knife placed in a dishwasher's cutlery tray. Investigations revealed a traumatic ventricular septum defect of the heart, with a pericardial effusion. Since the patient remained haemodynam......A five year-old girl was admitted to hospital following an accidental stab wound to the chest, inflicted by a knife placed in a dishwasher's cutlery tray. Investigations revealed a traumatic ventricular septum defect of the heart, with a pericardial effusion. Since the patient remained...

  20. Socioeconomic differences in injury risks in childhood and adolescence: a nation-wide study of intentional and unintentional injuries in Sweden

    DEFF Research Database (Denmark)

    Engström, K; Diderichsen, F; Laflamme, L

    2002-01-01

    , interpersonal violence, and self inflicted injuries. RESULTS: Injury incidences were relatively low and socioeconomic differences negligible in the 0-4 year olds. Thereafter, significant socioeconomic differences were observed in all diagnostic groups except falls. The highest absolute differences were...... in traffic injuries, especially among 15-19 year olds, and in self inflicted injuries among 15-19 year old girls. Relative differences were highest in both categories of intentional injuries for the age group 10-14. Social circumstances in the household other than family socioeconomic status affected...

  1. الجزاءات الإدارية: بين ضرورات الفعالية الإدارية وقيود حماية الحقوق والحريات الأساسية -دراسة مقارنة -

    Directory of Open Access Journals (Sweden)

    صلاح الدين بوجلال

    2014-12-01

    Full Text Available in each system of law, the administrative sanctions take a distinct place along the criminal and civil sanctions. Administrative sanctions are inflicted by administrative bodies to ensure the fulfillment of certain obligations or restoring some legal conditions, such as withdrawing, suspending or denial of an advantage or facility provided by law. The punitive character of these sanctions required the applicability of some law principles from the criminal law into the administrative law, to ensure the protection against abuse in inflicting a punitive sanction, and also guarantees for each person the right to a fair trial.

  2. Diagnostic imaging of child abuse

    Energy Technology Data Exchange (ETDEWEB)

    Oguma, Eiji; Aihara, Toshinori [Saitama Children' s Medical Center, Iwatsuki (Japan)

    2002-04-01

    The major role of imaging in cases of suspected child abuse is to identify the physical injuries and to confirm the occurrence of abuse. In severely abused infants, the imaging findings may be the only evidence for a diagnosis of inflicted injury. Imaging may be the first clue to abuse in children seen with apparent other conditions and lead to appropriate measures to protect them from the risk of more serious injury. The radiologist must be familiar with imaging findings of inflicted injuries to fulfill these roles. (author)

  3. Diagnostic imaging of child abuse

    International Nuclear Information System (INIS)

    Oguma, Eiji; Aihara, Toshinori

    2002-01-01

    The major role of imaging in cases of suspected child abuse is to identify the physical injuries and to confirm the occurrence of abuse. In severely abused infants, the imaging findings may be the only evidence for a diagnosis of inflicted injury. Imaging may be the first clue to abuse in children seen with apparent other conditions and lead to appropriate measures to protect them from the risk of more serious injury. The radiologist must be familiar with imaging findings of inflicted injuries to fulfill these roles. (author)

  4. An αII Spectrin-Based Cytoskeleton Protects Large-Diameter Myelinated Axons from Degeneration.

    Science.gov (United States)

    Huang, Claire Yu-Mei; Zhang, Chuansheng; Zollinger, Daniel R; Leterrier, Christophe; Rasband, Matthew N

    2017-11-22

    Axons must withstand mechanical forces, including tension, torsion, and compression. Spectrins and actin form a periodic cytoskeleton proposed to protect axons against these forces. However, because spectrins also participate in assembly of axon initial segments (AISs) and nodes of Ranvier, it is difficult to uncouple their roles in maintaining axon integrity from their functions at AIS and nodes. To overcome this problem and to determine the importance of spectrin cytoskeletons for axon integrity, we generated mice with αII spectrin-deficient peripheral sensory neurons. The axons of these neurons are very long and exposed to the mechanical forces associated with limb movement; most lack an AIS, and some are unmyelinated and have no nodes. We analyzed αII spectrin-deficient mice of both sexes and found that, in myelinated axons, αII spectrin forms a periodic cytoskeleton with βIV and βII spectrin at nodes of Ranvier and paranodes, respectively, but that loss of αII spectrin disrupts this organization. Avil-cre;Sptan1 f/f mice have reduced numbers of nodes, disrupted paranodal junctions, and mislocalized Kv1 K + channels. We show that the density of nodal βIV spectrin is constant among axons, but the density of nodal αII spectrin increases with axon diameter. Remarkably, Avil-cre;Sptan1 f/f mice have intact nociception and small-diameter axons, but severe ataxia due to preferential degeneration of large-diameter myelinated axons. Our results suggest that nodal αII spectrin helps resist the mechanical forces experienced by large-diameter axons, and that αII spectrin-dependent cytoskeletons are also required for assembly of nodes of Ranvier. SIGNIFICANCE STATEMENT A periodic axonal cytoskeleton consisting of actin and spectrin has been proposed to help axons resist the mechanical forces to which they are exposed (e.g., compression, torsion, and stretch). However, until now, no vertebrate animal model has tested the requirement of the spectrin cytoskeleton in

  5. The role of Gpi-anchored axonal glycoproteins in neural development and neurological disorders.

    Science.gov (United States)

    Gennarini, Gianfranco; Bizzoca, Antonella; Picocci, Sabrina; Puzzo, Daniela; Corsi, Patrizia; Furley, Andrew J W

    2017-06-01

    This review article focuses on the Contactin (CNTN) subset of the Immunoglobulin supergene family (IgC2/FNIII molecules), whose components share structural properties (the association of Immunoglobulin type C2 with Fibronectin type III domains), as well as a general role in cell contact formation and axonal growth control. IgC2/FNIII molecules include 6 highly related components (CNTN 1-6), associated with the cell membrane via a Glycosyl Phosphatidyl Inositol (GPI)-containing lipid tail. Contactin 1 and Contactin 2 share ~50 (49.38)% identity at the aminoacid level. They are components of the cell surface, from which they may be released in soluble forms. They bind heterophilically to multiple partners in cis and in trans, including members of the related L1CAM family and of the Neurexin family Contactin-associated proteins (CNTNAPs or Casprs). Such interactions are important for organising the neuronal membrane, as well as for modulating the growth and pathfinding of axon tracts. In addition, they also mediate the functional maturation of axons by promoting their interactions with myelinating cells at the nodal, paranodal and juxtaparanodal regions. Such interactions also mediate differential ionic channels (both Na + and K + ) distribution, which is of critical relevance in the generation of the peak-shaped action potential. Indeed, thanks to their interactions with Ankyrin G, Na + channels map within the nodal regions, where they drive axonal depolarization. However, no ionic channels are found in the flanking Contactin1-containing paranodal regions, where CNTN1 interactions with Caspr1 and with the Ig superfamily component Neurofascin 155 in cis and in trans, respectively, build a molecular barrier between the node and the juxtaparanode. In this region K + channels are clustered, depending upon molecular interactions with Contactin 2 and with Caspr2. In addition to these functions, the Contactins appear to have also a role in degenerative and inflammatory

  6. Resveratrol attenuates oxidative stress and improves behaviour in 1 -methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) challenged mice

    OpenAIRE

    Anandhan, Annadurai; Tamilselvam, Kuppusamy; Vijayraja, Dhanraj; Ashokkumar, Nataraj; Rajasankar, Srinivasagam; Manivasagam, Thamilarasan

    2010-01-01

    Background Parkinson's disease (PD) is the most common neurodegenerative disorder, characterized by loss of dopaminergic neurons in substantia nigra and depletion of dopamine in striatum due to mitochondrial dysfunction, oxidative stress, excitotoxicity, apoptosis, inflammation and proteasome failure. Purpose The present study deals with the neuroprotective effect of resveratrol, a wine polyphenol (50 mg/kg body weight) against MPTP (30mg/kg body weight as i.p. administration) induced mice mo...

  7. Role of neuroinflammation in ischemic stroke

    Institute of Scientific and Technical Information of China (English)

    Rui Liu; Meng-Xian Pan; Jun-Chun Tang; Ya Zhang; Hua-Bao Liao; Yang Zhuang; Dan Zhao; Qi Wan

    2017-01-01

    Ischemic stroke causes the depletion of energy and induce excitotoxicity and neuroinflammation in the brain that results from thrombotic blockage. Neuroinflammation occurs initially depending on activated resident microglia that has the same function as the macrophage. Activated microglia participates in the neuroinflammatory process by phagocytosing the injured brain cells and producing the pro- and anti-inflammatory mediators. In this review, the authors present an overview of the role of microglia in mediating neuroinflammation in ischemic stroke.

  8. Differential effects of fresh frozen plasma and normal saline on secondary brain damage in a large animal model of polytrauma, hemorrhage and traumatic brain injury

    DEFF Research Database (Denmark)

    Hwabejire, John O; Imam, Ayesha M; Jin, Guang

    2013-01-01

    We have previously shown that the extent of traumatic brain injury (TBI) in large animal models can be reduced with early infusion of fresh frozen plasma (FFP), but the precise mechanisms remain unclear. In this study, we investigated whether resuscitation with FFP or normal saline differed in th...... in their effects on cerebral metabolism and excitotoxic secondary brain injury in a model of polytrauma, TBI, and hemorrhagic shock....

  9. Srovnání vlivu systémové aplikace non-kompetitivních a use-dependentních NMDA antagonistů na lokomoční aktivitu a kognitivní funkce u laboratorního potkana

    Czech Academy of Sciences Publication Activity Database

    Valeš, Karel; Rambousek, Lukáš; Stuchlík, Aleš; Chodounská, Hana; Vyklický ml., Ladislav

    2010-01-01

    Roč. 14, Suppl.2 (2010), s. 26-30 ISSN 1211-7579 R&D Projects: GA MŠk(CZ) 1M0517; GA MZd(CZ) NR9180; GA MZd(CZ) NS10365; GA ČR(CZ) GA203/08/1498 Institutional research plan: CEZ:AV0Z50110509; CEZ:AV0Z40550506 Keywords : NMDA receptor * glutamate excitotoxicity * NMDA antagonists Subject RIV: FH - Neurology

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

    Science.gov (United States)

    2017-07-01

    Award Number: W81XWH-14-1-0195 TITLE: Novel Mechanism for Reducing Acute and Chronic Neurodegeneration after Traumatic Brain Injury...Purpose: The purpose of this project is to develop a radically different strategy to reduce brain glutamate excitotoxicity and treat TBI. We will...objective of reducing blood levels of glutamate. This will produce a brain -to-blood gradient of glutamate which will enhance the removal of excess

  11. Arctigenin reduces neuronal responses in the somatosensory cortex via the inhibition of non-NMDA glutamate receptors

    OpenAIRE

    Borbély, S; Jocsak, Gergely; Moldovan, Kinga; Sedlak, Lucie; Preininger, Eva; Boldizsar, Imre; Toth, Attila; Atlason, Palmi T; Molnar, Elek; Vilagi, Ildiko

    2016-01-01

    Lignans are biologically active phenolic compounds related to lignin, produced in different plants. Arctigenin, a dibenzylbutyrolactone-type lignan, has been used as a neuroprotective agent for the treatment of encephalitis. Previous studies of cultured rat cerebral cortical neurones raised the possibility that arctigenin inhibits kainate-induced excitotoxicity. The aims of the present study were: 1) to analyse the effect of arctigenin on normal synaptic activity in ex vivo brain slices, 2) t...

  12. Biological Signatures of Brain Damage Associated with High Serum Ferritin Levels in Patients with Acute Ischemic Stroke and Thrombolytic Treatment

    Directory of Open Access Journals (Sweden)

    Mónica Millán

    2008-01-01

    Full Text Available Background and purpose: Increased body iron stores have been related to greater oxidative stress and brain injury in clinical and experimental cerebral ischemia and reperfusion. We aimed to investigate the biological signatures of excitotoxicity, inflammation and blood brain barrier disruption potentially associated with high serum ferritin levels-related damage in acute stroke patients treated with i.v. t-PA.

  13. Identification and Validation of Plasma Biomarkers in California Sea Lions

    Science.gov (United States)

    2014-04-24

    clinical studies to proceed. Several studies have suggested that domoic acid causes temporal lobe epilepsy in humans, rats, and sea lions. Temporal ...neatly into expression profiles of temporal lobe epilepsy and may be specific to excitotoxic injury in sea lions or denote some novel mechanistic... lobe epilepsy is partially characterized by a widening of the dentate gyrus granular cell layer known as granular cell dispersion (GCD). However, in

  14. Ginseng Rb fraction protects glia, neurons and cognitive function in a rat model of neurodegeneration.

    Directory of Open Access Journals (Sweden)

    Kangning Xu

    Full Text Available The loss and injury of neurons play an important role in the onset of various neurodegenerative diseases, while both microgliosis and astrocyte loss or dysfunction are significant causes of neuronal degeneration. Previous studies have suggested that an extract enriched panaxadiol saponins from ginseng has more neuroprotective potential than the total saponins of ginseng. The present study investigated whether a fraction of highly purified panaxadiol saponins (termed as Rb fraction was protective for both glia and neurons, especially GABAergic interneurons, against kainic acid (KA-induced excitotoxicity in rats. Rats received Rb fraction at 30 mg/kg (i.p., 40 mg/kg (i.p. or saline followed 40 min later by an intracerebroventricular injection of KA. Acute hippocampal injury was determined at 48 h after KA, and impairment of hippocampus-dependent learning and memory as well as delayed neuronal injury was determined 16 to 21 days later. KA injection produced significant acute hippocampal injuries, including GAD67-positive GABAergic interneuron loss in CA1, paralbumin (PV-positive GABAergic interneuron loss, pyramidal neuron degeneration and astrocyte damage accompanied with reactive microglia in both CA1 and CA3 regions of the hippocampus. There was also a delayed loss of GAD67-positive interneurons in CA1, CA3, hilus and dentate gyrus. Microgliosis also became more severe 21 days later. Accordingly, KA injection resulted in hippocampus-dependent spatial memory impairment. Interestingly, the pretreatment with Rb fraction at 30 or 40 mg/kg significantly protected the pyramidal neurons and GABAergic interneurons against KA-induced acute excitotoxicity and delayed injury. Rb fraction also prevented memory impairments and protected astrocytes from KA-induced acute excitotoxicity. Additionally, microglial activation, especially the delayed microgliosis, was inhibited by Rb fraction. Overall, this study demonstrated that Rb fraction protected both

  15. Spreading Depressions as Secondary Insults after Traumatic Injury to the Human Brain

    Science.gov (United States)

    2012-09-01

    excitotoxicity.10 Since the 1990s, spontaneous waves of peri-infarct spreading depolar- isations have been appreciated as a central mechanism of the...for webappendix Articles 1060 www.thelancet.com/neurology Vol 10 December 2011 We analysed recordings offline for spreading depolar- isations ...further tissue is terminally depolarised,24,25 whereas necrosis is not observed in remote tissue, where shorter depolar- isations cause transient

  16. Role of astrocytic transport processes in glutamatergic and GABAergic neurotransmission

    DEFF Research Database (Denmark)

    Schousboe, A; Sarup, A; Bak, L K

    2004-01-01

    The fine tuning of both glutamatergic and GABAergic neurotransmission is to a large extent dependent upon optimal function of astrocytic transport processes. Thus, glutamate transport in astrocytes is mandatory to maintain extrasynaptic glutamate levels sufficiently low to prevent excitotoxic...... neuronal damage. In GABA synapses hyperactivity of astroglial GABA uptake may lead to diminished GABAergic inhibitory activity resulting in seizures. As a consequence of this the expression and functional activity of astrocytic glutamate and GABA transport is regulated in a number of ways...

  17. Quinolinic Acid - Iron(II) Complexes: Slow Autoxidation, but Enhanced Hydroxyl Radical Production in the Fenton Reaction

    Czech Academy of Sciences Publication Activity Database

    Pláteník, J.; Stopka, Pavel; Vejražka, M.; Štípek, S.

    2001-01-01

    Roč. 34, č. 5 (2001), s. 445-459 ISSN 1071-5762 R&D Projects: GA ČR GA203/97/0642; GA ČR GA309/99/0211 Institutional research plan: CEZ:AV0Z4032918 Keywords : iron chelator * reactive oxygen species * excitotoxicity Subject RIV: CA - Inorganic Chemistry Impact factor: 2.735, year: 2001

  18. Naked mole-rat cortical neurons are resistant to acid-induced cell death

    OpenAIRE

    Husson, Zoé; Smith, Ewan S

    2018-01-01

    Abstract Regulation of brain pH is a critical homeostatic process and changes in brain pH modulate various ion channels and receptors and thus neuronal excitability. Tissue acidosis, resulting from hypoxia or hypercapnia, can activate various proteins and ion channels, among which acid-sensing ion channels (ASICs) a family of primarily Na+ permeable ion channels, which alongside classical excitotoxicity causes neuronal death. Naked mole-rats (NMRs, Heterocephalus glaber) are ...

  19. Pine needle extract prevents hippocampal memory impairment in acute restraint stress mouse model.

    Science.gov (United States)

    Lee, Jin-Seok; Kim, Hyeong-Geug; Lee, Hye-Won; Kim, Won-Yong; Ahn, Yo-Chan; Son, Chang-Gue

    2017-07-31

    The Pinus densiflora leaf has been traditionally used to treat mental health disorders as a traditional Chinese medicine. Here we examined the ethnopharmacological relevance of pine needle on memory impairment caused by stress. To elucidate the possible modulatory actions of 30% ethanolic pine needle extract (PNE) on stress-induced hippocampal excitotoxicity, we adopted an acute restraint stress mouse model. Mice were orally administered with PNE (25, 50, or 100mg/kg) or ascorbic acid (100mg/kg) for 9 days, and were then subjected to restraint stress (6h/day) for 3 days (from experimental day 7-9). To evaluate spatial cognitive and memory function, the Morris water maze was performed during experimental days 5-9. Restraint stress induced the memory impairment (the prolonged escape latency and cumulative path-length, and reduced time spent in the target quadrant), and these effects were significantly prevented by PNE treatment. The levels of corticosterone and its receptor in the sera/hippocampus were increased by restraint stress, which was normalized by PNE treatment. Restraint stress elicited the hippocampal excitotoxicity, the inflammatory response and oxidative injury as demonstrated by the increased glutamate levels, altered levels of tumor necrosis factor (TNF)-α and imbalanced oxidant-antioxidant balance biomarkers. Two immunohistochemistry activities against glial fibrillary acidic protein (GFAP)-positive astrocytes and neuronal nuclei (NeuN)-positive neurons supported the finding of excitotoxicity especially in the cornu ammonis (CA)3 region of the hippocampus. Those alterations were notably attenuated by administration of PNE. The above findings showed that PNE has pharmacological properties that modulate the hippocampal excitotoxicity-derived memory impairment under severe stress conditions. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  20. Pathophysiology of perinatal hypoxic-ischemic encephalopathy – biomarkers, animal models and treatment perspectives

    Czech Academy of Sciences Publication Activity Database

    Riljak, V.; Kraf, J.; Daryanani, A.; Jiruška, Přemysl; Otáhal, Jakub

    2016-01-01

    Roč. 65, Suppl.5 (2016), S533-S545 ISSN 0862-8408 R&D Projects: GA MZd(CZ) NV15-33115A; GA ČR(CZ) GA15-08565S; GA ČR(CZ) GA14-02634S; GA MŠk LM2015062 Institutional support: RVO:67985823 Keywords : hypoxic-ischemic encephalopathy * excitotoxicity * oxidative stress * inflammation * biomarkers Subject RIV: FH - Neurology Impact factor: 1.461, year: 2016

  1. Effect of Endogenous Androgens on 17β-Estradiol-Mediated Protection after Spinal Cord Injury in Male Rats

    OpenAIRE

    Kachadroka, Supatra; Hall, Alicia M.; Niedzielko, Tracy L.; Chongthammakun, Sukumal; Floyd, Candace L.

    2010-01-01

    Several groups have recently shown that 17β-estradiol is protective in spinal cord injury (SCI). Testosterone can be aromatized to 17β-estradiol and may increase estrogen-mediated protection. Alternatively, testosterone has been shown to increase excitotoxicity in models of central nervous system (CNS) injury. These experiments test the hypothesis that endogenous testosterone in male rats alters 17β-estradiol-mediated protection by evaluating a delayed administration over a clinically relevan...

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

    Science.gov (United States)

    2016-07-01

    Sham-TBI group performed consistently near the maximum 120 seconds per trial over the 28 day testing period. TBI caused impairment of performance in...on other disciplines? The positive results of the rGOT treatment can have an impact on other neurological disorders that are mediated by glutamate...excitotoxicity such as stroke and epilepsy . What was the impact on technology transfer? The rGOT technology devised by collaborator Dr. Mirelman

  3. Protective effect of green tea polyphenol EGCG against neuronal damage and brain edema after unilateral cerebral ischemia in gerbils.

    Science.gov (United States)

    Lee, Hyung; Bae, Jae Hoon; Lee, Seong-Ryong

    2004-09-15

    Previous studies have demonstrated that a green tea polyphenol, (-)-epigallocatechine gallate (EGCG), has a potent free radical scavenging and antioxidant effect. Glutamate leads to excitotoxicity and oxidative stress, which are important pathophysiologic responses to cerebral ischemia resulting in brain edema and neuronal damage. We investigated the effect of EGCG on excitotoxic neuronal damage in a culture system and the effect on brain edema formation and lesion after unilateral cerebral ischemia in gerbils. In vitro, excitotoxicity was induced by 24-hr incubation with N-methyl-D-aspartate (NMDA; 10 microM), AMPA (10 microM), or kainate (20 microM). EGCG (5 microM) was added to the culture media alone or with excitotoxins. We examined malondialdehyde (MDA) level and neuronal viability to evaluate the effect of EGCG. In vivo, unilateral cerebral ischemia was induced by occlusion of the right common carotid artery for 30, 60, or 90 min and followed by reperfusion of 24 hr. Brain edema, MDA, and infarction were examined to evaluate the protective effect of EGCG. EGCG (25 or 50 mg/kg, intraperitoneally) was administered twice, at 30 min before and immediately after ischemia. EGCG reduced excitotoxin-induced MDA production and neuronal damage in the culture system. In the in vivo study, treatment of gerbils with the lower EGCG dose failed to show neuroprotective effects; however, the higher EGCG dose attenuated the increase in MDA level caused by cerebral ischemia. EGCG also reduced the formation of postischemic brain edema and infarct volume. These results demonstrate EGCG may have future possibilities as a neuroprotective agent against excitotoxicity-related neurologic disorders such as brain ischemia.

  4. Rat intra-hippocampal NMDA infusion induces cell-specific damage and changes in expression of NMDA and GABA(A) receptor subunits

    Czech Academy of Sciences Publication Activity Database

    Rambousek, Lukáš; Kletečková, Lenka; Kubesová, A.; Jirák, D.; Valeš, Karel; Fritschy, J.M.

    2016-01-01

    Roč. 105, Jun (2016), s. 594-606 ISSN 0028-3908 R&D Projects: GA ČR(CZ) GBP304/12/G069; GA ČR(CZ) GA14-20613S; GA ČR(CZ) GAP303/12/1464 Institutional support: RVO:67985823 Keywords : excitotoxicity * NMDA receptor * GABA A receptor * hippocampus * neuroinflammation * neurodegeneration * interneurons * spatial learning * carousel maze Subject RIV: FH - Neurology Impact factor: 5.012, year: 2016

  5. Glucose and Intermediary Metabolism and Astrocyte-Neuron Interactions Following Neonatal Hypoxia-Ischemia in Rat.

    Science.gov (United States)

    Brekke, Eva; Berger, Hester Rijkje; Widerøe, Marius; Sonnewald, Ursula; Morken, Tora Sund

    2017-01-01

    Neonatal hypoxia-ischemia (HI) and the delayed injury cascade that follows involve excitotoxicity, oxidative stress and mitochondrial failure. The susceptibility to excitotoxicity of the neonatal brain may be related to the capacity of astrocytes for glutamate uptake. Furthermore, the neonatal brain is vulnerable to oxidative stress, and the pentose phosphate pathway (PPP) may be of particular importance for limiting this kind of injury. Also, in the neonatal brain, neurons depend upon de novo synthesis of neurotransmitters via pyruvate carboxylase in astrocytes to increase neurotransmitter pools during normal brain development. Several recent publications describing intermediary brain metabolism following neonatal HI have yielded interesting results: (1) Following HI there is a prolonged depression of mitochondrial metabolism in agreement with emerging evidence of mitochondria as vulnerable targets in the delayed injury cascade. (2) Astrocytes, like neurons, are metabolically impaired following HI, and the degree of astrocytic malfunction may be an indicator of the outcome following hypoxic and hypoxic-ischemic brain injury. (3) Glutamate transfer from neurons to astrocytes is not increased following neonatal HI, which may imply that astrocytes fail to upregulate glutamate uptake in response to the massive glutamate release during HI, thus contributing to excitotoxicity. (4) In the neonatal brain, the activity of the PPP is reduced following HI, which may add to the susceptibility of the neonatal brain to oxidative stress. The present review aims to discuss the metabolic temporal alterations observed in the neonatal brain following HI.

  6. Neuroprotective effect and mechanism of daucosterol palmitate in ameliorating learning and memory impairment in a rat model of Alzheimer's disease.

    Science.gov (United States)

    Ji, Zhi-Hong; Xu, Zhong-Qi; Zhao, Hong; Yu, Xin-Yu

    2017-03-01

    Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by progressive memory decline and cognitive impairment. Amyloid beta (Aβ) has been proposed as the causative role for the pathogenesis of AD. Accumulating evidence demonstrates that Aβ neurotoxicity is mediated by glutamate excitotoxicity. Daucosterol palmitate (DSP), a plant steroid with anti-glutamate excitotoxicity effect, was isolated from the anti-aging traditional Chinese medicinal herb Alpinia oxyphylla Miq. in our previous study. Based on the anti-glutamate excitotoxicity effect of DSP, in this study we investigated potential benefit and mechanism of DSP in ameliorating learning and memory impairment in AD model rats. Results from this study showed that DSP administration effectively ameliorated Aβ-induced learning and memory impairment in rats, markedly inhibited Aβ-induced hippocampal ROS production, effectively prevented Aβ-induced hippocampal neuronal damage and significantly restored hippocampal synaptophysin expression level. This study suggests that DSP may be a potential candidate for development as a therapeutic agent for AD cognitive decline. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Creatine Protects against Excitoxicity in an In Vitro Model of Neurodegeneration

    Science.gov (United States)

    Genius, Just; Geiger, Johanna; Bender, Andreas; Möller, Hans-Jürgen; Klopstock, Thomas; Rujescu, Dan

    2012-01-01

    Creatine has been shown to be neuroprotective in aging, neurodegenerative conditions and brain injury. As a common molecular background, oxidative stress and disturbed cellular energy homeostasis are key aspects in these conditions. Moreover, in a recent report we could demonstrate a life-enhancing and health-promoting potential of creatine in rodents, mainly due to its neuroprotective action. In order to investigate the underlying pharmacology mediating these mainly neuroprotective properties of creatine, cultured primary embryonal hippocampal and cortical cells were challenged with glutamate or H2O2. In good agreement with our in vivo data, creatine mediated a direct effect on the bioenergetic balance, leading to an enhanced cellular energy charge, thereby acting as a neuroprotectant. Moreover, creatine effectively antagonized the H2O2-induced ATP depletion and the excitotoxic response towards glutamate, while not directly acting as an antioxidant. Additionally, creatine mediated a direct inhibitory action on the NMDA receptor-mediated calcium response, which initiates the excitotoxic cascade. Even excessive concentrations of creatine had no neurotoxic effects, so that high-dose creatine supplementation as a health-promoting agent in specific pathological situations or as a primary prophylactic compound in risk populations seems feasible. In conclusion, we were able to demonstrate that the protective potential of creatine was primarily mediated by its impact on cellular energy metabolism and NMDA receptor function, along with reduced glutamate spillover, oxidative stress and subsequent excitotoxicity. PMID:22347384

  8. Fast, non-competitive and reversible inhibition of NMDA-activated currents by 2-BFI confers neuroprotection.

    Directory of Open Access Journals (Sweden)

    Zhao Han

    Full Text Available Excessive activation of the N-methyl-D-aspartic acid (NMDA type glutamate receptors (NMDARs causes excitotoxicity, a process important in stroke-induced neuronal death. Drugs that inhibit NMDA receptor-mediated [Ca(2+]i influx are potential leads for development to treat excitotoxicity-induced brain damage. Our previous studies showed that 2-(2-benzofu-ranyl-2-imidazoline (2-BFI, an immidazoline receptor ligand, dose-dependently protects rodent brains from cerebral ischemia injury. However, the molecular mechanisms remain unclear. In this study, we found that 2-BFI transiently and reversibly inhibits NMDA, but not AMPA currents, in a dose-dependent manner in cultured rat cortical neurons. The mechanism of 2-BFI inhibition of NMDAR is through a noncompetitive fashion with a faster on (Kon = 2.19±0.33×10(-9 M(-1 sec(-1 and off rate (Koff = 0.67±0.02 sec(-1 than those of memantine, a gold standard for therapeutic inhibition NMDAR-induced excitotoxicity. 2-BFI also transiently and reversibly blocked NMDA receptor-mediated calcium entry to cultured neurons and provided long-term neuroprotection against NMDA toxicity in vitro. Collectively, these studies demonstrated a potential mechanism of 2-BFI-mediated neuroprotection and indicated that 2-BFI is an excellent candidate for repositioning as a drug for stroke treatment.

  9. Overexpression of GmCaM4 in soybean enhances resistance to pathogens and tolerance to salt stress

    Science.gov (United States)

    Soybean (Glycine max (L.) Merr.) is the major oilseed crop in the world and is a main source of oil and high-quality protein for both humans and animals worldwide. Plant diseases inflict heavy losses on soybean yield that negatively impact the US economy. Implicit in the high economic value of this ...

  10. The persistence to slaughter age of scars resulting from damage ...

    African Journals Online (AJOL)

    Cut wounds were persistent to slaughter as were scratch marks, with only a small percentage of scratch wounds incurred at a young age not persisting to slaughter age. Mean scar size at slaughter became smaller with an increase in age at which the wounds were inflicted, except at 13 months of age where it was assumed ...

  11. An Analysis of Benefit and Cost of Local Chicken Production By the ...

    African Journals Online (AJOL)

    Newcastle disease (ND) has high seroprevalence rate and inflicts heavy economic losses on poultry as often the case in rural poultry production. This study examined the socialeconomic characteristics of the respondents and the benefit/ cost analysis of rural chicken farmers in two local council areas of Kogi State of igeria ...

  12. Ultrastructure of antennal sensillae of the samsum ant ...

    African Journals Online (AJOL)

    Black ant (Samsum), Pachycodyla sennarrensis, stings and injects venom and inflicts allergy (a rare clinical problem) due to its local and systemic reaction, which is considered as a health hazard amongst Saudi society. Thus, black ant is a source of serious concern for the government and experts as well.

  13. Aerobic bacteria cultured from the mouth of the American opossum (Didelphis virginiana) with reference to bacteria associated with bite infections.

    OpenAIRE

    Howell, J M; Dalsey, W C

    1990-01-01

    The American opossum inflicts bite injuries both when hunted for food and when accidentally provoked when handled in captivity. This study involved aerobically culturing organisms from the mouths of seven wild opossums (Didelphis virginiana). Isolates included streptococci, coagulase-positive and -negative staphylococci, Aeromonas spp., Citrobacter freundii, Eikenella corrodens, and Escherichia coli.

  14. Aerobic bacteria cultured from the mouth of the American opossum (Didelphis virginiana) with reference to bacteria associated with bite infections.

    Science.gov (United States)

    Howell, J M; Dalsey, W C

    1990-01-01

    The American opossum inflicts bite injuries both when hunted for food and when accidentally provoked when handled in captivity. This study involved aerobically culturing organisms from the mouths of seven wild opossums (Didelphis virginiana). Isolates included streptococci, coagulase-positive and -negative staphylococci, Aeromonas spp., Citrobacter freundii, Eikenella corrodens, and Escherichia coli. PMID:2229365

  15. Mutual mortality of great horned owl and southern black racer: a potential risk of raptors preying on snakes

    Science.gov (United States)

    Roger W. Perry; Raymond E. Brown; D. Craig Rudolph

    2001-01-01

    We encountered a dead southern black racer snake (Coluber constrictor priapus) coiled around a dead Great Horned Owl (Bubo virginianus). We suggest the owl was strangled by the snake before the snake did of wounds inflicted by the owl. There are previous reports of intense physical struggle between Great Horned Owls (and...

  16. Suicide and suicide risk factors: A literature review | Masango ...

    African Journals Online (AJOL)

    Suicide can be defined as intentional self-inflicted death. 1 It is a serious cause of mortality worldwide. Suicide is considered as a psychiatric emergency and the awareness of the seriousness of suicide in our society should not be overlooked. It is a significant cause of death worldwide.1 It accounts for about 30,000 deaths ...

  17. A Pedagogy of Empathy for a World of Atrocity

    Science.gov (United States)

    Lezra, Esther

    2014-01-01

    An act of atrocity is an act of violence that is perceived to exceed the boundaries of what a legitimate punitive measure--either against an individual or a collective group of people-would be for retribution for the unjust infliction of an injury. Atrocities are enacted, experienced, witnessed, and translated. They take multiple forms. What makes…

  18. Discipline or Punish? Some Suggestions for School Policy and Teacher Practice

    Science.gov (United States)

    Yang, K. Wayne

    2009-01-01

    This article seeks to restore a counter-narrative of discipline as distinct from punishment. Punishment is retribution for an offense, an exclusionary act by which students are removed from the opportunity to learn. It is harm inflicted by an external agent as a mechanism through which outside regulation becomes internalized subjectivity. Too…

  19. 3 R's in the Marital Treatment of Alcohol Abuse.

    Science.gov (United States)

    Schlesinger, Stephen E.

    Alcohol abuse imposes financial, social, and emotional burdens on drinkers and their families. Couples suffering from alcohol-related problems who seek therapy often have expectations of retribution, restitution, and refuge. Although thoughts of retribution are difficult to elicit in therapy, non-drinking spouses often expect to inflict pain on…

  20. ASR 2.indd

    African Journals Online (AJOL)

    hilarybenjamin

    2010-08-30

    Aug 30, 2010 ... Akiwowo offers a view of sociology of knowledge which defends a perspective of man .... contemporary problems which in the present period are self inflicted. ... defense of a thought which is often used to define wrongly the ...

  1. Working to Alleviate Gendered Violence on College Campuses by Designing Public Service Announcement Storyboards

    Science.gov (United States)

    Staggers, Sydney M.; Myers, Scott A.

    2011-01-01

    Gendered violence is considered to be the "physical, verbal, emotional, sexual, and visual brutality that is inflicted disproportionately or exclusively on members of one sex". According to the World Health Organization (WHO, 2010), gendered violence is a major public health concern that often goes unnoticed because it takes place in private…

  2. The Coast Artillery Journal. Volume 66, Number 6, June 1927

    Science.gov (United States)

    1927-06-01

    of the Paris and the Jaime I inflicted little damage on the Riffian works, failed to demoralize the defenders, and, had not Abdel-Krim scattered his...researches of Sabine and Watson. Not tbe least important part of the book is the bibliographical data, which are carefully indexed under many subjects

  3. Acute endocrine correlates of attack by lactating females in male mice: effects on plasma prolactin, luteinizing hormone and corticosterone levels.

    Science.gov (United States)

    Broida, J; Michael, S D; Svare, B

    1984-05-01

    Immediately following defeat inflicted by lactating Rockland-Swiss (R-S) albino mice, adult R-S male mice exhibited significant reductions in circulating prolactin (PRL) and luteinizing hormone (LH), but not corticosterone (CORT). These results suggest that acute neuroendocrine responses to intersex competition may be as dramatic as those previously reported for intermale encounters.

  4. Using an in vitro system for maintaining Varroa destructor mites on Apis mellifera hosts: Studies of mite longevity and feeding behavior

    Science.gov (United States)

    Varroa destructor mites (Vd) are ectoparasites of Apis mellifera honey bees, and the damage they inflict on hosts is a likely causative factor of recent poor honey bee colony performance. Much research has produced an arsenal of control agents against Vd, which have become resistant to many chemical...

  5. A Study on Technical High School Teachers' Views Concerning Corporal Punishment

    Science.gov (United States)

    Tas, Said

    2016-01-01

    Corporal punishment is defined as inflicting pain on body of someone who presents undesired behavior or does not present expected behavior. In the developed world, experiencing information society, corporal punishment is still in the agenda in educational system in Turkey. In this study, it was aimed to determine technical high school teachers'…

  6. The Art Association/Higher Education Partnership: Implementing Residential Professional Development

    Science.gov (United States)

    Charland, William

    2006-01-01

    In-service professional development in education began informally in the early nineteenth-century as a means of disseminating classroom management techniques, specifically addressing ways in which corporal punishment could be delivered to a child without inflicting serious injury. This initial effort paralleled a concern regarding children's…

  7. Forest Products: Apparatus for Removing Bark from Whole Logs

    International Nuclear Information System (INIS)

    Poole, Lauren; Recca, Lee

    1999-01-01

    Order this fact sheet now to learn how replacing the ''closed drum'' debarking technology method used in the forest industry with the ''open drum'' method saves time and production costs, and increases the economic value of wood products by inflicting less damage on logs so that they can be used for high-value economic products

  8. 32 CFR 11.6 - Crimes and elements.

    Science.gov (United States)

    2010-07-01

    ... damaged or endangered the physical or mental health or appearance of such person or persons. (D) The... substance or a weapon that releases a substance as a result of its employment; (B) The substance was such...) The accused inflicted severe physical or mental pain or suffering upon one or more persons; (B) The...

  9. 75 FR 12566 - Agency Information Collection Activities: Existing Collection; Comments Requested

    Science.gov (United States)

    2010-03-16

    ... appearances and bringing them back to detention, discharging inmates at the behest of the court or other... previous year to June 30 of the current collection year: the number of inmate-inflicted physical assaults...: how many jail operation employees did the facility hire for employment; how many jail operation...

  10. The impact of mechanical log surface damage on chip size ...

    African Journals Online (AJOL)

    Mechanised harvesting operations are becoming more prevalent in South Africa with the realisation that motormanual and manual harvesting operations pose significant health and safety risks to workers. The damage inflicted by single-grip harvester feed rollers and delimbing knives on log surfaces during debranching ...

  11. Livestock Husbandry and Snow Leopard Conservation

    NARCIS (Netherlands)

    Mohammad, Ghulam; Mostafawi, Sayed Naqibullah; Dadul, Jigmet; Rosen, Tatjana; Mishra, Charudutt; Bhatnagar, Yash Veer; Trivedi, Pranav; Timbadia, Radhika; Bijoor, Ajay; Murali, Ranjini; Sonam, Karma; Thinley, Tanzin; Namgail, Tsewang; Prins, Herbert H.T.; Nawaz, Muhammad Ali; Ud Din, Jaffar; Buzdar, Hafeez

    2016-01-01

    Livestock depredation is a key source of snow leopard mortality across much of the species' range. Snow leopards break into livestock corrals, killing many domestic animals and thereby inflicting substantial economic damage. Locals may retaliate by killing the cat and selling its parts.

  12. Non-fatal Suicidal and Life-threatening Behavior among 13- to 17-Year Old Adolescents Seeking Emergency Medical Care.

    Science.gov (United States)

    Deykin, Eva Y.; And Others

    1985-01-01

    In suicidal behavior emergency room admissions of adolescents at Brockton Hospital (Massachusetts), females predominated over males by almost two to one. Also, repeat episodes of self-inflicted injury were common among females. The type of the initial episode was a powerful predictor of a repeat occurrence. (Author/KH)

  13. Feeding, growth and metabolism of the marine heterotrophic dinoflagellate Gyrodinium dominans

    DEFF Research Database (Denmark)

    Schmoker, Claire; Thor, Peter; Hernández-león, Santiago

    2011-01-01

    may inflict high metabolic costs. Gross growth efficiencies (GGEs), determined for G. dominans in both food availability conditions, were within the range of values reported for other heterotrophic protozoans, and while GGE decreased when concentrations of food were high in organisms fed a single...... pulse of food, the opposite was observed in organisms acclimatized to a constant level of food....

  14. Paternal Alcoholism: Consequences for Female Children

    Science.gov (United States)

    Dehn, Julia

    2010-01-01

    The consequences of substance abuse and addiction are profound and depredating. The desolation is incalculable in estimating the psychological damage and trauma inflicted on the children of addicted parents. According to studies and statistics gathered by the National Association for Children of Alcoholics, "there are more than 20 million children…

  15. Oceanography for Divers: Hazardous Marine Life. Diver Education Series.

    Science.gov (United States)

    Somers, Lee H.

    Most people find that the life of the marine environment is beautiful and fascinating. Of the thousands of marine animals and plants, relatively few constitute a real hazard to the diver. Although some species are dangerous and may, in some instances, inflict serious wounds, with a few exceptions marine animals are not aggressive. Most…

  16. 75 FR 76295 - Defense Federal Acquisition Regulation Supplement; Restrictions on the Use of Mandatory...

    Science.gov (United States)

    2010-12-08

    ..., including assault and battery, intentional infliction of emotional distress, false imprisonment, or.... Regulatory Flexibility Act DoD has prepared a final regulatory flexibility analysis consistent with 5 U.S.C. 604. A copy of the analysis may be obtained from the point of contact specified herein. The analysis...

  17. 75 FR 27946 - Defense Federal Acquisition Regulation Supplement; Restrictions on the Use of Mandatory...

    Science.gov (United States)

    2010-05-19

    ... harassment, including assault and battery, intentional infliction of emotional distress, false imprisonment... Flexibility Act DoD has prepared an initial regulatory flexibility analysis consistent with 5 U.S.C. 603. A copy of the analysis may be obtained from the point of contact specified herein. The analysis is...

  18. Assessing the information desire of patients with advanced cancer by providing information with a decision aid, which is evaluated in a randomized trial: a study protocol

    NARCIS (Netherlands)

    Oostendorp, L.J.M.; Ottevanger, P.B.; Graaf, W.T.A. van der; Stalmeier, P.F.M.

    2011-01-01

    BACKGROUND: There is a continuing debate on the desirability of informing patients with cancer and thereby involving them in treatment decisions. On the one hand, information uptake may be hampered, and additional stress could be inflicted by involving these patients. On the other hand, even

  19. Antidepressants for Children and Teens

    Science.gov (United States)

    ... et al. Antidepressant drugs and the risk of suicide in children and adolescents. Pediatric Drugs. 2014;16:115. Gibbons RD, et al. Antidepressant treatment and suicide attempts and self-inflicted injury in children and adolescents. Pharmacoepidemiology and Drug Safety. 2015;24: ...

  20. Hepatic Enzyme Decline after Pediatric Blunt Trauma: A Tool for Timing Child Abuse?

    Science.gov (United States)

    Baxter, Amy L.; Lindberg, Daniel M.; Burke, Bonnie L.; Shults, Justine; Holmes, James F.

    2008-01-01

    Objectives: Previous research in adult patients with blunt hepatic injuries has suggested a pattern of serum hepatic transaminase concentration decline. Evaluating this decline after pediatric blunt hepatic trauma could establish parameters for estimating the time of inflicted injuries. Deviation from a consistent transaminase resolution pattern…

  1. Folic acid supplementation is not the sole factor in determining ...

    African Journals Online (AJOL)

    user user

    2012-07-10

    Jul 10, 2012 ... diabetes drugs, such as metformin to combat metabolic syndromes (Yanovski et al., 2011). Psychologically, 30% of adults inflicted with NTDs are isolated .... reduction of NTD cases in Argentina, Brazil and Chile, respectively after years of post- fortification. However, the author suggested this study will only ...

  2. Dermatitis artefacta

    DEFF Research Database (Denmark)

    Økland, Camilla; Petersen, Niels Erik; Bygum, Anette

    2016-01-01

    Dermatitis artefacta is a self-inflicted skin disease with a multifactorial aetiology. The condition can be a symptom of an underlying psychiatric condition or a sign of psycho-social stressors. This paper gives an updated view on dermatitis artefacta. The majority of the patients have some form...

  3. Comparative Analysis of Termiteria and Surrounding Soil

    African Journals Online (AJOL)

    Magashi

    2013-06-01

    Jun 1, 2013 ... or are important nutrients hot-spots for plants and their associated fauna. Therefore, it has a high ecological role which cannot be disregarded. Generally, termites are affected by the environment where they live when inflicting physical and chemical changes in the plant-litter- soil system. They do so through ...

  4. Reciprocal signals between microglia and neurons regulate alpha-synuclein secretion by exophagy through a neuronal cJU-N-Nterminal kinase-signaling axis

    DEFF Research Database (Denmark)

    Christensen, Dan Ploug; Ejlerskov, Patrick; Rasmussen, Izabela

    2016-01-01

    implicate stress kinases of the JNK family in the regulation of exophagy and release of alpha-SNC following endogenous or exogenous stimulation. In a wider scope, our results imply that microglia not only inflict bystander damage to neurons in late phases of inflammatory brain disease but may also be active...

  5. Long-term results of incisional hernia repair with retromuscular mesh

    Directory of Open Access Journals (Sweden)

    Miran Rems

    2011-04-01

    Conclusions: The retromuscular mesh placement for postoperative hernia repair results in a low rate of recurrences and postoperative complications. Complications are more common in patients admitted due to incarceration and in patients having suffered from stoma. Pain inflicted by postoperative hernia repair is an underrated with treatment results.

  6. Curriculum as Conversation: Vulnerability, Violence, and Pedagogy in Prison

    Science.gov (United States)

    O'Donnell, Aislinn

    2015-01-01

    It is difficult to respond creatively to humiliation, affliction, degradation, or shame, just as it is difficult to respond creatively to the experience of undergoing or inflicting violence. In this article Aislinn O'Donnell argues that if we are to think about how to address gun violence--including mass shootings- in schools, then we need to talk…

  7. Moving beyond a Destructive Past to a Decolonised and Inclusive Future: The Role of "Ubuntu"-Style Education in Providing Culturally Relevant Pedagogy for Namibia

    Science.gov (United States)

    Biraimah, Karen L.

    2016-01-01

    Namibia has one of the most dehumanising and destructive colonial pasts of any nation in Africa, or, for that matter, the world. Before colonisation, the area now known as Namibia was home to diverse cultural groups. The successive colonial regimes of Germany and South Africa inflicted genocide, brutality and apartheid on the region. Namibia…

  8. Combating a Global Threat to a Clonal Crop: Banana Black Sigatoka Pathogen Pseudocercospora fijiensis (Synonym Mycosphaerella fijiensis) Genomes Reveal Clues for Disease Control

    NARCIS (Netherlands)

    Arango Isaza, Rafael E.; Diaz-Trujillo, Caucasella; Dhillon, Braham; Aerts, Andrea; Carlier, Jean; Crane, Charles F.; V. de Jong, Tristan; de Vries, Ineke; Dietrich, Robert; Farmer, Andrew D.; Fortes Fereira, Claudia; Garcia, Suzana; Guzman, Mauricio; Hamelin, Richard C.; Lindquist, Erika A.; Mehrabi, Rahim; Quiros, Olman; Schmutz, Jeremy; Shapiro, Harris; Reynolds, Elizabeth; Scalliet, Gabriel; Souza Manoel, Jr.; Stergiopoulos, Ioannis; Van der Lee, Theo A. J.; De Wit, Pierre J. G. M.; Zapater, Marie-Françoise; Zwiers, Lute-Harm; Grigoriev, Igor V.; Goodwin, Stephen B.; Kema, Gert H. J.

    2016-01-01

    Black Sigatoka or black leaf streak disease, caused by the ascomycete fungus Pseudocercospora fijiensis, inflicts huge costs on banana producers, due to crop losses and expenses for disease control. The global banana export trade relies on Cavendish clones that are highly susceptible to P.

  9. Pattern of domestic violence among pregnant women in Jos, Nigeria ...

    African Journals Online (AJOL)

    Background: Domestic violence is a global concern. Domestic violence refers to violence inflicted on a partner (mostly females) within the context of the family or an intimate relationship. It is known to be responsible for numerous hospital visits undertaken by women, although they mostly fail to complain of abuse. There is ...

  10. Effectiveness of Dialectical Behavior Therapy in a Community Mental Health Center

    Science.gov (United States)

    Comtois, Katherine Anne; Elwood, Lynn; Holdcraft, Laura C.; Smith, Wayne R.; Simpson, Tracy L.

    2007-01-01

    Dialectical behavior therapy (DBT) has been shown to be effective in randomized controlled trials with women with borderline personality disorder and histories of chronic self-inflicted injury including suicide attempts. The present study is a pre-post replication of a comprehensive DBT program in a community mental health center for individuals…

  11. evaluation of native fungal isolates of metrahizium anisopliae var

    African Journals Online (AJOL)

    preferred customer

    damage to honey bees (Desalegn Begna, 2001;. Desalegn Begna and Amsalu Bezabeh, 2001). Damage to honey bees is the result of the direct impacts of GWM larvae and the indirect effects inflicted by adult wax moths. The damage by larvae is manifested in such a way that they eat and destroy beeswax combs, form ...

  12. Birds sacrifice oxidative protection for reproduction

    NARCIS (Netherlands)

    Wiersma, P; Selman, C; Speakman, [No Value; Verhulst, S; Speakman, John R.

    2004-01-01

    Oxidative metabolism has reactive oxygen species (ROS) as unavoidable by-products, and the damage ROS inflicts on DNA, proteins and lipids is considered to be a major agent of senescence. Increasing reproductive effort accelerates senescence, but whether reproductive effort is increased at the

  13. 76 FR 54978 - Special Immigrant Juvenile Petitions

    Science.gov (United States)

    2011-09-06

    ... physical or mental injury upon the child and sexual abuse or exploitation of a child. The law also... abuse, neglect (including severe and general neglect), sexual abuse, and emotional abuse. The basic definition of child abuse or neglect includes physical injury inflicted by other than accidental means upon a...

  14. Rescue Emergency Drone (RED) for Fast Response to Medical Emergencies Due to Traffic Accidents

    DEFF Research Database (Denmark)

    Mehmood, Saqib; Kristensen, Anders Schmidt; Ahmed, Shakeel

    2017-01-01

    of inflicted persons can be reduced significantly. Smart and innovative technologies can play a pivotal role to respond faster to traffic crash emergencies comparing conventional means of transportation. For instance, Rescue Emergency Drone (RED) can provide faster and real-time crash site risk assessment...

  15. Laser system for identification, tracking, and control of flying insects

    Science.gov (United States)

    Flying insects are common vectors for transmission of pathogens and inflict significant harm on humans in large parts of the developing world. Besides the direct impact to humans, these pathogens also cause harm to crops and result in agricultural losses. Here, we present a laser-based system that c...

  16. Influence of anoxia on the induction of mutations by phenylalanine radicals during gamma-irradiation of plasmid DNA in aqueous solution.

    NARCIS (Netherlands)

    Kuipers, G.K.; Slotman, B.J.; Reitsma-Wijker, CA; Andel, R.J.; Poldervaart, H.A.; Lafleur, M.V.M.

    2004-01-01

    When DNA is irradiated in aqueous solution, most of the damage is inflicted by water-derived radicals. This is called the indirect effect of ionizing radiation. However in whole cells not only the primary formed water radicals play a role, because some cellular compounds form secondary radicals

  17. Rationalised panics : The consequences of strategic uncertainty during financial crises

    NARCIS (Netherlands)

    Daniëls, T.

    2009-01-01

    This dissertation is about currency and related financial crises such as the contagious Southeast Asian crisis of 1997 or Argentina's collapse and default in 2001. It argues that key to understanding these crises is the doubt that they inflict on market participants about the intentions and actions

  18. ISSN 2070-0083

    African Journals Online (AJOL)

    FIRST LADY

    Obekpa (2001) view child abuse as any condition injurious to physical or emotional health that has been ... defines it as a non-accidental injury inflicted on a child by a parent or guardian. ... potential for or has actually caused serious emotional cognitive, mental or behavioral .... Child abuse and parenting styles in. Nigerian ...

  19. Donor-derived circulating endothelial cells after kidney transplantation

    NARCIS (Netherlands)

    Popa, ER; Kas-Deelen, AM; Hepkema, BG; van Son, WJ; The, TH; Harmsen, MC

    2002-01-01

    Background. In solid-organ transplantation, the allograft vasculature, in particular the endothelium, is prone to injury inflicted by peritransplantational and posttransplantational factors. Previously, we have shown that circulating endothelial cells (cEC) can be detected in the peripheral blood of

  20. Relational Aggression in School Settings: Definition, Development, Strategies, and Implications

    Science.gov (United States)

    Dailey, Alicia L.; Frey, Andy J.; Walker, Hill M.

    2015-01-01

    Relational aggression (RA) is a nonphysical form of aggression whereby the perpetrator's goal is to inflict or threaten damage to relationships, including harm to the target child's social standing or reputation. This form of aggression may result in long-term psychological harm to victims. This article defines RA, summarizes its development, and…

  1. Bruising in children: Evaluation in cases of suspected non ...

    African Journals Online (AJOL)

    Background: Bruises commonly occur in children and are often due to minor accidental injuries. However, they can also occur in bleeding disorders or inflicted injuries (physical abuse) and is often the most common visible manifestation of child physical abuse. Objective: This paper aims at highlighting the factors that ...

  2. A rapid and non-destructive method to assess leaf injury caused by the cassava green mite, Mononychellus tanajoa (Bondar) (Acarina: Tetranychidae)

    DEFF Research Database (Denmark)

    Tomkiewicz, Jonna; Skovgård, Henrik; Nachman, Gösta

    1993-01-01

    . The difference in photosynthetically active area that arises between uninjured and injured plants over a period of time provides a measure of spider mite injury that can be related to growth and yield. The method integrates the injury inflicted over a period of time, allows successive observations of the same...

  3. Study of the reduced indium oxide (In2O3)/mc-silicon:hydrogen interface by means of factor analysis

    NARCIS (Netherlands)

    Nijs, de J.M.M.; Aarts, R.G.K.M.

    1991-01-01

    The overgrowth of an In2O3 layer by a µc-Si:H layer, deposited by means of plasma-enhanced chemical vapour deposition, will inflict the reduction of the In2O3. AES is combination with Ar+ depth profiling is used for the study of the interfacial deterioration that takes place. The results of a factor

  4. Understanding the Anorectic Student

    Science.gov (United States)

    Rothenberg, Susan A.

    1976-01-01

    A teacher may be the first to recognize the symptoms of self-inflicted starvation, anorexia nervosa, a psychological complex malady, should be supportive of the child and alert the school principal to the problem, which should be dealt with by parents and a psychiatrist. (JD)

  5. Research needs in the Transkei and Ciskei coastal zone

    CSIR Research Space (South Africa)

    Branch, GM

    1988-01-01

    Full Text Available , highlighting the damage that may be inflicted if insufficient power is provided to police the regulations. The same Act makes provision for the licencing and registration of skiboats to control their use in our water systems. It is, however, difficult...

  6. [The historical aspects of the notion of "self-striking" in the Russian- and foreign-language literature].

    Science.gov (United States)

    Ivanov, I N

    2015-01-01

    This article was designed to illustrate specific features of the injuries inflicted by the sharp objects as a result of the so-called self-striking based on the examples from the historical and literary works. The forensic medical characteristics of such cases are provided.

  7. Designing Trojan Horses | Center for Cancer Research

    Science.gov (United States)

    Waging battle against cancer cells without inflicting damage on normal tissue has long been a goal for cancer treatment. A new type of drug called immunotoxins may help make this goal a reality. Much like the Greeks used a wooden horse to get soldiers inside the gates of Troy, immunotoxins use clever genetic engineering to get a lethal toxin inside cancer cells. Each

  8. Targeting the Parasite's DNA with Methyltriazenyl Purine Analogs Is a Safe, Selective, and Efficacious Antitrypanosomal Strategy

    NARCIS (Netherlands)

    Rodenko, B.; Wanner, M.J.; Alkhaldi, A.A.M.; Ebiloma, G.U.; Barnes, R.L.; Kaiser, M.; Brun, R.; McCulloch, R.; Koomen, G.J.; de Koning, H.P.

    2015-01-01

    The human and veterinary disease complex known as African trypanosomiasis continues to inflict significant global morbidity, mortality, and economic hardship. Drug resistance and toxic side effects of old drugs call for novel and unorthodox strategies for new and safe treatment options. We designed

  9. Fruit fly infestation in mango: A threat to the Horticultural sector in ...

    African Journals Online (AJOL)

    Fruit flies (Diptera: Tephtritidae) are one of the most important insect pests to fruits worldwide. In Uganda, fruit flies have inflicted considerable yield losses especially in mangos (Mangifera indica L.), However, there has been no recent assessment of the associated economic damage impact despite the outcries from the ...

  10. Cerebral damage caused by nail gun injury

    Directory of Open Access Journals (Sweden)

    Andersen Chris Hedeman

    2016-06-01

    Full Text Available Background Accidents with nail guns are rather common, especially in the construction industry. Most injuries involve the extremities and several present with intracerebral injuries. When the patient is unconscious, it can be a big challenge to determine whether the injury is an accident, self-inflicted or a criminal act.

  11. Extensive tissue damage of bovine ovaries after bipolar ovarian drilling compared to monopolar electrocoagulation or carbon dioxide laser

    NARCIS (Netherlands)

    Hendriks, M.L.; van der Valk, P.; Lambalk, C.B.; Broeckaert, M.A.M.; Homburg, R.R.; Hompes, P.G.A.

    2010-01-01

    Objective: To evaluate the size of ovarian damage caused by ovarian drilling in polycystic ovary syndrome, the amount of inflicted damage was assessed for the most frequently used ovarian drilling techniques. Design: Experimental prospective design. Setting: University clinic. Patient(s): Six fresh

  12. Taurolidine-citrate-heparin lock reduces catheter-related bloodstream infections in intestinal failure patients dependent on home parenteral support

    DEFF Research Database (Denmark)

    Tribler, Siri; Brandt, Christopher F.; Petersen, Anne H.

    2017-01-01

    Background: In patients with intestinal failure who are receiving home parenteral support (HPS), catheter-related bloodstream infections (CRBSIs) inflict health impairment and high costs.Objective: This study investigates the efficacy and safety of the antimicrobial catheter lock solution, taurol...

  13. The Mechanisms of Centalla asiatica's Wound Healing Molecule ...

    African Journals Online (AJOL)

    Asiaticoside is a triterpene obtained from Centella asiatica and demonstrated to have healing potential against various wound models. Wounds are inflicted for constructive reasons even though more often they are results of accidents. This work aims at identifying molecular targets which account for the therapeutic results ...

  14. Recognizing and managing sapstreak disease of sugar maple

    Science.gov (United States)

    David R. Houston; David R. Houston

    1993-01-01

    Sapstreak disease, a potentially serious problem of sugarbushes and forest stands, occurs when the causal fungus, Ceratocystis virescens, invades the sapwood of roots and bases of stems through wounds inflicted during logging, saphauling, or other activities. Describes how to recognize the disease, the factors that affect its occurrence and development, and management...

  15. Case Study: Severe Self-Injurious Behavior in Comorbid Tourette's Disorder and OCD

    Science.gov (United States)

    Hood, Korey K.; Baptista-Neto, Lourival; Beasley, Pamela J.; Lobis, Robert; Pravdova, Iva

    2004-01-01

    This case report describes the successful treatment of severe self-injurious behavior in a 16-year-old adolescent with Tourette's disorder and obsessive-compulsive disorder. Treatment is described from initial presentation to the emergency department for severe self-inflicted oral lacerations through discharge from the inpatient psychiatric…

  16. Tri-trophic interactions affect density dependence of seed fate in a tropical forest palm

    NARCIS (Netherlands)

    Visser, Marco D.; Muller-Landau, Helene C.; Wright, S. Joseph; Rutten, Gemma; Jansen, Patrick A.

    2011-01-01

    Natural enemies, especially host-specific enemies, are hypothesised to facilitate the coexistence of plant species by disproportionately inflicting more damage at increasing host abundance. However, few studies have assessed such Janzen-Connell mechanisms on a scale relevant for coexistence and no

  17. Developing a model for measuring fear of pain in Norwegian samples: The Fear of Pain Questionnaire Norway

    DEFF Research Database (Denmark)

    Vambheim, Sara M; Lyby, Peter Solvoll; Aslaksen, Per M

    2017-01-01

    Fear of pain is highly correlated with pain report and physiological measures of arousal when pain is inflicted. The Fear of Pain Questionnaire III (FPQ-III) and The Fear of Pain Questionnaire Short Form (FPQ-SF) are self-report inventories developed for assessment of fear of pain (FOP). A previous...

  18. Promoting Reduced-Impact Logging in Tropical Developing Countries: A Success Story of Technology Transfer

    Science.gov (United States)

    Dennis P. Dykstra

    2007-01-01

    Industrial timber harvesting operations commonly employ heavy machinery and thus have the potential to inflict significant damage on soils, streams, and residual vegetation. Impacts associated with such operations have been especially troubling in many tropical countries, where mature trees often have large crowns capable of destroying other trees when they fall; soils...

  19. Vaginismus : Heightened Harm Avoidance and Pain Catastrophizing Cognitions

    NARCIS (Netherlands)

    Borg, Charmaine; Peters, Madelon L.; Schultz, Willibrord Weijmar; de Jong, Peter J.

    Introduction. Catastrophic appraisal of experienced pain may promote hypervigilance and intense pain, while the personality trait of harm avoidance (HA) might prevent the occurrence of correcting such experiences. Women inflicted with vaginismus may enter a self-perpetuating downward spiral of

  20. Forensic aspects of gene expression signatures for age determination in bruises as evaluated in an experimental porcine model

    DEFF Research Database (Denmark)

    Barington, Kristiane; Jensen, Henrik Elvang; Skovgaard, Kerstin

    2017-01-01

    Determining the age of bruises and the force used to inflict the trauma is of crucial importance in both human and veterinary forensic pathology. In the present study, the expression of more than 50 different genes in subcutaneous fat and muscle tissue from experimental bruises in pigs...... provide valuable information in human forensic science....

  1. A Study of Preventing Email (Spear) Phishing by Enabling Human Intelligence

    NARCIS (Netherlands)

    M.S. Bargh; A. Padmos; R. Choenni; F. Jansen; N. Stembert

    2015-01-01

    Cyber criminals use phishing emails in high-volume and spear phishing emails in low volume to achieve their malicious objectives. Hereby they inflict financial, reputational, and emotional damages on individuals and organizations. These (spear) phishing attacks get steadily more sophisticated as

  2. First report of clinical presentation of a bite by a running spider ...

    African Journals Online (AJOL)

    This article describes the clinical progression of symptoms over a period of 5 days of a bite inflicted by a Philodromus sp. spider. Commonly known as 'running spiders', these are not considered to be harmful to humans. This report, however, is the first description of an actual bite by a member of this group of spiders ...

  3. Conflict and Society: Advances in Research

    DEFF Research Database (Denmark)

    Grassing, Erella; Horstmann, Alexander; Segal, Lotte Buch

    2015-01-01

    Violence, defined as the intentional inflicting of injury and damage, seems to always have been a fact of human life. Whether in the shape of raids, ambushes, wars, massacres, genocides, insurgences, terrorism, or gang assaults, socially organized violence, that is, human groups orchestrating and...... icts focused on international relations and great power politics....

  4. Intentional intravenous mercury injection | Yudelowitz | South African ...

    African Journals Online (AJOL)

    Intravenous mercury injection is rarely seen, with few documented cases. Treatment strategies are not clearly defined for such cases, although a few options do show benefit. This case report describes a 29-year-old man suffering from bipolar disorder, who presented following self-inflicted intravenous injection of mercury.

  5. Movements, Markets and Fields: The Effects of Anti-Sweatshop Campaigns on U.S. Firms, 1993-2000

    Science.gov (United States)

    Bartley, Tim; Child, Curtis

    2011-01-01

    How do social movements influence corporations? Recent work suggests that movements can inflict material damage on their targets and shape categories of evaluation in organizational fields. Extending these ideas, we examine the effects of anti-sweatshop campaigns on sales, stock performance, reputation and specialized ratings of U.S. firms, using…

  6. Socio-demographic and behavioural correlates of the malaria ...

    African Journals Online (AJOL)

    ... the equator, including much of Sub-Saharan Africa, Asia, and the Americas. It inflicts significant costs on households and on the economy of malaria endemic ... Mothers were the primary care-giver of these subjects; accounting for 79.3%.

  7. Protein Dynamics in Mammalian Genome Maintenance

    NARCIS (Netherlands)

    A. Zotter (Angelika)

    2008-01-01

    textabstractThe integrity of the genome, carrier of the blueprint for each organism, is under constant attack from environmental as well as endogenous DNA damaging agents. An agent with substantial impact on our DNA is the UV-fraction of sunlight. It inflicts bulky DNA lesions, which can interfere

  8. Euripides' Medea: a psychodynamic model of severe divorce pathology.

    Science.gov (United States)

    Jacobs, J W

    1988-04-01

    Analysis of Euripides' play, Medea, and a divorcing family suggests that divorce between a narcissistically scarred, embittered, dependent woman and a pathologically narcissistic, devaluing man may lead to the mother's attempt to sever father-child contact as a means of revenging the injury inflicted on her by the loss of a selfobject, her hero-husband.

  9. A re-reading of John 8:1–11 from a pastoral liberative perspective ...

    African Journals Online (AJOL)

    This article intends to unmask collusion with patriarchal societies including the Jewish society in Jesus' time by mapping out the forms of harassment and embarrassment inflicted upon women. The study shows how pastoral care can help victims of oppression. A re-reading of John 8:1–11 will inform the, how can the verses ...

  10. Transcriptomic analysis of the Olea europaea L. roots during the Verticillium dahliae early infection process

    DEFF Research Database (Denmark)

    Jiménez-Ruiz, Jaime; Pérez, Maria De la O Leyva; Schilirò, Elisabetta

    2017-01-01

    Olive cultivation is affected by a wide range of biotic constraints. Verticillium wilt of olive is one of the most devastating diseases affecting this woody crop, inflicting major economic losses in many areas, particularly within the Mediterranean Basin. Little is known about gene-expression cha...

  11. Use of remote sensing and molecular markers to detect toxic ...

    African Journals Online (AJOL)

    Jane

    2010-12-20

    Dec 20, 2010 ... exposure of the cells to high radiation, inflicting irreversible damage to the genetic constitution of the upper layer of ... (12,300 µg/l) in the absence of sunlight irradiation and photolysis by UV light. ... and eye irritation, with the latter symptoms, possibly as a ... the crust layer and their effect on the synthesis of.

  12. Matran (50% clove oil) broadcast application for broadleaf weed control in spring-transplanted onions

    Science.gov (United States)

    Although corn gluten meal has shown promise as an early-season pre-emergent organic herbicide in sweet onion production, uncontrolled weeds can inflict serious yield reductions by the end of the growing season. Research was conducted in southeast Oklahoma to determine the effectiveness of Matran EC...

  13. Safety in the Operating Theatre | a Multi Factor Approach for Patients and Teams

    NARCIS (Netherlands)

    Wauben, L.S.G.L.

    2010-01-01

    Due to the advances in high-tech technology in the operating theatre, the increased number of persons involved, and the increased complexity of surgical procedures, medical errors are inflicted. To answer the main question: How to improve patient safety in the operating theatre during surgery? this

  14. Rescue Emergency Drone for Fast Response to Medical Emergencies Due to Traffic Accidents

    DEFF Research Database (Denmark)

    Kristensen, Anders Schmidt; Ahsan, Dewan; Mehmood, Saqib

    2017-01-01

    of inflicted persons can be reduced significantly. Smart and innovative technologies can play a pivotal role to respond faster to traffic crash emergencies comparing conventional means of transportation. For instance, Rescue Emergency Drone (RED) can provide faster and real-time crash site risk assessment...

  15. Decubital shoulder ulcers in sows - a review of classification, pain and welfare consequences

    DEFF Research Database (Denmark)

    Herskin, Mette S; Bonde, Marianne; Jørgensen, Erik

    2011-01-01

    Decubital shoulder ulcers are lesions on the shoulders of sows kept in production systems, reported to have a relatively high prevalence, and to some extent be comparable with human pressure ulcers. In sows, the ulcers are caused by pressure inflicted by the flooring, leading to oxygen deficiency...

  16. Mechanisms of cytolysin-induced cell damage -- a role for auto- and paracrine signalling

    DEFF Research Database (Denmark)

    Skals, Marianne Gerberg; Prætorius, Helle

    2013-01-01

    Cytolysins inflict cell damage by forming pores in the plasma membrane. The Na(+) conductivity of these pores results in an ion influx that exceeds the capacity of the Na(+) /K(+) -pump to extrude Na(+) . This net load of intracellular osmolytes results in swelling and eventual lysis of the attac...

  17. Ecology, life history and management of tropilaelaps mites

    Science.gov (United States)

    Parasitic mites are the major threat of the Western honey bee, Apis mellifera. For much of the world, Varroa destructor single-handedly inflicts unsurmountable problems to A. mellifera beekeeping. However, A. mellifera in Asia is also faced with another genus of destructive parasitic mite, Tropilae...

  18. Exploring the Link between Corporal Punishment and Children's Cruelty to Animals.

    Science.gov (United States)

    Flynn, Clifton P.

    1999-01-01

    Study of college undergraduates (N=267) examined the relationship between corporal punishment inflicted by parents and perpetration of animal abuse. Analyses showed that the association between fathers' corporal punishment and sons' childhood animal cruelty persisted after controlling for child abuse, father-to-mother violence, and father's…

  19. Corporal Punishment in Schools and Fundamental Human Rights: A South African Perspective.

    Science.gov (United States)

    Prinsloo, Justus

    In many western countries, corporal punishment has been abolished as a form of punishment in criminal trials and in schools. Under South African common law, persons entitled to enforce discipline may inflict corporal punishment within certain guidelines established by the Supreme Court. For the first time in the Republic of South Africa (RSA), the…

  20. 29 CFR 2590.702 - Prohibiting discrimination against participants and beneficiaries based on a health factor.

    Science.gov (United States)

    2010-07-01

    ...-inflicted injuries or injuries sustained in connection with attempted suicide. Because of depression.... In this Example 1, the suicide attempt is the result of a medical condition (depression). Accordingly... full-time in an institution of higher learning (full-time students)). There is no evidence to suggest...

  1. 45 CFR 146.121 - Prohibiting discrimination against participants and beneficiaries based on a health factor.

    Science.gov (United States)

    2010-10-01

    ...-inflicted injuries or injuries sustained in connection with attempted suicide. Because of depression.... In this Example 1, the suicide attempt is the result of a medical condition (depression). Accordingly... full-time in an institution of higher learning (full-time students)). There is no evidence to suggest...

  2. Sympathy and misery in families with drinking problems

    DEFF Research Database (Denmark)

    Järvinen, Margaretha; Bloch, Charlotte

    2017-01-01

    the sympathy, showing gratitude and/or acknowledging their problems and trying to solve them. Third, the interviewees’ sympathygiving is related to the moral status they ascribe to problem drinkers, and especially their conceptions of alcohol problems as being self-inflicted or caused by circumstances...

  3. Non-accidental injury: a review of the radiology

    International Nuclear Information System (INIS)

    Carty, H.

    1997-01-01

    There have been many descriptions of the radiological features of non-accidental injury since John Caffey introduced the concept of inflicted injury and initially described some of the patterns of injury. Since then, our understanding of the radiologically detectable injuries has increased. This article provides a review of our current understanding of the lesions. (orig.)

  4. Penile hair coil strangulation of the child

    African Journals Online (AJOL)

    shanker

    complete urethral transection and corporal injury in an uncircum- cised boy inflicted by ligation of thread at ... among adolescents and adults with the concept of helping improve erection in some of them and with ... For the severe cases of penile injury with a glans hanging to the penis by a very slim pedicle, El Bahnasawy ...

  5. Impact of corrosion on the reliability of low voltage cables with aluminium conductors

    NARCIS (Netherlands)

    van Deursen, A.; Kruizinga, B.; Wouters, P.A.A.F.; Steennis, E.F.

    2017-01-01

    Aluminium is widely used as conductor material for power cables, but corrosion taking place under specific circumstances can have impact on its reliability. Aluminium corrosion under the influence of an alternating current was studied experimentally. Submerged cable segments with inflicted damage

  6. Changing therapeutic geographies of the Iraqi and Syrian wars

    NARCIS (Netherlands)

    Dewachi, O.; Skelton, M.; Nguyen, V.K.; Fouad, F.M.; Ghassan, A.S.; Maasri, Z.; Giacaman, R.

    2014-01-01

    The health consequences of the ongoing US-led war on terror and civil armed conflicts in the Arab world are much more than the collateral damage inflicted on civilians, infrastructure, environment, and health systems. Protracted war and armed conflicts have displaced populations and led to lasting

  7. Exposure to Domestic Violence between Parents: A Perspective from Tehran, Iran

    Science.gov (United States)

    Vameghi, Meroe; Feizzadeh, Ali; Mirabzadeh, Arash; Feizzadeh, Golnaz

    2010-01-01

    Women may bear the brunt of domestic violence, but children are also inflicted by the consequences of violence between their parents. We sought to evaluate the lifetime prevalence of exposure to physical violence between parents among some senior secondary school students in Tehran. The study was conducted on senior secondary school students in…

  8. Children's Experiences of Domestic Violence: Developing an Integrated Response from Police and Child Protection Services

    Science.gov (United States)

    Stanley, Nicky; Miller, Pam; Richardson Foster, Helen; Thomson, Gill

    2011-01-01

    Police notifications of incidents of domestic violence to child protection services constitute an acknowledgement of the harm that domestic violence inflicts on children. However, these notifications represent a substantial demand on child welfare services and the outcomes for children and victims of domestic violence have been questioned. This…

  9. Women's Political Representation & Participation in Decentralized ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    x31

    2008, inflicted women's rights since it accused women become sexual material and will be sanctioned because arousing lust and desire of men. • The ongoing debate to suspend the Draft Law on Health for about 14 years, particularly on the regulation of safe abortion. Yet, there are. 2.3 million unsafe abortion per year in.

  10. Occupational cow horn eye injuries in Ibadan, Nigeria | Ibrahim ...

    African Journals Online (AJOL)

    This case series aims to describe the clinical features, management, and outcome of occupational eye injuries caused by cow horns and to recommend possible preventive measures. A review of patients with cow horn inflicted eye injuries seen at the University College Hospital, Ibadan between January 2006, and ...

  11. A skin-picking disorder case report: a psychopathological explanation

    Directory of Open Access Journals (Sweden)

    Ângela Ribeiro

    2015-06-01

    Full Text Available We describe the case of a 44-year-old woman, without known previous psychiatric history, hospitalized after a significant hemorrhage caused by self-inflicted deep facial dermal lesions (with muscle exposition. Psychopathological possible explanations of this case, as in similar reviewed ones, are related to frustration, aggression, and impulsivity.

  12. Barriers to and facilitators for screening women for intimate partner violence in surgical fracture clinics: a qualitative descriptive approach

    NARCIS (Netherlands)

    Sprague, Sheila; Swinton, Marilyn; Madden, Kim; Swaleh, Rukia; Goslings, J. Carel; Petrisor, Brad; Bhandari, Mohit

    2013-01-01

    Intimate Partner Violence (IPV) is a major health issue that involves any physical, sexual or psychological harm inflicted by a current or former partner. Musculoskeletal injuries represent the second most prevalent clinical manifestation of IPV. Health care professionals, however, rarely screen

  13. Critical C Course 2

    African Journals Online (AJOL)

    Most southern African scorpions are relatively harmless to humans, and although they can inflict quite a painful sting, no other toxic effects are expected to develop. However, a small number of scorpion species can cause life-threatening systemic envenoming. Children are especially vulnerable, with a mortality rate of close ...

  14. An Economic Model of Workplace Mobbing in Academe

    Science.gov (United States)

    Faria, Joao Ricardo; Mixon, Franklin G., Jr.; Salter, Sean P.

    2012-01-01

    Workplace bullying or mobbing can be defined as the infliction of various forms of abuse (e.g., verbal, emotional, psychological) against a colleague or subordinate by one or more other members of a workplace. Even in the presence of academic tenure, workplace mobbing remains a prevalent issue in academe. This study develops an economic model that…

  15. Emotional Health and Well-Being: A Practical Guide for Schools

    Science.gov (United States)

    Cowie, Helen; Boardman, Chrissy; Dawkins, Judith; Jennifer, Dawn

    2004-01-01

    Daily educators are confronted with children who self-abuse through self-harm behaviours, eating disorders, drug or alcohol abuse or observe incidents that involve social isolation, for example racial abuse. Educators are also aware of cases of bullying and aggression that reaches extremes and they witness the harm inflicted on children through a…

  16. Surveillance of Suicidal Behavior January through December 2013

    Science.gov (United States)

    2015-06-01

    Disorder . i Substance Use Disorder includes Drug or Alcohol Use Disorders . j Personality Disorders include Borderline or Antisocial Personality ...include Borderline or Antisocial Personality Disorders . Public Health Report No. S.0008057-13, January through December 2013 D-27 Figure D-8... Antisocial Personality Disorders . m Based on ICE-9 E-codes for self-inflicted injuries which first appear in medical

  17. Vellykket konservativ behandling efter knivtraume mod hjertet

    DEFF Research Database (Denmark)

    Wærsted, Stian; Schou-Jensen, Katrine; Jensen, Tim

    2012-01-01

    A five year-old girl was admitted to hospital following an accidental stab wound to the chest, inflicted by a knife placed in a dishwasher's cutlery tray. Investigations revealed a traumatic ventricular septum defect of the heart, with a pericardial effusion. Since the patient remained haemodynam...

  18. Eavesdropping on coconut rhinoceros beetles, red palm weevils, Asian longhorned beetles, and other invasive travelers

    Science.gov (United States)

    As global trade increases, invasive insects inflict increasing economic damage to agriculture and urban landscapes in the United States yearly, despite a sophisticated array of interception methods and quarantine programs designed to exclude their entry. Insects that are hidden inside soil, wood, or...

  19. Self-injury, converting emotional distress into physical pain

    DEFF Research Database (Denmark)

    Møhl, Bo; Rubæk, Lotte

    2017-01-01

    Self-inflicted pain by cutting, hitting or burning oneself has become a common way to regulate emotions and to serve as coping strategy. 21.5-32% of adolescents in non-clinical populations have a history of non-suicidal self-injury. Non-suicidal self-injury has a momentarily relieving effect...

  20. Skeletal imaging of child abuse (non-accidental injury)

    International Nuclear Information System (INIS)

    Offiah, Amaka; Rijn, Rick R. van; Perez-Rossello, Jeanette Mercedes; Kleinman, Paul K.

    2009-01-01

    In recent years there has been a worldwide increased awareness that children are physically abused by their carers. Radiologists play a vital role in the detection of inflicted injuries. This article reviews the skeletal imaging findings seen in child abuse. (orig.)

  1. Multiple fractures of infant suffering from chronic subdural hematoma as a consequence of physical abuse?

    International Nuclear Information System (INIS)

    Mihal, V.; Petrova, Z.; Michalkova, K.

    2015-01-01

    Infants with multiple unexplained fractures are often victims of inflicted injury. Fractures from child abuse are significantly more common in children under 18 months of age than in older children, which should inform the differential diagnostic approach in this age group. The authors describe multiple unrecognized fractures of infant suffering from chronic subdural hematoma. (author)

  2. Moral masochism : On the connection between guilt and self-punishment

    NARCIS (Netherlands)

    Inbar, Y.; Pizarro, D.A.; Gilovich, T.; Ariely, D.

    2013-01-01

    Do people sometimes seek to atone for their transgressions by harming themselves physically? The current results suggest that they do. People who wrote about a past guilt-inducing event inflicted more intense electric shocks on themselves than did those who wrote about feeling sad or about a neutral

  3. Artefactual skin lesions in children and adolescents

    DEFF Research Database (Denmark)

    Ring, Hans Christian; Miller, Iben M; Benfeldt, Eva

    2015-01-01

    BACKGROUND: Self harm is a great diagnostic and treatment challenge. In addition, psychocutaneous conditions are rare in the pediatric population and may therefore be misdiagnosed. Dermatitis artefacta is a psychocutaneous syndrome, which is a subgroup of the general spectrum of self-inflicted skin...

  4. Joining Hands against Bullying

    Science.gov (United States)

    Weissbourd, Richard; Jones, Stephanie

    2012-01-01

    Over the last 20 years, high-profile episodes of bullying have stirred up broad public alarm. This attention may appear to be merely trendy, but it's important. Bullying--commonly defined as systematic exclusion, aggression, or harassment that one child or a group of children inflicts on less powerful children--is pervasive in schools. Many…

  5. Acta theologica supplementum 12-2009

    African Journals Online (AJOL)

    University of the Free State

    of Yoruba identity formation and the Yoruba antislavery struggle in the 1800s will help ... identifications across multiple dialects and has given women and lower ... and Catholic liberation theology inflict a certain degree of social disruption on in .... cultural path of Christianity in West Africa from Islam” (Peel 2000:189). Earlier.

  6. Variations in Wounding by Relationship Intimacy in Homicide Cases

    Science.gov (United States)

    Trojan, Carrie; Krull, Amy C.

    2012-01-01

    There are numerous examples in the homicide literature of a presumed connection between the victim-offender relationship and the manner, extent, and body location of wounds inflicted in homicides. The current study examined variations in wounding patterns according to the intimacy of the victim-offender relationship in a sample of urban homicides…

  7. Differentiating Adolescent Self-Injury from Adolescent Depression: Possible Implications for Borderline Personality Development

    Science.gov (United States)

    Crowell, Sheila E.; Beauchaine, Theodore P.; Hsiao, Ray C.; Vasilev, Christina A.; Yaptangco, Mona; Linehan, Marsha M.; McCauley, Elizabeth

    2012-01-01

    Self-inflicted injury (SII) in adolescence marks heightened risk for suicide attempts, completed suicide, and adult psychopathology. Although several studies have revealed elevated rates of depression among adolescents who self injure, no one has compared adolescent self injury with adolescent depression on biological, self-, and informant-report…

  8. Cottoning on

    Science.gov (United States)

    Non-healing or chronic wounds are an often unacknowledged burden to healthcare sectors worldwide. When left unresolved they can inflict untold suffering, result in high mortality and contribute to burgeoning health service expenditure. In the US, for example, more than 6 million people currently suf...

  9. Feather pecking and monoamines - a behavioral and neurobiological approach

    NARCIS (Netherlands)

    Kops, M.S.|info:eu-repo/dai/nl/341590649

    2014-01-01

    Severe feather pecking (SFP) remains one of the major welfare issues in laying hens. SFP is the pecking at and pulling out of feathers, inflicting damage to the plumage and skin of the recipient. The neurobiological profile determining the vulnerability of individual hens to develop into a severe

  10. Deforestation crimes and conflicts in the Amazon

    NARCIS (Netherlands)

    Boekhout van Solinge, T.

    2010-01-01

    This article explores and explains deforestation of the Brazilian Amazon rainforest. It primarily takes a green criminological perspective and looks at the harm that is inflicted on many of the Amazon’s inhabitants, including indigenous populations such as ‘uncontacted’ tribes of hunters-gatherers,

  11. When Teens Turn Cyberbullies

    Science.gov (United States)

    Strom, Paris S.; Strom, Robert D.

    2005-01-01

    Cyber harassment involves using an electronic medium to threaten or harm others. E-mail, chat rooms, cell phones, instant messaging, pagers, text messaging, and online voting booths are tools used to inflict humiliation, fear, and a sense of helplessness. This type of intimidation differs from traditional bullying in several important ways. Unlike…

  12. Expression of immune system-related genes during ontogeny in experimentally wounded common carp (Cyprinus carpio) larvae and juveniles

    DEFF Research Database (Denmark)

    Schmidt, Jacob; Nielsen, Michael Engelbrecht

    2014-01-01

    We investigated the effect of full-thickness incisional wounding on expression of genes related to the immune system in larvae and juveniles of common carp (Cyprinus carpio). The wounds were inflicted by needle puncture immediately below the anterior part of the dorsal fin on days 7, 14, 28 and 49...

  13. Skeletal imaging of child abuse (non-accidental injury)

    Energy Technology Data Exchange (ETDEWEB)

    Offiah, Amaka [Great Ormond Street Hospital, Radiology Department, London (United Kingdom); Rijn, Rick R. van [Academic Medical Centre Amsterdam, Department of Radiology, Amsterdam Zuid-Oost (Netherlands); Perez-Rossello, Jeanette Mercedes; Kleinman, Paul K. [Children' s Hospital Boston, Radiology Department, Boston, MA (United States)

    2009-05-15

    In recent years there has been a worldwide increased awareness that children are physically abused by their carers. Radiologists play a vital role in the detection of inflicted injuries. This article reviews the skeletal imaging findings seen in child abuse. (orig.)

  14. Childhood Falls With Occipital Impacts

    NARCIS (Netherlands)

    Atkinson, Norrell; van Rijn, Rick R.; Starling, Suzanne P.

    2017-01-01

    Falls are commonly reported in children who present with both accidental and inflicted brain injuries. Short falls rarely result in serious or life-threatening injuries. Our purpose is to describe a series of cases of short falls with occipital impact leading to subdural hemorrhage (SDH). We present

  15. History of Arsenic as a Poison and Medicinal

    Science.gov (United States)

    Since ancient times, human exposure to the metalloid arsenic has been both intentional and unintentional. The intentional exposure to arsenic has been to inflict harm on others as well as to be a curative agent for those who are ill. The unintentional exposure has either been f...

  16. How effective were mangroves as a defence against the recent tsunami?

    Science.gov (United States)

    Dahdouh-Guebas, F; Jayatissa, L P; Di Nitto, D; Bosire, J O; Lo Seen, D; Koedam, N

    2005-06-21

    Whether or not mangroves function as buffers against tsunamis is the subject of in-depth research, the importance of which has been neglected or underestimated before the recent killer tsunami struck. Our preliminary post-tsunami surveys of Sri Lankan mangrove sites with different degrees of degradation indicate that human activity exacerbated the damage inflicted on the coastal zone by the tsunami.

  17. How effective were mangroves as a defence against the recent tsunami?

    OpenAIRE

    Dahdouh-Guebas, F.; Jayatissa, L.P.; Di Nitto, D.; Bosire, J.O.; Lo Seen, D.; Koedam, N.

    2005-01-01

    Whether or not mangroves function as buffers against tsunamis is the subject of in-depth research, the importance of which has been neglected or underestimated before the recent killer tsunami struck. Our preliminary post-tsunami surveys of Sri Lankan mangrove sites with different degrees of degradation indicate that human activity exacerbated the damage inflicted on the coastal zone by the tsunami.

  18. The Insider Threat Security Architecture: An Integrated, Inseparable, and Uninterrupted Self-Protection Autonomic Framework

    Science.gov (United States)

    Jabbour, Ghassan

    2010-01-01

    The increasing proliferation of globally interconnected complex information systems has elevated the magnitude of attacks and the level of damage that they inflict on such systems. This open environment of intertwined financial, medical, defense, and other systems has attracted hackers to increase their malicious activities to cause harm or to…

  19. Counselor Liability: Does the Risk Require Insurance Coverage?

    Science.gov (United States)

    Hendrickson, Robert M.

    1982-01-01

    Discusses the legal concept of liabiltiy and the potential risks facing the practicing counselor. Outlines the standard of care that psychiatrists must meet to protect themselves against negligence charges. Discusses actions resulting in false imprisonment, battery, infliction of mental distress, defamation, and "duty to warn." (RC)

  20. Does Lycoperscon Esculentum (Tomato) Accelerate or Retard ...

    African Journals Online (AJOL)

    The study aimed at determining the effects of Lycoperscon esculentum on the wound healing processes of wistar rats. Excisional wounds were inflicted on the upper dorsolateral trunk of 20 adult male wistar rats. The wounds were dressed every three days (experimental with methanol extract of Lycoperscon esculentum and ...

  1. Pre-natal effects of ethanol and folic acid supplements on the ...

    African Journals Online (AJOL)

    Pre-natal effects of ethanol and folic acid supplements on the mineralisation of bones in ... folic acid deficiency, in particular at pregnancy; thus inflicting severe skeletal ... or 'catch-up' growth was displayed in the ethanol plus folate treated rats.

  2. Cell kinetics during regeneration in the sponge Halisarca caerulea: how local is the response to tissue damage?

    NARCIS (Netherlands)

    Alexander, B.E.; Achlatis, M.; Osinga, R.; van der Geest, H.G.; Cleutjens, J.P.M.; Schutte, B.; de Goeij, J.M.

    2015-01-01

    Sponges have a remarkable capacity to rapidly regenerate in response to wound infliction. In addition, sponges rapidly renew their filter systems (choanocytes) to maintain a healthy population of cells. This study describes the cell kinetics of choanocytes in the encrusting reef sponge Halisarca

  3. Development and application of a loop-mediated isothermal ...

    African Journals Online (AJOL)

    Haemophilus parasuis is the causative agent of Glässer's disease that has received much attention recently, due to the increasing economic losses this disease inflicts upon the pig industry worldwide. In this study, loop-mediated isothermal amplification method (LAMP) methodology was designed for diagnosing H.

  4. Does Theorizing on Reciprocal Altruism Apply to the Relationships of Individuals with a Spinal Cord Injury?

    NARCIS (Netherlands)

    Buunk, A. P.; Zurriaga, Rosario; Gonzalez, Pilar

    2012-01-01

    From the perspective of reciprocal altruism, we examined the role of reciprocity in the close relationships of people inflicted with a spinal cord injury (SCI) (n = 70). We focused on the help receiver rather than on the help giver. Participants perceived more reciprocity in relationships with

  5. Neutron scattering from myelin revisited: bilayer asymmetry and water-exchange kinetics

    Energy Technology Data Exchange (ETDEWEB)

    Denninger, Andrew R. [Boston College, Chestnut Hill, MA 02467 (United States); Demé, Bruno; Cristiglio, Viviana [Institut Laue–Langevin (ILL), CS 20156, F-38042 Grenoble CEDEX 9 (France); LeDuc, Géraldine [European Synchrotron Radiation Facility (ESRF), CS 40220, F-38043 Grenoble CEDEX 9 (France); Feller, W. Bruce [NOVA Scientific Inc., Sturbridge, MA 01566 (United States); Kirschner, Daniel A., E-mail: kirschnd@bc.edu [Boston College, Chestnut Hill, MA 02467 (United States)

    2014-12-01

    The structure of internodal myelin in the rodent central and peripheral nervous systems has been determined using neutron diffraction. The kinetics of water exchange in these tissues is also described. Rapid nerve conduction in the central and peripheral nervous systems (CNS and PNS, respectively) of higher vertebrates is brought about by the ensheathment of axons with myelin, a lipid-rich, multilamellar assembly of membranes. The ability of myelin to electrically insulate depends on the regular stacking of these plasma membranes and on the presence of a number of specialized membrane-protein assemblies in the sheath, including the radial component, Schmidt–Lanterman incisures and the axo–glial junctions of the paranodal loops. The disruption of this fine-structure is the basis for many demyelinating neuropathies in the CNS and PNS. Understanding the processes that govern myelin biogenesis, maintenance and destabilization requires knowledge of myelin structure; however, the tight packing of internodal myelin and the complexity of its junctional specializations make myelin a challenging target for comprehensive structural analysis. This paper describes an examination of myelin from the CNS and PNS using neutron diffraction. This investigation revealed the dimensions of the bilayers and aqueous spaces of myelin, asymmetry between the cytoplasmic and extracellular leaflets of the membrane, and the distribution of water and exchangeable hydrogen in internodal multilamellar myelin. It also uncovered differences between CNS and PNS myelin in their water-exchange kinetics.

  6. Deficiency of a membrane skeletal protein, 4.1G, results in myelin abnormalities in the peripheral nervous system.

    Science.gov (United States)

    Saitoh, Yurika; Ohno, Nobuhiko; Yamauchi, Junji; Sakamoto, Takeharu; Terada, Nobuo

    2017-12-01

    We previously demonstrated that a membrane skeletal molecular complex, 4.1G-membrane palmitoylated protein 6 (MPP6)-cell adhesion molecule 4, is incorporated in Schwann cells in the peripheral nervous system (PNS). In this study, we evaluated motor activity and myelin ultrastructures in 4.1G-deficient (-/-) mice. When suspended by the tail, aged 4.1G -/- mice displayed spastic leg extension, especially after overwork. Motor-conduction velocity in 4.1G -/- mice was slower than that in wild-type mice. Using electron microscopy, 4.1G -/- mice exhibited myelin abnormalities: myelin was thicker in internodes, and attachment of myelin tips was distorted in some paranodes. In addition, we found a novel function of 4.1G for sorting a scaffold protein, Lin7, due to disappearance of the immunolocalization and reduction of the production of Lin7c and Lin7a in 4.1G -/- sciatic nerves, as well as the interaction of MPP6 and Lin7 with immunoprecipitation. Thus, we herein propose 4.1G functions as a signal for proper formation of myelin in PNS.

  7. Mutations in GLDN, Encoding Gliomedin, a Critical Component of the Nodes of Ranvier, Are Responsible for Lethal Arthrogryposis.

    Science.gov (United States)

    Maluenda, Jérôme; Manso, Constance; Quevarec, Loic; Vivanti, Alexandre; Marguet, Florent; Gonzales, Marie; Guimiot, Fabien; Petit, Florence; Toutain, Annick; Whalen, Sandra; Grigorescu, Romulus; Coeslier, Anne Dieux; Gut, Marta; Gut, Ivo; Laquerrière, Annie; Devaux, Jérôme; Melki, Judith

    2016-10-06

    Arthrogryposis multiplex congenita (AMC) is a developmental condition characterized by multiple joint contractures resulting from reduced or absent fetal movements. Through linkage analysis, homozygosity mapping, and exome sequencing in four unrelated families affected by lethal AMC, we identified biallelic mutations in GLDN in the affected individuals. GLDN encodes gliomedin, a secreted cell adhesion molecule involved in the formation of the nodes of Ranvier. Transmission electron microscopy of the sciatic nerve from one of the affected individuals showed a marked lengthening defect of the nodes. The GLDN mutations found in the affected individuals abolish the cell surface localization of gliomedin and its interaction with its axonal partner, neurofascin-186 (NF186), in a cell-based assay. The axoglial contact between gliomedin and NF186 is essential for the initial clustering of Na + channels at developing nodes. These results indicate a major role of gliomedin in node formation and the development of the peripheral nervous system in humans. These data indicate that mutations of GLDN or CNTNAP1 (MIM: 616286), encoding essential components of the nodes of Ranvier and paranodes, respectively, lead to inherited nodopathies, a distinct disease entity among peripheral neuropathies. Copyright © 2016 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  8. Myelination and nodal formation of regenerated peripheral nerve fibers following transplantation of acutely prepared olfactory ensheathing cells

    Science.gov (United States)

    Dombrowski, Mary A.; Sasaki, Masanori; Lankford, Karen L.; Kocsis, Jeffery D.; Radtke, Christine

    2009-01-01

    Transplantation of olfactory ensheathing cells (OECs) into injured spinal cord results in improved functional outcome. Mechanisms suggested to account for this functional improvement include axonal regeneration, remyelination and neuroprotection. OECs transplanted into transected peripheral nerve have been shown to modify peripheral axonal regeneration and functional outcome. However, little is known of the detailed integration of OECs at the transplantation site in peripheral nerve. To address this issue cells populations enriched in OECs were isolated from the olfactory bulbs of adult green fluorescent protein (GFP)-expressing transgenic rats and transplanted into a sciatic nerve crush lesion which transects all axons. Five weeks to six months after transplantation the nerves were studied histologically. GFP-expressing OECs survived in the lesion and distributed longitudinally across the lesion zone. The internodal regions of individual teased fibers distal to the transection site were characterized by GFP expression in the cytoplasmic and nuclear compartments of cells surrounding the axons. Immuno-electron microscopy for GFP indicated that the transplanted OECs formed peripheral type myelin. Immunostaining for sodium channel and Caspr revealed a high density of Nav1.6 at the newly formed nodes of Ranvier which were flanked by paranodal Caspr staining. These results indicate that transplanted OECs extensively integrate into transected peripheral nerve and form myelin on regenerated peripheral nerve fibers, and that nodes of Ranvier of these axons display proper sodium channel organization. PMID:17112480

  9. Non-fatal suicide attempt by intentional stab wound: Clinical management, psychiatric assessment, and multidisciplinary considerations

    Directory of Open Access Journals (Sweden)

    James M Badger

    2012-01-01

    Full Text Available Background: Suicide by means of self-inflicted stab wounds is relatively uncommon and little is known about this population and their management. Materials and Methods: Retrospective review of adult trauma patients admitted to our Level-1 trauma center between January 2005 and October 2009 for management of non-fatal, self-inflicted stab wounds. Results: Fifty-eight patients were evaluated with self-inflicted stab wounds. Four patients died due to their injuries (mortality, 7%. Of the non-fatal stab wounds, 78% were male ranging in age from 19-82 (mean: 45 years. The most common injury sites were the abdomen (46%, neck (33%, and chest (20%. In terms of operative interventions, 56% of abdominal operations were therapeutic, whereas 100% of neck and chest operations were therapeutic. When assessing for suicidal ideation, 44 patients (81% admitted to suicidal intentions whereas 10 patients (19% described "accidental" circumstances. Following psychiatric evaluation, 8 of the 10 patients with "accidental injuries" were found to be suicidal. Overall, 54 patients (98% met criteria for a formal psychiatric diagnosis with 48 patients (89% necessitating inpatient or outpatient psychiatric assistance at discharge. Conclusions: Compared to previous reports of stab wounds among trauma patients, patients with self- inflicted stab wounds may have a higher incidence of operative interventions and significant injuries depending on the stab location. When circumstances surrounding a self-inflicted stabbing are suspicious, additional interviews by psychiatric care providers may uncover a suicidal basis to the event. Given the increased incidence of psychiatric illness in this population, it is imperative to approach the suicidal patient in a multidisciplinary fashion.

  10. Activation of NMDA receptor by elevated homocysteine in chronic liver disease contributes to encephalopathy.

    Science.gov (United States)

    Choudhury, Sabanum; Borah, Anupom

    2015-07-01

    Liver diseases lead to a complex syndrome characterized by neurological, neuro-psychiatric and motor complications, called hepatic encephalopathy, which is prevalent in patients and animal models of acute, sub-chronic and chronic liver failure. Although alterations in GABAergic, glutamatergic, cholinergic and serotonergic neuronal functions have been implicated in HE, the molecular mechanisms that lead to HE in chronic liver disease (CLD) is least illustrated. Due to hepatocellular failure, levels of ammonia and homocysteine (Hcy), in addition to others, are found to increase in the brain as well as plasma. Hcy, a non-protein forming amino acid and an excitotoxin, activates ionotropic glutamate (n-methyl-d-aspartate; NMDA) receptors, and thereby leads to influx of Ca(2+) into neurons, which in turn activates several pathways that trigger oxidative stress, inflammation and apoptosis, collectively called excitotoxicity. Elevated levels of Hcy in the plasma and brain, a condition called Hyperhomocysteinemia (HHcy), and the resultant NMDA receptor-mediated excitotoxicity has been implicated in several diseases, including Parkinson's disease and Alzheimer's disease. Although, hyperammonemia has been shown to cause excitotoxicity, the role of HHcy in the development of behavioral and neurochemical alterations that occur in HE has not been illustrated yet. It is hypothesized that CLD-induced HHcy plays a major role in the development of HE through activation of NMDA receptors. It is further hypothesized that HHcy synergizes with hyperammonemia to activate NMDA receptor in the brain, and thereby cause oxidative stress, inflammation and apoptosis, and neuronal loss that leads to HE. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Acacetin inhibits glutamate release and prevents kainic acid-induced neurotoxicity in rats.

    Directory of Open Access Journals (Sweden)

    Tzu-Yu Lin

    Full Text Available An excessive release of glutamate is considered to be a molecular mechanism associated with several neurological diseases that causes neuronal damage. Therefore, searching for compounds that reduce glutamate neurotoxicity is necessary. In this study, the possibility that the natural flavone acacetin derived from the traditional Chinese medicine Clerodendrum inerme (L. Gaertn is a neuroprotective agent was investigated. The effect of acacetin on endogenous glutamate release in rat hippocampal nerve terminals (synaptosomes was also investigated. The results indicated that acacetin inhibited depolarization-evoked glutamate release and cytosolic free Ca(2+ concentration ([Ca(2+]C in the hippocampal nerve terminals. However, acacetin did not alter synaptosomal membrane potential. Furthermore, the inhibitory effect of acacetin on evoked glutamate release was prevented by the Cav2.2 (N-type and Cav2.1 (P/Q-type channel blocker known as ω-conotoxin MVIIC. In a kainic acid (KA rat model, an animal model used for excitotoxic neurodegeneration experiments, acacetin (10 or 50 mg/kg was administrated intraperitoneally to the rats 30 min before the KA (15 mg/kg intraperitoneal injection, and subsequently induced the attenuation of KA-induced neuronal cell death and microglia activation in the CA3 region of the hippocampus. The present study demonstrates that the natural compound, acacetin, inhibits glutamate release from hippocampal synaptosomes by attenuating voltage-dependent Ca(2+ entry and effectively prevents KA-induced in vivo excitotoxicity. Collectively, these data suggest that acacetin has the therapeutic potential for treating neurological diseases associated with excitotoxicity.

  12. Rosiglitazone Suppresses In Vitro Seizures in Hippocampal Slice by Inhibiting Presynaptic Glutamate Release in a Model of Temporal Lobe Epilepsy.

    Directory of Open Access Journals (Sweden)

    Shi-Bing Wong

    Full Text Available Peroxisomal proliferator-activated receptor gamma (PPARγ is a nuclear hormone receptor whose agonist, rosiglitazone has a neuroprotective effect to hippocampal neurons in pilocarpine-induced seizures. Hippocampal slice preparations treated in Mg2+ free medium can induce ictal and interictal-like epileptiform discharges, which is regarded as an in vitro model of N-methyl-D-aspartate (NMDA receptor-mediated temporal lobe epilepsy (TLE. We applied rosiglitazone in hippocampal slices treated in Mg2+ free medium. The effects of rosiglitazone on hippocampal CA1-Schaffer collateral synaptic transmission were tested. We also examined the neuroprotective effect of rosiglitazone toward NMDA excitotoxicity on cultured hippocampal slices. Application of 10 μM rosiglitazone significantly suppressed amplitude and frequency of epileptiform discharges in CA1 neurons. Pretreatment with the PPARγ antagonist GW9662 did not block the effect of rosiglitazone on suppressing discharge frequency, but reverse the effect on suppressing discharge amplitude. Application of rosiglitazone suppressed synaptic transmission in the CA1-Schaffer collateral pathway. By miniature excitatory-potential synaptic current (mEPSC analysis, rosiglitazone significantly suppressed presynaptic neurotransmitter release. This phenomenon can be reversed by pretreating PPARγ antagonist GW9662. Also, rosiglitazone protected cultured hippocampal slices from NMDA-induced excitotoxicity. The protective effect of 10 μM rosiglitazone was partially antagonized by concomitant high dose GW9662 treatment, indicating that this effect is partially mediated by PPARγ receptors. In conclusion, rosiglitazone suppressed NMDA receptor-mediated epileptiform discharges by inhibition of presynaptic neurotransmitter release. Rosiglitazone protected hippocampal slice from NMDA excitotoxicity partially by PPARγ activation. We suggest that rosiglitazone could be a potential agent to treat patients with TLE.

  13. Somatostatin receptor 1 and 5 double knockout mice mimic neurochemical changes of Huntington's disease transgenic mice.

    Directory of Open Access Journals (Sweden)

    Padmesh S Rajput

    Full Text Available Selective degeneration of medium spiny neurons and preservation of medium sized aspiny interneurons in striatum has been implicated in excitotoxicity and pathophysiology of Huntington's disease (HD. However, the molecular mechanism for the selective sparing of medium sized aspiny neurons and vulnerability of projection neurons is still elusive. The pathological characteristic of HD is an extensive reduction of the striatal mass, affecting caudate putamen. Somatostatin (SST positive neurons are selectively spared in HD and Quinolinic acid/N-methyl-D-aspartic acid induced excitotoxicity, mimic the model of HD. SST plays neuroprotective role in excitotoxicity and the biological effects of SST are mediated by five somatostatin receptor subtypes (SSTR1-5.To delineate subtype selective biological responses we have here investigated changes in SSTR1 and 5 double knockout mice brain and compared with HD transgenic mouse model (R6/2. Our study revealed significant loss of dopamine and cAMP regulated phosphoprotein of 32 kDa (DARPP-32 and comparable changes in SST, N-methyl-D-aspartic acid receptors subtypes, calbindin and brain nitric oxide synthase expression as well as in key signaling proteins including calpain, phospho-extracellular-signal-regulated kinases1/2, synapsin-IIa, protein kinase C-α and calcineurin in SSTR1/5(-/- and R6/2 mice. Conversely, the expression of somatostatin receptor subtypes, enkephalin and phosphatidylinositol 3-kinases were strain specific. SSTR1/5 appears to be important in regulating NMDARs, DARPP-32 and signaling molecules in similar fashion as seen in HD transgenic mice.This is the first comprehensive description of disease related changes upon ablation of G- protein coupled receptor gene. Our results indicate that SST and SSTRs might play an important role in regulation of neurodegeneration and targeting this pathway can provide a novel insight in understanding the pathophysiology of Huntington's disease.

  14. From the Cover: Selective Enhancement of Domoic Acid Toxicity in Primary Cultures of Cerebellar Granule Cells by Lowering Extracellular Na+ Concentration.

    Science.gov (United States)

    Pérez-Gómez, Anabel; Cabrera-García, David; Warm, Davide; Marini, Ann M; Salas Puig, Javier; Fernández-Sánchez, Maria Teresa; Novelli, Antonello

    2018-01-01

    Domoic acid (DOM) is an excitatory amino acid analog of kainic acid (KA) that acts through glutamic acid (GLU) receptors, inducing a fast and potent neurotoxic response. Here, we present evidence for an enhancement of excitotoxicity following exposure of cultured cerebellar granule cells to DOM in the presence of lower than physiological Na+ concentrations. The concentration of DOM that reduced by 50% neuronal survival was approximately 3 µM in Na+-free conditions and 16 µM in presence of a physiological concentration of extracellular Na+. The enhanced neurotoxic effect of DOM was fully prevented by AMPA/KA receptor antagonist, while N-methyl-D-aspartate-receptor-mediated neurotoxicity did not seem to be involved, as the absence of extracellular Na+ failed to potentiate GLU excitotoxicity under the same experimental conditions. Lowering of extracellular Na+ concentration to 60 mM eliminated extracellular recording of spontaneous electrophysiological activity from cultured neurons grown on a multi electrode array and prevented DOM stimulation of the electrical activity. Although changes in the extracellular Na+ concentration did not alter the magnitude of the rapid increase in intracellular Ca2+ levels associated to DOM exposure, they did change significantly the contribution of voltage-sensitive calcium channels (VScaCs) and the recovery time to baseline. The prevention of Ca2+ influx via VSCaCs by nifedipine failed to prevent DOM toxicity at any extracellular Na+ concentration, while the reduction of extracellular Ca2+ concentration ameliorated DOM toxicity only in the absence of extracellular Na+, enhancing it in physiological conditions. Our data suggest a crucial role for extracellular Na+ concentration in determining excitotoxicity by DOM. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  15. Bax regulates neuronal Ca2+ homeostasis.

    Science.gov (United States)

    D'Orsi, Beatrice; Kilbride, Seán M; Chen, Gang; Perez Alvarez, Sergio; Bonner, Helena P; Pfeiffer, Shona; Plesnila, Nikolaus; Engel, Tobias; Henshall, David C; Düssmann, Heiko; Prehn, Jochen H M

    2015-01-28

    Excessive Ca(2+) entry during glutamate receptor overactivation ("excitotoxicity") induces acute or delayed neuronal death. We report here that deficiency in bax exerted broad neuroprotection against excitotoxic injury and oxygen/glucose deprivation in mouse neocortical neuron cultures and reduced infarct size, necrotic injury, and cerebral edema formation after middle cerebral artery occlusion in mice. Neuronal Ca(2+) and mitochondrial membrane potential (Δψm) analysis during excitotoxic injury revealed that bax-deficient neurons showed significantly reduced Ca(2+) transients during the NMDA excitation period and did not exhibit the deregulation of Δψm that was observed in their wild-type (WT) counterparts. Reintroduction of bax or a bax mutant incapable of proapoptotic oligomerization equally restored neuronal Ca(2+) dynamics during NMDA excitation, suggesting that Bax controlled Ca(2+) signaling independently of its role in apoptosis execution. Quantitative confocal imaging of intracellular ATP or mitochondrial Ca(2+) levels using FRET-based sensors indicated that the effects of bax deficiency on Ca(2+) handling were not due to enhanced cellular bioenergetics or increased Ca(2+) uptake into mitochondria. We also observed that mitochondria isolated from WT or bax-deficient cells similarly underwent Ca(2+)-induced permeability transition. However, when Ca(2+) uptake into the sarco/endoplasmic reticulum was blocked with the Ca(2+)-ATPase inhibitor thapsigargin, bax-deficient neurons showed strongly elevated cytosolic Ca(2+) levels during NMDA excitation, suggesting that the ability of Bax to support dynamic ER Ca(2+) handling is critical for cell death signaling during periods of neuronal overexcitation. Copyright © 2015 the authors 0270-6474/15/351706-17$15.00/0.

  16. 24S-hydroxycholesterol and 25-hydroxycholesterol differentially impact hippocampal neuronal survival following oxygen-glucose deprivation.

    Directory of Open Access Journals (Sweden)

    Min-Yu Sun

    Full Text Available N-methyl-D-aspartate receptors (NMDARs, a major subtype of glutamate receptor mediating excitatory transmission throughout the CNS, participate in ischemia-induced neuronal death. Unfortunately, undesired side effects have limited the strategy of inhibiting/blocking NMDARs as therapy. Targeting endogenous positive allosteric modulators of NMDAR function may offer a strategy with fewer downsides. Here, we explored whether 24S-hydroxycholesterol (24S-HC, an endogenous positive NMDAR modulator characterized recently by our group, participates in NMDAR-mediated excitotoxicity following oxygen-glucose deprivation (OGD in primary neuron cultures. 24S-HC is the major brain cholesterol metabolite produced exclusively in neurons near sites of glutamate transmission. By selectively potentiating NMDAR current, 24S-HC may participate in NMDAR-mediated excitotoxicity following energy failure, thus impacting recovery after stroke. In support of this hypothesis, our findings indicate that exogenous application of 24S-HC exacerbates NMDAR-dependent excitotoxicity in primary neuron culture following OGD, an ischemic-like challenge. Similarly, enhancement of endogenous 24S-HC synthesis reduced survival rate. On the other hand, reducing endogenous 24S-HC synthesis alleviated OGD-induced cell death. We found that 25-HC, another oxysterol that antagonizes 24S-HC potentiation, partially rescued OGD-mediated cell death in the presence or absence of exogenous 24S-HC application, and 25-HC exhibited NMDAR-dependent/24S-HC-dependent neuroprotection, as well as NMDAR-independent neuroprotection in rat tissue but not mouse tissue. Our findings suggest that both endogenous and exogenous 24S-HC exacerbate OGD-induced damage via NMDAR activation, while 25-HC exhibits species dependent neuroprotection through both NMDAR-dependent and independent mechanisms.

  17. Characterization of the 1H-cyclopentapyrimidine-2,4(1H,3H)-dione derivative (S)-CPW399 as a novel, potent, and subtype-selective AMPA receptor full agonist with partial desensitization properties

    DEFF Research Database (Denmark)

    Campiani, G; Morelli, E; Nacci, V

    2001-01-01

    (S)-CPW399 (2b) is a novel, potent, and subtype-selective AMPA receptor full agonist that, unlike (S)-willardiine and related compounds, in mouse cerebellar granule cells, stimulated an increase in [Ca(2+)](i), and induced neuronal cell death in a time- and concentration-dependent manner. Compound...... 2b appears to be a weakly desensitizing, full agonist at AMPA receptors and therefore represents a new pharmacological tool to investigate the role of AMPA receptors in excitotoxicity and their molecular mechanisms of desensitization....

  18. Piroxicam-mediated modulatory action of 5-hydroxytryptamine serves as a "brake" on neuronal excitability in ischemic stroke

    Directory of Open Access Journals (Sweden)

    Pallab Bhattacharya

    2015-01-01

    Full Text Available Our previous studies indicated an increase in extracellular γ-aminobutyric acid (GABA in rodent′s ischemic brain after Piroxicam administration, leading to alleviation of glutamate mediated excitotoxicity through activation of type A GABA receptor (GABAA. This study was to investigate if GABAA activation by Piroxicam affects extracellular 5-hydroxytryptamine or not. High performance liquid chromatography revealed that there was a significant decrease in extracellular 5-hydroxytryptamine release in ischemic cerebral cortex and striatum in Piroxicam pre-treated rat brains. This suggests a probable role of Piroxicam in reducing extracellular 5-hydroxytryptamine release in ischemic cerebral cortex and striatum possibly due to the GABAA activation by Piroxicam.

  19. The role of inflammation in the pathogenesis of glaucoma

    DEFF Research Database (Denmark)

    Vohra, Rupali; Tsai, James C; Kolko, Miriam

    2013-01-01

    Glaucoma is an ocular disorder characterized by the progressive loss of retinal ganglion cells (RGC) and their axons. There are various hypotheses concerning the cause of RGC death. Previously, glaucoma was defined by high intraocular pressure (IOP); during the past decade, however, glaucoma...... specialists have acknowledged that elevated IOP is the most important risk factor for glaucoma, but does not define the disease. Other factors such as genetics, blood flow, and excitotoxicity are suggested as potential causal factors for progressive RGC death observed in glaucoma. We review recent studies...... elucidating a possible role of low-grade inflammation as a causal factor in the pathogenesis of glaucoma....

  20. Ion Channels and Zinc: Mechanisms of Neurotoxicity and Neurodegeneration

    Directory of Open Access Journals (Sweden)

    Deborah R. Morris

    2012-01-01

    Full Text Available Ionotropic glutamate receptors, such as NMDA, AMPA and kainate receptors, are ligand-gated ion channels that mediate much of the excitatory neurotransmission in the brain. Not only do these receptors bind glutamate, but they are also regulated by and facilitate the postsynaptic uptake of the trace metal zinc. This paper discusses the role of the excitotoxic influx and accumulation of zinc, the mechanisms responsible for its cytotoxicity, and a number of disorders of the central nervous system that have been linked to these neuronal ion channels and zinc toxicity including ischemic brain injury, traumatic brain injury, and epilepsy.

  1. Post-traumatic contrast enhancing brain lesion

    International Nuclear Information System (INIS)

    Kim, Dae Jung; Kim, Hyun Sook; Jeong, Min Sun; Kim, Deok Ryeong; Cho, Young Kwon; Choi, Yun Sun

    2014-01-01

    Only a few studies have been reported on the MR contrast enhancement and the apparent diffusion coefficient (ADC) findings of the post-traumatic lesion of the brain. We report a case of the venous ischemia in the left frontal lobe observed in the MRI obtained one day after the incidence of trauma. Considering the presented slight increase in the ADC, the vasogenic edema was thought to be the major mechanism of the venous ischemia and excitotoxic injury. In spite of a slight increase in the ADC, the hyperintensity in the diffusion weighted imaging and contrast-enhanced areas eventually changed into hemorrhagic lesions.

  2. Post-traumatic contrast enhancing brain lesion

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Dae Jung; Kim, Hyun Sook; Jeong, Min Sun; Kim, Deok Ryeong; Cho, Young Kwon; Choi, Yun Sun [Eulji Hospital, Eulji University College of Medicine, Seoul (Korea, Republic of)

    2014-10-15

    Only a few studies have been reported on the MR contrast enhancement and the apparent diffusion coefficient (ADC) findings of the post-traumatic lesion of the brain. We report a case of the venous ischemia in the left frontal lobe observed in the MRI obtained one day after the incidence of trauma. Considering the presented slight increase in the ADC, the vasogenic edema was thought to be the major mechanism of the venous ischemia and excitotoxic injury. In spite of a slight increase in the ADC, the hyperintensity in the diffusion weighted imaging and contrast-enhanced areas eventually changed into hemorrhagic lesions.

  3. Bilirubin-Induced Neurotoxicity in the Preterm Neonate.

    Science.gov (United States)

    Watchko, Jon F

    2016-06-01

    Bilirubin-induced neurotoxicity in preterm neonates remains a clinical concern. Multiple cellular and molecular cascades likely underlie bilirubin-induced neuronal injury, including plasma membrane perturbations, excitotoxicity, neuroinflammation, oxidative stress, and cell cycle arrest. Preterm newborns are particularly vulnerable secondary to central nervous system immaturity and concurrent adverse clinical conditions that may potentiate bilirubin toxicity. Acute bilirubin encephalopathy in preterm neonates may be subtle and manifest primarily as recurrent symptomatic apneic events. Low-bilirubin kernicterus continues to be reported in preterm neonates, and although multifactorial in nature, is often associated with marked hypoalbuminemia. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Citicoline: a food beneficial for patients suffering from or threated with glaucoma

    Directory of Open Access Journals (Sweden)

    Pawel eGrieb

    2016-04-01

    Full Text Available Oral form of citicoline, a nootropic and neuroprotective drug in use for almost five decades, recently was pronounced a food supplement in both USA and EU. The idea of adding citicoline to topical treatment of primary open angle glaucoma (POAG aimed at decreasing intraocular pressure appeared as a logical consequence of accepting neurodegenerative character of this disease. Experimental data, and also few clinical studies indicate that this substance has potential to counteract some important pathological mechanisms which seem to contribute to POAG initiation and progression, such as excitotoxicity and oxidative stress.

  5. [A role of the autonomic nervous system in cerebro-cardiac disorders].

    Science.gov (United States)

    Basantsova, N Yu; Tibekina, L M; Shishkin, A N

    The authors consider anatomical/physiological characteristics and a role of different autonomic CNS regions, including insula cortex, amygdala complex, anterior cingulate cortex, ventral medial prefrontal cortex, hypothalamus and epiphysis, involved in the regulation of cardiovascular activity. The damage of these structures, e.g., due to the acute disturbance of cerebral blood circulation, led to arrhythmia, including fatal arrhythmia, in previously intact myocardium; systolic and diastolic dysfunction, ischemic changes considered in the frames of cerebro-cardial syndrome. On the cellular level, the disturbance of autonomic regulation resulted in catechol amine excitotoxicity, oxidative stress and free radical myocardium injury.

  6. Hypoxia-ischemia or excitotoxin-induced tissue plasminogen activator- dependent gelatinase activation in mice neonate brain microvessels.

    Directory of Open Access Journals (Sweden)

    Priscilla L Omouendze

    Full Text Available Hypoxia-ischemia (HI and excitotoxicity are validated causes of neonatal brain injuries and tissue plasminogen activator (t-PA participates in the processes through proteolytic and receptor-mediated pathways. Brain microvascular endothelial cells from neonates in culture, contain and release more t-PA and gelatinases upon glutamate challenge than adult cells. We have studied t-PA to gelatinase (MMP-2 and MMP-9 activity links in HI and excitotoxicity lesion models in 5 day-old pups in wild type and in t-PA or its inhibitor (PAI-1 genes inactivated mice. Gelatinolytic activities were detected in SDS-PAGE zymograms and by in situ fluorescent DQ-gelatin microscopic zymographies. HI was achieved by unilateral carotid ligature followed by a 40 min hypoxia (8%O₂. Excitotoxic lesions were produced by intra parenchymal cortical (i.c. injections of 10 µg ibotenate (Ibo. Gel zymograms in WT cortex revealed progressive extinction of MMP-2 and MMP-9 activities near day 15 or day 8 respectively. MMP-2 expression was the same in all strains while MMP-9 activity was barely detectable in t-PA⁻/⁻ and enhanced in PAI-1⁻/⁻ mice. HI or Ibo produced activation of MMP-2 activities 6 hours post-insult, in cortices of WT mice but not in t-PA⁻/⁻ mice. In PAI-1⁻/⁻ mice, HI or vehicle i.c. injection increased MMP-2 and MMP-9 activities. In situ zymograms using DQ-gelatin revealed vessel associated gelatinolytic activity in lesioned areas in PAI-1⁻/⁻ and in WT mice. In WT brain slices incubated ex vivo, glutamate (200 µM induced DQ-gelatin activation in vessels. The effect was not detected in t-PA⁻/⁻ mice, but was restored by concomitant exposure to recombinant t-PA (20 µg/mL. In summary, neonatal brain lesion paradigms and ex vivo excitotoxic glutamate evoked t-PA-dependent gelatinases activation in vessels. Both MMP-2 and MMP-9 activities appeared t-PA-dependent. The data suggest that vascular directed protease inhibition may have

  7. Ketogenic Diet Provides Neuroprotective Effects against Ischemic Stroke Neuronal Damages

    Directory of Open Access Journals (Sweden)

    Sheida Shaafi

    2014-12-01

    Full Text Available Ischemic stroke is a leading cause of death and disability in the world. Many mechanisms contribute in cell death in ischemic stroke. Ketogenic diet which has been successfully used in the drug-resistant epilepsy has been shown to be effective in many other neurologic disorders. The mechanisms underlying of its effects are not well studied, but it seems that its neuroprotective ability is mediated at least through alleviation of excitotoxicity, oxidative stress and apoptosis events. On the basis of these mechanisms, it is postulated that ketogenic diet could provide benefits to treatment of cerebral ischemic injuries.

  8. Naphthazarin protects against glutamate-induced neuronal death via activation of the Nrf2/ARE pathway.

    Science.gov (United States)

    Son, Tae Gen; Kawamoto, Elisa M; Yu, Qian-Sheng; Greig, Nigel H; Mattson, Mark P; Camandola, Simonetta

    2013-04-19

    Nuclear factor E2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway is an important cellular stress response pathway involved in neuroprotection. We previously screened several natural phytochemicals and identified plumbagin as a novel activator of the Nrf2/ARE pathway that can protect neurons against ischemic injury. Here we extended our studies to natural and synthetic derivatives of plumbagin. We found that 5,8-dimethoxy-1,4-naphthoquinone (naphthazarin) is a potent activator of the Nrf2/ARE pathway, up-regulates the expression of Nrf2-driven genes in primary neuronal and glial cultures, and protects neurons against glutamate-induced excitotoxicity. Published by Elsevier Inc.

  9. Effects of Cyberbullying Experience and Cyberbullying Tendency on School Violence in Early Adolescence

    Science.gov (United States)

    Cho, Mi-Kyoung; Kim, Miyoung

    2017-01-01

    Background: School violence in early adolescence, whose frequency and status have recently changed significantly. Objective: This study attempts to detect the cyber bullying inclination of youth in early adolescence when aggressiveness reaches its peak, to identify school violence, and to develop a school violence prevention program. Method: This study was a survey research, investigating participants who were 470 middle school students in South Korea. For the analysis, independent t-test, one-way ANOVA and hierarchical regression analysis. Results: It is suggested that the school violence victimization experience and cyber bullying infliction experience has an influence in the school violence infliction. And the cyber bullying victimization experience and school violence victimization experience variables exert effects. Conclusion: The results of this study suggest that school nurses who are connecting to the community-school-home should take an active part in the development of school violence mediation education program, considering the cultural characteristics of the country. PMID:29081871

  10. The nature of culture: technological variation in chimpanzee predation on army ants revisited

    DEFF Research Database (Denmark)

    Schöning, Caspar; Humle, Tatyana; Möbius, Yasmin

    2008-01-01

    -eating may represent local behavioral responses of the chimpanzees to the anti-predator traits of the army ant species present at the different sites. We examined assemblages of available prey species, their behavior and morphology, consumption by chimpanzees, techniques employed, and tool lengths at 14...... sites in eastern, central, and western Africa. Where army ants are eaten, tool length and concomitant technique are a function of prey type. Epigaeically foraging species with aggressive workers that inflict painful bites are harvested with longer tools and usually by the "pull-through" technique......; species foraging in leaf-litter with less aggressive workers that inflict less painful bites are harvested with short tools and by the "direct-mouthing" technique. However, prey species characteristics do not explain several differences in army-ant-eating between Bossou (Guinea) and Taï (Ivory Coast...

  11. Parental social determinants of risk for intentional injury: a cross-sectional study of Swedish adolescents

    DEFF Research Database (Denmark)

    Engström, Karin; Diderichsen, Finn; Laflamme, Lucie

    2004-01-01

    OBJECTIVES: We investigated the effect of family social and economic circumstances on intentional injury among adolescents. METHODS: We conducted a cross-sectional register study of youths aged 10 to 19 years who lived in Sweden between 1990 and 1994. We used socioeconomic status, number of parents...... in the household (1- or 2-parent home), receipt of welfare benefits, parental country of birth, and population density as exposures and compiled relative risks and population-attributable risks (PARs) for self-inflicted and interpersonal violence-related injury. RESULTS: For both genders and for both injury types......, receipt of welfare benefits showed the largest crude and net relative risks and the highest PARs. The socioeconomic status-related PAR for self-inflicted injury and the PAR related to number of parents in the household for interpersonal violence-related injury also were high. CONCLUSIONS: Intentional...

  12. Skin conductance response to the pain of others predicts later costly helping.

    Directory of Open Access Journals (Sweden)

    Grit Hein

    Full Text Available People show autonomic responses when they empathize with the suffering of another person. However, little is known about how these autonomic changes are related to prosocial behavior. We measured skin conductance responses (SCRs and affect ratings in participants while either receiving painful stimulation themselves, or observing pain being inflicted on another person. In a later session, they could prevent the infliction of pain in the other by choosing to endure pain themselves. Our results show that the strength of empathy-related vicarious skin conductance responses predicts later costly helping. Moreover, the higher the match between SCR magnitudes during the observation of pain in others and SCR magnitude during self pain, the more likely a person is to engage in costly helping. We conclude that prosocial motivation is fostered by the strength of the vicarious autonomic response as well as its match with first-hand autonomic experience.

  13. Human punishment is not primarily motivated by inequality.

    Science.gov (United States)

    Marczyk, Jesse

    2017-01-01

    Previous theorizing about punishment has suggested that humans desire to punish inequality per se. However, the research supporting such an interpretation contains important methodological confounds. The main objective of the current experiment was to remove those confounds in order to test whether generating inequality per se is punished. Participants were recruited from an online market to take part in a wealth-alteration game with an ostensible second player. The participants were given an option to deduct from the other player's payment as punishment for their behavior during the game. The results suggest that human punishment does not appear to be motivated by inequality per se, as inequality that was generated without inflicting costs on others was not reliably punished. Instead, punishment seems to respond primarily to the infliction of costs, with inequality only becoming relevant as a secondary input for punishment decisions. The theoretical significance of this finding is discussed in the context of its possible adaptive value.

  14. The seductive superego: the trauma of self-betrayal.

    Science.gov (United States)

    Josephs, L

    2001-08-01

    The author describes a pathological manifestation of the approving superego that functions as a perversely seductive superego. In this process, the seductive superego rationalises and makes ego-syntonic a gratification of forbidden wishes that will result in unconscious punishment. The author argues that the seductive superego torments the self by teasing it with the presence of a tantalising but forbidden object of desire and then by inflicting shame on the self for its timidity, which prevents it from pursuing the object in spite of the dangers. He suggests that the seductive superego inflicts a betrayal trauma upon the self by unconsciously actualising a sado-masochistic fantasy of seduction, surrender and betrayal, along with a humiliating punishment for surrendering.

  15. Evidence of interpersonal violence or a special funeral rite in the Neolithic multiple burial from Koszyce in southern Poland – a forensic analysis

    Directory of Open Access Journals (Sweden)

    Konopka Tomasz

    2016-03-01

    Full Text Available This study uses anthropological and forensic medical analyses to determine the cause of fractures found in the remains of 15 individuals buried at a site associated with the Globular Amphora Culture (2875-2670 BC. The intent was to determine the mechanism underlying the injuries and to indicate the types of tools that might have inflicted the blows. The fractures were diversified in their forms, but the majority of the injuries appear to have been inflicted by a flint axe, which is frequently found in graves of the Globular Amphora Culture. Apart from the forearm being severed in one of the victims, all the remaining skeletons showed from 1 to 4 injuries involving solely the skulls. The grave might contain victims attacked by invaders who executed the captives, or else the feature is ritual in character and it reflects the beliefs of the Neolithic community.

  16. Consideration of Cosmetic Surgery As Part of Women's Benefit-Provisioning Mate Retention Strategy.

    Science.gov (United States)

    Atari, Mohammad; Barbaro, Nicole; Sela, Yael; Shackelford, Todd K; Chegeni, Razieh

    2017-01-01

    Individuals perform mate retention behaviors to minimize the risk of partner infidelity and relationship dissolution. The current study investigates whether consideration of cosmetic surgery can be conceptualized as part of a broader strategy of mate retention for women, but not men. We hypothesized that women's consideration of cosmetic surgery would be positively associated with performance frequencies of Benefit-Provisioning and Cost-Inflicting mate retention behaviors. We recruited 203 individuals (54% women) in committed heterosexual relationships from Tehran, Iran. Results indicate a positive association between consideration of cosmetic surgery and Benefit-Provisioning mate retention behaviors for women, but not men. There was no association between consideration of cosmetic surgery and Cost-Inflicting mate retention behaviors. Women therefore may consider cosmetic surgery to improve their physical attractiveness as part of a Benefit-Provisioning strategy to retain a long-term mate. We discuss limitations of the study and highlight future directions for research from an evolutionary perspective.

  17. Does aspiration of bones and joints affect results of later bone scanning

    International Nuclear Information System (INIS)

    Canale, S.T.; Harkness, R.M.; Thomas, P.A.; Massie, J.D.

    1985-01-01

    To determine the effect, if any, of needle aspiration on /sup 99m/Tc bone scanning, three different areas of 15 dogs were first aspirated and then imaged with technetium bone scintigraphy. The hip joint was aspirated, the distal femoral metaphysis was drilled and aspirated, and the tibial periosteum was scraped with an 18- or 20-gauge needle. Varying amounts of trauma were inflicted to simulate varying difficulties at aspiration. /sup 99m/Tc bone scans were obtained from 5 h to 10 days later. There was no evidence of focal technetium uptake after any hip joint aspiration. This was consistent regardless of the amount of trauma inflicted or the time from aspiration to bone scanning. Metaphyseal cortical drilling and tibial periosteal scraping occasionally caused some focal uptake when scanning was delayed greater than 2 days. When osteomyelitis or pyarthrosis is clinically suspected, joint aspiration can be performed without fear of producing a false- positive bone scan

  18. Egg Predation Risk Trigger Adult Hoverfly (Diptera: Syrphidae to Avoid Laying Eggs in Patches Attended by Ladybird Larvae (Coleoptera: Coccinellidae

    Directory of Open Access Journals (Sweden)

    Nugroho Susetya Putra

    2005-12-01

    Full Text Available Oviposition preference of a predatory hoverfly, Episyrphus balteatus on the presence of its potential predators, the ladybird larvae which are inflicted serious impacts on its eggs was examined in a non-choice test. Our results revealed that the biggest and the most aggressive species of ladybird, Harmonia axyridis caused the worst impact on hoverfly eggs by attacking and feeding on. The species and developmental stages of ladybird were attributed to the level of predation risk. We correlated the oviposition site selection by hoverfly females to the egg predation risk level inflicted by ladybird larvae. Hoverfly females laid the least number of eggs on the patches attended by the strongest competitor, the larva of H. axyridis, and tended to lay the highest number of eggs on colonies attended by the weakest competitor, the larva of Scymnus posticalis. In addition, the impact of the fourth instar larva of ladybirds was stronger than of the first instar larva.

  19. Human punishment is not primarily motivated by inequality

    Science.gov (United States)

    Marczyk, Jesse

    2017-01-01

    Previous theorizing about punishment has suggested that humans desire to punish inequality per se. However, the research supporting such an interpretation contains important methodological confounds. The main objective of the current experiment was to remove those confounds in order to test whether generating inequality per se is punished. Participants were recruited from an online market to take part in a wealth-alteration game with an ostensible second player. The participants were given an option to deduct from the other player’s payment as punishment for their behavior during the game. The results suggest that human punishment does not appear to be motivated by inequality per se, as inequality that was generated without inflicting costs on others was not reliably punished. Instead, punishment seems to respond primarily to the infliction of costs, with inequality only becoming relevant as a secondary input for punishment decisions. The theoretical significance of this finding is discussed in the context of its possible adaptive value. PMID:28187166

  20. Human punishment is not primarily motivated by inequality.

    Directory of Open Access Journals (Sweden)

    Jesse Marczyk

    Full Text Available Previous theorizing about punishment has suggested that humans desire to punish inequality per se. However, the research supporting such an interpretation contains important methodological confounds. The main objective of the current experiment was to remove those confounds in order to test whether generating inequality per se is punished. Participants were recruited from an online market to take part in a wealth-alteration game with an ostensible second player. The participants were given an option to deduct from the other player's payment as punishment for their behavior during the game. The results suggest that human punishment does not appear to be motivated by inequality per se, as inequality that was generated without inflicting costs on others was not reliably punished. Instead, punishment seems to respond primarily to the infliction of costs, with inequality only becoming relevant as a secondary input for punishment decisions. The theoretical significance of this finding is discussed in the context of its possible adaptive value.