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Sample records for acid-induced status epilepticus

  1. Administration of Simvastatin after Kainic Acid-Induced Status Epilepticus Restrains Chronic Temporal Lobe Epilepsy

    Xie, Chuncheng; Sun, Jiahang; Qiao, Weidong; Lu, Dunyue; Wei, Lanlan; NA, MENG; Song, Yuanyuan; Hou, Xiaohua; LIN, ZHIGUO

    2011-01-01

    In this study, we examined the effect of chronic administration of simvastatin immediately after status epilepticus (SE) on rat brain with temporal lobe epilepsy (TLE). First, we evaluated cytokines expression at 3 days post KA-lesion in hippocampus and found that simvastatin-treatment suppressed lesion-induced expression of interleukin (IL)-1β and tumor necrosis factor-α (TNF-α). Further, we quantified reactive astrocytosis using glial fibrillary acidic protein (GFAP) staining and neuron los...

  2. Status Epilepticus.

    Seinfeld, Syndi; Goodkin, Howard P; Shinnar, Shlomo

    2016-01-01

    Although the majority of seizures are brief and cause no long-term consequences, a subset is sufficiently prolonged that long-term consequences can result. These very prolonged seizures are termed "status epilepticus" (SE) and are considered a neurological emergency. The clinical presentation of SE can be diverse. SE can occur at any age but most commonly occurs in the very young and the very old. There are numerous studies on SE in animals in which the pathophysiology, medication responses, and pathology can be rigorously studied in a controlled fashion. Human data are consistent with the animal data. In particular, febrile status epilepticus (FSE), a form of SE common in young children, is associated with injury to the hippocampus and subsequent temporal lobe epilepsy (TLE) in both animals and humans. PMID:26931807

  3. Fresh green tea and gallic acid ameliorate oxidative stress in kainic acid-induced status epilepticus.

    Huang, Hsiao-Ling; Lin, Chih-Cheng; Jeng, Kee-Ching G; Yao, Pei-Wun; Chuang, Lu-Te; Kuo, Su-Ling; Hou, Chien-Wei

    2012-03-01

    Green tea is one of the most-consumed beverages due to its taste and antioxidative polyphenols. However, the protective effects of green tea and its constituent, gallic acid (GA), against kainic acid (KA)-induced seizure have not been studied. We investigated the effect of fresh green tea leaf (GTL) and GA on KA-induced neuronal injury in vivo and in vitro. The results showed that GTL and GA reduced the maximal seizure classes, predominant behavioral seizure patterns, and lipid peroxidation in male FVB mice with status epilepticus (SE). GTL extract and GA provided effective protection against KA-stressed PC12 cells in a dose-dependent manner. In the protective mechanism study, GTL and GA decreased Ca(2+) release, ROS, and lipid peroxidation from KA-stressed PC12 cells. Western blot results revealed that mitogen-activated protein kinases (MAPKs), RhoA, and COX-2 expression were increased in PC12 cells under KA stress, and expression of COX-2 and p38 MAPK, but not RhoA, was significantly reduced by GTL and GA. Furthermore, GTL and GA were able to reduce PGE(2) production from KA-stressed PC12 cells. Taken together, the results showed that GTL and GA provided neuroprotective effects against excitotoxins and may have a clinical application in epilepsy. PMID:22324774

  4. Partial motor status epilepticus

    Gilberto Rebello de Mattos; José C. Rollemberg Filho

    1992-01-01

    We report the case of a young female patient with photosensitive primary epilepsy who presented partial motor status epilepticus provoked by the act of shutting the eyes. Clinical, EEG and neuroimage data are presented and discussed.

  5. STATUS EPILEPTICUS: A REVIEW

    B. Adibeik

    2009-01-01

    Full Text Available ObjectiveStatus Epilepticus (SE has been described as a series of major motor seizure without recovery of consciousness between seizures.SE is a medical emergency that requires prompt diagnosis and appropriate treatment.In this article we shall conclude history, epidemiology, etiology, risk factors, thebest management as well as the prognosis of the condition.Keywords:Status Epilepticus (SE, adults, children, neonates.

  6. Transcriptome analysis of the hippocampal CA1 pyramidal cell region after kainic acid-induced status epilepticus in juvenile rats.

    Hanna B Laurén

    Full Text Available Molecular mechanisms involved in epileptogenesis in the developing brain remain poorly understood. The gene array approach could reveal some of the factors involved by allowing the identification of a broad scale of genes altered by seizures. In this study we used microarray analysis to reveal the gene expression profile of the laser microdissected hippocampal CA1 subregion one week after kainic acid (KA-induced status epilepticus (SE in 21-day-old rats, which are developmentally roughly comparable to juvenile children. The gene expression analysis with the Chipster software generated a total of 1592 differently expressed genes in the CA1 subregion of KA-treated rats compared to control rats. The KEGG database revealed that the identified genes were involved in pathways such as oxidative phosporylation (26 genes changed, and long-term potentiation (LTP; 18 genes changed. Also genes involved in Ca(2+ homeostasis, gliosis, inflammation, and GABAergic transmission were altered. To validate the microarray results we further examined the protein expression for a subset of selected genes, glial fibrillary protein (GFAP, apolipoprotein E (apo E, cannabinoid type 1 receptor (CB1, Purkinje cell protein 4 (PEP-19, and interleukin 8 receptor (CXCR1, with immunohistochemistry, which confirmed the transcriptome results. Our results showed that SE resulted in no obvious CA1 neuronal loss, and alterations in the expression pattern of several genes during the early epileptogenic phase were comparable to previous gene expression studies of the adult hippocampus of both experimental epileptic animals and patients with temporal lobe epilepsy (TLE. However, some changes seem to occur after SE specifically in the juvenile rat hippocampus. Insight of the SE-induced alterations in gene expression and their related pathways could give us hints for the development of new target-specific antiepileptic drugs that interfere with the progression of the disease in the

  7. Refractory status epilepticus

    Sanjay P Singh

    2014-01-01

    Full Text Available Refractory status epilepticus is a potentially life-threatening medical emergency. It requires early diagnosis and treatment. There is a lack of consensus upon its semantic definition of whether it is status epilepticus that continues despite treatment with benzodiazepine and one antiepileptic medication (AED, i.e., Lorazepam + phenytoin. Others regard refractory status epilepticus as failure of benzodiazepine and 2 antiepileptic medications, i.e., Lorazepam + phenytoin + phenobarb. Up to 30% patients in SE fail to respond to two antiepileptic drugs (AEDs and 15% continue to have seizure activity despite use of three drugs. Mechanisms that have made the treatment even more challenging are GABA-R that is internalized during status epilepticus and upregulation of multidrug transporter proteins. All patients of refractory status epilepticus require continuous EEG monitoring. There are three main agents used in the treatment of RSE. These include pentobarbital or thiopental, midazolam and propofol. RSE was shown to result in mortality in 35% cases, 39.13% of patients were left with severe neurological deficits, while another 13% had mild neurological deficits.

  8. Pharmacotherapy for Status Epilepticus

    Trinka, Eugen; Höfler, Julia; Leitinger, Markus; Brigo, Francesco

    2015-01-01

    Status epilepticus (SE) represents the most severe form of epilepsy. It is one of the most common neurologic emergencies, with an incidence of up to 61 per 100,000 per year and an estimated mortality of 20 %. Clinically, tonic-clonic convulsive SE is divided into four subsequent stages: early, established, refractory, and super-refractory. Pharmacotherapy of status epilepticus, especially of its later stages, represents an “evidence-free zone,” due to a lack of high-quality, controlled trials...

  9. STATUS EPILEPTICUS: A REVIEW

    B. Adibeik

    2008-10-01

    Full Text Available ObjectiveStatus Epilepticus (SE has been described as a series of major motor seizure without recovery of consciousness between seizures.SE is a medical emergency that requires prompt diagnosis and appropriate treatment.In this article we shall conclude history, epidemiology, etiology, risk factors, thebest management as well as the prognosis of the condition.

  10. Nonconvulsive Status Epilepticus

    Ayhan Aköz

    2014-08-01

    Full Text Available Status epilepticus (SE can be divided into two subgroups, convulsive status epilepticus (CSE and nonconvulsive status epilepticus (NCSE. NCSE is clinically characterized by recurrence or persistence of absence or complex partial seizures which unconsciousness persists. Seizures are lasted more than 30 minutes, and accompanied by mental and behavioral changes. Although the main feature is the change of level of consciousness, affective, memory, cognitive, speech, motor systems, behavioral and psychiatric disorders can be also seen. Electroencephalography (EEG is the single diagnostic method in this situation. NCSE constitutes approximately 25% of all SE, however it is thought that sometimes it is misdiagnosed and the incidence of NCSE may be higher. The causes are disorders of central nervous system (stroke, infection, trauma, tumor, and metabolic factors (hypoxia, renal diseases, drugs, failure to use antiepileptic drug. The treatment contains the standard therapy of SE. Short-acting benzodiazepines are preferred in initial treatment. For more resistant cases, loading of phenytoin is applied. If there is no response to treatment, midazolam and propofol additionally to barbiturates can be used. We aimed to present a case admitted to our ED with altered mental status and diagnosed as NCSE that is under-diagnosed.

  11. Status epilepticus in scleromyxedema

    Soifa Markoula; Soifa Zouroudi; Soitrios Giannopoulos; Kimon Tsoukanelis; Ananstasia Zikou; Athanassios P Kyritsis

    2016-01-01

    Scleromyxedema is a rare dermatologic disorder, characterized by erythematous or yelowish lichenoid waxy papules. Neurological manifestations are rare but wel-recognized. A 51-year-old woman, diagnosed with scleromyxedema, was admitted to the hospital with status epilepticus, caused by brain lesions, as disclosed in a brain magnetic resonance imaging (MRI). The patient was treated with anticonvulsants and corticosteroids and gradualy recovered fuly. A complete remission of the lesions was shown in a folow-up brain MRI. In cases with scleromyxedema and the presence of neurological manifestations, we need to pay attention to central nervous system involvement, especialy when combined with brain MRI lesions, and treat the patient appropriately.

  12. Pharmacotherapy for Status Epilepticus.

    Trinka, Eugen; Höfler, Julia; Leitinger, Markus; Brigo, Francesco

    2015-09-01

    Status epilepticus (SE) represents the most severe form of epilepsy. It is one of the most common neurologic emergencies, with an incidence of up to 61 per 100,000 per year and an estimated mortality of 20 %. Clinically, tonic-clonic convulsive SE is divided into four subsequent stages: early, established, refractory, and super-refractory. Pharmacotherapy of status epilepticus, especially of its later stages, represents an "evidence-free zone," due to a lack of high-quality, controlled trials to inform clinical decisions. This comprehensive narrative review focuses on the pharmacotherapy of SE, presented according to the four-staged approach outlined above, and providing pharmacological properties and efficacy/safety data for each antiepileptic drug according to the strength of scientific evidence from the available literature. Data sources included MEDLINE and back-tracking of references in pertinent studies. Intravenous lorazepam or intramuscular midazolam effectively control early SE in approximately 63-73 % of patients. Despite a suboptimal safety profile, intravenous phenytoin or phenobarbital are widely used treatments for established SE; alternatives include valproate, levetiracetam, and lacosamide. Anesthetics are widely used in refractory and super-refractory SE, despite the current lack of trials in this field. Data on alternative treatments in the later stages are limited. Valproate and levetiracetam represent safe and effective alternatives to phenobarbital and phenytoin for treatment of established SE persisting despite first-line treatment with benzodiazepines. To date there are no class I data to support recommendations for most antiepileptic drugs for established, refractory, and super-refractory SE. Limiting the methodologic heterogeneity across studies is required and high-class randomized, controlled trials to inform clinicians about the best treatment in established and refractory status are needed. PMID:26310189

  13. Sesamin ameliorates oxidative stress and mortality in kainic acid-induced status epilepticus by inhibition of MAPK and COX-2 activation

    Lin Ching-Huei; Shen Mei-Lin; Peng Yu-Fen; Wu Szu-Pei; Yao Pei-Wun; Hou Chien-Wei; Hsieh Peiyuan F; Chao Ya-Yun; Chang Ming-Hong; Jeng Kee-Ching

    2011-01-01

    Abstract Background Kainic acid (KA)-induced status epilepticus (SE) was involved with release of free radicals. Sesamin is a well-known antioxidant from sesame seeds and it scavenges free radicals in several brain injury models. However the neuroprotective mechanism of sesamin to KA-induced seizure has not been studied. Methods Rodents (male FVB mice and Sprague-Dawley rats) were fed with sesamin extract (90% of sesamin and 10% sesamolin), 15 mg/kg or 30 mg/kg, for 3 days before KA subcutane...

  14. Outcome of Refractory Status Epilepticus

    J Gordon Millichap

    2002-01-01

    Full Text Available The records of twenty-two children, ages 4.5 months to 18 years, treated for refractory status epilepticus (RSE between 1992 and 2000, were reviewed retrospectively at Children’s Hospital, Boston.

  15. Management of Status Epilepticus in Children

    Smith, Douglas M.; Emily L. McGinnis; Diana J. Walleigh; Nicholas S. Abend

    2016-01-01

    Status epilepticus is a common pediatric neurological emergency. Management includes prompt administration of appropriately selected anti-seizure medications, identification and treatment of seizure precipitant(s), as well as identification and management of associated systemic complications. This review discusses the definitions, classification, epidemiology and management of status epilepticus and refractory status epilepticus in children.

  16. Sesamin ameliorates oxidative stress and mortality in kainic acid-induced status epilepticus by inhibition of MAPK and COX-2 activation

    Lin Ching-Huei

    2011-05-01

    Full Text Available Abstract Background Kainic acid (KA-induced status epilepticus (SE was involved with release of free radicals. Sesamin is a well-known antioxidant from sesame seeds and it scavenges free radicals in several brain injury models. However the neuroprotective mechanism of sesamin to KA-induced seizure has not been studied. Methods Rodents (male FVB mice and Sprague-Dawley rats were fed with sesamin extract (90% of sesamin and 10% sesamolin, 15 mg/kg or 30 mg/kg, for 3 days before KA subcutaneous injection. The effect of sesamin on KA-induced cell injury was also investigated on several cellular pathways including neuronal plasticity (RhoA, neurodegeneration (Caspase-3, and inflammation (COX-2 in PC12 cells and microglial BV-2 cells. Results Treatment with sesamin extract (30 mg/kg significantly increased plasma α-tocopherol level 50% and 55.8% from rats without and with KA treatment, respectively. It also decreased malondialdehyde (MDA from 145% to 117% (p = 0.017 and preserved superoxide dismutase from 55% of the vehicle control mice to 81% of sesamin-treated mice, respectively to the normal levels (p = 0.013. The treatment significantly decreased the mortality from 22% to 0% in rats. Sesamin was effective to protect PC12 cells and BV-2 cells from KA-injury in a dose-dependent manner. It decreased the release of Ca2+, reactive oxygen species, and MDA from PC12 cells. Western blot analysis revealed that sesamin significantly reduced ERK1/2, p38 mitogen-activated protein kinases, Caspase-3, and COX-2 expression in both cells and RhoA expression in BV-2 cells. Furthermore, Sesamin was able to reduce PGE2 production from both cells under KA-stimulation. Conclusions Taken together, it suggests that sesamin could protect KA-induced brain injury through anti-inflammatory and partially antioxidative mechanisms.

  17. [Treatment of non-convulsive status epilepticus].

    Liimatainen, Suvi; Ollikainen, Jyrki; Peltola, Jukka

    2011-01-01

    Non-convulsive status epilepticus is an insidious condition and a challenging diagnosis for neurologists on call. The condition must, however, be recognized, since it constitutes a neurological emergency. Non-convulsive status epilepticus may also be associated as an additional complication with an acute neurologic disease, in which case an EEG recording is usually required. In addition, non-convulsive status epilepticus can be found in a significant proportion of patients with unconsciousness of unknown origin. PMID:21995129

  18. Genetic mutations associated with status epilepticus.

    Bhatnagar, M; Shorvon, S

    2015-08-01

    This paper reports the results of a preliminary search of the literature aimed at identifying the genetic mutations reported to be strongly associated with status epilepticus. Genetic mutations were selected for inclusion if status epilepticus was specifically mentioned as a consequence of the mutation in standard genetic databases or in a case report or review article. Mutations in 122 genes were identified. The genetic mutations identified were found in only rare conditions (sometimes vanishingly rare) and mostly in infants and young children with multiple other handicaps. Most of the genetic mutations can be subdivided into those associated with cortical dysplasias, inborn errors of metabolism, mitochondrial disease, or epileptic encephalopathies and childhood syndromes. There are no identified 'pure status epilepticus genes'. The range of genes underpinning status epilepticus differs in many ways from the range of genes underpinning epilepsy, which suggests that the processes underpinning status epilepticus differ from those underpinning epilepsy. It has been frequently postulated that status epilepticus is the result of a failure of 'seizure termination mechanisms', but the wide variety of genes affecting very diverse biochemical pathways identified in this survey makes any unitary cause unlikely. The genetic influences in status epilepticus are likely to involve a wide range of mechanisms, some related to development, some to cerebral energy production, some to diverse altered biochemical pathways, some to transmitter and membrane function, and some to defects in networks or systems. The fact that many of the identified genes are involved with cerebral development suggests that status epilepticus might often be a system or network phenomenon. To date, there are very few genes identified which are associated with adult-onset status epilepticus (except in those with preexisting neurological damage), and this is disappointing as the cause of many adult

  19. [Simple partial frontal nonconvulsive status epilepticus].

    Thomas, P; Mottin, Y

    1997-07-01

    Non convulsive status epilepticus (NCSE) of frontal origin is a rare cause of mental confusion. The present case of possible frontal-onset NCSE proved to have a neuropsychological examination that was suggestive either of a disruption of attentional function or a left prefrontal dysfunction, exhibiting disturbances of immediate memory and logical programmation, perseverations and affective disinhibition. Vigilance was not impaired. This case was therefore, on a nosographic point of view, more consistent with a simple partial status epilepticus with cognitive and affective symptomatology rather than with a complex partial status epilepticus of extra-temporal origin. PMID:9684010

  20. Nonconvulsive status epilepticus disguising as hepatic encephalopathy

    Jo, Yong Min; Lee, Sung Wook; Han, Sang Young; Baek, Yang Hyun; Ahn, Ji Hye; Choi, Won Jong; Lee, Ji Young; Kim, Sang Ho; Yoon, Byeol A

    2015-01-01

    Nonconvulsive status epilepticus has become an important issue in modern neurology and epileptology. This is based on difficulty in definitively elucidating the condition and its various clinical phenomena and on our inadequate insight into the intrinsic pathophysiological processes. Despite nonconvulsive status epilepticus being a situation that requires immediate treatment, this disorder may not be appreciated as the cause of mental status impairment. Although the pathophysiology of nonconv...

  1. Prognostic Factors for Refractory Status Epilepticus

    J. Gordon Millichap

    2013-03-01

    Full Text Available Researchers at the Mayo Clinic, Rochester, MN studied the outcome and identified prognostic factors for refractory status epilepticus (RSE in 54 adult patients, median age 52 years [range 18-93].

  2. Managing Status Epilepticus in the Older Adult

    Stephane Legriel; Brophy, Gretchen M.

    2016-01-01

    The aim of this systematic review was to describe particularities in epidemiology, outcome, and management modalities in the older adult population with status epilepticus. There is a higher incidence of status epilepticus in the older adult population, and it commonly has a nonconvulsive presentation. Diagnosis in this population may be difficult and requires an unrestricted use of EEG. Short and long term associated-mortality are high, and age over 60 years is an independent factor associat...

  3. Nonconvulsive status epilepticus after electroconvulsive therapy

    Povlsen, Uffe Juul; Wildschiødtz, Gordon; Høgenhaven, Hans;

    2003-01-01

    SUMMARY: We describe three cases of nonconvulsive status epilepticus induced by electroconvulsive therapy (ECT). Nonconvulsive status epilepticus is an important differential diagnosis in patients who develop prolonged confusion after ECT. The present cases exemplify the difficulty in defining the...... diagnosis on the basis of the clinical manifestations. The application of electroencephalography is recommended in monitoring patients with prolonged confusion following ECT. Concurrent drug therapy and ECT is discussed....

  4. Early Developmental Outcome Following Convulsive Status Epilepticus

    J Gordon Millichap

    2013-08-01

    Full Text Available Investigators at the Developmental Cognitive Neurosciences Unit, Institute of Child Health, London, other centers in the UK, and Dartmouth School of Medicine, NH, USA, prospectively recruited children aged between 1 and 42 months from North London who had at least one episode of convulsive status epilepticus (CSE and classified them as prolonged febrile seizures (PFS or nonfebrile CSE.

  5. Risk of Status Epilepticus in Epilepsy

    J Gordon Millichap

    2004-10-01

    Full Text Available The occurrence of status epilepticus (SE after the initial diagnosis of epilepsy was determined in a prospective community-based cohort study of 613 children at Montefiore Medical Center, Bronx, NY; Yale Medical School, New Haven, CT; and BIOS/NIU, DeKalb, IL.

  6. Acute polyhydramnios after maternal status epilepticus

    Shindo, Ryosuke; Aoki, Shigeru; Kasai, Michi; Takahashi, Tsuneo; Hirahara, Fumiki

    2015-01-01

    Key Clinical Message Maternal status epilepticus can cause fetal hypoxic ischemic encephalopathy that in turn results in acute polyhydramnios caused by fetal dysphagia; thus, acute polyhydramnios is a symptom that should lead to a suspicion of fetal dysphagia caused by hypoxic ischemic encephalopathy.

  7. Management of super refractory status epilepticus with isoflurane and hypothermia

    Charles Patrick Gilman

    2015-01-01

    Full Text Available Super-refractory status epilepticus is status epilepticus that continues beyond 24 hours and includes those cases in which epilepsy is recurrent upon reduction or withdrawal of treatment. We describe the presentation and successful management of a male patient with super-refractory status epilepticus using the inhaled anesthetic, isoflurane, and mild hypothermia (HT. The potential utility of combined HT and volatile anesthesia is discussed.

  8. Management of super refractory status epilepticus with isoflurane and hypothermia

    Charles Patrick Gilman

    2015-01-01

    Super-refractory status epilepticus is status epilepticus that continues beyond 24 hours and includes those cases in which epilepsy is recurrent upon reduction or withdrawal of treatment. We describe the presentation and successful management of a male patient with super-refractory status epilepticus using the inhaled anesthetic, isoflurane, and mild hypothermia (HT). The potential utility of combined HT and volatile anesthesia is discussed.

  9. Status epilepticus: Analysis of refractory cases

    B. P. Gladov; O. A. Podgornaya; P. N. Vlasov

    2016-01-01

    Objective: to analyze refractory status epilepticus (SE) cases.Patients and methods. Fifteen female patients aged 21 to 62 years with refractory SE were comprehensively examined using long-term electroencephalography monitoring. The investigators evaluated the efficiency of treatment regimens with intravenous antiepileptic drugs (AEDs), such as diazepam (DZP); valproic acid (VPA); levetiracetam; and lacosamide and their combinations, at the prehospital and hospital stages, as well as SE thera...

  10. Managing Status Epilepticus in the Older Adult.

    Legriel, Stephane; Brophy, Gretchen M

    2016-01-01

    The aim of this systematic review was to describe particularities in epidemiology, outcome, and management modalities in the older adult population with status epilepticus. There is a higher incidence of status epilepticus in the older adult population, and it commonly has a nonconvulsive presentation. Diagnosis in this population may be difficult and requires an unrestricted use of EEG. Short and long term associated-mortality are high, and age over 60 years is an independent factor associated with poor outcome. Stroke (acute or remote symptomatic), miscellaneous metabolic causes, dementia, infections hypoxemia, and brain injury are among the main causes of status epilepticus occurrence in this age category. The use of anticonvulsive agents can be problematic as well. Thus, it is important to take into account the specific aspects related to the pharmacokinetic and pharmacodynamic changes in older critically-ill adults. Beyond these precautions, the management may be identical to that of the younger adult, including prompt initiation of symptomatic and anticonvulsant therapies, and a broad and thorough etiological investigation. Such management strategies may improve the vital and functional prognosis of these patients, while maintaining a high overall quality of care. PMID:27187485

  11. Managing Status Epilepticus in the Older Adult

    Stephane Legriel

    2016-05-01

    Full Text Available The aim of this systematic review was to describe particularities in epidemiology, outcome, and management modalities in the older adult population with status epilepticus. There is a higher incidence of status epilepticus in the older adult population, and it commonly has a nonconvulsive presentation. Diagnosis in this population may be difficult and requires an unrestricted use of EEG. Short and long term associated-mortality are high, and age over 60 years is an independent factor associated with poor outcome. Stroke (acute or remote symptomatic, miscellaneous metabolic causes, dementia, infections hypoxemia, and brain injury are among the main causes of status epilepticus occurrence in this age category. The use of anticonvulsive agents can be problematic as well. Thus, it is important to take into account the specific aspects related to the pharmacokinetic and pharmacodynamic changes in older critically-ill adults. Beyond these precautions, the management may be identical to that of the younger adult, including prompt initiation of symptomatic and anticonvulsant therapies, and a broad and thorough etiological investigation. Such management strategies may improve the vital and functional prognosis of these patients, while maintaining a high overall quality of care.

  12. Pediatric Super-Refractory Status Epilepticus Treated with Allopregnanolone

    Broomall, Eileen; Natale, JoAnne E.; Grimason, Michele; Goldstein, Joshua; Smith, Craig M.; Chang, Celia; Kanes, Stephen; Rogawski, Michael A.; Wainwright, Mark S.

    2015-01-01

    Super-refractory status epilepticus is a life-threatening condition. Resistance to benzodiazepine and barbiturate treatment for this disorder is thought to be due to internalization of synaptic γ-aminobutyric acid (GABA)A receptors, and withdrawal of benzodiazepines and barbiturates during treatment often triggers seizure recurrence. The neurosteroid allopregnanolone acts as a positive allosteric modulator of synaptic and extrasynaptic GABAA receptors. Here we describe the use of allopregnanolone in 2 pediatric patients with super-refractory status epilepticus. This treatment allowed the general anesthetic infusions to be weaned with resolution of status epilepticus. This is the first report of allopregnanolone use to treat status epilepticus in children. PMID:25363147

  13. Status Epilepticus in Adults: A Review of Diagnosis and Treatment.

    Lawson, Thomas; Yeager, Susan

    2016-04-01

    Status epilepticus is a medical emergency that requires rapid diagnosis and treatment. Nonconvulsive status epilepticus is frequently underdiagnosed and therefore undertreated, which can lead to permanent neuronal damage resulting in disability or death. Despite the frequent occurrence and morbidity associated with status epilepticus, this topic has received little attention within the literature. A systematic approach to treatment should start with management of airway, breathing, and circulation, followed by administration of benzodiazepines and intravenous antiepileptic drugs, and rapid escalation of therapy to prevent morbidity and mortality. Armed with the information in this article, nurses will have a higher-level understanding of what to do when encountering a patient in status epilepticus. PMID:27037340

  14. New lessons: Classic treatments in convulsive status epilepticus.

    Renganathan, R

    2012-02-03

    Convulsive status epilepticus is a relatively common life-threatening illness requiring prompt intervention. There has been much debate about the appropriate protocol for management of convulsive status epilepticus. Published data on the management of this condition in Ireland is limited. Our aim was to establish if there was a structured, evidence-based or consensus-based protocol being implemented in the management of status epilepticus in our centre. We retrospectively audited all charts with a diagnosis of \\'Status Epilepticus\\' admitted to our hospital from January 1998 to December 2002. A total of 95 episodes of convulsive status epilepticus were recorded. 34 charts were reviewed. Benzodiazepines were the drug class of first choice in 96% of patients. However, the doses of benzodiazepines used varied widely. The most frequent dose of phenytoin used was 1 gram. No one received continuous EEG monitoring during treatment of refractory status epilepticus. Overall mortality was 18%. The results of this study show that there is no consistent protocol was being followed for the management of convulsive status epilepticus in our centre. The drugs of first choice varied between diazepam and lorazepam in most cases. Although phenytoin was used as second line drug, the dose used was frequently suboptimal. We have developed a protocol for the management for convulsive status in our centre.

  15. Prallethrin Poisoning Presenting as Status Epilepticus

    D Vijayaraju

    2014-02-01

    Full Text Available Mosquito repellents contain pyrethroid derivatives, as the active ingredient. Data regarding human toxicity following oral intake is limited. This is a case report of an individual who presented with neurotoxicity following oral ingestion of prallethrin (2.4% w/w of a higher concentration present in formulations commercially available than previously. A 22 year old male presented to the emergency Room (ER in status epilepticus. He was managed in the Intensive Care Unit (ICU. No cause for his status could be determined after all laboratory investigations. A review of history with the patient revealed that he had ingested a bottle of liquid mosquito repellent (45 ml. The patient has had no further symptoms on follow up and has been off anti epileptics. Pyrethroid containing mosquito repellents act on neuronal sodium channels causing hyperexcitiability. With no known specific antidotes, symptomatic treatment is the main stay of management.

  16. Clinical decision making in seizures and status epilepticus.

    Teran, Felipe; Harper-Kirksey, Katrina; Jagoda, Andy

    2015-01-01

    Seizures and status epilepticus are frequent neurologic emergencies in the emergency department, accounting for 1% of all emergency department visits. The management of this time-sensitive and potentially life-threatening condition is challenging for both prehospital providers and emergency clinicians. The approach to seizing patients begins with differentiating seizure activity from mimics and follows with identifying potential secondary etiologies, such as alcohol-related seizures. The approach to the patient in status epilepticus and the patient with nonconvulsive status epilepticus constitutes a special clinical challenge. This review summarizes the best available evidence and recommendations regarding diagnosis and resuscitation of the seizing patient in the emergency setting. PMID:25902572

  17. Emergency Neurological Life Support: Status Epilepticus.

    Claassen, Jan; Riviello, James J; Silbergleit, Robert

    2015-12-01

    Patients with prolonged or rapidly recurring convulsions lasting more than 5 min are in status epilepticus (SE) and require immediate resuscitation. Although there are relatively few randomized clinical trials, available evidence and experience suggest that early and aggressive treatment of SE improves patient outcomes, for which reason this was chosen as an Emergency Neurological Life Support protocol. The current approach to the emergency treatment of SE emphasizes rapid initiation of adequate doses of first-line therapy, as well as accelerated second-line anticonvulsant drugs and induced coma when these fail, coupled with admission to a unit capable of neurological critical care and electroencephalography monitoring. This protocol will focus on the initial treatment of SE but also review subsequent steps in the protocol once the patient is hospitalized. PMID:26438462

  18. Primary Amoebic (Naegleria fowleri Meningoencephalitis Presenting as Status Epilepticus

    A Sharma

    2011-04-01

    Full Text Available Primary amebic meningoencephalitis (PAM is a rare entity. Usual presenting features are fever, headache and seizures with meningeal signs and this disease carries high mortality rate. We present a case report of PAM presenting as status epilepticus.

  19. Ketogenic diet in 3 cases of childhood refractory status epilepticus

    Sort, Rune; Born, Alfred P; Pedersen, Karen N.;

    2013-01-01

    Refractory status epilepticus (RSE) in children is associated with a significant risk of death or neurological morbidity. Recently attention has been drawn to the ketogenic diet (KD) as an acute treatment, as it has shown promise in controlling seizures in otherwise refractory status epilepticus in...... several cases. We have listed these and reviewed all cases of KD used in RSE at our centre. KD was given as 4:1 fat:carbohydrate-protein solution....

  20. Status epilepticus: Analysis of refractory cases

    B. P. Gladov

    2016-01-01

    Full Text Available Objective: to analyze refractory status epilepticus (SE cases.Patients and methods. Fifteen female patients aged 21 to 62 years with refractory SE were comprehensively examined using long-term electroencephalography monitoring. The investigators evaluated the efficiency of treatment regimens with intravenous antiepileptic drugs (AEDs, such as diazepam (DZP; valproic acid (VPA; levetiracetam; and lacosamide and their combinations, at the prehospital and hospital stages, as well as SE therapy complications noted only in the intravenous administration of narcotics (propofol, sodium thiopental.Results and discussion. A fetal outcome due to multiple organ dysfunction indirectly related to SE was recorded in 2 (13.3% patients with acute symptomatic status. SE was abolished in the other 13 cases. The preliminary findings may suggest that it is appropriate to prescribe VPA just at the prehospital stage. The co-administration of VPA and DZP substantially enhances the efficiency of SE therapy. The maximum acceptable doses of AEDs using the whole available therapeutic arsenal should be administered within the first hours of acute symptomatic SE.

  1. Cocaine-Associated Seizures and Incidence of Status Epilepticus

    Majlesi, Nima DO

    2010-05-01

    Full Text Available Objectives: Acute complications from cocaine abuse are commonly treated in the emergency department (ED; one of the most consequential is status epilepticus. The incidence of this complication is not clearly defined in the prior literature on cocaine-associated sequelae. We evaluated the incidence of status epilepticus in patients with seizures secondary to suspected cocaine use.Methods: We performed a retrospective multi-center study of patients with seizures resulting from cocaine use. We identified study subjects at 15 hospitals by record review and conducted a computer-assisted records search to identify patients with seizures for each institution over a four-year period. We selected subjects from this group on the basis of cocaine use and determined the occurrence of status epilepticus among them. Data were collected on each subject using a standardized data collection form.Results: We evaluated 43 patients in the ED for cocaine-associated seizures. Their age range was 17 to 54, with a mean age was 31 years; 53% were male. Of 43 patients, 42 experienced a single tonic-clonic seizure and one developed status epilepticus. All patients had either a history of cocaine use or positive urine drug screen for cocaine.Conclusion: Despite reported cases of status epilepticus with cocaine-induced seizures, the incidence of this complication was unclear based on prior literature. This study shows that most cocaine-associated seizures are self-limited. [West J Emerg Med. 2010; 11(2:157-160.

  2. Status epilepticus in the elderly: differential diagnosis and treatment

    Mauricio EA

    2011-03-01

    Full Text Available Elizabeth Ann Mauricio, William David FreemanMayo Clinic, Jacksonville, FL, USADate of Preparation 28th January 2011 Conflict of interest: None declaredAbstract: Seizures are not an uncommon occurrence in older adults, and the incidence of status epilepticus is much greater in the elderly than in younger populations. Status epilepticus is a neurologic emergency and requires prompt intervention to minimize morbidity and mortality. Treatment involves both supportive care as well as initiation of medications to stop all clinical and electrographic seizure activity. Benzodiazepines are used as first-line agents, followed by antiepileptic drugs when seizures persist. In refractory status epilepticus, urgent neurologic consultation is indicated for the titration of anesthetic agents to a level of appropriate background suppression on EEG. In light of our aging population, physician awareness and competence in the management of status epilepticus is imperative and should be recognized as a growing public health concern.Keywords: status epilepticus, convulsive, generalized, nonconvulsive, refractory, elderly, treatment 

  3. How to Manage Electrical Status Epilepticus in Sleep.

    Veggiotti, Pierangelo; Pera, Maria Carmela; Olivotto, Sara; De Giorgis, Valentina

    2016-02-01

    Electrical status epilepticus in sleep is an age-dependent syndrome with the characteristic pattern of continuous spike and waves during non-rapid eye movement sleep. Most children can present developmental deterioration. The demonstration of the EEG pattern has to rely on all night long EEG recordings. A comprehensive neuropsychologic evaluation with periodic reassessment should be performed. For the idiopathic forms of electrical status epilepticus in sleep, clobazam could be considered as the first-line therapy; in the other cases, corticosteroids, in particular intravenous methylprednisolone pulse therapy, remain the most effective and should be considered the therapy of choice. PMID:26840869

  4. On Etiology and Mortality Rate of Status Epilepticus

    F Ashraf Zadeh

    2000-01-01

    The etiology and mortality rate of Status Epilepticus in 60 pediatric patients, aged 2 months to 13 years, during 10 years has been evaluated. The results show that: -41.7% of the patients were female and 58.3% male. -65% of patients were<3 years and 35% >3 years old. - Mortality rate was 21.6%, 46.1% of which were referral patients. -Major causes of Status Epilepticus were: Idiopathic epilepsy 33%, prolonged febrile seizure 17%, electrolyte imbalance 13%, meningitis 10%, sepsis 8%, enc...

  5. Consequences of Inappropriate ER Management of Status Epilepticus

    J Gordon Millichap

    2004-11-01

    Full Text Available The clinical features of status epilepticus (SE requiring admission to pediatric intensive care (PTC and the emergency pre-PIC treatment of SE compared to standard guidelines were studied in relation to the course of SE after admission to PIC at Great Ormond Street Hospital for Children, London, UK.

  6. Partial status epilepticus - rapid genetic diagnosis of Alpers' disease.

    McCoy, Bláthnaid

    2011-11-01

    We describe four children with a devastating encephalopathy characterised by refractory focal seizures and variable liver dysfunction. We describe their electroencephalographic, radiologic, genetic and pathologic findings. The correct diagnosis was established by rapid gene sequencing. POLG1 based Alpers\\' disease should be considered in any child presenting with partial status epilepticus.

  7. Supra-recommendation Treatment of Super-refractory Status Epilepticus

    Vyas, Devashish Dhiren; Dash, Gopal Krishna

    2016-01-01

    A 28-year old female was admitted with recurrent seizures following 2 days of febrile illness, after which she developed status epilepticus. Midazolam and later thiopentone infusions were started after failure of regular intravenous antiepileptics. Burst suppression was achieved at doses of 3 mg/kg/hr for midazolam and 6 mg/kg/hr of thiopentone. Adjunctive medications included methylprednisolone, intravenous immunoglobulin and acyclovir. Imaging and biochemical parameters were normal. She required 3 cycles of midazolam and 2 cycles of thiopentone for complete cessation of seizures. She recovered with mild attentional and recent memory deficits on follow up. Treatment of super-refractory status epilepticus requires individualized regimens and may need doses beyond conventional limits. To the best of our knowledge, there is no such reported case from India. PMID:27390680

  8. On Etiology and Mortality Rate of Status Epilepticus

    F Ashraf Zadeh

    2000-07-01

    Full Text Available The etiology and mortality rate of Status Epilepticus in 60 pediatric patients, aged 2 months to 13 years, during 10 years has been evaluated. The results show that: -41.7% of the patients were female and 58.3% male. -65% of patients were<3 years and 35% >3 years old. - Mortality rate was 21.6%, 46.1% of which were referral patients. -Major causes of Status Epilepticus were: Idiopathic epilepsy 33%, prolonged febrile seizure 17%, electrolyte imbalance 13%, meningitis 10%, sepsis 8%, encephalitis 5%, encephalopathy 5%, cerebral palsy 5%, intracranial hemorrhage 1.6%, inborn error of metabolism 1.6%. -No mortality occurred in patients with febrile seizures and electrolyte imbalance.

  9. Complex partial status epilepticus associated with cyclosporin A therapy.

    Appleton, R E; Farrell, K; Teal, P.; Hashimoto, S.A.; Wong, P K

    1989-01-01

    Significant neurotoxicity including seizures, encephalopathy and coma may complicate the use of cyclosporin A (CyA). Two patients are described, receiving CyA, who presented with abnormal behaviour, stupor, focal motor activity and were shown to be in complex partial status epilepticus (CPSE). Abnormalities of behaviour and/or stupor in patients receiving CyA may be a manifestation of CPSE. Patients receiving CyA who develop an encephalopathy should have electroencephalography performed at th...

  10. Supra-recommendation Treatment of Super-refractory Status Epilepticus

    Vyas, Devashish Dhiren; Dash, Gopal Krishna

    2016-01-01

    A 28-year old female was admitted with recurrent seizures following 2 days of febrile illness, after which she developed status epilepticus. Midazolam and later thiopentone infusions were started after failure of regular intravenous antiepileptics. Burst suppression was achieved at doses of 3 mg/kg/hr for midazolam and 6 mg/kg/hr of thiopentone. Adjunctive medications included methylprednisolone, intravenous immunoglobulin and acyclovir. Imaging and biochemical parameters were normal. She req...

  11. Pediatric Super-Refractory Status Epilepticus Treated with Allopregnanolone

    Broomall, Eileen; Natale, JoAnne E.; Grimason, Michele; Goldstein, Joshua; Smith, Craig M.; Chang, Celia; Kanes, Stephen; Rogawski, Michael A.; Wainwright, Mark S

    2014-01-01

    Super-refractory status epilepticus is a life-threatening condition. Resistance to benzodiazepine and barbiturate treatment for this disorder is thought to be due to internalization of synaptic γ-aminobutyric acid (GABA)A receptors, and withdrawal of benzodiazepines and barbiturates during treatment often triggers seizure recurrence. The neurosteroid allopregnanolone acts as a positive allosteric modulator of synaptic and extrasynaptic GABAA receptors. Here we describe the use of allopregnano...

  12. Nonconvulsive status epilepticus secondary to paclitaxel administration ☆

    Ignacio Illán-Gala; Francisco Javier Díaz de Terán; Pablo Alonso; María-José Aguilar-Amat

    2015-01-01

    Nonconvulsive status epilepticus (NCSE) can be triggered by metabolic disturbances and drugs in adults without previous epilepsy. We present the case of a 51-year-old woman without previous history of epilepsy and recently diagnosed with infiltrating lobular breast carcinoma. Following the administration of paclitaxel–cremophor, she presented a striking disinhibited behavior with episodic spatial disorientation, emotional indifference, and irritability. Urgent EEG was consistent with NCSE. Cl...

  13. STATUS EPILEPTICUS: ETIOLOGY, OUTCOME AND PREDICTORS OF MORTALITY

    A. Moayedi; A. Atashabparvar; E.Eftekhari

    2008-01-01

    ObjectiveThis study was designed to determine the etiology of status epilepticus (SE) andits relation to mortality.Materials and MethodsThis descriptive study was carried out based on the medical records of 40 patients with diagnosis of SE discharged from pediatric hospital of Bandar Abbas between March 2002 and March 2004. Multivariant analysis was pereformed to determine the prevalence of the disorder and the relation between SE and other factors such as gender, age, response to treatment, ...

  14. Cefepime- Induced Non-Convulsive Status Epilepticus (NCSE)

    Kim, Ahro; KIM, Ji-Eun; Paek, Young-Min; Hong, Keun-Sik; Cho, Young-Jin; Cho, Joong-Yang; Park, Hee-Kyung; Koo, Hyeon-Kyoung; Song, Pamela

    2013-01-01

    Cefepime is a fourth-generation B-lactam cephalosporin, commonly used in immunosuppressed patients. Neurotoxicity, which present as nonconvulsive status epilepticus (NCSE), has been reported previously especially in adult patients with impaired renal function. We present a case of cefepime induced NCSE after recovering from acute renal failure. A 71-year-old woman was hospitalized for right lower lobe lobectomy after diagnosis of lung cancer. Although she had successful lobectomy, she underwe...

  15. STATUS EPILEPTICUS: ETIOLOGY, OUTCOME AND PREDICTORS OF MORTALITY

    A. Moayedi

    2008-11-01

    Full Text Available ObjectiveThis study was designed to determine the etiology of status epilepticus (SE andits relation to mortality.Materials and MethodsThis descriptive study was carried out based on the medical records of 40 patients with diagnosis of SE discharged from pediatric hospital of Bandar Abbas between March 2002 and March 2004. Multivariant analysis was pereformed to determine the prevalence of the disorder and the relation between SE and other factors such as gender, age, response to treatment, and mortality. We classified the etiology according to international league against epilepsy (ILAE classification and also uses another classification regarding underlying causes such as fever (non-CNS infection, central nervous system infection, hypoxia, and metabolic causes.ResultsStatus epilepticus was responsible for 0.3% of all hospital  dmissions during the study period. Based on the ILAE classification, frequencies for acute symptomatic, febrile, progressive encephalopathic, remote, and cryptogenic SE were 42.5%, 32.5%, 10%, 7.5%, and 7.5%, respectively.The most common underlying causes resulting in SE were fever (45%, metabolic disorders (15%, CNS infection (12.5%, chronic neurologic diseases (7.5%, idiopathic (7.5%, hypoxia (5%, drug withdrawal (2.5%, CNS hemorrhage (2.5%, neurodegenerative disease (2.5%, brain abscess (2.5%, and post DPT (Diphteria,Pertusis,Tetanus vaccination (2.5%. Mortality rate was 25% (80% in the patients younger than 5 years and 40% in those aged less than 1 year. Occurrence of SE and its mortality was found to be related to age (pConclusionFor SE, if seizures continue for more than 5 minutes, treatment must beinitiated. The outcome is determined by etiology, age, seizure duration and management; however, all we can do is enhance the management and increase its effectiveness.Keywords:Status epilepticus, Etiology, Underlying cause

  16. Complete recovery after severe myxoedema coma complicated by status epilepticus

    Fjølner, Jesper; Opstrup, Ulla Kampmann; Søndergaard, Esben;

    2015-01-01

    We report a case of life-threatening myxoedema presenting with hypothermia, hypotension, bradycardia, pericardial effusion and deep coma. The condition was complicated by prolonged status epilepticus. The optimal treatment strategy has been debated over the years and the literature is briefly...... reviewed. Treatment with l-thyroxine (LT4) monotherapy without initial loading dose and with no l-triiodothyronine (LT3) treatment was successful with full recovery after hospitalisation for more than a month. Myxoedema coma is a rare, reversible condition with a high mortality and should be considered as...

  17. Refractory status epilepticus following self-poisoning with the organochlorine pesticide endosulfan.

    Roberts, Darren M; Dissanayake, Wasantha; Rezvi Sheriff, M H; Eddleston, Michael

    2004-09-01

    We describe a case of refractory status epilepticus presenting to a rural general hospital in Sri Lanka. This patient's condition was precipitated by intentional self-poisoning with the organochlorine insecticide endosulfan. Although rarely seen in developed countries, pesticide poisoning particularly with endosulfan is an important cause of difficult-to-manage seizures in Asian countries. In this case report, we discuss the management of status epilepticus and refractory status epilepticus. Further, we specifically discuss the clinical pharmacology and toxicology of endosulfan. PMID:15337143

  18. Generalized status epilepticus associated with massive pulmonary aspiration and transient central diabetes insipidus: case report

    CARVALHO MAURICIO

    2000-01-01

    Full Text Available Status epilepticus causes significant morbidity and mortality. A case of generalized status epilepticus followed by massive pulmonary aspiration, acute respiratory failure and transient central diabetes insipidus is presented. Seizures were promptly controlled, but the patient required mechanical ventilation and correction of polyuria with desmopressin acetate. During hospitalization mental status improved, diabetes insipidus spontaneously remitted and he was discharged without neurologic sequelae. The clinical and pathophysiological features of this case are discussed.

  19. Ketogenic diet for adults in super-refractory status epilepticus

    Thakur, Kiran T.; Probasco, John C.; Hocker, Sara E.; Roehl, Kelly; Henry, Bobbie; Kossoff, Eric H.; Kaplan, Peter W.; Geocadin, Romergryko G.; Hartman, Adam L.; Venkatesan, Arun

    2014-01-01

    Objective: To describe a case series of adult patients in the intensive care unit in super-refractory status epilepticus (SRSE; refractory status lasting 24 hours or more despite appropriate anesthetic treatment) who received treatment with the ketogenic diet (KD). Methods: We performed a retrospective case review at 4 medical centers of adult patients with SRSE treated with the KD. Data collected included demographic features, clinical presentation, diagnosis, EEG data, anticonvulsant treatment, and timing and duration of the KD. Primary outcome measures were resolution of status epilepticus (SE) after initiation of KD and ability to wean from anesthetic agents. Results: Ten adult patients at 4 medical centers were started on the KD for SRSE. The median age was 33 years (interquartile range [IQR] 21), 4 patients (40%) were male, and 7 (70%) had encephalitis. The median duration of SE before initiation of KD was 21.5 days (IQR 28) and the median number of antiepileptic medications used before initiation of KD was 7 (IQR 7). Ninety percent of patients achieved ketosis, and SE ceased in all patients achieving ketosis in a median of 3 days (IQR 8). Three patients had minor complications of the KD including transient acidosis and hypertriglyceridemia and 2 patients ultimately died of causes unrelated to the KD. Conclusion: We describe treatment of critically ill adult patients with SRSE with the KD, with 90% of patients achieving resolution of SE. Prospective trials are warranted to examine the efficacy of the KD in adults with refractory SE. Classification of evidence: This study provides Class IV evidence that for intensive care unit patients with refractory SE, a KD leads to resolution of the SE. PMID:24453083

  20. STATUS EPILEPTICUS: ETIOLOGY, OUTCOME AND PREDICTORS OF MORTALITY

    A. Moayedi

    2007-11-01

    Full Text Available ObjectiveThis study was designed to determine the etiology of status epilepticus (SE and its relation to mortality.Materials and MethodsThis descriptive study was carried out based on the medical records of 40 patients with diagnosis of SE discharged from pediatric hospital of Bandar Abbas between March 2002 and March 2004. Multivariant analysis was pereformed to determine the prevalence of the disorder and the relation between SE and other factors such as gender, age, response to treatment, and mortality. We classified the etiology according to international league against epilepsy (ILAE classification and also uses another classification regarding underlying causes such as fever (non-CNS infection, central nervous system infection, hypoxia, and metabolic causes.Results Status epilepticus was responsible for 0.3% of all hospital admissions during the study period. Based on the ILAE classification, frequencies for acute symptomatic, febrile, progressive encephalopathic, remote, and cryptogenic SE were 42.5%, 32.5%, 10%, 7.5%, and 7.5%, respectively.The most common underlying causes resulting in SE were fever (45%, metabolic disorders (15%, CNS infection (12.5%, chronic neurologic diseases (7.5%, idiopathic (7.5%, hypoxia (5%, drug withdrawal (2.5%, CNS hemorrhage (2.5%, neurodegenerative disease (2.5%, brain abscess (2.5%, and post DPT(Diphteria,Pertusis,Tetanus vaccination (2.5%. Mortality rate was 25% (80% in the patients younger than 5 years and 40% in those aged less than 1 year. Occurrence of SE and its mortality was found to be related to age (p< 0.05.ConclusionFor SE, if seizures continue for more than 5 minutes, treatment must be initiated. The outcome is determined by etiology, age, seizure duration and management; however, all we can do is enhance the management and increase its effectiveness.

  1. Encephalopathy with status epilepticus during sleep (ESES) induced by oxcarbazepine in idiopathic focal epilepsy in childhood

    Pavlidis, Elena; Rubboli, Guido; Nikanorova, Marina;

    2015-01-01

    Encephalopathy with status epilepticus during sleep (ESES) is an age-related disorder characterized by neuropsychological regression, epilepsy and a typical EEG pattern of continuous epileptiform activity (> 85%) during NREM sleep. Cases of worsening or induction of ESES with phenytoin...

  2. Management of Super-Refractory Status Epilepticus with Isoflurane and Hypothermia

    Zhumadilov, Agzam; Gilman, Charles P.; Viderman, Dmitriy

    2015-01-01

    Super-refractory status epilepticus (SRSE) is defined as status epilepticus that continues 24 h or more after the onset of anesthesia, and includes those cases in which epilepsy is recurrent upon treatment reduction. We describe the presentation and successful management of a male patient with SRSE using the inhaled anesthetic isoflurane, and mild hypothermia (HT). The potential utility of combined HT and volatile anesthesia is discussed. PMID:25674075

  3. Management of Super-Refractory Status Epilepticus with Isoflurane and Hypothermia

    Zhumadilov, Agzam; Gilman, Charles P.; Viderman, Dmitriy

    2015-01-01

    Super-refractory status epilepticus (SRSE) is defined as status epilepticus that continues 24 h or more after the onset of anesthesia, and includes those cases in which epilepsy is recurrent upon treatment reduction. We describe the presentation and successful management of a male patient with SRSE using the inhaled anesthetic isoflurane, and mild hypothermia (HT). The potential utility of combined HT and volatile anesthesia is discussed.

  4. Comparison of Intravenous Anesthetic Agents for the Treatment of Refractory Status Epilepticus

    Michael E. Reznik; Karen Berger; Jan Claassen

    2016-01-01

    Status epilepticus that cannot be controlled with first- and second-line agents is called refractory status epilepticus (RSE), a condition that is associated with significant morbidity and mortality. Most experts agree that treatment of RSE necessitates the use of continuous infusion intravenous anesthetic drugs such as midazolam, propofol, pentobarbital, thiopental, and ketamine, each of which has its own unique characteristics. This review compares the various anesthetic agents while provid...

  5. Is Favorable Outcome Possible After Prolonged Refractory Status Epilepticus?

    Alvarez, Vincent; Drislane, Frank W

    2016-02-01

    When status epilepticus (SE) remains refractory to appropriate therapy, it is associated with high mortality and with substantial morbidity in survivors. Many outcome predictors such as age, seizure type, level of consciousness before treatment, and mostly, etiology, are well-established. A longer duration of SE is often associated with worse outcome, but duration may lose its prognostic value after several hours. Several terms and definitions have been used to describe prolonged, refractory SE, including "malignant SE," "prolonged" SE, and more recently, "super refractory" SE, defined as "SE that has continued or recurred despite 24 hours of general anesthesia (or coma-inducing anticonvulsants)." There are few data available regarding the outcome of prolonged refractory SE, and even fewer for SE remaining refractory to anesthetic drugs. This article reviews reports of outcome after prolonged, refractory, and "super refractory" SE. Most information detailing the clinical outcome of patients surviving these severe illnesses, in which seizures can persist for days or weeks (and especially those concerning "super-refractory" SE) come from case reports and retrospective cohort studies. In many series, prolonged, refractory SE has a mortality of 30% to 50%, and several studies indicate that most survivors have a substantial decline in functional status. Nevertheless, several reports demonstrate that good functional outcome is possible even after several days of SE and coma induction. Treatment of refractory SE should not be withdrawn from younger patients without structural brain damage at presentation solely because of the duration of SE. PMID:26840875

  6. STATUS EPILEPTICUS IN CHILDREN CLINICO ETIOLOGICAL PROFILE AND OUTCOME

    Gunasekhara Raju

    2015-11-01

    Full Text Available Status epilepticus is a common condition in acute medical care. Approximately 4.5 million SE events occur worldwide every year.SE in children differs from adult SE in aspects of epidemiology, pathophysiology and clinical presentations, which justifies a separate analysis. The incidence in children is about 18-20/100,000 children/year and distribution of etiologies is markedly age-dependent: Febrile and acute symptomatic convulsive SE is most common in children aged less than 2 years, whereas cryptogenic/idiopathic and remote symptomatic etiologies are more common in older children. A prospective study where 46 children, admitted in Pediatric Intensive Care Unit with seizures lasting >30 minutes in King George Hospital, Visakhapatnam, were studied over a period from 2012 June to 2013 oct. These patients were evaluated for their clinical presentation, laboratory parameters, treatment profile and immediate outcome. As mortality is higher in younger age groups and status with acute symptomatic etiology, there is a need to aggressively treat these groups. As the longer a seizure continues the harder it is to be controlled and as both the mortality and sequelae were found to be significantly lesser in the patients who attained good seizure control within 1 hour of presentation to the hospital.

  7. Acetazolamide for electrical status epilepticus in slow-wave sleep.

    Fine, Anthony L; Wirrell, Elaine C; Wong-Kisiel, Lily C; Nickels, Katherine C

    2015-09-01

    Electrical status epilepticus in slow-wave sleep (ESES) is characterized by nearly continuous spike-wave discharges during non-rapid eye movement (REM) sleep. ESES is present in Landau-Kleffner syndrome (LKS) and continuous spike and wave in slow-wave sleep (CSWS). Sulthiame has demonstrated reduction in spike-wave index (SWI) in ESES, but is not available in the United States. Acetazolamide (AZM) is readily available and has similar pharmacologic properties. Our aims were to assess the effect of AZM on SWI and clinical response in children with LKS and CSWS. Children with LKS or CSWS treated with AZM at our institution were identified retrospectively. Pre- and posttherapy electroencephalography (EEG) studies were evaluated for SWI. Parental and teacher report of clinical improvement was recorded. Six children met criteria for inclusion. Three children (50%) demonstrated complete resolution or SWI <5% after AZM. All children had improvement in clinical seizures and subjective improvement in communication skills and school performance. Five of six children had subjective improvement in hyperactivity and attention. AZM is a potentially effective therapy for children with LKS and CSWS. This study lends to the knowledge of potential therapies that can be used for these disorders, which can be challenging for families and providers. PMID:26230617

  8. A definition and classification of status epilepticus--Report of the ILAE Task Force on Classification of Status Epilepticus.

    Trinka, Eugen; Cock, Hannah; Hesdorffer, Dale; Rossetti, Andrea O; Scheffer, Ingrid E; Shinnar, Shlomo; Shorvon, Simon; Lowenstein, Daniel H

    2015-10-01

    The Commission on Classification and Terminology and the Commission on Epidemiology of the International League Against Epilepsy (ILAE) have charged a Task Force to revise concepts, definition, and classification of status epilepticus (SE). The proposed new definition of SE is as follows: Status epilepticus is a condition resulting either from the failure of the mechanisms responsible for seizure termination or from the initiation of mechanisms, which lead to abnormally, prolonged seizures (after time point t1 ). It is a condition, which can have long-term consequences (after time point t2 ), including neuronal death, neuronal injury, and alteration of neuronal networks, depending on the type and duration of seizures. This definition is conceptual, with two operational dimensions: the first is the length of the seizure and the time point (t1 ) beyond which the seizure should be regarded as "continuous seizure activity." The second time point (t2 ) is the time of ongoing seizure activity after which there is a risk of long-term consequences. In the case of convulsive (tonic-clonic) SE, both time points (t1 at 5 min and t2 at 30 min) are based on animal experiments and clinical research. This evidence is incomplete, and there is furthermore considerable variation, so these time points should be considered as the best estimates currently available. Data are not yet available for other forms of SE, but as knowledge and understanding increase, time points can be defined for specific forms of SE based on scientific evidence and incorporated into the definition, without changing the underlying concepts. A new diagnostic classification system of SE is proposed, which will provide a framework for clinical diagnosis, investigation, and therapeutic approaches for each patient. There are four axes: (1) semiology; (2) etiology; (3) electroencephalography (EEG) correlates; and (4) age. Axis 1 (semiology) lists different forms of SE divided into those with prominent motor

  9. Feasibility of Automatic Extraction of Electronic Health Data to Evaluate a Status Epilepticus Clinical Protocol.

    Hafeez, Baria; Paolicchi, Juliann; Pon, Steven; Howell, Joy D; Grinspan, Zachary M

    2016-05-01

    Status epilepticus is a common neurologic emergency in children. Pediatric medical centers often develop protocols to standardize care. Widespread adoption of electronic health records by hospitals affords the opportunity for clinicians to rapidly, and electronically evaluate protocol adherence. We reviewed the clinical data of a small sample of 7 children with status epilepticus, in order to (1) qualitatively determine the feasibility of automated data extraction and (2) demonstrate a timeline-style visualization of each patient's first 24 hours of care. Qualitatively, our observations indicate that most clinical data are well labeled in structured fields within the electronic health record, though some important information, particularly electroencephalography (EEG) data, may require manual abstraction. We conclude that a visualization that clarifies a patient's clinical course can be automatically created using the patient's electronic clinical data, supplemented with some manually abstracted data. Future work could use this timeline to evaluate adherence to status epilepticus clinical protocols. PMID:26518205

  10. [Acute alterations of neurotransmitters levels in striatum of young rat after pilocarpine-induced status epilepticus].

    de Freitas, Rivelilson Mendes; de Sousa, Francisca Cléa Florenço; Vasconcelos, Silvânia Maria Mendes; Viana, Glauce Socorro Barros; Fonteles, Marta Maria de França

    2003-06-01

    High doses of the muscarinic cholinergic agonist, pilocarpine, result in behavioural changes, seizures and status epilepticus in rats. The purpose of the present work is to invetigate the striatal neurotransmissors level in young rats after status epilepticus induced by pilocarpine. Wistar rats were treated with a single dose of pilocarpine (400mg/Kg; s.c.). Controls received saline. Young animals were closed observed for behavioural changes during 1 and 24h. In these periods, the animals that developed status epilepticus and didn't survive this acute phase of seizures had the brains removed and striatal neurotransmissors level determined by HPLC. The concentration of dopamine, serotonine, dihydroxyphenylacetic acid, 5-hydroxyindolacetic acid was reduced and an increase in 4-hydroxy-3-methoxy-phenylacetic acid was observed. These results suggest that cholinergic activation can interage with dopaminergic and serotonergic systems in acute phase of the convulsive process in immature striatum. PMID:12894279

  11. Early Use of the NMDA Receptor Antagonist Ketamine in Refractory and Superrefractory Status Epilepticus

    F. A. Zeiler

    2015-01-01

    Full Text Available Refractory status epilepticus (RSE and superrefractory status epilepticus (SRSE pose a difficult clinical challenge. Multiple cerebral receptor and transporter changes occur with prolonged status epilepticus leading to pharmacoresistance patterns unfavorable for conventional antiepileptics. In particular, n-methyl-d-aspartate (NMDA receptor upregulation leads to glutamate mediated excitotoxicity. Targeting these NMDA receptors may provide a novel approach to otherwise refractory seizures. Ketamine has been utilized in RSE. Recent systematic review indicates 56.5% and 63.5% cessation in seizures in adults and pediatrics, respectively. No complications were described. We should consider earlier implementation of ketamine or other NMDA receptor antagonists, for RSE. Prospective study of early implementation of ketamine should shed light on the role of such medications in RSE.

  12. Levetiracetam versus phenytoin in management of status epilepticus.

    Chakravarthi, Sudheer; Goyal, Manoj Kumar; Modi, Manish; Bhalla, Ashish; Singh, Parampreet

    2015-06-01

    The purpose of this study was to compare safety and efficacy of intravenous (IV) levetiracetam (LEV) with IV phenytoin (PHT) in management of status epilepticus (SE). The second-line treatment of SE is limited to a few drugs available in an IV formulation such as PHT, fosphenytoin and valproate. The relative lack of serious side effects and favourable pharmacokinetics of LEV made it a promising option in management of SE. Randomized trials comparing relative efficacy of second-line agents are remarkably lacking. In this study, consecutive patients of SE (n=44) were randomized to receive either IV PHT (20mg/kg) or IV LEV (20mg/kg). The primary end point was successful clinical termination of seizure activity within 30min after the beginning of the drug infusion. Secondary end points included recurrence of seizures within 24 hours, drug related adverse effects, neurological outcome at discharge, need for ventilatory assistance, and mortality during hospitalization. Both LEV and PHT were equally effective with regard to primary and secondary outcome measures. PHT achieved control of SE in 15 (68.2%) patients compared to LEV in 13 (59.1%; p=0.53). Both the groups showed comparable results with respect to recurrence of seizures within 24 hours (p=0.34), outcome at discharge as assessed by functional independence measure (p=0.68), need of ventilatory assistance (p=0.47) and death (p=1). From this study it can be concluded that LEV may be an attractive and effective alternative to PHT in management of SE. PMID:25899652

  13. MIDAZOLAM EFFICACY AND SIDE EFFECTS IN GENERALIZED AND PARTIAL REFRACTORY STATUS EPILEPTICUS IN CHILDREN

    M.R. Salehi Omran

    2009-04-01

    Full Text Available ObjectiveMidazolam is a significant and effective drug for control of a life-threatening condition, generalized and partial refractory convulsive status epilepticus. The goal of this study was evaluation of midazolam efficacy for management of this serious disease and its two side effects, hypotension and respiratory failure.Materials & MethodsOur study was done using a quasi experimental method; 22 children with generalized refractory convulsive status epilepticus and 13 with partial refractory convulsive status epilepticus were enrolled for the study. All patients received 0.2mg/kg/dose as a bolus intravenous midazolam followed by 1-6 mcg/kg/min continuous intravenous midazolam. Following this, termination of seizures as well as hypotension and respiratory failure were evaluated.ResultsMidazolam ceased stop convulsions in 81.81% (18 patients with generalized seizures, and in 76.92% (10 patients with partial seizures, showing no significant difference between these two types of seizures (p=0.52 Hypotension was induced in 18.18% (4 patients with generalized seizures and in 30.70% (4 patients with partial seizures, again difference not significant (p=0.14. There was respiratory failure in 21.73% (5 patients with generalized seizure and in 7.69% (1 patients with partial seizure, difference not significant.(p=0.09ConclusionThere was no significant difference in efficacy and creation of hypotension and respiratory failure after continuous intravenous infusion of midazolam between generalized and partial refractory convulsive status epilepticus.Key words:Midazolam, Refractory convulsive status epilepticus, Convulsive status epilepticus.

  14. Changes on diffusion-weighted MRI with focal motor status epilepticus: case report

    Transient imaging abnormalities, including changes on diffusion-weighted imaging (DWI), may be seen in focal status epilepticus. The changes on DWI provide an insight into the pathophysiology. We report a 53-year-old man with focal motor status epilepticus involving the left hand, arm and face with focal slowing on EEG. The apparent diffusion coefficients (ADC) were higher in the affected hemisphere than on the other side. At 10 days and 6 weeks after the end of the seizures, we saw normal ADCs and atrophy of the affected hemisphere. We conclude that the MRI findings indicate both cytotoxic and vasogenic oedema during seizure activity and subsequent loss of brain parenchyma. (orig.)

  15. Comparison of Intravenous Anesthetic Agents for the Treatment of Refractory Status Epilepticus

    Reznik, Michael E.; Berger, Karen; Claassen, Jan

    2016-01-01

    Status epilepticus that cannot be controlled with first- and second-line agents is called refractory status epilepticus (RSE), a condition that is associated with significant morbidity and mortality. Most experts agree that treatment of RSE necessitates the use of continuous infusion intravenous anesthetic drugs such as midazolam, propofol, pentobarbital, thiopental, and ketamine, each of which has its own unique characteristics. This review compares the various anesthetic agents while providing an approach to their use in adult patients, along with possible associated complications. PMID:27213459

  16. Comparison of Intravenous Anesthetic Agents for the Treatment of Refractory Status Epilepticus

    Michael E. Reznik

    2016-05-01

    Full Text Available Status epilepticus that cannot be controlled with first- and second-line agents is called refractory status epilepticus (RSE, a condition that is associated with significant morbidity and mortality. Most experts agree that treatment of RSE necessitates the use of continuous infusion intravenous anesthetic drugs such as midazolam, propofol, pentobarbital, thiopental, and ketamine, each of which has its own unique characteristics. This review compares the various anesthetic agents while providing an approach to their use in adult patients, along with possible associated complications.

  17. Febrile infection-related status epilepticus in a child after a common infection

    Andersen, Anne Helene; Hansen, Lars Kjærsgaard

    2014-01-01

    A 13-year-old boy developed seizures and intractable status epilepticus a week after having had a sore throat. Ketogenic diet possibly had some effect. Antibodies to calmodulin dependent protein kinase II were found and could possibly suggest an immunologic aetiology.......A 13-year-old boy developed seizures and intractable status epilepticus a week after having had a sore throat. Ketogenic diet possibly had some effect. Antibodies to calmodulin dependent protein kinase II were found and could possibly suggest an immunologic aetiology....

  18. Refractory Status Epilepticus Due To Cerebral Venous Thrombosis During Late Pregnancy with Successful Outcome

    Kumar S

    2004-01-01

    Full Text Available Status epilepticus complicating pregnancy is uncommon and may be associated with poor maternal and foetal outcome. We report a 24-Year-old lady who presented with refractory status epilepticus at 27 weeks of gestation. The underlying causes identified was extensive was extensive dural cerebral venous sinus thrombosis. She required admission in Neurology intensive car unit and aggressive treatment including mechanical ventilation, anticoagulation and antiepileptic therapy with intravenous phenytoin, & midazolam and thiopentone infusion. She delivered a healthy baby after a spontaneous preterm labour 28 weeks of gestation. At the time of discharge, both mother and child were healthy. A brief literature review is also presented.

  19. Antagomirs targeting microRNA-134 increase hippocampal pyramidal neuron spine volume in vivo and protect against pilocarpine-induced status epilepticus.

    Jimenez-Mateos, Eva M; Engel, Tobias; Merino-Serrais, Paula; Fernaud-Espinosa, Isabel; Rodriguez-Alvarez, Natalia; Reynolds, James; Reschke, Cristina R; Conroy, Ronan M; McKiernan, Ross C; deFelipe, Javier; Henshall, David C

    2015-07-01

    Emerging data support roles for microRNA (miRNA) in the pathogenesis of various neurologic disorders including epilepsy. MicroRNA-134 (miR-134) is enriched in dendrites of hippocampal neurons, where it negatively regulates spine volume. Recent work identified upregulation of miR-134 in experimental and human epilepsy. Targeting miR-134 in vivo using antagomirs had potent anticonvulsant effects against kainic acid-induced seizures and was associated with a reduction in dendritic spine number. In the present study, we measured dendritic spine volume in mice injected with miR-134-targeting antagomirs and tested effects of the antagomirs on status epilepticus triggered by the cholinergic agonist pilocarpine. Morphometric analysis of over 6,400 dendritic spines in Lucifer yellow-injected CA3 pyramidal neurons revealed increased spine volume in mice given antagomirs compared to controls that received a scrambled sequence. Treatment of mice with miR-134 antagomirs did not alter performance in a behavioral test (novel object location). Status epilepticus induced by pilocarpine was associated with upregulation of miR-134 within the hippocampus of mice. Pretreatment of mice with miR-134 antagomirs reduced the proportion of animals that developed status epilepticus following pilocarpine and increased animal survival. In antagomir-treated mice that did develop status epilepticus, seizure onset was delayed and total seizure power was reduced. These studies provide in vivo evidence that miR-134 regulates spine volume in the hippocampus and validation of the seizure-suppressive effects of miR-134 antagomirs in a model with a different triggering mechanism, indicating broad conservation of anticonvulsant effects. PMID:24874920

  20. Status epilepticus ausência de novo: relato de caso "De novo" absence status: case report

    Gloria M. Almeida Tedrus

    1997-09-01

    Full Text Available Existem poucos relatos na literatura de pacientes adultos com status epilepticus não convulsivo, do tipo ausência típica. Apresentamos o caso de paciente do sexo feminino de 53 anos de idade, diabética, que iniciou quadro de confusão mental após crise tônico-clônica generalizada. O eletrencefalograma mostrou descargas contínuas generalizadas caracterizadas por complexos ponta-onda irregulares. As descargas ao eletrencefalograma desapareceram após diazepan endovenoso. A tomografia computadorizada de crânio foi normal. Esse caso mostra que o reconhecimento dessa entidade clínico-eletrencefalográfica é essencial, devido à semelhança com distúrbio psiquiátrico e da pronta resposta ao tratamento medicamentoso.There are few descriptions about middle-aged patients who have nonconvulsive status epilepticus, absence status. We reported the clinical case of a woman, 52-year-old, diabetic, referred to the emergency room in a confusional state. Initial electroencephalogram showed continuous typical, bilateral, symmetric and synchronous spike-and-wave discharges. Clinical and electroencephalogram normalization occurred immediatelly following intravenous injection of benzodiazepine. Computerized axial tomography was normal. The recognition of this entity is essential because of its similarity to psychiatric disturbance and its prompt response to proper treatment.

  1. Treatment of convulsive status epilepticus in the UMCG: A retrospective, observational study

    Vlaskamp, D.R.M.; Brouwer, O.F.; Callenbach, P.M.C.

    2013-01-01

    Objectives: Little is known about clinical practice with respect to the application of guidelines in the treatment of Convulsive Status Epilepticus (CSE). This retrospective, observational study evaluated treatment of episodes of CSE in children at the University Medical Centre Groningen (UMCG). Mat

  2. Inappropriate emergency management of status epilepticus in children contributes to need for intensive care

    Chin, R; Verhulst, L; Neville, B.; Peters, M; Scott, R.

    2004-01-01

    Objectives: To characterise the clinical features, emergency pre-paediatric intensive care (PIC) treatment, and course of status epilepticus (SE) in children admitted to PIC. This may provide insight into reasons for admission to PIC and provide a framework for the development of strategies that decrease the requirement for intensive care.

  3. Blood-brain barrier leakage after status epilepticus in rapamycin-treated rats II: Potential mechanisms

    E.A. van Vliet; W.M. Otte; W.J. Wadman; E. Aronica; G. Kooij; H.E. de Vries; R.M. Dijkhuizen; J.A. Gorter

    2016-01-01

    OBJECTIVE: Blood-brain barrier (BBB) leakage may play a pro-epileptogenic role after status epilepticus. In the accompanying contrast-enhanced magnetic resonance imaging (CE-MRI) study we showed that the mammalian target of rapamycin (mTOR) inhibitor rapamycin reduced BBB leakage and seizure activit

  4. Blood-brain barrier leakage after status epilepticus in rapamycin-treated rats II : Potential mechanisms

    van Vliet, Erwin A; Otte, Wim M; Wadman, Wytse J; Aronica, Eleonora; Kooij, Gijs; de Vries, Helga E; Dijkhuizen, Rick M; Gorter, Jan A

    2016-01-01

    OBJECTIVE: Blood-brain barrier (BBB) leakage may play a pro-epileptogenic role after status epilepticus. In the accompanying contrast-enhanced magnetic resonance imaging (CE-MRI) study we showed that the mammalian target of rapamycin (mTOR) inhibitor rapamycin reduced BBB leakage and seizure activit

  5. Neuronal degeneration induced by status epilepticus in the nucleus accumens of immature rats

    Druga, Rastislav; Mareš, Pavel; Kubová, Hana

    2007-01-01

    Roč. 48, s6 (2007), s. 19-20. ISSN 0013-9580. [Annual Meeting of the American Epilepsy Society. 31.112007-3.12.2007, Philadelphia] R&D Projects: GA ČR GA304/07/1137 Institutional research plan: CEZ:AV0Z50110509 Keywords : cpo1 * neuronal degeneration * status epilepticus * immature rat Subject RIV: FH - Neurology

  6. Thyroid-stimulating hormone elevation misdiagnosed as subclinical hypothyroidism following non-convulsive status epilepticus: a case report

    Kunii Yasuto

    2011-09-01

    Full Text Available Abstract Introduction Non-convulsive status epilepticus is a form of epileptic seizure that occurs without convulsions. Recent reviews suggest that the diagnosis of non-convulsive status epilepticus remains difficult. Here, we report the case of a patient with thyroid-stimulating hormone elevation misdiagnosed as subclinical hypothyroidism following non-convulsive status epilepticus. Case presentation Our patient was a 68-year-old Japanese woman. The results of endocrine testing after her first episode of non-convulsive status epilepticus suggested latent subclinical hypothyroidism: she had elevated thyroid-stimulating hormone with normal levels of free tri-iodothyronine and free thyroxine. On examination, a diagnosis of thyroid disorder was not supported by other test results and our patient remained untreated. A follow-up examination revealed that her thyroid-stimulating hormone levels had spontaneously normalized. When she consulted another doctor for confusion, the transient increase in thyroid-stimulating hormone levels following non-convulsive status epilepticus was mistaken for subclinical hypothyroidism, and unfortunately treated with levothyroxine. Our patient then experienced levothyroxine-induced non-convulsive status epilepticus. Conclusions In this report, we suggested possible mechanisms for latent hypothyroid-like hormone abnormality following epileptic seizures and the possibility of provoking epileptic seizures by administering levothyroxine for misdiagnosed subclinical hypothyroidism.

  7. Refractory nonconvulsive status epilepticus in coma: analysis of the evolution of ictal patterns

    Paulo Breno Noronha Liberalesso

    2012-07-01

    Full Text Available OBJECTIVE: Nonconvulsive status epilepticus (NCSE is currently considered as one of the most frequent types of status epilepticus (SE. The objective of the present study was to identify the natural history of the electrographical evolution of refractory NCSE and to establish the relationship between ictal patterns and prognosis. METHODS: We analyzed, retrospectively, 14 patients with loss of consciousness and NCSE. The ictal patterns were classified as discrete seizures (DS, merging seizures (MS, continuous ictal discharges (CID, continuous ictal discharges with flat periods (CID-F, and periodic lateralized epileptiform discharges (PLEDs. RESULTS: The ictal patterns were DS (n=7; 50.0%, PLEDs (n=3; 1.4%, CID (n=2; 14.3%, MS (n=1; 7.1%, and CID-F (n=1; 7.1%. CONCLUSIONS: NCSE electrographic findings are heterogeneous and do not follow a stereotyped sequence. PLEDs were related to a higher probability of neurological morbidity and mortality.

  8. Refractory status epilepticus due to pneumococcal meningitis in an infant with congenital immunodeficiency

    Prasanth, Sudhakaran; Shaji, Velayudhan Cheruvallil; Lyla, Chacko; Jayalakshmi, Vasudevapanicker

    2016-01-01

    Pneumococcal meningitis remains a life-threatening infection, with varied presentations. A 3 month-old-baby with pneumococcal meningitis presented with clusters of seizures evolving into refractory status epilepticus despite standard antibiotic and aggressive anticonvulsant therapy. Progressive illness despite antibiotic initially suggested possible antibiotic resistance and resulted in addition of another antibiotic. Nonresponse to standard treatment and previous history of abscess in the back of neck pointed to some underlying congenital immunodeficiency. Further evaluation showed a deficiency of complement factor C3. This case underlines the need to consider underlying immunodeficiency in cases of refractory status epilepticus due to bacterial meningitis. Gram-staining of cerebrospinal fluid sample showing plenty of Gram-positive bacteria and comparatively fewer pus cells is a clue regarding some underlying immunodeficiency.

  9. USE OF INJECTABLE VALPROATE FORMULATIONS IN STATUS EPILEPTICUS IN ADULTS AND CHILDREN

    A. A. Kholin

    2015-01-01

    One of the most actual problems in emergency neurology is therapy of status epilepticus (SE). Antiepileptic drugs used in therapy of SE must be: 1) simple in usage; 2) have rapid action; 3) have prolonged antiepileptic action; 4) demonstrate minimal side effects on cardiorespiratory system and other vital functions. Unfortunately, such drugs traditional used in therapy of SE as benzodiazepines, phenytoin and barbiturates don’t fulfill all this four qualities. Numerous clinical investigations ...

  10. Lithium-methomyl induced seizures in rats: A new model of status epilepticus?

    Behavioral, electroencephalographic (EEG) and neuropathological effects of methomyl, a carbamate insecticide reversibly inhibiting acetylcholinesterase activity, were studied in naive or lithium chloride (24 h, 3 mEq/kg, s.c.) pretreated male Wistar rats. In naive animals, methomyl with equal potency produced motor limbic seizures and fatal status epilepticus. Thus, the CD50 values (50% convulsant dose) for these seizure endpoints were almost equal to the LD50 (50% lethal dose) of methomyl (13 mg/kg). Lithium pretreated rats were much more susceptible to convulsant, but not lethal effect of methomyl. CD50 values of methomyl for motor limbic seizures and status epilepticus were reduced by lithium pretreatment to 3.7 mg/kg (a 3.5-fold decrease) and 5.2 mg/kg (a 2.5-fold decrease), respectively. In contrast, lithium pretreatment resulted in only 1.3-fold decrease of LD50 value of methomyl (9.9 mg/kg). Moreover, lithium-methomyl treated animals developed a long-lasting status epilepticus, which was not associated with imminent lethality observed in methomyl-only treated rats. Scopolamine (10 mg/kg) or diazepam (10 mg/kg) protected all lithium-methomyl treated rats from convulsions and lethality. Cortical and hippocampal EEG recordings revealed typical epileptic discharges that were consistent with behavioral seizures observed in lithium-methomyl treated rats. In addition, convulsions induced by lithium-methomyl treatment were associated with widespread neurodegeneration of limbic structures. Our observations indicate that lithium pretreatment results in separation between convulsant and lethal effects of methomyl in rats. As such, seizures induced by lithium-methomyl administration may be an alternative to lithium-pilocarpine model of status epilepticus, which is associated with high lethality

  11. Minocycline fails to exert antiepileptogenic effects in a rat status epilepticus model.

    Russmann, Vera; Goc, Joanna; Boes, Katharina; Ongerth, Tanja; Salvamoser, Josephine D; Siegl, Claudia; Potschka, Heidrun

    2016-01-15

    The tetracycline antibiotic minocycline can exert strong anti-inflammatory, antioxidant, and antiapoptotic effects. There is cumulating evidence that epileptogenic brain insults trigger neuroinflammation and anti-inflammatory concepts can modulate the process of epileptogenesis. Based on the mechanisms of action discussed for minocycline, the compound is of interest for intervention studies as it can prevent the polarization of microglia into a pro-inflammatory state. Here, we assessed the efficacy of sub-chronic minocycline administration initiated immediately following an electrically-induced status epilepticus in rats. The treatment did not affect the development of spontaneous seizures. However, minocycline attenuated behavioral long-term consequences of status epilepticus with a reduction in hyperactivity and hyperlocomotion. Furthermore, the compound limited the spatial learning deficits observed in the post-status epilepticus model. The typical status epilepticus-induced neuronal cell loss was evident in the hippocampus and the piriform cortex. Minocycline exposure selectively protected neurons in the piriform cortex and the hilus, but not in the hippocampal pyramidal layer. In conclusion, the data argue against an antiepileptogenic effect of minocycline in adult rats. However, the findings suggest a disease-modifying impact of the tetracycline affecting the development of behavioral co-morbidities, as well as long-term consequences on spatial learning. In addition, minocycline administration resulted in a selective neuroprotective effect. Although strong anti-inflammatory effects have been proposed for minocycline, we could not verify these effects in our experimental model. Considering the multitude of mechanisms claimed to contribute to minocycline's effects, it is of interest to further explore the exact mechanisms underlying the beneficial effects in future studies. PMID:26681545

  12. Contributions of Astrocytes to Epileptogenesis Following Status Epilepticus: Opportunities for Preventive Therapy?

    Gibbons, M.B.; Smeal, R.M.; Takahashi, D.K.; Vargas, J.R.; Wilcox, K.S.

    2012-01-01

    Status epilepticus (SE) is a life threatening condition that often precedes the development of epilepsy. Traditional treatments for epilepsy have been focused on targeting neuronal mechanisms contributing to hyperexcitability, however, approximately 30% of patients with epilepsy do not respond to existing neurocentric pharmacotherapies. A growing body of evidence has demonstrated that profound changes in the morphology and function of astrocytes accompany SE and persist in epilepsy. Astrocyte...

  13. Refractory status epilepticus and glutamic acid decarboxylase antibodies in adults: presentation, treatment and outcomes.

    Khawaja, Ayaz M; Vines, Brannon L; Miller, David W; Szaflarski, Jerzy P; Amara, Amy W

    2016-03-01

    Glutamic acid decarboxylase antibodies (GAD-Abs) have been implicated in refractory epilepsy. The association with refractory status epilepticus in adults has been rarely described. We discuss our experience in managing three adult patients who presented with refractory status epilepticus associated with GAD-Abs. Case series with retrospective chart and literature review. Three patients without pre-existing epilepsy who presented to our institution with generalized seizures between 2013 and 2014 were identified. Seizures proved refractory to first and second-line therapies and persisted beyond 24 hours. Patient 1 was a 22-year-old female who had elevated serum GAD-Ab titres at 0.49 mmol/l (normal: partial seizure control. Patient 2 was a 61-year-old black female whose serum GAD-Ab titre was 0.08 mmol/l. EEG showed persistent generalized periodic discharges despite maximized therapy with anticonvulsants but no immunotherapy, resulting in withdrawal of care and discharge to nursing home. Patient 3 was a 50-year-old black female whose serum GAD-Ab titre was 0.08 mmol/l, and was discovered to have pulmonary sarcoidosis. Treatment with steroids and intravenous immunoglobulin resulted in seizure resolution. Due to the responsiveness to immunotherapy, there may be an association between GAD-Abs and refractory seizures, including refractory status epilepticus. Causation cannot be established since GAD-Abs may be elevated secondary to concurrent autoimmune diseases or formed de novo in response to GAD antigen exposure by neuronal injury. Based on this report and available literature, there may be a role for immuno- and chemotherapy in the management of refractory status epilepticus associated with GAD-Abs. PMID:26878120

  14. Efficacy and Safety of Intravenous Valproate for Status Epilepticus: A Systematic Review

    Trinka, Eugen; Höfler, Julia; Zerbs, Alexander; Brigo, Francesco

    2014-01-01

    Introduction The effectiveness of valproate (VPA) in the treatment of focal and generalized epilepsies is well established. The drug has a wide spectrum of action, good tolerability, and has been available as an injectable formulation since 1993. Despite the lack of class A evidence, it has been used extensively in various forms of status epilepticus (SE). Aim Our aim was to present a systematic review of data from randomized and non-randomized controlled trials to evaluate the efficacy and s...

  15. Treatment of experimental status epilepticus in immature rats: dissociation between anticonvulsant and antiepileptogenic effects

    Suchomelová, Lucie; Baldwin, R. A.; Kubová, Hana; Thompson, K. W.; Sankar, R.; Wasterlain, C. G.

    2006-01-01

    Roč. 59, č. 2 (2006), s. 237-243. ISSN 0031-3998 Grant ostatní: ILAE(BE) Fellowship; Johnson&Johnson´s(US) Pharm. Res. Institute; NINDS(US) NS13515; NINDS(US) NS046516; NINDS(US) NS045911 Institutional research plan: CEZ:AV0Z50110509 Keywords : status epilepticus * treatment * immature rats Subject RIV: ED - Physiology Impact factor: 2.619, year: 2006

  16. Tetramethylenedisulfotetramine contaminated milk powder induced status epilepticus in two siblings and two dogs.

    Intusoma, Utcharee; Sornsrivichai, Vorasith

    2009-10-01

    A cluster of patients with tetramethylenedisulfotetramine (TETS) intoxication was reported in Thailand. Two siblings, a-six-month-old boy and a-four-year-old girl, and their domestic dogs presented with status epilepticus within 10 minutes after ingesting milk prepared from the same tin container of milk powder. Although the cases showed normal neurodevelopment at one-year follow-up, physicians should be informed of this lethal neurotoxic agent, especially in an era of terroristic activity. PMID:19845251

  17. Analysis on the factors associated with treatment failure of using anesthetics in refractory status epilepticus

    Su, Ying-ying; Guo-ping REN; Wei-bi CHEN; Zhang, Yan; YE Hong; Dai-quan GAO

    2015-01-01

    Objective To analyze the related factors associated with immediate treatment failure of using anesthetics in refractory status epilepticus (RSE).  Methods Thirty patients derived from Neurocritical Care Unit of Xuanwu Hospital from January 2004 to December 2013 were divided into 2 groups (acute treatment failure group and acute treatment success group) based on the treatment outcome 6 h after intravenous injection of anesthetics. Univariate and multivariate forward Logistic regression ...

  18. Olfactory and gustatory hallucinations presenting as partial status epilepticus because of glioblastoma multiforme.

    Capampangan, Dan J; Hoerth, Matthew T; Drazkowski, Joseph F; Lipinski, Christopher A

    2010-10-01

    Olfactory and gustatory hallucinations are not often encountered in the acute care setting but may represent the subtle presenting features of a significant underlying disease process. We describe a patient whose most striking presenting symptoms were of olfactory and gustatory hallucinations and in whom the diagnosis and treatment of a new brain tumor and partial status epilepticus occurred entirely in the emergency department. The lesion was subsequently identified as glioblastoma multiforme involving the hippocampus and amygdala. PMID:20303620

  19. Are morphologic and functional consequences of status epilepticus in infant rats progressive?

    Kubová, Hana; Mareš, Pavel

    2013-01-01

    Roč. 235, APR 3 (2013), s. 232-249. ISSN 0306-4522 R&D Projects: GA ČR(CZ) GAP302/10/0971; GA ČR(CZ) GBP304/12/G069; GA MŠk(CZ) ME08045 Institutional research plan: CEZ:AV0Z50110509 Institutional support: RVO:67985823 Keywords : status epilepticus * immature brain * brain atrophy * epilepsy * cognitive impairment Subject RIV: FH - Neurology Impact factor: 3.327, year: 2013

  20. Changes of cortical epileptic afterdischarges after status epilepticus in immature rats

    Tsenov, Grygoriy; Kubová, Hana; Mareš, Pavel

    2008-01-01

    Roč. 78, 2-3 (2008), s. 178-185. ISSN 0920-1211 R&D Projects: GA ČR(CZ) GA309/03/0770; GA ČR(CZ) GA304/05/2582 Institutional research plan: CEZ:AV0Z50110509 Keywords : pilocarpine * status epilepticus * cortical afterdischarges Subject RIV: FH - Neurology Impact factor: 2.405, year: 2008

  1. Study on etiology and treatment of convulsive status epilepticus in children

    Dong LI

    2015-11-01

    Full Text Available The clinical data of 182 children with convulsive status epilepticus (CSE were analyzed. There were 21 cases with refractory status epilepticus (RSE and 161 cases with non-refractory status epilepticus (non-RSE. Etiological factors mainly included epilepsy in 54 cases, intracranial infection in 49 cases, and complex febrile seizure in 44 cases. In the ictal stage, 102 cases were treated with clonazepam by intravenous injection, 54 cases with diazepam by intravenous injection, 46 cases with midazolam by intravenous injection, 36 cases with phenobarbital by muscular injection, and 32 cases with 6.5% chloral hydrate by nosal feeding or clyster. The etiology of CSE in children is various. Epilepsy, intracranial infection and complex febrile seizure are the main causes. Poor prognosis and high mortality often occur in RSE caused by severe viral encephalitis. So the fundamental principle of treatment is to control CSE quickly and avoid the damage of brain and other important organs. DOI: 10.3969/j.issn.1672-6731.2015.11.009

  2. Mitochondrial and nuclear changes in hippocampal neurons in a lithium-pilocarpine-induced status epilepticus rat model

    Shuhai Tang; Li Zhang; Jianying Sun; Xiaojun Pan

    2009-01-01

    BACKGROUND: Mitochondrial damage plays a key role in neuronal damage.OBJECTIVE: To observe ultrastructural damage to mitochondria and nuclei, as well as caspase-3 expression, in hippocampal CA3 neurons of lithium-pilocarpine-induced status epilepticus rats.DESIGN, TIME AND SETTING: The neuropathological, randomized, controlled study was performed at the Animal Experimental Center, Shandong University, China in May 2008.MATERIALS: A total of 75 healthy, adult, male, Wistar rats were randomly assigned into model (n = 45) and control (n = 30) groups. Lithium-pilocarpine (Sigma, USA) was used in this study.METHODS: Rats in the model group were intraperitoneally injected with lithium chloride (3 mEq/kg),and 24 hours later with pilocarpine (45 mg/kg), to induce seizures for 2 hours. Rats in the control group were intraperitoneally infused with the same volume of saline. Rat hippocampal CA3 tissue was obtained at 3, 12, and 24 hours following status epilepticus.MAIN OUTCOME MEASURES: Neuronal changes were observed under an optical microscope. Ultrastructural changes in mitochondria and nuclei were observed using an electron microscope.caspase-3 mRNA levels were quantified by semiquantitative RT-PCR.RESULTS: After 3 hours of status epilepticus, mitochondria with swollen cristae and ruptured membranes were observed by electron microscopy. Nuclei with marginated chromatin were observed after 24 hours status epilepticus. RT-PCR results demonstrated increased caspase-3 expression at 12 hours, and significantly increased expression at 24 hours following termination of status epilepticus. This was in accordance with acidophilia occurrence, as indicated by hematoxylin-eosin staining, and time of ultrastructural damage to nuclei.CONCLUSION: In lithium-pilocarpine-induced status epilepticus rat models, ultrastructural damage to mitochondria in hippocampal neurons occurred during early stages, followed by increased caspase-3 expression and nuclear changes. These results suggested

  3. Interleukin-1 receptor is a target for adjunctive control of diazepam-refractory status epilepticus in mice.

    Xu, Zheng-Hao; Wang, Yi; Tao, An-Feng; Yu, Jie; Wang, Xiao-Yu; Zu, Yun-Yun; Zhang, Shi-Hong; Chen, Zhong

    2016-07-22

    Proinflammatory cytokine interleukin-1 beta (IL-1β) may accumulate in the brain during status epilepticus, but whether it contributes to the progressive refractoriness of SE remains unclear. By using a kainic acid-induced SE mice model, we tested whether pharmacological blockade or knock-out of interleukin-1 receptor type 1 (IL-1R1) could influence the diazepam-refractory phenomenon of prolonged SE. We confirmed diazepam failed to terminate prolonged SE (allowed to continue for 40min before diazepam administration). The expression level of IL-1β in the hippocampus during prolonged SE was significantly higher than that of baseline. Interestingly, prolonged SE was not diazepam-refractory in IL-1R1 knock-out mice. Moreover, administration of interleukin-1 receptor antagonist (IL-1RA) combined with diazepam terminated established prolonged SE, while IL-1RA alone is not capable to terminate prolonged SE. On the contrary, administration of recombinant human IL-1β weakens the efficacy of diazepam by prolonging its latency to terminate non-prolonged SE. Thus, the present study provides direct evidence that accumulated IL-1β contributed to the diazepam refractoriness of prolonged SE, and suggests that interleukin-1 receptor is a target for adjunctive control of diazepam-refractory SE. PMID:27133574

  4. Complex partial non-convulsive status epilepticus masquerading as hepatic encephalopathy: a case report

    Badshah Maaz B

    2012-12-01

    Full Text Available Abstract Introduction Hepatic encephalopathy is usually suspected in patients who are cirrhotic with neuropsychiatric manifestations. We present a case of suspected hepatic encephalopathy that did not respond to standard empiric therapy and was eventually diagnosed as non-convulsive status epilepticus of complex partial type. Our patient responded dramatically to anti-convulsive therapy. Case presentation We report the case of a 45-year-old African-American man with hepatitis C virus cirrhosis and human immunodeficiency virus who presented to our facility with a one-day history of confusion and a variable mental status. Our patient’s vital signs were stable and all his electrolytes were within normal range. A clinical diagnosis of hepatic encephalopathy was made and our patient was started on empiric therapy with lactulose and rifaximin. Our patient did not respond to therapy. After five days of treatment, alternative diagnoses were sought and a neurology consult was requested. An electroencephalogram was eventually performed which showed seizure activity in the right parietal lobe. A diagnosis of non-convulsive status epilepticus was made and our patient was started on oral levetiracetam. On day two of therapy, our patient was alert and oriented. He continues to do well on follow-up approximately one year after discharge. Conclusions Non-convulsive status epilepticus should be considered in the differential diagnosis of patients with suspected hepatic encephalopathy who do not respond to empirical treatment. Further studies are needed to investigate the incidence of this entity in patients with persistent hepatic encephalopathy.

  5. MicroRNAs in the pathophysiology and treatment of status epilepticus

    David Henshall

    2013-11-01

    Full Text Available MicroRNAs are an important class of non-coding RNA which function as post-transcriptional regulators of gene expression in cells, repressing and fine-tuning protein output. Prolonged seizures (status epilepticus, SE can cause damage to brain regions such as the hippocampus and result in cognitive deficits and the pathogenesis of epilepsy. Emerging work in animal models has found that SE produces select changes to microRNAs within the brain. Similar changes in over 20 microRNAs have been found in the hippocampus in two or more studies, suggesting conserved microRNA responses after SE. The microRNA changes that accompany SE are predicted to impact levels of multiple proteins involved in neuronal morphology and function, gliosis, neuroinflammation and cell death. MicroRNA expression also displays select changes in the blood after SE, supporting blood genomic profiling as potential molecular biomarkers of seizure-damage or epileptogenesis. Intracerebral delivery of chemically-modified antisense oligonucleotides (antagomirs has been shown to have potent, specific and long-lasting effects on brain levels of microRNAs. Targeting miR-34a, miR-132 and miR-184 has been reported to alter seizure-induced neuronal death, whereas targeting miR-134 was neuroprotective, reduced seizure severity during status epilepticus and reduced the later emergence of recurrent spontaneous seizures. These studies support roles for microRNAs in the pathophysiology of status epilepticus and microRNAs may represent novel therapeutic targets to reduce brain injury and epileptogenesis.

  6. Efficacy and Safety of Intravenous Sodium Valproate in Convulsive Status Epilepticus in Children in Shahid Sadoughi Hospital

    Razieh FALLAH

    2012-06-01

    Full Text Available How to Cite this Article: Fallah R, Yadegari Y, Salmani Nodushan M. Efficacy and Safety of Intravenous Sodium Valproate in Convulsive Status Epilepticus in Children in Shahid Sadoughi Hospital. Iran. J. Child. Neurol 2012;6(2:39-44. Objective Status epilepticus (SE is the most common pediatric neurologic emergency with high mortality and morbidity. There is no consensus on the drug of choice in the treatment of children. The purpose of this study was to evaluate the clinical efficacy and safety of intravenous sodium valproate as a third-line drug in the treatment of generalized convulsive SE of children. Materials & Methods In a retrospective study, medical records of those children who were admitted to Shahid Sadoughi Hospital of Yazd due to refractory generalized convulsive SE and were treated by intravenous sodium valproate as a third-line drug from 2009 to 2011 were evaluated. Results Six girls and five boys with a mean age of 5.12 ± 1.2 years (range: 3 - 9.6 years were evaluated. Intravenous valproate was effective for cessation of seizures in seven patients (63.6 %. The mean dose of valproate for stopping seizures was 27.1 ± 1.4 mg/kg/day. Children whose seizures were controlled by sodium valproate were older than non- responsive children (mean± SD: 4.8 ± 1.2 years vs. 3.1 ± 0.43 years, p= 0.03 and they also had shorter ICU stay days (mean± SD: 2.6 ± 1.4 days vs. 5.6 ± 2.8 days, p= 0.01. Two children had mild and transient nausea and vomiting. None of them had cardiopulmonary or severe paraclinical side effects. Conclusion Intravenous sodium valproate may be used as an effective and safe third-line antiepileptic drug in the treatment of pediatric generalized convulsive status epilepticus.References Raj D, Gulati S, Lodha R. Status epilepticus. Indian J Pediatr 2011;78(2:219-26. Shearer P, Riviello J. Generalized convulsive status epilepticus in adults and children: treatment guidelines and protocols. Emerg Med Clin North Am 2011

  7. Disconnective Hemispherotomy for Medically Intractable Status Epilepticus in an 8-Year-Old Child.

    Bradley, Lucas; Bahgat, Diaa; Sharp, Gregory; Willis, Erin; Ocal, Eylem; Albert, Gregory; Serletis, Demitre

    2015-10-01

    We report here the unusual case of an 8-year-old child with left hemispheric focal epilepsy secondary to a perinatal infarction who presented with new onset absence seizures and eventual nonconvulsive status epilepticus that was refractory to medical management. Following review at our multidisciplinary Epilepsy Surgery conference, the patient underwent disconnective surgical hemispherotomy with immediate cessation of his seizures; and has remained seizure-free at 4 months following surgery. In this context, we present here an overview of hemispherectomy and related procedures, including peri-insular disconnective hemispherotomy, and we discuss the efficacy of surgery for challenging hemispheric epilepsies. PMID:26552284

  8. p75NTR, but Not proNGF, Is Upregulated Following Status Epilepticus in Mice

    VonDran, Melissa W.; LaFrancois, John; Padow, Victoria A.; Friedman, Wilma J.; Scharfman, Helen E.; Milner, Teresa A.; Hempstead, Barbara L.

    2014-01-01

    ProNGF and p75NTR are upregulated and induce cell death following status epilepticus (SE) in rats. However, less is known about the proneurotrophin response to SE in mice, a more genetically tractable species where mechanisms can be more readily dissected. We evaluated the temporal- and cell-specific induction of the proneurotrophins and their receptors, including p75NTR, sortilin, and sorCS2, following mild SE induced with kainic acid (KA) or severe SE induced by pilocarpine. We found that m...

  9. Diagnosis and interpretation of EEG on non-convulsive status epilepticus

    Xiao-gang KANG

    2015-11-01

    Full Text Available It is difficult to diagnose non-convulsive status epilepticus (NCSE clinically because of the complicated etiology and various clinical and electroencephalographic features of NCSE without a universally accepted definition. Although the diagnosis of NCSE relies largely on electroencephalogram (EEG findings, the determination of NCSE on EEG is inevitably subjective, and the EEG changes of most patients is lack of specificity. As the diagnosis of NCSE is related to clinical and electroencephalographic manifestations, diagnostic criteria for NCSE should take into account both clinical and electroencephalographic features, and their response to antiepileptic drugs (AEDs. DOI: 10.3969/j.issn.1672-6731.2015.11.005

  10. Status Epilepticus Due to Severe HHV-6 Encephalitis in an Allogeneic Stem Cell Transplant Recipient

    Poorvi Chordia

    2013-12-01

    Full Text Available Reactivation of human herpes virus-6 (HHV-6 after stem cell transplantation occurs frequently. It is associated with clinical manifestations varying from nonspecific symptoms such as fevers or rash, to severe life threatening complications including post-transplantation limbic encephalitis. We report a case of severe HHV-6 encephalitis with viremia in an allogeneic peripheral stem cell transplant recipient who presented with status epilepticus unresponsive to antiepileptic therapy.  With intravenous ganciclovir and supportive care, the patient’s condition improved. Awareness of HHV-6 infection in stem cell transplant recipients may help with early diagnosis and improved outcome.

  11. Intravenous ketamine for treatment of super-refractory convulsive status epilepticus with septic shock: A report of two cases

    Gentle Sunder Shrestha

    2015-01-01

    Full Text Available Refractory and super-refractory status epilepticus is a life-threatening neurological emergency, associated with high morbidity and mortality. Treatment should be aimed to stop seizure and to avoid cerebral damage and another morbidity. Published data about effectiveness, safety and outcome of various therapies and treatment approaches are sparse and are mainly based on small case series and retrospective data. Here we report successful management of two cases of super-refractory status epilepticus refractory to anesthetic therapy with midazolam and complicated by septic shock, managed successfully with ketamine infusion.

  12. Intravenous ketamine for treatment of super-refractory convulsive status epilepticus with septic shock: A report of two cases

    Shrestha, Gentle Sunder; Joshi, Pankaj; Chhetri, Santosh; Karn, Ragesh; Acharya, Subhash Prasad

    2015-01-01

    Refractory and super-refractory status epilepticus is a life-threatening neurological emergency, associated with high morbidity and mortality. Treatment should be aimed to stop seizure and to avoid cerebral damage and another morbidity. Published data about effectiveness, safety and outcome of various therapies and treatment approaches are sparse and are mainly based on small case series and retrospective data. Here we report successful management of two cases of super-refractory status epilepticus refractory to anesthetic therapy with midazolam and complicated by septic shock, managed successfully with ketamine infusion. PMID:25983437

  13. Slow pseudoperiodic lateralized epileptiform discharges in nonconvulsive status epilepticus in a patient with cerebral palsy and a large central meningioma

    Y.Z. Imam

    2014-01-01

    Full Text Available The presence of cerebral palsy and that of slow growing brain tumors are risk factors for convulsive and nonconvulsive status epilepticus. Nonconvulsive status epilepticus (NCSE needs electroencephalographic (EEG monitoring to be confirmed as it may be clinically subtle. Furthermore, it may present with a variety of ictal EEG morphologies. We report a case of a patient with cerebral palsy and a large central meningioma. Electroencephalogram showed a slow pattern of periodic lateralized epileptiform discharges (PLEDs (a pattern considered as being situated in the ictal–interictal continuum on an alpha background. The patient was treated for NCSE successfully with benzodiazepines followed by up-titration of his antiepileptic drug doses.

  14. Glucose utilisation during status epilepticus in an epilepsy model induced by pilocarpine: a qualitative study

    Scorza Fulvio Alexandre

    2002-01-01

    Full Text Available Status epilepticus (SE is a medical emergency and it is associated to brain damage. 2-deoxy-[14C] glucose (2-DG procedure has been used to measure the alterations in the functional activity of the brain induced by various pharmacological and toxicological agents. The aim of this study was to determine which changes occur in the seizure anatomic substrates during the SE induced by pilocarpine (PILO using [14C]-2 deoxyglucose functional mapping technique. Wistar male adult rats were submitted to SE PILO-induced for 6h and received [14C] 2-deoxyglucose injection via jugular vein 45 min before the 6th hour of SE. The control animals were submitted to all procedures but received saline and not pilocarpine. Brain sections were prepared and exposed X-ray film about seven days. The optical density of each region was obtained using a solid state digital analyser. The analysis revealed that 14C-2DG utilisation was pronounced in the SE rats on the areas corresponding to the hippocampal formation (+50.6%, caudate-putamen (+30.6%, frontoparietal cortex (+32.2%, amygdala (+31.7%, entorrinal cortex (+28.2%, thalamic nucleus (+93.5%, pre-tectal area (+50.1% and substantia nigra (+50.3% when compared to control. Our results suggest that the different activation levels of the distinct structures may be particularly important for understanding triggering and spreading mechanisms underlying epileptic activity during status epilepticus.

  15. Analysis of factors influencing admission to intensive care following convulsive status epilepticus in children.

    Tirupathi, Sandya

    2012-02-01

    OBJECTIVES: To identify clinical features and therapeutic decisions that influence admission to the Intensive Care unit (ICU) in children presenting with convulsive status epilepticus (CSE). METHODS: We evaluated 47 admissions with status epilepticus to a tertiary paediatric hospital A&E over a three year period (2003-2006). Following initial management 23 episodes required admission to ICU and 24 were managed on a paediatric ward. We compared clinical, demographic data and compliance with our CSE protocol between the ICU and ward groups. RESULTS: Median age at presentation in the ICU group was 17 months (range 3 months-11 years) compared to 46 months in the ward group (range 3 months-10 years). Fifty per cent of patients in both groups had a previous history of seizures. Median duration of pre-hospital seizure activity was 30 min in both groups. More than two doses of benzodiazepines were given as first line medication in 62% of the ICU group and 33% of the ward group. Among children admitted to ICU with CSE, 26% had been managed according to the CSE protocol, compared to 66% of children who were admitted to a hospital ward. Febrile seizures were the most common aetiology in both groups. CONCLUSION: Younger age at presentation, administration of more than two doses of benzodiazepines and deviation from the CSE protocol appear to be factors which influence admission of children to ICU. Recognition of pre-hospital administration of benzodiazepines and adherence to therapeutic guidelines may reduce the need for ventilatory support in this group.

  16. A Case Of Primary Central Nervous System Vasculitis Who Presented With Status Epilepticus

    Sırma Geyik

    2014-12-01

    Full Text Available Primary central nervous system vasculitis (PCNV is limited with central nervous system and rare vasculitis that mostly seen in middle-aged men. PCNV vasculitis is usually presented that headache, dementia, stroke and multifocal common neurological symptoms. PCNV especially involves small medium-sized leptomeningeal and cortical arteries. 43 years old male patient who have been progressive forgetfulness and headache for 3 years. He applied with recurrent that before starting right focal and than sprawling whole body which generalized tonic-clonic seizures to us. During management that he was transfered to the intensive care unit due to status epilepticus (SE. Later than we found right hemiparesis, motor aphasia and right babinski positivity in neurologic examination. Diffusion restriction was revealed in left MCA territory in diffusion magnetic resonance imaging(MRI. EEG showed two types abnormality that a slow background ritm and epileptiform activity. Biochemistry of blood, complete blood count, blood sedimentation rate, CRP and markers of vasculitis were found in the normal range. Cerebral anjiography revealed that irregularities in the distal vascular areas and fusiform aneurysm at the top of basilar artery. He was consulted with rheumatology and diagnosed central nervous system vasculitis with the existing findings. Biopsy couldn't be taken from the brain to verify the diagnosis. Finally, we applied treatment that pulse steroid and cyclophosphamide to patient. This case has been presented due to emphasize that PCNV rarely may play a role in the etiology of recurrent stroke and status epilepticus.

  17. The CNTF-derived peptide mimetic Cintrofin attenuates spatial-learning deficits in a rat post-status epilepticus model

    Russmann, Vera; Seeger, Natalie; Zellinger, Christina; Hadamitzky, Martin; Pankratova, Stanislava; Wendt, Hannes; Bock, Elisabeth; Berezin, Vladimir; Potschka, Heidrun

    2013-01-01

    Ciliary neurotrophic growth factor is considered a potential therapeutic agent for central nervous system diseases. We report first in vivo data of the ciliary neurotrophic growth factor peptide mimetic Cintrofin in a rat post-status epilepticus model. Cintrofin prevented long-term alterations in...

  18. Impact of the NCAM derived mimetic peptide plannexin on the acute cellular consequences of a status epilepticus

    Zellinger, Christina; Hadamitzky, Martin; Bock, Elisabeth;

    2011-01-01

    hippocampal subregions. The comparison between the vehicle- and plannexin-treated animals with status epilepticus did not reveal neuroprotective effects of plannexin on mature neurons. However, treatment with plannexin partially prevented the reduction in the number of doublecortin-labeled neuronal progenitor...

  19. Time course of neuronal damage in the hippocampus following lithium-pilocarpine status epilepticus in 12-day-old rats

    Druga, R.; Mareš, Pavel; Kubová, Hana

    2010-01-01

    Roč. 1355, - (2010), s. 174-176. ISSN 0006-8993 R&D Projects: GA ČR GA304/04/0464; GA ČR(CZ) GA304/07/1137 Institutional research plan: CEZ:AV0Z50110509 Keywords : degenerating neurons * status epilepticus * ontogeny Subject RIV: FH - Neurology Impact factor: 2.623, year: 2010

  20. Transcriptional response of polycomb group genes to status epilepticus in mice is modified by prior exposure to epileptic preconditioning

    James eReynolds

    2015-03-01

    Full Text Available Exposure of the brain to brief, non-harmful seizures can activate protective mechanisms that temporarily generate a damage-refractory state. This process, termed epileptic tolerance, is associated with large-scale down-regulation of gene expression. Polycomb group proteins are master controllers of gene silencing during development that are re-activated by injury to the brain. Here we explored the transcriptional response of genes associated with polycomb repressor complex (PRC 1 (Ring1A and Ring1B and Bmi1 and PRC2 (Ezh1, Ezh2 and Suz12, as well as additional transcriptional regulators Sirt1, Yy1 and Yy2, in a mouse model of status epilepticus. Findings were contrasted to changes after status epilepticus in mice previously given brief seizures to evoke tolerance. Real-time quantitative PCR showed status epilepticus prompted an early (1 h increase in expression of several genes in PRC1 and PRC2 in the hippocampus, followed by down-regulation of many of the same genes at later times points (4 , 8 and 24 h. Spatio-temporal differences were found among PRC2 genes in epileptic tolerance, including increased expression of Ezh2, Suz12 and Yy2 relative to the normal injury response to status epilepticus. In contrast, PRC1 complex genes including Ring 1B and Bmi1 displayed differential down-regulation in epileptic tolerance. The present study characterizes polycomb group gene expression following status epilepticus and shows prior seizure exposure produces select changes to PRC1 and PRC2 composition that may influence differential gene expression in epileptic tolerance.

  1. Intravenous ketamine for treatment of super-refractory convulsive status epilepticus with septic shock: A report of two cases

    Gentle Sunder Shrestha; Pankaj Joshi; Santosh Chhetri; Ragesh Karn; Subhash Prasad Acharya

    2015-01-01

    Refractory and super-refractory status epilepticus is a life-threatening neurological emergency, associated with high morbidity and mortality. Treatment should be aimed to stop seizure and to avoid cerebral damage and another morbidity. Published data about effectiveness, safety and outcome of various therapies and treatment approaches are sparse and are mainly based on small case series and retrospective data. Here we report successful management of two cases of super-refractory status epile...

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

    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.

  3. Pilocarpine-Induced Status Epilepticus in Rats Involves Ischemic and Excitotoxic Mechanisms

    Fabene, Paolo Francesco; Merigo, Flavia; Galiè, Mirco; Benati, Donatella; Bernardi, Paolo; Farace, Paolo; Nicolato, Elena; Marzola, Pasquina; Sbarbati, Andrea

    2007-01-01

    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. PMID:17971868

  4. A case of recurrent acute encephalopathy with febrile convulsive status epilepticus with carnitine palmitoyltransferase II variation.

    Sakai, Eiko; Yamanaka, Gaku; Kawashima, Hisashi; Morishima, Yasuyuki; Ishida, Yu; Oana, Shingo; Miyajima, Tasuku; Shinohara, Mayu; Saitoh, Makiko; Mizuguchi, Masashi

    2013-08-01

    Acute encephalopathy with febrile convulsive status epilepticus (AEFCSE) is the most common type of acute encephalopathy in childhood in Japan, which develops with prolonged febrile convulsion, followed by mild unconsciousness. It is generally sporadic and nonrecurrent. In this report, a 1-year-old girl showed signs of AEFCSE triggered by respiratory syncytial virus infection. Two years later, she presented with AEFCSE triggered by influenza virus infection, resulting in severe neurologic sequelae. The patient had a thermolabile genotype of carnitine palmitoyltransferase II (CPT II) variations consisting of three single nucleotide polymorphisms in exons 4 [1055T > G/F352C and 1102G > A/V368I] and 5 [1939A > G/M647V]. The polymorphism has been identified as a genetic predisposition for acute encephalopathy. This report presents the first case of recurrent encephalopathy with CPT II variations that may partially associate with pathogenesis of recurrent AEFCSE. PMID:23450341

  5. Anticonvulsant discovery through animal models of status epilepticus induced by organophosphorus nerve agents and pesticides.

    McCarren, Hilary S; McDonough, John H

    2016-06-01

    Organophosphorus pesticides (OPs) and nerve agents (NAs) are highly toxic chemicals that pose a significant threat to human health worldwide. These compounds induce status epilepticus (SE) by irreversibly blocking the ability of acetylcholinesterase to break down acetylcholine at neural synapses. Animal models of organophosphate-induced SE are a crucial resource for identifying new anticonvulsant therapies. Here, we describe the development of various animal models of SE induced by NA or OP exposure. Experiments in nonhuman primates, rats, mice, and guinea pigs have helped to identify novel therapeutic targets in the central nervous system, with particular success at modulating GABAergic and glutamatergic receptors. The anticonvulsants identified by NA- and OP-induced SE models are well poised for fast advancement into clinical development, and their potential utility in the broader field of epilepsy should make them all the more attractive for commercial pursuit. PMID:27258770

  6. Status epilepticus associated with initiation of theophylline in an elderly patient with diabetic ketoacidosis

    Chung-Hsing Chou

    2007-01-01

    Full Text Available An 80-year-old man with a history of Type 2 diabetes mellitus was hospitalized due to generalized convulsive status epilepticus. Initially, hyperglycemia and ketoacidosis were diagnosed, but his seizures were refractory to the medical treatment. Additionally, a high level of serum theophylline (29.1 mg/mL was detected. Following detoxification of theophylline by oral activated charcoal, the patient regained consciousness and was free from seizures without antiepileptic drug treatment. Brain magnetic resonance imaging revealed subacute subdural hematomas at the bilateral occipital hemispheres. This case suggests that theophylline toxicity may be a predisposing factor for seizures in patients with a history of traumatic brain injury in spite of the presence of diabetic ketoacidosis that may have an anticonvulsant action.

  7. Combined use of intravenous anesthetics and hypothermia in treating refractory status epilepticus

    Guo-ping REN

    2015-11-01

    Full Text Available The primary choice of treating refractory status epilepticus (RSE is intravenous anesthetics, but the seizures of some patients can not get a good control. Thus, other therapies must be combined. Hypothermia not only can terminate seizures, but also play a part in brain protection. Though combined use of intravenous anesthetics and hypothermia is not a regular clinical scheme, the favorable effect has been proved by a lot of clinical research. This paper mainly focuses on the dose of intravenous anesthetics, the time, temperature and procedure of hypothermia, the indications and contraindications of combined therapy, and so on. DOI: 10.3969/j.issn.1672-6731.2015.11.006

  8. Opercular myoclonic-anarthric status epilepticus: A report of two cases

    Janapareddy Vijaya Bhaskara Rao

    2013-01-01

    Full Text Available Opercular myoclonic-anarthric status epilepticus (OMASE is an uncommon disorder of diverse etiology. This condition is characterized by fluctuating cortical dysarthria associated with epileptic myoclonus involving glossopharyngeal musculature bilaterally. We report two cases of OMASE of vascular etiology in adults. In both patients, ictally clonic expression was consistent with epilepsia partialis continua and bilateral, symmetrical involvement of soft palate in one patient and tongue, lips, chin and inferior jaw in both patients due to bilateral projections of the inferior corticonuclear pathways. The inferior rolandic area of dominant and high frontal region in non-dominant hemispheres were involved by an epileptogenic lesion of vascular etiology, which was confirmed by magnetic resonance imaging of brain and single photon emission computerized tomography. Carotid Doppler study showed thrombosis of internal carotid artery in both patients, suggestive of an embolic origin. Early recognition of OMASE is important for early management of carotid occlusive disease.

  9. Analysis on the factors associated with treatment failure of using anesthetics in refractory status epilepticus

    Ying-ying SU

    2015-11-01

    Full Text Available Objective To analyze the related factors associated with immediate treatment failure of using anesthetics in refractory status epilepticus (RSE.  Methods Thirty patients derived from Neurocritical Care Unit of Xuanwu Hospital from January 2004 to December 2013 were divided into 2 groups (acute treatment failure group and acute treatment success group based on the treatment outcome 6 h after intravenous injection of anesthetics. Univariate and multivariate forward Logistic regression analyses were used to analyze and screen the risk factors associated with immediate treatment failure, and calculate the failure rate of final outcome.  Results According to the results of univariate and multivariate Logistic regression analyses, among influencing factors such as sex, age, etiology, Acute Physiology and Chronic Health EvaluationⅡ (APACHEⅡ, type of status epilepticus (SE, type of antiepileptic drugs (AEDs, total duration of primary treatment, duration of prehospital primary treatment, duration of posthospital primary treatment, type of RSE and primary choice of anesthetics, only total duration of primary treatment was the independent risk factor for immediate treatment failure (OR = 1.007, 95%CI: 1.000-1.014; P = 0.047. The rate of immediate treatment failure of RSE by using anesthetics was 50% (15/30, and the rate of final treatment failure was 43.33% (13/30. The ratio of final treatment failure was much higher in acute treatment failure group than that in acute treatment success group (10/15 vs 3/15, P = 0.025.  Conclusions The acute treatment result of RSE depends on the total duration of primary treatment, and determinates the final result of treatment. On the basis of treating primary disease, the therapy to terminate SE or RSE should be started as early as possible. DOI: 10.3969/j.issn.1672-6731.2015.11.008

  10. Is pentobarbital safe and efficacious in the treatment of super-refractory status epilepticus: a cohort study

    Pugin, Deborah; Foreman, Brandon; De Marchis, Gian Marco; Fernandez, Andres; Schmidt, J. Michael; Czeisler, Barry M; Mayer, Stephan A; Agarwal, Sachin; Lesch, Christine; Lantigua, Hector; Claassen, Jan

    2014-01-01

    Introduction Seizures refractory to third-line therapy are also labeled super-refractory status epilepticus (SRSE). These seizures are extremely difficult to control and associated with poor outcome. We aimed to characterize efficacy and side-effects of continuous infusions of pentobarbital (cIV-PTB) treating SRSE. Methods We retrospectively reviewed continuous electroencephalography (cEEG) reports for all adults with RSE treated with cIV-PTB between May 1997 and April 2010 at our institution...

  11. Free radical scavenger, N-tert-butyl-alfa-phenylnitrone, affects long-term outcome of status epilepticus in immature rats

    Kubová, Hana; Rejchrtová, Jana; Folbergrová, Jaroslava; Mareš, Pavel

    2005-01-01

    Roč. 46, č. S8 (2005), s. 111-112. [Joint Annual Meeting of the American Epilepsy Society and American Clinical Neurophysiology Society. 02.12.2005-06.12.2005, Washington, DC] R&D Projects: GA ČR(CZ) GA304/05/2582 Institutional research plan: CEZ:AV0Z50110509 Keywords : status epilepticus * PBN * rat Subject RIV: ED - Physiology

  12. Kontinuierliche EEG Überwachung für die Therapie von Hunden und Katzen im Status epilepticus

    Raith, Karina

    2010-01-01

    Goal of this case series was to describe the management of Status epilepticus in dogs and cats with the aid of continuous electroencephalographic (EEG) monitoring. Ten patients (7 dogs, 3 cats) with SE of differing etiology (idiopathic epilepsy, n=3; toxicity, n=4; meningoencephalitis, n=2; undefined, n=1) were included in the study. The EEG was recorded continuously from five stainless steel needle-electrodes inserted subcutaneously. Animals were treated with diazepam and phenobarbital follo...

  13. Effects of LiCl/PILOCARPINE-induced status epilepticus on rat brain benzodiazepine receptor binding: regional and ontogenetic study

    Kubová, Hana; Suchomelová, Lucie; Rocha, L.

    Praha : The Czech Neuroscience Society, 2007. s. 32-32. [Conference of the Czech Neuroscience Society /6./. 19.11.2007-20.11.2007, Praha] R&D Projects: GA ČR(CZ) GA304/05/2582; GA ČR(CZ) GD305/03/H148 Grant ostatní: CONACyT(MX) 45943-M Institutional research plan: CEZ:AV0Z50110509 Keywords : spr2 * status epilepticus * LiCl/pilocarpine * ontogeny Subject RIV: FH - Neurology

  14. Loss of p53 results in protracted electrographic seizures and development of an aggravated epileptic phenotype following status epilepticus

    Engel, T.; K.Tanaka; Jimenez-Mateos, E M; Caballero-Caballero, A; Prehn, J. H. M.; HENSHALL, D. C.

    2010-01-01

    The p53 tumor suppressor is a multifunctional protein, which regulates cell cycle, differentiation, DNA repair and apoptosis. Experimental seizures up-regulate p53 in the brain, and acute seizure-induced neuronal death can be reduced by genetic deletion or pharmacologic inhibition of p53. However, few long-term functional consequences of p53 deficiency have been explored. Here, we investigated the development of epilepsy triggered by status epilepticus in wild-type and p53-deficient mice. Ana...

  15. P2X7 receptor-mediated PARP1 activity regulates astroglial death in the rat hippocampus following status epilepticus

    Ji-Eun Kim

    2015-01-01

    Poly(ADP-ribose) polymerase-1 (PARP1) plays a regulatory role in apoptosis, necrosis, and other cellular processes after injury. Recently, we revealed that PARP1 regulates the differential neuronal/astroglial responses to pilocarpine-induced status epilepticus (SE) in the distinct brain regions. In addition, P2X7 receptor (P2X7R), an ATP-gated ion channel, activation accelerates astroglial apoptosis, while it attenuates clasmatodendrosis (lysosome-derived autophagic astroglial death). Therefo...

  16. Valnoctamide enhances phasic inhibition: a potential target mechanism for the treatment of benzodiazepine-refractory status epilepticus

    Spampanato, Jay; Dudek, F. Edward

    2014-01-01

    Valnoctamide (VCD), a derivative of valproate, suppresses electrographic seizures in animal models of status epilepticus (SE), even when the seizures are resistant to benzodiazepines (BZDs). We therefore tested the effect of VCD on miniature inhibitory post-synaptic currents (mIPSCs) in CA1 pyramidal cells to determine if VCD acts directly on GABAA receptors. Bath-applied VCD induced a specific, rapid, dose-dependent, and reversible slowing of the decay of mIPSCs (i.e., increased time constan...

  17. Does status epilepticus induced at early postnatal period change excitability after cortical epileptic afterdischarges?

    Mareš, Pavel; Kubová, Hana

    2016-08-01

    Possible changes of cortical excitability after status epilepticus (SE) elicited in 12-day-old rats were studied by means of paired cortical afterdischarges (ADs). Consequences of lithium-pilocarpine status were studied in animals with implanted electrodes 3, 6, 9, 13, and 26 days after SE. Paired low-frequency stimulation with a 1-min interval was repeated after 10 min, and duration of ADs was measured. Control rats received saline instead of pilocarpine; other treatments were the same as in SE group. Postictal refractoriness (i.e., the testing response significantly shorter than the conditioning one) appeared at the age of 18 days in lithium-paraldehyde controls, whereas SE animals exhibited this phenomenon since postnatal day 21. The only significant difference between SE and lithium-paraldehyde controls was found in the second conditioning AD in the oldest group studied-it was longer in 38-day-old SE animals. Our results demonstrated moderate signs of higher excitability of SE rats in comparison with control ones long before appearance of spontaneous seizures. PMID:27346862

  18. The potential of sec-butylpropylacetamide (SPD) and valnoctamide and their individual stereoisomers in status epilepticus.

    Shekh-Ahmad, Tawfeeq; Mawasi, Hafiz; McDonough, John H; Yagen, Boris; Bialer, Meir

    2015-08-01

    sec-Butylpropylacetamide (SPD) is a one-carbon homologue of valnoctamide (VCD), a chiral constitutional isomer of valproic acid's (VPA) corresponding amide--valpromide. Racemic-SPD and racemic-VCD possess a unique and broad-spectrum antiseizure profile superior to that of VPA. In addition, SPD blocks behavioral and electrographic status epilepticus (SE) induced by pilocarpine and the organophosphates soman and paraoxon. Valnoctamide has similar activity as SPD in the soman-induced SE model. The activity of SPD and VCD against SE is superior to that of diazepam and midazolam in terms of rapid onset, potency, and ability to block SE when given 20 to 60 min after seizure onset. sec-Butylpropylacetamide and VCD possess two stereogenic carbons in their chemical structure and, thus, exist as a racemic mixture of four individual stereoisomers. The anticonvulsant activity of the individual stereoisomers of SPD and VCD was comparatively evaluated in several anticonvulsant rodent models including the benzodiazepine-resistant SE model. sec-Butylpropylacetamide has stereoselective pharmacokinetics (PK) and pharmacodynamics (PD). The higher clearance of (2R,3S)-SPD and (2S,3R)-SPD led to a 50% lower plasma exposure and, consequently, to a lower anticonvulsant activity compared to racemic-SPD and its two other stereoisomers. Racemic-SPD, (2S,3S)-SPD, and (2R,3R)-SPD have similar anticonvulsant activities and PK profiles that are better than those of (2R,3S)-SPD and (2S,3R)-SPD. Valnoctamide has a stereoselective PK with (2S,3S)-VCD exhibiting the lowest clearance and, consequently, a twice-higher plasma exposure than all other stereoisomers. Nevertheless, there was less stereoselectivity in VCD anticonvulsant activity, and each stereoisomer had similar ED50 values in most models. sec-Butylpropylacetamide and VCD stereoisomers did not cause teratogenicity (i.e., neural tube defect) in mice at doses 3-12 times higher than their anticonvulsant-ED50 values. This article is part of a

  19. Exposure to Mozart music reduces cognitive impairment in pilocarpine-induced status epilepticus rats.

    Xing, Yingshou; Qin, Yi; Jing, Wei; Zhang, Yunxiang; Wang, Yanran; Guo, Daqing; Xia, Yang; Yao, Dezhong

    2016-02-01

    Patients with temporal lobe epilepsy (TLE) often display cognitive deficits. However, current epilepsy therapeutic interventions mainly aim at how to reduce the frequency and degree of epileptic seizures. Recovery of cognitive impairment is not attended enough, resulting in the lack of effective approaches in this respect. In the pilocarpine-induced temporal lobe epilepsy rat model, memory impairment has been classically reported. Here we evaluated spatial cognition changes at different epileptogenesis stages in rats of this model and explored the effects of long-term Mozart music exposure on the recovery of cognitive ability. Our results showed that pilocarpine rats suffered persisting cognitive impairment during epileptogenesis. Interestingly, we found that Mozart music exposure can significantly enhance cognitive ability in epileptic rats, and music intervention may be more effective for improving cognitive function during the early stages after Status epilepticus. These findings strongly suggest that Mozart music may help to promote the recovery of cognitive damage due to seizure activities, which provides a novel intervention strategy to diminish cognitive deficits in TLE patients. PMID:26834859

  20. Refractory status epilepticus after inadvertent intrathecal injection of tranexamic acid treated by magnesium sulfate.

    Hatch, D M; Atito-Narh, E; Herschmiller, E J; Olufolabi, A J; Owen, M D

    2016-05-01

    We present a case of accidental injection of tranexamic acid during spinal anesthesia for an elective cesarean delivery. Immediately following intrathecal injection of 2mL of solution, the patient complained of severe back pain, followed by muscle spasm and tetany. As there was no evidence of spinal block, the medications given were checked and a 'used' ampoule of tranexamic acid was found on the spinal tray. General anesthesia was induced but muscle spasm and tetany persisted despite administration of a non-depolarizing muscle relaxant. Hemodynamic instability, ventricular tachycardia, and status epilepticus developed, which were refractory to phenytoin, diazepam, and infusions of thiopental, midazolam and amiodarone. Magnesium sulfate was administered postoperatively in the intensive care unit, following which the frequency of seizures decreased, eventually stopping. Unfortunately, on postoperative day three the patient died from cardiopulmonary arrest after an oxygen supply failure that was not associated with the initial event. This report underlines the importance of double-checking medications before injection in order to avoid a drug error. As well, it suggests that magnesium sulfate may be useful in stopping seizures caused by the intrathecal injection of tranexamic acid. PMID:26775897

  1. Optogenetic delay of status epilepticus onset in an in vivo rodent epilepsy model.

    Inna Sukhotinsky

    Full Text Available Epilepsy is a devastating disease, currently treated with medications, surgery or electrical stimulation. None of these approaches is totally effective and our ability to control seizures remains limited and complicated by frequent side effects. The emerging revolutionary technique of optogenetics enables manipulation of the activity of specific neuronal populations in vivo with exquisite spatiotemporal resolution using light. We used optogenetic approaches to test the role of hippocampal excitatory neurons in the lithium-pilocarpine model of acute elicited seizures in awake behaving rats. Hippocampal pyramidal neurons were transduced in vivo with a virus carrying an enhanced halorhodopsin (eNpHR, a yellow light activated chloride pump, and acute seizure progression was then monitored behaviorally and electrophysiologically in the presence and absence of illumination delivered via an optical fiber. Inhibition of those neurons with illumination prior to seizure onset significantly delayed electrographic and behavioral initiation of status epilepticus, and altered the dynamics of ictal activity development. These results reveal an essential role of hippocampal excitatory neurons in this model of ictogenesis and illustrate the power of optogenetic approaches for elucidation of seizure mechanisms. This early success in controlling seizures also suggests future therapeutic avenues.

  2. Status Epilepticus as a Presenting Sign of Reversible Posterior Leukoencephalopathy Syndrome in a Liver Transplant Recipient

    Seyed-Mohammadali Musavi

    2009-03-01

    Full Text Available Background: Reversible posterior leukoencephalopathy syndrome (RPLE is an increasingly recognized disorder, most commonly associated with immunosuppressive and cytotoxic agent, malignant hypertension and toxemia of pregnancy. Neurological symptoms are headache, mental and visual disturbance, and seizures. Brain MRI findings are symmetrical bilateral hyper intense areas of occipital and parietal lobes in T2-weighted magnetic resonance (MR images. This finding is reversible with prompt successful treatment which may take days to weeks for full reversal. Case Presentation: We observed a case of status epilepticus which occurred 32 days after liver transplantation in a patient on regimen consisting of Tacrolimus (FK 506. He had no history of neurologic disease or metabolic abnormalities. Typical findings of RPLE were present on brain MRI. The recurrence of seizures terminated after a few hours with adding Na-valproate to Phenytoin, Phenobarbital and Midazolam. The radiological finding of brain MRI gradually diminished after several weeks. Conclusion: A physician should be alert of seizures during early post transplant period of liver transplantation. He should bear in mind the diagnosis of RPLE and consider discontinuation of immunosuppressive drugs.

  3. Lorazepam or diazepam for convulsive status epilepticus: A meta-analysis.

    Wu, Wei; Zhang, Liqun; Xue, Rong

    2016-07-01

    Convulsive status epilepticus (CSE) is a neurological emergency in adults and children. However, whether a particular benzodiazepine is of superior efficacy and safety in management of CSE is controversial. We performed a meta-analysis to compare the outcome of lorazepam and diazepam for treating CSE. We searched the PubMed, Medline, Embase, Cochrane Central Register of Controlled Trials, and Google Scholar databases from 1966 to February 2014. No language restriction was applied. Reference lists of all the selected articles were hand-searched for any additional trials. Trial quality was assessed using the modified Jadad scale and the Consolidated Standards Of Reporting Trials (CONSORT) checklist. Two authors independently extracted data from all eligible studies, including study design, participants, interventions, and outcomes. The data was analyzed using fixed-effects or random-effects models with mean differences and risk ratios for continuous and dichotomous variables, respectively. A total of six studies involving 970 patients were included in this analysis. The majority of patients were children (n=574) and 396 patients were adults. Meta-analysis showed no significant difference between the two treatment groups regarding seizure control and adverse effects regardless of patient age. This meta-analysis demonstrates that diazepam and lorazepam have equal efficacy and side effects for treating CSE in adults and children, and either can be chosen as a reasonable first-line therapy. More high quality randomized controlled trials are needed to support this finding. PMID:27052258

  4. Minocycline inhibits brain inflammation and attenuates spontaneous recurrent seizures following pilocarpine-induced status epilepticus.

    Wang, N; Mi, X; Gao, B; Gu, J; Wang, W; Zhang, Y; Wang, X

    2015-02-26

    Mounting evidence suggests that brain inflammation mediated by glial cells may contribute to epileptogenesis. Minocycline is a second-generation tetracycline and has potent antiinflammatory effects independent of its antimicrobial action. The present study aimed to investigate whether minocycline could exert antiepileptogenic effects in a rat lithium-pilocarpine model of temporal lobe epilepsy. The temporal patterns of microglial and astrocytic activation were examined in the hippocampal CA1 and the adjacent cortex following pilocarpine-induced status epilepticus (SE). These findings displayed that SE caused acute and persistent activation of microglia and astrocytes. Based on these findings, Minocycline was administered once daily at 45 mg/kg for 14 days following SE. Six weeks after termination of minocycline treatment, spontaneous recurrent seizures (SRS) were recorded by continuous video monitoring. Minocycline inhibited the SE-induced microglial activation and the increased production of interleukin-1β and tumor necrosis factor-α in the hippocampal CA1 and the adjacent cortex, without affecting astrocytic activation. In addition, Minocycline prevented the SE-induced neuronal loss in the brain regions examined. Moreover, minocycline significantly reduced the frequency, duration, and severity of SRS during the two weeks monitoring period. These results demonstrated that minocycline could mitigate SE-induced brain inflammation and might exert disease-modifying effects in an animal model of temporal lobe epilepsy. These findings offer new insights into deciphering the molecular mechanisms of epileptogenesis and exploring a novel therapeutic strategy for prevention of epilepsy. PMID:25541249

  5. Evaluation of a clinical tool for early etiology identification in status epilepticus

    Alvarez, Vincent; Westover, M. Brandon; Drislane, Frank W.; Dworetzky, Barbara A.; Curley, David

    2016-01-01

    Summary Objectives Because early etiologic identification is critical to select appropriate specific status epilepticus (SE) management, we aim to validate a clinical tool we developed that uses history and readily available investigations to guide prompt etiologic assessment. Methods This prospective multicenter study included all adult patients treated for SE of all but anoxic causes from four academic centers. The proposed tool is designed as a checklist covering frequent precipitating factors for SE. The study team completed the checklist at the time the patient was identified by electroencephalography (EEG) request. Only information available in the emergency department or at the time of in-hospital SE identification was used. Concordance between the etiology indicated by the tool and the determined etiology at hospital discharge was analyzed, together with interrater agreement. Results Two hundred twelve patients were included. Concordance between the etiology hypothesis generated using the tool and the finally determined etiology was 88.7% (95% confidence interval (CI) 86.4–89.8) (κ = 0.88). Interrater agreement was 83.3% (95% CI 80.4–96) (κ = 0.81). Significance This tool is valid and reliable for identification early the etiology of an SE. Physicians managing patients in SE may benefit from using it to identify promptly the underlying etiology, thus facilitating selection of the appropriate treatment. PMID:25385281

  6. Focal hemodynamic patterns of status epilepticus detected by susceptibility weighted imaging (SWI)

    Aellen, Jerome; Kottke, Raimund; Springer, Elisabeth; Weisstanner, Christian; El-Koussy, Marwan; Schroth, Gerhard; Wiest, Roland; Gralla, Jan; Verma, Rajeev K. [University of Bern, University Institute for Diagnostic and Interventional Neuroradiology, University Hospital Bern and Inselspital, Bern (Switzerland); Abela, Eugenio; Schindler, Kaspar [University of Bern, Department of Neurology, Inselspital, Bern (Switzerland); Buerki, Sarah E. [Inselspital, Department of Neuropaediatrics, University Children' s Hospital, Bern (Switzerland)

    2014-11-15

    To investigate pathological findings in the susceptibility weighted imaging (SWI) of patients experiencing convulsive (CSE) or non-convulsive status epilepticus (NCSE) with focal hyperperfusion in the acute setting. Twelve patients (six with NCSE confirmed by electroencephalogram (EEG) and six patients with CSE with seizure event clinically diagnosed) underwent MRI in this acute setting (mean time between onset of symptoms and MRI was 3 h 8 min), including SWI, dynamic susceptibility contrast MR imaging (DSC) and diffusion-weighted imaging (DWI). MRI sequences were retrospectively evaluated and compared with EEG findings (10/12 patients), and clinical symptoms. Twelve out of 12 (100 %) patients showed a focal parenchymal area with pseudo-narrowed cortical veins on SWI, associated with focal hyperperfused areas (increased cerebral blood flow (CBF) and mean transit time (MTT) shortening), and cortical DWI restriction in 6/12 patients (50 %). Additionally, these areas were associated with ictal or postical EEG patterns in 8/10 patients (80 %). Most frequent acute clinical findings were aphasia and/or hemiparesis in eight patients, and all of them showed pseudo-narrowed veins in those parenchymal areas responsible for these symptoms. In this study series with CSE and NCSE patients, SWI showed focally pseudo-narrowed cortical veins in hyperperfused and ictal parenchymal areas. Therefore, SWI might have the potential to identify an ictal region in CSE/NCSE. (orig.)

  7. Focal hemodynamic patterns of status epilepticus detected by susceptibility weighted imaging (SWI)

    To investigate pathological findings in the susceptibility weighted imaging (SWI) of patients experiencing convulsive (CSE) or non-convulsive status epilepticus (NCSE) with focal hyperperfusion in the acute setting. Twelve patients (six with NCSE confirmed by electroencephalogram (EEG) and six patients with CSE with seizure event clinically diagnosed) underwent MRI in this acute setting (mean time between onset of symptoms and MRI was 3 h 8 min), including SWI, dynamic susceptibility contrast MR imaging (DSC) and diffusion-weighted imaging (DWI). MRI sequences were retrospectively evaluated and compared with EEG findings (10/12 patients), and clinical symptoms. Twelve out of 12 (100 %) patients showed a focal parenchymal area with pseudo-narrowed cortical veins on SWI, associated with focal hyperperfused areas (increased cerebral blood flow (CBF) and mean transit time (MTT) shortening), and cortical DWI restriction in 6/12 patients (50 %). Additionally, these areas were associated with ictal or postical EEG patterns in 8/10 patients (80 %). Most frequent acute clinical findings were aphasia and/or hemiparesis in eight patients, and all of them showed pseudo-narrowed veins in those parenchymal areas responsible for these symptoms. In this study series with CSE and NCSE patients, SWI showed focally pseudo-narrowed cortical veins in hyperperfused and ictal parenchymal areas. Therefore, SWI might have the potential to identify an ictal region in CSE/NCSE. (orig.)

  8. Venous stroke and status epilepticus due to milk-induced anemia in a child.

    Finkel, Leslie; Piantino, Juan; Goldstein, Joshua; Wainwright, Mark S

    2015-02-01

    The risk factors for cerebral sinus venous thrombosis include dehydration, infection, and anemia. The clinical presentation in children of venous strokes associated with cerebral venous thrombosis is variable and may include seizures. Acute management should focus on the treatment of the primary cause and anticoagulation or antiplatelet therapy if needed. Early recognition and targeted treatment is important because survivors are at increased risk for long-term neurologic complications. We report a case of a 4-year-old girl who presented with status epilepticus and was subsequently found to have a cerebral venous sinus thrombosis in the transverse and sigmoid sinus, with venous infarction in the temporal lobe. Laboratory results were significant for a microcytic anemia caused by excessive milk intake. Although iron deficiency anemia is a common pediatric disorder, this uncommon presentation demonstrates the potential for neurologic complications secondary to anemia, as well as the need for a high index of suspicion in order to identify venous stroke as a cause in children who present to the emergency department with seizures. PMID:25513978

  9. Evidence for Status Epilepticus and Pro-Inflammatory Changes after Intranasal Kainic Acid Administration in Mice.

    Mounira Sabilallah

    Full Text Available Kainic acid (KA is routinely used to elicit status epilepticus (SE and epileptogenesis. Among the available KA administration protocols, intranasal instillation (IN remains understudied. Dosages of KA were instilled IN in mice. Racine Scale and Video-EEG were used to assess and quantify SE onset. Time spent in SE and spike activity was quantified for each animal and confirmed by power spectrum analysis. Immunohistochemistry and qPCR were performed to define brain inflammation occurring after SE, including activated microglial phenotypes. Long term video-EEG recording was also performed. Titration of IN KA showed that a dose of 30 mg/kg was associated with low mortality while eliciting SE. IN KA provoked at least one behavioral and electrographic SE in the majority of the mice (>90%. Behavioral and EEG SE were accompanied by a rapid and persistent microglial-astrocytic cell activation and hippocampal neurodegeneration. Specifically, microglial modifications involved both pro- (M1 and anti-inflammatory (M2 genes. Our initial long-term video-EEG exploration conducted using a small cohort of mice indicated the appearance of spike activity or SE. Our study demonstrated that induction of SE is attainable using IN KA in mice. Typical pro-inflammatory brain changes were observed in this model after SE, supporting disease pathophysiology. Our results are in favor of the further development of IN KA as a means to study seizure disorders. A possibility for tailoring this model to drug testing or to study mechanisms of disease is offered.

  10. Mechanisms of levetiracetam in the control of status epilepticus and epilepsy

    Laxmikant S Deshpande

    2014-01-01

    Full Text Available Status epilepticus (SE is a major clinical emergency that is associated with high mortality and morbidity. SE causes significant neuronal injury and survivors are at a greater risk of developing acquired epilepsy and other neurological morbidities, including depression and cognitive deficits. Benzodiazepines and some anticonvulsant agents are drugs of choice for initial SE management. Despite their effectiveness, over 40% of SE cases are refractory to the initial treatment with two or more medications. Thus there is an unmet need of developing newer anti-SE drugs. Levetiracetam (LEV is a widely prescribed anti-epileptic drug that has been reported to be used in SE cases, especially in benzodiazepine-resistant SE or where phenytoin cannot be used due to allergic side-effects. Levetiracetam’s non-classical antiepileptic mechanisms of action, favorable pharmacokinetic profile, general lack of central depressant effects and lower incidence of drug interactions contributes to its use in SE management. This review will focus on LEV’s unique mechanism of action that makes it a viable candidate for SE treatment.

  11. Acute inhibition of neurosteroid estrogen synthesis suppresses status epilepticus in an animal model

    Sato, Satoru M; Woolley, Catherine S

    2016-01-01

    Status epilepticus (SE) is a common neurological emergency for which new treatments are needed. In vitro studies suggest a novel approach to controlling seizures in SE: acute inhibition of estrogen synthesis in the brain. Here, we show in rats that systemic administration of an aromatase (estrogen synthase) inhibitor after seizure onset strongly suppresses both electrographic and behavioral seizures induced by kainic acid (KA). We found that KA-induced SE stimulates synthesis of estradiol (E2) in the hippocampus, a brain region commonly involved in seizures and where E2 is known to acutely promote neural activity. Hippocampal E2 levels were higher in rats experiencing more severe seizures. Consistent with a seizure-promoting effect of hippocampal estrogen synthesis, intra-hippocampal aromatase inhibition also suppressed seizures. These results reveal neurosteroid estrogen synthesis as a previously unknown factor in the escalation of seizures and suggest that acute administration of aromatase inhibitors may be an effective treatment for SE. DOI: http://dx.doi.org/10.7554/eLife.12917.001 PMID:27083045

  12. Peri-ictal signal changes in seven patients with status epilepticus: interesting MRI observations

    Goyal, Manoj K.; Sinha, Sanjib [National Institute of Mental Health and Neurosciences (NIMHANS), Department of Neurology, Bangalore, Karnataka (India); Ravishankar, Shivshankar; Shivshankar, Jai Jai [National Institute of Mental Health and Neurosciences (NIMHANS), Department of Neuroimaging and Interventional Radiology, Bangalore (India)

    2009-03-15

    Transient peri-ictal changes on imaging had been described following status epilepticus (SE), but its cause is not very well understood. We analyzed the magnetic resonance imaging (MRI) findings in SE patients in order to elucidate such changes including peri-ictal signal. This prospective study involved 34 patients (M/F 23:11, mean age 25.8 {+-} 17.2 years) who experienced SE. MRI was performed during or within 96 h of cessation of seizures. Twenty-five patients had generalized convulsive status epilectus (GCSE; ten secondary GCSE and 15 primary GCSE). Seven patients had epilepsia partialis continua and two patients non-convulsive SE. Eight patients had a history of seizures and three patients previous SE. The mean duration of SE prior to MRI was 89.2 {+-} 105.3 h (range 2-360 h). MRI provided diagnosis in 17 patients, and in 13 patients, no structural cause was identified. Peri-ictal focal signal changes with restricted diffusion on apparent diffusion coefficient maps were present in seven (20.6%) patients with SE (generalized convulsive, three; partial, three; non-convulsive, one). The changes were observed when MRI was performed during SE in 3/10 (30%) patients, or within 24 h in 1/7 (14.3%), 48 h in 1/5 (20%), 72 h in 1/6 (16.7%), or 96 h in 1/6 (16.7%) patients after cessation of seizures. Repeat MRI revealed disappearance of signal changes in two patients. Peri-ictal MR changes with restricted diffusion appear to be an effect rather than the cause of SE. (orig.)

  13. Peri-ictal signal changes in seven patients with status epilepticus: interesting MRI observations

    Transient peri-ictal changes on imaging had been described following status epilepticus (SE), but its cause is not very well understood. We analyzed the magnetic resonance imaging (MRI) findings in SE patients in order to elucidate such changes including peri-ictal signal. This prospective study involved 34 patients (M/F 23:11, mean age 25.8 ± 17.2 years) who experienced SE. MRI was performed during or within 96 h of cessation of seizures. Twenty-five patients had generalized convulsive status epilectus (GCSE; ten secondary GCSE and 15 primary GCSE). Seven patients had epilepsia partialis continua and two patients non-convulsive SE. Eight patients had a history of seizures and three patients previous SE. The mean duration of SE prior to MRI was 89.2 ± 105.3 h (range 2-360 h). MRI provided diagnosis in 17 patients, and in 13 patients, no structural cause was identified. Peri-ictal focal signal changes with restricted diffusion on apparent diffusion coefficient maps were present in seven (20.6%) patients with SE (generalized convulsive, three; partial, three; non-convulsive, one). The changes were observed when MRI was performed during SE in 3/10 (30%) patients, or within 24 h in 1/7 (14.3%), 48 h in 1/5 (20%), 72 h in 1/6 (16.7%), or 96 h in 1/6 (16.7%) patients after cessation of seizures. Repeat MRI revealed disappearance of signal changes in two patients. Peri-ictal MR changes with restricted diffusion appear to be an effect rather than the cause of SE. (orig.)

  14. Protective effects of endoplasmic reticulum stress preconditioning on hippocampal neurons in rats with status epilepticus

    Yi ZHANG

    2014-12-01

    Full Text Available Objective To evaluate the protective effects of endoplasmic reticulum stress preconditioning induced by 2-deoxyglucose (2-DG on hippocampal neurons of rats with status epilepticus (SE and the possible mechanism.  Methods Ninety Sprague-Dawley (SD rats were randomly enrolled into preconditioning group (N = 30, SE group (N = 30 and control group (N = 30. Each group was divided into 6 subsets (N = 5 according to six time points (before seizure, 6 h, 12 h, 1 d, 2 d and 7 d after seizure. The preconditioning group was administered 2-DG intraperitoneally with a dose of 150 mg/kg for 7 days, and the lithium-pilocarpine induced SE rat model was established on both preconditioning group and SE group. The rats were sacrificed at the above six time points, and the brains were removed to make paraffin sections. Nissl staining was performed by toluidine blue to evaluate the hippocampal neuronal damage after seizure, and the number of survival neurons in hippocampal CA1 and CA3 regions of the rats were counted. Immunohistochemical staining was performed to detect the expressions of glucose regulated protein 78 (GRP78 and X-box binding protein 1 (XBP-1 in hippocampal CA3 region of the rats.  Results The number of survival neurons in preconditioning group was much more than that in SE group at 7 d after seizure (t = 5.353, P = 0.000, and was more obvious in CA1 region. There was no significant hippocampal neuronal damage in control group. The expressions of GRP78 and XBP-1 in CA3 region of hippocampus in SE group at 6 h after seizure were significantly higher than that in control group (P = 0.000, and then kept increasing until reaching the peak at 2 d (P = 0.000, for all. The expressions of GRP78 and XBP-1 in hippocampal CA3 region in preconditioning group were significantly higher than that in control group before seizure (P = 0.000, for all. The level of GRP78 maintained the highest at 24 h and 2 d after seizure (P = 0.000, for all, while the XBP-1 level

  15. Combinations of ketamine and atropine are neuroprotective and reduce neuroinflammation after a toxic status epilepticus in mice

    Epileptic seizures and status epilepticus (SE) induced by the poisoning with organophosphorus nerve agents (OP), like soman, are accompanied by neuroinflammation whose role in seizure-related brain damage (SRBD) is not clear. Antagonists of the NMDA glutamate ionotropic receptors are currently among the few compounds able to arrest seizures and provide neuroprotection even during refractory status epilepticus (RSE). Racemic ketamine (KET), in combination with atropine sulfate (AS), was previously shown to counteract seizures and SRBD in soman-poisoned guinea-pigs. In a mouse model of severe soman-induced SE, we assessed the potentials of KET/AS combinations as a treatment for SE/RSE-induced SRBD and neuroinflammation. When starting 30 min after soman challenge, a protocol involving six injections of a sub-anesthetic dose of KET (25 mg/kg) was evaluated on body weight loss, brain damage, and neuroinflammation whereas during RSE, anesthetic protocols were considered (KET 100 mg/kg). After confirming that during RSE, KET injection was to be repeated despite some iatrogenic deaths, we used these proof-of-concept protocols to study the changes in mRNA and related protein contents of some inflammatory cytokines, chemokines and adhesion molecules in cortex and hippocampus 48 h post-challenge. In both cases, the KET/AS combinations showed important neuroprotective effects, suppressed neutrophil granulocyte infiltration and partially suppressed glial activation. KET/AS could also reduce the increase in mRNA and related pro-inflammatory proteins provoked by the poisoning. In conclusion, the present study confirms that KET/AS treatment has a strong potential for SE/RSE management following OP poisoning. The mechanisms involved in the reduction of central neuroinflammation remain to be studied. -- Highlights: ► During soman-induced status epilepticus, ketamine-atropine limit brain damage. ► Molecular neuroinflammatory response is strongly decreased. ► Glial activation is

  16. Combinations of ketamine and atropine are neuroprotective and reduce neuroinflammation after a toxic status epilepticus in mice

    Dhote, Franck, E-mail: franck.dhote@irba.fr [Département de Toxicologie et risques chimiques, Institut de Recherche Biomédicale des armées – Centre de recherches du Service de santé des armées IRBA-CRSSA, 24 avenue des Maquis du Grésivaudan, B.P. 87, 38702 La Tronche cedex (France); Carpentier, Pierre; Barbier, Laure [Département de Toxicologie et risques chimiques, Institut de Recherche Biomédicale des armées – Centre de recherches du Service de santé des armées IRBA-CRSSA, 24 avenue des Maquis du Grésivaudan, B.P. 87, 38702 La Tronche cedex (France); Peinnequin, André [Département Effets biologiques des rayonnements, Institut de Recherche Biomédicale des armées – Centre de recherches du Service de santé des armées IRBA-CRSSA, 24 avenue des Maquis du Grésivaudan, B.P. 87, 38702 La Tronche cedex (France); Baille, Valérie; Pernot, Fabien; Testylier, Guy; Beaup, Claire; Foquin, Annie [Département de Toxicologie et risques chimiques, Institut de Recherche Biomédicale des armées – Centre de recherches du Service de santé des armées IRBA-CRSSA, 24 avenue des Maquis du Grésivaudan, B.P. 87, 38702 La Tronche cedex (France); and others

    2012-03-01

    Epileptic seizures and status epilepticus (SE) induced by the poisoning with organophosphorus nerve agents (OP), like soman, are accompanied by neuroinflammation whose role in seizure-related brain damage (SRBD) is not clear. Antagonists of the NMDA glutamate ionotropic receptors are currently among the few compounds able to arrest seizures and provide neuroprotection even during refractory status epilepticus (RSE). Racemic ketamine (KET), in combination with atropine sulfate (AS), was previously shown to counteract seizures and SRBD in soman-poisoned guinea-pigs. In a mouse model of severe soman-induced SE, we assessed the potentials of KET/AS combinations as a treatment for SE/RSE-induced SRBD and neuroinflammation. When starting 30 min after soman challenge, a protocol involving six injections of a sub-anesthetic dose of KET (25 mg/kg) was evaluated on body weight loss, brain damage, and neuroinflammation whereas during RSE, anesthetic protocols were considered (KET 100 mg/kg). After confirming that during RSE, KET injection was to be repeated despite some iatrogenic deaths, we used these proof-of-concept protocols to study the changes in mRNA and related protein contents of some inflammatory cytokines, chemokines and adhesion molecules in cortex and hippocampus 48 h post-challenge. In both cases, the KET/AS combinations showed important neuroprotective effects, suppressed neutrophil granulocyte infiltration and partially suppressed glial activation. KET/AS could also reduce the increase in mRNA and related pro-inflammatory proteins provoked by the poisoning. In conclusion, the present study confirms that KET/AS treatment has a strong potential for SE/RSE management following OP poisoning. The mechanisms involved in the reduction of central neuroinflammation remain to be studied. -- Highlights: ► During soman-induced status epilepticus, ketamine-atropine limit brain damage. ► Molecular neuroinflammatory response is strongly decreased. ► Glial activation is

  17. Status epilepticus triggers early mitochondrial fusion in the rat hippocampus in a lithium-pilocarpine model.

    Córdova-Dávalos, Laura; Carrera-Calvo, Dulce; Solís-Navarrete, Jael; Mercado-Gómez, Octavio Fabián; Arriaga-Ávila, Virginia; Agredano-Moreno, Lourdes Teresa; Jiménez-García, Luis Felipe; Guevara-Guzmán, Rosalinda

    2016-07-01

    Many reports investigating the hippocampus have demonstrated an increase in neuronal damage, cellular loss, oxidative stress and mitochondrial DNA damage during status epilepticus (SE); however, information regarding alterations in mitochondrial fission and fusion events in SE is lacking. The aim of the present study was to examine the possible imbalance between mitochondrial fission and fusion in the hippocampus of male rats after acute seizure mediated by SE. In this study, we used ninety animals were randomly divided into control and SE groups and subjected to the lithium-pilocarpine model of epilepsy. Hippocampi were obtained at 3, 24 and 72h after SE, and the cytoplasmic and mitochondrial fractions of the cells were used to analyze changes in the Drp1 and Fis1 fission proteins and the Mfn1 and Opa1 fusion proteins by western blot analysis. Moreover, changes in the expression of fission and fusion mRNA transcripts were evaluated by real-time PCR. Mitochondrial morphology was also analyzed using standard transmission electron microscopy. Our data showed that the fission-related mRNA Drp1 was down-regulated rapidly after SE, while Fis1 did not show any significant changes in expression. Moreover, the mitochondrial fusion-associated proteins Mfn1 and Opa1 exhibited an increase in expression at 72h after SE. Electron microphotography revealed several morphological changes, such as swollen mitochondria and damage of the inner mitochondrial membrane, at 24h; at 72h elongation of some mitochondrial was also observed. Our results suggest that after the initiation of SE, the main regulator of the fission mRNA Drp1 is down-regulated, which in turn regulates mitochondrial fission and leads to an increase in the Mfn1 and Opa1 proteins to induce mitochondrial fusion, suggesting an imbalance of the fission and fusion processes. PMID:27045873

  18. Hyperthermia aggravates status epilepticus-induced epileptogenesis and neuronal loss in immature rats.

    Suchomelova, L; Lopez-Meraz, M L; Niquet, J; Kubova, H; Wasterlain, C G

    2015-10-01

    This study tightly controlled seizure duration and severity during status epilepticus (SE) in postnatal day 10 (P10) rats, in order to isolate hyperthermia as the main variable and to study its consequences. Body temperature was maintained at 39 ± 1 °C in hyperthermic SE rats (HT+SE) or at 35 ± 1 °C in normothermic SE animals (NT+SE) during 30 min of SE, which was induced by lithium-pilocarpine (3 mEq/kg, 60 mg/kg) and terminated by diazepam and cooling to NT. All video/EEG measures of SE severity were similar between HT+SE and NT+SE pups. At 24h, neuronal injury was present in the amygdala in the HT+SE group only, and was far more severe in the hippocampus in HT+SE than NT+SE pups. Separate groups of animals were monitored four months later for spontaneous recurrent seizures (SRS). Only HT+SE animals developed convulsive SRS. Both HT+SE and NT+SE animals developed electrographic SRS (83% vs. 55%), but SRS frequency and severity were higher in hyperthermic animals (12.5 ± 3.5 vs. 4.2 ± 2.0 SRS/day). The density of hilar neurons was lower, thickness of the amygdala and perirhinal cortex was reduced, and lateral ventricles were enlarged in HT+SE over NT+SE littermates and HT/NT controls. In this model, hyperthermia greatly increased the epileptogenicity of SE and its neuropathological sequelae. PMID:26259902

  19. Beneficial influence of physical exercise following status epilepticus in the immature brain of rats.

    Gomes, F G Novaes; Gomes Da Silva, S; Cavalheiro, E A; Arida, R M

    2014-08-22

    Studies in adult animals have demonstrated a beneficial effect of physical exercise on epileptic insults. Although the effects of physical exercise on the mature nervous system are well documented, its influence on the developing nervous system subjected to injuries in childhood has been little explored. The purpose of our study was to investigate whether a physical exercise program applied during brain development could influence the hippocampal plasticity of rats submitted to status epilepticus (SE) induced by pilocarpine model at two different ages of the postnatal period. Male Wistar rats aged 18 (P18) and 28 (P28) days were randomly divided into four groups: Control (CTRL), Exercise (EX), SE (SE) and SE Exercise (SE/EX) (n=17 per group). After the aerobic exercise program, histological and behavioral (water maze) analyses were performed. Our results showed that only animals subjected to pilocarpine-induced SE at P28 presented spontaneous seizures during the observational period. A significant reduction in seizure frequency was observed in the SE/EX group compared to the SE group. In adulthood, animals submitted to early-life SE displayed impairment in long-term memory in the water maze task, while the exercise program reversed this deficit. Reduced mossy fiber sprouting in the dentate gyrus was noted in animals that presented spontaneous seizures (SE/EX vs SE). Exercise increased cell proliferation (Ki-67 staining) and anti-apoptotic response (bcl-2 staining) and reduced pro-apoptotic response (Bax staining) in animals of both ages of SE induction (P18/28). Exercise also modified the brain-derived neurotrophic factor (BDNF) levels in EX and SE/EX animals. Our findings indicate that in animals subjected to SE in the postnatal period a physical exercise program brings about beneficial effects on seizure frequency and hippocampal plasticity in later stages of life. PMID:24857853

  20. Anti-NMDA-R encephalitis: Should we consider extreme delta brush as electrical status epilepticus?

    Chanson, Eve; Bicilli, Élodie; Lauxerois, Michel; Kauffmann, Sophie; Chabanne, Russell; Ducray, François; Honnorat, Jérome; Clavelou, Pierre; Rosenberg, Sarah

    2016-02-01

    Seizures are common clinical manifestations in anti-N-methyl-d-aspartate receptor (anti-NMDA-R) encephalitis, among other neurological and psychiatric symptoms. During the course of the disease, some specific EEG patterns have been described: generalized rhythmic delta activity (GRDA) and extreme delta brush (EDB). In comatose patients, the association of these EEG abnormalities with subtle motor manifestations can suggest ongoing non-convulsive status epilepticus (NCSE). We report the case of a 28-year-old woman admitted for a clinical presentation typical of anti-NMDA-R encephalitis, which was confirmed by CSF analysis. She was rapidly intubated because of severe dysautonomia and disturbed consciousness. Clinical examination revealed subtle paroxysmal and intermittent myoclonic and tonic movements, correlated on video-EEG with GRDA and/or EDB. NCSE was then suspected, but electroclinical manifestations persisted despite many anti-epileptic drugs combinations, or reappeared when barbiturate anesthesia was decreased. In order to confirm or dismiss the diagnosis, intracranial pressure (ICP) and surface video-EEG monitoring were performed simultaneously and revealed no ICP increase, thus being strongly against a diagnosis of seizures. Sedation was progressively weaned, and clinical condition as well as EEG appearance progressively improved. Literature review revealed 11 similar cases, including 2 with focal NCSE. Of the nine other cases, NCSE diagnosis was finally excluded in 5 cases. NCSE diagnosis in association with anti-NMDA-R encephalitis is sometimes very difficult and its occurrence might be overestimated. Video-EEG is highly recommended and more invasive techniques may sometimes be necessary. PMID:26922283

  1. The effect of STAT3 Inhibition on status epilepticus and subsequent spontaneous seizures in the Pilocarpine Model of Acquired Epilepsy

    Grabenstatter, H. L.; Angel, Y. Cruz Del; Carlsen, J.; Wempe, M. F.; White, A. M.; Cogswell, M.; Russek, S. J.; BROOKS-KAYAL, A. R.

    2013-01-01

    Pilocarpine-induced status epilepticus (SE), which results in temporal lobe epilepsy (TLE) in rodents, activates the JAK/STAT pathway. In the current study, we evaluate whether brief exposure to a selective inhibitor of the JAK/STAT pathway (WP1066) early after the onset of SE effects the severity of SE or reduces later spontaneous seizure frequency via inhibition of STAT3-regulated gene transcription. Rats that received systemic WP1066 or vehicle at the onset of SE were continuously video-EE...

  2. Photodynamic therapy using 5-aminolevulinic acid-induced photosensitization: current clinical status

    Marcus, Stuart L.; Golub, Allyn L.; Shulman, D. Geoffrey

    1995-03-01

    Photodynamic therapy using 5-aminolevulinic acid-induced photosensitization (ALA PDT) via endogenous protoporphyrin IX (PpIX) synthesis has been reported as efficacious, using topical formulations, in the treatment of a variety of dermatologic diseases including superficial basal cell carcinoma, Bowen's disease, and actinic (solar) keratoses. Application of ALA PDT to the detection and treatment of both malignant and non-malignant diseases of internal organs has recently been reported. Local internal application of ALA has been used for the detection, via PpIX fluorescence, of pathological conditions of the human urinary bladder and for selective endometrial ablation in animal model systems. Systemic, oral administration of ALA has been used for ALA PDT of superficial head and neck cancer and of colorectal cancer. This paper reviews the current clinical status of ALA PDT.

  3. Continuous infusion of midazolam in the treatment of refractory generalized convulsive status epilepticus.

    Ulvi, H; Yoldas, T; Müngen, B; Yigiter, R

    2002-10-01

    We studied the efficacy and safety of midazolam given as a continuous infusion in the treatment of refractory generalized convulsive status epilepticus (RGCSE). We carried out a prospective, open study, in 19 patients (11 men) with RGCSE in the intensive care unit at Firat Medical Center in Elazig. When intravenous administration of 0.3 mg/kg diazepam (three times at 5-min intervals), 20 mg/kg phenytoin, and 20 mg/kg phenobarbital failed to bring the episode under control, patients were administered an intravenous bolus of midazolam (200 microg/kg) followed by a continuous infusion at 1 microg/kg min. The dose was increased by 1 microg/kg min every 15 min until the episode of seizure was brought under control. The time from beginning of treatment to control of seizures, infusion rate, and side-effects were monitored. The mean age of the patients was 40.4 years (range 16-87 years). The clinical etiology of RGCSE was idiopathic epilepsy (6 cases), anoxicischemic cerebral insult due to cardiac arrest (3), viral encephalitis (2), intrahemispheric hematoma due to hemorrhagic stroke (1), cerebral infarct due to ischemic stroke (1), pituitary adenoma (1), post-traumatic epilepsy (1), renal failure (1), tuberculous meningitis (1), and unknown (2). In eighteen (94.7%) patients, seizures were completely controlled in a mean time of 45 min (range, 5-120 min) at a mean infusion rate of 8 microg/kg min (range, 3-21 microg/kg min). In one patient seizures did not stop. Midazolam administration did not cause any significant change in blood pressure, heart rate, oxygen saturation, or respiratory status. The mean time to full consciousness for patients after stopping the infusion was 1.6 hours (range, 2.0-8.5 hours). The mean infusion duration of midazolam was 14.5 hours (range, 12-25 hours). Midazolam is an effective and safe drug to control RGCSE, and may represent a substantial improvement over current therapeutic approaches such as pentobarbital anesthesia. PMID:12536286

  4. Region-specific vulnerability to endoplasmic reticulum stress-induced neuronal death in rat brain after status epilepticus

    Jing Chen; Hu Guo; Guo Zheng; Zhong-Nan Shi

    2013-12-01

    We sought to clarify the involvement and the intra-cerebral distribution variability of C/EBP homologous protein (CHOP), a representative molecule related to endoplasmic reticulum (ER) stress-induced cell death signalling pathways, in neuronal death resulting from status epilepticus in rats. The expression patterns of CHOP and glucose-regulated protein (GRP) 78, a good marker of ER stress, were assessed by Western blotting, real-time PCR, Hoechst and immunohistochemistry in the hippocampus, cortex and striatum on a status epilepticus (SE) model. Double-fluorescent staining of CHOP and the terminal deoxynucleotidyl transferase-mediated DNA nick-end labelling (TUNEL) method were performed to clarify the involvement of CHOP in cell death. SE resulted in a time-dependent increase in the expression of GRP78 and CHOP. The expression of GRP78 protein was increased at 3, 6 and 12 h after SE and no brain region variability was found. The expression of CHOP protein was also increased, reached its peak at 24 h and remained high at 48 h. CHOP protein expression, however, showed brain region variability with highest expression noted in the hippocampus followed by the striatum, and lowest in the cortex. The up-regulation of CHOP occurring at the transcriptional level was demonstrated by real-time PCR. Double fluorescence showed that CHOP expression strongly correlated with neurons undergoing apoptosis. The results indicated that SE compromises the function of the ER and that the hippocampus is more vulnerable than the cortex and the striatum.

  5. A rare case of neonatal sepsis/meningitis caused by Pasteurella multocida complicated with status epilepticus and focal cerebritis.

    Spadafora, R; Pomero, G; Delogu, A; Gozzoli, L; Gancia, P

    2011-01-01

    Pasteurella multocida is normally present in respiratory and digestive tract of many domestic and wild animals, but is a rare pathogen in neonatal infection. Here we describe for the first time a case of meningitis complicated by status epilepticus and right parietal lobe cerebritis. The patient showed a dramatic clinical onset characterized by septic appearance and prolonged seizures. Multidrug anticonvulsivant therapy was used to control the status epilepticus, but despite the aggressive treatment electrical crises were still evident 24 hours after the admission. Furthermore, a brain MRI, performed to investigate a persistent intermittent fever even if CSF became sterile, showed a focus cerebritis in the right parietal lobe, early stage of the cerebral abscess. Prolonged antibiotic therapy with steroids was requested to solve the cerebritis area. Interestingly, direct contact between the patient and domestic animals was denied by the family, but the father reported a contact with a rooster, killed and cooked few days before, suggesting, as previously described, that Pasteurella may also be transmitted through asymptomatic human carrier. The patient had a favourable outcome with no medium-term sequelae one month after discharge, but the severity of the clinical course and the unpredictable way of transmission highlight the importance of hygiene measures approaching infants. PMID:22423481

  6. Brain-derived neurotrophic factor ameliorates brain stem cardiovascular dysregulation during experimental temporal lobe status epilepticus.

    Ching-Yi Tsai

    Full Text Available BACKGROUND: Status epilepticus (SE is an acute, prolonged epileptic crisis with a mortality rate of 20-30%; the underlying mechanism is not completely understood. We assessed the hypothesis that brain stem cardiovascular dysregulation occurs during SE because of oxidative stress in rostral ventrolateral medulla (RVLM, a key nucleus of the baroreflex loop; to be ameliorated by brain-derived neurotrophic factor (BDNF via an antioxidant action. METHODOLOGY/PRINCIPAL FINDINGS: In a clinically relevant experimental model of temporal lobe SE (TLSE using Sprague-Dawley rats, sustained hippocampal seizure activity was accompanied by progressive hypotension that was preceded by a reduction in baroreflex-mediated sympathetic vasomotor tone; heart rate and baroreflex-mediated cardiac responses remained unaltered. Biochemical experiments further showed concurrent augmentation of superoxide anion, phosphorylated p47(phox subunit of NADPH oxidase and mRNA or protein levels of BDNF, tropomyosin receptor kinase B (TrkB, angiotensin AT1 receptor subtype (AT1R, nitric oxide synthase II (NOS II or peroxynitrite in RVLM. Whereas pretreatment by microinjection bilaterally into RVLM of a superoxide dismutase mimetic (tempol, a specific antagonist of NADPH oxidase (apocynin or an AT1R antagonist (losartan blunted significantly the augmented superoxide anion or phosphorylated p47(phox subunit in RVLM, hypotension and the reduced baroreflex-mediated sympathetic vasomotor tone during experimental TLSE, pretreatment with a recombinant human TrkB-Fc fusion protein or an antisense bdnf oligonucleotide significantly potentiated all those events, alongside peroxynitrite. However, none of the pretreatments affected the insignificant changes in heart rate and baroreflex-mediated cardiac responses. CONCLUSIONS/SIGNIFICANCE: We conclude that formation of peroxynitrite by a reaction between superoxide anion generated by NADPH oxidase in RVLM on activation by AT1R and NOS II

  7. Gabapentin Administration Reduces Reactive Gliosis and Neurodegeneration after Pilocarpine-Induced Status Epilepticus

    Rossi, Alicia Raquel; Angelo, Maria Florencia; Villarreal, Alejandro; Lukin, Jerónimo; Ramos, Alberto Javier

    2013-01-01

    The lithium-pilocarpine model of epilepsy reproduces in rodents several features of human temporal lobe epilepsy, by inducing an acute status epilepticus (SE) followed by a latency period. It has been proposed that the neuronal network reorganization that occurs during latency determines the subsequent appearance of spontaneous recurrent seizures. The aim of this study was to evaluate neuronal and glial responses during the latency period that follows SE. Given the potential role of astrocytes in the post-SE network reorganization, through the secretion of synaptogenic molecules such as thrombospondins, we also studied the effect of treatment with the α2δ1 thrombospondin receptor antagonist gabapentin. Adult male Wistar rats received 3 mEq/kg LiCl, and 20 h later 30 mg/kg pilocarpine. Once SE was achieved, seizures were stopped with 20 mg/kg diazepam. Animals then received 400 mg/kg/day gabapentin or saline for either 4 or 14 days. In vitro experiments were performed in dissociated mixed hippocampal cell culture exposed to glutamate, and subsequently treated with gabapentin or vehicle. During the latency period, the hippocampus and pyriform cortex of SE-animals presented a profuse reactive astrogliosis, with increased GFAP and nestin expression. Gliosis intensity was dependent on the Racine stage attained by the animals and peaked 15 days after SE. Microglia was also reactive after SE, and followed the same pattern. Neuronal degeneration was present in SE-animals, and also depended on the Racine stage and the SE duration. Polysialic-acid NCAM (PSA-NCAM) expression was increased in hippocampal CA-1 and dentate gyrus of SE-animals. Gabapentin treatment was able to reduce reactive gliosis, decrease neuronal loss and normalize PSA-NCAM staining in hippocampal CA-1. In vitro, gabapentin treatment partially prevented the dendritic loss and reactive gliosis caused by glutamate excitotoxicity. Our results show that gabapentin treatment during the latency period after SE

  8. LiCl/Pilocarpine - induced status epilepticus and ischemic hippocampal lesion induced by endothelin-1:two models of epileptogenesis in immature rats

    Kubová, Hana

    Sitges: -, 2008. s. 89-89. [Eilat conference on new antiepileptic drugs /9./. 15.06.2008-19.06.2008, Sitges] Institutional research plan: CEZ:AV0Z50110509 Keywords : spo2 * status epilepticus * ischemic lesion * immature rats Subject RIV: FH - Neurology

  9. Efficacy and safety of non-intravenous midazolam for the treatment of status epilepticus in children: a Meta-analysis

    Yan LIN

    2016-02-01

    Full Text Available Objective To evaluate the clinical efficacy and safety of non-intravenous midazolam for treating status epilepticus (SE in children.  Methods Taking midazolam, status epilepticus and children both in Chinese and English as search terms, retrieve in databases such as PubMed, ScienceDirect, China National Knowledge Infrastructure (CNKI, VIP and Wanfang Data, assisted by manual searching and Google Scholar, in order to collect randomized controlled trials (RCTs about non-intravenous midazolam for treating SE in children from January 2000 to January 2015. Jadad Scale was used to evaluate the quality of literatures. Meta-analysis was performed by using RevMan 5.3 software. Results There were a total of 258 records after preliminary searching, and 6 RCTs involving 766 episodes were finally included after excluding duplicate ones and those which did not meet the inclusion criteria. The results were as follows: 1 midazolam via intranasal administration was as effective as intravenous diazepam in achieving seizure control in children (RD = -0.070, 95%CI: -0.200—0.060, P = 0.290. However, non-intravenous (intranasal or buccal midazolam showed better effects on seizure control than rectal diazepam (RD = 0.170, 95% CI: 0.030—0.320; P = 0.020. 2 The mean time from arrival at hospital to cessation was not significantly different between intranasal midazolam and intravenous diazepam (SMD = -1.570, 95%CI: -3.280—0.140; P = 0.070. 3 There was no statistical difference between intranasal midazolam and intravenous diazepam for the time from giving drug to cessation (SMD = 0.240, 95%CI: -0.110—0.590; P = 0.170. 4 There was no statistical difference on the occurrence rate of adverse drug reactions between non-intravenous midazolam and intravenous or non-intravenous diazepam (RD = -0.010, 95% CI: -0.030—0.200; P = 0.500.  Conclusions Non-intravenous midazolam is safe and effective in the treatment for status epilepticus in children. However, the

  10. COMPARATIVE EFFECTS OF DIAZEPAM INFUSION AND DIVIDED DOSES OF DIAZEPAM ON THE TREATMENT OF ABSENCE STATUS EPILEPTICUS

    L. Afshar khas

    2009-06-01

    Full Text Available ObjectiveAbsence status epilepticus (ASE is a common form of nonconvulsive status epilepcticus. It is characterized by loss of consciousness with spike and wave discharges in EEG simultaneously. The most effective treatment of ASE is diazepam, either infusion or in divided doses; the former is more expensive since patients must be admitted in an Intensive Care Unit. The aim of this study was to evaluate and compare the efficacy of diazepam infusion and parenteral diazepam in divided doses in the treatment of ASE.Materials & MethodsThis randomized controlled clinical trial, enrolled 20 patients with absence status epilepticus. Diagnosis was made based on the clinical manifestations and electroencephalogram (EEG. Prior to treatment, all patients underwent EEG and imaging. Patients were randomized to receive 0.2 mg/kg/h diazepam infusion or 0.2 mg/kg in six daily doses. Clinical and EEG improvements were considered to be optimal responses.ResultsOf the 20 patients studied, 13 (65% were boys and the remaining 7(35% were girls. There were no differences between the two groups regarding age and sex (non-significant. Following treatments after 48 hours, 1 week and 1 month respectively, clinical improvement in previous problems (loss of consciousness, ataxia, behavior and speech problems and EEGs was similar in both groups (p=1. There were controlled seizures in 18 (90%, abnormal CT scans in 5 (25%, abnormal EEGs after treatments in 6 (30% cases; however no significant differences were seen between the two groups.ConclusionThis study demonstrates that there are no significant differences between treatments of ASE with diazepam infusion and parenteral diazepam in divided doses. Treatment of ASE, with divided doses of diazepam is easier, less expensive and patients do not require to be hospitalized in an Intensive Care unit.

  11. Focal and Generalized Patterns of Cerebral Cortical Veins Due to Non-Convulsive Status Epilepticus or Prolonged Seizure Episode after Convulsive Status Epilepticus – A MRI Study Using Susceptibility Weighted Imaging

    Verma, Rajeev Kumar; Abela, Eugenio; Schindler, Kaspar; Krestel, Heinz; Springer, Elisabeth; Huber, Adrian; Weisstanner, Christian; Hauf, Martinus; Gralla, Jan; Wiest, Roland

    2016-01-01

    Objective The aim of this study was to investigate variant patterns of cortical venous oxygenation during status epilepticus (SE) using susceptibility-weighted imaging (SWI). Methods We analyzed magnetic resonance imaging (MRI) scans of 26 patients with clinically witnessed prolonged seizures and/or EEG-confirmed SE. All MRI exams encompassed SWI, dynamic susceptibility contrast perfusion MRI (MRI-DSC) and diffusion-weighted imaging (DWI). We aimed to identify distinct patterns of SWI signal alterations that revealed regional or global increases of cerebral blood flow (CBF) and DWI restrictions. We hypothesized that SWI-related oxygenation patterns reflect ictal or postictal patterns that resemble SE or sequelae of seizures. Results Sixteen patients were examined during nonconvulsive status epilepticus (NCSE) as confirmed by EEG, a further ten patients suffered from witnessed and prolonged seizure episode ahead of imaging without initial EEG. MRI patterns of 15 of the 26 patients revealed generalized hyperoxygenation by SWI in keeping with either global or multifocal cortical hyperperfusion. Eight patients revealed a focal hyperoxygenation pattern related to focal CBF increase and three patients showed a focal deoxygenation pattern related to focal CBF decrease. Conclusions SWI-related hyper- and deoxygenation patterns resemble ictal and postictal CBF changes within a range from globally increased to focally decreased perfusion. In all 26 patients the SWI patterns were in keeping with ictal hyperperfusion (hyperoxygenation patterns) or postictal hypoperfusion (deoxygenation patterns) respectively. A new finding of this study is that cortical venous patterns in SWI can be not only focally, but globally attenuated. SWI may thus be considered as an alternative contrast-free MR sequence to identify perfusion changes related to ictal or postictal conditions. PMID:27486662

  12. Effects of LiCl/pilocarpine-induced status epilepticus on rat brain mu and benzodiazepine receptor binding: Regional and ontogenetic studies

    Rocha, L.; Suchomelová, Lucie; Mareš, Pavel; Kubová, Hana

    2007-01-01

    Roč. 1181, - (2007), s. 104-117. ISSN 0006-8993 R&D Projects: GA MŠk(CZ) LC554; GA ČR GA304/05/2582 Grant ostatní: CONACyT(MX) 45943-M Institutional research plan: CEZ:AV0Z50110509 Keywords : benzodiazepine receptor * µ receptor binding * status epilepticus Subject RIV: ED - Physiology Impact factor: 2.218, year: 2007

  13. Evaluation of the efficacy of sodium valproate in convulsive status epilepticus following to ıschemic stroke

    Hasan Hüseyin Özdemir

    2015-04-01

    Full Text Available Objective : Convulsive status epilepticus (CSE is very rarely observed after ischaemic stroke. Sodium valproate (SV is one of the agents used in the treatment of CSE, but its role still controversial, and its degree of efficacy in treating CSE that develops following stroke is unclear. Method : We evaluated 19 patients who were treated with intravenous (IV SV (20 mg/kg, 2 mg/kg/h-12h after diazepam. Patients’ modified Rankin scores (mRS, SE types, and changes in biochemical parameters after treatment were assessed. Results : CSE was successfully treated in 12 (63.15% patients. Side effects such as hypotension and allergic reactions were observed in two patients. Refractory SE development was observed in 5 (29.4% patients with high mRS (˃ 3. No significant deterioration in patients’ laboratory evaluations, conducted before and after status, was observed. Conclusion : SV may be safe and effective in the treatment of CSE observed after ischaemic stroke, especially in patients with low mRS.

  14. Níveis dos neurotransmissores estriatais durante o estado epiléptico Striatal monoamines levels during status epilepticus

    Rivelilson Mendes de Freitas

    2003-01-01

    Full Text Available O objetivo desse estudo foi verificar os níveis dos neurotransmissores estriatais de ratas adultas durante o estado epiléptico induzido pela pilocarpina. Ratas wistar foram tratadas com uma única dose de pilocarpina (400 mg/kg por via subcutânea (S.C.; P400 e os controles receberam salina. A concentração dos neurotransmissores foi determinada através do HPLC eletroquímico, no corpo estriado de ratas que no período de observação de 1 hora desencadearam estado epiléptico e que sobreviveram à fase aguda do quadro convulsivo. Foi observada redução nos níveis de dopamina, serotonina, ácido diidroxifenilacético e aumento na concentração do ácido 5-hidroxiindolacético. Nenhuma alteração foi observada no 4-hidroxi-3-metoxi-fenilacético. Os resultados sugerem que a ativação do sistema colinérgico pode interagir com os sistemas dopaminérgico e serotonérgico nos mecanismos referentes à fase aguda do processo convulsivo no corpo estriado de ratos desenvolvidos.The purpose of the present work to investigate the striatal neurotransmissors level in adult rats after status epilepticus induced by pilocarpine. Wistar rats were treated with a single dose of pilocarpine (400 mg/kg; s.c.; P400 and the controls received saline. Adult animals were closed observed for behavioural changes during 1h. In this period, the animals that developed status epilepticus and survive this acute phase of seizures had the brains removed and striatal neurotransmissors level determiden by HPLC. The concentration of dopamine, serotonine, dihydroxyphenylacetic acid was reduced and an concentration increase in 5-hydroxyindolacetic acid. Didn't observed alteration in 4-hydroxy-3-methoxy-phenylacetic acid. These results suggest that cholinergic activation can interage with dopaminergic and serotonergic systems in acute phase of the convulsive process in rat mature striatum.

  15. Reduced expression of calsenilin/DREAM/KChIP3 in the brains of kainic acid-induced seizure and epilepsy patients.

    Hong, Yeon-Mi; Jo, Dong-Gyu; Lee, Min-Cheol; Kim, So-Young; Jung, Yong-Keun

    2003-04-01

    Calsenilin is a neuronal calcium binding protein that may function in calcium signaling and cell death. Kainic acid, an analog of the excitatory amino acid L-glutamate, produced excitotoxic cell death and induced the pathophysiology of status epilepticus. The expression of calsenilin was investigated in the mouse brain after kainic acid-induced seizure and seizure-induced hippocampal neuronal cell culture system using immunostaining analysis. Calsenilin was markedly decreased not only in the damaged cortex and CA3 region of hippocampus at 24 h after kainic acid-induced seizure but also in a cell-culture model of seizure-like activity. In addition, immunoreactivity of calsenilin in the hippocampus derived from human epilepsy patient was significantly decreased compared with normal brain. These results demonstrate that the reduced expression of calsenilin may functionally be associated with the pathophysiology of status epilepticus. PMID:12648752

  16. Histamine 1 receptor knock out mice show age-dependent susceptibility to status epilepticus and consequent neuronal damage.

    Kukko-Lukjanov, Tiina-Kaisa; Grönman, Maria; Lintunen, Minnamaija; Laurén, Hanna B; Michelsen, Kimmo A; Panula, Pertti; Holopainen, Irma E

    2012-06-01

    The central histaminergic neuron system is an important regulator of activity stages such as arousal and sleep. In several epilepsy models, histamine has been shown to modulate epileptic activity and histamine 1 (H1) receptors seem to play a key role in this process. However, little is known about the H1 receptor-mediated seizure regulation during the early postnatal development, and therefore we examined differences in severity of kainic acid (KA)-induced status epilepticus (SE) and consequent neuronal damage in H1 receptor knock out (KO) and wild type (WT) mice at postnatal days 14, 21, and 60 (P14, P21, and P60). Our results show that in P14 H1 receptor KO mice, SE severity and neuronal damage were comparable to those of WT mice, whereas P21 KO mice had significantly decreased survival, more severe seizures, and enhanced neuronal damage in various brain regions, which were observed only in males. In P60 mice, SE severity did not differ between the genotypes, but in KO group, neuronal damage was significantly increased. Our results suggest that H1 receptors could contribute to regulation of seizures and neuronal damage age-dependently thus making the histaminergic system as a challenging target for novel drug design in epilepsy. PMID:22348791

  17. Effect of Argemone mexicana (L.) against lithium-pilocarpine induced status epilepticus and oxidative stress in Wistar rats.

    Asuntha, G; Raju, Y Prasanna; Sundaresan, C R; Rasheed, Arun; Chowdary, V Harini; Vandana, K R; Babu, K Satish; Prasad, K V S R G

    2015-01-01

    Argemone mexicana (L.) has a role in the treatment of epileptic disorders in Indian traditional system of medicine. We studied its effect on induced status epilepticus (SE) and oxidative stress in rats. SE was induced in male albino rats by administration of pilocarpine (30 mg/kg, ip) 24 h after injection of lithium chloride (3 mEq/kg, ip). Different doses of the ethanol extract of A. mexicana were administered orally 1 h before the injection of pilocarpine. The severity of SE was observed and recorded every 15 min for 90 min and thereafter at every 30 min for another 90 min, using the Racine scoring system. In vivo lipid peroxidation of rat brain tissue was measured utilizing thiobarbiturate-reactive substances. Both in vitro free radical nitric oxide and 2,2-diphenyl-1-picryl hydrazyl scavenging activities of the extract were also determined. The SE severity was significantly reduced following oral administration of the extract at 250, 500 and 1000 mg/kg doses. None of the animals from groups 3 to 5 (with A. mexicana extract) have exhibited forelimb clonus of stage 4 seizure. The extract also exhibited both in vivo and in vitro antioxidant activities. PMID:25675709

  18. Nonconvulsive status epilepticus--a possible cause of mental retardation in patients with Lennox-Gastaut syndrome.

    Hoffmann-Riem, M; Diener, W; Benninger, C; Rating, D; Unnebrink, K; Stephani, U; Ernst, H P; Korinthenberg, R

    2000-08-01

    Lennox-Gastaut syndrome (LGS) is one of the most severe types of childhood epilepsy. It is usually resistant to treatment and associated with mental retardation. To delineate the risk factors associated with the outcome of LGS, we evaluated, in a retrospective and multicentre study, the course of the disease, EEG tracings, and intellectual function in 101 patients. Inclusion criteria were the presence of tonic seizures as well as slow spike and wave complexes in the EEG. The average documented observation period was 16 years (range 4-31 years). Overall, the intellectual and neurological outcome was poor. At the last follow-up, 38% of the patients could not speak, 21% were unable to walk and only 4% were free of seizures. Four independent risk factors for severe mental retardation were identified by multivariate analysis. These were in a decreasing order of importance: nonconvulsive status epilepticus (NCSE), odds ratio (OR) 25.2, a previous diagnosis of West syndrome (OR 11.6), a symptomatic etiology of epilepsy (OR 9.5), and an early age at onset of epilepsy (OR 4.7). The results highlight the association between NCSE and the severity of mental retardation in patients with LGS; this association appears to be independent of symptomatic etiology. Our data provide an indirect evidence that, at least in some of the patients, NCSE is not only a concomitant feature, but also a cause of severe mental retardation. PMID:11071139

  19. P2X7 receptor-mediated PARP1 activity regulates astroglial death in the rat hippocampus following status epilepticus

    Ji Yang eKim

    2015-09-01

    Full Text Available Poly(ADP-ribose polymerase-1 (PARP1 plays a regulatory role in apoptosis, necrosis, and other cellular processes after injury. Recently, we revealed that PARP1 regulates the differential neuronal/astroglial responses to pilocarpine-induced status epilepticus (SE in the distinct brain regions. In addition, P2X7 receptor (P2X7R, an ATP-gated ion channel, activation accelerates astroglial apoptosis, while it attenuates clasmatodendrosis (lysosome-derived autophagic astroglial death. Therefore, we investigated whether P2X7R regulates regional specific astroglial PARP1 expression/activation in response to SE. In the present study, P2X7R activation exacerbates SE-induced astroglial apoptosis, while P2X7R inhibition attenuates it accompanied by increasing PARP1 activity in the molecular layer of the dentate gyrus following SE. In the CA1 region, however, P2X7R inhibition deteriorates SE-induced clasmatodendrosis via PARP1 activation following SE. Taken together, our findings suggest that P2X7R function may affect SE-induced astroglial death by regulating PARP1 activation/expression in regional-specific manner. Therefore, the selective modulation of P2X7R-mediated PARP1 functions may be a considerable strategy for controls in various types of cell deaths.

  20. Convulsive status epilepticus duration as determinant for epileptogenesis and interictal discharge generation in the rat limbic system

    Bortel, Aleksandra; Lévesque, Maxime; Biagini, Giuseppe; Gotman, Jean; Avoli, Massimo

    2016-01-01

    We analyzed with EEG-video monitoring the epileptic activity recorded during the latent and chronic periods in rats undergoing 30 or 120 min pilocarpine-induced convulsive status epilepticus (SE). Interictal discharges frequency in the entorhinal cortex (EC) of animals exposed to 120 min SE was significantly higher in the chronic than in the latent period. Following seizure appearance, interictal spikes diminished in duration in the CA3 of the 120 min SE group, and occurred at higher rates in the amygdala in all animals. Rats exposed to 120 min SE generated shorter seizures but presented twice as many non-convulsive seizures per day as the 30 min group. Finally, seizures most frequently initiated in CA3 in the 120 min SE group but had similar onset in CA3 and EC in the 30 min group. These findings indicate that convulsive SE duration influences the development of interictal and ictal activity, and that interictal discharges undergo structure-specific changes after seizure appearance. PMID:20682341

  1. Assessment of effect of ethanolic extract of Tephrosia purpurea (L. Pers., Fabaceae, activity on lithium-pilocarpine induced Status epilepticus and oxidative stress in Wistar rats Avaliação do efeito do extrato etanólico da Tephrosia purpurea (L. Pers., Fabaceae, sobre o status epilepticus induzido por lítio-pilocarpina e estresse oxidativo, em ratos Wistar

    G Asuntha

    2010-11-01

    Full Text Available Tephrosia purpurea (L. Pers., Fabaceae, is claimed to be of use in the control and treatment of a variety of epileptic disorders in Indian system of medicine. The present study plans to systematically evaluate T. purpurea and to verify this claim. Status epilepticus was induced in male albino rats of Wistar strain by administration of pilocarpine (30 mg/kg, i.p. 24 h after lithium chloride (3 mEq/kg, i.p.. Different doses of the extract of T. purpurea were administered orally one hour before the injection of pilocarpine. The severity of status epilepticus was observed and recorded every 15 min till 90 min and thereafter every 30 min till 180 min, using the scoring system. The in vivo lipid peroxidation of rat brain tissue was measured. The in vitro NO free radical scavenging activity of plant extract was assessed. The interaction between plant extract and 2-diphenyl-2-picryl hydrazyl (DPPH was also observed for in vitro free radical scavenging activity. The severity of status epilepticus was reduced with the administration of ethanolic extract of T. purpurea. Ethanolic extract of the plant exhibited both in vivo and in vitro antioxidant activity. The ethanolic extract of T. purpurea was found to be useful to control lithium-pilocarpine induced status epilepticus in albino rats of Wistar strain.Tephrosia purpurea (L. Pers., Fabaceae, é conhecida pelo seu uso no controle e tratamento de uma variedade de distúrbios epilépticos no sistema indiano de medicina. O presente estudo pretende avaliar de forma sistemática T. purpurea e verificar essa alegação. Status epilepticus foi induzido em ratos albinos machos da linhagem Wistar pela administração de pilocarpina (30 mg/kg, i.p. 24 h após o cloreto de lítio (3 mEq/kg, i.p.. Diferentes doses do extrato de T. purpurea foram administrados por via oral uma hora antes da injeção de pilocarpina. A gravidade do status epilepticus foi observada e registrada a cada 15 min até 90 min e

  2. Status epilepticus after prolonged umbilical cord occlusion is associated with greater neural injury in [corrected] fetal sheep at term-equivalent.

    Paul P Drury

    Full Text Available The majority of pre-clinical studies of hypoxic-ischemic encephalopathy at term-equivalent have focused on either relatively mild insults, or on functional paradigms of cerebral ischemia or hypoxia-ischemia/hypotension. There is surprisingly little information on the responses to single, severe 'physiological' insults. In this study we examined the evolution and pattern of neural injury after prolonged umbilical cord occlusion (UCO. 36 chronically instrumented fetal sheep at 125-129 days gestational age (term = 147 days were subjected to either UCO until mean arterial pressure was < = 8 mmHg (n = 29, or sham occlusion (n = 7. Surviving fetuses were killed after 72 hours for histopathologic assessment with acid-fuchsin thionine. After UCO, 11 fetuses died with intractable hypotension and 5 ewes entered labor and were euthanized. The remaining 13 fetuses showed marked EEG suppression followed by evolving seizures starting at 5.8 (6.8 hours (median (interquartile range. 6 of 13 developed status epilepticus, which was associated with a transient secondary increase in cortical impedance (a measure of cytotoxic edema, p<0.05. All fetuses showed moderate to severe neuronal loss in the hippocampus and the basal ganglia but mild cortical cell loss (p<0.05 vs sham occlusion. Status epilepticus was associated with more severe terminal hypotension (p<0.05 and subsequently, greater neuronal loss (p<0.05. In conclusion, profound UCO in term-equivalent fetal sheep was associated with delayed seizures, secondary cytotoxic edema, and subcortical injury, consistent with the predominant pattern after peripartum sentinel events at term. It is unclear whether status epilepticus exacerbated cortical injury or was simply a reflection of a longer duration of asphyxia.

  3. The effect of STAT3 inhibition on status epilepticus and subsequent spontaneous seizures in the pilocarpine model of acquired epilepsy.

    Grabenstatter, H L; Del Angel, Y Cruz; Carlsen, J; Wempe, M F; White, A M; Cogswell, M; Russek, S J; Brooks-Kayal, A R

    2014-02-01

    Pilocarpine-induced status epilepticus (SE), which results in temporal lobe epilepsy (TLE) in rodents, activates the JAK/STAT pathway. In the current study, we evaluate whether brief exposure to a selective inhibitor of the JAK/STAT pathway (WP1066) early after the onset of SE affects the severity of SE or reduces later spontaneous seizure frequency via inhibition of STAT3-regulated gene transcription. Rats that received systemic WP1066 or vehicle at the onset of SE were continuously video-EEG monitored during SE and for one month to assess seizure frequency over time. Protein and/or mRNA levels for pSTAT3, and STAT3-regulated genes including: ICER, Gabra1, c-myc, mcl-1, cyclin D1, and bcl-xl were evaluated in WP1066 and vehicle-treated rats during stages of epileptogenesis to determine the acute effects of WP1066 administration on SE and chronic epilepsy. WP1066 (two 50mg/kg doses) administered within the first hour after onset of SE results in transient inhibition of pSTAT3 and long-term reduction in spontaneous seizure frequency. WP1066 alters the severity of chronic epilepsy without affecting SE or cell death. Early WP1066 administration reduces known downstream targets of STAT3 transcription 24h after SE including cyclin D1 and mcl-1 levels, known for their roles in cell-cycle progression and cell survival, respectively. These findings uncover a potential effect of the JAK/STAT pathway after brain injury that is physiologically important and may provide a new therapeutic target that can be harnessed for the prevention of epilepsy development and/or progression. PMID:24051278

  4. Inhibition of sodium glucose cotransporters following status epilepticus induced by intrahippocampal pilocarpine affects neurodegeneration process in hippocampus.

    Melo, Igor S; Santos, Yngrid M O; Costa, Maísa A; Pacheco, Amanda L D; Silva, Nívea K G T; Cardoso-Sousa, L; Pereira, U P; Goulart, L R; Garcia-Cairasco, Norberto; Duzzioni, Marcelo; Gitaí, Daniel L G; Tilelli, Cristiane Q; Sabino-Silva, Robinson; Castro, Olagide W

    2016-08-01

    Temporal lobe epilepsy (TLE) is characterized by spontaneous recurrent seizures, starting from secondary functional disorders due to several insults, including self-sustaining continuous seizures identified as status epilepticus (SE). Although hypoglycemia has been associated with SE, the effect of inhibition of the Na(+)/glucose cotransporters (SGLTs) on hippocampus during SE is still unknown. Here we evaluated the functional role of SGLT in the pattern of limbic seizures and neurodegeneration process after pilocarpine (PILO)-induced SE. Vehicle (VEH, 1μL) or phlorizin, a specific SGLT inhibitor (PZN, 1μL, 50μg/μL), was administered in the hippocampus of rats 30min before PILO (VEH+PILO or PZN+PILO, respectively). The limbic seizures were classified using the Racine's scale, and the amount of wet dog shakes (WDS) was quantified before and during SE. Neurodegeneration process was evaluated by Fluoro-Jade C (FJ-C), and FJ-C-positive neurons (FJ-C+) were counted 24h and 15days after SE. The PZN-treated rats showed higher (pclass 5 seizures repeated themselves more times (pclasses in the PZN group at 50min after SE induction. The PZN+PILO animals had a higher (p<0.05) number of FJ-C+ cells in the dentate gyrus (DG), hilus, and CA3 and CA1 of hippocampus, when compared with VEH+PILO. The PZN+PILO animals had a decreased number (p<0.05) of FJ-C+ cells in CA1 compared with VEH+PILO 15days after SE induction. Taken together, our data suggest that SGLT inhibition with PZN increased the severity of limbic seizures during SE and increased neurodegeneration in hippocampus 24h after SE, suggesting that SGLT1 and SGLT2 could participate in the modulation of earlier stages of epileptogenic processes. PMID:27429292

  5. Microglia are less pro-inflammatory than myeloid infiltrates in the hippocampus of mice exposed to status epilepticus.

    Vinet, Jonathan; Vainchtein, Ilia D; Spano, Carlotta; Giordano, Carmela; Bordini, Domenico; Curia, Giulia; Dominici, Massimo; Boddeke, Hendrikus W G M; Eggen, Bart J L; Biagini, Giuseppe

    2016-08-01

    Activated microglia, astrogliosis, expression of pro-inflammatory cytokines, blood brain barrier (BBB) leakage and peripheral immune cell infiltration are features of mesial temporal lobe epilepsy. Numerous studies correlated the expression of pro-inflammatory cytokines with the activated morphology of microglia, attributing them a pro-epileptogenic role. However, microglia and myeloid cells such as macrophages have always been difficult to distinguish due to an overlap in expressed cell surface molecules. Thus, the detrimental role in epilepsy that is attributed to microglia might be shared with myeloid infiltrates. Here, we used a FACS-based approach to discriminate between microglia and myeloid infiltrates isolated from the hippocampus 24 h and 96 h after status epilepticus (SE) in pilocarpine-treated CD1 mice. We observed that microglia do not express MHCII whereas myeloid infiltrates express high levels of MHCII and CD40 96 h after SE. This antigen-presenting cell phenotype correlated with the presence of CD4(pos) T cells. Moreover, microglia only expressed TNFα 24 h after SE while myeloid infiltrates expressed high levels of IL-1β and TNFα. Immunofluorescence showed that astrocytes but not microglia expressed IL-1β. Myeloid infiltrates also expressed matrix metalloproteinase (MMP)-9 and 12 while microglia only expressed MMP-12, suggesting the involvement of both cell types in the BBB leakage that follows SE. Finally, both cell types expressed the phagocytosis receptor Axl, pointing to phagocytosis of apoptotic cells as one of the main functions of microglia. Our data suggests that, during early epileptogenesis, microglia from the hippocampus remain rather immune supressed whereas myeloid infiltrates display a strong inflammatory profile. GLIA 2016 GLIA 2016;64:1350-1362. PMID:27246930

  6. A girl with tuberous sclerosis complex presenting with severe epilepsy and electrical status epilepticus during sleep, and with high-functioning autism and mutism.

    Pacheva, Iliyana; Panov, Georgi; Gillberg, Christopher; Neville, Brian

    2014-06-01

    Most patients with tuberous sclerosis complex (TSC) suffer from epilepsy, and many have cognitive and behavioral problems like severe intellectual disability, autism, and hyperactivity. Only rare patients with TSC and autism have a normal intelligence quotient. We report a 13-year-old girl with definite TSC who had early-onset severe epilepsy, autistic behavior, and moderate developmental delay. By school age, however, she had normal intelligence; her intelligence quotient was at least 70 based on a Stanford-Binet test that she refused to complete. She showed good reading, writing, and language comprehension skills, and the special abilities of hyperlexia, hypermnesia, and hypercalculia. However, she did not speak. Criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, and her Childhood Autism Rating Scale score of 36 indicated mild to moderate autism. She had severe electroencephalographic abnormalities: hypsarrhythmia, multifocal or generalized epileptiform discharges, and electrical status epilepticus during sleep, with a continuous left temporal focus. Magnetic resonance imaging showed many cortical tubers in all brain lobes, and subependymal nodules. We discuss possible explanations for her lack of speech. Considered as speech apraxia, her mutism could be either a symptom of her TSC or a component of her autism. Another possibility is that long-lasting electrical status epilepticus during sleep led to her autistic behavior and language arrest. Still another possibility is that a disinhibited mammalian target of rapamycin (mTOR) pathway was at the root of all of her neuropsychiatric symptoms. PMID:24968009

  7. Experience in using injectable valproic acid (convulex in patients with serial epileptic seizures and status epilepticus at the prehospital stage

    A. V. Lebedeva

    2014-01-01

    Full Text Available Objective: to evaluate the efficacy of injectable valproate (convulex in patients with serial epileptic seizures and status epilepticus (SE at the prehospital stage.Patients and methods. Thirty-two adult patients, including 17 (53% men and 15 (47% women, were examined. Most patients were aged over 40 years (mean age 54.7±9.4 years. To define the required dose of the drug, the authors estimated the patient's weight that averaged 76.8±1.9 kg, i.e. there was a preponderance of patients who needed convulex, more than 500 mg, to achieve a therapeutic effect.Results. It was impossible to reliably and validly evaluate the type of a seizure as the medical emergency team (MET generally observed the patient with a just evolving seizure and the medical history data were not always valid therefore the type of convulsions and the type of a seizure were evaluated. In most cases, solitary convulsive attacks (tonic and/or clonic convulsions and/or serial seizures were observed in 12 (37.5% and 14 (43.7% patients, respectively; SE was recorded in 6 (8.8% patients. Generalized seizures (without a clear focal onset were prevalent in 24 (75% patients while 8 (25% patients were found to have partial seizures (seizure onset lateralization, a focal onset. According to the pattern of convulsions, seizures may be classified into three types: tonic-clonic, clonic, and tonic in 22 (68.8%, 7 (21.9%, and 3 (9.3% patients, respectively. Analysis of the efficacy of intravenously injectable valproate (convulex in the group of patients with SE and epileptic seizures indicated that complete cessation of seizures could be achieved in 68.8%, their rate decreased in other 9.4% of the patients. Seizures were preserved in 7 (21.8% cases, which required additional administration of drugs. Conclusion. Injectable valproic acid (convulex has a high efficacy and may be preclinically used as the drug of choice to arrest SE and serial seizures caused by both epilepsy and other

  8. Changes of AMPA receptor properties in the neocortex and hippocampus following pilocarpine-induced status epilepticus in rats.

    Malkin, Sergey L; Amakhin, Dmitry V; Veniaminova, Ekaterina A; Kim, Kira Kh; Zubareva, Olga E; Magazanik, Lev G; Zaitsev, Aleksey V

    2016-07-01

    Temporal lobe epilepsy (TLE) is the most common type of epilepsy in humans. The lithium-pilocarpine model in rodents reproduces some of the main features of human TLE. Three-week-old Wistar rats were used in this study. The changes in AMPA receptor subunit composition were investigated in several brain areas, including the medial prefrontal cortex (mPFC), the temporal cortex (TC), and the dorsal (DH) and ventral hippocampus (VH) during the first week following pilocarpine-induced status epilepticus (PILO-induced SE). In the hippocampus, GluA1 and GluA2 mRNA expression slightly decreased after PILO-induced SE and returned to the initial level on the seventh day. We did not detect any significant changes in mRNA expression of the GluA1 and GluA2 subunits in the TC, whereas in the mPFC we observed a significant increase of GluA1 mRNA expression on the third day and a decrease in GluA2 mRNA expression during the entire first week. Accordingly, the GluA1/GluA2 expression ratio increased in the mPFC, and the functional properties of the pyramidal cell excitatory synapses were disturbed. Using whole-cell voltage-clamp recordings, we found that on the third day following PILO-induced SE, isolated mPFC pyramidal neurons showed an inwardly rectifying current-voltage relation of kainate-evoked currents, suggesting the presence of GluA2-lacking calcium-permeable AMPARs (CP-AMPARs). IEM-1460, a selective antagonist of CP-AMPARs, significantly reduced the amplitude of evoked EPSC in pyramidal neurons from mPFC slices on the first and third days, but not on the seventh day. The antagonist had no effects on EPSC amplitude in slices from control animals. Thus, our data demonstrate that PILO-induced SE affects subunit composition of AMPARs in different brain areas, including the mPFC. SE induces transient (up to few days) incorporation of CP-AMPARs in the excitatory synapses of mPFC pyramidal neurons, which may disrupt normal circuitry functions. PMID:27109923

  9. Is pentobarbital safe and efficacious in the treatment of super-refractory status epilepticus: a cohort study

    2014-01-01

    Introduction Seizures refractory to third-line therapy are also labeled super-refractory status epilepticus (SRSE). These seizures are extremely difficult to control and associated with poor outcome. We aimed to characterize efficacy and side-effects of continuous infusions of pentobarbital (cIV-PTB) treating SRSE. Methods We retrospectively reviewed continuous electroencephalography (cEEG) reports for all adults with RSE treated with cIV-PTB between May 1997 and April 2010 at our institution. Patients with post-anoxic SE and those receiving cIV-PTB for reasons other than RSE were excluded. We collected baseline information, cEEG findings, side-effects and functional outcome at discharge and one year. Results Thirty one SRSE patients treated with cIV-PTB for RSE were identified. Mean age was 48 years old (interquartile range (IQR) 28,63), 26% (N = 8) had a history of epilepsy. Median SE duration was 6.5 days (IQR 4,11) and the mean duration of cIV-PTB was 6 days (IQR 3,14). 74% (N = 23) presented with convulsive SE. Underlying etiology was acute symptomatic seizures in 52% (N = 16; 12/16 with encephalitis), remote 30% (N = 10), and unknown 16% (N = 5). cIV-PTB controlled seizures in 90% (N = 28) of patients but seizures recurred in 48% (N = 15) while weaning cIV-PTB, despite the fact that suppression-burst was attained in 90% (N = 28) of patients and persisted >72 hours in 56% (N = 17). Weaning was successful after adding phenobarbital in 80% (12/15 of the patients with withdrawal seizures). Complications during or after cIV-PTB included pneumonia (32%, N = 10), hypotension requiring pressors (29%, N = 9), urinary tract infection (13%, N = 4), and one patient each with propylene glycol toxicity and cardiac arrest. One-third (35%, N = 11) had no identified new complication after starting cIV-PTB. At one year after discharge, 74% (N = 23) were dead or in a state of unresponsive wakefulness, 16% (N = 5

  10. Status epilepticus and cardiopulmonary arrest in a patient with carbon monoxide poisoning with full recovery after using a neuroprotective strategy: a case report

    Abdulaziz Salman

    2012-12-01

    Full Text Available Abstract Introduction Carbon monoxide poisoning can be associated with life-threatening complications, including significant and disabling cardiovascular and neurological sequelae. Case presentation We report a case of carbon monoxide poisoning in a 25-year-old Saudi woman who presented to our facility with status epilepticus and cardiopulmonary arrest. Her carboxyhemoglobin level was 21.4 percent. She made a full recovery after we utilized a neuroprotective strategy and normobaric oxygen therapy, with no delayed neurological sequelae. Conclusions Brain protective modalities are very important for the treatment of complicated cases of carbon monoxide poisoning when they present with neurological toxicities or cardiac arrest. They can be adjunctive to normobaric oxygen therapy when the use of hyperbaric oxygen is not feasible.

  11. Alterative application of five anticonvulsants according to the half life for the treatment of status epilepticus in children with severe viral encephalitis

    2007-01-01

    BACKGROUND: Traditional subhibernation therapy may easily cause complications, such as respiratory depression and hyportension because of application of chlorpromazine hydrochloride and promethazine in a large dosage.OBJECTIVE: To observe therapeutic effect of modified subhibernation therapy (alterative application of five anticonvulsants according to the half life) on status epilepticus in children with severe viral encephalitis (VE).DESIGN: Contrast observation.SETTING: Department of Pediatrics, the First Hospital of Jilin University.PARTICIPANTS: The participants in present study were 96 patients withsevere viral encephalitis including 52 boys and 44 girls who received treatment in the Department of Pediatrics, the First Hospital of Jilin University from February 2000 to March 2006. All children met the diagnostic criteria of Zhufutong Practice Pediatrics (the seventh edition). Two weeks ago, they ever got upper respiratory infection or enteronitis and so on before the onset, spirit abnormal, behavior disorder, limbs act disorder, vomit, headache, convulsion,nervous system masculine signs such as limbs act disord, autonomic nerve damage manifestation, brain nerve palsy, dysreflexia, meningeal irritation sign, cerebrospinal fluid and electroencephalography (EEG)abnormity. All parents provided the confirmed consent. The patients were randomly divided into control group (n =40) and experimental group (n =56).METHODS: Patients in the control group received anticonvulsion, ice compress and routine treatment. The convulsion was treated with five drugs: 0.5 mg/kg wintermin and phenergan, respectively, 100 g/L chlorpromazine hydrochloride (0.5 mL/kg), 5 mg/kg luminal, 0.3 mg/kg ansiolin. When convulsion attacked,those five drugs were given alternatively; however, those were not given if the convulsion did not attack.Children in the experimental group were treated with improved subhibernation therapy based on routine treatment. The dosages of anticonvulsants were as the

  12. Long-term decrease in Na+,K+-ATPase activity after pilocarpine-induced status epilepticus is associated with nitration of its alpha subunit.

    Funck, Vinícius Rafael; Ribeiro, Leandro Rodrigo; Pereira, Letícia Meier; de Oliveira, Clarissa Vasconcelos; Grigoletto, Jéssica; Fighera, Michele Rechia; Royes, Luiz Fernando Freire; Furian, Ana Flávia; Oliveira, Mauro Schneider

    2014-12-01

    Temporal lobe epilepsy (TLE) is the most common type of epilepsy with about one third of TLE patients being refractory to antiepileptic drugs. Knowledge about the mechanisms underlying seizure activity is fundamental to the discovery of new drug targets. Brain Na(+),K(+)-ATPase activity contributes to the maintenance of the electrochemical gradients underlying neuronal resting and action potentials as well as the uptake and release of neurotransmitters. In the present study we tested the hypothesis that decreased Na(+),K(+)-ATPase activity is associated with changes in the alpha subunit phosphorylation and/or redox state. Activity of Na(+),K(+)-ATPase decreased in the hippocampus of C57BL/6 mice 60 days after pilocarpine-induced status epilepticus (SE). In addition, the Michaelis-Menten constant for ATP of α2/3 isoforms increased at the same time point. Nitration of the α subunit may underlie decreased Na(+),K(+)-ATPase activity, however no changes in expression or phosphorylation state at Ser(943) were found. Further studies are necessary define the potential of nitrated Na(+),K(+)-ATPase as a new therapeutic target for seizure disorders. PMID:25311690

  13. Expressions of tumor necrosis factor alpha and microRNA-155 in immature rat model of status epilepticus and children with mesial temporal lobe epilepsy.

    Ashhab, Muhammad Usman; Omran, Ahmed; Kong, Huimin; Gan, Na; He, Fang; Peng, Jing; Yin, Fei

    2013-11-01

    Recently, the role of inflammation has attracted great attention in the pathogenesis of mesial temporal lobe epilepsy (MTLE), and microRNAs start to emerge as promising new players in MTLE pathogenesis. In this study, we investigated the dynamic expression patterns of tumor necrosis factor alpha (TNF-α) and microRNA-155 (miR-155) in the hippocampi of an immature rat model of status epilepticus (SE) and children with MTLE. The expressions of TNF-α and miR-155 were significantly upregulated in the seizure-related acute and chronic stages of MTLE in the immature rat model and also in children with MTLE. Modulation of TNF-α expression, either by stimulation using myeloid-related protein (MRP8) or lipopolysaccharide or inhibition using lenalidomide on astrocytes, leads to similar dynamic changes in miR-155 expression. Our study is the first to focus on the dynamic expression pattern of miR-155 in the immature rat of SE lithium-pilocarpine model and children with MTLE and to detect their relationship at the astrocyte level. TNF-α and miR-155, having similar expression patterns in the three stages of MTLE development, and their relationship at the astrocyte level may suggest a direct interactive relationship during MTLE development. Therefore, modulation of the TNF-α/miR-155 axis may be a novel therapeutic target for the treatment of MTLE. PMID:23636891

  14. [Abnormal cerebral blood flow distributions during the post-ictal phase of febrile status epilepticus in three pediatric patients measured by arterial spin labeling perfusion MRI].

    Hirano, Keiko; Fukuda, Tokiko

    2016-05-01

    The ability to visualize brain perfusion is important for identifying epileptic foci. We present three pediatric cases showing asymmetrical cerebral blood flow (CBF) distributions during the post-ictal phase of febrile status epilepticus measured by arterial spin labeling (ASL) perfusion MRI. During the acute phase, regional CBF measurements in the areas considered including epileptic foci were higher than in the corresponding area of the contralateral hemisphere, though the exact quantitative value varied between cases. We could not identify the correct epileptogenic foci, because those ASL images were taken after the prolonged and extraordinary activation of neurons in the affected area. During the recovery phase, the differences reduced and the average regional CBF measurement was 54.6 ± 6.1 ml/100 g per minute, which was a little less than the number of previous ASL studies. ASL perfusion MRI imaging provides a method for evaluating regional CBF by using magnetically labeled arterial blood water as an endogenous tracer. With this technique, we can repeatedly evaluate both the brain structure and the level of perfusion at the same time. ASL is noninvasive and easily accessible, and therefore it could become a routine tool for assessment of perfusion in daily practice of pediatric neurology. PMID:27349086

  15. The Effects of Quinacrine, Proglumide, and Pentoxifylline on Seizure Activity, Cognitive Deficit, and Oxidative Stress in Rat Lithium-Pilocarpine Model of Status Epilepticus

    Mohammad Ahmad

    2014-01-01

    Full Text Available The present data indicate that status epilepticus (SE induced in adult rats is associated with cognitive dysfunctions and cerebral oxidative stress (OS. This has been demonstrated using lithium-pilocarpine (Li-Pc model of SE. OS occurring in hippocampus and striatum of mature brain following SE is apparently due to both the increased free radicals production and the limited antioxidant defense. Pronounced alterations were noticed in the enzymatic, glutathione-S transferase (GST, catalase (CAT, and superoxide dismutase (SOD, as well as in the nonenzymatic; thiobarbituric acid (TBARS and reduced glutathione (GST, indices of OS in the hippocampus and striatum of SE induced animals. Quinacrine (Qcn, proglumide (Pgm, and pentoxifylline (Ptx administered to animals before inducing SE, were significantly effective in ameliorating the seizure activities, cognitive dysfunctions, and cerebral OS. The findings suggest that all the drugs were effective in the order of Ptx < Pgm < Qcn indicating that these drugs are potentially antiepileptic as well as antioxidant; however, further studies are needed to establish this fact. It can be assumed that these antiepileptic substances with antioxidant properties combined with conventional therapies might provide a beneficial effect in treatment of epilepsy through ameliorating the cerebral OS.

  16. Immediate Epileptogenesis after Kainate-Induced Status Epilepticus in C57BL/6J Mice: Evidence from Long Term Continuous Video-EEG Telemetry.

    Sreekanth Puttachary

    Full Text Available The C57BL/6J mouse as a model of seizure/epilepsy is challenging due to high mortality and huge variability in response to kainate. We have recently demonstrated that repeated administration of a low dose of kainate by intraperitoneal route can induce severe status epilepticus (SE with 94% survival rate. In the present study, based on continuous video-EEG recording for 4-18 weeks from epidurally implanted electrodes on the cortex, we demonstrate that this method also induces immediate epileptogenesis (<1-5 days post-SE. This finding was based on identification of two types of spontaneous recurrent seizures; behavioral convulsive seizures (CS and electrographic nonconvulsive seizures (NCS. The identification of the spontaneous CS, stage 3-5 types, was based on the behaviors (video that were associated with the EEG characteristics (stage 3-5 epileptiform spikes, the power spectrum, and the activity counts. The electrographic NCS identification was based on the stage 1-2 epileptiform spike clusters on the EEG and their associated power spectrum. Severe SE induced immediate epileptogenesis in all the mice. The maximum numbers of spontaneous CS were observed during the first 4-6 weeks of the SE and they decreased thereafter. Mild SE also induced immediate epileptogenesis in some mice but the CS were less frequent. In both the severe and the mild SE groups, the spontaneous electrographic NCS persisted throughout the 18 weeks observation period, and therefore this could serve as a chronic model for complex seizures. However, unlike rat kainate models, the C57BL/6J mouse kainate model is a unique regressive CS model of epilepsy. Further studies are required to understand the mechanism of recovery from spontaneous CS in this model, which could reveal novel therapeutic targets for epilepsy.

  17. Benign childhood epilepsy with Centro-Temporal spikes (BCECTSs), electrical status epilepticus in sleep (ESES), and academic decline--how aggressive should we be?

    Uliel-Sibony, Shimrit; Kramer, Uri

    2015-03-01

    Since many of the children with BCECTSs display electrical status epilepticus during sleep and many present with different comorbidities, mainly ADHD and behavioral disturbances, clinicians are often confronted with the dilemma of how aggressive they should be with their efforts of normalizing the EEG. We conducted a retrospective study by screening medical records of all consecutive patients with BCECTSs, spike-wave index (SWI) >30%, and ADHD/ADD that were evaluated in our pediatric epilepsy service and were followed up for at least two years. Patients with neurocognitive deterioration detected by formal testing were excluded. A total of 17 patients with mean age of 6.9years at BCECTS diagnosis were identified. The patients' mean SWI was 60% and that dense electrical activity lasted 1.5years on average (range: 1-4.5years). Six children were formally diagnosed with learning disabilities in addition to ADD/ADHD. All of them were treated with an average of three antiepileptic medications, mainly for the purpose of normalizing the EEG, but none of them was treated with steroids or high-dose diazepam. The mean duration of follow-up was 5.5years. A cognitive or behavioral deterioration was not detected in any of them. Our data suggest that when treating a child with BCECTSs, high SWI, and school difficulties, the most critical parameter that determines the necessity of using second-line antiepileptic agents such as steroids or high-dose diazepam is a formal psychological evaluation that proves cognitive (I.Q.) decline. Otherwise, these agents may be avoided. PMID:25678032

  18. Neuroprotective effect of therapeutic hypothermia versus standard care alone after convulsive status epilepticus: protocol of the multicentre randomised controlled trial HYBERNATUS.

    Legriel, Stephane; Pico, Fernando; Tran-Dinh, Yves-Roger; Lemiale, Virginie; Bedos, Jean-Pierre; Resche-Rigon, Matthieu; Cariou, Alain

    2016-12-01

    Convulsive status epilepticus (CSE) is a major medical emergency associated with a 50 % morbidity rate. CSE guidelines have recommended prompt management for many years, but there is no evidence to date that they have significantly improved practices or outcomes. Developing neuroprotective strategies for use after CSE holds promise for diminishing morbidity and mortality rates. Hypothermia has been shown to afford neuroprotection in various health conditions. We therefore designed a trial to determine whether 90-day outcomes in mechanically ventilated patients with CSE requiring management in the intensive care unit (ICU) are improved by early therapeutic hypothermia (32-34 °C) for 24 h with propofol sedation. We are conducting a multicentre, open-label, parallel-group, randomised, controlled trial (HYBERNATUS) of potential neuroprotective effects of therapeutic hypothermia and routine propofol sedation started within 8 h after CSE onset in ICU patients requiring mechanical ventilation. Included patients are allocated to receive therapeutic hypothermia (32-34 °C) plus standard care or standard care alone. We plan to enrol 270 patients in 11 ICUs. An interim analysis is scheduled after the inclusion of 135 patients. The main study objective is to evaluate the effectiveness of therapeutic hypothermia (32-34 °C) for 24 h in diminishing 90-day morbidity and mortality (defined as a Glasgow Outcome Scale score <5). The HYBERNATUS trial is expected to a decreased proportion of patients with a Glasgow Outcome Scale score lower than 5 after CSE requiring ICU admission and mechanical ventilation. Trial registration Clinicaltrials.gov identifier NCT01359332 (registered on 23 May 2011). PMID:27325409

  19. Temporal profiles of age-dependent changes in cytokine mRNA expression and glial cell activation after status epilepticus in postnatal rat hippocampus

    Ruohonen Saku

    2011-04-01

    Full Text Available Abstract Background Status epilepticus (SE is proposed to lead to an age-dependent acute activation of a repertoire of inflammatory processes, which may contribute to neuronal damage in the hippocampus. The extent and temporal profiles of activation of these processes are well known in the adult brain, but less so in the developing brain. We have now further elucidated to what extent inflammation is activated by SE by investigating the acute expression of several cytokines and subacute glial reactivity in the postnatal rat hippocampus. Methods SE was induced by an intraperitoneal (i.p. injection of kainic acid (KA in 9- and 21-day-old (P9 and P21 rats. The mRNA expression of interleukin-1 beta (IL-1β, tumor necrosis factor-alpha (TNF-α, interleukin-10 (IL-10, matrix metalloproteinase-9 (MMP-9, glial-derived neurotrophic factor (GDNF, interferon gamma (IFN-γ, and transforming growth factor-beta 1 (TGF-β1 were measured from 4 h up to 3 days after KA injection with real-time quantitative PCR (qPCR. IL-1β protein expression was studied with ELISA, GFAP expression with western blotting, and microglial and astrocyte morphology with immunohistochemistry 3 days after SE. Results SE increased mRNA expression of IL-1β, TNF-α and IL-10 mRNA in hippocampus of both P9 and P21 rats, their induction being more rapid and pronounced in P21 than in P9 rats. MMP-9 expression was augmented similarly in both age groups and GDNF expression augmented only in P21 rats, whereas neither IFN-γ nor TGF-β1 expression was induced in either age group. Microglia and astrocytes exhibited activated morphology in the hippocampus of P21 rats, but not in P9 rats 3 d after SE. Microglial activation was most pronounced in the CA1 region and also detected in the basomedial amygdala. Conclusion Our results suggest that SE provokes an age-specific cytokine expression in the acute phase, and age-specific glial cell activation in the subacute phase as verified now in the

  20. Lovastatin reduces neuronal cell death in hippocampal CA1 subfield after pilocarpine-induced status epilepticus: preliminary results Lovastatina reduz a lesão celular na região CA1 do hipocampo após o status epilepticus induzido pela pilocarpina: resultados preliminares

    Pauline Rangel

    2005-12-01

    Full Text Available OBJECTIVE: To further characterize the capacity of lovastatin to prevent hippocampal neuronal loss after pilocarpine-induced status epilepticus (SE METHOD: Adult male Wistar rats were divided into four groups: (A control rats, received neither pilocarpine nor lovastatin (n=5; (B control rats, received just lovastatin (n=5; (C rats that received just pilocarpine (n=5; (D rats that received pilocarpine and lovastatin (n=5. After pilocarpine injection (350mg/kg, i.p., only rats that displayed continuous, convulsive seizure activity were included in our study. Seizure activity was monitored behaviorally and terminated with an injection of diazepam (10 mg/kg, i.p. after 4 h of convulsive SE. The rats treated with lovastatin received two doses of 20mg/kg via an oesophagic probe immediately and 24 hours after SE induction. Seven days after pilocarpine-induced SE, all the animals were perfused and their brains were processed for histological analysis through Nissl method. RESULTS: The cell counts in the Nissl-stained sections performed within the hippocampal formation showed a significant cell loss in rats that received pilocarpine and presented SE (CA1= 26.8 ± 13.67; CA3= 38.1 ± 7.2; hilus= 43.8 ± 3.95 when compared with control group animals (Group A: CA1= 53.2 ± 9.63; CA3= 63.5 ± 13.35; hilus= 59.08 ± 10.24; Group B: CA1= 74.3 ± 8.16; CA3= 70.1 ± 3.83; hilus= 70.6 ± 5.10. The average neuronal cell number of CA1 subfield of rats that present SE and received lovastatin (44.4 ± 17.88 was statically significant increased when compared with animals that just presented SE. CONCLUSION: Lovastatin exert a neuroprotective role in the attenuation of brain damage after SE.OBJETIVO: Capacidade da lovastatina em prevenir a perda de neurônios hipocampais após o status epilepticus (SE induzido pela pilocarpina. MÉTODO: Ratos adultos Wistar foram divididos em 4 grupos: (A ratos controles que não receberam pilocarpina nem lovastatina (n=5; (B ratos

  1. A New Derivative of Valproic Acid Amide Possesses a Broad-spectrum Antiseizure Profile and Unique Activity Against Status Epilepticus and Organophosphate Neuronal Damage

    White, H. Steve; Alex, Anitha B.; Pollock, Amanda; Hen, Naama; Shekh-Ahmad, Tawfeeq; Wilcox, Karen S.; McDonough, John H.; Stables, James P.; Kaufmann, Dan; Yagen, Boris; Bialer, Meir

    2011-01-01

    Summary Purpose sec-Butyl-propylacetamide (SPD) is a one-carbon homologue of valnoctamide (VCD), a CNS-active amide derivative of valproic acid (VPA) currently in phase II clinical trials. The current study evaluated the anticonvulsant activity of SPD in a battery of rodent seizure and epilepsy models and assessed its efficacy in rat and guinea pig models of status epilepticus (SE) and neuroprotection in an organotypic hippocampal slice model of excitotoxic cell death. Methods SPD’s anticonvulsant activity was evaluated in several rodent seizure and epilepsy models including: maximal electroshock (MES), 6Hz psychomotor, subcutaneous (s.c.) metrazol-, s.c., picrotoxin, s.c. bicuculline, audiogenic and corneal and hippocampal kindled seizures following intraperitoneal administration. Results obtained with SPD are discussed in relationship to those obtained with VPA and VCD. SPD was also evaluated for its ability to block benzodiazepine-resistant SE induced by pilocarpine (rats) and soman (rats and guinea pigs) following intraperitoneal administration. SPD was tested for its ability to block excitotoxic cell death induced by the glutamate agonists N-methyl-D-Aspartate (NMDA) and kainic acid (KA) using organotypic hippocampal slices and SE-induced hippocampal cell death using FluoroJade B staining. The cognitive function of SPD-treated rats that were protected against pilocarpine-induced convulsive SE was examined 10-14 days post SE using the Morris water maze (MWM). The relationship between the pharmacokinetic profile of SPD and its efficacy against soman-induced SE was evaluated in two parallel studies following SPD (60 mg/kg, i.p.) administration in the soman SE rat model. Key Findings SPD was highly effective and displayed a wide protective index (PI=TD50/ED50) in the standardized seizure and epilepsy models employed. SPD’s wide PI values demonstrate that it is effective at doses well below those that produce behavioral impairment. Unlike VCD, SPD also

  2. (R)-[11C]Verapamil PET studies to assess changes in P-glycoprotein expression and functionality in rat blood-brain barrier after exposure to kainate-induced status epilepticus

    Increased functionality of efflux transporters at the blood-brain barrier may contribute to decreased drug concentrations at the target site in CNS diseases like epilepsy. In the rat, pharmacoresistant epilepsy can be mimicked by inducing status epilepticus by intraperitoneal injection of kainate, which leads to development of spontaneous seizures after 3 weeks to 3 months. The aim of this study was to investigate potential changes in P-glycoprotein (P-gp) expression and functionality at an early stage after induction of status epilepticus by kainate. (R)-[11C]verapamil, which is currently the most frequently used positron emission tomography (PET) ligand for determining P-gp functionality at the blood-brain barrier, was used in kainate and saline (control) treated rats, at 7 days after treatment. To investigate the effect of P-gp on (R)-[11C]verapamil brain distribution, both groups were studied without or with co-administration of the P-gp inhibitor tariquidar. P-gp expression was determined using immunohistochemistry in post mortem brains. (R)-[11C]verapamil kinetics were analyzed with approaches common in PET research (Logan analysis, and compartmental modelling of individual profiles) as well as by population mixed effects modelling (NONMEM). All data analysis approaches indicated only modest differences in brain distribution of (R)-[11C]verapamil between saline and kainate treated rats, while tariquidar treatment in both groups resulted in a more than 10-fold increase. NONMEM provided most precise parameter estimates. P-gp expression was found to be similar for kainate and saline treated rats. P-gp expression and functionality does not seem to change at early stage after induction of anticipated pharmacoresistant epilepsy by kainate

  3. Nonkonvulsif Status Epileptikus

    Ayhan AKÖZ; ÖZEL, Lütfi; Bayramoğlu, Atıf; Saritemur, Murat; Recep DEMİR; Zeynep GÖKCAN ÇAKIR

    2013-01-01

    Status epilepticus (SE) can be divided into two subgroups, convulsive status epilepticus (CSE) and nonconvulsive status epilepticus (NCSE). NCSE is clinically characterized by recurrence or persistence of absence or complex partial seizures which unconsciousness persists. Seizures are lasted more than 30 minutes, and accompanied by mental and behavioral changes. Although the main feature is the change of level of consciousness, affective, memory, cognitive, speech, motor systems, behavioral a...

  4. EEG Diagnosis and Clinical Treatment of Electrical Status Epilepticus during Sleep%睡眠中癫痫性电持续状态的脑电诊断及临床治疗

    曹晓春; 刘希娟; 丁勇民; 宋小华; 刘燕玲; 叶春风; 李国林; 刘洋; 龚丹

    2015-01-01

    目的:探讨睡眠中癫痫性电持续状态(electrical status epilepticus during sleep,ESES)的脑电诊断及临床治疗。方法脑电图棘慢波指数(SWI)≥50%并完成治疗的癫痫患儿30例(A 组16例:50%≤SWI<85%;B 组14例:SWI≥85%),按就诊顺序随机分为 C、D 2组,每组15例,行不同疗程(C 组6个月,D 组12个月)激素治疗,治疗前后均进行神经心理损伤评估,并随访治疗后的疗效及不良反应。结果A、B 2组治疗前均有程度不一的神经心理损伤,言语智商(VIQ)、操作智商(PIQ)及总智商(FIQ)均较正常值低,以 VIQ 下降最显著,B 组 VIQ 和 FIQ较 A 组低,差异有统计学意义(P <0.05);C、D 组 VIQ、FIQ 较激素治疗前均有增高(P <0.05),其中 ESES 消失者VIQ、FIQ 明显高于治疗前(P <0.05),但 C、D 2组间神经心理损伤改善程度及总有效率比较差异无统计学意义(P >0.05);D 组不良反应大于 C 组(P <0.05)。结论SWI≥50%定为 ESES 的脑电诊断标准有助于 ESES 的合理诊断,早期干预;激素治疗 ESES 安全有效,疗程6个月更合理。%ABSTRACT:Objective To investigate the EEG diagnosis and clinical treatment of electrical sta-tus epilepticus during sleep(ESES).Methods According to the spike-wave index(SWI),30 chil-dren with epilepsy were divided into group A(50% ≤ SWI0.05).Conclusion The criterion of SWI≥50%contributes to the reasonable diagnosis and early intervention of ESES.Hormone treatment for 6 months is effective and reasonable for ESES.

  5. Increased expression of the chemokines CXCL1 and MIP-1α by resident brain cells precedes neutrophil infiltration in the brain following prolonged soman-induced status epilepticus in rats

    Koemeter-Cox Andrew I

    2011-05-01

    Full Text Available Abstract Background Exposure to the nerve agent soman (GD causes neuronal cell death and impaired behavioral function dependent on the induction of status epilepticus (SE. Little is known about the maturation of this pathological process, though neuroinflammation and infiltration of neutrophils are prominent features. The purpose of this study is to quantify the regional and temporal progression of early chemotactic signals, describe the cellular expression of these factors and the relationship between expression and neutrophil infiltration in damaged brain using a rat GD seizure model. Methods Protein levels of 4 chemokines responsible for neutrophil infiltration and activation were quantified up to 72 hours in multiple brain regions (i.e. piriform cortex, hippocampus and thalamus following SE onset using multiplex bead immunoassays. Chemokines with significantly increased protein levels were localized to resident brain cells (i.e. neurons, astrocytes, microglia and endothelial cells. Lastly, neutrophil infiltration into these brain regions was quantified and correlated to the expression of these chemokines. Results We observed significant concentration increases for CXCL1 and MIP-1α after seizure onset. CXCL1 expression originated from neurons and endothelial cells while MIP-1α was expressed by neurons and microglia. Lastly, the expression of these chemokines directly preceded and positively correlated with significant neutrophil infiltration in the brain. These data suggest that following GD-induced SE, a strong chemotactic response originating from various brain cells, recruits circulating neutrophils to the injured brain. Conclusions A strong induction of neutrophil attractant chemokines occurs following GD-induced SE resulting in neutrophil influx into injured brain tissues. This process may play a key role in the progressive secondary brain pathology observed in this model though further study is warranted.

  6. Alpha-Linolenic Acid-Induced Increase in Neurogenesis is a Key Factor in the Improvement in the Passive Avoidance Task After Soman Exposure.

    Piermartiri, Tetsade C B; Pan, Hongna; Chen, Jun; McDonough, John; Grunberg, Neil; Apland, James P; Marini, Ann M

    2015-09-01

    Exposure to organophosphorous (OP) nerve agents such as soman inhibits the critical enzyme acetylcholinesterase (AChE) leading to excessive acetylcholine accumulation in synapses, resulting in cholinergic crisis, status epilepticus and brain damage in survivors. The hippocampus is profoundly damaged after soman exposure leading to long-term memory deficits. We have previously shown that treatment with three sequential doses of alpha-linolenic acid, an essential omega-3 polyunsaturated fatty acid, increases brain plasticity in naïve animals. However, the effects of this dosing schedule administered after a brain insult and the underlying molecular mechanisms in the hippocampus are unknown. We now show that injection of three sequential doses of alpha-linolenic acid after soman exposure increases the endogenous expression of mature BDNF, activates Akt and the mammalian target of rapamycin complex 1 (mTORC1), increases neurogenesis in the subgranular zone of the dentate gyrus, increases retention latency in the passive avoidance task and increases animal survival. In sharp contrast, while soman exposure also increases mature BDNF, this increase did not activate downstream signaling pathways or neurogenesis. Administration of the inhibitor of mTORC1, rapamycin, blocked the alpha-linolenic acid-induced neurogenesis and the enhanced retention latency but did not affect animal survival. Our results suggest that alpha-linolenic acid induces a long-lasting neurorestorative effect that involves activation of mTORC1 possibly via a BDNF-TrkB-mediated mechanism. PMID:25920465

  7. Salicylic acid-induced glutathione status in tomato crop and resistance to root-knot nematode, Meloidogyne incognita (Kofoid & White Chitwood

    Hari C. Meher

    2011-10-01

    Full Text Available Salicylic acid-(SA is a plant defense stimulator. Exogenous application of SA might influence the status of glutathione-(GSH. GSH activates and SA alters the expression of defense genes to modulate plant resistance against pathogens. The fate of GSH in a crop following SA treatment is largely unknown. The SA-induced profiles of free reduced-, free oxidized-(GSSG and protein bound-(PSSG glutathione in tomato crop following foliar treatment of transplant at 5.0-10.0 μg mL–1 were measured by liquid chromatography. Resistance to root-knot nematode, Meloidogyne incognita damaging tomato and crop performance were also evaluated. SA treatment at 5.0-10.0 μg mL–1 to tomato transplants increased GSH, GSSG and PSSG in plant leaf and root, more so in leaf, during crop growth and development. As the fruits ripened, GSH and PSSG increased and GSSG declined. SA reduced the root infection by M. incognita, nematode reproduction and thus, improved the resistance of tomato var. Pusa Ruby, but reduced crop growth and redox status. SA at 5.0 μg mL–1 improved yield and fruit quality. The study firstly linked SA with activation of glutathione metabolism and provided an additional dimension to the mechanism of induced resistance against obligate nematode pathogen. SA increased glutathione status in tomato crop, imparted resistance against M. incognita, augmented crop yield and functional food quality. SA can be applied at 5.0 μg mL–1 for metabolic engineering of tomato at transplanting to combine host-plant resistance and health benefits in formulating a strategic nematode management decision.

  8. 中老年复杂部分性发作癫痫持续状态的临床特征及误诊分析%Complex partial status epilepticus in the elderly: clinical features and causes of misdiagnosis

    刘晓蓉; 宋兴旺; 常好会; 王玉良; 邹欣

    2009-01-01

    Objective To investigate the clinical features and causes of misdiagnosis of complex partial status epilepticus (CPSE) in the elderly. Methods The clinical data of elderly patients with CPSE admitted in our department between January and December, 2008 with previous misdiagnosis were reviewed. The diagnosis of CPSE was established according to the diagnostic criteria of the International League Against Epilepsy (ILAE). All the patients underwent video-EEG examination, head magnetic resonance imaging (MRI), and routine biochemical examination, and were followed up for at least 3 months. Results Seven female CPSE patients were involved in this analysis including 2 with frontal lobe epilepsy and 5 with temporal lobe epilepsy. The conditions were misdiagnosed as a variety of diseases including Alzheimer's disease, cerebral infarction, coronary heart disease, encephalitis, hysterism, and schizophrenia, and the duration of the misdiagnoses ranged from 2 days to 40 years. Video-EEG showed slow background, continuous interictal discharges or high-voltage slow waves in the temporal or frontal lobe, or ictal discharges of complex partial seizures. After treatment with antiepileptic medications, 3 patients were free of epileptic episodes within 3 months, 3 still remained in complex partial status, and 1 had repeated CPSE. Conclusions Complex symptoms, atypical EEG, co-morbidity and social factors all contribute to misdiagnosis of CPSE in the elderly. Suspected patients should undergo video-EEG examination for a definite diagnosis as early as possible.%目的 分析中老年复杂部分性发作癫痫持续状态(CPSE)的临床特点及误诊原因.方法 收集广州医学院第二附属医院神经内科自2008年1月至12月收治、曾被外院误诊的中老年CPSE患者的临床资料,进行视频脑电图(EEG)、头颅MR、生化检查,根据国际抗癫痫联盟的CPSE诊断标准进行诊断,并随访3个月以上. 结果 本组患者7例,均

  9. Alterações agudas dos níveis de neurotransmissores em corpo estriado de ratos jovens após estado epiléptico induzido por pilocarpina Acute alterations of neurotransmitters levels in striatum of young rat after pilocarpine-induced status epilepticus

    Rivelilson Mendes de Freitas

    2003-06-01

    Full Text Available Altas doses de agonista colinérgico muscarínico, pilocarpina, produzem alterações comportamentais, convulsões e estado epiléptico em ratos. O objetivo desse estudo foi verificar as alterações nas concentrações dos neurotransmissores em corpo estriado de ratos em desenvolvimento após estado epiléptico induzido pela pilocarpina. Ratas Wistar foram tratadas com uma única dose de pilocarpina (400mg/Kg; s.c.. Controles receberam salina. A concentração dos neurotransmissores foi determinada através do HPLC, no corpo estriado de ratos que no período de observação de 1 e 24h desencadearam estado epiléptico e não sobreviveram à fase aguda do quadro convulsivo. Foi observada redução nos níveis de dopamina, serotonina, ácido dihidroxifenilacético, ácido 5-hidroxiindolacético, e aumento no ácido 4-hidroxi-3-metoxi-fenilacético. Os resultados mostraram que a ativação do sistema colinérgico pode interagir com os sistemas dopaminérgico e serotonérgico nos mecanismos referentes à fase aguda do processo convulsivo.High doses of the muscarinic cholinergic agonist, pilocarpine, result in behavioural changes, seizures and status epilepticus in rats. The purpose of the present work is to invetigate the striatal neurotransmissors level in young rats after status epilepticus induced by pilocarpine. Wistar rats were treated with a single dose of pilocarpine (400mg/Kg; s.c.. Controls received saline. Young animals were closed observed for behavioural changes during 1 and 24h. In these periods, the animals that developed status epilepticus and didn't survive this acute phase of seizures had the brains removed and striatal neurotransmissors level determined by HPLC. The concentration of dopamine, serotonine, dihydroxyphenylacetic acid, 5-hydroxyindolacetic acid was reduced and an increase in 4-hydroxy-3-methoxy-phenylacetic acid was observed. These results suggest that cholinergic activation can interage with dopaminergic and

  10. Neurogenesis and neuronal regeneration in status epilepticus

    Rotheneichner, Peter; Marschallinger, Julia; Couillard-Despres, Sebastien; Aigner, Ludwig

    2013-01-01

    Neurogenesis in the adult central nervous system has been well documented in several mammals including humans. By now, a plethora of data has been generated with the aim of understanding the molecular and cellular events governing neurogenesis. This growing comprehension will provide the basis for modulation of neurogenesis for therapeutic purposes, in particular in neurodegenerative diseases. Herein, we review the current knowledge on neurogenesis, in particular in the frame of epilepsy, sin...

  11. Behandlingsrefraktaert status epilepticus med letal rabdomyolyse

    Kreft, Andreas; Rasmussen, Niels; Hansen, Lars Kjaersgård

    2008-01-01

    approximately one day both developed severe rhabdomyolysis with progressive DIC and acute renal failure, causing death despite intensive care, including acute hemodialysis. The aim of this case report is to emphasise one of the rare but severe consequences of SE and also to suggest that patients with known...

  12. Hippocampal neuropathology of domoic acid-induced epilepsy in California sea lions (Zalophus californianus)

    Buckmaster, Paul S.; Wen, Xiling; TOYODA, Izumi; Gulland, Frances M. D.; Van Bonn, William

    2014-01-01

    California sea lions (Zalophus californianus) are abundant human-sized carnivores with large gyrencephalic brains. They develop epilepsy after experiencing status epilepticus when naturally exposed to domoic acid. We tested whether sea lions previously exposed to DA (chronic DA sea lions) display hippocampal neuropathology similar to that of human patients with temporal lobe epilepsy. Hippocampi were obtained from control and chronic DA sea lions. Stereology was used to estimate numbers of Ni...

  13. Establishment of post-status epilepticus model of temporal lobe epilepsy induced by electrical stimulation of the amygdala in rats and spontaneous recurrent seizures%大鼠杏仁核电刺激癫痫持续状态模型的建立及其自发性反复癫痫发作的研究

    齐兆鹏; 金澎; 刘占涛; 孙鹏; 苏明明

    2011-01-01

    Objective To establish a reliable post-status epilepticus model of temporal lobe epilepsy in rats that mimics human temporal lobe epilepsy, and observe the occurrence of spontaneous recurrent seizures (SRS). Methods Status epilepticus which was monitored for 3 h was induced by a 20-min stimulation of the amygdala ( 100 ms train of 1 ms, 60 Hz bipolar pulses, 400 μA, every 0. 5 s). Stimulated rats ( n =21 ) were monitored with a video recording system for the 3-months follow-up period to record the appearance of SRS. Results SRS (total number 181 ) were detected in 14 of the 21 animals (67%) after a latency period of 8 to 73 days (mean 43 days), including 10 times of stage 3 seizure (5.53%), 77 times of stage 4 seizure (42. 54% ), and 94 times of stage 5 seizure (51.93%). Of all the 14 rats, the seizure number beyond 30 was observed in 3 animals, from 20 to 30 in one animal, from 10 to 20 in 2 animals, between 5 and 10 in 2 animals, and less than 5 in 6 animals. Seventy-three percent of SRS appeared during daytime (07: 00-19: 00) and 74 percent of secondarily generalized seizures occurred during daytime. Conclusion This study has been successfully designed to develop a post-status epilepticus animal model induced by electrical stimulation of the amygdale.%目的 建立癫痫持续状态后颞叶癫痫模型,观察大鼠自发性反复发作(SRS)。方法 持续电刺激大鼠杏仁核20 min(单相方波,强度400μA,波宽1 ms,串长100 ms,串隔0.5s,频率60Hz)引发癫痫持续状态(SE),随后进行3h的SE观察,包括大鼠行为表现和脑电变化。SE状态引出后,进行3个月的视频监测,观察大鼠自发性发作的发作情况并进行分组。结果 经过为期3个月的视频观察,出现SRS14只(67%);未出现者7只(33%)。共记录到3~5级发作181次。其中3级发作10次(5.53%),4级发作77次(42.54%),5级发作94次(51.93%)。发作在30次以上者3只;20 ~ 30次者1只;10 ~20次者2只,5~10次者2只;5

  14. Valproic Acid Induced Hyperammonaemic Encephalopathy

    Objective: To observe clinical and laboratory features of valproic acid-induced hyperammonaemic encephalopathy in patients taking valproic acid. Methods: Observational study was conducted at the Neurology Department, Dow University of Health Sciences, Civil Hospital, Karachi, from February 26, 2010 to March 20, 2011. Ten patients on valproic acid therapy of any age group with idiopathic or secondary epilepsy, who presented with encephalopathic symptoms, were registered and followed up during the study. Serum ammonia level, serum valproic acid level, liver function test, cerebrospinal fluid examination, electroencephalogram and brain imaging of all the patients were done. Other causes of encephalopathy were excluded after clinical and appropriate laboratory investigations. Microsoft Excel 2007 was used for statistical analysis. Results: Hyperammonaemia was found in all patients with encephalopathic symptoms. Rise in serum ammonia was independent of dose and serum level of valproic acid. Liver function was also found to be normal in 80% (n=8) of the patients. Valproic acid was withdrawn in all patients. Three (30%) patients improved only after the withdrawal of valproic acid. Six (60%) patients improved after L-Carnitine replacement, one (10%) after sodium benzoate. On followup, serum ammonia had reduced to normal in five (50%) patients and to more than half of the baseline level in two (20%) patients. Three (30%) patients were lost to followup after complete clinical improvement. Conclusion: Within therapeutic dose and serum levels, valproic acid can cause symptomatic hyperammonaemia resulting in encephalopathy. All patients taking valproic acid presenting with encephalopathic symptoms must be monitored for the condition. (author)

  15. FREQUENCY, ETIOLOGY AND IMMEDIATE OUTCOME OF CHILDREN ADMITTED TO PEDIATRIC INTENSIVE CARE UNIT (PICU) WITH CONVULSIVE STATUS EPI LEPTICUS IN KASHMIR NORTH INDIA

    Muzafar; Suhail; Sartaj; Waseem; Aliya; Mudasir

    2015-01-01

    BACKGROUND: Convulsive status epilepticus (CSE) is one of the common causes of childhood hospitalization to PICU with significant morbidity and mortality. Objective of current study was to know the Frequency, etiology and immediate outcome of children admitted to Pediatric Intensive Care Unit (PICU) with convulsive Status Epilepticus in Kashmir Nor...

  16. Valproic acid induced pancreatitis: a case report

    Bhupen Barman

    2014-08-01

    Full Text Available Valproic acid is a commonly used antiepileptic drug. Apart from its common side effect there is definite association between valproic acid therapy and acute pancreatitis. Since 1979, many cases of acute pancreatitis induced by valproic acid have been published in medical literature. Here we are reporting a case of valproic acid induced acute pancreatitis in a 27 years old boy. The treatment is supportive, re-challenge is hazardous and should be avoided. [Int J Res Med Sci 2014; 2(4.000: 1765-1767

  17. Mefenamic Acid Induced Nephrotoxicity: An Animal Model

    Muhammad Nazrul Somchit

    2014-12-01

    Full Text Available Purpose: Nonsteroidal anti-inflammatory drugs (NSAIDs are used for the treatment of many joint disorders, inflammation and to control pain. Numerous reports have indicated that NSAIDs are capable of producing nephrotoxicity in human. Therefore, the objective of this study was to evaluate mefenamic acid, a NSAID nephrotoxicity in an animal model. Methods: Mice were dosed intraperitoneally with mefenamic acid either as a single dose (100 or 200 mg/kg in 10% Dimethyl sulfoxide/Palm oil or as single daily doses for 14 days (50 or 100 mg/kg in 10% Dimethyl sulfoxide/Palm oil per day. Venous blood samples from mice during the dosing period were taken prior to and 14 days post-dosing from cardiac puncture into heparinized vials. Plasma blood urea nitrogen (BUN and creatinine activities were measured. Results: Single dose of mefenamic acid induced mild alteration of kidney histology mainly mild glomerular necrosis and tubular atrophy. Interestingly, chronic doses induced a dose dependent glomerular necrosis, massive degeneration, inflammation and tubular atrophy. Plasma blood urea nitrogen was statistically elevated in mice treated with mefenamic acid for 14 days similar to plasma creatinine. Conclusion: Results from this study suggest that mefenamic acid as with other NSAIDs capable of producing nephrotoxicity. Therefore, the study of the exact mechanism of mefenamic acid induced severe nephrotoxicity can be done in this animal model.

  18. Status of memory loss.

    Iyer, Parameswaran Mahadeva

    2012-01-01

    A 72-year-old woman presented with first onset of seizure with no prior history of cognitive dysfunction. EEG revealed focal non-convulsive status epilepticus. MRI brain showed a left temporal non-enhancing lesion. Temporal pole biopsy showed acute neuronal necrosis and astrocyte hyperplasia together with extensive amyloid plaques and neurofibrillary tangles. Perivascular oligodendroglial hyperplasia was present. Postmortem examination revealed extensive plaque and tangle disease. Perivascular oligodendroglial hyperplasia was limited to the left temporal area. The presence of focal perivascular oligodendroglial hyperplasia in the left temporal cortex, combined with extensive plaque and tangle disease may have contributed to the focal status epilepticus in this patient. Although the presence of focal perivascular oligodendroglial hyperplasia has been reported in cases of temporal lobe epilepsy, it has not been reported as a cause of seizure in patients with Alzheimer\\'s disease previously. Further studies for clinical-pathologic correlation would be required to confirm this hypothesis.

  19. Clinical Characteristics and Prognosis of Idiopathic Occipital Epilepsy and Electrical Status Epilepticus in Sleeping Children%特发性儿童枕叶癫(癎)伴睡眠期癫(癎)性电持续状态的临床特征及预后

    张胜; 罗序峰; 付四毛; 朱建平; 吴涛

    2012-01-01

    Objective To investigate the clinical manifestations, electroencephalogram(EEG) characteristics, treatment response and prognosis of children with idiopathic occipital epilepsy and electrical status epilepticus in sleep (ESES) . Methods Clinical and EEG data of 8 cases with idiopathic occipital epilepsy and ESES were analyzed together with follow - up for treatment and prognosis. Results The onset age varied from 5 years and 8 months to 8 years and 4 months in the 8 cases. All the 8 cases had neuropsychological injury and motor regression, but had no history of family epilepsy and clear abnormalities by brain imaging examination. Seven patients had seizures, performing exercise - induced limited seizures after waking up; seizures could also attack during awaking period ,including exercise - induced limited seizures (5/7 cases) and overall tonic -clonic seizures (2/7 cases). Antiepileptic drugs (AEDs) reduced attacks in 4 cases,but did not improve the psychological damage to nerve and motor rcgression obviously. Mild improvement in neuropsychological injury and EEG were observed in 3 cases treated with single drug Oxcarbazepine ( OXC). Six cases, who were treated with intravenous methylprednisolone shock therapy, had ideal control, and 1 case had marked improvement of nerve injury and psychological setback in movement. Eight patients were followed up by EEG for 0. 5 -2. 0 years,and 2 cases improved in ESES phenomenon. Up to follow - up,the 8 cases of patients still had mental retardation compared with healthy children in the same age. Conclusions Idiopathic occipital epilepsy is an age - dependent benign epilepsy in children; AEDs are often ineffective when the EEG showes ESES of the patients; hormones can reduce the clinical attack, but can not improve the psychological nerve damage and phenomenon of EEG ESES. Children with poor response to corticosteroids can be treated with OXC monothe-rapy or combined therapy.%目的 探讨特发性枕叶癫(癎)伴睡眠期

  20. Transient changes in the limbic histaminergic system after systemic kainic acid-induced seizures.

    Lintunen, Minnamaija; Sallmen, Tina; Karlstedt, Kaj; Panula, Pertti

    2005-10-01

    Increased brain histamine is reported to protect against convulsions. We used systemic kainic acid (KA) administration to study possible changes of the histaminergic system in rat brain in status epilepticus (SE). Robust increases in brain histamine concentrations and numbers of histamine-immunoreactive nerve fibers were detected in the piriform cortex (Pir) and amygdala after KA injection, suggesting a reactive increase, which is opposite to other published aminergic transmitter responses. These changes, lasting several weeks, might be coupled to a mechanism unrelated to the anticonvulsive function of histamine. Transient increases in mRNA expression of H(3) receptor isoforms with a full-length third intracellular loop, coupled to mitogen-activated protein kinase pathway, were detected first in the hippocampal CA3c area, followed by the Pir and amygdala and then the hippocampal CA1 area. These results suggest that histamine and H3 receptors, which also control the release of GABA and glutamate, might be involved in convulsive SE. PMID:16137576

  1. Absence status associated with focal activity and polydipsia-induced hyponatremia

    Azuma, Hideki

    2008-01-01

    Hideki Azuma, Tatsuo Akechi, Toshi A FurukawaDepartment of Psychiatry and Cognitive-Behavioral Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, JapanAbstract: We report a case of de novo absence status associated with focal discharge and polydipsia-induced hyponatremia. Nonconvulsive status epilepticus (NCSE) is classified as absence status or complex partial status. Absence status is characterized by bilateral synchronized spike and wave complex bursts and a vari...

  2. Acid-induced changes of brain protein buffering

    Kraig, Richard P.; Wagner, Robert J.

    1987-01-01

    Excessive cellular acidosis is thought to enhance destruction of brain from ischemia. Protein denaturation may contribute to such injury although the behavior of brain proteins to acidosis is poorly defined. As a first approach to detect acid-induced changes in brain proteins and to characterize buffer content, homogenates were acidified for 20 min (as low as pH 3.1), returned to baseline pH (6.9), and then titrated. Titration curves show a significant (P < 0.0001) and permanent increase in b...

  3. Increased isoprostane levels in oleic acid-induced lung injury

    Ono, Koichi [Department of Anesthesiology and Resuscitation, Shinshu University School of Medicine, Matsumoto (Japan); Koizumi, Tomonobu, E-mail: tomonobu@shinshu-u.ac.jp [First Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto (Japan); Tsushima, Kenji; Yoshikawa, Sumiko; Yokoyama, Toshiki [First Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto (Japan); Nakagawa, Rikimaru [Department of Anesthesiology and Resuscitation, Shinshu University School of Medicine, Matsumoto (Japan); Obata, Toru [Department of Molecular Cell Biology, Institute of DNA Medicine, Jikei University School of Medicine, Tokyo (Japan)

    2009-10-16

    The present study was performed to examine a role of oxidative stress in oleic acid-induced lung injury model. Fifteen anesthetized sheep were ventilated and instrumented with a lung lymph fistula and vascular catheters for blood gas analysis and measurement of isoprostanes (8-epi prostaglandin F2{alpha}). Following stable baseline measurements, oleic acid (0.08 ml/kg) was administered and observed 4 h. Isoprostane was measured by gas chromatography mass spectrometry with the isotope dilution method. Isoprostane levels in plasma and lung lymph were significantly increased 2 h after oleic acid administration and then decreased at 4 h. The percent increases in isoprostane levels in plasma and lung lymph at 2 h were significantly correlated with deteriorated oxygenation at the same time point, respectively. These findings suggest that oxidative stress is involved in the pathogenesis of the pulmonary fat embolism-induced acute lung injury model in sheep and that the increase relates with the deteriorated oxygenation.

  4. Metformin protects rat hepatocytes against bile acid-induced apoptosis.

    Titia E Woudenberg-Vrenken

    Full Text Available BACKGROUND: Metformin is used in the treatment of Diabetes Mellitus type II and improves liver function in patients with non-alcoholic fatty liver disease (NAFLD. Metformin activates AMP-activated protein kinase (AMPK, the cellular energy sensor that is sensitive to changes in the AMP/ATP-ratio. AMPK is an inhibitor of mammalian target of rapamycin (mTOR. Both AMPK and mTOR are able to modulate cell death. AIM: To evaluate the effects of metformin on hepatocyte cell death. METHODS: Apoptotic cell death was induced in primary rat hepatocytes using either the bile acid glycochenodeoxycholic acid (GCDCA or TNFα in combination with actinomycin D (actD. AMPK, mTOR and phosphoinositide-3 kinase (PI3K/Akt were inhibited using pharmacological inhibitors. Apoptosis and necrosis were quantified by caspase activation, acridine orange staining and Sytox green staining respectively. RESULTS: Metformin dose-dependently reduces GCDCA-induced apoptosis, even when added 2 hours after GCDCA, without increasing necrotic cell death. Metformin does not protect against TNFα/ActD-induced apoptosis. The protective effect of metformin is dependent on an intact PI3-kinase/Akt pathway, but does not require AMPK/mTOR-signaling. Metformin does not inhibit NF-κB activation. CONCLUSION: Metformin protects against bile acid-induced apoptosis and could be considered in the treatment of chronic liver diseases accompanied by inflammation.

  5. Sphingoid bases inhibit acid-induced demineralization of hydroxyapatite.

    Valentijn-Benz, Marianne; van 't Hof, Wim; Bikker, Floris J; Nazmi, Kamran; Brand, Henk S; Sotres, Javier; Lindh, Liselott; Arnebrant, Thomas; Veerman, Enno C I

    2015-01-01

    Calcium hydroxyapatite (HAp), the main constituent of dental enamel, is inherently susceptible to the etching and dissolving action of acids, resulting in tooth decay such as dental caries and dental erosion. Since the prevalence of erosive wear is gradually increasing, there is urgent need for agents that protect the enamel against erosive attacks. In the present study we studied in vitro the anti-erosive effects of a number of sphingolipids and sphingoid bases, which form the backbone of sphingolipids. Pretreatment of HAp discs with sphingosine, phytosphingosine (PHS), PHS phosphate and sphinganine significantly protected these against acid-induced demineralization by 80 ± 17%, 78 ± 17%, 78 ± 7% and 81 ± 8%, respectively (p < 0.001). On the other hand, sphingomyelin, acetyl PHS, octanoyl PHS and stearoyl PHS had no anti-erosive effects. Atomic force measurement revealed that HAp discs treated with PHS were almost completely and homogeneously covered by patches of PHS. This suggests that PHS and other sphingoid bases form layers on the surface of HAp, which act as diffusion barriers against H(+) ions. In principle, these anti-erosive properties make PHS and related sphingosines promising and attractive candidates as ingredients in oral care products. PMID:25300299

  6. Rare presentation of a common disease: Idiopathic hypoparathyroidism presenting with extrapyramidal symptoms and status epilepticus

    Kaushik Ghosh

    2012-01-01

    Full Text Available We report of an 18-year-old male who presented with an epileptiform disorder, features of hypocalcemia, and an extrapyramidal symptom in the form of choreoathetosis. On evaluation he had idiopathic hypoparathyroidism with extensive calcifications in the extrapyramidal system of the brain; basal ganglion, as well as in the cerebral cortex and cerebellum, which is a rare entity. We report the rare presentation of a common disorder, which requires to be considered in evaluating hypoparathyroidism.

  7. Status epilepticus induces changes in the expression and localization of endogenous palmitoyl-protein thioesterase 1.

    Suopanki, J; Lintunen, M; Lahtinen, H; Haltia, M; Panula, P; Baumann, M; Tyynelä, J

    2002-08-01

    Kainic acid (KA)-induced experimental epilepsy, a model of excitotoxicity, leads to selective neuronal death and synaptic restructuring. We used this model to investigate the effects of neuronal hyperactivation on palmitoyl-protein thioesterase 1 (PPT1), the deficiency of which causes drastic neurodegeneration. Immunological stainings showed that epileptic seizures in adult rats led to a progressive and remarkable increase of PPT1 in limbic areas of the brain. Within 1 week, the maximal expression was observed in CA3 and CA1 pyramidal neurons of the hippocampus. In the surviving pyramidal neurons, PPT1 localized in vesicular structures in cell soma and neuritic extensions. After seizures, colocalization of PPT1 with synaptic membrane marker (NMDAR2B) was enhanced. Further, synaptic fractionation revealed that after seizures PPT1 was readily observed on the presynaptic side of synaptic junction. These data suggest that PPT1 may protect neurons from excitotoxicity and have a role in synaptic plasticity. PMID:12270687

  8. Squamous Cell Lung Carcinoma Presenting With Refractory Status Epilepticus: A Case Report of Paraneoplastic Limbic Encephalitis.

    Hurley, Killian; Herron, Malcolm; McDermott, Sean; Farrell, Terence; O'Riordan, Deirdre

    2015-08-01

    Lung cancer-associated paraneoplastic syndromes affecting the central nervous system present significant diagnostic and treatment challenges. In this case, the patient presented with personality change, cognitive impairment, complex partial seizures, ataxia, dyspraxia, and dysphasia. Shortly after admission, the patient suffered refractory generalized tonic-clonic seizures and a decreased level of consciousness and required intubation, ventilation, and admission to the ICU. He was subsequently diagnosed with paraneoplastic limbic encephalitis based on recognized criteria, including a compatible clinical picture, elevated protein content in his cerebrospinal fluid with negative cytology, a positive positron emission tomography-computed tomography scan showing a right upper lobe tumor, and the exclusion of other neuro-oncological complications. Histopathology confirmed the tissue diagnosis as squamous cell cancer. Initial immunotherapy with steroids and intravenous immunoglobulin and subsequent lobectomy and adjuvant chemotherapy were partially successful, leading to partial resolution of his cognitive impairment. This report highlights the diagnostic and therapeutic challenges of lung-related paraneoplastic syndromes. In addition, it illustrates the poor outcomes for patients and identifies squamous cell cancer as an extremely rare cause of paraneoplastic limbic encephalitis. PMID:25784771

  9. Delays and Factors Related to Cessation of Generalized Convulsive Status Epilepticus.

    Kämppi, Leena; Ritvanen, Jaakko; Mustonen, Harri; Soinila, Seppo

    2015-01-01

    Introduction. This study was designed to identify the delays and factors related to and predicting the cessation of generalized convulsive SE (GCSE). Methods. This retrospective study includes 70 consecutive patients (>16 years) diagnosed with GCSE and treated in the emergency department of a tertiary hospital over 2 years. We defined cessation of SE stepwise using clinical seizure freedom, achievement of burst-suppression, and return of consciousness as endpoints and calculated delays for these cessation markers. In addition 10 treatment delay parameters and 7 prognostic and GCSE episode related factors were defined. Multiple statistical analyses were performed on their relation to cessation markers. Results. Onset-to-second-stage-medication (p = 0.027), onset-to-burst-suppression (p = 0.005), and onset-to-clinical-seizure-freedom (p = 0.035) delays correlated with the onset-to-consciousness delay. We detected no correlation between age, epilepsy, STESS, prestatus period, type of SE onset, effect of the first medication, and cessation of SE. Conclusion. Our study demonstrates that rapid administration of second-stage medication and early obtainment of clinical seizure freedom and burst-suppression predict early return of consciousness, an unambiguous marker for the end of SE. We propose that delays in treatment chain may be more significant determinants of SE cessation than the previously established outcome predictors. Thus, streamlining the treatment chain is advocated. PMID:26347816

  10. Delays and Factors Related to Cessation of Generalized Convulsive Status Epilepticus

    Leena Kämppi

    2015-01-01

    Full Text Available Introduction. This study was designed to identify the delays and factors related to and predicting the cessation of generalized convulsive SE (GCSE. Methods. This retrospective study includes 70 consecutive patients (>16 years diagnosed with GCSE and treated in the emergency department of a tertiary hospital over 2 years. We defined cessation of SE stepwise using clinical seizure freedom, achievement of burst-suppression, and return of consciousness as endpoints and calculated delays for these cessation markers. In addition 10 treatment delay parameters and 7 prognostic and GCSE episode related factors were defined. Multiple statistical analyses were performed on their relation to cessation markers. Results. Onset-to-second-stage-medication (p=0.027, onset-to-burst-suppression (p=0.005, and onset-to-clinical-seizure-freedom (p=0.035 delays correlated with the onset-to-consciousness delay. We detected no correlation between age, epilepsy, STESS, prestatus period, type of SE onset, effect of the first medication, and cessation of SE. Conclusion. Our study demonstrates that rapid administration of second-stage medication and early obtainment of clinical seizure freedom and burst-suppression predict early return of consciousness, an unambiguous marker for the end of SE. We propose that delays in treatment chain may be more significant determinants of SE cessation than the previously established outcome predictors. Thus, streamlining the treatment chain is advocated.

  11. Brain metabolism and diffusion in the rat cerebral cortex during pilocarpine-induced status epilepticus

    Šlais, Karel; Voříšek, Ivan; Zoremba, N.; Homola, Aleš; Dmytrenko, Lesia; Syková, Eva

    2008-01-01

    Roč. 209, č. 1 (2008), s. 145-154. ISSN 0014-4886 R&D Projects: GA MŠk 1M0538; GA MŠk(CZ) LC554 Grant ostatní: EU(DE) 512146 Institutional research plan: CEZ:AV0Z50390512; CEZ:AV0Z50390703 Source of funding: R - rámcový projekt EK Keywords : Diffusion * Microdialysis * Pilocarpine Subject RIV: FH - Neurology Impact factor: 3.974, year: 2008

  12. Nonconvulsive status epilepticus and Creutzfeldt–Jakob-like EEG changes in a case of lithium toxicity

    B.K. Madhusudhan

    2014-01-01

    This case highlights the importance of therapeutic drug-level monitoring of lithium, especially where toxicity is suspected, and the important role electroencephalography plays in diagnosing NCSE and its management.

  13. Hyperthermia aggravates status epilepticus-induced epileptogenesis and neuronal loss in immature rats

    Suchomelová, L.; Lopes-Meraz, M. L.; Niquet, J.; Kubová, Hana; Wasterlain, C. G.

    2015-01-01

    Roč. 305, Oct 1 (2015), s. 209-224. ISSN 0306-4522 R&D Projects: GA ČR(CZ) GAP302/10/0971; GA MŠk(CZ) ME08045; GA MŠk(CZ) LC554 Institutional support: RVO:67985823 Keywords : neuronal injury * temperature * immature brain * lithium/pilocarpine model * EEG monitoring Subject RIV: FH - Neurology Impact factor: 3.357, year: 2014

  14. Status epilepticus in immature rats leads to behavioural and cognitive impairment and epileptogenesis

    Kubová, Hana; Mareš, Pavel; Suchomelová, Lucie; Brožek, Gustav; Druga, Rastislav; Pitkanen, A.

    2004-01-01

    Roč. 19, č. 12 (2004), s. 3255-3265. ISSN 0953-816X R&D Projects: GA MZd NF6474; GA ČR GA309/01/0285 Institutional research plan: CEZ:AV0Z5011922 Keywords : epilepsy * elevated plus-maze * Morris water-maze Subject RIV: FH - Neurology Impact factor: 3.820, year: 2004

  15. Interstrain differences in cognitive functions in rats in relation to status epilepticus

    Hort, J.; Brožek, Gustav; Komárek, V.; Langmeier, M.; Mareš, Pavel

    2000-01-01

    Roč. 112, - (2000), s. 77-83. ISSN 0166-4328 R&D Projects: GA MZd IZ2904; GA MZd IZ3510; GA AV ČR KSK2011602 Grant ostatní: GA UK(XC) 25/1966 Subject RIV: ED - Physiology Impact factor: 2.263, year: 2000

  16. The BRPF2/BRD1-MOZ complex is involved in retinoic acid-induced differentiation of embryonic stem cells.

    Cho, Hye In; Kim, Min Seong; Jang, Yeun Kyu

    2016-08-01

    The scaffold protein BRPF2 (also called BRD1), a key component of histone acetyltransferase complexes, plays an important role in embryonic development, but its function in the differentiation of embryonic stem cells (ESCs) remains unknown. In the present study, we investigated whether BRPF2 is involved in mouse ESC differentiation. BRPF2 depletion resulted in abnormal formation of embryoid bodies, downregulation of differentiation-associated genes, and persistent maintenance of alkaline phosphatase activity even after retinoic acid-induced differentiation, indicating impaired differentiation of BRPF2-depleted ESCs. We also found reduced global acetylation of histone H3 lysine 14 (H3K14) in BRPF2-depleted ESCs, irrespective of differentiation status. Further, co-immunoprecipitation analysis revealed a physical association between BRPF2 and the histone acetyltransferase MOZ in differentiated ESCs, suggesting the role of BRPF2-MOZ complexes in ESC differentiation. Together, these results suggest that BRPF2-MOZ complexes play an important role in the differentiation of ESCs via H3K14 acetylation. PMID:27256846

  17. The role of MAPK signalling pathways in acetic acid-induced cell death of Saccharomyces cerevisiae

    Azevedo, Flávio Humberto Torres Dias Feio de

    2011-01-01

    Dissertação de mestrado em Genética Molecular Mitogenic Activated Protein Kinase (MAPK) cascades are important signalling pathways that allow yeast cells to swiftly adapt to changing environmental conditions. Previous studies suggested that the High Osmolarity Glycerol (HOG) MAPK pathway and ceramide production are involved in acetic-acid induced apoptosis in yeast. Evidence that changes in the levels of endogenous ceramides can affect yeast cell fate has also been put forth...

  18. Acid mediates a prolonged antinociception via substance P signaling in acid-induced chronic widespread pain

    Chen, Wei-Nan; Chen, Chih-Cheng

    2014-01-01

    Background Substance P is an important neuropeptide released from nociceptors to mediate pain signals. We recently revealed antinociceptive signaling by substance P in acid-sensing ion channel 3 (ASIC3)-expressing muscle nociceptors in a mouse model of acid-induced chronic widespread pain. However, methods to specifically trigger the substance P antinociception were still lacking. Results Here we show that acid could induce antinociceptive signaling via substance P release in muscle. We preve...

  19. Mefenamic acid-induced neutropenia and renal failure in elderly females with hypothyroidism.

    Handa, S I; FREESTONE, S.

    1990-01-01

    We report mefenamic acid-induced non-oliguric renal failure and severe neutropenia occurring simultaneously in two elderly females. The neutropenia was due to maturation arrest of the myeloid series in one patient. Both patients were also hypothyroid, but it is not clear whether this was a predisposing factor to the development of these adverse reactions. However, it would seem prudent not to use mefenamic acid in hypothyroid patients until the hypothyroidism has been corrected.

  20. Minocycline ameliorates prenatal valproic acid induced autistic behaviour, biochemistry and blood brain barrier impairments in rats.

    Kumar, Hariom; Sharma, Bhupesh

    2016-01-01

    Autism is a neurodevelopment disorder. One percent worldwide population suffers with autism and males suffer more than females. Microglia plays an important role in neurodevelopment, neuropsychiatric and neurodegenerative disorders. The present study has been designed to investigate the role of minocycline in prenatal valproic acid induced autism in rats. Animals with prenatal valproic acid have reduced social interaction (three chamber social behaviour apparatus), spontaneous alteration (Y-Maze), exploratory activity (Hole board test), intestinal motility, serotonin levels (both in prefrontal cortex and ileum) and prefrontal cortex mitochondrial complex activity (complexes I, II, IV). Furthermore, prenatal valproic acid treated animals have shown an increase in locomotion (actophotometer), anxiety (elevated plus maze), brain oxidative stress (thiobarbituric acid reactive species, glutathione, catalase), nitrosative stress (nitrite/nitrate), inflammation (both in brain and ileum myeloperoxidase activity), calcium and blood brain barrier permeability. Treatment with minocycline significantly attenuated prenatal valproic acid induced reduction in social interaction, spontaneous alteration, exploratory activity intestinal motility, serotonin levels and prefrontal cortex mitochondrial complex activity. Furthermore, minocycline has also attenuated prenatal valproic acid induced increase in locomotion, anxiety, brain oxidative and nitrosative stress, inflammation, calcium and blood brain barrier permeability. Thus, it may be concluded that prenatal valproic acid has induced autistic behaviour, biochemistry and blood brain barrier impairment in animals, which were significantly attenuated by minocycline. Minocycline should be explored further for its therapeutic benefits in autism. PMID:26551768

  1. Tiagabine: efficacy and safety in partial seizures – current status

    Jürgen Bauer

    2008-09-01

    Full Text Available Jürgen Bauer, Déirdre Cooper-MahkornDepartment of Epileptology, Bonn University Hospital, GermanyAbstract: Tiagabine hydrochloride (TGB is a selective gamma-aminobutyric acid (GABA reuptake inhibitor. TGB is effective as an add-on medication in adults and children 12 years and older in the treatment of partial seizures. Results of nonrandomized add-on trials with TGB show treatment success with seizure reduction of at least 50% in 33% to 46% of patients. In newly diagnosed patients with partial epilepsy, TGB monotherapy was as effective as carbamazepine. Comedication with TGB elevates the risk of nonconvulsive status (7.8% vs 2.7% without TGB. The most common side effects include dizziness/lightheadedness, asthenia/lack of energy and somnolence. TGB has no negative effects on cognition; it does not increase the risk of fractures or rash. TGB may interfere with color perception. TGB presents an intermediate risk for depression in patients with epilepsy (approximately 4%. Regarding the risk of overdose, 96–680 mg TGB (mean 224 mg caused seizures or coma. TGB is an antiepileptic drug exhibiting a specific anticonvulsive mechanism of action, the efficacy of which is relatively low when used in comedication. Critical side effects, such as the induction of nonconvulsive status epilepticus, further limit its use.Keywords: epilepsy, tiagabine, antiepileptic drugs, status epilepticus, pharmacotherapy

  2. Salivary a-amylase protects enamel surface against acid induced softening

    Lazovic, Maja Bruvo; Moe, Dennis; Kirkeby, Svend;

    -TOF mass fingerprinting following trypsin digestion. Each persistent peak in the HPLC chromatograms was related to the protective effect against acid-induced enamel softening obtained by the corresponding saliva sample by multiple regression analysis. Results: One peak identified as a-amylase had an...... explanatory power of 39% in the analysis with high concentrations being most protective (p<0.001). In addition, a smaller peak retrieved later in the chromatograms also had a strong protective effect. Inclusion of this peak in the analysis increased the explanatory power of amylase on protective effect to 65...

  3. Reduction of sodium deoxycholic acid-induced scratching behaviour by bradykinin B2 receptor antagonists

    Hayashi, Izumi; Majima, Masataka

    1999-01-01

    Subcutaneous injection of sodium deoxycholic acid into the anterior of the back of male ddY mice elicited dose-dependent scratching of the injected site with the forepaws and hindpaws.Up to 100 μg of sodium deoxycholic acid induced no significant increase in vascular permeability at the injection site as assessed by a dye leakage method.Bradykinin (BK) B2 receptor antagonists, FR173657 and Hoe140, significantly decreased the frequency of scratching induced by sodium deoxycholic acid.Treatment...

  4. DECREASED APOPTOSIS DURING CAR-MEDIATED HEPATOPROTECTION AGAINST LITHOCHOLIC ACID-INDUCED LIVER INJURY IN MICE

    Beilke, Lisa D.; Aleksunes, Lauren M.; Olson, Erik R.; Besselsen, David G; Klaassen, Curtis D.; Dvorak, Katerina; Cherrington, Nathan J.

    2009-01-01

    Myeloid cell leukemia-1 (Mcl-1) is an anti-apoptotic protein that is regulated by the constitutive androstane receptor (CAR). Activation of CAR can protect the liver against bile acid-induced toxicity and it may have a role in cell death via apoptosis by altering expression of Bcl-2 family proteins such as myeloid cell leukemia-1 (Mcl-1). Our aim was to determine if activation of CAR reduces hepatocellular apoptosis during cholestasis as a mechanism of hepatoprotection. CAR+/+ (WT) and CAR−/−...

  5. Luteolin prevents uric acid-induced pancreatic β-cell dysfunction

    Ding, Ying; Shi, Xuhui; Shuai, Xuanyu; Xu, Yuemei; Liu, Yun; Liang, Xiubin; Wei, Dong; Su, Dongming

    2014-01-01

    Abstract Elevated uric acid causes direct injury to pancreatic β-cells. In this study, we examined the effects of luteolin, an important antioxidant, on uric acid-induced β-cell dysfunction. We first evaluated the effect of luteolin on nitric oxide (NO) formation in uric acid-stimulated Min6 cells using the Griess method. Next, we performed transient transfection and reporter assays to measure transcriptional activity of nuclear factor (NF)-κB. Western blotting assays were also performed to a...

  6. Polyunsaturated Branched-Chain Fatty Acid Geranylgeranoic Acid Induces Unfolded Protein Response in Human Hepatoma Cells.

    Chieko Iwao

    Full Text Available The acyclic diterpenoid acid geranylgeranoic acid (GGA has been reported to induce autophagic cell death in several human hepatoma-derived cell lines; however, the molecular mechanism for this remains unknown. In the present study, several diterpenoids were examined for ability to induce XBP1 splicing and/or lipotoxicity for human hepatoma cell lines. Here we show that three groups of diterpenoids emerged: 1 GGA, 2,3-dihydro GGA and 9-cis retinoic acid induce cell death and XBP1 splicing; 2 all-trans retinoic acid induces XBP1 splicing but little cell death; and 3 phytanic acid, phytenic acid and geranylgeraniol induce neither cell death nor XBP1 splicing. GGA-induced ER stress/ unfolded protein response (UPR and its lipotoxicity were both blocked by co-treatment with oleic acid. The blocking activity of oleic acid for GGA-induced XBP1 splicing was not attenuated by methylation of oleic acid. These findings strongly suggest that GGA at micromolar concentrations induces the so-called lipid-induced ER stress response/UPR, which is oleate-suppressive, and shows its lipotoxicity in human hepatoma cells.

  7. Obestatin Accelerates the Healing of Acetic Acid-Induced Colitis in Rats

    Aleksandra Matuszyk

    2016-01-01

    Full Text Available Obestatin, a 23-amino acid peptide derived from the proghrelin, has been shown to exhibit some protective and therapeutic effects in the gut. The aim of present study was to determine the effect of obestatin administration on the course of acetic acid-induced colitis in rats. Materials and Methods. Studies have been performed on male Wistar rats. Colitis was induced by a rectal enema with 3.5% acetic acid solution. Obestatin was administered intraperitoneally twice a day at a dose of 8 nmol/kg, starting 24 h after the induction of colitis. Seven or 14 days after the induction of colitis, the healing rate of the colon was evaluated. Results. Treatment with obestatin after induction of colitis accelerated the healing of colonic wall damage and this effect was associated with a decrease in the colitis-evoked increase in mucosal activity of myeloperoxidase and content of interleukin-1β. Moreover, obestatin administration significantly reversed the colitis-evoked decrease in mucosal blood flow and DNA synthesis. Conclusion. Administration of exogenous obestatin exhibits therapeutic effects in the course of acetic acid-induced colitis and this effect is related, at least in part, to the obestatin-evoked anti-inflammatory effect, an improvement of local blood flow, and an increase in cell proliferation in colonic mucosa.

  8. STRUCTURAL REMODELING OF PROTEOGLYCANS UPON RETINOIC ACID-INDUCED DIFFERENTIATION OF NCCIT CELLS*

    Gasimli, Leyla; Stansfield, Hope E.; Nairn, Alison V.; Liu, Haiying; Paluh, Janet L.; Yang, Bo; Dordick, Jonathan S.; Moremen, Kelley W.; Linhardt, Robert J.

    2012-01-01

    Pluripotent and multipotent cells become increasingly lineage restricted through differentiation. Alterations to the cellular proteoglycan composition and structure should accompany these changes to influence cell proliferation, delineation of tissues and acquisition of cell migration capabilities. Retinoic acid plays an important role in pre-patterning of the early embryo. Retinoic acid can be used in vitro to induce differentiation, causing pluripotent and multipotent cells to become increasingly lineage restricted. We examined retinoic acid-induced changes in the cellular proteoglycan composition of the well-characterized teratocarcinoma line NCCIT. Our analysis revealed changes in the abundance of transcripts for genes encoding core proteins, enzymes that are responsible for early and late linkage region biosynthesis, as well as enzymes for GAG chain extension and modification. Transcript levels for genes encoding core proteins used as backbones for polysaccharide synthesis revealed highly significant increases in expression of lumican and decorin, 1500-fold and 2800-fold, respectively. Similarly, glypican 3, glypican 5, versican and glypican 6 showed increases between 5 and 70-fold. Significant decreases in biglycan, serglycin, glypican 4, aggrecan, neurocan, CD74 and glypican 1 were observed. Disaccharide analysis of the glycans in heparin/heparan sulfate and chondroitin/dermatan sulfate revealed retinoic acid-induced changes restricted to chondroitin/dermatan sulfate glycans. Our study provides the first detailed analysis of changes in the glycosaminoglycan profile of human pluripotent cells upon treatment with the retinoic acid morphogen. PMID:23053635

  9. Structural remodeling of proteoglycans upon retinoic acid-induced differentiation of NCCIT cells.

    Gasimli, Leyla; Stansfield, Hope E; Nairn, Alison V; Liu, Haiying; Paluh, Janet L; Yang, Bo; Dordick, Jonathan S; Moremen, Kelley W; Linhardt, Robert J

    2013-07-01

    Pluripotent and multipotent cells become increasingly lineage restricted through differentiation. Alterations to the cellular proteoglycan composition and structure should accompany these changes to influence cell proliferation, delineation of tissues and acquisition of cell migration capabilities. Retinoic acid plays an important role in pre-patterning of the early embryo. Retinoic acid can be used in vitro to induce differentiation, causing pluripotent and multipotent cells to become increasingly lineage restricted. We examined retinoic acid-induced changes in the cellular proteoglycan composition of the well-characterized teratocarcinoma line NCCIT. Our analysis revealed changes in the abundance of transcripts for genes encoding core proteins, enzymes that are responsible for early and late linkage region biosynthesis, as well as enzymes for GAG chain extension and modification. Transcript levels for genes encoding core proteins used as backbones for polysaccharide synthesis revealed highly significant increases in expression of lumican and decorin, 1,500-fold and 2,800-fold, respectively. Similarly, glypican 3, glypican 5, versican and glypican 6 showed increases between 5 and 70-fold. Significant decreases in biglycan, serglycin, glypican 4, aggrecan, neurocan, CD74 and glypican 1 were observed. Disaccharide analysis of the glycans in heparin/heparan sulfate and chondroitin/dermatan sulfate revealed retinoic acid-induced changes restricted to chondroitin/dermatan sulfate glycans. Our study provides the first detailed analysis of changes in the glycosaminoglycan profile of human pluripotent cells upon treatment with the retinoic acid morphogen. PMID:23053635

  10. Curcumin-attenuated trinitrobenzene sulphonic acid induces chronic colitis by inhibiting expression of cyclooxygenase-2

    Hua Jiang; Chang-Sheng Deng; Ming Zhang; Jian Xia

    2006-01-01

    AIM: To explore the possible mechanisms of curcumin in rat colitis induced by trinitrobenzene sulfonic (TNBS) acid. METHODS: Rats with TNBS acid-induced colitis were treated with curcumin (30 mg/kg or 60 mg/kg per day ip). Changes of body weight and histological scores as well as survival rate were evaluated. Leukocyte infiltration was detected by myeloperoxidase (MPO)activity assay. The expression of cyclooxygenase-2(COX-2) was detected by RT-PCR and Western blot.Inflammation cytokines were determined by RT-PCR.Local concentration of prostaglandin E2 (PGE2) in colon mucosa was determined by ELISA.RESULTS: Curcumin improved survival rate and histological image, decreased the macroscopic scores and MPO activity. Also curcumin reduced the expression of COX-2 and inflammation cytokines. In addition,treatment with curcumin increased the PGE2 level.CONCLUSION: Curcumin has therapeutic effects on TNBS acid-induced colitis, the mechanisms seem to be related to COX-2 inhibition and PGE2 improvement.

  11. Properties of acid-induced currents in mouse dorsal root ganglia neurons.

    Ergonul, Zuhal; Yang, Lei; Palmer, Lawrence G

    2016-05-01

    Acid-sensing ion channels (ASICs) are cation channels that are activated by protons (H(+)). They are expressed in neurons throughout the nervous system and may play important roles in several neurologic disorders including inflammation, cerebral ischemia, seizures, neurodegeneration, anxiety, depression, and migraine. ASICs generally produce transient currents that desensitize in response to a decrease in extracellular pH Under certain conditions, the inactivation of ASICs can be incomplete and allow them to produce sustained currents. Here, we characterize the properties of both transient and sustained acid-induced currents in cultured mouse dorsal root ganglia (DRG) neurons. At pH levels between 7.3 and 7.1 they include "window currents" through ASICs. With stronger acid signals sustained currents are maintained in the absence of extracellular Na(+) or the presence of the ASIC blockers amiloride and Psalmotoxin-1(PcTx1). These sustained responses may have several different origins in these cells, including acid-induced stimulation of inward Cl(-) currents, block of outward K(+) currents, and augmentation of inward H(+) currents, properties that distinguish these novel sustained currents from the well-characterized transient currents. PMID:27173673

  12. Icariin, a major constituent from Epimedium brevicornum, attenuates ibotenic acid-induced excitotoxicity in rat hippocampus.

    Zong, Nan; Li, Fei; Deng, Yuanyuan; Shi, Jingshan; Jin, Feng; Gong, Qihai

    2016-10-15

    Excitotoxicity is one of the most extensively studied causes of neuronal death and plays an important role in Alzheimer's disease (AD). Icariin is a flavonoid component of a traditional Chinese medicine reported to possess a broad spectrum of pharmacological effects. The present study was designed to investigate the effects of icariin against learning and memory impairment induced by excitotoxicity. Here, we demonstrated that rats receiving intracerebroventricular injection of excitatory neurotoxin ibotenic acid exhibited impaired learning and memory. Oral administration of icariin at doses of 20 and 40mg/kg rescued behavioral performance and protected against neurotoxicity in rat hippocampus by suppressing ibotenic acid induced pro-apoptosis. Furthermore, Western blott of hippocampal specimens revealed that icariin up-regulated the expression of calbindin-D28k protein following ibotenic acid administration. Additionally, icariin inhibited mitogen-activated protein kinase (MAPK) family phosphorylation and nuclear factor kappa B (NF-κB) signaling, implicating the MAPK signaling and NF-κB signaling pathways were involved in the mechanism underlying icariin-mediated neuroprotection against ibotenic acid-induced excitotoxicity. These data suggested that icariin could be a potential agent for treatment of excitotoxicity-related diseases, including AD. PMID:27368415

  13. Hepatoprotective effect of vitamin C on lithocholic acid-induced cholestatic liver injury in Gulo(-/-) mice.

    Yu, Su Jong; Bae, Seyeon; Kang, Jae Seung; Yoon, Jung-Hwan; Cho, Eun Ju; Lee, Jeong-Hoon; Kim, Yoon Jun; Lee, Wang Jae; Kim, Chung Yong; Lee, Hyo-Suk

    2015-09-01

    Prevention and restoration of hepatic fibrosis from chronic liver injury is essential for the treatment of patients with chronic liver diseases. Vitamin C is known to have hepatoprotective effects, but their underlying mechanisms are unclear, especially those associated with hepatic fibrosis. Here, we analyzed the impact of vitamin C on bile acid induced hepatocyte apoptosis in vitro and lithocholic acid (LCA)-induced liver injury in vitamin C-insufficient Gulo(-/-) mice, which cannot synthesize vitamin C similarly to humans. When Huh-BAT cells were treated with bile acid, apoptosis was induced by endoplasmic reticulum stress-related JNK activation but vitamin C attenuated bile acid-induced hepatocyte apoptosis in vitro. In our in vivo experiments, LCA feeding increased plasma marker of cholestasis and resulted in more extensive liver damage and hepatic fibrosis by more prominent apoptotic cell death and recruiting more intrahepatic inflammatory CD11b(+) cells in the liver of vitamin C-insufficient Gulo(-/-) mice compared to wild type mice which have minimal hepatic fibrosis. However, when vitamin C was supplemented to vitamin C-insufficient Gulo(-/-) mice, hepatic fibrosis was significantly attenuated in the liver of vitamin C-sufficient Gulo(-/-) mice like in wild type mice and this hepatoprotective effect of vitamin C was thought to be associated with both decreased hepatic apoptosis and necrosis. These results suggested that vitamin C had hepatoprotective effect against cholestatic liver injury. PMID:26057690

  14. Acid-induced hyperalgesia and anxio-depressive comorbidity in rats.

    Liu, Yu-Ting; Shao, Yen-Wen; Yen, Chen-Tung; Shaw, Fu-Zen

    2014-05-28

    Fibromyalgia is a prevalent disorder characterized by chronic widespread pain (CWP) and complex comorbid symptoms. A CWP model is developed through repeated unilateral intramuscular injections of acid saline resulting in bilateral mechanical hyperalgesia in rats. The present study aims to evaluate whether both anxious and depressive comorbidities exist in this acid-induced pain model, similarly to patients with CWP syndromes. The anxiety-like behaviors were evaluated using the open field and elevated plus maze tests, and depression-like behaviors were measured by the forced swimming, sucrose consumption, and sucrose preference tests. The pain group receiving acidic saline displayed significantly lower paw withdrawal thresholds for 4weeks than animals in the vehicle group after repetitive intramuscular injections. The pain group showed a significantly shorter duration of exploring the central zone of the open field and the open arms of the elevated plus maze compared to the vehicle group. The pain group had a significantly lower preference for and consumption of the hedonic sucrose. Moreover, rats with chronic pain showed significantly longer immobility than the vehicle group in the forced swimming test. The results indicate that psychiatric behaviors are exacerbated in the CWP model. This study provides evidence for the validity of the acid-induced pain model analogous to patients with CWP syndromes. PMID:24726391

  15. Exogenous Ghrelin Accelerates the Healing of Acetic Acid-Induced Colitis in Rats.

    Matuszyk, Aleksandra; Ceranowicz, Piotr; Warzecha, Zygmunt; Cieszkowski, Jakub; Ceranowicz, Dagmara; Gałązka, Krystyna; Bonior, Joanna; Jaworek, Jolanta; Bartuś, Krzysztof; Gil, Krzysztof; Olszanecki, Rafał; Dembiński, Artur

    2016-01-01

    Previous studies have shown that ghrelin reduces colonic inflammation induced by trinitrobenzene sulfonic acid and dextran sodium sulfate. In the present study we determined the effect of treatment with ghrelin on the course of acetic acid-induced colitis in rats. Rectal administration of 3% acetic acid solution led to induction of colitis in all animals. Damage of the colonic wall was accompanied by an increase in mucosal concentration of pro-inflammatory interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), as well mucosal activity of myeloperoxidase. Moreover, induction of colitis led to a reduction in colonic blood flow and DNA synthesis. Administration of ghrelin after induction of colitis led to faster regeneration of the colonic wall and reduction in colonic levels of IL-1β, TNF-α, and myeloperoxidase. In addition, treatment with ghrelin improved mucosal DNA synthesis and blood flow. Our study disclosed that ghrelin exhibits a strong anti-inflammatory and healing effect in acetic acid-induced colitis. Our current observation in association with previous findings that ghrelin exhibits curative effect in trinitrobenzene sulfonic acid- and dextran sodium sulfate-induced colitis suggest that therapeutic effect of ghrelin in the colon is universal and independent of the primary cause of colitis. PMID:27598133

  16. Genetic Deletion of the Neuronal Glutamate Transporter, EAAC1, Results in Decreased Neuronal Death after Pilocarpine-Induced Status Epilepticus

    Lane, Meredith C.; Jackson, Joshua G.; Krizman, Elizabeth N.; Rothstein, Jeffery D.; Porter, Brenda E.; Robinson, Michael B.

    2013-01-01

    Excitatory amino acid carrier 1 (EAAC1, also called EAAT3) is a Na+-dependent glutamate transporter expressed by both glutamatergic and GABAergic neurons. It provides precursors for the syntheses of glutathione and GABA and contributes to the clearance of synaptically released glutamate. Mice deleted of EAAC1 are more susceptible to neurodegeneration in models of ischemia, Parkinson’s disease, and aging. Antisense knock-down of EAAC1 causes an absence seizure-like phenotype. Additionally, EAA...

  17. Nonconvulsive status epilepticus in the elderly associated with newer antidepressants used at therapeutic doses: A report of three cases

    Go Taniguchi

    2015-01-01

    All three patients were male and were 73 years of age or older. One patient was recently diagnosed with temporal lobe epilepsy and treated with low-dose lamotrigine. In all patients, newer antidepressants were initiated because of depressive symptoms. After titrating to therapeutic doses (paroxetine 20 mg/day, sertraline 50 mg/day, and combination of sertraline 50 mg/day and mirtazapine 30 mg/day in one patient each, impaired consciousness appeared. Electroencephalography (EEG showed generalized slow waves with intermittent spike–slow-wave complexes. Intravenous injection of antiepileptic drugs improved EEG findings and clinical symptoms. After discontinuance of the abovementioned antidepressants, NCSE did not recur in any of patients. These reports raise the question of whether the newer antidepressants, like classic antidepressants, might also induce NCSE in the elderly, even when used at therapeutic doses. Physicians should consider monitoring for possible NCSE when using newer antidepressants in patients who may have low drug tolerability. Active continuous video-EEG monitoring is essential when behavioral and psychological symptoms or change in consciousness level is suspected.

  18. Níveis dos neurotransmissores estriatais durante o estado epiléptico Striatal monoamines levels during status epilepticus

    Rivelilson Mendes de Freitas; Glauce Socorro de Barros Viana; Marta Maria de França Fonteles

    2003-01-01

    O objetivo desse estudo foi verificar os níveis dos neurotransmissores estriatais de ratas adultas durante o estado epiléptico induzido pela pilocarpina. Ratas wistar foram tratadas com uma única dose de pilocarpina (400 mg/kg por via subcutânea (S.C.); P400) e os controles receberam salina. A concentração dos neurotransmissores foi determinada através do HPLC eletroquímico, no corpo estriado de ratas que no período de observação de 1 hora desencadearam estado epiléptico e que sobreviveram à ...

  19. Status epilepticus stimulates NDEL1 expression via the CREB/CRE pathway in the adult mouse brain.

    Choi, Yun-Sik; Lee, Boyoung; Hansen, Katelin F; Aten, Sydney; Horning, Paul; Wheaton, Kelin L; Impey, Soren; Hoyt, Kari R; Obrietan, Karl

    2016-09-01

    Nuclear distribution element-like 1 (NDEL1/NUDEL) is a mammalian homolog of the Aspergillus nidulans nuclear distribution molecule NudE. NDEL1 plays a critical role in neuronal migration, neurite outgrowth and neuronal positioning during brain development; however within the adult central nervous system, limited information is available regarding NDEL1 expression and functions. Here, the goal was to examine inducible NDEL1 expression in the adult mouse forebrain. Immunolabeling revealed NDEL1 within the forebrain, including the cortex and hippocampus, as well as the midbrain and hypothalamus. Expression was principally localized to perikarya. Using a combination of immunolabeling and RNA seq profiling, we detected a marked and long-lasting upregulation of NDEL1 expression within the hippocampus following a pilocarpine-evoked repetitive seizure paradigm. Chromatin immunoprecipitation (ChIP) analysis identified a cAMP response element-binding protein (CREB) binding site within the CpG island proximal to the NDEL1 gene, and in vivo transgenic repression of CREB led to a marked downregulation of seizure-evoked NDEL1 expression. Together these data indicate that NDEL1 is inducibly expressed in the adult nervous system, and that signaling via the CREB/CRE transcriptional pathway is likely involved. The role of NDEL1 in neuronal migration and neurite outgrowth during development raises the interesting prospect that inducible NDEL1 in the mature nervous system could contribute to the well-characterized structural and functional plasticity resulting from repetitive seizure activity. PMID:27298008

  20. Practice parameters in management of status epileptics

    Usha Kant Misra

    2014-01-01

    Full Text Available Status epilepticus (SE is an emergency neurological problem, more common in the developing countries due to high incidence of infection, stroke and head injury. The protocol for management of SE is intravenous benzodiazepine, followed by phenytoin, valproate (VPA and phenobarbitone and if uncontrolled general anesthesia (GA. World Federation of Neurology recommends special guidelines for resource poor countries. Use of GA results in hypotension and respiratory depression needing intensive care management. There is a paucity of intensive care facilities hence the recommended antiepileptic drugs (AEDs which have inherent toxicity of hypotension and respiratory failure cannot be given safely. Under these situations AEDs such as VPA, levetiracetam and lacosamide may be evaluated in SE because of cardiovascular and respiratory safety profile. In this review, the limitations of existing guidelines in the developing countries have been discussed and a way forward has been suggested.

  1. Heat shock protein 70-dependent protective effect of polaprezinc on acetylsalicylic acid-induced apoptosis of rat intestinal epithelial cells.

    Qin, Ying; Naito, Yuji; Handa, Osamu; Hayashi, Natsuko; Kuki, Aiko; Mizushima, Katsura; Omatsu, Tatsushi; Tanimura, Yuko; Morita, Mayuko; Adachi, Satoko; Fukui, Akifumi; Hirata, Ikuhiro; Kishimoto, Etsuko; Nishikawa, Taichiro; Uchiyama, Kazuhiko; Ishikawa, Takeshi; Takagi, Tomohisa; Yagi, Nobuaki; Kokura, Satoshi; Yoshikawa, Toshikazu

    2011-11-01

    Protection of the small intestine from mucosal injury induced by nonsteroidal anti-inflammatory drugs including acetylsalicylic acid is a critical issue in the field of gastroenterology. Polaprezinc an anti-ulcer drug, consisting of zinc and L-carnosine, provides gastric mucosal protection against various irritants. In this study, we investigated the protective effect of polaprezinc on acetylsalicylic acid-induced apoptosis of the RIE1 rat intestinal epithelial cell line. Confluent rat intestinal epithelial cells were incubated with 70 µM polaprezinc for 24 h, and then stimulated with or without 15 mM acetylsalicylic acid for a further 15 h. Subsequent cellular viability was quantified by fluorometric assay based on cell lysis and staining. Acetylsalicylic acid-induced cell death was also qualified by fluorescent microscopy of Hoechst33342 and propidium iodide. Heat shock proteins 70 protein expression after adding polaprezinc or acetylsalicylic acid was assessed by western blotting. To investigate the role of Heat shock protein 70, Heat shock protein 70-specific small interfering RNA was applied. Cell viability was quantified by fluorometric assay based on cell lysis and staining and apoptosis was analyzed by fluorescence-activated cell sorting. We found that acetylsalicylic acid significantly induced apoptosis of rat intestinal epithelial cells in a dose- and time-dependent manner. Polaprezinc significantly suppressed acetylsalicylic acid-induced apoptosis of rat intestinal epithelial cells at its late phase. At the same time, polaprezinc increased Heat shock protein 70 expressions of rat intestinal epithelial cells in a time-dependent manner. However, in Heat shock protein 70-silenced rat intestinal epithelial cells, polaprezinc could not suppress acetylsalicylic acid -induced apoptosis at its late phase. We conclude that polaprezinc-increased Heat shock protein 70 expression might be an important mechanism by which polaprezinc suppresses acetylsalicylic

  2. Effect of Tanshitone on prevention and treatment of retinoic acid-induced osteoporosis in mice

    ZHOU Yan-meng; LIU Yu-bo; GAO Yun-sheng

    2008-01-01

    Objective To observe the prevention and therapeutic effects of tanshitone (TAN) on retinoic acid induced osteoporosis in mice. Methods The mice osteoporosis was induced by given retinoic acid intragasttrically for two weeks. The histomorphological features of bone were observed and biochemical indexes in serum (Ca, P, ALP, TRAP, E2, BGP) were determined after mice were given TAN at the dose of 40, 80, 160 mg·kg-1 respectively. Results Tanshitone can induce high conversion of osteoporosis. The levels of P, ALP, TRAP and BGP in the TAN groups were lower than the model group, while the E2 level was higher than the model group. Conclusions Tanshitone can prevent the loss bone in the experimental mice. The mechanism may be that it improves the level of estrogenic hormone and inhibits the high bone turnover.

  3. Valproic Acid-Induced Severe Acute Pancreatitis with Pseudocyst Formation: Report of a Case.

    Ray, Sukanta; Khamrui, Sujan; Kataria, Mohnish; Biswas, Jayanta; Saha, Suman

    2015-08-01

    Valproic acid is the most widely used anti-epilep-tic drug in children, and it is probably the most frequent cause of drug-induced acute pancreatitis. Outcomes for patients with valproic acid-associated pancreatitis vary from full recovery after discontinuation of the drug to severe acute pancreatitis and death. Here, we present a case of valproic acid-induced severe acute pancreatitis with pseudocyst formation in a 10-year-old girl with cerebral palsy and generalized tonic-clonic seizure. There was no resolution of the pseudocyst after discontinuation of valproic acid. The patient became symptomatic with a progressive increase in the size of the pseudocyst. She was successfully treated with cystogastrostomy and was well at 12-month follow-up. PMID:26366333

  4. Cell wall dynamics modulate acetic acid-induced apoptotic cell death of Saccharomyces cerevisiae

    António Rego

    2014-08-01

    Full Text Available Acetic acid triggers apoptotic cell death in Saccharomyces cerevisiae, similar to mammalian apoptosis. To uncover novel regulators of this process, we analyzed whether impairing MAPK signaling affected acetic acid-induced apoptosis and found the mating-pheromone response and, especially, the cell wall integrity pathways were the major mediators, especially the latter, which we characterized further. Screening downstream effectors of this pathway, namely targets of the transcription factor Rlm1p, highlighted decreased cell wall remodeling as particularly important for acetic acid resistance. Modulation of cell surface dynamics therefore emerges as a powerful strategy to increase acetic acid resistance, with potential application in industrial fermentations using yeast, and in biomedicine to exploit the higher sensitivity of colorectal carcinoma cells to apoptosis induced by acetate produced by intestinal propionibacteria.

  5. CD36 Mediated Fatty Acid-Induced Podocyte Apoptosis via Oxidative Stress.

    Wei Hua

    Full Text Available Hyperlipidemia-induced apoptosis mediated by fatty acid translocase CD36 is associated with increased uptake of ox-LDL or fatty acid in macrophages, hepatocytes and proximal tubular epithelial cells, leading to atherosclerosis, liver damage and fibrosis in obese patients, and diabetic nephropathy (DN, respectively. However, the specific role of CD36 in podocyte apoptosis in DN with hyperlipidemia remains poorly investigated.The expression of CD36 was measured in paraffin-embedded kidney tissue samples (Ctr = 18, DN = 20 by immunohistochemistry and immunofluorescence staining. We cultured conditionally immortalized mouse podocytes (MPC5 and treated cells with palmitic acid, and measured CD36 expression by real-time PCR, Western blot analysis and immunofluorescence; lipid uptake by Oil red O staining and BODIPY staining; apoptosis by flow cytometry assay, TUNEL assay and Western blot analysis; and ROS production by DCFH-DA fluorescence staining. All statistical analyses were performed using SPSS 21.0 statistical software.CD36 expression was increased in kidney tissue from DN patients with hyperlipidemia. Palmitic acid upregulated CD36 expression and promoted its translocation from cytoplasm to plasma membrane in podocytes. Furthermore, palmitic acid increased lipid uptake, ROS production and apoptosis in podocytes, Sulfo-N-succinimidyloleate (SSO, the specific inhibitor of the fatty acid binding site on CD36, decreased palmitic acid-induced fatty acid accumulation, ROS production, and apoptosis in podocytes. Antioxidant 4-hydroxy-2,2,6,6- tetramethylpiperidine -1-oxyl (tempol inhibited the overproduction of ROS and apoptosis in podocytes induced by palmitic acid.CD36 mediated fatty acid-induced podocyte apoptosis via oxidative stress might participate in the process of DN.

  6. Rho Kinase ROCK2 Mediates Acid-Induced NADPH Oxidase NOX5-S Expression in Human Esophageal Adenocarcinoma Cells.

    Jie Hong

    Full Text Available Mechanisms of the progression from Barrett's esophagus (BE to esophageal adenocarcinoma (EA are not fully understood. We have shown that NOX5-S may be involved in this progression. However, how acid upregulates NOX5-S is not well known. We found that acid-induced increase in NOX5-S expression was significantly decreased by the Rho kinase (ROCK inhibitor Y27632 in BE mucosal biopsies and FLO-1 EA cells. In addition, acid treatment significantly increased the Rho kinase activity in FLO-1 cells. The acid-induced increase in NOX5-S expression and H2O2 production was significantly decreased by knockdown of Rho kinase ROCK2, but not by knockdown of ROCK1. Conversely, the overexpression of the constitutively active ROCK2, but not the constitutively active ROCK1, significantly enhanced the NOX5-S expression and H2O2 production. Moreover, the acid-induced increase in Rho kinase activity and in NOX5-S mRNA expression was blocked by the removal of calcium in both FLO-1 and OE33 cells. The calcium ionophore A23187 significantly increased the Rho kinase activity and NOX5-S mRNA expression. We conclude that acid-induced increase in NOX5-S expression and H2O2 production may depend on the activation of ROCK2, but not ROCK1, in EA cells. The acid-induced activation of Rho kinase may be mediated by the intracellular calcium increase. It is possible that persistent acid reflux present in BE patients may increase the intracellular calcium, activate ROCK2 and thereby upregulate NOX5-S. High levels of reactive oxygen species derived from NOX5-S may cause DNA damage and thereby contribute to the progression from BE to EA.

  7. Rho Kinase ROCK2 Mediates Acid-Induced NADPH Oxidase NOX5-S Expression in Human Esophageal Adenocarcinoma Cells

    Cao, Weibiao

    2016-01-01

    Mechanisms of the progression from Barrett’s esophagus (BE) to esophageal adenocarcinoma (EA) are not fully understood. We have shown that NOX5-S may be involved in this progression. However, how acid upregulates NOX5-S is not well known. We found that acid-induced increase in NOX5-S expression was significantly decreased by the Rho kinase (ROCK) inhibitor Y27632 in BE mucosal biopsies and FLO-1 EA cells. In addition, acid treatment significantly increased the Rho kinase activity in FLO-1 cells. The acid-induced increase in NOX5-S expression and H2O2 production was significantly decreased by knockdown of Rho kinase ROCK2, but not by knockdown of ROCK1. Conversely, the overexpression of the constitutively active ROCK2, but not the constitutively active ROCK1, significantly enhanced the NOX5-S expression and H2O2 production. Moreover, the acid-induced increase in Rho kinase activity and in NOX5-S mRNA expression was blocked by the removal of calcium in both FLO-1 and OE33 cells. The calcium ionophore A23187 significantly increased the Rho kinase activity and NOX5-S mRNA expression. We conclude that acid-induced increase in NOX5-S expression and H2O2 production may depend on the activation of ROCK2, but not ROCK1, in EA cells. The acid-induced activation of Rho kinase may be mediated by the intracellular calcium increase. It is possible that persistent acid reflux present in BE patients may increase the intracellular calcium, activate ROCK2 and thereby upregulate NOX5-S. High levels of reactive oxygen species derived from NOX5-S may cause DNA damage and thereby contribute to the progression from BE to EA. PMID:26901778

  8. Anacardic acid induces apoptosis-like cell death in the rice blast fungus Magnaporthe oryzae.

    Muzaffar, Suhail; Bose, Chinchu; Banerji, Ashok; Nair, Bipin G; Chattoo, Bharat B

    2016-01-01

    Anacardic acid (6-pentadecylsalicylic acid), extracted from cashew nut shell liquid, is a natural phenolic lipid well known for its strong antibacterial, antioxidant, and anticancer activities. Its effect has been well studied in bacterial and mammalian systems but remains largely unexplored in fungi. The present study identifies antifungal, cytotoxic, and antioxidant activities of anacardic acid in the rice blast fungus Magnaporthe oryzae. It was found that anacardic acid causes inhibition of conidial germination and mycelial growth in this ascomycetous fungus. Phosphatidylserine externalization, chromatin condensation, DNA degradation, and loss of mitochondrial membrane potential suggest that growth inhibition of fungus is mainly caused by apoptosis-like cell death. Broad-spectrum caspase inhibitor Z-VAD-FMK treatment indicated that anacardic acid induces caspase-independent apoptosis in M. oryzae. Expression of a predicted ortholog of apoptosis-inducing factor (AIF) was upregulated during the process of apoptosis, suggesting the possibility of mitochondria dependent apoptosis via activation of apoptosis-inducing factor. Anacardic acid treatment leads to decrease in reactive oxygen species rather than increase in reactive oxygen species (ROS) accumulation normally observed during apoptosis, confirming the antioxidant properties of anacardic acid as suggested by earlier reports. Our study also shows that anacardic acid renders the fungus highly sensitive to DNA damaging agents like ethyl methanesulfonate (EMS). Treatment of rice leaves with anacardic acid prevents M. oryzae from infecting the plant without affecting the leaf, suggesting that anacardic acid can be an effective antifungal agent. PMID:26381667

  9. Transcriptional Elongation Factor Elongin A Regulates Retinoic Acid-Induced Gene Expression during Neuronal Differentiation

    Takashi Yasukawa

    2012-11-01

    Full Text Available Elongin A increases the rate of RNA polymerase II (pol II transcript elongation by suppressing transient pausing by the enzyme. Elongin A also acts as a component of a cullin-RING ligase that can target stalled pol II for ubiquitylation and proteasome-dependent degradation. It is not known whether these activities of Elongin A are functionally interdependent in vivo. Here, we demonstrate that Elongin A-deficient (Elongin A−/− embryos exhibit abnormalities in the formation of both cranial and spinal nerves and that Elongin A−/− embryonic stem cells (ESCs show a markedly decreased capacity to differentiate into neurons. Moreover, we identify Elongin A mutations that selectively inactivate one or the other of the aforementioned activities and show that mutants that retain the elongation stimulatory, but not pol II ubiquitylation, activity of Elongin A rescue neuronal differentiation and support retinoic acid-induced upregulation of a subset of neurogenesis-related genes in Elongin A−/− ESCs.

  10. Phenylbutyric acid induces the cellular senescence through an Akt/p21WAF1 signaling pathway

    Highlights: ► Phenylbutyric acid induces cellular senescence. ► Phenylbutyric acid activates Akt kinase. ► The knockdown of PERK also can induce cellular senescence. ► Akt/p21WAF1 pathway activates in PERK knockdown induced cellular senescence. -- Abstract: It has been well known that three sentinel proteins – PERK, ATF6 and IRE1 – initiate the unfolded protein response (UPR) in the presence of misfolded or unfolded proteins in the ER. Recent studies have demonstrated that upregulation of UPR in cancer cells is required to survive and proliferate. Here, we showed that long exposure to 4-phenylbutyric acid (PBA), a chemical chaperone that can reduce retention of unfolded and misfolded proteins in ER, induced cellular senescence in cancer cells such as MCF7 and HT1080. In addition, we found that treatment with PBA activates Akt, which results in p21WAF1 induction. Interestingly, the depletion of PERK but not ATF6 and IRE1 also induces cellular senescence, which was rescued by additional depletion of Akt. This suggests that Akt pathway is downstream of PERK in PBA induced cellular senescence. Taken together, these results show that PBA induces cellular senescence via activation of the Akt/p21WAF1 pathway by PERK inhibition.

  11. Rotavirus nonstructural protein 1 antagonizes innate immune response by interacting with retinoic acid inducible gene I

    Qin Lan

    2011-12-01

    Full Text Available Abstract Background The nonstructural protein 1 (NSP1 of rotavirus has been reported to block interferon (IFN signaling by mediating proteasome-dependent degradation of IFN-regulatory factors (IRFs and (or the β-transducin repeat containing protein (β-TrCP. However, in addition to these targets, NSP1 may subvert innate immune responses via other mechanisms. Results The NSP1 of rotavirus OSU strain as well as the IRF3 binding domain truncated NSP1 of rotavirus SA11 strain are unable to degrade IRFs, but can still inhibit host IFN response, indicating that NSP1 may target alternative host factor(s other than IRFs. Overexpression of NSP1 can block IFN-β promoter activation induced by the retinoic acid inducible gene I (RIG-I, but does not inhibit IFN-β activation induced by the mitochondrial antiviral-signaling protein (MAVS, indicating that NSP1 may target RIG-I. Immunoprecipitation experiments show that NSP1 interacts with RIG-I independent of IRF3 binding domain. In addition, NSP1 induces down-regulation of RIG-I in a proteasome-independent way. Conclusions Our findings demonstrate that inhibition of RIG-I mediated type I IFN responses by NSP1 may contribute to the immune evasion of rotavirus.

  12. Synergistic action of famotidine and chlorpheniramine on acetic acid-induced chronic gastric ulcer in rats

    Zhen Qin; Chao Chen

    2005-01-01

    AIM: To assess the synergistic action of famotidine (FMD)and chlorpheniramine (CPA) on acetic acid-induced chronic gastric ulcer in rats.METHODS: Chronic gastric lesions were induced in male Sprague-Dawley (SD) rats by serosal application of the acetic acid. Forty SD rats were randomly divided into blank group (n = 8), control group (n = 8), FMD group (n= 8), CPA group (n = 8), and FMD+CPA group (n = 8).Each group was given intraperitoneally (i.p.) 0.5 mL/100g distilled water, 9 g/L NaCl saline, 4 mg/kg FMD, 10mg/kg CPA, 4 mg/kg FMD+10 mg/kg CPA, respectively,daily for 10 d. On d 10, ulcer area was determined by planimetry. The level of myeloperoxidase (MPO) in the liver homogenation was determined by biochemical methods and the plasma levels of 6-ketoprostaglandin F1 alpha (6-keto-PGF1a)and IL-8 were determined by radioimmunoassay.RESULTS: The synergistic effects of FMD+CPA group on the lesion, IL-8, 6-keto-PGF1a and MPO were confirmed.The effect of FMlD+CPA group was significantly different as compared to the control and FMD groups. The lesion (mm2) was reduced from 40.18±2.6 in control group to 6.83±2.97 in PMD+CPA group, P<0.01, and from 32.9±3.27 in FMD group to 6.83±2.97 in pMlD+CPA group,P<0.01. The plasma levels of IL-8 decreased from 0.69±0.11 ng/L in control group to 0.4±0.04 ng/L in PMD+CPA group, P<0.01, and from 0.51±0.08 ng/L in FMD group to 0.4±0.04 ng/L in PMD+CPA group, P<0.05. The level of 6-keto-PGF1a increased from 7.55±1.65 ng/L in control group to 16.62±0.97 ng/L in PMD+CPA group, P<0.01,and from 13.15±1.48 ng/L in FMD group to 16.62±0.97ng/L in PMD+CPA group, P<0.05. The levels of MPO in the liver homogenate decreased from 9.12±2.05 u/Lin control group to 4.33±0.95 u/L in PMD+CPA group,P<0.01, and from 8.3±1.29 u/L in FMD group to 4.33±0.95 u/L, P<0.01.CONCLUSION: The synergistic action of FMD and CPA on acetic acid-induced chronic gastric ulcer in rats decreases the incidence of ulcer and also enhances the

  13. Bile acid-induced necrosis in primary human hepatocytes and in patients with obstructive cholestasis

    Woolbright, Benjamin L.; Dorko, Kenneth [Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); Antoine, Daniel J.; Clarke, Joanna I. [MRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool (United Kingdom); Gholami, Parviz [Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS (United States); Li, Feng [Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); Kumer, Sean C.; Schmitt, Timothy M.; Forster, Jameson [Department of Surgery, University of Kansas Medical Center, Kansas City, KS (United States); Fan, Fang [Department of Pathology, University of Kansas Medical Center, Kansas City, KS (United States); Jenkins, Rosalind E.; Park, B. Kevin [MRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool (United Kingdom); Hagenbuch, Bruno [Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); Olyaee, Mojtaba [Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS (United States); Jaeschke, Hartmut, E-mail: hjaeschke@kumc.edu [Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States)

    2015-03-15

    Accumulation of bile acids is a major mediator of cholestatic liver injury. Recent studies indicate bile acid composition between humans and rodents is dramatically different, as humans have a higher percent of glycine conjugated bile acids and increased chenodeoxycholate content, which increases the hydrophobicity index of bile acids. This increase may lead to direct toxicity that kills hepatocytes, and promotes inflammation. To address this issue, this study assessed how pathophysiological concentrations of bile acids measured in cholestatic patients affected primary human hepatocytes. Individual bile acid levels were determined in serum and bile by UPLC/QTOFMS in patients with extrahepatic cholestasis with, or without, concurrent increases in serum transaminases. Bile acid levels increased in serum of patients with liver injury, while biliary levels decreased, implicating infarction of the biliary tracts. To assess bile acid-induced toxicity in man, primary human hepatocytes were treated with relevant concentrations, derived from patient data, of the model bile acid glycochenodeoxycholic acid (GCDC). Treatment with GCDC resulted in necrosis with no increase in apoptotic parameters. This was recapitulated by treatment with biliary bile acid concentrations, but not serum concentrations. Marked elevations in serum full-length cytokeratin-18, high mobility group box 1 protein (HMGB1), and acetylated HMGB1 confirmed inflammatory necrosis in injured patients; only modest elevations in caspase-cleaved cytokeratin-18 were observed. These data suggest human hepatocytes are more resistant to human-relevant bile acids than rodent hepatocytes, and die through necrosis when exposed to bile acids. These mechanisms of cholestasis in humans are fundamentally different to mechanisms observed in rodent models. - Highlights: • Cholestatic liver injury is due to cytoplasmic bile acid accumulation in hepatocytes. • Primary human hepatocytes are resistant to BA-induced injury

  14. Role of ion transporters in the bile acid-induced esophageal injury.

    Laczkó, Dorottya; Rosztóczy, András; Birkás, Klaudia; Katona, Máté; Rakonczay, Zoltán; Tiszlavicz, László; Róka, Richárd; Wittmann, Tibor; Hegyi, Péter; Venglovecz, Viktória

    2016-07-01

    Barrett's esophagus (BE) is considered to be the most severe complication of gastro-esophageal reflux disease (GERD), in which the prolonged, repetitive episodes of combined acidic and biliary reflux result in the replacement of the squamous esophageal lining by columnar epithelium. Therefore, the acid-extruding mechanisms of esophageal epithelial cells (EECs) may play an important role in the defense. Our aim was to identify the presence of acid/base transporters on EECs and to investigate the effect of bile acids on their expressions and functions. Human EEC lines (CP-A and CP-D) were acutely exposed to bile acid cocktail (BAC) and the changes in intracellular pH (pHi) and Ca(2+) concentration ([Ca(2+)]i) were measured by microfluorometry. mRNA and protein expression of ion transporters was investigated by RT-PCR, Western blot, and immunohistochemistry. We have identified the presence of a Na(+)/H(+) exchanger (NHE), Na(+)/HCO3 (-) cotransporter (NBC), and a Cl(-)-dependent HCO3 (-) secretory mechanism in CP-A and CP-D cells. Acute administration of BAC stimulated HCO3 (-) secretion in both cell lines and the NHE activity in CP-D cells by an inositol triphosphate-dependent calcium release. Chronic administration of BAC to EECs increased the expression of ion transporters compared with nontreated cells. A similar expression pattern was observed in biopsy samples from BE compared with normal epithelium. We have shown that acute administration of bile acids differently alters ion transport mechanisms of EECs, whereas chronic exposure to bile acids increases the expression of acid/base transporters. We speculate that these adaptive processes of EECs represent an important mucosal defense against the bile acid-induced epithelial injury. PMID:27198194

  15. Bile acid-induced arrhythmia is mediated by muscarinic M2 receptors in neonatal rat cardiomyocytes.

    Siti H Sheikh Abdul Kadir

    Full Text Available BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP is a common disease affecting up to 5% of pregnancies and which can cause fetal arrhythmia and sudden intrauterine death. We previously demonstrated that bile acid taurocholate (TC, which is raised in the bloodstream of ICP, can acutely alter the rate and rhythm of contraction and induce abnormal calcium destabilization in cultured neonatal rat cardiomyocytes (NRCM. Apart from their hepatic functions bile acids are ubiquitous signalling molecules with diverse systemic effects mediated by either the nuclear receptor FXR or by a recently discovered G-protein coupled receptor TGR5. We aim to investigate the mechanism of bile-acid induced arrhythmogenic effects in an in-vitro model of the fetal heart. METHODS AND RESULTS: Levels of bile acid transporters and nuclear receptor FXR were studied by quantitative real time PCR, western blot and immunostaining, which showed low levels of expression. We did not observe functional involvement of the canonical receptors FXR and TGR5. Instead, we found that TC binds to the muscarinic M(2 receptor in NRCM and serves as a partial agonist of this receptor in terms of inhibitory effect on intracellular cAMP and negative chronotropic response. Pharmacological inhibition and siRNA-knockdown of the M(2 receptor completely abolished the negative effect of TC on contraction, calcium transient amplitude and synchronisation in NRCM clusters. CONCLUSION: We conclude that in NRCM the TC-induced arrhythmia is mediated by the partial agonism at the M(2 receptor. This mechanism might serve as a promising new therapeutic target for fetal arrhythmia.

  16. Decreased apoptosis during CAR-mediated hepatoprotection against lithocholic acid-induced liver injury in mice.

    Beilke, Lisa D; Aleksunes, Lauren M; Olson, Erik R; Besselsen, David G; Klaassen, Curtis D; Dvorak, Katerina; Cherrington, Nathan J

    2009-07-10

    Myeloid cell leukemia-1 (Mcl-1) is an anti-apoptotic protein that is regulated by the constitutive androstane receptor (CAR). Activation of CAR can protect the liver against bile acid-induced toxicity and it may have a role in cell death via apoptosis by altering expression of Bcl-2 family proteins such as myeloid cell leukemia-1 (Mcl-1). Our aim was to determine if activation of CAR reduces hepatocellular apoptosis during cholestasis as a mechanism of hepatoprotection. CAR(+/+) (WT) and CAR(-/-) (CAR-null) mice were pre-treated with compounds known to activate CAR prior to induction of intrahepatic cholestasis using the secondary bile acid lithocholic acid (LCA). Pre-treatment with the CAR activators phenobarbital (PB) and TCPOBOP (TC), as well as the non-CAR activator pregnenolone 16alpha-carbontrile (PCN), protected against LCA-induced liver injury in WT mice, whereas liver injury was more extensive without CAR (CAR-null). Unexpectedly, expression of anti-apoptotic Mcl-1 and Bcl-x(L) was not increased in hepatoprotected mice. Compared to unprotected groups, apoptosis was decreased in hepatoprotected mice as evidenced by the absence of cleaved caspase 3 (cCasp3). In contrast to the cytoplasmic localization in the injured livers (LCA and oltipraz), Mcl-1 protein was localized in the nucleus of hepatoprotected livers to potentially promote cell survival. This study demonstrates that although apoptosis is reduced in hepatoprotected mice pre-treated with CAR and non-CAR activators; hepatoprotection is not directly a result of CAR-induced Mcl-1 expression. PMID:19433268

  17. Bile acid-induced necrosis in primary human hepatocytes and in patients with obstructive cholestasis

    Accumulation of bile acids is a major mediator of cholestatic liver injury. Recent studies indicate bile acid composition between humans and rodents is dramatically different, as humans have a higher percent of glycine conjugated bile acids and increased chenodeoxycholate content, which increases the hydrophobicity index of bile acids. This increase may lead to direct toxicity that kills hepatocytes, and promotes inflammation. To address this issue, this study assessed how pathophysiological concentrations of bile acids measured in cholestatic patients affected primary human hepatocytes. Individual bile acid levels were determined in serum and bile by UPLC/QTOFMS in patients with extrahepatic cholestasis with, or without, concurrent increases in serum transaminases. Bile acid levels increased in serum of patients with liver injury, while biliary levels decreased, implicating infarction of the biliary tracts. To assess bile acid-induced toxicity in man, primary human hepatocytes were treated with relevant concentrations, derived from patient data, of the model bile acid glycochenodeoxycholic acid (GCDC). Treatment with GCDC resulted in necrosis with no increase in apoptotic parameters. This was recapitulated by treatment with biliary bile acid concentrations, but not serum concentrations. Marked elevations in serum full-length cytokeratin-18, high mobility group box 1 protein (HMGB1), and acetylated HMGB1 confirmed inflammatory necrosis in injured patients; only modest elevations in caspase-cleaved cytokeratin-18 were observed. These data suggest human hepatocytes are more resistant to human-relevant bile acids than rodent hepatocytes, and die through necrosis when exposed to bile acids. These mechanisms of cholestasis in humans are fundamentally different to mechanisms observed in rodent models. - Highlights: • Cholestatic liver injury is due to cytoplasmic bile acid accumulation in hepatocytes. • Primary human hepatocytes are resistant to BA-induced injury

  18. A dual inhibitor of cyclooxygenase and 5-lipoxygenase protects against kainic acid-induced brain injury.

    Minutoli, Letteria; Marini, Herbert; Rinaldi, Mariagrazia; Bitto, Alessandra; Irrera, Natasha; Pizzino, Gabriele; Pallio, Giovanni; Calò, Margherita; Adamo, Elena Bianca; Trichilo, Vincenzo; Interdonato, Monica; Galfo, Federica; Squadrito, Francesco; Altavilla, Domenica

    2015-06-01

    Systemic administration of kainic acid causes inflammation and apoptosis in the brain, resulting in neuronal loss. Dual cyclooxygenase/5-lipoxygenase (COX/5-LOX) inhibitors could represent a possible neuroprotective approach in preventing glutamate excitotoxicity. Consequently, we investigated the effects of a dual inhibitor of COX/5-LOX following intraperitoneal administration of kainic acid (KA, 10 mg/kg) in rats. Animals were randomized to receive either the dual inhibitor of COX/5-LOX (flavocoxid, 20 mg/kg i.p.) or its vehicle (1 ml/kg i.p.) 30 min after KA administration. Sham brain injury rats were used as controls. We evaluated protein expression of phosphorylated extracellular signal-regulated kinase (p-ERK1/2) and tumor necrosis factor alpha (TNF-α) as well as levels of malondialdehyde (MDA), prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) in the hippocampus. Animals were also observed for monitoring behavioral changes according to Racine Scale. Finally, histological analysis and brain edema evaluation were carried out. Treatment with the dual inhibitor of COX/5-LOX decreased protein expression of p-ERK1/2 and TNF-α in hippocampus, markedly reduced MDA, LTB4 and PGE2 hippocampal levels, and also ameliorated brain edema. Histological analysis showed a reduction in cell damage in rats treated with the dual inhibitor of COX/5-LOX, particularly in hippocampal subregion CA3c. Moreover, flavocoxid significantly improved behavioral signs following kainic acid administration. Our results suggest that dual inhibition of COX/5-LOX by flavocoxid has neuroprotective effects during kainic acid-induced excitotoxicity. PMID:25893744

  19. Nephroprotective effect of Corn Silk extract on oxalic acid-induced nephrocalcinosis in rabbit model

    Faruk Hassan Al-Jawad

    2012-04-01

    Full Text Available ABSTRACT Background : Nephrocalcinosis is a state of deposition of calcium phosphate or oxalate in the renal parenchyma. It may occur in patients with renal tubular acidosis, vitamin D intoxication, and hyperparathyroidism. Corn silk was used in traditional Chinese medicine to relieve renal pains. Aim: To evaluate the effect of Corn silk aqueous extract in reducing calcium deposits from renal parenchyma in oxalic acid-induced nephrocalcinosis model. Materials and methods: Fourteen healthy rabbits were allocated to two groups. Two hours before induction of nephrocalcinosis, one group received water and the other received aqueous extract of corn silk and continued feeding for ten days. Blood samples were collected for biochemical analysis before induction and in the fifth and tenth post-induction day. Urine samples were taken to estimate urinary ca+2 levels and crystals. The histopathological examination was carried to check for crystal deposits in renal tissues. Results: Corn silk aqueous extract produced a significant reduction of blood urea nitrogen(5.2+/-0.08 vs 7.3+/-0.2 mmol/l, serum creatinine (85.9+/-0.2 vs 97.3+/-0.5 mmol/l and serum Na+ levels (137+/-0.2 vs 142.16+/-0.7 mmol/l with non-significant reduction in serum K+ (4.0+/-0.02 vs 4.2+/-0.05. There is a significant reduction in calcium deposition in renal parenchyma in comparison to the control group after ten days of treatment. Conclusion: Corn silk had a significant diuretic effect that accelerates the excretion of urinary calcium. [J Intercult Ethnopharmacol 2012; 1(2.000: 75-78

  20. Anti-inflammatory effect of Moringa oleifera Lam. seeds on acetic acid-induced acute colitis in rats

    Mohsen Minaiyan; Gholamreza Asghari; Diana Taheri; Mozhgan Saeidi; Salar Nasr-Esfahani

    2014-01-01

    Objective: Anti-inflammatory, immuno-modulatory, and antioxidant properties of Moringa oleifera Lam. suggest that it might have beneficial effects on colitis. The present study was performed to investigate the anticolitis effect of Moringa oleifera seeds hydro-alcoholic extract (MSHE) and its chloroform fraction (MCF) on acetic acid-induced colitis in rats. Materials and Methods: Both MSHE and MCF with three increasing doses (50, 100, and 200 mg/kg) were administered orally to separate groups...

  1. Heat shock protein 70-dependent protective effect of polaprezinc on acetylsalicylic acid-induced apoptosis of rat intestinal epithelial cells

    Qin, Ying; NAITO, Yuji; Handa, Osamu; Hayashi, Natsuko; Kuki, Aiko; Mizushima, Katsura; Omatsu, Tatsushi; Tanimura, Yuko; Morita, Mayuko; Adachi, Satoko; Fukui, Akifumi; Hirata, Ikuhiro; Kishimoto, Etsuko; Nishikawa, Taichiro; Uchiyama, Kazuhiko

    2011-01-01

    Protection of the small intestine from mucosal injury induced by nonsteroidal anti-inflammatory drugs including acetylsalicylic acid is a critical issue in the field of gastroenterology. Polaprezinc an anti-ulcer drug, consisting of zinc and L-carnosine, provides gastric mucosal protection against various irritants. In this study, we investigated the protective effect of polaprezinc on acetylsalicylic acid-induced apoptosis of the RIE1 rat intestinal epithelial cell line. Confluent rat intest...

  2. Subchronic Treatment of Donepezil Rescues Impaired Social, Hyperactive, and Stereotypic Behavior in Valproic Acid-Induced Animal Model of Autism

    Ji-Woon Kim; Hana Seung; Kyung Ja Kwon; Mee Jung Ko; Eun Joo Lee; Hyun Ah Oh; Chang Soon Choi; Ki Chan Kim; Edson Luck Gonzales; Jueng Soo You; Dong-Hee Choi; Jongmin Lee; Seol-Heui Han; Sung Min Yang; Jae Hoon Cheong

    2014-01-01

    Autism spectrum disorder (ASD) is a group of pervasive developmental disorders with core symptoms such as sociability deficit, language impairment, and repetitive/restricted behaviors. Although worldwide prevalence of ASD has been increased continuously, therapeutic agents to ameliorate the core symptoms especially social deficits, are very limited. In this study, we investigated therapeutic potential of donepezil for ASD using valproic acid-induced autistic animal model (VPA animal model). W...

  3. Comparative Study of Berberis vulgaris Fruit Extract and Berberine Chloride Effects on Acetic Acid-Induced Colitis in Rats

    Minaiyan, Mohsen; Ghannadi, Alireza; Mahzouni, Parvin; Jaffari-Shirazi, Elham

    2011-01-01

    Antioxidant and immunomodulatory effects of anthocyanins are abundant in berberry fruits suggesting that they may have beneficial effects on inflammatory bowel diseases (IBD). The present study was carried out to investigate the anti-colitic effect of Berberis vulgaris fruit extract (BFE) compared to berberine chloride (BEC) and corticosteroids using an animal model of acetic acid induced experimental colitis. BFE with three different doses (375, 750, and 1500 mg/Kg) was administered orally o...

  4. Ameliorative effects of polyunsaturated fatty acids against palmitic acid-induced insulin resistance in L6 skeletal muscle cells

    Sawada Keisuke

    2012-03-01

    Full Text Available Abstract Background Fatty acid-induced insulin resistance and impaired glucose uptake activity in muscle cells are fundamental events in the development of type 2 diabetes and hyperglycemia. There is an increasing demand for compounds including drugs and functional foods that can prevent myocellular insulin resistance. Methods In this study, we established a high-throughput assay to screen for compounds that can improve myocellular insulin resistance, which was based on a previously reported non-radioisotope 2-deoxyglucose (2DG uptake assay. Insulin-resistant muscle cells were prepared by treating rat L6 skeletal muscle cells with 750 μM palmitic acid for 14 h. Using the established assay, the impacts of several fatty acids on myocellular insulin resistance were determined. Results In normal L6 cells, treatment with saturated palmitic or stearic acid alone decreased 2DG uptake, whereas unsaturated fatty acids did not. Moreover, co-treatment with oleic acid canceled the palmitic acid-induced decrease in 2DG uptake activity. Using the developed assay with palmitic acid-induced insulin-resistant L6 cells, we determined the effects of other unsaturated fatty acids. We found that arachidonic, eicosapentaenoic and docosahexaenoic acids improved palmitic acid-decreased 2DG uptake at lower concentrations than the other unsaturated fatty acids, including oleic acid, as 10 μM arachidonic acid showed similar effects to 750 μM oleic acid. Conclusions We have found that polyunsaturated fatty acids, in particular arachidonic and eicosapentaenoic acids prevent palmitic acid-induced myocellular insulin resistance.

  5. Rabbit gastric ulcer models: comparison and evaluation of acetic acid-induced ulcer and mucosectomy-induced ulcer

    Maeng, Jin Hee; Lee, Eunhye; Lee, Don Haeng; YANG, SU-GEUN

    2013-01-01

    In this study, we examined rabbit gastric ulcer models that can serve as more clinically relevant models. Two types of ulcer model were studied: acetic acid-induced ulcers (AAU) and mucosal resection-induced ulcers (MRU). For AAU, rabbit gastric mucosa was exposed by median laparotomy and treated with bottled acetic acid. MRU was examined as a model for endoscopic mucosal resection (EMR). Normal saline was injected into the submucosal layer and the swollen mucosa was resected with scissors. E...

  6. The influence of pretreatment with ghrelin on the development of acetic-acid-induced colitis in rats.

    Maduzia, D; Matuszyk, A; Ceranowicz, D; Warzecha, Z; Ceranowicz, P; Fyderek, K; Galazka, K; Dembinski, A

    2015-12-01

    Ghrelin has been primarily shown to exhibit protective and therapeutic effect in the gut. Pretreatment with ghrelin inhibits the development of acute pancreatitis and accelerates pancreatic recovery in the course of this disease. In the stomach, ghrelin reduces gastric mucosal damage induced by ethanol, stress or alendronate, as well as accelerates the healing of acetic acid-induced gastric and duodenal ulcer. The aim of present studies was to investigate the effect of pretreatment with ghrelin on the development of acetic acid-induced colitis. Studies have been performed on male Wistar rats. Animals were treated intraperitoneally with saline (control) or ghrelin (4, 8 or 16 nmol/kg/dose). Saline or ghrelin was given twice: 8 and 1 h before induction of colitis. Colitis was induced by a rectal enema with 1 ml of 4% solution of acetic acid and the severity of colitis was assessed 1 or 24 hours after induction of inflammation. Rectal administration of acetic acid induced colitis in all animals. Damage of colonic wall was seen at the macroscopic and microscopic level. This effect was accompanied by a reduction in colonic blood flow and mucosal DNA synthesis. Moreover, induction of colitis significantly increased mucosal concentration of pro-inflammatory interleukin-1β (IL-1β), activity of myeloperoxidase and concentration of malondialdehyde (MDA). Mucosal activity of superoxide dismutase (SOD) was reduced. Pretreatment with ghrelin reduced the area and grade of mucosal damage. This effect was accompanied by an improvement of blood flow, DNA synthesis and SOD activity in colonic mucosa. Moreover, ghrelin administration reduced mucosal concentration of IL-1β and MDA, as well as decreased mucosal activity of myeloperoxidase. Administration of ghrelin protects the large bowel against the development of the acetic acid-induced colitis and this effect seems to be related to the ghrelin-evoked anti-inflammatory and anti-oxidative effects. PMID:26769837

  7. Effects of Pfaffia glomerata (Spreng pedersen aqueous extract on healing acetic acid-induced ulcers

    Cristina Setim Freitas

    2008-08-01

    Full Text Available The present study was carried out to evaluate the acute toxicity and the effect of the aqueous extract of the roots from Pfaffia glomerata (Spreng Pedersen (Amaranthaceae (AEP on the prevention of acetic acid-induced ulcer and on the healing process of previously induced ulcers. The acute toxicity was evaluated in Swiss mice after oral administration of a single dose and the chronic gastric ulcer was induced with local application of acetic acid. The results showed that the LD50 of the extract was 684.6 mg.kg-1 for the intraperitoneal administration and higher than 10 mg.kg-1by the oral route. The administration of the AEP did not prevent ulcers formation. However, the AEP increased of the healing process of previously induced ulcers. The results suggest that AEP chronically administered promote an increase of tissue healing, after the damage induced by acetic acid and the extract seemed to be destituted of toxic effects in the mice by the oral route.Pfaffia glomerata (Spreng Pedersen (Amaranthaceae, uma planta conhecida popularmente como "Ginseng Brasileiro" e "paratudo", é utilizada para tratar distúrbios gástricos e como cicatrizante. Em estudos anteriores, foi demonstrado que o extrato aquoso bruto da P. glomerata (AEP protegeu a mucosa gástrica contra úlceras induzidas por etanol e estresse e reduziu a secreção ácida gástrica basal e estimulada em ratos com ligadura de piloro. Além disso, a secreção gástrica de animais tratados com AEP apresentou níveis de nitrato e nitrito aumentados. O objetivo deste estudo foi avaliar se o AEP previne o desenvolvimento de úlceras induzidas por ácido acético e o efeito desse extrato no processo de cicatrização em úlceras previamente formadas. A administração do AEP em diferentes doses produziu efeitos tóxicos baixos e não preveniu a formação de úlceras, porém aumentou o processo de cicatrização em úlceras já existentes, como evidenciado no estudo histopatológico. Em

  8. Gene expression in retinoic acid-induced neural tube defects A cDNA mieroarray analysis

    Xiaodong Long; Zhong Yang; Yi Zeng; Hongli Li; Yangyun Han; Chao You

    2009-01-01

    the cranium and abnormal changes of the metencephalon and face.cDNA microarray analysis suggested that the changes in expression of seven different genes were similar on both days E10.5 and E11.5. These were downregulation of NekT, Igfbp5, Zw10,Csf3r, Psmc6 and Rbl, and upregulation of Apoa-4. This study also indicated that Cdk5 expression was downregulated in the retinoic acid group on day E11.5. The results of the cDNA microarray analysis were partly confirmed by Northern blotting.CONCLUSION: Cdk5, NekT, Igfbp5, ZwlO, Csf3r, Psmc6, Rb 1 and Apoa-4 may be key factors in retinoic acid-induced neural tube defects.

  9. Effects of low potassium dextran glucose solution on oleic acid-induced acute lung injury in juvenile piglets

    LING Feng; LIU Ying-long; LIU Ai-jun; WANG Dong; WANG Qiang

    2011-01-01

    Background Epithelial dysfunction in lungs plays a key role in the pathogenesis of acute lung injury. The beneficial effects of low potassium dextran glucose solution (LPD) have been reported in lung preservation, and LPD enables injured alveolar pneumocytes to recover. So we hypothesized that systemic administration of LPD may have benefits in treating acute lung injury. We investigated the effects of LPD on arterial blood gas and levels of some cytokines in oleic acid-induced acute lung injury in juvenile piglets.Methods Oleic acid (0.1 ml/kg) was intrapulmonarily administered to healthy anesthetized juvenile piglets. Ten animals were randomly assigned to two groups (n=5 each): oleic acid-induced group (control group) with intravenous infusion of 12.5 ml/kg of lactated Ringer's solution 30 minutes before administration of oleic acid and LPD group with systemic administration of LPD (12.5 ml/kg) 30 minutes before injecting oleic acid. Blood gas variables and concentrations of tumor necrosis factor alpha, endothelin 1 and interleukin 10 were measured before and every 1 hour for 6 hours after initial lung injury.Results Compared with control group, blood pH, partial pressure of arterial oxygen to fraction of inspired oxygen ratio,partial pressure of arterial carbon dioxide, and mean pulmonary arterial pressure in LPD group were improved (P<0.05or 0.01). Six hours after lung injury, concentration of tumor necrosis factor alpha in lung tissue was lower in LPD group than control group (P<0.05). Plasmic concentration of endothelin 1 showed lower in LPD group while plasmic concentration of interleukin 10 showed higher in LPD group (P<0.05).Conclusions Before lung injury, systemic administration of LPD can improve gas exchange, attenuate pulmonary hypertension, decrease plasmic levels of endothelin 1, increase interleukin 10 and decrease concentration of tumor necrosis factor alpha in lung tissue in oleic acid-induced acute lung injury in juvenile piglets.

  10. Genetic parameters for rennet- and acid-induced coagulation properties in milk from Swedish Red dairy cows.

    Gustavsson, F; Glantz, M; Poulsen, N A; Wadsö, L; Stålhammar, H; Andrén, A; Lindmark Månsson, H; Larsen, L B; Paulsson, M; Fikse, W F

    2014-01-01

    Milk coagulation is an important processing trait, being the basis for production of both cheese and fermented products. There is interest in including technological properties of these products in the breeding goal for dairy cattle. The aim of the present study was therefore to estimate genetic parameters for milk coagulation properties, including both rennet- and acid-induced coagulation, in Swedish Red dairy cattle using genomic relationships. Morning milk samples and blood samples were collected from 395 Swedish Red cows that were selected to be as genetically unrelated as possible. Using a rheometer, milk samples were analyzed for rennet- and acid-induced coagulation properties, including gel strength (G'), coagulation time, and yield stress (YS). In addition to the technological traits, milk composition was analyzed. A binary trait was created to reflect that milk samples that had not coagulated 40min after rennet addition were considered noncoagulating milk. The cows were genotyped by using the Illumina BovineHD BeadChip (Illumina Inc., San Diego, CA). Almost 600,000 markers remained after quality control and were used to construct a matrix of genomic relationships among the cows. Multivariate models including fixed effects of herd, lactation stage, and parity were fitted using the ASReml software to obtain estimates of heritabilities and genetic and phenotypic correlations. Heritability estimates (h(2)) for G' and YS in rennet and acid gels were found to be high (h(2)=0.38-0.62) and the genetic correlations between rennet-induced and acid-induced coagulation properties were weak but favorable, with the exception of YSrennet with G'acid and YSacid, both of which were strong. The high heritability (h(2)=0.45) for milk coagulating ability expressed as a binary trait suggests that noncoagulation could be eliminated through breeding. Additionally, the results indicated that the current breeding objective could increase the frequency of noncoagulating milk and

  11. Mitochondrial genome depletion in human liver cells abolishes bile acid-induced apoptosis: role of the Akt/mTOR survival pathway and Bcl-2 family proteins.

    Marin, Jose J G; Hernandez, Alicia; Revuelta, Isabel E; Gonzalez-Sanchez, Ester; Gonzalez-Buitrago, Jose M; Perez, Maria J

    2013-08-01

    Acute accumulation of bile acids in hepatocytes may cause cell death. However, during long-term exposure due to prolonged cholestasis, hepatocytes may develop a certain degree of chemoresistance to these compounds. Because mitochondrial adaptation to persistent oxidative stress may be involved in this process, here we have investigated the effects of complete mitochondrial genome depletion on the response to bile acid-induced hepatocellular injury. A subline (Rho) of human hepatoma SK-Hep-1 cells totally depleted of mitochondrial DNA (mtDNA) was obtained, and bile acid-induced concentration-dependent activation of apoptosis/necrosis and survival signaling pathways was studied. In the absence of changes in intracellular ATP content, Rho cells were highly resistant to bile acid-induced apoptosis and partially resistant to bile acid-induced necrosis. In Rho cells, both basal and bile acid-induced generation of reactive oxygen species (ROS), such as hydrogen peroxide and superoxide anion, was decreased. Bile acid-induced proapoptotic signals were also decreased, as evidenced by a reduction in the expression ratios Bax-α/Bcl-2, Bcl-xS/Bcl-2, and Bcl-xS/Bcl-xL. This was mainly due to a downregulation of Bax-α and Bcl-xS. Moreover, in these cells the Akt/mTOR pathway was constitutively activated in a ROS-independent manner and remained similarly activated in the presence of bile acid treatment. In contrast, ERK1/2 activation was constitutively reduced and was not activated by incubation with bile acids. In conclusion, these results suggest that impaired mitochondrial function associated with mtDNA alterations, which may occur in liver cells during prolonged cholestasis, may activate mechanisms of cell survival accounting for an enhanced resistance of hepatocytes to bile acid-induced apoptosis. PMID:23597504

  12. Saturated Fatty Acid Induces Insulin Resistance Partially Through Nucleotide-binding Oligomerization Domain 1 Signaling Pathway in Adipocytes

    Yi-jun Zhou; Yin-si Tang; Yu-ling Song; Ai Li; Hui Zhou; Yan Li

    2013-01-01

    Objective To investigate the potential role of nucleotide-binding oligomerization domain 1 (NOD1), a component of the innate immune system, in mediating lipid-induced insulin resistance in adipocytes. Methods Adipocytes from Toll-like receptor 4 deficiency mice were used for stimulation experiments. The effect of oleate/palmitate mixture on nuclear factor-κB (NF-κB) activation was analyzed by reporter plasmid assay. The release of proinflammatory chemokine/cytokines production was determined by using real-time PCR. Insulin-stimulated glucose uptake was measured by 2-deoxy-D-[3H] glucose uptake assay. Chemokine/cytokine expression and glucose uptake in adipocytes transfected with small interfering RNA (siRNA) targeting NOD1 upon fatty acids treatment were analyzed. Results Oleate/palmitate mixture activated the NF-κB pathway and induced interleukin-6, tumor necrosis factor-α, and monocyte chemoattractant protein-1 mRNA expressions in adipocytes from mice deficient in Toll-like receptor 4, and these effects were blocked by siRNA targeting NOD1. Furthermore, saturated fatty acids decreased the ability of insulin-stimulated glucose uptake. Importantly, siRNA targeting NOD1 partially reversed saturated fatty acid-induced suppression of insulin-induced glucose uptake. Conclusion NOD1 might play an important role in saturated fatty acid-induced insulin resistance in adipocytes, suggesting a mechanism by which reduced NOD1 activity confers beneficial effects on insulin action.

  13. Modulation of the retinoic acid-induced cell apoptosis and differentiation by the human TR4 orphan nuclear receptor

    In our previous studies, the TR4 orphan nuclear receptor (TR4) has been demonstrated to suppress retinoic acid (RA)-induced transactivation via a negative feedback control mechanism and in situ analysis showed that TR4 is extensively expressed in mouse brain, especially in regions where the cells are proliferating. To further study the potential roles of TR4 during cell differentiation, a tetracycline-inducible system with anti-sense TR4 in teratocarcinoma P19 cell lines was generated to analyze the retinoic acid-induced differentiation of these cells. The results indicated that the expression of TR4 reduced by doxycycline anti-sense TR4 would alter the retinoic acid-induced differentiation pathway that results in the changes of cell morphology and cell cycle profile. Unexpectedly, our data further indicated that the RA-induced apoptosis, judging by DNA fragmentation, could also be altered by the induction of anti-sense TR4. Together, these findings provide the first in vivo evidence that an orphan nuclear receptor, such as TR4, may play major roles in the RA-mediated apoptosis or differentiation in P19 cells

  14. Combinatorial localized dissolution analysis: Application to acid-induced dissolution of dental enamel and the effect of surface treatments.

    Parker, Alexander S; Al Botros, Rehab; Kinnear, Sophie L; Snowden, Michael E; McKelvey, Kim; Ashcroft, Alexander T; Carvell, Mel; Joiner, Andrew; Peruffo, Massimo; Philpotts, Carol; Unwin, Patrick R

    2016-08-15

    A combination of scanning electrochemical cell microscopy (SECCM) and atomic force microscopy (AFM) is used to quantitatively study the acid-induced dissolution of dental enamel. A micron-scale liquid meniscus formed at the end of a dual barrelled pipette, which constitutes the SECCM probe, is brought into contact with the enamel surface for a defined period. Dissolution occurs at the interface of the meniscus and the enamel surface, under conditions of well-defined mass transport, creating etch pits that are then analysed via AFM. This technique is applied to bovine dental enamel, and the effect of various treatments of the enamel surface on acid dissolution (1mM HNO3) is studied. The treatments investigated are zinc ions, fluoride ions and the two combined. A finite element method (FEM) simulation of SECCM mass transport and interfacial reactivity, allows the intrinsic rate constant for acid-induced dissolution to be quantitatively determined. The dissolution of enamel, in terms of Ca(2+) flux ( [Formula: see text] ), is first order with respect to the interfacial proton concentration and given by the following rate law: [Formula: see text] , with k0=0.099±0.008cms(-1). Treating the enamel with either fluoride or zinc ions slows the dissolution rate, although in this model system the partly protective barrier only extends around 10-20nm into the enamel surface, so that after a period of a few seconds dissolution of modified surfaces tends towards that of native enamel. A combination of both treatments exhibits the greatest protection to the enamel surface, but the effect is again transient. PMID:27209395

  15. Synergistic effect of natural compounds on the fatty acid-induced autophagy of activated hepatic stellate cells.

    Lee, Kuan-Wei; Thiyagarajan, Varadharajan; Sie, Huei-Wun; Cheng, Ming-Fan; Tsai, May-Jywan; Chia, Yi-Chen; Weng, Ching-Feng

    2014-09-01

    Autophagy, a lysosomal pathway to maintain cellular homeostasis, is mediated via the mammalian target of rapamycin (mTOR)-dependent pathways. Hepatic stellate cells (HSCs), previously termed fat- or vitamin A-storing cells, can transdifferentiate into myofibroblast-like cells and are the most relevant cell type for overproduction of extracellular matrix (ECM) and development of liver fibrosis during injury. However, the role of autophagy in fat metabolism of HSCs remains unclear. This study investigates the regulatory effect of natural compounds on fatty acid-induced autophagy pathways of nonchemical-induced HSC (NHSC) and thioacetamide-induced HSC. Oleic acid (OA) and palmitic acid (PA) have shown a significant effect on cell proliferation with oil red O staining and Western blot confirming that OA and PA induce fat storage ability and autophagy protein expression in NHSC. Natural compounds rutin, curcumin, antroquinonol and benzyl cinnamate treatment have shown no effect on the autophagy protein expression. Nevertheless, cells pretreated with OA and PA then treated with rutin, curcumin, antroquinonol and benzyl cinnamate could significantly induce the light chain I/II (LC3 I/II) protein expression. In mTOR-dependent pathway, the PI3K-Class I, Akt, and p-mTOR proteins were decreased with PA treatment. However, there were no significant changes in PI3K-Class III and Beclin-1 protein expressions found to imply that this autophagy is unrelated to the mTOR-independent pathway. Taken together, the present study unveils rutin and curcumin as a possible effective stimulation for fatty acid-induced autophagy via mTOR-dependent pathways in NHSC. We further suggest the benefits of these natural compounds for alleviating liver fibrosis. PMID:24857031

  16. Preventive effect of a pectic polysaccharide of the common cranberry Vaccinium oxycoccos L. on acetic acid-induced colitis in mice

    Sergey V Popov; Pavel A Markov; Ida R Nikitina; Sergey Petrishev; Vasily Smirnov; Yury S Ovodov

    2006-01-01

    AIM: To study isolation and chemical characterization of pectin derived from the common cranberry Vaccinium oxycoccos L. (oxycoccusan OP) and the testing of its preventive effect on experimental colitis.METHODS: Mice were administrated orally with OP two days prior to a rectal injection of 5% acetic acid and examined for colonic damage 24 h later. Colonic inflammation was characterized by macroscopical injury and enhanced levels of myeloperoxidase activity measured spectrophotometrically with o-phenylene diamine as the substrate. The mucus contents of the colon were determined by the Alcian blue dye binding method. Vascular permeability was estimated using 4%Evans blue passage after i.p. injection of 0.05 mol/L acetic acid.RESULTS: In the mice treated with OP, colonic macroscopic scores (1.1 ± 0.4 vs 2.7, P < 0.01) and the total square area of damage (10 ± 2 vs 21 ± 7, P < 0.01)were significantly reduced when compared with the vehicle-treated colitis group. OP was shown to decrease the tissue myeloperoxidase activity in colons (42 ± 11 vs 112 ± 40, P < 0.01) and enhance the amount of mucus of colitis mice (0.9 ± 0.1 vs 0.4 ± 0.1, P < 0.01). The level of colonic malondialdehyde was noted to decrease in OP-pretreated mice (3.6 ± 0.7 vs 5.1 ± 0.8, P < 0.01).OP was found to decrease the inflammatory status of mice as was determined by reduction of vascular permeability (161 ± 34 vs 241 ± 21, P < 0.01). Adhesion of peritoneal neutrophils and macrophages was also shown to decrease after administration of OP (141 ± 50vs 235 ± 37, P < 0.05).CONCLUSION: Thus, a preventive effect of pectin from the common cranberry, namely oxycoccusan OP,on acetic acid-induced colitis in mice was detected.A reduction of neutrophil infiltration and antioxidant action may be implicated in the protective effect of oxycoccusan.

  17. Herpes simplex virus infection is sensed by both Toll-like receptors and retinoic acid-inducible gene- like receptors, which synergize to induce type I interferon production

    Rasmussen, Simon Brandtoft; Jensen, Søren B; Nielsen, C;

    2009-01-01

    The innate antiviral response is initiated by pattern recognition receptors, which recognize viral pathogen-associated molecular patterns. Here we show that retinoic acid-inducible gene (RIG)-I-like receptors (RLRs) in cooperation with Toll-like receptor (TLR) 9 is required for expression of type I...

  18. Evaluation of potential gender-related differences in behavioral and cognitive alterations following pilocarpine-induced status epilepticus in C57BL/6 mice.

    Oliveira, Clarissa Vasconcelos de; Grigoletto, Jéssica; Funck, Vinícius Rafael; Ribeiro, Leandro Rodrigo; Royes, Luiz Fernando Freire; Fighera, Michele Rechia; Furian, Ana Flávia; Oliveira, Mauro Schneider

    2015-05-01

    Together with pharmacoresistant seizures, the quality of life of temporal lobe epilepsy (TLE) patients is negatively impacted by behavioral comorbidities including but not limited to depression, anxiety and cognitive deficits. The pilocarpine model of TLE has been widely used to study characteristics of human TLE, including behavioral comorbidities. Since the outcomes of pilocarpine-induced TLE might vary depending on several experimental factors, we sought to investigate potential gender-related differences regarding selected behavioral alterations in C57BL6 mice. We found that epileptic mice, independent of gender, displayed increased anxiety-like behavior in the open-field test. In the object recognition test, epileptic mice, regardless of gender, showed a decreased recognition index at 24 (but not at 4) hours after training. On the other hand, no significant differences were found regarding mice learning and memory performance in the Barnes maze paradigm. Motor coordination and balance as assessed by the beam walk and rotarod tests were not impaired in epileptic mice of both genders. However, female mice, independent of epilepsy, performed the beam walk and rotarod tasks better than their male counterparts. We also found that only male epileptic mice displayed disturbed behavior in the forced swim test, but the mice of both genders displayed anhedonia-like behavior in the taste preference test. Lastly, we found that the extent of hilar cell loss is similar in both genders. In summary, both genders can be successfully employed to study behavioral comorbidities of TLE; however, taking the potential gender differences into account may help choose the more appropriated gender for a given task, which may be of value for the minimization of the number of animals used during the experiments. PMID:25749198

  19. WITHDRAWN: Evaluation of potential gender-related differences in behavioral and cognitive alterations following pilocarpine-induced status epilepticus in C57BL/6 mice.

    de Oliveira, Clarissa Vasconcelos; Grigoletto, Jéssica; Funck, Vinícius Rafael; Ribeiro, Leandro Rodrigo; Royes, Luiz Fernando Freire; Fighera, Michele Rechia; Furian, Ana Flávia; Oliveira, Mauro Schneider

    2014-03-10

    This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy. PMID:24625817

  20. Lithium pilocarpine-induced status epilepticus in postnatal day 20 rats results in greater neuronal injury in ventral versus dorsal hippocampus

    Ekstrand, Jeffrey J.; Pouliot, Wendy; Scheerlinck, Peter; Dudek, F. Edward

    2011-01-01

    Many quantitative animal studies examining the possible relationship between hippocampal neuronal loss and the development of epilepsy have examined only the dorsal hippocampus. The ventral hippocampus, however, represents the more homologous structure to the anterior hippocampus in humans which is the area associated with the maximal damage in patients with temporal lobe epilepsy. This study tested the hypothesis that the ventral hippocampus has greater neuronal injury than the dorsal hippoc...

  1. N-w-Propyl-L-arginine (L-NPA) reduces status epilepticus and early epileptogenic events in a mouse model of epilepsy: behavioural, EEG and immunohistochemical analyses

    Beamer, E.; Otáhal, Jakub; Sills, G.J.; Thippeswamy, T.

    2012-01-01

    Roč. 36, č. 9 (2012), s. 3194-3203. ISSN 0953-816X R&D Projects: GA ČR(CZ) GAP303/10/0999 Institutional research plan: CEZ:AV0Z50110509 Institutional support: RVO:67985823 Keywords : aberrant sprouting * gliosis * nitric oxide * seizure * telemetry Subject RIV: FH - Neurology Impact factor: 3.753, year: 2012

  2. Antitussive Activity of the Water-Extracted Carbohydrate Polymer from Terminalia chebula on Citric Acid-Induced Cough

    Chatterjee, Udipta Ranjan; Majee, Sujay Kumar; Ray, Bimalendu

    2013-01-01

    Terminalia chebula, a medicinal plant, is widely used in the management of various diseases. As the water extract of its dried ripe fruit is a frequently used preparation, we decided to look for bioactive polysaccharide in this extract. We demonstrate that the obtained polysaccharide fraction, CP, contained a highly branched arabinogalactan protein having a (1 → 3)-, (1 → 6)- and (1 → 3, 6)-linked β-D-Galp together with (1 → 5)- and (1 → 3)-linked α-L-Araf and nonreducing end units of α-L-Araf. This polymer possesses strong antitussive property. Our results showed that the number of citric acid-induced cough efforts decreased significantly after the oral application of polysaccharide fraction in a dose of 50 mg kg−1 body weight. Its antitussive efficacy was higher than cough suppressive effect of standard drug codeine. Therefore, traditional aqueous extraction method provides a major polysaccharide, which induces a pharmacological effect: this could represent an attractive approach in phytotherapeutic managements. PMID:23878602

  3. Antitussive Activity of the Water-Extracted Carbohydrate Polymer from Terminalia chebula on Citric Acid-Induced Cough

    Gabriela Nosalova

    2013-01-01

    Full Text Available Terminalia chebula, a medicinal plant, is widely used in the management of various diseases. As the water extract of its dried ripe fruit is a frequently used preparation, we decided to look for bioactive polysaccharide in this extract. We demonstrate that the obtained polysaccharide fraction, CP, contained a highly branched arabinogalactan protein having a 1→3-, 1→6- and 1→3,6-linked β-D-Galp together with 1→5- and 1→3-linked α-L-Araf and nonreducing end units of α-L-Araf. This polymer possesses strong antitussive property. Our results showed that the number of citric acid-induced cough efforts decreased significantly after the oral application of polysaccharide fraction in a dose of 50 mg kg−1 body weight. Its antitussive efficacy was higher than cough suppressive effect of standard drug codeine. Therefore, traditional aqueous extraction method provides a major polysaccharide, which induces a pharmacological effect: this could represent an attractive approach in phytotherapeutic managements.

  4. Inhibition of acid-induced apoptosis by targeting ASIC1a mRNA with short hairpin RNA

    Xie-chuan WENG; Jian-quan ZHENG; Qing-e JIN; Xiao-yun MA

    2007-01-01

    Aim: To study the role of acid-sensing ion channel (ASIC) la in the cell death and apoptosis induced by extracellular acid in C6 glioma cells. Methods: The stable ASICla-silenced C6 cell line, built with RNA interference technology, were con-firmed by RT-PCR and Western blot analysis. The cell viability following acid exposure was analyzed with lactate dehydrogenase (LDH) and 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. The apoptotic cells dyed with Annexin-V and propidium iodide were measured with a flow cytometer, while the changes of cell cycle were also assayed. Results: The downregulation of ASIC 1 a proteins by stable transfection of short hairpin RNA decreased the cell death percentage and increased cell viability following acid exposure with LDH and the MTT assay. The rate of apoptosis was lower in the ASIC la-silenced cell line than that in the wild-type C6 cell line. The percentage of sub-G0 cells was lower in the ASICla-silenced C6 cells than that in the wild-type cells. Conclusion: Extracellular acid induced cell death and apoptosis viaASICla mechanisms in the C6 glioma cells.

  5. Possible protective role of pregnenolone-16 alpha-carbonitrile in lithocholic acid-induced hepatotoxicity through enhanced hepatic lipogenesis.

    Miyata, Masaaki; Nomoto, Masahiro; Sotodate, Fumiaki; Mizuki, Tomohiro; Hori, Wataru; Nagayasu, Miho; Yokokawa, Shinya; Ninomiya, Shin-ichi; Yamazoe, Yasushi

    2010-06-25

    Lithocholic acid (LCA) feeding causes both liver parenchymal and cholestatic damages in experimental animals. Although pregnenolone-16 alpha-carbonitrile (PCN)-mediated protection against LCA-induced hepatocyte injury may be explained by induction of drug metabolizing enzymes, the protection from the delayed cholestasis remains incompletely understood. Thus, the PCN-mediated protective mechanism has been studied from the point of modification of lipid metabolism. At an early stage of LCA feeding, an imbalance of biliary bile acid and phospholipid excretion was observed. Co-treatment with PCN reversed the increase in serum alanine aminotransferase (ALT) as well as alkaline phosphatase (ALP) activities and hepatic hydrophobic bile acid levels. LCA feeding decreased hepatic mRNA levels of several fatty acid- and phospholipid-related genes before elevation of serum ALT and ALP activities. On the other hand, PCN co-treatment reversed the decrease in the mRNA levels and hepatic levels of phospholipids, triglycerides and free fatty acids. PCN co-treatment also reversed the decrease in biliary phospholipid output in LCA-fed mice. Treatment with PCN alone increased hepatic phospholipid, triglyceride and free fatty acid concentrations. Hepatic fatty acid and phosphatidylcholine synthetic activities increased in mice treated with PCN alone or PCN and LCA, compared to control mice, whereas these activities decreased in LCA-fed mice. These results suggest the possibility that PCN-mediated stimulation of lipogenesis contributes to the protection from lithocholic acid-induced hepatotoxicity. PMID:20359477

  6. TGF-β-SMAD3 signaling mediates hepatic bile acid and phospholipid metabolism following lithocholic acid-induced liver injury.

    Matsubara, Tsutomu; Tanaka, Naoki; Sato, Misako; Kang, Dong Wook; Krausz, Kristopher W; Flanders, Kathleen C; Ikeda, Kazuo; Luecke, Hans; Wakefield, Lalage M; Gonzalez, Frank J

    2012-12-01

    Transforming growth factor-β (TGFβ) is activated as a result of liver injury, such as cholestasis. However, its influence on endogenous metabolism is not known. This study demonstrated that TGFβ regulates hepatic phospholipid and bile acid homeostasis through MAD homolog 3 (SMAD3) activation as revealed by lithocholic acid-induced experimental intrahepatic cholestasis. Lithocholic acid (LCA) induced expression of TGFB1 and the receptors TGFBR1 and TGFBR2 in the liver. In addition, immunohistochemistry revealed higher TGFβ expression around the portal vein after LCA exposure and diminished SMAD3 phosphorylation in hepatocytes from Smad3-null mice. Serum metabolomics indicated increased bile acids and decreased lysophosphatidylcholine (LPC) after LCA exposure. Interestingly, in Smad3-null mice, the metabolic alteration was attenuated. LCA-induced lysophosphatidylcholine acyltransferase 4 (LPCAT4) and organic solute transporter β (OSTβ) expression were markedly decreased in Smad3-null mice, whereas TGFβ induced LPCAT4 and OSTβ expression in primary mouse hepatocytes. In addition, introduction of SMAD3 enhanced the TGFβ-induced LPCAT4 and OSTβ expression in the human hepatocellular carcinoma cell line HepG2. In conclusion, considering that Smad3-null mice showed attenuated serum ALP activity, a diagnostic indicator of cholangiocyte injury, these results strongly support the view that TGFβ-SMAD3 signaling mediates an alteration in phospholipid and bile acid metabolism following hepatic inflammation with the biliary injury. PMID:23034213

  7. Chromosomal localization of a novel retinoic acid induced gene RA28 and the protein distribution of its encoded protein

    2000-01-01

    Gene RA28 is a retinoic acid induced novel gene isolated in our laboratory previously. All-trans retinoic acid (ATRA) was used to induce lung adenocarcinoma cell line GLC-82, and RA28 was obtained by subtractive hybridization. Green fluorescent protein (GFP) has emerged as a unique tool for examining introcellular phenomena in living cells. GFP possesses an intrinsic fluorescence at 488 nm that does not require other co-factors. In this report, an eukaryotic expression plasmid pEGFP-C1-RA28 was constructed and transfected with parental cell line GLC-82 to analyze protein expression and its distribution in living cells. Moreover, radiation hybrid (RH) technique was used to localize RA28 to the chromosome. The results show that gene RA28 is mapped to the chromosome 19q13.1 region, its encoded protein is distributed on cell membrane. All the results further demonstrate that GFP and RH techniques are accurate, fast, repetitive, and will be powerful methods for investigating the gene and protein localization.

  8. Phenylbutyric acid induces the cellular senescence through an Akt/p21{sup WAF1} signaling pathway

    Kim, Hag Dong [Laboratory of Biochemistry, School of Life Sciences and Biotechnology, and BioInstitute, Korea University, Seoul 136-701 (Korea, Republic of); Jang, Chang-Young [Research Center for Cell Fate Control, College of Pharmacy, Sookmyung Women' s University, Seoul 140-742 (Korea, Republic of); Choe, Jeong Min [Laboratory of Biochemistry, School of Life Sciences and Biotechnology, and BioInstitute, Korea University, Seoul 136-701 (Korea, Republic of); Department of Biochemistry, Korea University College of Medicine, Seoul 136-705 (Korea, Republic of); Korean Institute of Molecular Medicine and Nutrition, Seoul 136-705 (Korea, Republic of); Sohn, Jeongwon, E-mail: biojs@korea.ac.kr [Department of Biochemistry, Korea University College of Medicine, Seoul 136-705 (Korea, Republic of); Korean Institute of Molecular Medicine and Nutrition, Seoul 136-705 (Korea, Republic of); Kim, Joon, E-mail: joonkim@korea.ac.kr [Laboratory of Biochemistry, School of Life Sciences and Biotechnology, and BioInstitute, Korea University, Seoul 136-701 (Korea, Republic of)

    2012-06-01

    Highlights: Black-Right-Pointing-Pointer Phenylbutyric acid induces cellular senescence. Black-Right-Pointing-Pointer Phenylbutyric acid activates Akt kinase. Black-Right-Pointing-Pointer The knockdown of PERK also can induce cellular senescence. Black-Right-Pointing-Pointer Akt/p21{sup WAF1} pathway activates in PERK knockdown induced cellular senescence. -- Abstract: It has been well known that three sentinel proteins - PERK, ATF6 and IRE1 - initiate the unfolded protein response (UPR) in the presence of misfolded or unfolded proteins in the ER. Recent studies have demonstrated that upregulation of UPR in cancer cells is required to survive and proliferate. Here, we showed that long exposure to 4-phenylbutyric acid (PBA), a chemical chaperone that can reduce retention of unfolded and misfolded proteins in ER, induced cellular senescence in cancer cells such as MCF7 and HT1080. In addition, we found that treatment with PBA activates Akt, which results in p21{sup WAF1} induction. Interestingly, the depletion of PERK but not ATF6 and IRE1 also induces cellular senescence, which was rescued by additional depletion of Akt. This suggests that Akt pathway is downstream of PERK in PBA induced cellular senescence. Taken together, these results show that PBA induces cellular senescence via activation of the Akt/p21{sup WAF1} pathway by PERK inhibition.

  9. Rabbit gastric ulcer models: comparison and evaluation of acetic acid-induced ulcer and mucosectomy-induced ulcer.

    Maeng, Jin Hee; Lee, Eunhye; Lee, Don Haeng; Yang, Su-Geun

    2013-06-01

    In this study, we examined rabbit gastric ulcer models that can serve as more clinically relevant models. Two types of ulcer model were studied: acetic acid-induced ulcers (AAU) and mucosal resection-induced ulcers (MRU). For AAU, rabbit gastric mucosa was exposed by median laparotomy and treated with bottled acetic acid. MRU was examined as a model for endoscopic mucosal resection (EMR). Normal saline was injected into the submucosal layer and the swollen mucosa was resected with scissors. Endoscopic mucosal resection (EMR) is frequently performed for treatment of early gastric cancers. This procedure inevitably leads to ulcers and bleeding. Bleeding control is the major concern in endoscopic mucosectomy, and some endoscopic hemostatic agents are currently under clinical and preclinical studies. MRU was developed as a model for these induced ulcers and the evaluation of the healing process. The clinical relevancy of those models was compared with that of rat models. Progressive healing was observed for 7 days based on histology. Rabbit models demonstrate round, deep ulcers with clear margins and well-defined healing stages that were difficult to define in rat models. PMID:23825482

  10. Standardized Extract of Bacopa monniera Attenuates Okadaic Acid Induced Memory Dysfunction in Rats: Effect on Nrf2 Pathway

    Subhash Dwivedi

    2013-01-01

    Full Text Available The aim of the present study is to investigate the effect of standardized extract of Bacopa monnieri (memory enhancer and Melatonin (an antioxidant on nuclear factor erythroid 2 related factor 2 (Nrf2 pathway in Okadaic acid induced memory impaired rats. OKA (200 ng was administered intracerebroventricularly (ICV to induce memory impairment in rats. Bacopa monnieri (BM-40 and 80 mg/kg and Melatonin (20 mg/kg were administered 1 hr before OKA injection and continued daily up to day 13. Memory functions were assessed by Morris water maze test on days 13–15. Rats were sacrificed for biochemical estimations of oxidative stress, neuroinflammation, apoptosis, and molecular studies of Nrf2, HO1, and GCLC expressions in cerebral cortex and hippocampus brain regions. OKA caused a significant memory deficit with oxidative stress, neuroinflammation, and neuronal loss which was concomitant with attenuated expression of Nrf2, HO1, and GCLC. Treatment with BM and Melatonin significantly improved memory dysfunction in OKA rats as shown by decreased latency time and path length. The treatments also restored Nrf2, HO1, and GCLC expressions and decreased oxidative stress, neuroinflammation, and neuronal loss. Thus strengthening the endogenous defense through Nrf2 modulation plays a key role in the protective effect of BM and Melatonin in OKA induced memory impairment in rats.

  11. Encephalitis with convulsive status in an immunocompetent pediatric patient caused by Bartonella henselae.

    Cerpa Polar, Rosario; Orellana, Gabriela; Silva Caso, Wilmer; Sánchez Carbonel, José; Santisteban, Javier; Del Valle Mendoza, Juana; Santisteban, Javier

    2016-06-01

    Cat scratch's disease caused by Bartonella henselae, is known to be a self-limited benign process in immunocompetent children. The association with neurologic manifestations is very uncommon especially in patient with no immunologic defects and in cases without specific treatment. A 7 years old male patient, without any immunocompromised defect, presented an atypic presentation of the cat scratch disease. The patient came to the hospital in two opportunities in a status epilepticus, in both cases the diagnosis was encephalitis by Bartonella henselae and the evolution with treatment was monitored with PCR (polymerase chain reaction) in cerebrospinal fluid and blood, as well as IFI (IgM, IgG) serology (indirect immunofluorescence). The patient had a favorable clinical and laboratory evolution for 6 months showing no recurrence of the disease. PMID:27262077

  12. Anti-inflammatory effect of Moringa oleifera Lam. seeds on acetic acid-induced acute colitis in rats

    Mohsen Minaiyan

    2014-02-01

    Full Text Available Objective: Anti-inflammatory, immuno-modulatory, and antioxidant properties of Moringa oleifera Lam. suggest that it might have beneficial effects on colitis. The present study was performed to investigate the anticolitis effect of Moringa oleifera seeds hydro-alcoholic extract (MSHE and its chloroform fraction (MCF on acetic acid-induced colitis in rats. Materials and Methods: Both MSHE and MCF with three increasing doses (50, 100, and 200 mg/kg were administered orally to separate groups of male Wistar rats, 2 h before ulcer induction (using acetic acid 4% and continued for 5 days. Prednisolone (4 mg/kg and normal saline (1 ml/kg were used in reference and control groups, respectively. All rats were sacrificed 24 h after the last dose (at day 6 and tissue injuries were assessed macroscopically and pathologically. Results: Extracts with three doses mentioned before were effective to reduce weight of distal colon (8 cm as a marker for inflammation and tissue edema. Three doses of MSHE and two greater doses of MCF (100 and 200 mg/kg were effective to reduce ulcer severity, area, and index as well as mucosal inflammation severity and extent, crypt damage, invasion involvement, total colitis index, and MPO activity compared with controls. MCF (50 mg/kg was not significantly effective in reducing evaluated parameters of colitis compared with controls. Conclusion: It is concluded that MSHE and MCF were both effective to treat experimental colitis and this might be attributed to their similar major components, biophenols and flavonoids. Since the efficacy was evident even in low doses of MSHE, presence of active constituents with high potency in seeds is persuasive.

  13. Priming by Hexanoic acid induce activation of mevalonic and linolenic pathways and promotes the emission of plant volatiles.

    Eugenio eLlorens

    2016-04-01

    Full Text Available Hexanoic acid is a short natural monocarboxylic acid present in some fruits and plants. Previous studies reported that soil drench application of this acid induces effective resistance in tomato plants against Botrytis cinerea and Pseudomonas syringae and in citrus against Alternaria alternata and Xanthomonas citri. In this work, we performed an in deep study of the metabolic changes produced in citrus by the application of hexanoic acid in response to the challenge pathogen Alternaria alternata, focusing on the response of the plant. Moreover, we used 13C labeled hexanoic to analyze its behavior inside the plants. Finally, we studied the volatile emission of the treated plants after the challenge inoculation. Drench application of 13C labeled hexanoic demonstrated that this molecule stays in the roots and is not mobilized to the leaves, suggesting long distance induction of resistance. Moreover, the study of the metabolic profile showed an alteration of more than two hundred molecules differentially induced by the application of the compound and the inoculation with the fungus. Bioinformatics analysis of data showed that most of these altered molecules could be related with the mevalonic and linolenic pathways suggesting the implication of these pathways in the induced resistance mediated by hexanoic acid. Finally, the application of this compound showed an enhancement of the emission of 17 volatile metabolites. Taken together, this study indicates that after the application of hexanoic acid this compound remains in the roots, provoking molecular changes that may trigger the defensive response in the rest of the plant mediated by changes in the mevalonic and linolenic pathways and enhancing the emission of volatile compounds, suggesting for the first time the implication of mevalonic pathway in response to hexanoic application.

  14. Priming by Hexanoic Acid Induce Activation of Mevalonic and Linolenic Pathways and Promotes the Emission of Plant Volatiles

    Llorens, Eugenio; Camañes, Gemma; Lapeña, Leonor; García-Agustín, Pilar

    2016-01-01

    Hexanoic acid (Hx) is a short natural monocarboxylic acid present in some fruits and plants. Previous studies reported that soil drench application of this acid induces effective resistance in tomato plants against Botrytis cinerea and Pseudomonas syringae and in citrus against Alternaria alternata and Xanthomonas citri. In this work, we performed an in deep study of the metabolic changes produced in citrus by the application of Hx in response to the challenge pathogen A. alternata, focusing on the response of the plant. Moreover, we used 13C labeled hexanoic to analyze its behavior inside the plants. Finally, we studied the volatile emission of the treated plants after the challenge inoculation. Drench application of 13C labeled hexanoic demonstrated that this molecule stays in the roots and is not mobilized to the leaves, suggesting long distance induction of resistance. Moreover, the study of the metabolic profile showed an alteration of more than 200 molecules differentially induced by the application of the compound and the inoculation with the fungus. Bioinformatics analysis of data showed that most of these altered molecules could be related with the mevalonic and linolenic pathways suggesting the implication of these pathways in the induced resistance mediated by Hx. Finally, the application of this compound showed an enhancement of the emission of 17 volatile metabolites. Taken together, this study indicates that after the application of Hx this compound remains in the roots, provoking molecular changes that may trigger the defensive response in the rest of the plant mediated by changes in the mevalonic and linolenic pathways and enhancing the emission of volatile compounds, suggesting for the first time the implication of mevalonic pathway in response to hexanoic application. PMID:27148319

  15. Subchronic treatment of donepezil rescues impaired social, hyperactive, and stereotypic behavior in valproic acid-induced animal model of autism.

    Ji-Woon Kim

    Full Text Available Autism spectrum disorder (ASD is a group of pervasive developmental disorders with core symptoms such as sociability deficit, language impairment, and repetitive/restricted behaviors. Although worldwide prevalence of ASD has been increased continuously, therapeutic agents to ameliorate the core symptoms especially social deficits, are very limited. In this study, we investigated therapeutic potential of donepezil for ASD using valproic acid-induced autistic animal model (VPA animal model. We found that prenatal exposure of valproic acid (VPA induced dysregulation of cholinergic neuronal development, most notably the up-regulation of acetylcholinesterase (AChE in the prefrontal cortex of affected rat and mouse offspring. Similarly, differentiating cortical neural progenitor cell in culture treated with VPA showed increased expression of AChE in vitro. Chromatin precipitation experiments revealed that acetylation of histone H3 bound to AChE promoter region was increased by VPA. In addition, other histone deacetyalse inhibitors (HDACIs such as trichostatin A and sodium butyrate also increased the expression of AChE in differentiating neural progenitor cells suggesting the essential role of HDACIs in the regulation of AChE expression. For behavioral analysis, we injected PBS or donepezil (0.3 mg/kg intraperitoneally to control and VPA mice once daily from postnatal day 14 all throughout the experiment. Subchronic treatment of donepezil improved sociability and prevented repetitive behavior and hyperactivity of VPA-treated mice offspring. Taken together, these results provide evidence that dysregulation of ACh system represented by the up-regulation of AChE may serve as an effective pharmacological therapeutic target against autistic behaviors in VPA animal model of ASD, which should be subjected for further investigation to verify the clinical relevance.

  16. Dietary interesterified fat enriched with palmitic acid induces atherosclerosis by impairing macrophage cholesterol efflux and eliciting inflammation.

    Afonso, Milessa Silva; Lavrador, Maria Silvia Ferrari; Koike, Marcia Kiyomi; Cintra, Dennys Esper; Ferreira, Fabiana Dias; Nunes, Valeria Sutti; Castilho, Gabriela; Gioielli, Luiz Antonio; Paula Bombo, Renata; Catanozi, Sergio; Caldini, Elia Garcia; Damaceno-Rodrigues, Nilsa Regina; Passarelli, Marisa; Nakandakare, Edna Regina; Lottenberg, Ana Maria

    2016-06-01

    Interesterified fats are currently being used to replace trans fatty acids. However, their impact on biological pathways involved in the atherosclerosis development was not investigated. Weaning male LDLr-KO mice were fed for 16weeks on a high-fat diet (40% energy as fat) containing polyunsaturated (PUFA), TRANS, palmitic (PALM), palmitic interesterified (PALM INTER), stearic (STEAR) or stearic interesterified (STEAR INTER). Plasma lipids, lipoprotein profile, arterial lesion area, macrophage infiltration, collagen content and inflammatory response modulation were determined. Macrophage cholesterol efflux and the arterial expression of cholesterol uptake and efflux receptors were also performed. The interesterification process did not alter plasma lipid concentrations. Although PALM INTER did not increase plasma cholesterol concentration as much as TRANS, the cholesterol enrichment in the LDL particle was similar in both groups. Moreover, PALM INTER induced the highest IL-1β, MCP-1 and IL-6 secretion from peritoneal macrophages as compared to others. This inflammatory response elicited by PALM INTER was confirmed in arterial wall, as compared to PALM. These deleterious effects of PALM INTER culminate in higher atherosclerotic lesion, macrophage infiltration and collagen content than PALM, STEAR, STEAR INTER and PUFA. These events can partially be attributed to a macrophage cholesterol accumulation, promoted by apoAI and HDL2-mediated cholesterol efflux impairment and increased Olr-1 and decreased Abca1 and Nr1h3 expressions in the arterial wall. Interesterified fats containing palmitic acid induce atherosclerosis development by promoting cholesterol accumulation in LDL particles and macrophagic cells, activating the inflammatory process in LDLr-KO mice. PMID:27142741

  17. Comparative gastroprotective effects of natural honey, nigella sativa and cimetidine against acetylsalicylic acid Induced gastric ulcer in albino rats

    Natural honey (NH) and Nigella sativa (NS) seeds have been in use as a natural remedy for over thousands of years in various parts of the world. The aim of this study was to assess the protective effects of NS (Nigella sativa) and NH (natural honey) on acetylsalicylic acid induced gastric ulcer in an experimental model with comparison to Cimetidine (CD). The study was conducted on 100 male albino rats, divided into 5 groups, with 20 animals in each group. Group A was used as a control and treated with Gum Tragacanth (GT). Eighty animals of the other groups were given acetylsalicylic acid (0.2 gm/kg body weight for 3 days) to produce ulcers by gavage. Two animals from each group were sacrificed for the detection of gastric ulcers. The remaining 72 animals were equally divided in four groups (B, C, D and E). The rats in group B, C and D were given NS, NH, and CD respectively while those in E were kept as such. No gastric lesions were seen in control group A while all the animals in group E revealed gastric ulcers. The animals of group B, C and D showed healing effects in 15/18 (83%), 14/18 (78%) and 17/18 (94%) animals grossly; 13/18 (72%), 14/18 (78%) and 16/18 (89%) rats showed recovery on microscopic examination respectively. The healing effects were almost the same in all three groups therefore, the statistical difference was not significant among them (p =0.40 and 0.65) while significant from group E (p=0.0000075, 0.0000016 and 0.0000012 respectively). NS and NH are equally effective in healing of gastric ulcer similar to cimetidine. Further broad spectrum studies as well as clinical trials should be conducted before the use of these products as routine medicines. (author)

  18. Anti-inflammatory effects of nesfatin-1 in rats with acetic acid - induced colitis and underlying mechanisms.

    Ozturk, C C; Oktay, S; Yuksel, M; Akakin, D; Yarat, A; Kasimay Cakir, O

    2015-10-01

    Mucosal balance impairment, bacterial over-proliferation, cytokines, inflammatory mediators are known as responsible for inflammatory bowel disease. Besides known anorexigenic, neuroprotective, and anti-apoptotic effects, the major effect of nesfatin-1 on colitis is unknown. Our aim was to investigate the possible anti-inflammatory effects of nesfatin-1 in acetic acid induced colitis model and potential underlying mechanisms. Male Spraque-Dawley rats were anesthetized by intraperitoneal ketamine (100 mg/kg) and chlorpromazine (0.75 mg/kg). For nesfatin-1 and antagonist applications some of the rats were intracerebroventricularly (i.c.v.) cannulated. In colitis group, intrarectally (i.r.) 4% acetic acid solution (1 ml) and 10 minutes later i.c.v. nesfatin-1 (0.05 μg/5 μl) or vehicle (5 μl) were administered. Treatments continued for 3 days. In control group, physiological saline solution was used intrarectally. To identify the underlying effective mechanism of nesfatin-1, rats were divided into 3 subgroups, 5 minutes following colitis induction; i.c.v. atosiban (oxytocin receptor antagonist), SHU9119 (melanocortin receptor antagonist) or GHSR-1a antagonist (ghrelin receptor antagonist) were administered, 5 minutes later nesfatin-1 was administered for 3 days. On the fourth day, rats were decapitated, and colon tissues were sampled. Macroscopic and microscopic damage scores of distal colon, and colonic tissue malondialdehyde, glutathione, myeloperoxidase, superoxide dismutase, catalase, luminol and lucigenin chemiluminescence measurements were analysed. The increased myeloperoxidase activity, malondialdehyde levels, luminol and lucigenin chemiluminescence measurements, macroscopic and microscopic damage scores with colitis induction (P Atosiban and GHSR-1a administration alleviated the protective effect of nesfatin-1 from microscopic and oxidant damage parameters and lipid peroxidation (P < 0.05 - 0.001). The results of the study suggest that nesfatin-1 had a

  19. Stability of the acetic acid-induced bladder irritation model in alpha chloralose-anesthetized female cats.

    F Aura Kullmann

    Full Text Available Time- and vehicle-related variability of bladder and urethral rhabdosphincter (URS activity as well as cardiorespiratory and blood chemistry values were examined in the acetic acid-induced bladder irritation model in α-chloralose-anesthetized female cats. Additionally, bladder and urethra were evaluated histologically using Mason trichrome and toluidine blue staining. Urodynamic, cardiovascular and respiratory parameters were collected during intravesical saline infusion followed by acetic acid (0.5% to irritate the bladder. One hour after starting acetic acid infusion, a protocol consisting of a cystometrogram, continuous infusion-induced rhythmic voiding contractions, and a 5 min "quiet period" (bladder emptied without infusion was precisely repeated every 30 minutes. Administration of vehicle (saline i.v. occurred 15 minutes after starting each of the first 7 cystometrograms and duloxetine (1mg/kg i.v. after the 8(th. Acetic acid infusion into the bladder increased URS-EMG activity, bladder contraction frequency, and decreased contraction amplitude and capacity, compared to saline. Bladder activity and URS activity stabilized within 1 and 2 hours, respectively. Duloxetine administration significantly decreased bladder contraction frequency and increased URS-EMG activity to levels similar to previous reports. Cardiorespiratory parameters and blood gas levels remained consistent throughout the experiment. The epithelium of the bladder and urethra were greatly damaged and edema and infiltration of neutrophils in the lamina propria of urethra were observed. These data provide an ample evaluation of the health of the animals, stability of voiding function and appropriateness of the model for testing drugs designed to evaluate lower urinary tract as well as cardiovascular and respiratory systems function.

  20. Stability of the acetic acid-induced bladder irritation model in alpha chloralose-anesthetized female cats.

    Kullmann, F Aura; Wells, Grace I; Langdale, Christopher L; Zheng, Jihong; Thor, Karl B

    2013-01-01

    Time- and vehicle-related variability of bladder and urethral rhabdosphincter (URS) activity as well as cardiorespiratory and blood chemistry values were examined in the acetic acid-induced bladder irritation model in α-chloralose-anesthetized female cats. Additionally, bladder and urethra were evaluated histologically using Mason trichrome and toluidine blue staining. Urodynamic, cardiovascular and respiratory parameters were collected during intravesical saline infusion followed by acetic acid (0.5%) to irritate the bladder. One hour after starting acetic acid infusion, a protocol consisting of a cystometrogram, continuous infusion-induced rhythmic voiding contractions, and a 5 min "quiet period" (bladder emptied without infusion) was precisely repeated every 30 minutes. Administration of vehicle (saline i.v.) occurred 15 minutes after starting each of the first 7 cystometrograms and duloxetine (1mg/kg i.v.) after the 8(th). Acetic acid infusion into the bladder increased URS-EMG activity, bladder contraction frequency, and decreased contraction amplitude and capacity, compared to saline. Bladder activity and URS activity stabilized within 1 and 2 hours, respectively. Duloxetine administration significantly decreased bladder contraction frequency and increased URS-EMG activity to levels similar to previous reports. Cardiorespiratory parameters and blood gas levels remained consistent throughout the experiment. The epithelium of the bladder and urethra were greatly damaged and edema and infiltration of neutrophils in the lamina propria of urethra were observed. These data provide an ample evaluation of the health of the animals, stability of voiding function and appropriateness of the model for testing drugs designed to evaluate lower urinary tract as well as cardiovascular and respiratory systems function. PMID:24040064

  1. The restrained expression of NF-kB in renal tissue ameliorates folic acid induced acute kidney injury in mice.

    Kumar, Dev; Singla, Surinder K; Puri, Veena; Puri, Sanjeev

    2015-01-01

    The Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) represent family of structurally-related eukaryotic transcription factors which regulate diverse array of cellular processes including immunological responses, inflammation, apoptosis, growth & development. Increased expression of NF-kB has often been seen in many diverse diseases, suggesting the importance of genomic deregulation to disease pathophysiology. In the present study we focused on acute kidney injury (AKI), which remains one of the major risk factor showing a high rate of mortality and morbidity. The pathology associated with it, however, remains incompletely known though inflammation has been reported to be one of the major risk factor in the disease pathophysiology. The role of NF-kB thus seemed pertinent. In the present study we show that high dose of folic acid (FA) induced acute kidney injury (AKI) characterized by elevation in levels of blood urea nitrogen & serum creatinine together with extensive tubular necrosis, loss of brush border and marked reduction in mitochondria. One of the salient observations of this study was a coupled increase in the expression of renal, relA, NF-kB2, and p53 genes and proteins during folic acid induced AKI (FA AKI). Treatment of mice with NF-kB inhibitor, pyrrolidine dithio-carbamate ammonium (PDTC) lowered the expression of these transcription factors and ameliorated the aberrant renal function by decreasing serum creatinine levels. In conclusion, our results suggested that NF-kB plays a pivotal role in maintaining renal function that also involved regulating p53 levels during FA AKI. PMID:25559736

  2. Berberine reverses free-fatty-acid-induced insulin resistance in 3T3-L1 adipocytes through targeting IKKβ

    2008-01-01

    AIM:To investigate the effects and molecular mechanisms of berberine on improving insulin resistance induced by free fatty acids (FFAs) in 3T3-LI adipocytes.METHODS:The model of insulin resistance in 3T3-L1 adipocytes was established by adding palmic acid (0.5 mmol/L) to the culture medium.Berberine treatment was performed at the same time.Glucose uptake rate was determined by the 2-deoxy-[3H]-Dglucose method.The levels of IkB kinase beta (IKKβ)Ser181 phosphorylation,insulin receptor substrate1(IRS-1) Ser307 phosphorylation,expression of IKKβ,IRS-1,nuclear transcription factor kappaB p65 (NF-κB p65),phosphatidylinositol-3-kinase p85(PI-3K p85) and glucose transporter 4 (GLUT4) proteins were detected by Western blotting.The distribution of NF-κB p65 proteins inside the adipocytes was observed through confocal laser scanning microscopy(CLSM).RESULTS:After the intervention of palmic acid for 24 h,the insulin-stimulated glucose transport in 3T3-L1 adipocytes was inhibited by 67%.Meanwhile,the expression of IRS-1 and PI-3K p85 protein was reduced,while the levels of IKKβ Ser181 and IRS-1 Ser307 phosphorylation,and nuclear translocation of NF-κB p65 protein were increased.However,the above indexes,which indicated the existence of insulin resistance,were reversed by berberine although the expression of GLUT4,IKKβ and total NF-κB p65 protein were not changed during this study.CONCLUSION:Insulin resistance induced by FFAs in 3T3-L1 adipocytes can be improved by berberine.Berberine reversed free-fatty-acid-induced insulin resistance in 3T3-L1 adipocytes through targeting IKKβ.

  3. Music application alleviates short-term memory impairments through increasing cell proliferation in the hippocampus of valproic acid-induced autistic rat pups

    Lee, Sung-Min; Kim, Bo-Kyun; Kim, Tae-Woon; Ji, Eun-Sang; Choi, Hyun-Hee

    2016-01-01

    Autism is a neurodevelopmental disorder and this disorder shows impairment in reciprocal social interactions, deficits in communication, and restrictive and repetitive patterns of behaviors and interests. The effect of music on short-term memory in the view of cell proliferation in the hippocampus was evaluated using valproic acid-induced autistic rat pups. Animal model of autism was made by subcutaneous injection of 400-mg/kg valproic acid into the rat pups on the postnatal day 14. The rat p...

  4. Palmitic acid induces interleukin-1β secretion via NLRP3 inflammasomes and inflammatory responses through ROS production in human placental cells.

    Shirasuna, Koumei; Takano, Hiroki; Seno, Kotomi; Ohtsu, Ayaka; Karasawa, Tadayoshi; Takahashi, Masafumi; Ohkuchi, Akihide; Suzuki, Hirotada; Matsubara, Shigeki; Iwata, Hisataka; Kuwayama, Takehito

    2016-08-01

    Maternal obesity, a major risk factor for adverse pregnancy complications, results in inflammatory cytokine release in the placenta. Levels of free fatty acids are elevated in the plasma of obese human. These fatty acids include obesity-related palmitic acids, which is a major saturated fatty acid, that promotes inflammatory responses. Increasing evidence indicates that nucleotide-binding oligomerization domain-like receptor pyrin domain-containing 3 (NLRP3) inflammasomes mediate inflammatory responses induced by endogenous danger signals. We hypothesized that inflammatory responses associated with gestational obesity cause inflammation. To test this hypothesis, we investigated the effect of palmitic acid on the activation of NLRP3 inflammasomes and inflammatory responses in a human Sw.71 trophoblast cell line. Palmitic acid stimulated caspase-1 activation and markedly increased interleukin (IL)-1β secretion in Sw.71 cells. Treatment with a caspase-1 inhibitor diminished palmitic acid-induced IL-1β release. In addition, NLRP3 and caspase-1 genome editing using a CRISPR/Cas9 system in Sw.71 cells suppressed IL-1β secretion, which was stimulated by palmitic acid. Moreover, palmitic acid stimulated caspase-3 activation and inflammatory cytokine secretion (e.g., IL-6 and IL-8). Palmitic acid-induced cytokine secretion were dependent on caspase-3 activation. In addition, palmitic acid-induced IL-1β, IL-6, and IL-8 secretion was depended on reactive oxygen species (ROS) generation. In conclusion, palmitic acid caused activation of NLRP3 inflammasomes and inflammatory responses, inducing IL-1β, IL-6, and IL-8 secretion, which is associated with ROS generation, in human Sw.71 placental cells. We suggest that obesity-related palmitic acid induces placental inflammation, resulting in association with pregnancy complications. PMID:27300134

  5. Constitutive Androstane Receptor-Mediated Changes in Bile Acid Composition Contributes to Hepatoprotection from Lithocholic Acid-Induced Liver Injury in MiceS⃞

    Beilke, Lisa D.; Aleksunes, Lauren M.; Holland, Ricky D; Besselsen, David G; Beger, Rick D.; Klaassen, Curtis D.; Cherrington, Nathan J.

    2009-01-01

    Pharmacological activation of the constitutive androstane receptor (CAR) protects the liver during cholestasis. The current study evaluates how activation of CAR influences genes involved in bile acid biosynthesis as a mechanism of hepatoprotection during bile acid-induced liver injury. CAR activators phenobarbital (PB) and 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP) or corn oil (CO) were administered to C57BL/6 wild-type (WT) and CAR knockout (CAR-null) mice ...

  6. TGF-β-SMAD3 signaling mediates hepatic bile acid and phospholipid metabolism following lithocholic acid-induced liver injury[S

    Matsubara, Tsutomu; Tanaka, Naoki; Sato, Misako; Kang, Dong Wook; Krausz, Kristopher W.; Flanders, Kathleen C.; Ikeda, Kazuo; Luecke, Hans; Wakefield, Lalage M.; Frank J. Gonzalez

    2012-01-01

    Transforming growth factor-β (TGFβ) is activated as a result of liver injury, such as cholestasis. However, its influence on endogenous metabolism is not known. This study demonstrated that TGFβ regulates hepatic phospholipid and bile acid homeostasis through MAD homolog 3 (SMAD3) activation as revealed by lithocholic acid-induced experimental intrahepatic cholestasis. Lithocholic acid (LCA) induced expression of TGFB1 and the receptors TGFBR1 and TGFBR2 in the liver. In addition, immunohisto...

  7. Stock Status

    National Oceanic and Atmospheric Administration, Department of Commerce — These data inform the public of the most recent stock status for all stocks (FSSI and non-FSSI) in the fishery management unit contained in a fishery managment...

  8. Blueberry polyphenols attenuate kainic acid-induced decrements in cognition and alter inflammatory gene expression in rat hippocampus

    Shukitt-Hale, Barbara; Lau, Francis C.; Carey, Amanda N.; Galli, Rachel L.; Spangler, Edward L.; Ingram, Donald K.; Joseph, James A.

    2016-01-01

    Cognitive impairment in age-related neurodegenerative diseases such as Alzheimer's disease may be partly due to long-term exposure and increased susceptibility to inflammatory insults. In the current study, we investigated whether polyphenols in blueberries can reduce the deleterious effects of inflammation induced by central administration of kainic acid by altering the expression of genes associated with inflammation. To this end, 4-month-old male Fischer-344 (F344) rats were fed a control, 0.015% piroxicam (an NSAID) or 2% blueberry diet for 8 weeks before either Ringer's buffer or kainic acid was bilaterally micro-infused into the hippocampus. Two weeks later, following behavioral evaluation, the rats were killed and total RNA from the hippocampus was extracted and used in real-time quantitative RT-PCR (qRT-PCR) to analyze the expression of inflammation-related genes. Kainic acid had deleterious effects on cognitive behavior as kainic acid-injected rats on the control diet exhibited increased latencies to find a hidden platform in the Morris water maze compared to Ringer's buffer-injected rats and utilized non-spatial strategies during probe trials. The blueberry diet, and to a lesser degree the piroxicam diet, was able to improve cognitive performance. Immunohistochemical analyses of OX-6 expression revealed that kainic acid produced an inflammatory response by increasing the OX-6 positive areas in the hippocampus of kainic acid-injected rats. Kainic acid up-regulated the expression of the inflammatory cytokines IL-1β and TNF-α, the neurotrophic factor IGF-1, and the transcription factor NF-κB. Blueberry and piroxicam supplementations were found to attenuate the kainic acid-induced increase in the expression of IL-1β, TNF-α, and NF-κB, while only blueberry was able to augment the increased IGF-1 expression. These results indicate that blueberry polyphenols attenuate learning impairments following neurotoxic insult and exert anti-inflammatory actions

  9. Role of cranial imaging in epileptic status

    Introduction: There is paucity of studies evaluating the role of cranial imaging in the management of status epilepticus (SE); therefore this study evaluates the role of imaging in predicting the outcome of SE. Methods: Consecutive patients with SE were prospectively evaluated. Clinical evaluation, blood counts, serum chemistry and cerebrospinal fluid (CSF) were carried out. Cranial CT scan was performed on a spiral CT and MRI on a 1.5 T scanner. Patients were treated with IV sodium valproate, phenytoin and benzodiazepines as per fixed protocol. Outcome was defined as seizure control at 1 h and mortality. Various clinical and radiological parameters were correlated. Results: There were 99 patients with SE whose mean age was 35 (1-78) years, 40 females and 17 were below 12 years of age. Fifty six patients had central nervous system (CNS) infections, 15 strokes, 13 metabolic encephalopathy, 5 drug default and in the remaining 10 patients various acute symptomatic causes were present. Cranial imaging was abnormal in 59% patients. CT was abnormal in 21 (47.7%) out of 44 patients whereas MRI was abnormal in 26 (63.4%) out of 41 patients. Both MRI and CT were carried out in 14 patients and 12 revealed abnormalities; 2 had abnormality only on MRI. Imaging revealed cortical lesions in 10, subcortical in 19 and both cortical as well as subcortical in 30 patients. One hour seizure control was achieved in 60, seizures recurred within 24 h in 38 and 27 patients died during hospital stay. Seizure type, duration of SE, seizure control at 1 h and mortality did not correlate with radiological abnormalities. Conclusion: Cranial imaging reveals structural abnormality in 59% patients with SE and was not related to SE control and mortality.

  10. Longitudinal variations of brain functional connectivity: A case report study based on a mouse model of epilepsy [v2; ref status: indexed, http://f1000r.es/5my

    A. Erramuzpe

    2015-07-01

    Full Text Available Brain Functional Connectivity (FC quantifies statistical dependencies between areas of the brain. FC has been widely used to address altered function of brain circuits in control conditions compared to different pathological states, including epilepsy, a major neurological disorder. However, FC also has the as yet unexplored potential to help us understand the pathological transformation of the brain circuitry. Our hypothesis is that FC can differentiate global brain interactions across a time-scale of days. To this end, we present a case report study based on a mouse model for epilepsy and analyze longitudinal intracranial electroencephalography data of epilepsy to calculate FC changes from the initial insult (status epilepticus and over the latent period, when epileptogenic networks emerge, and at chronic epilepsy, when unprovoked seizures occur as spontaneous events. We found that the overall network FC at low frequency bands decreased immediately after status epilepticus was provoked, and increased monotonously later on during the latent period. Overall, our results demonstrate the capacity of FC to address longitudinal variations of brain connectivity across the establishment of pathological states.

  11. Neuronal acid-induced [Zn²⁺]i elevations calibrated using the low-affinity ratiometric probe FuraZin-1.

    Kiedrowski, Lech

    2015-11-01

    The experiments were carried out on primary cultures of murine cortical neurons from cryopreserved preparations obtained from embryonic-day-16 fetuses. To calibrate acid-induced intracelluar [Zn(2+) ] ([Zn(2+) ]i ) elevations, a low affinity (Kd = 39 μM at pH 6.1) ratiometric Zn(2+) probe, FuraZin-1, was used. A pHi drop from 7.2 to 6.1 caused [Zn(2+) ]i elevations reaching 2 μM; when the thiol-reactive agent N-ethylmaleimide (NEM) was subsequently applied, [Zn(2+) ]i increased further to 5.6 μM; analogous acid- and NEM-induced [Zn(2+) ]i elevations could also be detected but not calibrated, using the high affinity Zn(2+) probe FluoZin-3. The data indicate that NEM causes Zn(2+) release from ligands that chelate Zn(2+) at pH 6.1. ATP could also chelate Zn(2+) at pH 6.1 because its pKa is about 6.8. Therefore, it was tested whether an ATP depletion affects the acid-induced [Zn(2+) ]i elevations. The ATP depletion was induced by inhibiting mitochondrial and glycolytic ATP production. Interestingly, an almost complete ATP depletion (confirmed using a luciferin/luciferase assay) failed to affect the acid-induced [Zn(2+) ]i increases. These data suggest that the total amount of Zn(2+) accumulated in intracellular ATP-dependent stores (Zn(2+) -ATP complexes and organelles that accumulate Zn(2+) in an ATP-dependent manner) is negligible compared to the amount of Zn(2+) accumulated in the acid-sensitive intracellular ligands. In vitro, upon acidification, Zn(2+) -cysteine complexes release Zn(2+) and ATP chelates the released Zn(2+) . However, in vivo (cultured neurons), an ATP depletion failed to enhance acid-induced [Zn(2+) ]i elevations. These [Zn(2+) ]i elevations were calibrated using a low affinity ratiometric probe FuraZin-1; they reached 2 µM levels and increased to 5 µM when a thiol-reactive agent, N-ethylmaleimide, compromised Zn(2+) binding by cysteines. PMID:26263185

  12. Evidence for genetic regulation of mRNA expression of the dosage-sensitive gene retinoic acid induced-1 (RAI1) in human brain

    Li Chen; Yu Tao; Fan Song; Xi Yuan; Jian Wang; David Saffen

    2016-01-01

    RAI1 (retinoic acid induced-1) is a dosage-sensitive gene that causes Smith-Magenis syndrome (SMS) when mutated or deleted and Potocki-Lupski Syndrome (PTLS) when duplicated, with psychiatric features commonly observed in both syndromes. How common genetic variants regulate this gene, however, is unknown. In this study, we found that RAI1 mRNA expression in Chinese prefrontal and temporal cortex correlate with genotypes of common single nucleotide polymorphisms (SNPs) located in the RAI1 5′-u...

  13. The role of amino acid-induced mammalian target of rapamycin complex 1(mTORC1) signaling in insulin resistance.

    Yoon, Mee-Sup; Choi, Cheol Soo

    2016-01-01

    Mammalian target of rapamycin (mTOR) controls cell growth and metabolism in response to nutrients, energy, and growth factors. Recent findings have placed the lysosome at the core of mTOR complex 1 (mTORC1) regulation by amino acids. Two parallel pathways, Rag GTPase-Ragulator and Vps34-phospholipase D1 (PLD1), regulate mTOR activation on the lysosome. This review describes the recent advances in understanding amino acid-induced mTOR signaling with a particular focus on the role of mTOR in insulin resistance. PMID:27534530

  14. "Protective Effects of Some Azo Derivatives of 5-aminosalicylic Acid and Their Pegylated Prodrugs on Acetic Acid-induced Rat Colitis "

    Alireza Garjani; Soodabeh Davaran; Mohamadreza Rashidi; Nasrin Malek

    2004-01-01

    The protective and anti-inflammatory effects of azo and azo-linked polymeric prodrugs of 5-aminosalicylic acid (5-ASA) on acetic acid induced colitis in rats were investigated. Three azo prodrugs; 4,4 -dihydroxy-azobenzene-3-carboxilic acid (azo compound I), 4-hydroxy-azobenzene-3,4-dicarboxilic acid (azo compound II), 4,4-dihydroxy-3-formyl-azobenzene-3-carboxylic acid (azo compound III) and their polyethylene glycol (PEG 6000) derivatives were synthesized. Rats were pretreated orally (1 hou...

  15. Compliance status

    Black, D.G.

    1995-06-01

    This section of the 1994 Hanford Site Environmental Report summarizes the activities conducted to ensure that the Hanford Site is in compliance with federal environmental protection statutes and related Washington State and local environmental protection regulations and the status of Hanford`s compliance with these requirements. Environmental permits required under the environmental protection regulations are discussed under the applicable statute.

  16. Use of Activated Carbon in Packaging to Attenuate Formaldehyde-Induced and Formic Acid-Induced Degradation and Reduce Gelatin Cross-Linking in Solid Dosage Forms.

    Colgan, Stephen T; Zelesky, Todd C; Chen, Raymond; Likar, Michael D; MacDonald, Bruce C; Hawkins, Joel M; Carroll, Sophia C; Johnson, Gail M; Space, J Sean; Jensen, James F; DeMatteo, Vincent A

    2016-07-01

    Formaldehyde and formic acid are reactive impurities found in commonly used excipients and can be responsible for limiting drug product shelf-life. Described here is the use of activated carbon in drug product packaging to attenuate formaldehyde-induced and formic acid-induced drug degradation in tablets and cross-linking in hard gelatin capsules. Several pharmaceutical products with known or potential vulnerabilities to formaldehyde-induced or formic acid-induced degradation or gelatin cross-linking were subjected to accelerated stability challenges in the presence and absence of activated carbon. The effects of time and storage conditions were determined. For all of the products studied, activated carbon attenuated drug degradation or gelatin cross-linking. This novel use of activated carbon in pharmaceutical packaging may be useful for enhancing the chemical stability of drug products or the dissolution stability of gelatin-containing dosage forms and may allow for the 1) extension of a drug product's shelf-life when the limiting attribute is a degradation product induced by a reactive impurity, 2) marketing of a drug product in hotter and more humid climatic zones than currently supported without the use of activated carbon, and 3) enhanced dissolution stability of products that are vulnerable to gelatin cross-linking. PMID:27262203

  17. Protective effect of cavidine on acetic acid-induced murine colitis via regulating antioxidant, cytokine profile and NF-κB signal transduction pathways.

    Niu, Xiaofeng; Zhang, Hailin; Li, Weifeng; Wang, Yu; Mu, Qingli; Wang, Xiumei; He, Zehong; Yao, Huan

    2015-09-01

    Ulcerative colitis is an inflammatory disorder characterized by neutrophils infiltration, oxidative stress, upregulation of pro-inflammatory mediators and cytokines. Cavidine possesses anti-inflammatory activity and has been used to treat various inflammatory diseases but its effect on ulcerative colitis has not been previously explored. The present study aims to evaluate the effect of cavidine on acetic acid-induced ulcerative colitis in mice. Colitis mice induced by intra-rectal acetic acid (5%, v/v) administration received cavidine (1, 5 and 10mg/kg, i.g) or sulfasalazine (500mg/kg, i.g) for seven consecutive days. After euthanized by cervical dislocation, colonic segments of mice were excised for clinical, macroscopic, biochemical and histopathological examinations. Results suggested treatment with cavidine significantly decreased mortality rate, body weight loss, disease activity index (DAI), wet colon weight, macroscopic and histological score when compared with that of acetic acid-induced controls. In addition, administration of cavidine effectively modulated expressions of MPO, GSH, SOD and MDA. Furthermore cavidine inhibited the level of TNF-α and IL-6 in the serum and colon tissue in response to the regulation of p65 NF-κB protein expression. All these results indicated cavidine exerts marked protective effect in experimental colitis, possibly by regulating the expression of oxygen metabolites, NF-κB and subsequent pro-inflammatory cytokines production. PMID:26102009

  18. Tevatron status

    The Fermilab Tevatron is both the world's highest energy accelerator system and first large-scale superconducting synchrotron. Since Tevatron commissioning in July 1983, the accelerator has operated in 1984, 1985 and 1987 with extracted beams of 800 GeV for three runs of fixed target physics, and in 1987, and 1988, with proton-antiproton colliding beams at 900 /times/ 900 GeV. This paper will focus on the collider operation of the Tevatron: its present status and the outlook for its longer-term future evolution. 18 refs., 3 figs., 2 tabs

  19. The mechanism of gentisic acid-induced relaxation of the guinea pig isolated trachea: the role of potassium channels and vasoactive intestinal peptide receptors

    J.F. Cunha

    2001-03-01

    Full Text Available We examined some of the mechanisms by which the aspirin metabolite and the naturally occurring metabolite gentisic acid induced relaxation of the guinea pig trachea in vitro. In preparations with or without epithelium and contracted by histamine, gentisic acid caused concentration-dependent and reproducible relaxation, with mean EC50 values of 18 µM and Emax of 100% (N = 10 or 20 µM and Emax of 92% (N = 10, respectively. The relaxation caused by gentisic acid was of slow onset in comparison to that caused by norepinephrine, theophylline or vasoactive intestinal peptide (VIP. The relative rank order of potency was: salbutamol 7.9 > VIP 7.0 > gentisic acid 4.7 > theophylline 3.7. Gentisic acid-induced relaxation was markedly reduced (24 ± 7.0, 43 ± 3.9 and 78 ± 5.6% in preparations with elevated potassium concentration in the medium (20, 40 or 80 mM, respectively. Tetraethylammonium (100 µM, a nonselective blocker of the potassium channels, partially inhibited the relaxation response to gentisic acid, while 4-AP (10 µM, a blocker of the voltage potassium channel, inhibited gentisic acid-induced relaxation by 41 ± 12%. Glibenclamide (1 or 3 µM, at a concentration which markedly inhibited the relaxation induced by the opener of ATP-sensitive K+ channels, levcromakalim, had no effect on the relaxation induced by gentisic acid. Charybdotoxin (0.1 or 0.3 µM, a selective blocker of the large-conductance Ca2+-activated K+ channels, caused rightward shifts (6- and 7-fold of the gentisic acid concentration-relaxation curve. L-N G-nitroarginine (100 µM, a NO synthase inhibitor, had no effect on the relaxant effect of gentisic acid, and caused a slight displacement to the right in the relaxant effect of the gentisic acid curve at 300 µM, while methylene blue (10 or 30 µM or ODQ (1 µM, the inhibitors of soluble guanylate cyclase, all failed to affect gentisic acid-induced relaxation. D-P-Cl-Phe6,Leu17[VIP] (0.1 µM, a VIP receptor antagonist

  20. Analgesic and Anti-Inflammatory Properties of Gelsolin in Acetic Acid Induced Writhing, Tail Immersion and Carrageenan Induced Paw Edema in Mice.

    Ashok Kumar Gupta

    Full Text Available Plasma gelsolin levels significantly decline in several disease conditions, since gelsolin gets scavenged when it depolymerizes and caps filamentous actin released in the circulation following tissue injury. It is well established that our body require/implement inflammatory and analgesic responses to protect against cell damage and injury to the tissue. This study was envisaged to examine analgesic and anti-inflammatory activity of exogenous gelsolin (8 mg/mouse in mice models of pain and acute inflammation. Administration of gelsolin in acetic acid-induced writhing and tail immersion tests not only demonstrated a significant reduction in the number of acetic acid-induced writhing effects, but also exhibited an analgesic activity in tail immersion test in mice as compared to placebo treated mice. Additionally, anti-inflammatory function of gelsolin (8 mg/mouse compared with anti-inflammatory drug diclofenac sodium (10 mg/kg] was confirmed in the carrageenan injection induced paw edema where latter was measured by vernier caliper and fluorescent tomography imaging. Interestingly, results showed that plasma gelsolin was capable of reducing severity of inflammation in mice comparable to diclofenac sodium. Analysis of cytokines and histopathological examinations of tissue revealed administration of gelsolin and diclofenac sodium significantly reduced production of pro-inflammatory cytokines, TNF-α and IL-6. Additionally, carrageenan groups pretreated with diclofenac sodium or gelsolin showed a marked decrease in edema and infiltration of inflammatory cells in paw tissue. Our study provides evidence that administration of gelsolin can effectively reduce the pain and inflammation in mice model.

  1. Analgesic and Anti-Inflammatory Properties of Gelsolin in Acetic Acid Induced Writhing, Tail Immersion and Carrageenan Induced Paw Edema in Mice

    Gupta, Ashok Kumar; Parasar, Devraj; Sagar, Amin; Choudhary, Vikas; Chopra, Bhupinder Singh; Garg, Renu; Ashish; Khatri, Neeraj

    2015-01-01

    Plasma gelsolin levels significantly decline in several disease conditions, since gelsolin gets scavenged when it depolymerizes and caps filamentous actin released in the circulation following tissue injury. It is well established that our body require/implement inflammatory and analgesic responses to protect against cell damage and injury to the tissue. This study was envisaged to examine analgesic and anti-inflammatory activity of exogenous gelsolin (8 mg/mouse) in mice models of pain and acute inflammation. Administration of gelsolin in acetic acid-induced writhing and tail immersion tests not only demonstrated a significant reduction in the number of acetic acid-induced writhing effects, but also exhibited an analgesic activity in tail immersion test in mice as compared to placebo treated mice. Additionally, anti-inflammatory function of gelsolin (8 mg/mouse) compared with anti-inflammatory drug diclofenac sodium (10 mg/kg)] was confirmed in the carrageenan injection induced paw edema where latter was measured by vernier caliper and fluorescent tomography imaging. Interestingly, results showed that plasma gelsolin was capable of reducing severity of inflammation in mice comparable to diclofenac sodium. Analysis of cytokines and histo-pathological examinations of tissue revealed administration of gelsolin and diclofenac sodium significantly reduced production of pro-inflammatory cytokines, TNF-α and IL-6. Additionally, carrageenan groups pretreated with diclofenac sodium or gelsolin showed a marked decrease in edema and infiltration of inflammatory cells in paw tissue. Our study provides evidence that administration of gelsolin can effectively reduce the pain and inflammation in mice model. PMID:26426535

  2. Deoxycholic acid induces the overexpression of intestinal mucin, MUC2, via NF-kB signaling pathway in human esophageal adenocarcinoma cells

    Mucin alterations are a common feature of esophageal neoplasia, and alterations in MUC2 mucin have been associated with tumor progression in the esophagus. Bile acids have been linked to esophageal adenocarcinoma and mucin secretion, but their effects on mucin gene expression in human esophageal adenocarcinoma cells is unknown. Human esophageal adenocarcinoma cells were treated 18 hours with 50–300 μM deoxycholic acid, chenodeoxycholic acid, or taurocholic acid. MUC2 transcription was assayed using a MUC2 promoter reporter luciferase construct and MUC2 protein was assayed by Western blot analysis. Transcription Nuclear factor-κB activity was measured using a Nuclear factor-κB reporter construct and confirmed by Western blot analysis for Nuclear factor-κB p65. MUC2 transcription and MUC2 protein expression were increased four to five fold by bile acids in a time and dose-dependent manner with no effect on cell viability. Nuclear factor-κB activity was also increased. Treatment with the putative chemopreventive agent aspirin, which decreased Nuclear factor-κB activity, also decreased MUC2 transcription. Nuclear factor-κB p65 siRNA decreased MUC2 transcription, confirming the significance of Nuclear factor-κB in MUC2 induction by deoxycholic acid. Calphostin C, a specific inhibitor of protein kinase C (PKC), greatly decreased bile acid induced MUC2 transcription and Nuclear factor-κB activity, whereas inhibitors of MAP kinase had no effect. Deoxycholic acid induced MUC2 overexpression in human esophageal adenocarcinoma cells by activation of Nuclear factor-κB transcription through a process involving PKC-dependent but not PKA, independent of activation of MAP kinase

  3. Chemometrics-assisted Spectrofluorimetric Determination of Two Co-administered Drugs of Major Interaction, Methotrexate and Aspirin, in Human Urine Following Acid-induced Hydrolysis.

    Maher, Hadir M; Ragab, Marwa A A; El-Kimary, Eman I

    2015-01-01

    Methotrexate (MTX) is widely used to treat rheumatoid arthritis (RA), mostly along with non-steroidal anti-inflammatory drugs (NSAIDs), the most common of which is aspirin or acetyl salicylic acid (ASA). Since NSAIDs impair MTX clearance and increase its toxicity, it was necessary to develop a simple and reliable method for the monitoring of MTX levels in urine samples, when coadministered with ASA. The method was based on the spectrofluorimetric measurement of the acid-induced hydrolysis product of MTX, 4-amino-4-deoxy-10-methylpteroic acid (AMP), along with the strongly fluorescent salicylic acid (SA), a product of acid-induced hydrolysis of aspirin and its metabolites in urine. The overlapping emission spectra were resolved using the derivative method (D method). In addition, the corresponding derivative emission spectra were convoluted using discrete Fourier functions, 8-points sin xi polynomials, (D/FF method) for better elimination of interferences. Validation of the developed methods was carried out according to the ICH guidelines. Moreover, the data obtained using derivative and convoluted derivative spectra were treated using the non-parametric Theil's method (NP), compared with the least-squares parametric regression method (LSP). The results treated with Theil's method were more accurate and precise compared with LSP since the former is less affected by the outliers. This work offers the potential of both derivative and convolution using discrete Fourier functions in addition to the effectiveness of using the NP regression analysis of data. The high sensitivity obtained by the proposed methods was promising for measuring low concentration levels of the two drugs in urine samples. These methods were efficiently used to measure the drugs in human urine samples following their co-administration. PMID:26234512

  4. RHIC status

    The design and construction status of the Relativistic Heavy Ion Collider, RHIC, which is in the seventh year of a nine year construction cycle, is discussed. Those novel performance features of a heavy ion collider that are distinct from hadron colliders in general are noted. These features are derived from the experimental requirements of operation with a variety of ion species over a wide energy range, including collisions between protons and ions, and between ions of unequal energies. Section 1 gives a brief introduction to the major parameters and overall layout of RHIC. A review of the superconducting magnet program is given in Section 2. Activities during the recent Sextant Test are briefly reviewed in Section 3. Finally, Section 4 presents the plans for RHIC commissioning in 1999

  5. Persistent impairment of mitochondrial and tissue redox status during lithium-pilocarpine-induced epileptogenesis

    Waldbaum, Simon; Liang, Li-Ping; Patel, Manisha

    2016-01-01

    Mitochondrial dysfunction and oxidative stress are known to occur following acute seizure activity but their contribution during epileptogenesis is largely unknown. The goal of this study was to determine the extent of mitochondrial oxidative stress, changes to redox status, and mitochondrial DNA (mtDNA) damage during epileptogenesis in the lithium-pilocarpine model of temporal lobe epilepsy. Mitochondrial oxidative stress, changes in tissue and mitochondrial redox status, and mtDNA damage were assessed in the hippocampus and neocortex of Sprague–Dawley rats at time points (24 h to 3 months) following lithium-pilocarpine administration. A time-dependent increase in mitochondrial hydrogen peroxide (H2O2) production coincident with increased mtDNA lesion frequency in the hippocampus was observed during epileptogenesis. Acute increases (24–48 h) in H2O2 production and mtDNA lesion frequency were dependent on the severity of convulsive seizure activity during initial status epilepticus. Tissue levels of GSH, GSH/GSSG, coenzyme A (CoASH), and CoASH/CoASSG were persistently impaired at all measured time points throughout epileptogenesis, that is, acutely (24–48 h), during the ‘latent period’ (48 h to 7 days), and chronic epilepsy (21 days to 3 months). Together with our previous work, these results demonstrate the model independence of mitochondrial oxidative stress, genomic instability, and persistent impairment of mitochondrial specific redox status during epileptogenesis. Lasting impairment of mitochondrial and tissue redox status during the latent period, in addition to the acute and chronic phases of epileptogenesis, suggests that redox-dependent processes may contribute to the progression of epileptogenesis in experimental temporal lobe epilepsy. PMID:21219330

  6. Increased expression of retinoic acid-induced gene 1 in the dorsolateral prefrontal cortex in schizophrenia, bipolar disorder, and major depression

    Haybaeck J

    2015-02-01

    Full Text Available Johannes Haybaeck,1 Magdalena Postruznik,1 Christine L Miller,2 Jeannette R Dulay,3 Ida C Llenos,3,4 Serge Weis3,4 1Department of Neuropathology, Institute of Pathology, Medical University Graz, Graz, Austria; 2Department of Pediatrics, Johns Hopkins University, Baltimore, 3Laboratory of Brain Research and Neuropathology, Departments of Psychiatry and Pathology, Uniformed Services University of the Health Sciences, and Stanley Medical Research Institute, Bethesda, MD, USA; 4Laboratory of Neuropathology, Department of Pathology and Neuropathology, State Neuropsychiatric Hospital Wagner-Jauregg, Medical School, Johannes Kepler University, Linz, Austria Background: Retinoids regulate gene expression in different cells and tissues at the transcriptional level. Retinoic acid transcriptionally regulates downstream regulatory molecules, including enzymes, transcription factors, cytokines, and cytokine receptors. Animal models indicate an involvement of retinoid signaling pathways in the regulation of synaptic plasticity and learning, especially in the hippocampus. Retinoic acid-inducible or induced gene 1 (RAI-1 is induced during neuronal differentiation, and was associated with the severity of the phenotype and response to medication in schizophrenic patients. Methods: In the present study, we used immunohistochemistry to investigate the expression of RAI-1 in 60 brains from the Stanley Neuropathology Consortium (15 cases each from controls and from patients with schizophrenia, bipolar disorder, and major depression. Rating scores for density and intensity were determined in the dorsolateral prefrontal cortex. Results: All four groups showed high interindividual variation. RAI-1-positive cells were identified as neurons and astrocytes. Significantly increased intensities in cortical neurons were noted in all three major psychiatric groups compared with controls. The density of RAI-1-positive neurons was increased (P=0.06 in schizophrenia and bipolar

  7. Evidence for genetic regulation of mRNA expression of the dosage-sensitive gene retinoic acid induced-1 (RAI1) in human brain.

    Chen, Li; Tao, Yu; Song, Fan; Yuan, Xi; Wang, Jian; Saffen, David

    2016-01-01

    RAI1 (retinoic acid induced-1) is a dosage-sensitive gene that causes Smith-Magenis syndrome (SMS) when mutated or deleted and Potocki-Lupski Syndrome (PTLS) when duplicated, with psychiatric features commonly observed in both syndromes. How common genetic variants regulate this gene, however, is unknown. In this study, we found that RAI1 mRNA expression in Chinese prefrontal and temporal cortex correlate with genotypes of common single nucleotide polymorphisms (SNPs) located in the RAI1 5'-upstream region. Using genotype imputation, "R(2)-Δ(2)" analysis, and data from the RegulomeDB database, we identified SNPs rs4925102 and rs9907986 as possible regulatory variants, accounting for approximately 30-40% of the variance in RAI1 mRNA expression in both brain regions. Specifically, rs4925102 and rs9907986 are predicted to disrupt the binding of retinoic acid RXR-RAR receptors and the transcription factor DEAF1 (Deformed epidermal autoregulatory factor-1), respectively. Consistent with these predictions, we observed binding of RXRα and RARα to the predicted RAI1 target in chromatin immunoprecipitation assays. Retinoic acid is crucial for early development of the central neural system, and DEAF1 is associated with intellectual disability. The observation that a significant portion of RAI1 mRNA expression is genetically controlled raises the possibility that common RAI1 5'-region regulatory variants contribute more generally to psychiatric disorders. PMID:26743651

  8. Effect of dietary fibers on cholic acid induced cell proliferation in the colonic epithelium of C57BL/6J mice

    It has been postulated that high fat diets promote tumorigenesis by increasing the level of secondary bile acids in the colonic lumen. Dietary fibers are thought to be protective perhaps through their interaction with bile acids. In the present study, animals were fed diets containing either 0%, 5%, or 10% cellulose (C), pectin (P), or wheat bran (WB). The diets were formulated to contain either 0% (control) or 0.2% cholic acid (test). After two weeks of dietary treatment the animals were injected with [3H]-thymidine and their colons were processed for autoradiography. The number of labeled cells (LC) in the colonic crypts was determined. Among the control diets, 10%P induced a two-fold increase in the LC. All the test groups had significantly higher LC than in their controls. However, the C group excited a higher LC than the P or WB groups (5.2 +/- 0.8 vs 3.9 +/- 0.8 or 3.9 +/- 0.6). These results were substantiated by metaphase arrest technique. The authors results show that nonfermentable fiber does not alleviate bile acid induced cell proliferative activity in the colon whereas fermentable fibers will counteract the promotional effect of a high fat diet

  9. Alkali- or acid-induced changes in structure, moisture absorption ability and deacetylating reaction of β-chitin extracted from jumbo squid (Dosidicus gigas) pens.

    Jung, Jooyeoun; Zhao, Yanyun

    2014-01-01

    Alkali- or acid-induced structural modifications in β-chitin from squid (Dosidicus gigas, d'Orbigny, 1835) pens and their moisture absorption ability (MAA) and deacetylating reaction were investigated and compared with α-chitin from shrimp shells. β-Chitin was converted into the α-form after 3h in 40% NaOH or 1-3 h in 40% HCl solution, and α-chitin obtained from NaOH treatment had higher MAA than had native α-chitin, due to polymorphic destructions. In contrast, induced α-chitin from acid treatment of β-chitin had few polymorphic modifications, showing no significant change (P>0.05) in MAA. β-Chitin was more susceptible to alkali deacetylation than was α-chitin, and required a lower concentration of NaOH and shorter reaction time. These results demonstrate that alkali- or acid-treated β-chitin retained high susceptibility toward solvents, which in turn resulted in good biological activity of β-chitosan for use as a natural antioxidant and antimicrobial substance or application as edible coatings and films for various food applications. PMID:24444948

  10. MicroRNA-31 negatively regulates peripherally derived regulatory T-cell generation by repressing retinoic acid-inducible protein 3.

    Zhang, Lingyun; Ke, Fang; Liu, Zhaoyuan; Bai, Jing; Liu, Jinlin; Yan, Sha; Xu, Zhenyao; Lou, Fangzhou; Wang, Hong; Zhu, Huiyuan; Sun, Yang; Cai, Wei; Gao, Yuanyuan; Li, Qun; Yu, Xue-Zhong; Qian, Youcun; Hua, Zichun; Deng, Jiong; Li, Qi-Jing; Wang, Honglin

    2015-01-01

    Peripherally derived regulatory T (pT(reg)) cell generation requires T-cell receptor (TCR) signalling and the cytokines TGF-β1 and IL-2. Here we show that TCR signalling induces the microRNA miR-31, which negatively regulates pT(reg)-cell generation. miR-31 conditional deletion results in enhanced induction of pT(reg) cells, and decreased severity of experimental autoimmune encephalomyelitis (EAE). Unexpectedly, we identify Gprc5a as a direct target of miR-31. Gprc5a is known as retinoic acid-inducible protein 3, and its deficiency leads to impaired pT(reg-)cell induction and increased EAE severity. By generating miR-31 and Gprc5a double knockout mice, we show that miR-31 promotes the development of EAE through inhibiting Gprc5a. Thus, our data identify miR-31 and its target Gprc5a as critical regulators for pT(reg)-cell generation, suggesting a previously unrecognized epigenetic mechanism for dysfunctional T(reg) cells in autoimmune diseases. PMID:26165721

  11. microRNA-34a-Upregulated Retinoic Acid-Inducible Gene-I Promotes Apoptosis and Delays Cell Cycle Transition in Cervical Cancer Cells.

    Wang, Jing-Hua; Zhang, Le; Ma, Yu-Wei; Xiao, Jing; Zhang, Yi; Liu, Min; Tang, Hua

    2016-06-01

    The function of retinoic acid-inducible gene-I (RIG-I) in viral replication is well documented, but its function in carcinogenesis and malignancies as well as relationship with microRNAs (miRNAs) remain poorly understood. miR-34a is an antioncogene in multiple tumors. In our study, RIG-I and miR-34a suppressed cell growth, proliferation, migration, and invasion in cervical cancer cells in vitro. miR-34a was validated as a new regulator of RIG-I by binding to its 3' untranslated region and upregulating its expression level. Furthermore, we revealed that RIG-I and miR-34a enhanced apoptosis, delayed the G1/S/G2 transition of the cell cycle, and inhibited the epithelial-mesenchymal transition process to modulate malignancies in cervical cancer cells. Phenotypic rescue experiments indicated that RIG-I mediates the effects of miR-34a in HeLa and C33A cells. These findings provide new insights into the mechanisms that underlie carcinogenesis and may provide new biomarkers for the diagnosis and therapy of cervical cancer. PMID:26910120

  12. Prednisolone-appended alpha-cyclodextrin: alleviation of systemic adverse effect of prednisolone after intracolonic administration in 2,4,6-trinitrobenzenesulfonic acid-induced colitis rats.

    Yano, H; Hirayama, F; Arima, H; Uekama, K

    2001-12-01

    The titled compound is a cyclodextrin derivative in which prednisolone 21-succinate (PDsuc) is covalently bound to one of the secondary hydroxyl groups of alpha-cyclodextrin (alpha-CyD) via an ester linkage. In this study, the PDsuc-appended alpha-CyD ester conjugate (PDsuc/alpha-CyD conjugate) was intracolonically administered to rats with 2,4,6-trinitrobenzensulfonic acid-induced colitis, and its antiinflammatory and systemic adverse effects were compared with those of prednisolone (PD) alone and the PD/2-hydroxypropyl-beta-CyD complex (PD/HP-beta-CyD complex), which is a noncovalent inclusion complex. Colonic damage score, ratio of distal colon wet weight to body weight, and myeloperoxidase activity were evaluated as measures of the therapeutic effect of PD, whereas the ratio of thymus wet weight to body weight was evaluated as a measure of the side effect of PD. The local antiinflammatory activity increased in the order of PD alone approximately PDsuc/alpha-CyD conjugate keeps the local concentration in the colon at a low but constant level. The results suggest that the PDsuc/alpha-CyD conjugate can alleviate the systemic adverse effect of PD while maintaining the therapeutic activity of PD. This kind of knowledge will be useful in the rational design of steroid prodrugs for the colon-specific drug delivery system. PMID:11745769

  13. Music application alleviates short-term memory impairments through increasing cell proliferation in the hippocampus of valproic acid-induced autistic rat pups.

    Lee, Sung-Min; Kim, Bo-Kyun; Kim, Tae-Woon; Ji, Eun-Sang; Choi, Hyun-Hee

    2016-06-01

    Autism is a neurodevelopmental disorder and this disorder shows impairment in reciprocal social interactions, deficits in communication, and restrictive and repetitive patterns of behaviors and interests. The effect of music on short-term memory in the view of cell proliferation in the hippocampus was evaluated using valproic acid-induced autistic rat pups. Animal model of autism was made by subcutaneous injection of 400-mg/kg valproic acid into the rat pups on the postnatal day 14. The rat pups in the music-applied groups were exposed to the 65-dB comfortable classic music for 1 hr once a day, starting postnatal day 15 and continued until postnatal day 28. In the present results, short-term memory was deteriorated by autism induction. The numbers of 5-bromo-2'-deoxyridine (BrdU)-positive, Ki-67-positive, and doublecortin (DCX)-positive cells in the hippocampal dentate gyrus were decreased by autism induction. Brain-derived neurotrophic factor (BDNF) and tyrosine kinase B (TrkB) expressions in the hippocampus were also suppressed in the autistic rat pups. Music application alleviated short-term memory deficits with enhancing the numbers of BrdU-positive, Ki-67-positive, and DCX-positive cells in the autistic rat pups. Music application also enhanced BDNF and TrkB expressions in the autistic rat pups. The present study show that application of music enhanced hippocampal cell proliferation and alleviated short-term memory impairment through stimulating BDNF-TrkB signaling in the autistic rat pups. Music can be suggested as the therapeutic strategy to overcome the autism-induced memory deficits. PMID:27419108

  14. Hepatitis C Virus Frameshift/Alternate Reading Frame Protein Suppresses Interferon Responses Mediated by Pattern Recognition Receptor Retinoic-Acid-Inducible Gene-I

    Park, Seung Bum; Seronello, Scott; Mayer, Wasima; Ojcius, David M.

    2016-01-01

    Hepatitis C virus (HCV) actively evades host interferon (IFN) responses but the mechanisms of how it does so are not completely understood. In this study, we present evidence for an HCV factor that contributes to the suppression of retinoic-acid-inducible gene-I (RIG-I)-mediated IFN induction. Expression of frameshift/alternate reading frame protein (F/ARFP) from HCV -2/+1 frame in Huh7 hepatoma cells suppressed type I IFN responses stimulated by HCV RNA pathogen-associated molecular pattern (PAMP) and poly(IC). The suppression occurred independently of other HCV factors; and activation of interferon stimulated genes, TNFα, IFN-λ1, and IFN-λ2/3 was likewise suppressed by HCV F/ARFP. Point mutations in the full-length HCV sequence (JFH1 genotype 2a strain) were made to introduce premature termination codons in the -2/+1 reading frame coding for F/ARFP while preserving the original reading frame, which enhanced IFNα and IFNβ induction by HCV. The potentiation of IFN response by the F/ARFP mutations was diminished in Huh7.5 cells, which already have a defective RIG-I, and by decreasing RIG-I expression in Huh7 cells. Furthermore, adding F/ARFP back via trans-complementation suppressed IFN induction in the F/ARFP mutant. The F/ARFP mutants, on the other hand, were not resistant to exogenous IFNα. Finally, HCV-infected human liver samples showed significant F/ARFP antibody reactivity, compared to HCV-uninfected control livers. Therefore, HCV F/ARFP likely cooperates with other viral factors to suppress type I and III IFN induction occurring through the RIG-I signaling pathway. This study identifies a novel mechanism of pattern recognition receptor modulation by HCV and suggests a biological function of the HCV alternate reading frame in the modulation of host innate immunity. PMID:27404108

  15. Identification of a retinoic acid-inducible gene I from Japanese eel (Anguilla japonica) and expression analysis in vivo and in vitro.

    Feng, Jianjun; Guo, Songlin; Lin, Peng; Wang, Yilei; Zhang, Ziping; Zhang, Zaipeng; Yu, Lili

    2016-08-01

    RIG-I (retinoic acid inducible gene-I) is one of the key cytosolic pattern recognition receptors (PRRs) for the recognition of cytosolic viral nucleic acids and the production of type I interferons (IFNs). The full-length cDNA sequence of RIG-I (AjRIG-I) in Japanese eel (Anguilla japonica) was identified and characterized in this article. The full-length cDNA of AjRIG-I was 3468 bp, including a 5'-untranslated region (UTR) of 52 bp, a 3'-UTR of 617 bp and an open reading frame (ORF) of 2799 bp encoding a polypeptide of 933 amino acid residues with a calculated molecular mass of 106.2 kDa. NCBI CDD analysis showed that the AjRIG-I protein had the typical conserved domains, including two adjacent caspase activation and recruitment domains (CARDs), a DEXDc domain, a HELICc domain and a C-terminal regulatory domain (RD). Quantitative real-time polymerase chain reaction (qRT-PCR) analysis revealed a broad expression for AjRIG-I in a wide range of tissues, with the predominant expression in liver, followed by the gills, spleen, kidney, intestine, skin, and the very low expression in muscle and heart. The AjRIG-I expressions in liver, spleen and kidney were significantly induced following injection with LPS, the viral mimic poly I:C, and Aeromonas hydrophila infection. In vitro, the AjRIG-I transcripts of Japanese eel liver cells were significantly enhanced by poly I:C and PGN stimulation, down-regulated with CpG-DNA treatment whereas no change of the expression level was found post LPS challenge. These results collectively suggested AjRIG-I transcripts expression possibly play an important role in fish defense against viral and bacterial infection. PMID:27238428

  16. Stearoyl-CoA desaturase-1 (SCD1 augments saturated fatty acid-induced lipid accumulation and inhibits apoptosis in cardiac myocytes.

    Hiroki Matsui

    Full Text Available Mismatch between the uptake and utilization of long-chain fatty acids in the myocardium leads to abnormally high intracellular fatty acid concentration, which ultimately induces myocardial dysfunction. Stearoyl-Coenzyme A desaturase-1 (SCD1 is a rate-limiting enzyme that converts saturated fatty acids (SFAs to monounsaturated fatty acids. Previous studies have shown that SCD1-deficinent mice are protected from insulin resistance and diet-induced obesity; however, the role of SCD1 in the heart remains to be determined. We examined the expression of SCD1 in obese rat hearts induced by a sucrose-rich diet for 3 months. We also examined the effect of SCD1 on myocardial energy metabolism and apoptotic cell death in neonatal rat cardiac myocytes in the presence of SFAs. Here we showed that the expression of SCD1 increases 3.6-fold without measurable change in the expression of lipogenic genes in the heart of rats fed a high-sucrose diet. Forced SCD1 expression augmented palmitic acid-induced lipid accumulation, but attenuated excess fatty acid oxidation and restored reduced glucose oxidation. Of importance, SCD1 substantially inhibited SFA-induced caspase 3 activation, ceramide synthesis, diacylglycerol synthesis, apoptotic cell death, and mitochondrial reactive oxygen species (ROS generation. Experiments using SCD1 siRNA confirmed these observations. Furthermore, we showed that exposure of cardiac myocytes to glucose and insulin induced SCD1 expression. Our results indicate that SCD1 is highly regulated by a metabolic syndrome component in the heart, and such induction of SCD1 serves to alleviate SFA-induced adverse fatty acid catabolism, and eventually to prevent SFAs-induced apoptosis.

  17. Carnitine palmitoyltransferase 1A prevents fatty acid-induced adipocyte dysfunction through suppression of c-Jun N-terminal kinase.

    Gao, Xuefei; Li, Kuai; Hui, Xiaoyan; Kong, Xiangping; Sweeney, Gary; Wang, Yu; Xu, Aimin; Teng, Maikun; Liu, Pentao; Wu, Donghai

    2011-05-01

    The adipocyte is the principal cell type for fat storage. CPT1 (carnitine palmitoyltransferase-1) is the rate-limiting enzyme for fatty acid β-oxidation, but the physiological role of CPT1 in adipocytes remains unclear. In the present study, we focused on the specific role of CPT1A in the normal functioning of adipocytes. Three 3T3-L1 adipocyte cell lines stably expressing hCPT1A (human CPT1A) cDNA, mouse CPT1A shRNA (short-hairpin RNA) or GFP (green fluorescent protein) were generated and the biological functions of these cell lines were characterized. Alteration in CPT1 activity, either by ectopic overexpression or pharmacological inhibition using etomoxir, did not affect adipocyte differentiation. However, overexpression of hCPT1A significantly reduced the content of intracellular NEFAs (non-esterified fatty acids) compared with the control cells when adipocytes were challenged with fatty acids. The changes were accompanied by an increase in fatty acid uptake and a decrease in fatty acid release. Interestingly, CPT1A protected against fatty acid-induced insulin resistance and expression of pro-inflammatory adipokines such as TNF-α (tumour necrosis factor-α) and IL-6 (interleukin-6) in adipocytes. Further studies demonstrated that JNK (c-Jun N terminal kinase) activity was substantially suppressed upon CPT1A overexpression, whereas knockdown or pharmacological inhibition of CPT1 caused a significant enhancement of JNK activity. The specific inhibitor of JNK SP600125 largely abolished the changes caused by the shRNA- and etomoxir-mediated decrease in CPT1 activity. Moreover, C2C12 myocytes co-cultured with adipocytes pre-treated with fatty acids displayed altered insulin sensitivity. Taken together, our findings have identified a favourable role for CPT1A in adipocytes to attenuate fatty acid-evoked insulin resistance and inflammation via suppression of JNK. PMID:21348853

  18. Constitutive androstane receptor-mediated changes in bile acid composition contributes to hepatoprotection from lithocholic acid-induced liver injury in mice.

    Beilke, Lisa D; Aleksunes, Lauren M; Holland, Ricky D; Besselsen, David G; Beger, Rick D; Klaassen, Curtis D; Cherrington, Nathan J

    2009-05-01

    Pharmacological activation of the constitutive androstane receptor (CAR) protects the liver during cholestasis. The current study evaluates how activation of CAR influences genes involved in bile acid biosynthesis as a mechanism of hepatoprotection during bile acid-induced liver injury. CAR activators phenobarbital (PB) and 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP) or corn oil (CO) were administered to C57BL/6 wild-type (WT) and CAR knockout (CAR-null) mice before and during induction of intrahepatic cholestasis using the secondary bile acid, lithocholic acid (LCA). In LCA-treated WT and all the CAR-null groups (excluding controls), histology revealed severe multifocal necrosis. This pathology was absent in WT mice pretreated with PB and TCPOBOP, indicating CAR-dependent hepatoprotection. Decreases in total hepatic bile acids and hepatic monohydroxy, dihydroxy, and trihydroxy bile acids in PB- and TCPOBOP-pretreated WT mice correlated with hepatoprotection. In comparison, concentrations of monohydroxylated and dihydroxylated bile acids were increased in all the treated CAR-null mice compared with CO controls. Along with several other enzymes (Cyp7b1, Cyp27a1, Cyp39a1), Cyp8b1 expression was increased in hepatoprotected mice, which could be suggestive of a shift in the bile acid biosynthesis pathway toward the formation of less toxic bile acids. In CAR-null mice, these changes in gene expression were not different among treatment groups. These results suggest CAR mediates a shift in bile acid biosynthesis toward the formation of less toxic bile acids, as well as a decrease in hepatic bile acid concentrations. We propose that these combined CAR-mediated effects may contribute to the hepatoprotection observed during LCA-induced liver injury. PMID:19196849

  19. Calcium-dependent nitric oxide production is involved in the cytoprotective properties of n-acetylcysteine in glycochenodeoxycholic acid-induced cell death in hepatocytes

    The intracellular oxidative stress has been involved in bile acid-induced cell death in hepatocytes. Nitric oxide (NO) exerts cytoprotective properties in glycochenodeoxycholic acid (GCDCA)-treated hepatocytes. The study evaluated the involvement of Ca2+ on the regulation of NO synthase (NOS)-3 expression during N-acetylcysteine (NAC) cytoprotection against GCDCA-induced cell death in hepatocytes. The regulation of Ca2+ pools (EGTA or BAPTA-AM) and NO (L-NAME or NO donor) production was assessed during NAC cytoprotection in GCDCA-treated HepG2 cells. The stimulation of Ca2+ entrance was induced by A23187 in HepG2. Cell death, Ca2+ mobilization, NOS-1, -2 and -3 expression, AP-1 activation, and NO production were evaluated. GCDCA reduced intracellular Ca2+ concentration and NOS-3 expression, and enhanced cell death in HepG2. NO donor prevented, and L-NAME enhanced, GCDCA-induced cell death. The reduction of Ca2+ entry by EGTA, but not its release from intracellular stores by BAPTA-AM, enhanced cell death in GCDCA-treated cells. The stimulation of Ca2+ entrance by A23187 reduced cell death and enhanced NOS-3 expression in GCDCA-treated HepG2 cells. The cytoprotective properties of NAC were related to the recovery of intracellular Ca2+ concentration, NOS-3 expression and NO production induced by GCDCA-treated HepG2 cells. The increase of NO production by Ca2+-dependent NOS-3 expression during NAC administration reduces cell death in GCDCA-treated hepatocytes.

  20. Music application alleviates short-term memory impairments through increasing cell proliferation in the hippocampus of valproic acid-induced autistic rat pups

    Lee, Sung-Min; Kim, Bo-Kyun; Kim, Tae-Woon; Ji, Eun-Sang; Choi, Hyun-Hee

    2016-01-01

    Autism is a neurodevelopmental disorder and this disorder shows impairment in reciprocal social interactions, deficits in communication, and restrictive and repetitive patterns of behaviors and interests. The effect of music on short-term memory in the view of cell proliferation in the hippocampus was evaluated using valproic acid-induced autistic rat pups. Animal model of autism was made by subcutaneous injection of 400-mg/kg valproic acid into the rat pups on the postnatal day 14. The rat pups in the music-applied groups were exposed to the 65-dB comfortable classic music for 1 hr once a day, starting postnatal day 15 and continued until postnatal day 28. In the present results, short-term memory was deteriorated by autism induction. The numbers of 5-bromo-2′-deoxyridine (BrdU)-positive, Ki-67-positive, and doublecortin (DCX)-positive cells in the hippocampal dentate gyrus were decreased by autism induction. Brain-derived neurotrophic factor (BDNF) and tyrosine kinase B (TrkB) expressions in the hippocampus were also suppressed in the autistic rat pups. Music application alleviated short-term memory deficits with enhancing the numbers of BrdU-positive, Ki-67-positive, and DCX-positive cells in the autistic rat pups. Music application also enhanced BDNF and TrkB expressions in the autistic rat pups. The present study show that application of music enhanced hippocampal cell proliferation and alleviated short-term memory impairment through stimulating BDNF-TrkB signaling in the autistic rat pups. Music can be suggested as the therapeutic strategy to overcome the autism-induced memory deficits. PMID:27419108

  1. Tauroursodeoxycholate Protects Rat Hepatocytes from Bile Acid-Induced Apoptosis via β1-Integrin- and Protein Kinase A-Dependent Mechanisms

    Annika Sommerfeld

    2015-05-01

    Full Text Available Background/Aims: Ursodeoxycholic acid, which in vivo is rapidly converted into its taurine conjugate, is frequently used for the treatment of cholestatic liver disease. Apart from its choleretic effects, tauroursodeoxycholate (TUDC can protect hepatocytes from bile acid-induced apoptosis, but the mechanisms underlying its anti-apoptotic effects are poorly understood. Methods: These mechanisms were investigated in perfused rat liver and isolated rat hepatocytes. Results: It was found that TUDC inhibited the glycochenodeoxycholate (GCDC-induced activation of the CD95 death receptor at the level of association between CD95 and the epidermal growth factor receptor. This was due to a rapid TUDC-induced β1-integrin-dependent cyclic AMP (cAMP signal with induction of the dual specificity mitogen-activated protein (MAP kinase phosphatase 1 (MKP-1, which prevented GCDC-induced phosphorylation of mitogen-activated protein kinase kinase 4 (MKK4 and c-jun-NH2-terminal kinase (JNK activation. Furthermore, TUDC induced a protein kinase A (PKA-mediated serine/threonine phosphorylation of the CD95, which was recently identified as an internalization signal for CD95. Furthermore, TUDC inhibited GCDC-induced CD95 targeting to the plasma membrane in a β1-integrin-and PKA-dependent manner. In line with this, the β1-integrin siRNA knockdown in sodium taurocholate cotransporting polypeptide (Ntcp-transfected HepG2 cells abolished the protective effect of TUDC against GCDC-induced apoptosis. Conclusion: TUDC exerts its anti-apoptotic effect via a β1-integrin-mediated formation of cAMP, which prevents CD95 activation by hydrophobic bile acids at the levels of JNK activation and CD95 serine/threonine phosphorylation.

  2. A comparative study of the antitussive activity of levodropropizine and dropropizine in the citric acid-induced cough model in normal subjects.

    Fumagalli, G; Cordaro, C I; Vanasia, M; Balzarotti, C; Camusso, L; Caiazzo, G; Maghini, L; Mazzocchi, M; Zennaro, M

    1992-01-01

    Levodropropizine is the levo-rotatory (S)-enantiomer of dropropizine, a racemic non-opiate antitussive agent which has been used clinically for many years. Compared with the racemic drug, levodropropizine exhibits in animal models similar antitussive activity but considerably lower central nervous system (CNS) depressant effects. It is also less likely to cause sedation in treated patients. Since the comparative antitussive potency of the two drugs in clinical experimental models has not been evaluated, the authors performed a randomized, double blind, cross over investigation in which the effects of single oral doses (60 and 90 mg) of levodropropizine and dropropizine were assessed by using the citric acid-induced cough model in eight normal volunteers. Stimulation tests involved inhalation of individual cumulative doses of citric acid (6.3 to 53.3 mg) which at pre-study assessment had been found to induce reproducibly at least ten coughs over a 30 sec period. Each subject was studied by repeating the citric acid stimulation test four times (0 h, 1 h, 2 h and 6 h) on each of five different days separated by intervals of at least three days. In the absence of drug administration (control session), cough response to citric inhalation was remarkably reproducible throughout the 6 h period of observation. A marked and statistically significant reduction in cough response (to about one third--one sixth of the pre-drug values) was observed 1 h after intake for both compounds. At subsequent testing 2 h and 6 h after dosing, cough response was still depressed and did not differ significantly from that observed at 1 h.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1295724

  3. BNL status and plans

    The present status and future plans for the Alternating Gradient Synchrotron are presented. The operating modes, accelerator improvement program, Booster synchrotron status, Stretcher ring proposal, and higher intensity options are described

  4. Status of EPR™ projects

    EPR licensing status, construction status and AREVA reactor portfolio are presented. Details are given for the construction of the Olkiluoto 3, Flamanville 3 Project (France) and Taishan 1 and 2 (China)

  5. USCIS My Case Status

    Department of Homeland Security — USCIS provide a way for the public who applied for U.S. citizenship to check the status of their application online. To view the status of a case, the application...

  6. The natural triterpene maslinic acid induces apoptosis in HT29 colon cancer cells by a JNK-p53-dependent mechanism

    Maslinic acid, a pentacyclic triterpene found in the protective wax-like coating of the leaves and fruit of Olea europaea L., is a promising agent for the prevention of colon cancer. We have shown elsewhere that maslinic acid inhibits cell proliferation to a significant extent and activates mitochondrial apoptosis in colon cancer cells. In our latest work we have investigated further this compound's apoptotic molecular mechanism. We used HT29 adenocarcinoma cells. Changes genotoxicity were analyzed by single-cell gel electrophoresis (comet assay). The cell cycle was determined by flow cytometry. Finally, changes in protein expression were examined by western blotting. Student's t-test was used for statistical comparison. HT29 cells treated with maslinic acid showed significant increases in genotoxicity and cell-cycle arrest during the G0/G1 phase after 72 hours' treatment and an apoptotic sub-G0/G1 peak after 96 hours. Nevertheless, the molecular mechanism for this cytotoxic effect of maslinic acid has never been properly explored. We show here that the anti-tumoral activity of maslinic acid might proceed via p53-mediated apoptosis by acting upon the main signaling components that lead to an increase in p53 activity and the induction of the rest of the factors that participate in the apoptotic pathway. We found that in HT29 cells maslinic acid activated the expression of c-Jun NH2-terminal kinase (JNK), thus inducing p53. Treatment of tumor cells with maslinic acid also resulted in an increase in the expression of Bid and Bax, repression of Bcl-2, release of cytochrome-c and an increase in the expression of caspases -9, -3, and -7. Moreover, maslinic acid produced belated caspase-8 activity, thus amplifying the initial mitochondrial apoptotic signaling. All these results suggest that maslinic acid induces apoptosis in human HT29 colon-cancer cells through the JNK-Bid-mediated mitochondrial apoptotic pathway via the activation of p53. Thus we propose

  7. Natural resistance to ascorbic acid induced oxidative stress is mainly mediated by catalase activity in human cancer cells and catalase-silencing sensitizes to oxidative stress

    Klingelhoeffer Christoph

    2012-05-01

    against oxidative stress mediated by ascorbic acid induced hydrogen peroxide production. The antioxidative enzyme catalase is important to protect cancer cells against cytotoxic hydrogen peroxide. Silenced catalase expression increased the susceptibility of the formerly resistant cancer cell line BT-20 to oxidative stress.

  8. Heuristic status polling

    Archer, Charles J.; Blocksome, Michael A.; Heidelberger, Philip; Kumar, Sameer; Parker, Jeffrey J.; Ratterman, Joseph D.

    2011-06-07

    Methods, compute nodes, and computer program products are provided for heuristic status polling of a component in a computing system. Embodiments include receiving, by a polling module from a requesting application, a status request requesting status of a component; determining, by the polling module, whether an activity history for the component satisfies heuristic polling criteria; polling, by the polling module, the component for status if the activity history for the component satisfies the heuristic polling criteria; and not polling, by the polling module, the component for status if the activity history for the component does not satisfy the heuristic criteria.

  9. Nonconvulsive Status Epilepticus in Elderly Patients Receiving SSRIs; Euglycemic Diabetic Ketoacidosis Associated with Canagliflozin Use in a Type 1 Diabetic Patient; Duloxetine-Induced Galactorrhea; Canagliflozin-Associated Severe Hypercalcemia and Hypernatremia; Vemurafenib-Induced Fanconi Syndrome.

    Mancano, Michael A

    2015-10-01

    The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration's (FDA's) MedWatch program (800-FDA-1088). If you have reported an interesting, preventable ADR to MedWatch, please consider sharing the account with our readers. Write to Dr. Mancano at ISMP, 200 Lakeside Drive, Suite 200, Horsham, PA 19044 (phone: 215-707-4936; e-mail: mmancano@temple.edu). Your report will be published anonymously unless otherwise requested. This feature is provided by the Institute for Safe Medication Practices (ISMP) in cooperation with the FDA's MedWatch program and Temple University School of Pharmacy. ISMP is an FDA MedWatch partner. PMID:26912914

  10. Service Level Status

    Lopienski, S

    2007-01-01

    Nowadays, IT departments provide, and people use, computing services of an increasingly heterogeneous nature. There is thus a growing need for a status display that groups these different services and reports status and availability in a uniform way. The Service Level Status (SLS) system addresses these needs by providing a web-based display that dynamically shows availability, basic information and statistics about various IT services, as well as the dependencies between them.

  11. SIS - Status Determination

    National Oceanic and Atmospheric Administration, Department of Commerce — The Status Determination dataset within the Species Information System (SIS) contains information related to overfishing, overfished, and approaching overfished...

  12. A case of apical ballooning syndrome in a male with status asthmaticus; highlighting the role of B2 agonists in the pathophysiology of a reversible cardiomyopathy

    Farah F. Salahuddin

    2013-07-01

    Full Text Available Apical ballooning syndrome (ABS, also known as Takotsubo cardiomyopathy, was first reported by Dote and colleagues in Japanese literature in 1991 in a review of five cases. Case series have highlighted the association of severe psychological stressors as the major precipitating factors of this syndrome. Status Epilepticus and Sub-Arachnoid hemorrhage are also now established independent etiologies for this phenomenon in patients without coronary artery disease. We report a case of reversible apical ventricular dysfunction in a 50-year-old male presenting with status asthmaticus who quickly underwent intubation. Following this, he had ST elevations in precordial leads with mild cardiac enzyme leak. Subsequent cardiac catheterization revealed a left ventricular ejection fraction of 25–30% with apical aneurismal segment. No obstructive disease was observed. Three days later there was marked clinical improvement; the patient was extubated and repeat echocardiography revealed a remarkable return to normal ventricular size and systolic function. Our case demonstrates that excess use of beta-agonists may be a potential risk factor for ABS and raises the possibility of cathecholamine cardiotoxicity being mediated via beta-receptors. Furthermore, it also negates the propensity of apical ballooning so far reported only in women with respiratory distress without confounding emotional stressors.

  13. Neu1 sialidase and matrix metalloproteinase-9 cross-talk regulates nucleic acid-induced endosomal TOLL-like receptor-7 and -9 activation, cellular signaling and pro-inflammatory responses.

    Abdulkhalek, Samar; Szewczuk, Myron R

    2013-11-01

    The precise mechanism(s) by which intracellular TOLL-like receptors (TLRs) become activated by their ligands remains unclear. Here, we report a molecular organizational G-protein coupled receptor (GPCR) signaling platform to potentiate a novel mammalian neuraminidase-1 (Neu1) and matrix metalloproteinase-9 (MMP-9) cross-talk in alliance with neuromedin B GPCR, all of which form a tripartite complex with TLR-7 and -9. siRNA silencing Neu1, MMP-9 and neuromedin-B GPCR in RAW-blue macrophage cells significantly reduced TLR7 imiquimod- and TLR9 ODN1826-induced NF-κB (NF-κB-pSer(536)) activity. Tamiflu, specific MMP-9 inhibitor, neuromedin B receptor specific antagonist BIM23127, and the selective inhibitor of whole heterotrimeric G-protein complex BIM-46174 significantly block nucleic acid-induced TLR-7 and -9 MyD88 recruitment, NF-κB activation and proinflammatory TNFα and MCP-1 cytokine responses. For the first time, Neu1 clearly plays a central role in mediating nucleic acid-induced intracellular TLR activation, and the interactions involving NMBR-MMP9-Neu1 cross-talk constitute a novel intracellular TLR signaling platform that is essential for NF-κB activation and pro-inflammatory responses. PMID:23827939

  14. Therapeutic Effect of Oridonin Tablet on Acetic Acid-induced Ulcerative Colitis in Mice%冬凌草甲素片对醋酸诱导的小鼠溃疡性结肠炎的治疗作用

    臧凯宏; 杜丽东; 刘晓梅; 马骏; 任远

    2012-01-01

    目的 考察冬凌草甲素片口服给药对醋酸诱导的小鼠溃疡性结肠炎的治疗作用.方法 醋酸诱导的溃疡性结肠炎小鼠分别给予不同剂量的冬凌草甲素片灌胃给药,给药7d后,考察冬凌草甲素片对溃疡性结肠炎小鼠病变活动(体质量、便潜血及粪便性状)的影响,以及对结肠病理组织学变化,结肠髓过氧化物酶活性及胸腺和脾脏指数的影响.结果 冬凌草甲素片口服给药可剂量依赖性的降低结肠炎小鼠的病变活动、减轻结肠炎症、降低髓过氧化物酶活性,改善免疫器官脏器指数,以冬凌草甲素片高剂量给药组的作用更为显著.结论 高剂量冬凌草甲素片口服给药对醋酸诱导的小鼠溃疡性结肠炎具有治疗作用,其机制可能与冬凌草甲素的抗炎和免疫调节作用有关.%OBJECTIVE To investigate the therapeutic effect of Oridonin tablet on acetic acid-induced ulcerative colitis in mice.METHODS Oridonin tablets at different dosages were administered orally to acetic acid-induced colitis mice.After 7 days of treatment,the effects of Oridonin tablet on disease activity (i.e.body weight,stool blood,and stool consistency),colonic macroscopic and histological score,myleoperoxidase activity,and thymic and splenic indexes were evaluated in acetic acid-induced ulcerative colitis in mice.RESULTS Oridonin tablet treatment dose-dependently reduced the disease activity,attenuated colonic inflammation and myleoperoxidase activity,and improved the thymic and splenic indexes in acetic acid-induced ulcerative colitis in mice,especially in high dose of Oridonin tablet treated group.CONCLUSION High dose of Oridonin tablet treatment shows therapeutic effect on acetic acid-induced ulcerative colitis in mice,the underlying mechanism may have close correlation with its anti-inflammatory and immune regulatory effects.

  15. Deadline Compliance Status Reports

    Department of Housing and Urban Development — These monthly Deadline Compliance Status Reports assist Participating Jurisdictions and HUD Field Offices in monitoring compliance with the 2-year commitment and...

  16. Topical report review status

    A Topical Report Review Status is scheduled to be published semi-annually. The primary purpose of this document is to provide periodic progress reports of on-going topical report reviews, to identify those topical reports for which the Nuclear Regulatory Commission (NRC) staff review has been completed and, to the extent practicable, to provide NRC management with sufficient information regarding the conduct of the topical report program to permit taking whatever actions deemed necessary or appropriate. This document is also intended to be a source of information to NRC Licensing Project Managers and other NRC personnel regarding the status of topical reports which may be referenced in applications for which they have responsibility. This status report is published primarily for internal NRC use in managing the topical report program, but is also used by NRC to advise the industry of report review status

  17. NAIP Status Maps Gallery

    Farm Service Agency, Department of Agriculture — NAIP Status Maps Gallery. These maps illustrate what aerial imagery collection is planned, whats been collected, when it is available and how it is available. These...

  18. STATUS GIZI DAN STATUS KESEHATAN SUKU BADUY

    Faisal Anwar

    2012-03-01

    Full Text Available 800x600 Normal 0 false false false IN X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:"Calibri","sans-serif"; mso-bidi-font-family:"Times New Roman";} The objectives of the study were: (1 To analyze the socio-economic and demographic characteristics of Baduy people; (2 To analyze the health status and nutritional status of Baduy people and its influential factors. This research is an explorative and descriptive study on the socio-cultural aspects of food system. The data were collected through a direct interview and discussion with respondents as well as a direct observation at the location of respondents. A sample size of 338 households was drawn from the population. To obtain the data on the cultural aspects, history and  socio aspect of food, in-depth interviews was conducted with 19 key persons. The study was last for 12 months. In Outer Baduy, the factors significantly related to nutritional status are age, number of household size, income, nutritional knowledge, and wife’s ability to read. In Moslem Baduy, only age and income are related to the nutritional status of children. In Moslem Baduy and the Outer Baduy, the correlation between age and W/A or W/H is similar: namely, the higher the age, the lower would the Z-score for the W/A or W/H. The income is significantly correlated to the child nutritional status according to Z-score for W/A with a high correlation coefficient, that is, 0.61. This means that the higher the income, the higher would be the Z-score value for the W/A.  The distribution of adults according to BMI classification in Outer Baduy it shows that 12.7% husbands and 17.6% wives are thin (wasted, while the

  19. COMMUNICATION ABOUT SOCIAL STATUS

    Fernald, Russell D.

    2014-01-01

    Dominance hierarchies are ubiquitous in social species and serve to organize social systems. Social and sexual status is communicated directly among animals via sensory systems evolved in the particular species. Such signals may be chemical, visual, auditory, postural or a combination of signals. In most species, status is initially established through physical conflict between individuals that leads to ritualized conflict or threats, reducing possibly dangerous results of fighting. Many of t...

  20. Status of numerical relativity

    Masaru Shibata

    2004-10-01

    I describe the current status of numerical relativity from my personal point of view. Here, I focus mainly on explaining the numerical implementations necessary for simulating general relativistic phenomena such as the merger of compact binaries and stellar collapse, emphasizing the well-developed current status of such implementations that enable simulations for several astrophysical phenomena. Some of our latest results for simulation of binary neutron star mergers are briefly presented.

  1. Status of ADSW 2005

    Hartmann, H.; Ahring, Birgitte Kiær

    2006-01-01

    The status of the recent developments in anaerobic digestion of solid waste (ADSW) is outlined on the basis of a selection of papers presented at the 4(th) International Symposium on ADSW 2005.......The status of the recent developments in anaerobic digestion of solid waste (ADSW) is outlined on the basis of a selection of papers presented at the 4(th) International Symposium on ADSW 2005....

  2. Safety system status monitoring

    The Pacific Northwest Laboratory has studied the safety aspects of monitoring the preoperational status of safety systems in nuclear power plants. The goals of the study were to assess for the NRC the effectiveness of current monitoring systems and procedures, to develop near-term guidelines for reducing human errors associated with monitoring safety system status, and to recommend a regulatory position on this issue. A review of safety system status monitoring practices indicated that current systems and procedures do not adequately aid control room operators in monitoring safety system status. This is true even of some systems and procedures installed to meet existing regulatory guidelines (Regulatory Guide 1.47). In consequence, this report suggests acceptance criteria for meeting the functional requirements of an adequate system for monitoring safety system status. Also suggested are near-term guidelines that could reduce the likelihood of human errors in specific, high-priority status monitoring tasks. It is recommended that (1) Regulatory Guide 1.47 be revised to address these acceptance criteria, and (2) the revised Regulatory Guide 1.47 be applied to all plants, including those built since the issuance of the original Regulatory Guide

  3. Maintained activity of glycogen synthase kinase-3{beta} despite of its phosphorylation at serine-9 in okadaic acid-induced neurodegenerative model

    Lim, Yong-Whan [Department of Anatomy and Cell Biology, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Yoon, Seung-Yong, E-mail: ysy@amc.seoul.kr [Department of Anatomy and Cell Biology, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Institute for Biomacromolecules, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Choi, Jung-Eun [Department of Anatomy and Cell Biology, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Institute for Biomacromolecules, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Kim, Sang-Min [Department of Anatomy and Cell Biology, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Lee, Hui-Sun; Choe, Han [Department of Physiology, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Institute for Biomacromolecules, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Lee, Seung-Chul [CrystalGenomics, Seoul (Korea, Republic of); Kim, Dong-Hou, E-mail: dhkim@amc.seoul.kr [Department of Anatomy and Cell Biology, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Institute for Biomacromolecules, University of Ulsan College of Medicine, Seoul (Korea, Republic of)

    2010-04-30

    Glycogen synthase kinase-3{beta} (GSK3{beta}) is recognized as one of major kinases to phosphorylate tau in Alzheimer's disease (AD), thus lots of AD drug discoveries target GSK3{beta}. However, the inactive form of GSK3{beta} which is phosphorylated at serine-9 is increased in AD brains. This is also inconsistent with phosphorylation status of other GSK3{beta} substrates, such as {beta}-catenin and collapsin response mediator protein-2 (CRMP2) since their phosphorylation is all increased in AD brains. Thus, we addressed this paradoxical condition of AD in rat neurons treated with okadaic acid (OA) which inhibits protein phosphatase-2A (PP2A) and induces tau hyperphosphorylation and cell death. Interestingly, OA also induces phosphorylation of GSK3{beta} at serine-9 and other substrates including tau, {beta}-catenin and CRMP2 like in AD brains. In this context, we observed that GSK3{beta} inhibitors such as lithium chloride and 6-bromoindirubin-3'-monoxime (6-BIO) reversed those phosphorylation events and protected neurons. These data suggest that GSK3{beta} may still have its kinase activity despite increase of its phosphorylation at serine-9 in AD brains at least in PP2A-compromised conditions and that GSK3{beta} inhibitors could be a valuable drug candidate in AD.

  4. Palmitic Acid Induces Production of Proinflammatory Cytokines Interleukin-6, Interleukin-1β, and Tumor Necrosis Factor-α via a NF-κB-Dependent Mechanism in HaCaT Keratinocytes

    Bing-rong Zhou

    2013-01-01

    Full Text Available To investigate whether palmitic acid can be responsible for the induction of inflammatory processes, HaCaT keratinocytes were treated with palmitic acid at pathophysiologically relevant concentrations. Secretion levels of interleukin-6 (IL-6, tumor necrosis factor-α (TNF-α, interleukin-1β (IL-1β, NF-κB nuclear translocation, NF-κB activation, Stat3 phosphorylation, and peroxisome proliferator-activated receptor alpha (PPARα mRNA and protein levels, as well as the cell proliferation ability were measured at the end of the treatment and after 24 hours of recovery. Pyrrolidine dithiocarbamate (PDTC, a selective chemical inhibitor of NF-κB and goat anti-human IL-6 polyclonal neutralizing antibody were used to inhibit NF-κB activation and IL-6 production, respectively. Our results showed that palmitic acid induced an upregulation of IL-6, TNF-α, IL-1β secretions, accompanied by NF-κB nuclear translocation and activation. Moreover, the effect of palmitic acid was accompanied by PPARα activation and Stat3 phosphorylation. Palmitic acid-induced IL-6, TNF-α, IL-1β productions were attenuated by NF-κB inhibitor PDTC. Palmitic acid was administered in amounts able to elicit significant hyperproliferation and can be attenuated by IL-6 blockage. These data demonstrate for the first time that palmitic acid can stimulate IL-6, TNF-α, IL-1β productions in HaCaT keratinocytes and cell proliferation, thereby potentially contributing to acne inflammation and pilosebaceous duct hyperkeratinization.

  5. Social Status and Personality Traits

    Alessandro Bucciol; Barbara Cavasso; Luca Zarri

    2014-01-01

    In this study we provide direct evidence on the relationship between social status and personality traits. Using survey data from the 2006-2012 waves of the HRS, we show that individuals’ self-perceived social status is associated with all the “Big Five” personality traits, after controlling for observable characteristics that arguably reflect one’s actual status. We also construct an objective status measure that in turn is influenced by personality traits. Objectively measured status is pos...

  6. Status of ATF, 2004

    Accelerator Test Facility (ATF) has already achieved the vertical emittance of GLC specification. In order to make the multi-bunch emittance achievement, high quality multi-bunch beam from photo-cathode rf gun was employed. The maximum allowable current was raised to 3 times more. From the study, it was found that the vacuum level of damping ring is related to the achieved vertical emittance. The ring scrubbing with high current accumulation made tail bunch emittance growth lower. We describe the status of multi-bunch emittance study together with the development status of the various emittance monitors and beam position monitors. (author)

  7. New Service Status Board

    2013-01-01

    On Monday 14 October, the Service Status Board for GS and IT will change. The new Status Board will be integrated with the CERN Service Portal and with the CERN Service Catalogue.   As of today, the SSB will display “Service Incidents”, “Planned Interventions” and “Service Changes”. References valid from 14 October: CERN SSB at https://cern.ch/ssb Computing SSB (previously IT SSB) at https://cern.ch/itssb   Nicole Cremel, IT and GS Service Management Support

  8. FRIB Cryogenic Plant Status

    Dixon, Kelly D. [Thomas Jefferson National Accelerator Facility (TJNAF), Newport News, VA (United States); Ganni, Venkatarao [Thomas Jefferson National Accelerator Facility (TJNAF), Newport News, VA (United States); Knudsen, Peter N. [Thomas Jefferson National Accelerator Facility (TJNAF), Newport News, VA (United States); Casagranda, Fabio [Michigan State Univ., East Lansing, MI (United States)

    2015-12-01

    After practical changes were approved to the initial conceptual design of the cryogenic system for MSU FRIB and an agreement was made with JLab in 2012 to lead the design effort of the cryogenic plant, many activities are in place leading toward a cool-down of the linacs prior to 2018. This is mostly due to using similar equipment used at CHLII for the 12 GeV upgrade at JLab and an aggressive schedule maintained by the MSU Conventional Facilities department. Reported here is an updated status of the cryogenic plant, including the equipment procurement status, plant layout, facility equipment and project schedule.

  9. INTRAHIPPOCAMPAL ADMINISTRATION OF IBOTENIC ACID INDUCED CHOLINERGIC DYSFUNCTION via NR2A/NR2B EXPRESSION: IMPLICATIONS OF RESVERATROL AGAINST ALZHEIMER DISEASE PATHOPHYSIOLOGY

    Chennakesavan eKarthick

    2016-04-01

    Full Text Available Although several drugs revealed moderate amelioration of symptoms, none of them have sufficient potency to prevent or reverse the progression towards Alzheimer’s disease (AD pathology. Resveratrol (RSV, a polyphenolic compound has shown an outstanding therapeutic effect on a broad spectrum of diseases like age-associated neurodegeneration, inflammation etc. The present study was thus conducted to assess the therapeutic efficacy of RSV in ameliorating the deleterious effects of Ibotenic acid (IBO in male Wistar rats. Stereotactic intrahippocampal administration of IBO (5µg/µl lesioned rats impairs cholinergic transmission, learning and memory performance that is rather related to AD and thus chosen as a suitable model to understand the drug efficacy in preventing AD pathophysiology. Since IBO is an agonist of glutamate, it is expected to exhibit an excitotoxic effect by altering glutamatergic receptors like NMDA receptor. The current study displayed significant alterations in the mRNA expression of NR2A and NR2B subunits of NMDA receptors, and further it is surprising to note that cholinergic receptors decreased in expression particularly α7-nAChR with increased m1AChR. RSV administration (20mg/kg body weight, i.p significantly reduced these changes in IBO induced rats. Glutamatergic and cholinergic receptor alterations were associated with significant changes in the behavioral parameters of rats induced by IBO. While RSV improved spatial learning performance, attenuated immobility and improvised open field activity in IBO induced rats. NR2B activation in the present study might mediate cell death through oxidative stress that form the basis of abnormal behavioral pattern in IBO induced rats. Interestingly, RSV that could efficiently encounter oxidative stress have significantly decreased stress markers viz., nitrite, PCO, and MDA levels by enhancing antioxidant status. Histopathological analysis displayed significant reduction in the

  10. Intrahippocampal Administration of Ibotenic Acid Induced Cholinergic Dysfunction via NR2A/NR2B Expression: Implications of Resveratrol against Alzheimer Disease Pathophysiology.

    Karthick, Chennakesavan; Periyasamy, Sabapathy; Jayachandran, Kesavan S; Anusuyadevi, Muthuswamy

    2016-01-01

    Although several drugs revealed moderate amelioration of symptoms, none of them have sufficient potency to prevent or reverse the progression toward Alzheimer's disease (AD) pathology. Resveratrol (RSV), a polyphenolic compound has shown an outstanding therapeutic effect on a broad spectrum of diseases like age-associated neurodegeneration, inflammation etc. The present study was thus conducted to assess the therapeutic efficacy of RSV in ameliorating the deleterious effects of Ibotenic acid (IBO) in male Wistar rats. Stereotactic intrahippocampal administration of IBO (5 μg/μl) lesioned rats impairs cholinergic transmission, learning and memory performance that is rather related to AD and thus chosen as a suitable model to understand the drug efficacy in preventing AD pathophysiology. Since IBO is an agonist of glutamate, it is expected to exhibit an excitotoxic effect by altering glutamatergic receptors like NMDA receptor. The current study displayed significant alterations in the mRNA expression of NR2A and NR2B subunits of NMDA receptors, and further it is surprising to note that cholinergic receptors decreased in expression particularly α7-nAChR with increased m1AChR. RSV administration (20 mg/kg body weight, i.p.) significantly reduced these changes in IBO induced rats. Glutamatergic and cholinergic receptor alterations were associated with significant changes in the behavioral parameters of rats induced by IBO. While RSV improved spatial learning performance, attenuated immobility, and improvised open field activity in IBO induced rats. NR2B activation in the present study might mediate cell death through oxidative stress that form the basis of abnormal behavioral pattern in IBO induced rats. Interestingly, RSV that could efficiently encounter oxidative stress have significantly decreased stress markers viz., nitrite, PCO, and MDA levels by enhancing antioxidant status. Histopathological analysis displayed significant reduction in the hippocampal

  11. Iraq: Country Status Report.

    McFerren, Margaret

    A survey of the status of language usage in Iraq begins with an overview of the usage patterns of Arabic and Kurdish, especially in the context of recent political events and the agreement to make Kurdish a second official language in the Kurdish autonomous region, and to allow limited use of Kurdish in instruction and public communication. A…

  12. Iran: Country Status Report.

    McFerren, Margaret

    A survey of the status of language usage in Iran begins with an overview of the usage pattern of Persian, the official language spoken by just over half the population, and the competing languages of six ethnic and linguistic minorities: Azerbaijani, Kurdish, Arabic, Gilaki, Luri-Bakhtiari, and Mazandarani. The development of language policy…

  13. Kurdish. Materials Status Report.

    Center for Applied Linguistics, Washington, DC. Language/Area Reference Center.

    The materials status report for Kurdish is one of a series intended to provide the nonspecialist with a picture of the availability and quality of texts for teaching a given language to English speakers. Each report consists of: (1) a brief narrative description of the language, the areas where it is spoken, its major dialects, its writing system,…

  14. Status of PHOKHARA

    A review of the status of the Monte Carlo event generator PHOKHARA, developed for experiments using the radiative return method. The four-pion production in electron-positron annihilation and in τ-lepton decays and the narrow resonances studies are described.

  15. Mental status testing

    ... Search Search MedlinePlus GO GO About MedlinePlus Site Map FAQs Contact Us Health Topics Drugs & Supplements Videos & Tools Español You Are Here: Home → Medical Encyclopedia → Mental status testing URL of this page: //medlineplus.gov/ ...

  16. Angola: Country Status Report.

    Bruhn, Thea C.

    A survey of the status of language usage in Angola begins with an overview of the usage and distribution of Portuguese as the official language, and the four most significant native languages and dialects spoken there: Umbundu, Kimbundu, Kikongo, and Lunda-Chokwe. The introduction of Spanish through Cuban trainers, teachers, and military advisors…

  17. WOMEN STATUS IN INDIA

    A. Prema

    2012-01-01

    This paper tries to explain the development of women movement in India and the status of women during the Vedic period and British period. It also tries to explain the position of women on the basis of socioeconomic – political empowerment.

  18. Stellarator status, 1989

    The present status of stellarator experiments and recent progress in stellarator research (both experimental and theoretical) are reported by groups in the United States, the USSR, Japan, Australia, and the European Community (the Federal Republic of Germany and Spain). Experiments under construction and studies of large, next-generation stellarators are also described. 73 refs., 11 figs., 4 tabs

  19. The Status of CMS

    Incandela, Joseph R.

    2007-01-01

    After a brief overview of the Compact Muon Solenoid (CMS) experiment, the status of construction, installation and commissioning is described. Very good progress has been achieved in the past year. Though many significant challenges still lie ahead, CMS should be ready for recording data from first collisions in the Large Hadron Collider (LHC) accelerator complex at CERN

  20. Fusion safety status report

    This report includes information on a) tritium handling and safety; b) activation product generation and release; c) lithium safety; d) superconducting magnet safety; e) operational safety and shielding; f) environmental impact; g) recycling, decommissioning and waste management; and h) accident analysis. Recommendations for high priority research and development are presented, as well as the current status in each area

  1. Women Status and their Discrimination

    PEŠKOVÁ, Pavlína

    2008-01-01

    My work deal with women status and their discrimination. Chapter one contains women status in different historical periods and development of their status to bigger equal with men. There is also written about present feminist trends. Chapter two is about women discrimination. There is about women´ job discrimination, job segregation according to gender and inequality in payment. There is also written about women status at home and unequal duties at home among family mates. Chapter three is ab...

  2. Evolutionary status of Entamoeba

    DONG Jiuhong; WEN Jianfan; XIN Dedong; LU Siqi

    2004-01-01

    In addition to its medical importance as parasitic pathogen, Entamoeba has aroused people's interest in its evolutionary status for a long time. Lacking mitochondrion and other intracellular organelles common to typical eukaryotes, Entamoeba and several other amitochondrial protozoans have been recognized as ancient pre-mitochondriate eukaryotes and named "archezoa", the most primitive extant eukaryotes. It was suggested that they might be living fossils that remained in a primitive stage of evolution before acquisition of organelles, lying close to the transition between prokaryotes and eukaryotes. However, recent studies revealed that Entamoeba contained an organelle, "crypton" or "mitosome", which was regarded as specialized or reductive mitochondrion. Relative molecular phylogenetic analyses also indicated the existence or the probable existence of mitochondrion in Entamoeba. Our phylogenetic analysis based on DNA topoisomerase II strongly suggested its divergence after some mitchondriate eukaryotes. Here, all these recent researches are reviewed and the evolutionary status of Entamoeba is discussed.

  3. Sibling Status Effects: Adult Expectations.

    Baskett, Linda Musun

    1985-01-01

    This study attempted to determine what expectations or beliefs adults might hold about a child based on his or her sibling status alone. Ratings on 50 adjective pairs for each of three sibling status types, only, oldest, and youngest child, were assessed in relation to adult expectations, birth order, and parental status of rater. (Author/DST)

  4. Status of the SLC

    The goals of the SLAC Linear Collider, SLC, are to develop the techniques of linear colliders and to do physics at and slightly above the energy necessary to produce the Z0. A short review is given of the physics goals of the SLC, followed by the status of the SLC and its detectors. Plans for accelerating polarized electrons at SLC are also discussed. 6 figs

  5. Status of fusion maintenance

    Effective maintenance will be an essential ingredient in determining fusion system productivity. This level of productivity will result only after close attention is paid to the entire system as an entity and appropriate integration of the elements is made. The status of fusion maintenance is reviewed in the context of the entire system. While there are many challenging developmental tasks ahead in fusion maintenance, the required technologies are available in several high-technology industries, including nuclear fission

  6. Tritium monitoring : present status

    The report summarizes the present status of techniques employed for the monitoring of tritium in water, air and other samples. A brief mention of the work done by numerous workers in the field, critical comments about the work and a fairly exhaustive list of references about the work done during the last 4 decades has been presented. On-line monitoring on real time basis in nuclear reactors is also discussed. (author). 83 refs., 10 refs., 2 tabs

  7. DUMAND II status report

    The scientific goals, design, capabilities, and status of the DUMAND II detector system are described. In June, 1989, the High Energy Physics Advisory Panel recommended support for construction of DUMAND II to the U.S. Department of Energy. Funding began in 1990, and prototype development for various detector subsystems is under way. Current plans include deployment of the shore cable, junction box and three strings of optical detector modules in 1992, and expansion to the full 9-string configuration in 1993

  8. MARS Flight Engineering Status

    Fast, James E.; Dorow, Kevin E.; Morris, Scott J.; Thompson, Robert C.; Willett, Jesse A.

    2010-04-06

    The Multi-sensor Airborne Radiation Survey Flight Engineering project (MARS FE) has designed a high purity germanium (HPGe) crystal array for conducting a wide range of field measurements. In addition to the HPGe detector system, a platform-specific shock and vibration isolation system and environmental housing have been designed to support demonstration activities in a maritime environment on an Unmanned Surface Vehicle (USV). This report describes the status of the equipment as of the end of FY09.

  9. Experimental status of physics

    H Yamamoto

    2000-07-01

    In a short period of time, we will have a large amount of results from -factories including ones on CP violation. In this talk, we briefly review the current experimental status of -physics. After a quick description of -facilities, we divide this vast field into two categories: (1) weak interaction and QCD, (2) unitarity triangle and CP violation. Only a few critical items are selected in each category for the sake of time and space.

  10. QCDSP A status report

    Chen, D; Christ, N H; Edwards, R G; Fleming, G R; Gara, A; Hansen, S; Jung, C; Kähler, A L; Kennedy, A D; Kilcup, G W; Luo, Y; Malureanu, C I; Mawhinney, Robert D; Parsons, H; Sexton, J C; Sui, C Z; Vranas, P M; Chen, Dong; Chen, Ping; Christ, Norman H.; Edwards, Robert G.; Fleming, George R.; Gara, Alan; Hansen, Sten; Jung, Chulwoo; Kaehler, Adrian L.; Kennedy, Anthony D.; Kilcup, Gregory W.; Luo, Yubing; Malureanu, Catalin I.; Mawhinney, Robert D.; Parsons, John; Sexton, James C.; Sui, ChengZhong; Vranas, Pavlos M.

    1997-01-01

    The QCDSP machine at Columbia University has grown to 2,048 nodes achieving a peak speed of 100 Gigaflops. Software for quenched and Hybrid Monte Carlo (HMC) evolution schemes has been developed for staggered fermions, with support for Wilson and clover fermions under development. We provide an overview of the runtime environment, the current status of the QCDSP construction program and preliminary results not presented elsewhere in these proceedings.

  11. CRESST - status and future

    We present results on WIMP dark matter interaction, obtained using cryogenic phonon-scintillation detectors. The targets are CaWO4 scintillating crystals with phonon sensors, while scintillation is detected with an associated cryogenic light detector. The combination of phonon and light signals leads to a strong suppression of nonnuclear recoil backgrounds. Results obtained before the upgrade of CRESST are presented and a status report on the upgrade itself is given

  12. QCDSP - a status report

    The QCDSP machine at Columbia University has grown to 2048 nodes achieving a peak speed of 100 Gigaflops. Software for quenched and hybrid Monte Carlo (HMC) evolution schemes has been developed for staggered fermions, with support for Wilson and clover fermions under development. We provide an overview of the runtime environment, the current status of the QCDSP construction program and preliminary results not presented elsewhere in these proceedings. (orig.)

  13. DUMAND status report

    DUMAND is a project to build a large deep underwater laboratory for the study of high energy neutrinos from extrasolar sources. The stage 11 array -consisting of 216 optical modules covering an effective area of about 20 000 m2 for neutrinos with energies above 500 GeV/c - is under construction. The fibre optic cable for data transmission has been deployed successfully. A report on the present status of the experiment is given. (orig.)

  14. OPERA: Status and prospects

    di Crescenzo, Antonia

    2014-03-01

    The Oscillation Project with Emulsion-tRacking Apparatus (OPERA) neutrino experiment was designed to perform a unique appearance measurement in the CNGS beam to confirm the oscillation mechanism in the atmospheric sector. Runs were successfully carried out from 2008 to 2012. The status of the analysis is reported and the topology and the kinematics of the first three ντ candidate events are described. A first result of the νμ→νe oscillation search is also presented.

  15. Uranium mining: Saskatchewan status

    This paper gives the status of uranium mining by Areva in Saskatchewan. Uranium production now meets 85% of world demand for power generation. 80% of world production of uranium comes from top 5 countries: Kazakhstan, Canada, Australia, Niger and Namibia. Saskatchewan is currently the only Canadian province with active uranium mines and mills and the largest exploration programs. Several mine projects are going through the environmental assessment process. Public opinion is in favour of mining activities in Saskatchewan.

  16. Status of VIRGO

    Virgo Collaboration; Acernese, F.; Amico, P.; Arnaud, N.; Babusci, D.; Ballardin, G.; Barillé, R.; Barone, F.; Barsuglia, M.; Beauville, F.; Bellachia, F.; Bizouard, M. A.; Boccara, C.; Boget, D.; Bondu, F.; Bourgoin, C.; Bozzi, A.; Braccini, S.; Bradaschia, C.; Brillet, A.; Brisson, V.; Brocco, L.; Buskulic, D.; Cachenaut, J.; Calamai, G.; Calloni, E.; Campagna, E.; Casciano, C.; Cattuto, C.; Cavalier, F.; Cavaliere, S.; Cavalieri, R.; Cella, G.; Chassande-Mottin, E.; Chollet, F.; Cleva, F.; Cokelaer, T.; Conforto, G.; Cortese, S.; Coulon, J. P.; Cuoco, E.; Dattilo, V.; Y Davíd, P.; Davier, M.; De Rosa, M.; De Rosa, R.; Di Fiore, L.; Di Virgilio, A.; Dujardin, B.; Dominici, P.; Eleuteri, A.; Enard, D.; Evangelista, G.; Ferrante, I.; Fidecaro, F.; Fiori, I.; Flaminio, R.; Forest, D.; Fournier, J. D.; Fournier, L.; Frasca, S.; Frasconi, F.; Gammaitoni, L.; Ganau, P.; Gennai, A.; Gennaro, G.; Giacobone, L.; Giazotto, A.; Giordano, G.; Girard, C.; Gougoulat, G.; Guidi, G. M.; Heitmann, H.; Hello, P.; Hermel, R.; Heusse, P.; Holloway, L.; Honglie, F.; Iannarelli, M.; Journet, L.; Krecklbergh, S.; Lagrange, B.; La Penna, P.; Leliboux, M.; Lieunard, B.; Lomtadze, T.; Loriette, V.; Losurdo, G.; Loupias, M.; Mackowski, J. M.; Majorana, E.; Man, C. N.; Marchesoni, F.; Marion, F.; Martelli, F.; Masserot, A.; Massonnet, L.; Mataguez, S.; Menzinger, F.; Mazzoni, M.; Michel, C.; Milano, L.; Montorio, J. L.; Moreau, F.; Moreau, J.; Morgado, N.; Mornet, F.; Mours, B.; Mugnier, P.; Nenci, F.; Pacheco, J.; Pai, A.; Palomba, C.; Paoletti, F.; Paoli, A.; Paoli, L.; Pasqualetti, A.; Passaquieti, R.; Passuello, D.; Perciballi, M.; Peruzzi, S.; Perniola, B.; Pinard, L.; Poggiani, R.; Popolizio, P.; Porter, E.; Puccinelli, S.; Punturo, M.; Puppo, P.; Qipiani, K.; Ramonet, J.; Rapagnani, P.; Reita, V.; Remillieux, A.; Ricci, F.; Richard, F.; Roger, J. P.; Ruggi, P.; Russo, G.; Solimeno, S.; Stanga, R.; Taddei, R.; Teuler, J. M.; Tournefier, E.; Travasso, F.; Trinquet, H.; Turri, E.; Varvella, M.; Verkindt, D.; Vetrano, F.; Veziant, O.; Viceré, A.; Vilalte, S.; Y Vinet, J.; Vocca, H.; Yvert, M.; Zhang, Z.

    2003-09-01

    We report on the status of the VIRGO detector as of the beginning of 2003. In particular, we summarize the results obtained during the commissioning of the central portion of the detector, consisting of a power-recycled Michelson interferometer, and we outline the steps which will lead during 2003 and 2004 to the commissioning and operation of the full scale, 3 km long VIRGO detector.

  17. SalSA status

    I review the status of SalSA, a proposed antenna array in a large volume salt formation for detecting ultra-high energy neutrinos. We report on measurements taken in 2007 of attenuation lengths in the 125-900 MHz frequency range at the Cote Blanche salt mine near New Iberia, Louisiana, which is the most precise in situ measurement of attenuation lengths in salt to date. We comment on the impact of these measurements on the feasibility of SalSA.

  18. SalSA status

    Connolly, Amy [Department of Physics and Astronomy, University College London, Gower Street, London WC1E 6BT (United Kingdom)], E-mail: amyc@hep.ucl.ac.uk

    2009-06-01

    I review the status of SalSA, a proposed antenna array in a large volume salt formation for detecting ultra-high energy neutrinos. We report on measurements taken in 2007 of attenuation lengths in the 125-900 MHz frequency range at the Cote Blanche salt mine near New Iberia, Louisiana, which is the most precise in situ measurement of attenuation lengths in salt to date. We comment on the impact of these measurements on the feasibility of SalSA.

  19. Model Validation Status Review

    E.L. Hardin

    2001-11-28

    The primary objective for the Model Validation Status Review was to perform a one-time evaluation of model validation associated with the analysis/model reports (AMRs) containing model input to total-system performance assessment (TSPA) for the Yucca Mountain site recommendation (SR). This review was performed in response to Corrective Action Request BSC-01-C-01 (Clark 2001, Krisha 2001) pursuant to Quality Assurance review findings of an adverse trend in model validation deficiency. The review findings in this report provide the following information which defines the extent of model validation deficiency and the corrective action needed: (1) AMRs that contain or support models are identified, and conversely, for each model the supporting documentation is identified. (2) The use for each model is determined based on whether the output is used directly for TSPA-SR, or for screening (exclusion) of features, events, and processes (FEPs), and the nature of the model output. (3) Two approaches are used to evaluate the extent to which the validation for each model is compliant with AP-3.10Q (Analyses and Models). The approaches differ in regard to whether model validation is achieved within individual AMRs as originally intended, or whether model validation could be readily achieved by incorporating information from other sources. (4) Recommendations are presented for changes to the AMRs, and additional model development activities or data collection, that will remedy model validation review findings, in support of licensing activities. The Model Validation Status Review emphasized those AMRs that support TSPA-SR (CRWMS M&O 2000bl and 2000bm). A series of workshops and teleconferences was held to discuss and integrate the review findings. The review encompassed 125 AMRs (Table 1) plus certain other supporting documents and data needed to assess model validity. The AMRs were grouped in 21 model areas representing the modeling of processes affecting the natural and

  20. 1998 status report

    Since its creation in 1945, the activities of Cea have been centered on the study and development of the pacific use of nuclear energy and on assuring the credibility of nuclear deterrent. This status report presents the research programs led by Cea in 1998. The main topics are: the designing of reactor cores, fuel cycle, nuclear safety, radiation protection, the activities for defense, high technologies for industry, biology and fundamental sciences. The quality of research work is assured by an independent and regular assessment of the scientific activities. (A.C.)

  1. Folate status and health

    Obeid, Rima; Oexle, Konrad; Rißmann, Anke; Pietrzik, Klaus; Koletzko, Berthold

    2015-01-01

    worldwide by applying fortification with folic acid. Periconceptional supplementation of folic acid also reduces the risk of congenital heart diseases, preterm birth, low birth weight, and health problems associated with child mortality and morbidity. All European governments failed to issue folic acid...... health centers for prenatal care and fortification with folic acid in Europe are urgently needed. Only such an action will sufficiently improve folate status, prevent at least 50% of the NTD cases, reduce child mortality and morbidity, and alleviate other health problems associated with low folate such...

  2. Model Validation Status Review

    The primary objective for the Model Validation Status Review was to perform a one-time evaluation of model validation associated with the analysis/model reports (AMRs) containing model input to total-system performance assessment (TSPA) for the Yucca Mountain site recommendation (SR). This review was performed in response to Corrective Action Request BSC-01-C-01 (Clark 2001, Krisha 2001) pursuant to Quality Assurance review findings of an adverse trend in model validation deficiency. The review findings in this report provide the following information which defines the extent of model validation deficiency and the corrective action needed: (1) AMRs that contain or support models are identified, and conversely, for each model the supporting documentation is identified. (2) The use for each model is determined based on whether the output is used directly for TSPA-SR, or for screening (exclusion) of features, events, and processes (FEPs), and the nature of the model output. (3) Two approaches are used to evaluate the extent to which the validation for each model is compliant with AP-3.10Q (Analyses and Models). The approaches differ in regard to whether model validation is achieved within individual AMRs as originally intended, or whether model validation could be readily achieved by incorporating information from other sources. (4) Recommendations are presented for changes to the AMRs, and additional model development activities or data collection, that will remedy model validation review findings, in support of licensing activities. The Model Validation Status Review emphasized those AMRs that support TSPA-SR (CRWMS M and O 2000bl and 2000bm). A series of workshops and teleconferences was held to discuss and integrate the review findings. The review encompassed 125 AMRs (Table 1) plus certain other supporting documents and data needed to assess model validity. The AMRs were grouped in 21 model areas representing the modeling of processes affecting the natural and

  3. Status of APE projects

    This talk is divided in two parts. In the first part, we will summarize the status of the APEmille project that will be completed by the end of the year. We will then devote the rest of the talk to the description of a new project for a multi-TeraFlop machine, apeNEXT. The interested reader will find a much more detailed discussion of all the items touched upon here in the full proposal of the project that will shortly appear on hep-lat

  4. NESTOR: a status report

    NESTOR is the detector for the underwater neutrino astrophysics laboratory to be located in the international waters off the southwest of Greece. The first phase of this experiment is the construction and deployment of one hexagonal tower, with effective area for TeV neutrinos of 20 000 m2, consisting of 168 optical modules. The tower will be deployed in a single operation in '97. Over the past few years detailed studies of the site have been carried out while many of the major constituents of the detector have been under test. The current status of the preparation of the experiment will be presented. (orig.)

  5. DUMAND status report

    DUMAND is a project to build a large deep underwater laboratory for the study of high energy neutrinos from extra solar sources. The stage II array -consisting of 216 optical modules covering an effective area of about 20000 m2 for neutrinos with energies above 500 GeV/c - is under construction. The complete detector will have an angular resolution of around 1 degree. The fibre optic cable for data transmission has been deployed successfully. A report on the present status of the experiment as well as a short outlook to the next generation detectors is given. (author). 5 figs., 6 refs

  6. Status of safeguards instrumentation

    The International Atomic Energy Agency is performing safeguards at some nuclear power reactors, 50 bulk processing facilities, and 170 research facilities. Its verification activities require the use of instruments to measure nuclear materials and of surveillance instruments to maintain continuity of knowledge of the locations of nuclear materials. Instruments that are in use and under development to measure weight, volume, concentration, and isotopic composition of nuclear materials, and the major surveillance instruments, are described in connection with their uses at representative nuclear facilities. The current status of safeguards instrumentation and the needs for future development are discussed

  7. Reactor gamma spectrometry: status

    Current work is described for Compton Recoil Gamma-Ray Spectrometry including developments in experimental technique as well as recent reactor spectrometry measurements. The current status of the method is described concerning gamma spectromoetry probe design and response characteristics. Emphasis is given to gamma spectrometry work in US LWR and BR programs. Gamma spectrometry in BR environments are outlined by focussing on start-up plans for the Fast Test Reactor (FTR). Gamma spectrometry results are presented for a LWR pressure vessel mockup in the Poolside Critical Assembly (PCA) at Oak Ridge National Laboratory

  8. Teleradiology - current status

    Tele-radiology is a term becoming increasingly popular in the medical literature. Nevertheless, terminological definitions in this particular field are still rather vague. The scope of applications extend from simple image presenting via analogue telephone lines to transmission of 3-D medical images through a satellite. It is a matter of standards highly differing in terms of data transmission rates, safety, technical demands on the systems and the like. In this article new information technologies, technical aspects, as well as some major applications of tele-radiology are discussed. The current status of tele-medicine/tele-radiology in this country is likewise briefly outlined

  9. NESTOR: A status report

    Anassontzis, E G; Barone, M; Foudas, C; Grammatikakis, G; Katsanevas, S; Kourkoumelis, C; Manousakis-Katsikakis, A; Resvanis, L K; Siotis, I; Sotiriou, S A; Voulgaris, G; Minkowski, P; Grieder, P K F; Ball, A E; Bottai, S; Cartacci, A M; Monteleoni, B; Naumov, Vadim A; Trasatti, L; Fahrun, E; Keusen, U; Koske, P; Rathlev, J; Schmidt, N P; Voight, G; Bezrukov, Leonid B; Butkevich, A V; Dedenko, L G; Karaevsky, S K; Mironovich, A A; Zakharov, L M; Zheleznykh, I M; Zhukov, V A; Demidova, T A; Deineko, A O; Eremeev, A P; Paka, V T; Permyakov, A A; Platonov, M N; Rukol, V Kh; Sheremet, N A; Surin, N M; Albul, V I; Ledenev, V V

    2000-01-01

    NESTOR is an underwater neutrino astrophysics laboratory to be located in the international waters of the southwest of Greece. The first phase of this experiment is the construction and deployment of one hexagonal tower consisting of 168 optical modules, with effective are of 20000m2 for E ⩾ TeV neutrinos. Over the past few years detailed studies of the site have been carried out while many tests have been performed. The current status of the preparation of the experiment and the future plans will be presented.

  10. Zinc status of vegetarians.

    Freeland-Graves, J H; Bodzy, P W; Eppright, M A

    1980-12-01

    The zinc status of seventy-nine vegetarians and forty-one non-vegetarians was investigated. The subjects provided 24-hr. dietary recalls and donated samples of blood, hair, and saliva that were subsequently analyzed for zinc content. Avoidance of animal products in the diet was associated with decreased intakes of energy, protein, fat, calcium, and zinc and increased consumption of crude fiber, potassium, vitamin A, and ascorbic acid. The low dietary intake of zinc by vegetarian women was believed to result from liberal use of foods low in zinc such as fruits and vegetables, whereas vegetarian men primarily consumed zinc-rich food such as legumes and cheeses Lacto-ovo-vegetarians consumed twice the amount of crude fiber consumed by non-vegetarians and vegans four times as much. The zinc content of salivary sediment was significantly lower in vegetarians than in non-vegetarians; vegans had the lowest mean level. The observed decrease in salivary zinc was inversely proportional to the amount of crude fiber in the diet. Zinc levels in the hair of vegetarians were significantly lower than those in the hair of non-vegetarians, while serum levels were also lower, but not significantly so. The increased crude fiber intake of vegetarians coupled with the decreased levels of zinc found in saliva and hair seem to indicate that some vegetarians, particularly women, have less than satisfactory zinc status. PMID:7440860

  11. Operating Room Status Monitoring System

    Kane, Francis R.

    1982-01-01

    A system has been devised at The Medical College of Virginia to schedule, monitor, and display the status of twenty-four operating rooms. A switch in each room indicates room status. Room status is matched with scheduling information to provide an airport-like display on 16 video monitors placed about the operating room area. Management and medical information is captured by the system.

  12. Caspase-3 expression in spinal tissue of retinoic acid induce spiua bifida fetal rat%维甲酸诱导脊柱裂胎鼠脊髓组织中Caspase-3表达情况

    马英桓; 袁正伟

    2012-01-01

    Objective To explore caspase-3 expression in spinal tissue of retinoic acid induced spina bifida fetal rat. Methods Pregnant Wister rats with 10 days were used. Retinoic acid dissolved in olive oil (40mg /ml) were stomach fed for preparing the rat model of spina bifida malformations 135mg / kg). Control group only received olive oil. The animals were divided into 4 groups: pregnancy of 12 days, 15 days, 17 days and 20 days. Immunohistochemical method was used to detect and compare caspase-3 expression in different groups. Results The expression of caspase-3 increased at the day 15 after pregnancy, and maintained until day 20 in the spinal tissue of modeled fetal rat, which presented significant difference compared to that of control groups at the same pregnant time. At day 15, day 17 and day 20 of pregnancy, the number of caspase-3 positive cells was more in model animals than the control. Conclusions Retinoic acid induced spina bifida fetal rat demonstrates the increased caspase-3 expression in spinal tissue of fetal rats.%目的 本文旨在探讨维甲酸诱导脊柱裂胎鼠脊髓组织Caspase-3表达情况.方法 选取孕10d Wistar大鼠,实验组用溶有维甲酸(40mg/ml)的橄榄油,以135mg/kg经胃管注入给药制作脊柱裂畸形大鼠模型;对照组选取孕10 d Wistar大鼠给等量橄榄油.将实验组及对照组按照孕12、15、17和20 d分为4组.应用免疫组织化学方法比较分析Caspase-3在对照组、畸形组胎鼠脊髓组织细胞中的分布和表达情况.结果 脊柱裂大鼠脊髓神经组织中Caspase-3在15d开始增多,一直持续到20 d胚胎大鼠.其增高情况明显高于同一时间点对照组大鼠.胚胎15、17和20 d显性脊柱裂畸形鼠脊髓组织Caspase-3阳性细胞数多于对照组,荧光强度高于对照组.结论 维甲酸诱导的脊柱裂胎鼠Caspase-3表达明显高于正常发育胎鼠.

  13. The CMS HF status

    Rahmat, Rahmat

    2012-01-01

    The experiments at the Large Hadron Collider will have to deal with unprecedented radiation levels. The design of the CMS forward calorimetry detector (HF) is now finalized. The present design of CMS calls for the HF calorimeter to be based on quartz fiber technology. It consists of two modules, located symmetrically at about 11 meters from either side of interaction point. They cover the pseudorapidity range 3-5. The length along the beam is 1.65m or 10 nuclear interaction lenghts. Each calorimeter consists of a large steel block that serves as the absorber. Embedded quartz fibers in the steel absorber run parallel to the beam and constitute the active component of the detector. In order to optimize energy resolution for E and ET flows and forward jets, the calorimeter is effectively segmented longitudinally by using two different fiber lengths. The present status will be discussed.

  14. Status of French reactors

    Ballagny, A. [Commissariat a l`Energie Atomique, Saclay (France)

    1997-08-01

    The status of French reactors is reviewed. The ORPHEE and RHF reactors can not be operated with a LEU fuel which would be limited to 4.8 g U/cm{sup 3}. The OSIRIS reactor has already been converted to LEU. It will use U{sub 3}Si{sub 2} as soon as its present stock of UO{sub 2} fuel is used up, at the end of 1994. The decision to close down the SILOE reactor in the near future is not propitious for the start of a conversion process. The REX 2000 reactor, which is expected to be commissioned in 2005, will use LEU (except if the fast neutrons core option is selected). Concerning the end of the HEU fuel cycle, the best option is reprocessing followed by conversion of the reprocessed uranium to LEU.

  15. Status of legislation

    The status of the House legislation, the major differences between the House and Senate legislation and a preview of what is likely to take place during the lame duck session in December are presented. The House legislation provides: long-term program leading toward permanent disposal of nuclear waste; an interim program for storage and for expansion of storage space for spent fuel; provides an R and D component through what is called a test and evaluation facility; an alternative long-term storage program based on a proposal to be completed by the Department of Energy on what's called Monitored Retrievable Storage; full upfront financing of the program through user fees based on contracts between the government and the users of the nuclear waste disposal services

  16. Status of RENO Experiment

    An experiment, RENO (Reactor Experiment for Neutrino Oscillation), is under construction to measure the smallest and unknown neutrino mixing angle (θ13) using anti-neutrinos emitted from the Yonggwang nuclear power plant in Korea. The experimental setup consists of two identical 16-ton Gadolinium loaded liquid scintillator detectors located near and far from the reactor array to measure the deviations from the inverse square distance law. The experiment is planned to start data-taking in early 2011. An estimated systematic uncertainty associated with the measurement is less than 0.6%. Based on three years of data, it would be sensitive to measure the neutrino mixing angle in the range of sin2(2θ13)>0.02. In this talk, the status of RENO experiment is described.

  17. Status of RENO Experiment

    The RENO (Reactor Experiment for Neutrino Oscillation) experiment is under construction to measure the smallest neutrino mixing angle θ13 using anti-neutrinos emitted from the Yonggwang nuclear power plant in Korea. The experiment is planning to start data-taking in early 2011 with two identical 16-ton Gadolinium loaded liquid scintillator detectors located near and far from the center of the reactor array. The estimated systematic uncertainty associated with the measurement is less than 0.6%. Based on three years of data, the expected statistical error is about 0.3% and it would be sensitive to measure the neutrino mixing angle in the range, sin2(2θ13)> 0.02. In this talk, the overview and status of RENO experiment are described.

  18. CLIC Status and Outlook

    Stapnes, Stapnes

    2012-01-01

    The Compact Linear Collider study (CLIC) is in the process of completing a Conceptual Design Report (CDR) for a multi-TeV linear electron-positron collider. The CLICconcept is based on high gradient normal-conducting accelerating structures. The RF power for the acceleration of the colliding beams is produced by a novel two beam acceleration scheme, where power is extracted from a high current drive beam that runs parallel with the main linac. In order to establish the feasibility of this concept a number of key issues have been addressed. A short summary of the progress and status of the corresponding studies will be given, as well as an outline of the preparation and work towards an implementation plan by 2016.

  19. ITER EDA project status

    The status of the ITER design is as presented in the interim design report accepted by the ITER council for considerations by ITER parties. Physical and technical parameters of the machine, conditions of operation of main nuclear systems, corresponding design and material choices are described, with conventional materials selected. To fully utilize the safety and economical potential of fusion advanced materials are necessary. ITER shall and can be built with materials already available. The ITER project and advanced fusion material developments can proceed in parallel. The role of ITER is to establish (experimentally) requirements to these materials and to provide a test bed for their final qualification in fusion reactor environment. To achieve this goal, the first wall/blanket modules test program is foreseen. (orig.)

  20. ITER EDA project status

    Chuyanov, V.A. [ITER San Diego JWS, La Jolla, CA (United States)

    1996-10-01

    The status of the ITER design is as presented in the interim design report accepted by the ITER council for considerations by ITER parties. Physical and technical parameters of the machine, conditions of operation of main nuclear systems, corresponding design and material choices are described, with conventional materials selected. To fully utilize the safety and economical potential of fusion advanced materials are necessary. ITER shall and can be built with materials already available. The ITER project and advanced fusion material developments can proceed in parallel. The role of ITER is to establish (experimentally) requirements to these materials and to provide a test bed for their final qualification in fusion reactor environment. To achieve this goal, the first wall/blanket modules test program is foreseen. (orig.).

  1. ITER EDA project status

    Chuyanov, V. A.

    1996-10-01

    The status of the ITER design is as presented in the Interim Design Report accepted by the ITER council for considerations by ITER parties. Physical and technical parameters of the machine, conditions of operation of main nuclear systems, corresponding design and material choices are described, with conventional materials selected. To fully utilize the safety and economical potential of fusion advanced materials are necessary. ITER shall and can be built with materials already available. The ITER project and advanced fusion material developments can proceed in parallel. The role of ITER is to establish (experimentally) requirements to these materials and to provide a test bed for their final qualification in fusion reactor environment. To achieve this goal, the first wall/blanket modules test program is foreseen.

  2. Stimulation of large-conductance calcium-activated potassium channels inhibits neurogenic contraction of human bladder from patients with urinary symptoms and reverses acetic acid-induced bladder hyperactivity in rats.

    La Fuente, José M; Fernández, Argentina; Cuevas, Pedro; González-Corrochano, Rocío; Chen, Mao Xiang; Angulo, Javier

    2014-07-15

    We have analysed the effects of large-conductance calcium-activated potassium channel (BK) stimulation on neurogenic and myogenic contraction of human bladder from healthy subjects and patients with urinary symptoms and evaluated the efficacy of activating BK to relief bladder hyperactivity in rats. Bladder specimens were obtained from organ donors and from men with benign prostatic hyperplasia (BPH). Contractions elicited by electrical field stimulation (EFS) and carbachol (CCh) were evaluated in isolated bladder strips. in vivo cystometric recordings were obtained in anesthetized rats under control and acetic acid-induced hyperactive conditions. Neurogenic contractions of human bladder were potentiated by blockade of BK and small-conductance calcium-activated potassium channels (SK) but were unaffected by the blockade of intermediate calcium-activated potassium channels (IK). EFS-induced contractions were inhibited by BK stimulation with NS-8 or NS1619 or by SK/IK stimulation with NS309 (3µM). CCh-induced contractions were not modified by blockade or stimulation of BK, IK or SK. The anti-cholinergic agent, oxybutynin (0.3µM) inhibited either neurogenic or CCh-induced contractions. Neurogenic contractions of bladders from BPH patients were less sensitive to BK inhibition and more sensitive to BK activation than healthy bladders. The BK activator, NS-8 (5mg/kg; i.v.), reversed bladder hyperactivity induced by acetic acid in rats, while oxybutynin was ineffective. NS-8 did not significantly impact blood pressure or heart rate. BK stimulation specifically inhibits neurogenic contractions in patients with urinary symptoms and relieves bladder hyperactivity in vivo without compromising bladder contractile capacity or cardiovascular safety, supporting its potential therapeutic use for relieving bladder overactivity. PMID:24747752

  3. Status as a Valued Resource

    Huberman, Bernardo A.; Loch, Christoph H.; Onculer, Ayse

    2004-01-01

    The striving for status has long been recognized in sociology and economics. Extensive theoretical arguments and empirical evidence propose that people view status as a sign of competence and pursue it as a means to achieve power and resources. A small literature, however, based on arguments from biology and evolutionary psychology, proposes that…

  4. SCIENTIFIC STATUS OF DIDACTICS

    I. M. Osmolovskaya

    2015-03-01

    Full Text Available The research is aimed at scientific justification of didactics referred to the social and humanitarian field of knowledge. The author deals with the scientific character criteria (verity, inter-subjectivity, systemacity and validity taking into account different scientific rationality types (classical and nonclassical and identifying post-modernism influence on didactics. Objectives and results of research. Attempts are made to systematize the didactic knowledge and identify its components and structure. Didactic concepts are classified in accordance with its objects: teaching process by the whole, its individual components or educative process aspects that enable to form definite teaching views, studying it from the specific positions. The author singles out holistic-didactic, component and aspect concepts; and specifies the concept of didactic systems and models with its hierarchy. The author highlights the didactic knowledge increment. Apart from traditional empirical theoretical researches, the author’s attention is drawn to the academic pursuit such as a scientific project based on the didactic object specificity of the teaching process which is fully human controlled and realized and doesn’texist without human being. It is shown that basic theoretical ideas of scientific projects are itemized, concretized and enlarged during co-current educative practice, i.e. an adhesion of theory and practice occurs.It is stressed that there are two special directions of didactic development multidimensionality: 1. extension of its semantic field in the context of modern socio-cultural conditions; 2. increase of scientific status related to a conceptual framework improvement, empirically accumulated information arrangement, new hypotheses, theories and concepts’ development. Scientific novelty. The research findings demonstrate well-reasoned statement of the didactics’ scientific status, its particular components and structure

  5. The Status of Glueballs

    Lindenbaum, S.J. [Brookhaven National Lab., Upton, NY (United States)]|[City Coll., New York, NY (United States)

    1993-04-14

    The Status of Glueballs is presented considering that most popular candidates from among the isoscalars in the J{sup PC} = 0{sup ++}, 0{sup {minus}+} and 2{sup ++} channels. It is shown that in the 0{sup ++} channel the f{sub 0}(1720) which was discovered earlier (the S*{prime}(1720)) at BNL is highly likely the same state as the SLAC {theta}(1720) now that its spin has been found to be 0 instead of the 2 claimed for a long period. In the {sup ++} channel there is likely a complex of 2-3 states {zeta}/{eta}(1280), {lambda}/{eta}(1420) and {iota}/{eta}(1520) involving at least one extra isosclar. In the 2{sup ++}, the g{sub T}(2010), g{sub T}{prime}(2300) and g{sub T}{double_prime}(2340) {phi}{phi} states found in {pi}{sup {minus}} p {yields} {phi}{phi}n (OZI forbidden glueball filter channel) strikingly, approximately, completely break the OZI suppression and comprise within the errors all the {phi}{phi} cross-section. The only viable explanation of these states in the context of QCD is that they are produced by 1-3 primary 2{sup ++} glueballs. All alternate explanations in the past 15 years have failed.

  6. LIL laser performance status

    The Laser Integration Line (LIL) was first designed as a prototype to validate the concepts and the laser architecture of the Laser MegaJoule (LMJ). The LIL facility is a 4-beam laser representing a quad structure of the LMJ. A set of test campaigns were conducted to safely ramp up laser performance. The main goal was to measure quad-specific features such as beam synchronization and focal spot (size, smoothing contrast ratio or irradiation nonuniformity) versus the LMJ requirements. Following the laser commissioning, the LIL has become a major instrument dedicated to the achievement of plasma physics experiments for the French Simulation Program and was also opened to the academic scientific community. One of the attributes of the LIL facility is to be very flexible to accommodate the requests of plasma physicists during campaigns. The LIL is constantly evolving to best meet the needs of target physicists. Changes made or planned are either to improve the quality of laser beams, or to increase the LIL Energy-Power operating space. To optimize preparation and design of shot campaigns, the LIL performance status has been elaborated. It gives information about the characteristics of the laser in terms of near field and far field, defines the steps to maintain performance, explains how the facility responds to the request, details settings (smoothing, shaping of the focal spot, energy, temporal pulse shaping, beam pointing) and gives the limits in energy and power. In this paper, an overview of the LIL performance is presented. (authors)

  7. Status of NESTOR

    NSC KIPT proposed to construct a new X-ray and soft ultraviolet source NESTOR with a 40 - 225 MeV electron storage ring in Kharkov. NESTOR is a new type radiation source on the base of Compton scattering and a storage ring. Electrons are injected in the storage ring at 100 MeV and ramped up to final energy of 225 MeV. So, using interaction angle 10 deg. and 150 deg., the facility covers operation energy range of radiation from soft ultraviolet trough synchrotron radiation from bending magnets up to hard X-ray radiation through Compton scattering (∼1 eV ∼1 MeV). It is supposed that stored electron beam current will be of about 200 mA. Along with use of Nd:Yag laser of 10 W average power which was developed by High-Q laser firm and optical resonator with accumulation gain of about 1000 it allows to provide X-ray radiation flux up to 1011 phot/s. NESTOR is the cooperative facility and its development is supported by Ukrainian government and NATO SfP project number 977982. It is supposed that NESTOR will be in operation by mid-2007 year. The status of the project and main facility systems are described in the report

  8. Biosimilar drugs: Current status.

    Kumar, Rajiv; Singh, Jagjit

    2014-07-01

    Biologic products are being developed over the past three decades. The expiry of patent protection for many biological medicines has led to the development of biosimilars in UK or follow on biologics in USA. This article reviews the literature on biosimilar drugs that covers the therapeutic status and regulatory guidelines. Appraisal of published articles from peer reviewed journals for English language publications, search from PubMed, and guidelines from European Medicines Agency, US Food Drug Administration (FDA) and India were used to identify data for review. Literature suggest that biosimilars are similar biological products, i.e., comparable but not identical to the reference product, are not generic version of innovator product and do not ensure therapeutic equivalence. Biosimilars present more challenges than conventional generics and marketing approval is also more complicated. To improve access, US Congress passed the Biologics Price Competition and Innovation act 2009 and US FDA allowed "abbreviated pathway" for their approval. U.S law has defined new standards and terms and EMA scientific guidelines have also set detailed approval standards. India being one of the most preferred manufacturing destinations of biosimilars, there is a need for stringent safety and regulatory guidelines. The New India Guidelines "Draft Guidelines on Similar Biologics were announced in June 2012, by Department of Biotechnology at Boston bio and available online. PMID:25143877

  9. Nanometals - Status and perspective

    Nanometals and nanotechnology have over the years been covered in papers, books and conferences - also in many Risoe International Symposia, where the 30th in 2009 dealt solely with nanostructured metals. Since then, rapid progress has been made in synthesis, characterization and modeling, and it is timely to discuss status and perspective also with a view on applications in an international forum such as the Risoe Symposium. Both keynote and contributed papers address important current problems illustrating global research and development in this field. Examples are the development of new synthesis techniques followed by characterization and modeling of microstructures both in 2D and 3D now starting to bridge the micrometer scales. The vital area of mechanical behavior is addressed by the development of new testing techniques and a broad effort to characterize and model mechanical properties of metals strengthened by dislocations and twins. This research has now led to new understanding of both strengthening mechanisms and strengh structure relationships based on experiments in combination with analytical and numerical modeling. The holistic approach to research on nanometals demonstrated by these proceedings can guide both scientists and technologists in their future work also with the aim of introducing into society this new group of advanced materials. Such an effort is important, as science and technology today is significantly affected by politics of governments and international institutions, and therefore a new initiative in the pressent is to include a discussion of research and development in the area of nanometals i USA, China and Japan. (Author)

  10. Nanometals - Status and perspective

    Faester, S.; Hansen, N.; Huang, X.; Juul Jensen, D.; Ralph, B. (eds.)

    2012-11-01

    Nanometals and nanotechnology have over the years been covered in papers, books and conferences - also in many Risoe International Symposia, where the 30th in 2009 dealt solely with nanostructured metals. Since then, rapid progress has been made in synthesis, characterization and modeling, and it is timely to discuss status and perspective also with a view on applications in an international forum such as the Risoe Symposium. Both keynote and contributed papers address important current problems illustrating global research and development in this field. Examples are the development of new synthesis techniques followed by characterization and modeling of microstructures both in 2D and 3D now starting to bridge the micrometer scales. The vital area of mechanical behavior is addressed by the development of new testing techniques and a broad effort to characterize and model mechanical properties of metals strengthened by dislocations and twins. This research has now led to new understanding of both strengthening mechanisms and strengh structure relationships based on experiments in combination with analytical and numerical modeling. The holistic approach to research on nanometals demonstrated by these proceedings can guide both scientists and technologists in their future work also with the aim of introducing into society this new group of advanced materials. Such an effort is important, as science and technology today is significantly affected by politics of governments and international institutions, and therefore a new initiative in the pressent is to include a discussion of research and development in the area of nanometals i USA, China and Japan. (Author)

  11. Present Status of Kamland

    Inoue, Kunio

    2001-01-01

    The KamLAND experiment can explore world lowest mass difference region of neutrino oscillation parameter with an artificial neutrino source. It observes anti-neutrinos from various power plants spread in Japan with about 175 km baseline. This baseline is two order of magnitude longer than those of previously performed reactor experiments 1,2. This challenging measurement requires very low background environment as low as 10-13 g/g Uranium and Thorium impurities. In order to achieve this very low impurity level, various techniques (detector design, material selection, construction scheme etc) have been invested. These efforts have been rewarded rather quickly and current achievement doesn't hinder even the 7Be solar neutrino observation requiring 10-16 g/g U and Th impurities. Various background sources relevant to the reactor and solar neutrino observation are considered and description of efforts to eliminate those backgrounds are the main issue of this manuscript. Physics goal and current successful construction status are also highlighted.

  12. Status of solar neutrino experiments

    A summary of the status of four solar neutrino experiments is presented. The Homestake 37Cl data are presented and the possible time dependence of the data is addressed. Data from 1040 days of operation of the Kamiokande II detector are presented next. The status of the 71Ga experiment in the Baksan Neutrino Observatory, which has operated for a short time, is discussed. The summary concludes with a discussion of the status of the Sudbury Neutrino Observatory, which has been under construction since the beginning of 1990. 7 refs., 6 figs

  13. Status of funded actions

    The GEDEPEON status workshop is organised to review the GEDEPEON research actions, which have been funded in 2003. Presentations are made by research teams actively involved in GEDEPEON research areas. Speakers were invited to show how the presented research data are related to the general goals of transmutation, for which 2006 is an important milestone, and innovative systems. This document gathers 18 presentations (slides) among the 32 given at this workshop and dealing with: 1 - nuclear data: measurement of cross-sections of neutron induced reactions at the nTof time of flight facilities of CERN and of Gelina at Geel (F. Gunsing), study of (n,xn) reactions thanks to prompt gamma spectroscopy (M. Kerveno), iodine 129 cross-sections (G. Noguere); 2 - reactor physics/cycles: CEA-CNRS scenarios (F. Varaine, D. Heuer), analysis of uncertainties and sensitivity factors of nuclear data on innovative systems (molten-salt reactors) (A. Bidaud); 3 - materials: contribution to the study of T91 steel fatigue by lead-bismuth (D. Gorse), kinetics and mechanisms of fatigue by liquid metals (V. Laporte), studies of molten salts corrosion in future reactors (S. Sanchez), stress-induced fatigue by liquid metal (A. Verleene), thermodynamic study of the Bi-Fe-Hg-O-Pb quinary system (A. Maitre), synchrotron imaging study of fatigue by liquid metals (D. Bellet); 4 - future systems: molten salts reprocessing strategy - impact on the molten salt reactors neutronics (L. Mathieu), microscopy technique for the characterization of the thermal properties of inert materials for gas-cooled reactors (L. David), modeling and application of sub-atomic phenomena (J. Maillard), forecasting of the chemical compatibility between fissile compounds and inert materials in future high temperature reactors using a thermodynamical approach (A. Maitre), hydrogen production by thermochemical cycles (S. Colette), development of Ni-W refractory alloys for high temperature and molten salts reactors (J

  14. Status Report on PERC

    Full text: Important open questions of particle physics and cosmology can be addressed with precision measurements in neutron beta decay. Main emphasis lies on the search for evidence of possible extensions to the Standard Model and searches for new symmetry concepts. In general, these measurements are complementary to direct searches in high-energy physics. Observables in neutron decay are abundant: Besides the neutron lifetime, angular correlations involving the neutron spin as well as momenta and spins of the emitted particles are characterized by individual coefficients. These coefficients can be related to the underlying coupling strengths of the weak interaction, including yet unobserved ones. Each coefficient in turn relates to an underlying broken symmetry. With the new facility PERC (http://www.physi.uni-heidelberg.de/Forschung/ANP/PERC/collaboration.php) several symmetry tests based on neutron decay data become accessible. PERC (Proton Electron Radiation Channel) is a novel source of neutron decay products: these are collected by a strong longitudinal magnetic eld of 1.5 T directly from inside a neutron guide. This combination provides highest phase space density of decay products. A magnetic mirror of up to 6 T serves to perform precise cuts in phase space, reducing related systematic errors. Altogether, the sensitivity of neutron decay studies will be improved by one order of magnitude. The new beam station PERC is currently under development by an international collaboration and will be installed at the FRM II in Garching, Germany. Besides the physics motivation, the concept, sensitivity, applications, and status of PERC are presented in this talk. (author)

  15. Refugee status determination: three challenges

    Martin Jones

    2009-04-01

    Full Text Available Refugee status determination (RSD, which is vital to the protection of so many asylum seekers worldwide, is at best an imperfect, haphazard and challenging process. It merits greater attention and appropriate reform.

  16. Status of Fermilab E-710

    This report give the current status of E-710, an experiment at the Fermilab bar pp Tevatron Collider to measure elastic scattering, total cross sections and diffraction dissociation up to √s = 1.8 TeV

  17. Experimental status of quantum electrodynamics

    This review of the experimental status of quantum electrodynamics covers the fine structure constant, the muon g-2 value, the Lamb shift in hydrogen, the finite proton radius, progress in muonium, and positronium. 37 references

  18. The bivariate current status model

    Groeneboom, P.

    2013-01-01

    For the univariate current status and, more generally, the interval censoring model, distribution theory has been developed for the maximum likelihood estimator (MLE) and smoothed maximum likelihood estimator (SMLE) of the unknown distribution function, see, e.g., [12], [7], [4], [5], [6], [10], [11] and [8]. For the bivariate current status and interval censoring models distribution theory of this type is still absent and even the rate at which we can expect reasonable estimators to converge...

  19. Sentinel-2 Mission status

    Hoersch, Bianca; Colin, Olivier; Gascon, Ferran; Arino, Olivier; Spoto, Francois; Marchese, Franco; Krassenburg, Mike; Koetz, Benjamin

    2016-04-01

    Copernicus is a joint initiative of the European Commission (EC) and the European Space Agency (ESA), designed to establish a European capacity for the provision and use of operational monitoring information for environment and security applications. Within the Copernicus programme, ESA is responsible for the development of the Space Component, a fully operational space-based capability to supply earth-observation data to sustain environmental information Services in Europe. The Sentinel missions are Copernicus dedicated Earth Observation missions composing the essential elements of the Space Component. In the global Copernicus framework, they are complemented by other satellites made available by third-parties or by ESA and coordinated in the synergistic system through the Copernicus Data-Access system versus the Copernicus Services. The Copernicus Sentinel-2 mission provides continuity to services relying on multi-spectral high-resolution optical observations over global terrestrial surfaces. Sentinel-2 capitalizes on the technology and the vast experience acquired in Europe and the US to sustain the operational supply of data for services such as forest monitoring, land cover changes detection or natural disasters management. The Sentinel-2 mission offers an unprecedented combination of the following capabilities: ○ Systematic global coverage of land surfaces: from 56°South to 84°North, coastal waters and Mediterranean sea; ○ High revisit: every 5 days at equator under the same viewing conditions with 2 satellites; ○ High spatial resolution: 10m, 20m and 60m; ○ Multi-spectral information with 13 bands in the visible, near infra-red and short wave infra-red part of the spectrum; ○ Wide field of view: 290 km. The data from the Sentinel-2 mission are available openly and freely for all users with online easy access since December 2015. The presentation will give a status report on the Sentinel-2 mission, and outlook for the remaining ramp-up Phase, the

  20. Status report, canister fabrication

    The report gives an account of the development of material and fabrication technology for copper canisters with cast inserts during the period from 2000 until the start of 2004. The engineering design of the canister and the choice of materials in the constituent components described in previous status reports have not been significantly changed. In the reference canister, the thickness of the copper shell is 50 mm. Fabrication of individual components with a thinner copper thickness is done for the purpose of gaining experience and evaluating fabrication and inspection methods for such canisters. As a part of the development of cast inserts, computer simulations of the casting processes and techniques used at the foundries have been performed for the purpose of optimizing the material properties. These properties have been evaluated by extensive tensile testing and metallographic inspection of test material taken from discs cut at different points along the length of the inserts. The testing results exhibit a relatively large spread. Low elongation values in certain tensile test specimens are due to the presence of poorly formed graphite, porosities, slag or other casting defects. It is concluded in the report that it will not be possible to avoid some presence of observed defects in castings of this size. In the deep repository, the inserts will be exposed to compressive loading and the observed defects are not critical for strength. An analysis of the strength of the inserts and formulation of relevant material requirements must be based on a statistical approach with probabilistic calculations. This work has been initiated and will be concluded during 2004. An initial verifying compression test of a canister in an isostatic press has indicated considerable overstrength in the structure. Seamless copper tubes are fabricated by means of three methods: extrusion, pierce and draw processing, and forging. It can be concluded that extrusion tests have revealed a

  1. Status report, canister fabrication

    Andersson, Claes-Goeran; Eriksson, Peter; Westman, Marika [Swedish Nuclear Fuel and Waste Management Co., Stockholm (Sweden); Emilsson, Goeran [CSM Materialteknik AB, Linkoeping (Sweden)

    2004-06-01

    The report gives an account of the development of material and fabrication technology for copper canisters with cast inserts during the period from 2000 until the start of 2004. The engineering design of the canister and the choice of materials in the constituent components described in previous status reports have not been significantly changed. In the reference canister, the thickness of the copper shell is 50 mm. Fabrication of individual components with a thinner copper thickness is done for the purpose of gaining experience and evaluating fabrication and inspection methods for such canisters. As a part of the development of cast inserts, computer simulations of the casting processes and techniques used at the foundries have been performed for the purpose of optimizing the material properties. These properties have been evaluated by extensive tensile testing and metallographic inspection of test material taken from discs cut at different points along the length of the inserts. The testing results exhibit a relatively large spread. Low elongation values in certain tensile test specimens are due to the presence of poorly formed graphite, porosities, slag or other casting defects. It is concluded in the report that it will not be possible to avoid some presence of observed defects in castings of this size. In the deep repository, the inserts will be exposed to compressive loading and the observed defects are not critical for strength. An analysis of the strength of the inserts and formulation of relevant material requirements must be based on a statistical approach with probabilistic calculations. This work has been initiated and will be concluded during 2004. An initial verifying compression test of a canister in an isostatic press has indicated considerable overstrength in the structure. Seamless copper tubes are fabricated by means of three methods: extrusion, pierce and draw processing, and forging. It can be concluded that extrusion tests have revealed a

  2. Status Equilibrium for Local Public Good Economies

    Anne van den Nouweland; Myrna H. Wooders

    2005-01-01

    We introduce a concept of status equilibrium for local public good economies. A status equilibrium specifies one status index for each agent in an economy. These indices determine agents' cost shares in any possible jurisdiction to which the agent might belong. We provide an axiomatic charaterization of status equilibrium using consistency properties.

  3. 法国海岸松树皮提取物碧萝芷对长链游离脂肪酸诱导的巨噬细胞perilipin2基因表达的影响%Pycnogenol, an Extract from French Martime Pine, Suppresses Oleic Acid-induced perilipin2 Expression in Macrophages

    范斌; 杜强; 谷剑秋; 张锦

    2011-01-01

    Abstract Objective To investigate the effect of Pycnogenol on oleic acid-induced perilipin2 expression in macrophages. Methods Realtime PCR and Western blot were performed to detect perilipin2 expression. Transient transfection and luciferase assay were employed to measure perilipin2 promoter activity. Results Oleic acid significantly induced perilipiti2 expression in a dose-and time-dependent manner in macrophages; oleic acid markedly enhanced perilipin2 promoter activity; Pycnogenol significantly suppressed oleic acid-induced perihpin2 expression and promoter activity. Conclusion For the first time,we demonstrated that Pycnogenol significantly suppressed oleic acid-induced perilipin2 expression and promoter activity.%目的 研究碧萝芷(PYC)对油酸诱导的巨噬细胞perilipin2表达的影响及其相关分子机制.方法 应用Real-time PCR 和Western blot测定油酸及PYC对perilipin2 mRNA和蛋白水平表达影响.应用荧光素酶活性分析方法检测油酸及PYC时perilipin2启动子活性的影响.结果油酸以剂量和浓度依赖方式上调perilipin2 mRNA和蛋白水平表达,并促进perilipin2启动子活性.PYC以剂量依赖方式抑制了油酸诱导的perilipin2表达及启动子活性.结论PYC抑制了巨噬细胞中油酸诱导的perilipin2的表达.PYC通过抑制perilipin2启动子活性,从而直接抑制perilipin2的表达.

  4. LARGE BLOCK TEST STATUS REPORT

    This report is intended to serve as a status report, which essentially transmits the data that have been collected to date on the Large Block Test (LBT). The analyses of data will be performed during FY98, and then a complete report will be prepared. This status report includes introductory material that is not needed merely to transmit data but is available at this time and therefore included. As such, this status report will serve as the template for the future report, and the information is thus preserved. The United States Department of Energy (DOE) is investigatinq the suitability of Yucca Mountain (YM) as a potential site for the nation's first high-level nuclear waste repository. As shown in Fig. 1-1, the site is located about 120 km northwest of Las Vegas, Nevada, in an area of uninhabited desert

  5. ANTIOXIDANT STATUS IN DIABETIC NEPHROPATHY

    Giriraja

    2015-12-01

    Full Text Available BACKGROUND Hyperglycemia and dislipidemia in DM induce increased lipid peroxdation and free radical formation. This is an important mechanism of microangiopathy. AIM To measure the antioxidant status in type 2 DM with nephropathy and compared with nondiabetic control group. MATERIALS AND METHODS 50 type 2 DM patients aged between 50 to 70 years according to national diabetes data group criteria with nephropathy diagnosed on the basis of history, physical examination and biochemical parameters were included. 50 age and sex matched apparently healthy individuals with normal plasma glucose, normal renal parameters and with no symptoms suggestive of DM were taken as controls. RESULTS Antioxidant status was significantly less in patients with diabetic nephropathy. CONCLUSION Data suggests that alteration in antioxidant status may help predict the risk of diabetic nephropathy.

  6. Status of Irish Aquaculture 2004

    Institute, Marine; Mhara, Bord Iascaigh; Teo, Taighde Mara

    2005-01-01

    This report is the second annual report on the status of Irish aquaculture (see Parsons et al., 2004). It has been produced in collaboration with the three main State agencies that provide support services in the areas of research and development to the industry – Bord Iascaigh Mhara (BIM), the Marine Institute and Taighde Mara. The aims of the report are to: (1) provide an objective and comprehensive source of information on the status of Irish aquaculture in 2004; (2) show the main trends i...

  7. The Epistemic Status of Intelligence

    Rønn, Kira Vrist; Høffding, Simon

    We argue that the majority of intelligence definitions fail to recognize that the normative epistemic status of intelligence is knowledge and not an inferior alternative. We refute the counter-arguments that intelligence ought not to be seen as knowledge because of 1) its action-oriented scope and...... robustness of claims to intelligence-knowledge can be assessed....

  8. 2010 Chemical Working Group Status

    Reid, Concha M.

    2010-01-01

    The Steering Group for the Interagency Advanced Power Group (IAPG) held their business meeting on November 30-December 1st in McLean, Virginia. Status reports were presented from each of the IAPG's Working Groups. These charts contain a brief summary of the IAPG Chemical Working Group's activities during 2010 and its plans for 2011.

  9. Status of Japanese university reactors

    Fujita, Yoshiaki [Research Reactor Institute, Kyoto Univ., Kumatori, Osaka (Japan)

    1999-08-01

    Status of Japanese university reactors, their role and value in research and education, and the spent fuel problem are presented. Some of the reactors are now faced by severe difficulties in continuing their operation services. The point of measures to solve the difficulties is suggested. (author)

  10. HEALTH STATUS OF INDIAN WOMEN

    Mohan

    2014-01-01

    Health status of women still is one of the most serious issues affecting the community particularly in developing countries. Community life is meant to include not only social, economic and nutritional conditions, however additionally the cultural systems of values, aspirations and satisfaction that influence mental and family behavior under reproductive habits.

  11. Present status of processing method

    Kosako, Kazuaki [Sumitomo Atomic Energy Industries Ltd., Tokyo (Japan)

    1998-11-01

    Present status of processing method for a high-energy nuclear data file was examined. The NJOY94 code is the only one available to the processing. In Japan, present processing used NJOY94 is orienting toward the production of traditional cross section library, because a high-energy transport code using a high-energy cross section library is indistinct. (author)

  12. Status of the QCDOC project

    Boyle, P A; Christ, N H; Cristian, C; Dong, Z; Gara, A; Joó, B; Kim, C; Levkova, L; Liao, X; Liu, G; Mawhinney, Robert D; Ohta, S; Wettig, T; Yamaguchi, A

    2002-01-01

    A status report is given of the QCDOC project, a massively parallel computer optimized for lattice QCD using system-on-a-chip technology. We describe several of the hardware and software features unique to the QCDOC architecture and present performance figures obtained from simulating the current VHDL design of the QCDOC chip with single-cycle accuracy.

  13. Standards development status. Summary report

    The Standards Development Status Summary Report is designed for scheduling, monitoring, and controlling the process by which Regulatory Standards, Guides, Reports, Petitions, and Environmental Statements are written. It is a summary of the current schedule plans for development of the above products

  14. The Medicina Station Status Report

    Orfei, Alessandro; Orlati, Andrea; Maccaferri, Giuseppe

    2013-01-01

    General information about the Medicina Radio Astronomy Station, the 32-m antenna status, and the staff in charge of the VLBI observations is provided. In 2012, the data from geodetic VLBI observations were acquired using the Mark 5A recording system with good results. Updates of the hardware were performed and are briefly described.

  15. Status of the OPERA Experiment

    In this article the physics motivation and the detector design of the OPERA experiment will be reviewed. The construction status of the detector, which will be situated in the CNGS beam from CERN to the Gran Sasso laboratory, will be reported. A survey on the physics performance will be given and the physics plan in 2006 will be presented. (author)

  16. Status of the OPERA experiment

    The OPERA hybrid apparatus consists of a large mass emulsion films/lead target complemented by electronic detectors. The OPERA experiment is currently in data taking and analysis, and the first ντ candidate event was observed in 2010. In this report, the status of the OPERA experiment and statistical significance of the first candidate observed so far are presented.

  17. The status of cold fusion

    Storms, E.

    This report attempts to update the status of the phenomenon of cold fusion. The new field is continuing to grow as a variety of nuclear reactions are discovered to occur in a variety of chemical environments at modest temperatures. However, it must be cautioned that most scientists consider cold fusion as something akin to UFO's, ESP, and numerology.

  18. Status of Japanese university reactors

    Status of Japanese university reactors, their role and value in research and education, and the spent fuel problem are presented. Some of the reactors are now faced by severe difficulties in continuing their operation services. The point of measures to solve the difficulties is suggested. (author)

  19. Experimental Status of $B$ Physics

    Stone, Sheldon

    2006-01-01

    A short summary is given of the current status of B physics. Reasons for physics beyond the Standard Model are discussed. Constraints on New Physics are given using measurements of B mixing, Bs mixing, and CP violation, along with |Vub. Future goals, and upcoming new experiments are also mentioned.

  20. Magnesium deficiency: what's our status?

    Low magnesium intake has been implicated in a broad range of cardiometabolic conditions, including diabetes, hypertension, and cardiovascular disease. Dietary magnesium and total body magnesium status have a widely-used but imperfect biomarker in serum magnesium. Despite serum magnesium’s limitation...

  1. Status of spallation neutron source

    Oyama, Yukio [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment

    1997-03-01

    Existing and planned facilities using proton accelerator driven spallation neutron source are reviewed. These include new project of neutron science proposed from Japan Atomic Energy Research Institute. The present status of facility requirement and accelerator technology leads us to new era of neutron science such as neutron scattering research and nuclear transmutation study using very intense neutron source. (author)

  2. 依达拉奉对海人酸致痫大鼠认知功能的影响%The effect of edaravone on cognitive function of kainic acid-induced epileptic rats

    刘惠卿; 孟丽; 冯荣芳; 张志英; 岳月红; 尹楠; 刘昌林; 郭宗成

    2015-01-01

    Objective To investigate the effect of edaravone on cognitive function of kainic acid-induced epileptic rats.Methods Thirty adult male Wistar rats ( weight 260±20g) , were randomly divided into three groups:①sham operation group ( n=6):administrated 0.9%saline the same volume as model group;②model group ( n=12):kainic acid ( 4μg· kg-1 ) was administrated in the right hippocampal CA3 region via stereotactic technique.③edaravone ( n=12): kainic acid ( 4μg · kg-1 · d-1 ) was administrated in the right hippocampus CA3 region via stereotactic technique, and immediately edaravone ( 10mg · kg-1 ) was administrated once daily i.p.until the time point of the sacrificed.The three groups of rats, respectively, were evaluated Morris water maze test in order to test cognitive function and learning capacity, at 24 h, 8w after operation.Results The escape latency periods in all rats at the beginning of place navigation test (PNT) at 24h were no significantly extended(P>0.05), and which in rats of model and edaravone groups was obviously prolonged in the PNT at 8w compared with the sham group( P0.05) ,the former was shortened, the latter decreased significantly in the model and edaravone groups at 8w SPT ( P>0.05) .The swimming time in the original platform quadrant in all rats was prolonger ( P<0.05) and the times of wear ring increased significantly compared with the model group( P<0.05) .Conclusion Repeated, chronic seizures can cause the declining of cognitive function, learning and memory capacity, edaravone can partly protect cognitive function.%目的:观察依达拉奉对海人酸( KA)致痫大鼠认知功能的影响。方法选用成年健康雄性Wistar大鼠30只,体质量260±20g,随机分为3组:①假手术组(sham)(n=6):右侧海马CA3区注入等量的生理盐水;②模型组(KA)(n=12):右侧海马CA3区注入KA 4μg· kg-1(4μg·μl-1);③依达拉奉组(n=12):右侧海马CA3区注入KA 4

  3. STATUS TAKSONOMI, DISTRIBUSI DAN KATEGORI STATUS KONSERVASI MAGNOLIACEAE DI INDONESIA

    Andes Hamuraby Rozak

    2012-01-01

    The Family of Magnoliaceae is one of the most primitive taxa in the world.  Knowledge of this family is essential for studies on the origin, evolution and systematics of Angiosperms.  There are 223 species belongs to this family in the world and 25 of them are found in Indonesia. This paper explains taxonomy, distribution, and conservation status of the family Magnoliaceae in Indonesia.

  4. STATUS TAKSONOMI, DISTRIBUSI DAN KATEGORI STATUS KONSERVASI MAGNOLIACEAE DI INDONESIA

    Andes Hamuraby Rozak

    2012-07-01

    Full Text Available The Family of Magnoliaceae is one of the most primitive taxa in the world.  Knowledge of this family is essential for studies on the origin, evolution and systematics of Angiosperms.  There are 223 species belongs to this family in the world and 25 of them are found in Indonesia. This paper explains taxonomy, distribution, and conservation status of the family Magnoliaceae in Indonesia.

  5. Singleton status and childhood obesity: Investigating effects and mechanisms Status :

    Maoyong Fan; Yanhong Jin

    2015-01-01

    Over the past four decades, paralleling the increasing prevalence of childhood obesity, the share of families with only one child has been rising steadily. Using three waves of the National Survey of Children's Health, we examine the effect of being the only child in a family on childhood obesity and the mechanisms through which singleton status might affect childhood obesity. We find gender-specific and age-dependent singleton effects. That is, singletons have a higher level of body mass ind...

  6. US Forest Service Land Status and Encumbrance

    US Forest Service, Department of Agriculture — A map service designed to portray US Forest Service Land Status Record System data. The map service is for querying and displaying Land Status Record System...

  7. Systematic Evaluation Program. Status summary report

    The Systematic Evaluation Program is intended to examine many safety-related aspects of 11 of the older light water reactors. This document provides the existing status of the review process including individual topic and overall completion status

  8. Dress to Impress: Brands as Status Symbols

    Rogério Mazali; José Rodrigues-Neto

    2011-01-01

    We analyzed the market for indivisible, pure status goods. Firms produce and sell different brands of pure status goods to a population that is willing to signal individual abilities to potential matches in another population. Individual status is determined by the most expensive status good one has. There is a strati.ed equilibrium with a finite number of brands. Under constant tax rates, a monopoly sells different brands to social classes of equal measure, while in contestable markets, soci...

  9. Puerto Rico - The Economics of Status

    Glenn Jenkins; J. TOMAS HEXNER

    1994-01-01

    This paper attempts to present an analysis of the economic and fiscal dimensions of Puerto Rican status. The status debate in Puerto Rico has, historically, been heavily concentrated in political analysis of the status options: commonwealth, statehood and independence. The document's key conclusion is that status has fundamental economic and fiscal implications for the island and for the United States. Statehood would stimulate greater investment and more rapid economic growth through full in...

  10. Status concerns and the organization of work

    Chaim FERSHTMAN; Hvide, Hans K.; Weiss, Yoram

    2001-01-01

    We study the effects of local status, where workers compare their wage to the wage of other workers within the same firm. We assume a competitive labor market with unobservable effort, where firms condition wages on output as incentive for effort. If workers who care about status are also more productive, such status concerns generate an equilibrium with heterogenous firms where workers who care and workers who do not care about status work together. Such firms provide workers who care about ...

  11. Status of the DIOS mission

    Tawara, Y.; Sakurai, I.; Furuzawa, A.; Ohashi, T.; Ishisaki, Y.; Ezoe, Y.; Hoshino, A.; Akamatsu, H.; Ishikawa, K.; Mitsuda, K.; Yamasaki, N. Y.; Takei, Y.; Shinozaki, K.; Masui, K.; Yoshino, T.; Hagihara, T.; Kimura, S.; Yoshitake, H.

    2008-07-01

    We present the current status of a small X-ray mission DIOS (Diffuse Intergalactic Oxygen Surveyor), consisting of a 4-stage X-ray telescope and an array of TES microcalorimeters, cooled with mechanical coolers, with a total weight of about 400 kg. The mission will perform survey observations of warm-hot intergalactic medium using OVII and OVIII emission lines, with the energy coverage up to 1.5 keV. The wide field of view of about 50' diameter, superior energy resolution close to 2 eV FWHM, and very low background will together enable us a wide range of science for diffuse X-ray sources. We briefly describe the current status of the development of the satellite, and the subsystems.

  12. Socioeconomic status and the Rorschach.

    Frank, G

    1994-02-01

    People from lower socioeconomic status are making increasing use of mental health facilities. Surveys have indicated that the Rorschach is still one of the more frequently used instruments by psychologists in such facilities, but research has also shown that clinicians tend to misinterpret Rorschachs of people from the lower socioeconomic group as reflecting greater psychopathology than the same Rorschachs identified as being given by people from the middle class. Research has also shown that growing up in conditions of poverty significantly affects how people perform on tests of abstract thinking, tests of intelligence, and tests of academic achievement; the question was raised as to whether this extends to the Rorschach. The lack of sufficient research on the effect of socioeconomic status on responsiveness to the Rorschach precluded that question being answered. The kind of research still needed was discussed. PMID:8153241

  13. Status and the evaluation of workplace deviance.

    Bowles, Hannah Riley; Gelfand, Michele

    2010-01-01

    Bias in the evaluation of workplace misbehavior is hotly debated in courts and corporations, but it has received little empirical attention. Classic sociological literature suggests that deviance by lower-status actors will be evaluated more harshly than deviance by higher-status actors. However, more recent psychological literature suggests that discrimination in the evaluation of misbehavior may be moderated by the relative status of the evaluator because status influences both rule observance and attitudes toward social hierarchy. In Study 1, the psychological experience of higher status decreased rule observance and increased preferences for social hierarchy, as we theorized. In three subsequent experiments, we tested the hypothesis that higher-status evaluators would be more discriminating in their evaluations of workplace misbehavior, evaluating fellow higher-status deviants more leniently than lower-status deviants. Results supported the hypothesized interactive effect of evaluator status and target status on the evaluation of workplace deviance, when both achieved status characteristics (Studies 2a and 2b) and ascribed status characteristics (i.e., race and gender in Study 3) were manipulated. PMID:20424022

  14. Perception of "Gilding" in Occupational Statuses

    Gitter, A. George; Mostofsky, David

    1972-01-01

    In examining the amount of gilding behavior a sample of female subjects attribute to different occupational statuses and to occupational statuses associated with specific ethnic minorities, results indicate that gilding approximates the general prestige rankings of the occupations when the status incumbent is perceived as similar to the subject.…

  15. Mental Status after West Nile Virus Infection

    Haaland, Kathleen Y.; Sadek, Joseph; Pergam, Steven; Echevarria, Leonor A.; Davis, Larry E.; Goade, Diane; Harnar, Joanne; Nofchissey, Robert A.; Sewel, C. Mack; Ettestad, Paul

    2006-01-01

    Mental status after acute West Nile virus infection has not been examined objectively. We compared Telephone Interview for Cognitive Status scores of 116 patients with West Nile fever or West Nile neuroinvasive disease. Mental status was poorer and cognitive complaints more frequent with West Nile neuroinvasive disease (p = 0.005).

  16. Lifting the Status of Learning Support Teachers

    Kusuma-Powell, Ochan; Powell, William

    2016-01-01

    Status, the perception of one's standing in relation to others in a group, negatively influence learning. Status issue have implications for educating students with special learning needs: Both these students and the learning support or special education teachers who serve them often hold low status in a school community. Like adults, children…

  17. Status of the GERDA experiment

    The GERDA experiment is being built in the LNGS underground laboratories for the search for neutrinoless double beta decay. Phase I of the experiment GERDA will be able to test the claim of observation of the neutrinoless double beta decay. In a second phase newly developed detectors will be added aiming to a total exposure of 100 kg yr. Status of the experiment and first results from segmented detectors operated in cryogenic liquid are presented.

  18. VERITAS: Status and Latest Results

    Maier, G

    2007-01-01

    VERITAS is an atmospheric Cherenkov telescope array designed to study astrophysi cal sources of very-high-energy gamma radiation. Located in southern Arizona, USA, the array consists of four 12m-diameter imaging Cherenkov telescopes. All four telescopes have been deployed at the basecamp of the Whipple Observatory and began full operation in early 2007. This paper describes the operational status of VERITAS, outlines the initial performance parameters of the instrument, and presents the latest results that have been obtained.

  19. Status report on ILDG activities

    A status report about the International Lattice Data Grid (ILDG) is given. Different countries participating in the ILDG have created regional lattice data grid solutions that are implemented, working and used. The remaining task and the focus of present activities is the development of the interoperability of these regional grids. A first, successful step in this direction is a metadata catalogue service which is already working interoperable. (orig.)

  20. Current Status of Graphene Transistors

    Lemme, Max. C.

    2009-01-01

    This paper reviews the current status of graphene transistors as potential supplement to silicon CMOS technology. A short overview of graphene manufacturing and metrology methods is followed by an introduction of macroscopic graphene field effect transistors (FETs). The absence of an energy band gap is shown to result in severe shortcomings for logic applications. Possibilities to engineer a band gap in graphene FETs including quantum confinement in graphene Nanoribbons (GNRs) and electricall...