Convulsive syncope related to a small dose of quetiapine in an adolescent with bipolar disorder

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Lai J

2017-07-01

Full Text Available Jianbo Lai,1,2 Qiaoqiao Lu,3 Tingting Huang,3 Shaohua Hu,1,2 Yi Xu1,2 1Department of Psychiatry, First Affiliated Hospital, Zhejiang University School of Medicine, 2Key Laboratory of Mental Disorder Management in Zhejiang Province, 3Department of Internal Medicine, Zhejiang University School of Medicine, Hangzhou, China Abstract: Quetiapine, an atypical antipsychotic, has been extensively used in patients with bipolar disorder. Overdose of quetiapine can result in severe complications, such as coma, seizure, respiratory depression, arrhythmia, and even death. However, the paucity of toxicological evaluation in adolescence causes more potential risks in this population. Herein, we present a case of hypotension and convulsive syncope after exposure to a small dose of quetiapine in a 16-year-old who was diagnosed with bipolar disorder. After cessation of quetiapine, no additional convulsive movements were reported. This case indicates that even in young patients without predisposing factors, close monitoring of adverse effects should be warranted for safety concerns, especially at the initiation of quetiapine treatment. Keywords: quetiapine, bipolar disorder, hypotension, convulsive syncope

Anticonvulsant evaluation of Rauvolfia ligustrina Willd. ex Roem. & Schult., Apocynaceae, in rodents

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Lucindo J. Quintans-Júnior

Full Text Available The Aim of this study was to evaluated the effects of the ethanol extract of Rauvolfia ligustrina Willd. ex Roem. & Schult., Apocynaceae, roots (EER in animal models of epilepsy. The EER increased the latency for convulsions significantly different from control (p<0,05 and in the PTZ induced convulsions test on 62,5 mg/kg (i.p. decreased mortality. This effect was blocked by flumazenil administration, suggesting an involvement of GABAergic system in the anticonvulsant activity of EER. The EER had a moderate effect only against PIC- or STR-induced convulsions at doses 125 and 250 mg/kg. But in the MES test it did not demonstrate effect on this animal model. Therefore, the EER reduced the development of PTZ-induced kindling in both experimental groups. It also significantly (p<0.05 decreased the latency for convulsions and reduced its percentage. Our results suggest that EER owns anticonvulsant property.

Intravenous infusion of docosahexaenoic acid increases serum concentrations in a dose-dependent manner and increases seizure latency in the maximal PTZ model.

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Trépanier, Marc-Olivier; Kwong, Kei-Man; Domenichiello, Anthony F; Chen, Chuck T; Bazinet, Richard P; Burnham, W M

2015-09-01

Docosahexaenoic acid (DHA) is an omega-3 polyunsaturated fatty acid (n-3 PUFA) that has been shown to raise seizure thresholds in the maximal pentylenetetrazole model following acute subcutaneous (s.c.) administration in rats. Following s.c. administration, however, the dose-response relationship for DHA has shown an inverted U-pattern. The purposes of the present experiment were as follows: (1) to determine the pattern of serum unesterified concentrations resulting from the intravenous (i.v.) infusions of various doses of DHA, (2) to determine the time course of these concentrations following the discontinuation of the infusions, and (3) to determine whether seizure protection in the maximal PTZ model would correlate with serum unesterified DHA levels. Animals received 5-minute i.v. infusions of saline or 25, 50, 100, or 200mg/kg of DHA via a cannula inserted into one of the tail veins. Blood was collected during and after the infusions by means of a second cannula inserted into the other tail vein (Experiment 1). A separate group of animals received saline or 12.5-, 25-, 50-, 100-, or 200 mg/kg DHA i.v. via a cannula inserted into one of the tail veins and were then seizure-tested in the maximal PTZ model either during infusion or after the discontinuation of the infusions. Slow infusions of DHA increased serum unesterified DHA concentrations in a dose-dependent manner, with the 200-mg/kg dose increasing the concentration approximately 260-fold compared with saline-infused animals. Following discontinuation of the infusions, serum concentrations rapidly dropped toward baseline, with half-lives of approximately 40 and 11s for the 25-mg/kg dose and 100-mg/kg dose, respectively. In the seizure-tested animals, DHA significantly increased latency to seizure onset in a dose-dependent manner. Following the discontinuation of infusion, seizure latency rapidly decreased toward baseline. Overall, our study suggests that i.v. infusion of unesterified DHA results in

The effect of leptin, ghrelin, and neuropeptide-Y on serum Tnf-Α, Il-1β, Il-6, Fgf-2, galanin levels and oxidative stress in an experimental generalized convulsive seizure model.

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Oztas, Berrin; Sahin, Deniz; Kir, Hale; Eraldemir, Fatma Ceyla; Musul, Mert; Kuskay, Sevinç; Ates, Nurbay

2017-02-01

The objective of this study is to examine the effects of the endogenous ligands leptin, ghrelin, and neuropeptide Y (NPY) on seizure generation, the oxidant/antioxidant balance, and cytokine levels, which are a result of immune response in a convulsive seizure model. With this goal, Wistar rats were divided into 5 groups-Group 1: Saline, Group 2: Saline+PTZ (65mg/kg), Group 3: leptin (4mg/kg)+PTZ, Group 4: ghrelin (80μg/kg)+PTZ, and Group 5: NPY (60μg/kg)+PTZ. All injections were delivered intraperitoneally, and simultaneous electroencephalography (EEG) records were obtained. Seizure activity was scored by observing seizure behavior, and the onset time, latency, and seizure duration were determined according to the EEG records. At the end of the experiments, blood samples were obtained in all groups to assess the serum TNF-α, IL-1β, IL-6, FGF-2, galanin, nitric oxide (NOֹ), malondialdehyde (MDA), and glutathione (GSH) levels. The electrophysiological and biochemical findings (p<0.05) of this study show that all three peptides have anticonvulsant effects in the pentylenetetrazol (PTZ)-induced generalized tonic-clonic convulsive seizure model. The reduction of the levels of the pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 caused by leptin, ghrelin, and NPY shows that these peptides may have anti-inflammatory effects in epileptic seizures. Also, leptin significantly increases the serum levels of the endogenous anticonvulsive agent galanin. The fact that each one of these endogenous peptides reduces the levels of MDA and increases the serum levels of GSH leads to the belief that they may have protective effects against oxidative damage that is thought to play a role in the pathogenesis of epilepsy. Our study contributes to the clarification of the role of these peptides in the brain in seizure-induced oxidative stress and immune system physiology and also presents new approaches to the etiology and treatment of tendency to epileptic seizures. Copyright �

ACT-Vision: active collaborative tracking for multiple PTZ cameras

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Broaddus, Christopher; Germano, Thomas; Vandervalk, Nicholas; Divakaran, Ajay; Wu, Shunguang; Sawhney, Harpreet

2009-04-01

We describe a novel scalable approach for the management of a large number of Pan-Tilt-Zoom (PTZ) cameras deployed outdoors for persistent tracking of humans and vehicles, without resorting to the large fields of view of associated static cameras. Our system, Active Collaborative Tracking - Vision (ACT-Vision), is essentially a real-time operating system that can control hundreds of PTZ cameras to ensure uninterrupted tracking of target objects while maintaining image quality and coverage of all targets using a minimal number of sensors. The system ensures the visibility of targets between PTZ cameras by using criteria such as distance from sensor and occlusion.

Preliminary Phytochemical Screening, Acute Oral Toxicity and ...

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PTZ-induced seizure mice in at the dose of 300 mg/kg p.o. The extract also reduced the frequency of convulsion and ... developing countries is 100 per 100,000 [3]. According to an ... Shanghai Demand Chemical Co., Ltd. Phenobarbital (100 ...

Anticonvulsant and proconvulsant roles of nitric oxide in experimental epilepsy models

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Del-Bel E.A.

1997-01-01

Full Text Available The effect of acute (120 mg/kg and chronic (25 mg/kg, twice a day, for 4 days intraperitonial injection of the nitric oxide (NO synthase (NOS inhibitor NG-nitro-L-arginine (L-NOARG was evaluated on seizure induction by drugs such as pilocarpine and pentylenetetrazole (PTZ and by sound stimulation of audiogenic seizure-resistant (R and audiogenic seizure-susceptible (S rats. Seizures were elicited by a subconvulsant dose of pilocarpine (100 mg/kg only after NOS inhibition. NOS inhibition also simultaneously potentiated the severity of PTZ-induced limbic seizures (60 mg/kg and protected against PTZ-induced tonic seizures (80 mg/kg. The audiogenic seizure susceptibility of S or R rats did not change after similar treatments. In conclusion, proconvulsant effects of NOS inhibition are suggested to occur in the pilocarpine model and in the limbic components of PTZ-induced seizures, while an anticonvulsant role is suggested for the tonic seizures induced by higher doses of PTZ, revealing inhibitor-specific interactions with convulsant dose and also confirming the hypothesis that the effects of NOS inhibitors vary with the model of seizure

Effects of Berberis vulgaris fractions on PTZ Induced seizure in male rats

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2017-11-01

Full Text Available Background and objectives: Berberis vulgaris L (Berberidaceae is a medicinal plant that is distributed in different parts of Iran; it is grown as a wild or cultivated plant. It has different pharmacological activities such as antioxidant, anti-inflammatory, anti-arrhythmic, sedative and anti-malaria effects. In this study, the anti-seizure activity of different fractions of this plant was evaluated. Methods: Seventy two rats were randomly divided in to nine groups (n=8 in each group. (1: negative control group (normal saline 10mL/kg, (2: positive control group (sodium valproate 1 mg/kg, (3, 4, 5: hydroalcoholic extract-treated groups (100, 200, 400 mg/kg, (6, 7: methanol fraction-treated groups (100 and 200 mg/kg and (8, 9: chloroform fraction-treated group (100 and 200 mg/kg. Thirty minute after peritoneal injection of different doses of extract, fractions, saline and gavage of sodium valproate, PTZ (45 mg/kg was injected and they were immediately transferred to a special cage, and the seizure parameters were evaluated for 30 min. Result: The injection of different doses of hydroalcoholic extract and different fractions had a dose-dependent effect on prolongation of latency to the onset of seizures. The effective dose was 400 mg/kg of hydroalcoholic extract and 200 mg/kg of methanol fraction. They decreased the rate of mortality and the number of suddenly seizures jumping significantly. Conclusion: The present study demonstrated that the hydroalcoholic extract and methanol fraction of B. vulgaris showed anticonvulsant activity in PTZ-induced seizures in mice. Therefore, this plant may be more useful in petit mal epilepsy.

Treatment of Convulsive Status Epilepticus.

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Grover, Eric H; Nazzal, Yara; Hirsch, Lawrence J

2016-03-01

Convulsive status epilepticus (CSE) is a medical emergency with an associated high mortality and morbidity. It is defined as a convulsive seizure lasting more than 5 min or consecutive seizures without recovery of consciousness. Successful management of CSE depends on rapid administration of adequate doses of anti-epileptic drugs (AEDs). The exact choice of AED is less important than rapid treatment and early consideration of reversible etiologies. Current guidelines recommend the use of benzodiazepines (BNZ) as first-line treatment in CSE. Midazolam is effective and safe in the pre-hospital or home setting when administered intramuscularly (best evidence), buccally, or nasally (the latter two possibly faster acting than intramuscular (IM) but with lower levels of evidence). Regular use of home rescue medications such as nasal/buccal midazolam by patients and caregivers for prolonged seizures and seizure clusters may prevent SE, prevent emergency room visits, improve quality of life, and lower health care costs. Traditionally, phenytoin is the preferred second-line agent in treating CSE, but it is limited by hypotension, potential arrhythmias, allergies, drug interactions, and problems from extravasation. Intravenous valproate is an effective and safe alternative to phenytoin. Valproate is loaded intravenously rapidly and more safely than phenytoin, has broad-spectrum efficacy, and fewer acute side effects. Levetiracetam and lacosamide are well tolerated intravenous (IV) AEDs with fewer interactions, allergies, and contraindications, making them potentially attractive as second- or third-line agents in treating CSE. However, data are limited on their efficacy in CSE. Ketamine is probably effective in treating refractory CSE (RCSE), and may warrant earlier use; this requires further study. CSE should be treated aggressively and quickly, with confirmation of treatment success with epileptiform electroencephalographic (EEG), as a transition to non-convulsive status

Soman- or kainic acid-induced convulsions decrease muscarinic receptors but not benzodiazepine receptors

International Nuclear Information System (INIS)

Churchill, L.; Pazdernik, T.L.; Cross, R.S.; Nelson, S.R.; Samson, F.E.

1990-01-01

[3H]Quinuclidinyl benzilate (QNB) binding to muscarinic receptors decreased in the rat forebrain after convulsions induced by a single dose of either soman, a potent inhibitor of acetylcholinesterase, or kainic acid, an excitotoxin. A Rosenthal plot revealed that the receptors decreased in number rather than affinity. When the soman-induced convulsions were blocked, the decrease in muscarinic receptors at 3 days was less extensive than when convulsions occurred and at 10 days they approached control levels in most of the brain areas. The most prominent decrements in QNB binding were in the piriform cortex where the decline in QNB binding is probably related to the extensive convulsion-associated neuropathology. The decrements in QNB binding after convulsions suggest that the convulsive state leads to a down-regulation of muscarinic receptors in some brain areas. In contrast to the decrease in QNB binding after convulsions, [3H]flunitrazepam binding to benzodiazepine receptors did not change even in the piriform cortex where the loss in muscarinic receptors was most prominent. Thus, it appears that those neuronal processes that bear muscarinic receptors are more vulnerable to convulsion-induced change than those with benzodiazepine receptors

Blockade of N-methyl-D-aspartate induced convulsions by 1-aminocyclopropanecarboxylates

International Nuclear Information System (INIS)

Skolnick, P.; Marvizon, J.C.G.; Jackson, B.W.; Monn, J.A.; Rice, K.C.; Lewin, A.H.

1989-01-01

1-Aminocyclopropanecarboxylic acid is a potent and selective ligand for the glycine modulatory site on the N-methyl-D-aspartate receptor complex. This compound blocks the convulsions and deaths produced by N-methyl-D-aspartate in a dose dependent fashion. In contrast, 1-aminocyclopropanecarboxylic acid does not protect mice against convulsions induced by pentylenetetrazole, strychnine, bicuculline, or maximal electroshock, and does not impair motor performance on either a rotarod or horizontal wire at doses of up to 2 g/kg. The methyl- and ethyl- esters of 1-aminocyclopropanecarboxylic acid are 5- and 2.3-fold more potent, respectively, than the parent compound in blocking the convulsant and lethal effects of N-methyl-D-aspartate. However, these esters are several orders of magnitude less potent than 1-aminocyclopropanecarboxylic acid as inhibitors of strychnine-insensitive [ 3 H]glycine binding, indicating that conversion to the parent compound may be required to elicit an anticonvulsant action

Anticonvulsant activity of the ethanolic extract of Punica granatum L. seed.

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Mehrzadi, Saeed; Sadr, Samir; Hosseinzadeh, Azam; Gholamine, Babak; Shahbazi, Ali; FallahHuseini, Hasan; Ghaznavi, Habib

2015-06-01

Various morphological parts of pomegranate (Punica granatum L.) have extensively been used in the folk medicine to treat an array of human ailments. The aim of the present study is to demonstrate the anticonvulsant potential of the ethanolic extract of P. granatum L. seed in chemoconvulsant-induced seizures in mice. The anticonvulsant activity of the ethanolic extract was investigated in strychnine (STR)-induced and pentylenetetrazole (PTZ)-induced seizure models in mice. Diazepam was used as reference anticonvulsant drug. Ethanolic extract (150, 300, and 600 mg/kg per os, p.o.), diazepam (1 mg/kg intraperitoneally, i.p.), and distilled water (10 ml/kg, i.p.) were administered before induction of seizures by PTZ (60 mg/kg, i.p.) or STR (2.5 mg/kg, i.p.). The latent time before the onset of convulsions, the duration of convulsions, the percentage of seizure protection, and mortality rate were recorded. The seed ethanolic extract did not show any toxicity and did not protect the animals against seizures but demonstrated a significant increase in seizure latency at 300 and 600 mg/kg in both STR and PTZ seizure models (P < 0.001). It also showed a significant reduction in seizure duration at 300 mg/kg (P < 0.05) and 600 mg/kg (P < 0.001) in the STR seizure model and 600 mg/kg (P < 0.01) in the PTZ seizure model compared with the control group. Ethanol extract has dose-dependent anticonvulsant activity against STR- and PTZ-induced seizures. This activity might be due to its saponins, flavonoids, triterpenes, and alkaloids ingredients.

Anticonvulsant activity of 1,2,3,4,6-penta-O-galloyl-β-D-glucopyranose isolated from leaves of Mangifera indica.

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Viswanatha, G L; Mohan, C G; Shylaja, H; Yuvaraj, H C; Sunil, V

2013-07-01

The present study was aimed to evaluate the anticonvulsant activity of 1,2,3,4,6-penta-O-galloyl-β-D-glucopyranose (PGG) isolated from methanolic leaf extracts of Mangifera indica in mice. Anticonvulsant activity of PGG was evaluated against pentylenetetrazole (PTZ)-induced and maximal electroshock (MES)-induced convulsions in mice. Additionally, locomotor activity and GABA levels in the brain were estimated to explore the possible CNS-depressant activity and mechanism behind the anticonvulsant activity, respectively. In these studies, PGG (2.5, 5, and 10 mg/kg, intraperitoneal (i.p.)) showed significant and dose-dependent inhibition of PTZ and MES-induced convulsions. Furthermore, PGG administration showed significant decrease in the locomotor activity as an indication of its CNS-depressant property; also, PGG has significantly increased the GABA levels in the cerebellum and whole brain other than the cerebellum. In conclusion, PGG isolated from M. indica showed potent anticonvulsant activity, and possible mechanism may be due to enhanced GABA levels in the brain.

Evaluation of anti-epileptic activity of leaf extracts of Punica granatum on experimental models of epilepsy in mice.

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Viswanatha, Gollapalle L; Venkataranganna, Marikunte V; Prasad, Nunna Bheema Lingeswara; Ashok, Godavarthi

2016-01-01

This study was aimed to examine the anti-epileptic activity of leaf extracts of Punica granatum in experimental models of epilepsy in Swiss albino mice. Petroleum ether leaf extract of P. granatum (PLPG), methanolic LPG (MLPG), and aqueous LPG (ALPG) extracts of P. granatum leaves was initially evaluated against 6-Hz-induced seizure model; the potent extract was further evaluated against maximal electroshock (MES) and pentylenetetrazole (PTZ)-induced convulsions. Further, the potent extract was evaluated for its influence on Gamma amino butyric acid (GABA) levels in brain, to explore the possible mechanism of action. In addition, the potent extract was subjected to actophotometer test to assess its possible locomotor activity deficit inducing action. In 6-Hz seizure test, the MLPG has alleviated 6-Hz-induced seizures significantly and dose dependently at doses 50, 100, 200, and 400 mg/kg. In contrast, PLPG and ALPG did not show any protection, only high dose of ALPG (400 and 800 mg/kg, p.o.) showed very slight inhibition. Based on these observations, only MLPG was tested in MES and PTZ models. Interestingly, the MLPG (50, 100, 200 and 400 mg/kg) has offered significant and dose-dependent protection against MES ( P < 0.01) and PTZ-induced ( P < 0.01) seizures in mice. Further, MLPG showed a significant increase in brain GABA levels ( P < 0.01) compared to control and showed insignificant change in locomotor activity in all tested doses (100, 200 and 400 mg/kg). Interestingly, higher dose of MLPG (400 mg/kg, p.o.) and Diazepam (5 mg/mg, p.o.) have completely abolished the convulsions in all the anticonvulsant tests. These findings suggest that MLPG possesses significant anticonvulsant property, and one of the possible mechanisms behind the anticonvulsant activity of MLPG may be through enhanced GABA levels in the brain.

Integration of multispectral face recognition and multi-PTZ camera automated surveillance for security applications

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Chen, Chung-Hao; Yao, Yi; Chang, Hong; Koschan, Andreas; Abidi, Mongi

2013-06-01

Due to increasing security concerns, a complete security system should consist of two major components, a computer-based face-recognition system and a real-time automated video surveillance system. A computerbased face-recognition system can be used in gate access control for identity authentication. In recent studies, multispectral imaging and fusion of multispectral narrow-band images in the visible spectrum have been employed and proven to enhance the recognition performance over conventional broad-band images, especially when the illumination changes. Thus, we present an automated method that specifies the optimal spectral ranges under the given illumination. Experimental results verify the consistent performance of our algorithm via the observation that an identical set of spectral band images is selected under all tested conditions. Our discovery can be practically used for a new customized sensor design associated with given illuminations for an improved face recognition performance over conventional broad-band images. In addition, once a person is authorized to enter a restricted area, we still need to continuously monitor his/her activities for the sake of security. Because pantilt-zoom (PTZ) cameras are capable of covering a panoramic area and maintaining high resolution imagery for real-time behavior understanding, researches in automated surveillance systems with multiple PTZ cameras have become increasingly important. Most existing algorithms require the prior knowledge of intrinsic parameters of the PTZ camera to infer the relative positioning and orientation among multiple PTZ cameras. To overcome this limitation, we propose a novel mapping algorithm that derives the relative positioning and orientation between two PTZ cameras based on a unified polynomial model. This reduces the dependence on the knowledge of intrinsic parameters of PTZ camera and relative positions. Experimental results demonstrate that our proposed algorithm presents substantially

Calibration of a dual-PTZ camera system for stereo vision

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Chang, Yau-Zen; Hou, Jung-Fu; Tsao, Yi Hsiang; Lee, Shih-Tseng

2010-08-01

In this paper, we propose a calibration process for the intrinsic and extrinsic parameters of dual-PTZ camera systems. The calibration is based on a complete definition of six coordinate systems fixed at the image planes, and the pan and tilt rotation axes of the cameras. Misalignments between estimated and ideal coordinates of image corners are formed into cost values to be solved by the Nelder-Mead simplex optimization method. Experimental results show that the system is able to obtain 3D coordinates of objects with a consistent accuracy of 1 mm when the distance between the dual-PTZ camera set and the objects are from 0.9 to 1.1 meters.

Evaluation of CNS activities of aerial parts of Cynodon dactylon Pers. in mice.

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Pal, Dilipkumar

2008-01-01

The dried extracts of aerial parts of Cynodon dactylon Pers. (Graminae) were evaluated for CNS activities in mice. The ethanol extract of aerial parts of C. dactylon (EECD) was found to cause significant depression in general behavioral profiles in mice. EECD significantly potentiated the sleeping time in mice induced by standard hypnotics viz. pentobarbitone sodium, diazepam, and meprobamate in a dose dependant manner. EECD showed significant analgesic properties as evidenced by the significant reduction in the number of writhes and stretches induced in mice by 1.2% acetic acid solution. It also potentiated analgesia induced by morphine and pethidine in mice. EECD inhibited the onset and the incidence of convulsion in a dose dependent manner against pentylenetetrazole (PTZ)-induced convulsion. The present study indicates that EECD has significant CNS depressant activities.

Anti-convulsant therapy in eclampsia.

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Maheshwari J

1989-04-01

Full Text Available Seventy four patients presented with eclampsia at N.W.M. Hospital. Bombay. Among the patients with eclampsia, 64.9% were primis, 29.7% were gravida II-IV and 5.4% were grand multis. As many as 40.5% patients were less than 20 years of age, while 2.7% were over 30 years of age. 48.7% had antepartum convulsions, 40.5% had intrapartum convulsions, while 8 patients convulsed in the postpartum period. Besides standard management of eclamptic patients, 3 protocols of anticonvulsant therapy were utilised. 27% were managed with diphenyl hydantoin sodium, 43% with magnesium sulphate, and 30% by combination of diazepam and pentazocine. The maternal and perinatal outcome was evaluated. Control of convulsions was superior with magnesium sulphate while perinatal outcome was best with diphenyl hydantoin.

Anticonvulsant activity of Granisetron in Albino mice

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Sathisha Aithal

2015-05-01

Full Text Available The objective of this study was to investigate the anticonvulsant activity of  5-HT3 antagonist, granisetron in albino mice. In this study granisetron (0.5mg/kg, i.p. was administered 30 minutes prior to application of electroshock (60mA, 02.seconds or administration of pentylenetetrazole. Granisetron significantly reduced the duration of tonic hind limb extension in maximum electroshock seizure (MES test. In pentylenetetrazole (PTZ test, granisetron delayed the onset and the decreased the duration of convulsions compared to control group. The percentage of animals protected in MES and PTZ  models were 66 and 83 respectively. The results showed that granisetron at dose of 0.5mg possess anticonvulsant activity in both MES and PTZ models.

Synthesis, potential anticonvulsant and antidepressant effects of 2-(5-methyl-2,3-dioxoindolin-1-ylacetamide derivatives

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Xinghua Zhen

2015-07-01

Full Text Available A new series of 2-(5-methyl-2,3-dioxoindolin-1-ylacetamide derivatives were synthesized and evaluated for their anticonvulsive activity in a pentylenetetrazole (PTZ-evoked convulsion model and antidepressant activity in the forced swimming test (FST model. Eleven synthesized compounds were found to be protective against PTZ-induced seizure and showed the anticonvulsant activity. In addition, four of the synthesized compounds (4l, 4m, 4p and 4q showed potent antidepressant-like activity. Among these compounds, compound 4l was found to have the most potent antidepressant-like activity, and significantly reduced the duration of immobility time at 100 mg/kg dose level when compared to the vehicle control, which is similar to the reference drug fluoxetine.

Febrile convulsions and sudden infant death syndrome

DEFF Research Database (Denmark)

Vestergaard, Mogens; Basso, Olga; Henriksen, Tine Brink

2002-01-01

It has been suggested that sudden infant death syndrome (SIDS) and febrile convulsions are related aetiologically. We compared the risk of SIDS in 9877 siblings of children who had had febrile convulsions with that of 20.177 siblings of children who had never had febrile convulsions. We found...

Intrastriatal methylmalonic acid administration induces rotational behavior and convulsions through glutamatergic mechanisms.

Science.gov (United States)

de Mello, C F; Begnini, J; Jiménez-Bernal, R E; Rubin, M A; de Bastiani, J; da Costa, E; Wajner, M

1996-05-20

The effect of intrastriatal administration of methylmalonic acid (MMA), a metabolite that accumulates in methylmalonic aciduria, on behavior of adult male Wistar rats was investigated. After cannula placing, rats received unilateral intrastriatal injections of MMA (buffered to pH 7.4 with NaOH) or NaCl. MMA induced rotational behavior toward the contralateral side of injection and clonic convulsions in a dose-dependent manner. Rotational behavior and convulsions were prevented by intrastriatal preadministration of MK-801 and attenuated by preadministration of succinate. This study provides evidence for a participation of NMDA receptors in the MMA-induced behavioral alterations, where succinate dehydrogenase inhibition seems to have a pivotal role.

Pharmacokinetics and clinical effect of phenobarbital in children with severe falciparum malaria and convulsions

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Kokwaro, Gilbert O; Ogutu, Bernhards R; Muchohi, Simon N; Otieno, Godfrey O; Newton, Charles R J C

2003-01-01

Aims Phenobarbital is commonly used to treat status epilepticus in resource-poor countries. Although a dose of 20 mg kg−1 is recommended, this dose, administered intramuscularly (i.m.) for prophylaxis, is associated with an increase in mortality in children with cerebral malaria. We evaluated a 15-mg kg−1 intravenous (i.v.) dose of phenobarbital to determine its pharmacokinetics and clinical effects in children with severe falciparum malaria and status epilepticus. Methods Twelve children (M/F: 11/1), aged 7–62 months, received a loading dose of phenobarbital (15 mg kg−1) as an i.v. infusion over 20 min and maintenance dose of 5 mg kg−1 at 24 and 48 h later. The duration of convulsions and their recurrence were recorded. Vital signs were monitored. Plasma and cerebrospinal fluid (CSF) phenobarbital concentrations were measured with an Abbott TDx FLx® fluorescence polarisation immunoassay analyser (Abbott Laboratories, Diagnostic Division, Abbott Park, IL, USA). Simulations were performed to predict the optimum dosage regimen that would maintain plasma phenobarbital concentrations between 15 and 20 mg l−1 for 72 h. Results All the children achieved plasma concentrations above 15 mg l−1 by the end of the infusion. Mean (95% confidence interval or median and range for Cmax) pharmacokinetic parameters were: area under curve [AUC (0, ∞) ]: 4259 (3169, 5448) mg l−1.h, t½: 82.9 (62, 103) h, CL: 5.8 (4.4, 7.3) ml kg−1 h−1, Vss: 0.8 (0.7, 0.9) l kg −1, CSF: plasma phenobarbital concentration ratio: 0.7 (0.5, 0.8; n = 6) and Cmax: 19.9 (17.9–27.9) mg l−1. Eight of the children had their convulsions controlled and none of them had recurrence of convulsions. Simulations suggested that a loading dose of 15 mg kg−1 followed by two maintenance doses of 2.5 mg kg−1 at 24 h and 48 h would maintain plasma phenobarbital concentrations between 16.4 and 20 mg l−1 for 72 h. Conclusions Phenobarbital, given as an i.v. loading dose, 15 mg kg−1

Anticonvulsant activity of Aloe vera leaf extract in acute and chronic models of epilepsy in mice.

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Rathor, Naveen; Arora, Tarun; Manocha, Sachin; Patil, Amol N; Mediratta, Pramod K; Sharma, Krishna K

2014-03-01

The effect of Aloe vera in epilepsy has not yet been explored. This study was done to explore the effect of aqueous extract of Aloe vera leaf powder on three acute and one chronic model of epilepsy. In acute study, aqueous extract of Aloe vera leaf (extract) powder was administered in doses 100, 200 and 400 mg/kg p.o. Dose of 400 mg/kg of Aloe vera leaf extract was chosen for chronic administration. Oxidative stress parameters viz. malondialdehyde (MDA) and reduced glutathione (GSH) were also estimated in brain of kindled animals. In acute study, Aloe vera leaf (extract) powder in a dose-dependent manner significantly decreased duration of tonic hind limb extension in maximal electroshock seizure model, increased seizure threshold current in increasing current electroshock seizure model, and increased latency to onset and decreased duration of clonic convulsion in pentylenetetrazole (PTZ) model as compared with control group. In chronic study, Aloe vera leaf (extract) powder prevented progression of kindling in PTZ-kindled mice. Aloe vera leaf (extract) powder 400 mg/kg p.o. also reduced brain levels of MDA and increased GSH levels as compared to the PTZ-kindled non-treated group. The results of study showed that Aloe vera leaf (extract) powder possessed significant anticonvulsant and anti-oxidant activity. © 2013 Royal Pharmaceutical Society.

Brain redox imaging in the pentylenetetrazole (PTZ)-induced kindling model of epilepsy by using in vivo electron paramagnetic resonance and a nitroxide imaging probe.

Science.gov (United States)

Emoto, Miho C; Yamato, Mayumi; Sato-Akaba, Hideo; Yamada, Ken-ichi; Fujii, Hirotada G

2015-11-03

Much evidence supports the idea that oxidative stress is involved in the pathogenesis of epilepsy, and therapeutic interventions with antioxidants are expected as adjunct antiepileptic therapy. The aims of this study were to non-invasively obtain spatially resolved redox data from control and pentylenetetrazole (PTZ)-induced kindled mouse brains by electron paramagnetic resonance (EPR) imaging and to visualize the brain regions that are sensitive to oxidative damage. After infusion of the redox-sensitive imaging probe 3-methoxycarbonyl-2,2,5,5-tetramethyl-piperidine-1-oxyl (MCP), a series of EPR images of PTZ-induced mouse heads were measured. Based on the pharmacokinetics of the reduction reaction of MCP in the mouse heads, the pixel-based rate constant of its reduction reaction was calculated as an index of redox status in vivo and mapped as a redox map. The obtained redox map showed heterogeneity in the redox status in PTZ-induced mouse brains compared with control. The co-registered image of the redox map and magnetic resonance imaging (MRI) for both control and PTZ-induced mice showed a clear change in the redox status around the hippocampus after PTZ. To examine the role of antioxidants on the brain redox status, the levels of antioxidants were measured in brain tissues of control and PTZ-induced mice. Significantly lower concentrations of glutathione in the hippocampus of PTZ-kindled mice were detected compared with control. From the results of both EPR imaging and the biochemical assay, the hippocampus was found to be susceptible to oxidative damage in the PTZ-induced animal model of epilepsy. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Molecular Docking and Anticonvulsant Activity of Newly Synthesized Quinazoline Derivatives

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Hatem A. Abuelizz

2017-06-01

Full Text Available A new series of quinazoline-4(3H-ones are evaluated for anticonvulsant activity. After intraperitoneal (ip injection to albino mice at a dose of 100 mg/kg body weight, synthesized quinazolin-4(3H-ones (1–24 were examined in the maximal electroshock (MES induced seizures and subcutaneous pentylenetetrazole (scPTZ induced seizure models in mice. The Rotarod method was applied to determine the neurotoxicity. Most of the compounds displayed anticonvulsant activity in the scPTZ screen at a dose range of 0.204–0.376 mmol/mL. Out of twenty-four, compounds 8, 13 and 19 proved to be the most active with a remarkable protection (100% against PTZ induced convulsions and four times more potent activity than ethosuximide. The structure-activity relationship concluded valuable pharmacophoric information, which was confirmed by the molecular docking studies using the target enzyme human carbon anhydrase II (HCA II. The studied quinazoline analogues suggested that the butyl substitution at position 3 has a significant effect on preventing the spread of seizure discharge and on raising the seizure threshold. However, benzyl substitution at position 3 has shown a strong anticonvulsant activity but with less seizure prevention compared to the butyl substitution.

Evaluation of Ashwagandha in alcohol withdrawal syndrome

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Ruby B

2012-10-01

Full Text Available Objective: To evaluate the effect of Ashwagandha (ASW in attenuation of alcohol withdrawal in ethanol withdrawal mice model. Methods: Alcohol dependence was induced in mice by the oral, once-daily administration of 10% v/v ethanol (2 g/kg for one week. Once the animals were withdrawn from alcohol, the efficacy of ASW (200mg/kg and 500mg/kg in comparison with diazepam (1 mg/kg in the attenuation of withdrawal was studied using, pentylenetetrazole (PTZ kindling test for seizure threshold, forced swim test (FST for depression and locomotor activity (LCA in open field test (OFT. 6 hours after the last ethanol administration, seizure threshold was measured in all the groups by administering the convulsant drug, PTZ with a subconvulsive dose of 30 mg/kg i.p. In FST, mice were forced to swim and the total duration of immobility (seconds was measured during the last 4 min of a single 6-min test session. In OFT, number of crossings of the lines marked on the floor was recorded for a period of 5 min. Results: Compared to ethanol group, ASW (500 mg/Kg has suppressed the PTZ kindling seizures in ethanol withdrawal animals [0% convulsion], FST has shown decreased immobility time and OFT has exhibited increase in the number of line crossing activity by mice which may be the consequence of anxiolytic activity of ASW similar to that of diazepam. Conclusions: The present study provides satisfactory evidence to use ASW as a safe and reliable alternative to diazepam in alcohol withdrawal conditions.

Some Aspects of Epilepsy and Convulsions in Childhood | Brett ...

African Journals Online (AJOL)

The diagnostic and therapeutic problems of epilepsy and convulsions in childhood are reviewed. Their non-specific aetiology is stressed, particularly with neonatal convulsions and infantile spasms. The role of febrile convulsions in causing later temporal lobe epilepsy and gross neurological deficit, underlines the ...

Effect of hydroalcoholic extract of Lavandula officinalis on nicotine-induced convulsion in mice.

Science.gov (United States)

Arzi, A; Ahamehe, M; Sarahroodi, S

2011-06-01

Epilepsy an important CNS (central nervous system) problem that about 1% of world's population suffer of it. The aim of study was to evaluate of anticonvulsant effect of hydroalcoholic extract of Lavandula officinalis. In this study, anticonvulsant activity of the hydroalcoholic extract of Lavandula officinalis (L. officinalis) was studied against chemoconvulsant-induced seizures in male mice. Lavandula officinalis (100, 200, 400, 600 and 800 mg kg(-1)), diazepam (0.15 mg kg(-1)) and normal saline (10 mL kg(-1)) were injected intraperitoneally, respectively in different groups of mice, 30 min before nicotine (5 mg kg(-) i.p.). The onset time intensity and duration of convulsions and the percentage of death were recorded. Also the time-response (0, 15, 30, 45, 60 min before nicotine injection) for most effective dose of plant extract (600 mg kg(-1)) was investigated. The results showed that hydroalcoholic extract of Lavandula officinalis had anticonvulsant effect. The most effective dose of plant extract was 600 mg kg(-1). In time-response study for the most effective dose of extract (600 mg kg(-1)), the onset, duration and intensity of convulsion significantly (p Lavandula.

Efficacy and safety of intravenous sodium valproate versus phenobarbital in controlling convulsive status epilepticus and acute prolonged convulsive seizures in children: a randomised trial.

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Malamiri, Reza Azizi; Ghaempanah, Mahdieh; Khosroshahi, Nahid; Nikkhah, Ali; Bavarian, Behrouz; Ashrafi, Mahmoud Reza

2012-09-01

Status epilepticus and acute prolonged seizures are the most commonly occurring neurological emergencies in children. Such events have high morbidity and mortality rates along with poor long-term outcomes, depending on their duration and causes. Therefore, such seizures warrant urgent treatment using appropriate doses of anticonvulsants. Benzodiazepines, phenobarbital, and phenytoin are the most commonly used anticonvulsants for controlling status epilepticus and acute prolonged seizures. However, these medications have several well-known adverse effects. Previous studies on both adults and children have shown the efficacy and safety of rapid infusion of valproate in controlling status epilepticus. However, few well-designed randomised trials have been carried out in children, and there remains a paucity of data regarding intravenous sodium valproate use in children. Therefore, our aim was to compare the efficacy and safety of rapid loading of valproate with those of intravenous phenobarbital in children with status epilepticus and acute prolonged seizures. Sixty children (30 in each group) with convulsive status epilepticus and acute prolonged seizures were enrolled and randomly assigned to receive either valproate or phenobarbital. The main outcome variable was termination of all convulsive activity within 20 min of starting anticonvulsant infusion. Intravenous rapid loading of valproate was successful in seizure termination in (27/30, 90%) of patients compared to phenobarbital (23/30, 77%) (p = 0.189). Clinically significant adverse effects occurred in 74% patients of the phenobarbital group and 24% patients of the valproate group (p < 0.001). In conclusion, rapid loading of valproate is effective and safe in controlling convulsive status epilepticus and acute prolonged convulsive seizures in children. Intravenous valproate should be considered as a suitable choice for terminating status epilepticus and acute prolonged seizures in children. Copyright �

Evaluation of anticonvulsant and nootropic effect of ondansetron in mice.

Science.gov (United States)

Jain, S; Agarwal, N B; Mediratta, P K; Sharma, K K

2012-09-01

The role of serotonin receptors have been implicated in various types of experimentally induced seizures. Ondansetron is a highly selective 5-hydroxytryptamine 3 (5-HT(3)) receptor antagonist used as antiemetic agent for chemotherapy-, and radiotherapy-induced nausea and vomiting. The present study was carried out to examine the effect of ondansetron on electroshock, pentylenetetrazole (PTZ)-induced seizures and cognitive functions in mice. Ondansetron was administered intraperitoneally (i.p.) at doses of 0.5, 1.0 and 2.0 mg/kg (single dose) to observe its effect on the increasing current electroshock seizure (ICES) test and PTZ-induced seizure test. In addition, a chronic study (21 days) was also performed to assess the effects of ondansetron on electroshock-induced convulsions and cognitive functions. The effect on cognition was assessed by elevated plus maze and passive avoidance paradigms. Phenytoin (25 mg/kg, i.p.) was used as a standard anticonvulsant drug and piracetam (200 mg/kg) was administered as a standard nootropic drug. The results were compared with an acute study, wherein it was found that the administration of ondansetron (1.0 and 2.0 mg/kg) significantly raised the seizure-threshold current as compared to control group in the ICES test. Similar results were observed after chronic administration of ondansetron. In PTZ test, ondansetron in all the three tested doses failed to show protective effect against PTZ-induced seizure test. Administration of ondansetron for 21 days significantly decreased the transfer latency (TL) and prolonged the step-down latency (SDL). The results of present study suggest the anticonvulsant and memory-enhancing effect of ondansetron in mice.

Soman-induced convulsions: The neuropathology revisited

International Nuclear Information System (INIS)

Baille, Valerie; Clarke, Peter G.H.; Brochier, Guy; Dorandeu, Frederic; Verna, Jean-Marc; Four, Elise; Lallement, Guy; Carpentier, Pierre

2005-01-01

The organophosphorus compound soman, an irreversible inhibitor of cholinesterases, produces seizure activity and related brain damage. Studies using various biochemical markers of programmed cell death (PCD) suggested that soman-induced cell damage in the brain was apoptotic rather than necrotic. However, it has recently become clear that not all PCD is apoptotic, and the unequivocal demonstration of apoptosis requires ultrastructural examination. Therefore, the present study was undertaken to reinvestigate the damage produced in the brains of mice sacrificed at various times within the first 24 h or at 7 days after a convulsive dose of soman. Classical histology and ultrastructural examination were performed. The immunohistochemical expression of proteins (p53, Bax) involved in PCD, DNA fragmentation (TUNEL method at light and electron microscopy levels) and the glial reaction were also explored. Our study confirms that the severity of lesions depended on the duration of convulsions and shows that cerebral changes were still occurring as late as 7 days after the onset of long-lasting convulsions. Our observations also establish that there was a large variety of ultrastructurally distinct types of cell damage, including hybrid forms between apoptosis and necrosis, but that pure apoptosis was very rare. A prominent expression of p53 and Bax proteins was detected indicating that PCD mechanisms were certainly involved in the morphologically diverse forms of cell death. Since purely apoptotic cells were very rare, these protein expressions were presumably involved either in nonapoptotic cell death mechanisms or in apoptotic mechanisms occurring in parallel with nonapoptotic ones. Moreover, evidence for DNA fragmentation by the TUNEL method was found in apoptotic but also in numerous other morphotypes of cell damage. Therefore, TUNEL-positivity and the expression of PCD-related proteins, in the absence of ultrastructural confirmation, were here shown not to provide

Anticonvulsant effects of isomeric nonimidazole histamine H3 receptor antagonists

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Sadek B

2016-11-01

Full Text Available Bassem Sadek,1 Ali Saad,1 Johannes Stephan Schwed,2,3 Lilia Weizel,2 Miriam Walter,2 Holger Stark2,3 1Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates; 2Biocenter, Institute of Pharmaceutical Chemistry, Goethe University, Frankfurt, Germany; 3Department of Pharmaceutical and Medicinal Chemistry, Institute of Pharmaceutical and Medicinal Chemistry, Heinrich Heine University, Düsseldorf, Germany Abstract: Phenytoin (PHT, valproic acid, and modern antiepileptic drugs (AEDs, eg, remacemide, loreclezole, and safinamide, are only effective within a maximum of 70%–80% of epileptic patients, and in many cases the clinical use of AEDs is restricted by their side effects. Therefore, a continuous need remains to discover innovative chemical entities for the development of active and safer AEDs. Ligands targeting central histamine H3 receptors (H3Rs for epilepsy might be a promising therapeutic approach. To determine the potential of H3Rs ligands as new AEDs, we recently reported that no anticonvulsant effects were observed for the (S-2-(4-(3-(piperidin-1-ylpropoxybenzylaminopropanamide (1. In continuation of our research, we asked whether anticonvulsant differences in activities will be observed for its R-enantiomer, namely, (R-2-(4-(3-(piperidin-1-ylpropoxybenzylaminopropaneamide (2 and analogs thereof, in maximum electroshock (MES-, pentylenetetrazole (PTZ-, and strychnine (STR-induced convulsion models in rats having PHT and valproic acid (VPA as reference AEDs. Unlike the S-enantiomer (1, the results show that animals pretreated intraperitoneally (ip with the R-enantiomer 2 (10 mg/kg were moderately protected in MES and STR induced models, whereas proconvulsant effect was observed for the same ligand in PTZ-induced convulsion models. However, animals pretreated with intraperitoneal doses of 5, 10, or 15 mg/kg of structurally bulkier (R-enantiomer (3

Comparative studies on the effects of clinically used anticonvulsants on the oxidative stress biomarkers in pentylenetetrazole-induced kindling model of epileptogenesis in mice.

Science.gov (United States)

Mazhar, Faizan; Malhi, Saima M; Simjee, Shabana U

2017-01-01

Oxidative stress plays a key role in the pathogenesis of epilepsy and contributes in underlying epileptogenesis process. Anticonvulsant drugs targeting the oxidative stress domain of epileptogenesis may provide better control of seizure. The present study was carried out to investigate the effect of clinically used anti-epileptic drugs (AEDs) on the course of pentylenetetrazole (PTZ)-induced kindling and oxidative stress markers in mice. Six mechanistically heterogeneous anticonvulsants: phenobarbital, phenytoin, levetiracetam, pregabalin, topiramate, and felbamate were selected and their redox profiles were determined. Diazepam was used as a drug control for comparison. Kindling was induced by repeated injections of a sub-convulsive dose of PTZ (50 mg/kg, s.c.) on alternate days until seizure score 5 was evoked in the control kindled group. Anticonvulsants were administered daily. Following PTZ kindling, oxidative stress biomarkers were assessed in homogenized whole brain samples and estimated for the levels of nitric oxide, peroxide, malondialdehyde, protein carbonyl, reduced glutathione, and activities of nitric oxide synthase and superoxide dismutase. Biochemical analysis revealed a significant increase in the levels of reactive oxygen species with a parallel decrease in endogenous anti-oxidants in PTZ-kindled control animals. Daily treatment with levetiracetam and felbamate significantly decreased the PTZ-induced seizure score as well as the levels of nitric oxide (panticonvulsant effect by the diversified mechanism of action such as levetiracetam, felbamate, and topiramate exhibited superior anti-oxidative stress activity in addition to their anticonvulsant activity.

MK-801, but not naloxone, attenuates high-dose dextromethorphan-induced convulsive behavior: Possible involvement of the GluN2B receptor.

Science.gov (United States)

Tran, Hai-Quyen; Chung, Yoon Hee; Shin, Eun-Joo; Tran, The-Vinh; Jeong, Ji Hoon; Jang, Choon-Gon; Nah, Seung-Yeol; Yamada, Kiyofumi; Nabeshima, Toshitaka; Kim, Hyoung-Chun

2017-11-01

Dextromethorphan (DM) is a dextrorotatory isomer of levorphanol, a typical morphine-like opioid. When administered at supra-antitussive doses, DM produces psychotoxic and neurotoxic effects in humans. Although DM abuse has been well-documented, few studies have examined the effects of high-dose DM. The present study aimed to explore the effects of a single high dose of DM on mortality and seizure occurrence. After intraperitoneal administration with a high dose of DM (80mg/kg), Sprague-Dawley rats showed increased seizure occurrence and intensity. Hippocampal expression levels of N-methyl-d-aspartate (NMDA) receptor subunits (GluN1dose DM, whereas an opioid antagonist, naloxone, did not affect DM-induced neurotoxicity. Moreover, pretreatment with a highly specific GluN2B subunit inhibitor, traxoprodil, was selectively effective in preventing DM-induced c-Fos expression and apoptotic changes. These results suggest that high-dose DM produces convulsive behaviors by activating GluN2B/NMDA signaling that leads to pro-apoptotic changes. Copyright © 2017. Published by Elsevier Inc.

Central effects of isolated fractions from the root of Petiveria alliacea L. (tipi) in mice.

Science.gov (United States)

Gomes, Patrícia B; Noronha, Emmanuelle C; de Melo, Carla Thiciane V; Bezerra, José N S; Neto, Manoel A; Lino, Cleide S; Vasconcelos, Silvânia M M; Viana, Glauce S B; de Sousa, Francisca Cléa F

2008-11-20

Petiveria alliacea L. (tipi) a shrub from Phytolaccaceae family is popularly used in folk medicine for treating a wide variety of disorders in South and Central America. To investigate the neuropharmacological properties on experimental animals. The acetate (FA), hexanic (FH), hydroalcoholic (FHA) and precipitated hydroalcoholic (FHAppt) fractions from the root of tipi were studied to investigate its pharmacological properties in the classical behavioral models (open-field, elevated plus maze-EPM, rotarod, barbiturate-induced sleeping time, forced swimming and pentylenetetrazole (PTZ)-induced convulsions tests) using mice. These fractions were administered intraperitoneally and orally to female mice at single doses of 100 and 200mg/kg. All these fractions decreased the locomotor activity, rearing and grooming in the open-field test, suggesting a possible central depressant action. No significant effect was evident on motor coordination of the animals in the rotarod test. On EPM, all the fractions of tipi presented a significant reduction on the time of permanence in the open arms, indicating an absence of anxiolytic-like effect. In addition, the fractions increased the immobility time in the forced swimming test and potentiated pentobarbital-induced sleeping time in mice, confirmed a probable sedative and central depressant effect. Furthermore, the fractions increased the latency to the first convulsion and the lethal time of the PTZ-induced convulsions test in the animals, confirmed its popular use as anticonvulsant. Our results suggest that the fractions of P. alliacea L. contains biologically active substance(s) that might be acting in the CNS and have significant depressant and anticonvulsant potentials, supporting folk medicine use of this plant.

Automated differentiation between epileptic and non-epileptic convulsive seizures

DEFF Research Database (Denmark)

Beniczky, Sándor; Conradsen, Isa; Moldovan, Mihai

2015-01-01

Our objective was the clinical validation of an automated algorithm based on surface electromyography (EMG) for differentiation between convulsive epileptic and psychogenic nonepileptic seizures (PNESs). Forty-four consecutive episodes with convulsive events were automatically analyzed with the a......%) and 18 PNESs (95%). The overall diagnostic accuracy was 95%. This algorithm is useful for distinguishing between epileptic and psychogenic convulsive seizures....

Protection against cyanide-induced convulsions with alpha-ketoglutarate.

Science.gov (United States)

Yamamoto, H

1990-04-30

Protection against convulsions induced by cyanide was observed after treatment with alpha-ketoglutarate, either alone or in combination with sodium thiosulfate, a classical antagonist for cyanide intoxication. However, sodium thiosulfate alone did not protect against cyanide (30 mg/kg)-induced convulsions. gamma-Aminobutyric acid (GABA) levels in brain were decreased by 31% in KCN-treated mice exhibiting convulsions. The combined administration of alpha-ketoglutarate and sodium thiosulfate completely abolished the decrease of GABA levels induced by cyanide. Furthermore, sodium thiosulfate alone also completely abolished the decrease of GABA levels. These results suggest that the depletion of brain GABA levels may not directly contribute to the development of convulsions induced by cyanide. On the other hand, cyanide increased calcium levels by 32% in brain crude mitochondrial fractions in mice with convulsions. The increased calcium levels were completely abolished by the combined administration of alpha-ketoglutarate and sodium thiosulfate, but not affected by sodium thiosulfate alone. These findings support the hypothesis proposed by Johnson et al. (Toxicol. Appl. Pharmacol., 84 (1986) 464) and Robinson et al. (Toxicology, 35 (1985) 59) that calcium may play an important role in mediating cyanide neurotoxicity.

Clinical research of benign infantile convulsions with mild gastroenteritis

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Wei-bing LI

2014-03-01

Full Text Available Cases of benign infantile convulsions with mild gastroenteritis (BICE treated in our hospital from 2008 to 2012 were analyzed retrospectively. Among the 65 cases of convulsions with acute diarrhea, there were 18 cases of BICE, 15 cases of febrile seizures, 13 cases of epilepsy, 6 cases of viral encephalitis, 6 cases of hyponatremia encephalopathy, 3 cases of hypernatremia encephalopathy, 2 cases of toxic encephalopathy, and 2 cases of hypocalcemia convulsion. The convulsion occurred mostly during the first 2 d of the illness and was in a generalized tonic or tonic-clonic form. Positive rotavirus antigens in the BICE patients were detected in 83.33％ (15/18. Phenobarbital was administered after the first convulsion (5-10 mg/kg, and diazepam was given intravenously in case of recurrence (0.10-0.30 mg/kg. BICE occurs frequently in infantile and controlling relapse is the main purpose. The prognosis is good. doi: 10.3969/j.issn.1672-6731.2014.03.019

The potential anticonvulsant activity of the ethanolic extracts of Achillea nobilis and Momordica charantia in rats

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Gamal A. Soliman

2016-06-01

Full Text Available Context: Currently available antiepileptic drugs have debilitating adverse effects. Natural products and plants already used in traditional medicine can be a good place to start in the search for safer and more effective options. Aims: To investigate the anticonvulsant potential of Achillea nobilis and Momordica charantia extracts in maximal electroshock (MES, as well as pentylenetetrazole (PTZ- and strychnine nitrate (STN- induced seizure models in rats. Methods: For each model, eight groups of 21-day-old male Albino rats were used. The 1st group was kept as control, 2nd as standard (diazepam, 7.5 mg/kg; 3rd – 5th treated with A. nobilis (100, 200 and 300 mg/kg; and 6th – 8th administered M. charantia (100, 200 and 300 mg/kg. After 30 min, rats were exposed to a shock of 150 mA by a convulsiometer, via ear electrodes for 2 s (in MES test or sc injection of PTZ (85 mg/kg or STN (2.5 mg/kg. Results: A. nobilis and M. charantia extracts (200 and 300 mg/kg demonstrated dose-dependent anticonvulsant effect against MES-induced seizures. In the PTZ induced convulsion, A. nobilis and M. charantia (200 and 300 mg/kg significantly slowed the commencement of convulsions and minimized the duration of seizures. A. nobilis (300 mg/kg showed 60% protection in rats against STN induced seizures. In contrast, A. nobilis (100 and 200 mg/kg and M. charantia (100, 200 and 300 mg/kg showed no significant protection against STN-induced seizures in rats. Conclusions: The results of the present study suggest that both extracts exhibited marked anticonvulsant activities.

5-(2-Cyclohexylideneethyl)-5-ethyl barbituric acid (CHEB): correlation of hypnotic and convulsant properties with alterations of synaptosomal 45Ca2+ influx

International Nuclear Information System (INIS)

Chandler, L.J.; Leslie, S.W.; Gonzales, R.

1986-01-01

Male ICR mice were given either 5-(2-cyclohexylideneethyl)-5-ethyl barbituric acid (CHEB) alone or CHEB after a 1 h pretreatment with phenobarbital CHEB alone produced excitatory behavior but not convulsive seizures. Higher doses produced convulsive seizures resulting in death. Pretreatment with phenobarbital prevented seizure activity. In vitro, CHEB significantly inhibited 'fast-phase' K + -stimulated 45 Ca 2+ uptake into cerebrocortical synaptosomes. CHEB also significantly increased basal 45 Ca 2+ uptake. The addition of CHEB or pentobarbital to striatal synaptosomes inhibited 'fast-phase' K + -stimulated 45 Ca 2+ uptake and endogenous dopamine release. CHEB, but not pentobarbital, produced a time- and dose-dependent increase in the resulting release of endogenous dopamine from striatal synaptosomes. The results of this study show that CHEB possesses hypnotic activity if its lethal convulsant actions are blocked. The hypnotic actions of CHEB appear to correlate with inhibition of voltage-dependent calcium channels in brain synaptosomes. (Auth.)

Collaborative real-time scheduling of multiple PTZ cameras for multiple object tracking in video surveillance

Science.gov (United States)

Liu, Yu-Che; Huang, Chung-Lin

2013-03-01

This paper proposes a multi-PTZ-camera control mechanism to acquire close-up imagery of human objects in a surveillance system. The control algorithm is based on the output of multi-camera, multi-target tracking. Three main concerns of the algorithm are (1) the imagery of human object's face for biometric purposes, (2) the optimal video quality of the human objects, and (3) minimum hand-off time. Here, we define an objective function based on the expected capture conditions such as the camera-subject distance, pan tile angles of capture, face visibility and others. Such objective function serves to effectively balance the number of captures per subject and quality of captures. In the experiments, we demonstrate the performance of the system which operates in real-time under real world conditions on three PTZ cameras.

CONVULSIVE DISORDERS IN CHILDREN WITH REFERENCE TO TREATMENT WITH KETOGENIC DIET.

Science.gov (United States)

KEITH, HADDOW M.

WRITTEN FOR THE MEDICAL PROFESSION, THIS BOOK PROVIDES INFORMATION ON CHILDHOOD CONVULSIONS (EPILEPSY) AND METHODS OF TREATMENT. VARIOUS CONVULSIVE DISORDERS, INCLUDING HYPSARHYTHMIA, AUTONOMIC SEIZURES, SYMPTOM COMPLEXES, FEBRILE CONVULSIONS, AND "PHOTOGENIC" DISORDERS, ARE DISCUSSED IN TERMS OF CAUSES, SYMPTOMS, AND TREATMENT.…

Prognosis and predictors of convulsion among pediatric lupus nephritis patients

International Nuclear Information System (INIS)

Beiraghdar, Fatemeh; Einollahi, Behzad; Taheri, Saeed; Panahi, Yunes; Maddani, Abbas; Esfahani, Taher; Sharifi-Bonab, Mir Mohsen

2009-01-01

In this study, we aimed to analyze features and outcome of convulsion in pediatric lupus nephritis patients. We retrospectively reviewed data of 14 Iranian children with lupus nephritis who developed seizures and compared them with a group of the same number of well matched pediatric lupus nephritis patients. Higher serum creatinine levels and higher frequencies of anemia and lymphopenia were observed in the convulsion group. Multivariable logistic regression analysis revealed that the only risk factor for development of convulsion in pediatric lupus patients with nephritis was lymphopenia. Survival analysis showed that convulsion had no impact on patient and renal function outcomes in our pediatric lupus nephritis subjects. In conclusion, we found that lymphopenia is a predictive factor for convulsion occurrence in our patients and special attention to neurological status assessment may be needed in this situation. (author)

Antiepileptic activity of total triterpenes isolated from Poria cocos is mediated by suppression of aspartic and glutamic acids in the brain.

Science.gov (United States)

Gao, Yanqiong; Yan, Hua; Jin, Ruirui; Lei, Peng

2016-11-01

Triterpenes from Poria cocos Wolf (Polyporaceae) have been used to treat various diseases in traditional Chinese medicine. However, the antiepileptic effects and mechanism are not fully understood. The objective of this study is to investigate the antiepileptic properties of total triterpenes (TTP) from the whole P. cocos. The ethanol extract TTP was identified by HPLC fingerprint analysis. Male ICR mice were gavaged (i.g.) with TTP (5, 20, 80 or 160 mg/kg) or reference drugs twice a day for 7 d. Antiepileptic activities of TTP were evaluated by maximal electroshock (MES)- and pentylenetetrazole (PTZ)-induced seizures in mice for 30 and 60 min, respectively. Locomotor activity and Rota-rod tests were performed for 60 min and 5 min, respectively. The levels of glutamic acid (Glu), aspartic acid (Asp), γ-aminobutyric acid (GABA) and glycine (Gly) in convulsive mice were estimated. The chronic epileptic model of Wistar rats was built to measure expressions of glutamate decarboxylase 65 (GAD65) and GABA A in rat brain after TTP treatment. The LC 50 of TTP (i.g.) was above 6 g/kg. TTP (5-160 mg/kg) protected mice against MES- and PTZ-induced convulsions at 65.0% and 62.5%, respectively, but have no effect on rota-rod treadmill; TTP (20-160 mg/kg) significantly reduced the locomotor activities, shortened the onset of pentobarbital sodium-induced sleep; TTP decreased Glu and Asp levels in convulsive mice, but increased the GAD65 and GABA A expressions in chronic epileptic rats at doses usage. TTP extracted from P. cocos possessed potential antiepileptic properties and is a candidate for further antiepileptic drug development.

Concussive convulsions as differential diagnosis of posttraumatic epilepsy

Directory of Open Access Journals (Sweden)

Vojvodić Nikola M.

2002-01-01

Full Text Available Concussive convulsions are motor manifestations in acute head injury. This clinical phenomenon should be distin- guished from epileptic seizures. We present two young men with motor and convulsive manifestations in acute head injury. Patient 1. A18-year old basketball player felt on the parquet during a game. Initially he was struck on the right shoulder which caused brief and vigorous twitch of the head towards the ground and additional temporal impact. At the moment of impact he lost consciousness and developed tonic leg and arm posturing with both clenched fists. His legs were extended during next 20 seconds. Thereafter he was still and his loss of consciousness lasted 3 minutes. Patient 2. A 26-year old man felt on the wooden ground from a 4 m high ferry. He got head impact and lost consciousness. In a few seconds he had tonic/clonic convulsions for the next 10-15 seconds. Ten minutes later he awaked. Results of subsequent neurological examination, electroencephalography and cerebral magnetic resonance imaging studies were normal in both patients. They returned to their occupations after four weeks without problems for a further one year. Conclusion. Described motor manifestations present concussive convulsions. These clinical features are due to transient functional decerebration and corticomedullary dissociation during cerebral concussion. Concussive convulsions are a non-epileptic phenomenon, they are not associated with structural brain injury and have good prognosis. Antiepileptic treatment is not indicated.

Home Management of Febrile Convulsion in Under-fives: an ...

African Journals Online (AJOL)

Home Management of Febrile Convulsion in Under-fives: an Assessment of Perceptions and Practices of Caregivers in Ojokoro Local Council Development Area, Lagos. ... Of the 46 respondents that reported previous history of febrile convulsion, 39(84.8%)carried out inappropriate pre-facility management practices.

Glufosinate ammonium induces convulsion through N-methyl-D-aspartate receptors in mice.

Science.gov (United States)

Matsumura, N; Takeuchi, C; Hishikawa, K; Fujii, T; Nakaki, T

2001-05-18

Glufosinate ammonium, a broad-spectrum herbicide, causes convulsion in rodents and humans. Because of the structural similarities between glufosinate and glutamate, the convulsion induced by glufosinate ammonium may be ascribed to glutamate receptor activation. Three N-methyl-D-asparate (NMDA) receptor antagonists, dizocilpine, LY235959, and Compound 40, and an alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)/kainate receptor antagonist, NBQX, were coadministrated with glufosinate ammonium (80 mg/kg, intraperitoneally) in mice. Statistical analyses showed that the NMDA receptor antagonists markedly inhibited the convulsions, while the AMPA/kainate receptor antagonist had no effect on the convulsion. These results suggest that the convulsion caused by glufosinate ammonium is mediated through NMDA receptors.

Evaluation of Behavioral and Pharmacological Effects of Hydroalcoholic Extract of Valeriana prionophylla Standl. from Guatemala

Directory of Open Access Journals (Sweden)

Iandra Holzmann

2011-01-01

Full Text Available There are few studies on the pharmacological properties of Valeriana prionophylla Standl. (VP, known as “Valeriana del monte”, and used in Mesoamerican folk medicine to treat sleep disorders. This study examines the pharmacological effects of the hydroalcoholic extract of the dry rhizome using the open field, rota rod, elevated plus-maze (EPM, forced swimming (FST, strychnine- and pentobarbital-induced sleeping time, PTZ-induced seizures, and the inhibitory avoidance tests. VP did not show any protective effect against PTZ-induced convulsions. In the EPM, exhibited an anxiolytic-like effect through the effective enhancement of the entries (38.5% and time spent (44.7% in the open arms, when compared with control group. Time spent and the numbers of entrances into the enclosed arms were decreased, similar to those effects observed with diazepam. In the FST, acute treatment with VP, produced a dose-dependent decrease in immobility time, similarly to imipramine. VP also produced a significant dose-dependent decrease in the latency of sleeping time, while producing an increase in total duration of sleep; influenced memory consolidation of the animals only at lower doses, unlike those that produced anti-depressant and anxiolytic effects. In summary, the results suggest that VP presents several psychopharmacological activities, including anxiolytic, antidepressant, and hypno-sedative effects.

The relationship between iron deficiency anemia and simple febrile convulsion in children.

Science.gov (United States)

Yousefichaijan, Parsa; Eghbali, Aziz; Rafeie, Mohammad; Sharafkhah, Mojtaba; Zolfi, Mohaddeseh; Firouzifar, Mohammadreza

2014-05-01

Simple febrile convulsion is the most common disease of the nervous system in children. There are hypotheses that iron deficiency may affect febrile convulsion and the threshold of neuron excitation. This study was conducted with the objective of finding the effects of iron deficiency anemia on simple febrile convulsion episodes. The study was conducted at AmirKabir Hospital of Arak Medical Sciences University, Arak, Iran. This is a case-control study. In this study, 382 children who were selected according to our inclusion and exclusion factors, were divided into two groups of case (febrile convulsion) and control (other factors causing fever) by their cause of hospitalization. After fever subsided, 5 ml blood sample was taken from each child and complete blood count and iron profile tests were performed. The results were interpreted using descriptive statistics and independent t-test. The prevalence of anemia in the group with febrile convulsion was significantly less than that in the control group: 22.5% of the children in the group with febrile convulsion and 34% in the control group exhibited anemia (P < 0.001). Moreover, the group with febrile convulsion had significantly higher blood indices, such as Hb, Hct, MCV, MCH, and MCHC, compared to the control group (P < 0.001). Iron deficiency can prevent febrile convulsion in children and probably increases the threshold of neuron excitation in fever.

Assessing Anticonvulsant Effect of Aqueous Extract of Datura Stramonium Seed on PTZ-Induced Seizures in the Male Mice

Directory of Open Access Journals (Sweden)

S Namvar Aghdash

2015-11-01

Full Text Available Background: Epilepsy is one of the most common neurological disorders that affect social, economic and biological aspects of the human life. Many epileptic patients have uncontrolled seizures and medication-related side effects despite adequate pharmacological treatment. The use of plant extracts is proposed as a therapeutic modality in order to treat different diseases. Datura plant has long been used in the traditional medicine in regard with some nervous disorders like epilepsy. Thus, this study aimed to provide a scientific basis investigating the effect of Datura aqueous extract on PTZ-induced seizures in the male mice. Methods: In this experimental study, 40 male mice were randomly allocated into 5 equal groups including: one control group, one sham group and three experimental groups. The experimental groups received 50, 100 and 150 mg/kg of aqueous extract of Datura Stramonium seed via gavage for 30 days, and the sham group received stilled water via gavage. Pentylenetetrazol (PTZ 35 mg/kg, i.p were injected into control, sham and experimental groups 30 minutes after gavage in order to induce the seizure. Then latency time of seizure onset, seizure duration and seizure phases were measured and recorded in the experimental, sham and control groups. The data analysis was carried out via one way ANOVA and Tukey post-hoc tests.  Moreover, difference less than 0.05 (P<0.05 was considered significant. Results: The study findings revealed that the aqueous extract of Datura Stramonium seed produced a significant effect on PTZ-induced seizure. In addition, Datura increases latency time of seizure onset (P˂0.01, inhibits progress of seizure stages (P˂0.05 and decreases seizure duration (P˂0.001. Conclusion: The results obtained from the present study indicated that extract of this plant has anticonvulsant effects on PTZ-induced seizure. As a result, it seems to be beneficial to the epilepsy treatment.

Effect of lamotrigine, oxcarbazepine and topiramate on cognitive functions and oxidative stress in PTZ-kindled mice.

Science.gov (United States)

Agarwal, Nidhi Bharal; Agarwal, Nitin Kumar; Mediratta, Pramod Kumari; Sharma, Krishna Kishore

2011-04-01

Cognitive impairment is frequently observed in epileptic patients. It has been seen that not only epilepsy but antiepileptic drugs also impair cognitive functions. The present study was undertaken to assess the effect of three anticonvulsants viz. lamotrigine (5mg/kg, p.o.), oxcarbazepine (15mg/kg, p.o.) and topiramate (10mg/kg, p.o.) on cognitive function and oxidative stress during pentylenetetrazole (PTZ)-kindling in mice. Kindling was induced by the administration of PTZ (25mg/kg, i.p.) on every alternate day till 5 weeks. Cognition was assessed after the development of kindling. Elevated plus maze (EPM) and passive avoidance response (PAR) tests were carried out after 24h and 48h of the last PTZ administration. After completion of behavioural tests malondialdehyde (MDA), glutathione levels, superoxide dismutase and catalase activity were measured as an indicator of oxidative stress. The results of the present study indicate that topiramate (10mg/kg) administration to kindled animals increased transfer latency and decreased step-down latency in EPM and PAR tests, respectively. However, lamotrigine and oxcarbazepine did not alter the two parameters. Topiramate administration to kindled as well as non-kindled animals has shown increase in MDA and decrease in glutathione levels. Lamotrigine and oxcarbazepine did not show significant alteration in oxidative stress parameters. To conclude, long term administration of topiramate impairs cognitive functions during experimental epilepsy while lamotrigine and oxcarbazepine are safer. Copyright © 2010 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Determination of feature generation methods for PTZ camera object tracking

Science.gov (United States)

Doyle, Daniel D.; Black, Jonathan T.

2012-06-01

Object detection and tracking using computer vision (CV) techniques have been widely applied to sensor fusion applications. Many papers continue to be written that speed up performance and increase learning of artificially intelligent systems through improved algorithms, workload distribution, and information fusion. Military application of real-time tracking systems is becoming more and more complex with an ever increasing need of fusion and CV techniques to actively track and control dynamic systems. Examples include the use of metrology systems for tracking and measuring micro air vehicles (MAVs) and autonomous navigation systems for controlling MAVs. This paper seeks to contribute to the determination of select tracking algorithms that best track a moving object using a pan/tilt/zoom (PTZ) camera applicable to both of the examples presented. The select feature generation algorithms compared in this paper are the trained Scale-Invariant Feature Transform (SIFT) and Speeded Up Robust Features (SURF), the Mixture of Gaussians (MoG) background subtraction method, the Lucas- Kanade optical flow method (2000) and the Farneback optical flow method (2003). The matching algorithm used in this paper for the trained feature generation algorithms is the Fast Library for Approximate Nearest Neighbors (FLANN). The BSD licensed OpenCV library is used extensively to demonstrate the viability of each algorithm and its performance. Initial testing is performed on a sequence of images using a stationary camera. Further testing is performed on a sequence of images such that the PTZ camera is moving in order to capture the moving object. Comparisons are made based upon accuracy, speed and memory.

Convulsions induced by centrally administered NMDA in mice: effects of NMDA antagonists, benzodiazepines, minor tranquilizers and anticonvulsants.

Science.gov (United States)

Moreau, J. L.; Pieri, L.; Prud'hon, B.

1989-01-01

1. Convulsions were induced reproducibly by intracerebroventricular injection of N-methyl-D-aspartic acid (NMDA) to conscious mice. 2. Competitive (carboxypiperazine-propylphosphonic acid, CPP; 2-amino-7-phosphonoheptanoic acid, AP7) and non-competitive (MK801; phencyclidine, PCP; thienylcyclohexylpiperidine, TCP; dextrorphan; dextromethorphan) NMDA antagonists prevented NMDA-induced convulsions. 3. Benzodiazepine receptor agonists and partial agonists (triazolam, diazepam, clonazepam, Ro 16-6028), classical anticonvulsants (diphenylhydantoin, phenobarbitone, sodium valproate) and meprobamate were also found to prevent NMDA-induced convulsions. 4. Flumazenil (a benzodiazepine receptor antagonist) and the GABA agonists THIP and muscimol (up to subtoxic doses) were without effect. 5. Flumazenil reversed the anticonvulsant action of diazepam, but not that of MK801. 6. Results obtained in this model differ somewhat from those described in a seizure model with systemic administration of NMDA. An explanation for this discrepancy is offered. 7. This model is a simple test for assessing the in vivo activity of NMDA antagonists and also expands the battery of chemically-induced seizure models for characterizing anticonvulsants not acting at NMDA receptors. PMID:2574061

Pharmacological evidence for GABAergic and glutamatergic involvement in the convulsant and behavioral effects of glutaric acid.

Science.gov (United States)

Lima, T T; Begnini, J; de Bastiani, J; Fialho, D B; Jurach, A; Ribeiro, M C; Wajner, M; de Mello, C F

1998-08-17

The effect of intrastriatal administration of glutaric acid (GTR), a metabolite that accumulates in glutaric acidemia type I (GA-I), on the behavior of adult male rats was investigated. After cannula placing, rats received unilateral intrastriatal injections of GTR buffered to pH 7.4 with NaOH or NaCl. GTR induced rotational behavior toward the contralateral side of injection and clonic convulsions in a dose-dependent manner. Rotational behavior was prevented by intrastriatal preadministration of DNQX and muscimol, but not by the preadministration of MK-801. Convulsions were prevented by intrastriatal preinjection of muscimol. This study provides evidence for a participation of glutamatergic non-NMDA and GABAergic mechanisms in the GTR-induced behavioral alterations. These findings may be of value in understanding the physiopathology of the neurological dysfunction in glutaric acidemia.

Epilepsy: MRI follow-up in paediatric convulsive status epilepticus

International Nuclear Information System (INIS)

Dulac, Olivier; Nabbout, Rima

2012-01-01

Convulsive status epilepticus (CSE)-defined as either a single convulsive seizure or a series of seizures without recovery of consciousness lasting for over 30 min - is a common disorder with an annual incidence of 18-20 cases per 100,000 people. CSE is primarily a disorder of infancy, observed in patients up to 4 years of age. (authors)

Epilepsy: MRI follow-up in paediatric convulsive status epilepticus

Energy Technology Data Exchange (ETDEWEB)

Dulac, Olivier; Nabbout, Rima [Paris Descartes Univ, Necker Enfants Malades Hosp, APHP, CEA, Inserm U1129, Neuropediat Dept, Orsay, (France)

2012-05-15

Convulsive status epilepticus (CSE)-defined as either a single convulsive seizure or a series of seizures without recovery of consciousness lasting for over 30 min - is a common disorder with an annual incidence of 18-20 cases per 100,000 people. CSE is primarily a disorder of infancy, observed in patients up to 4 years of age. (authors)

Effect of Brewer's Yeast-Induced Pyrexia on Aminophylline-Elicited Convulsions in Mice

OpenAIRE

Ochi, Rika; Suemaru, Katsuya; Kawasaki, Hiromu; Araki, Hiroaki

2009-01-01

Theophylline-associated convulsions have been observed most frequently in children with fever, but the mechanism is not fully understood. In this study, we investigated the basic mechanism of aminophylline [theophylline-2-ethylenediamine]-induced convulsions and the effects of Brewer's yeast-induced pyrexia in mice. Diazepam (5-10mg/kg, i.p.), a benzodiazepine receptor agonist, significantly prolonged the onset and significantly decreased the incidence of convulsions induced by aminophylline ...

Evaluation of central nervous system effects of Citrus limon essential oil in mice

Directory of Open Access Journals (Sweden)

Lidianne Mayra Lopes Campêlo

2011-05-01

Full Text Available The central nervous system (CNS depressant and anticonvulsant activities of Citrus limon (L. Osbeck, Rutaceae, essential oil (EO were investigated in animal models. The EO (50, 100 and 150 mg/kg injected by oral route (p.o. in mice caused a significant decrease in the motor activity of animals when compared with the control group, up to thirty days after the administration and the dose of 150 mg/kg significantly reduced the remaining time of the animals on the Rota-rod apparatus. Additionally, C. limon essential oil was also capable to promote an increase of latency for development of convulsions induced by pentylenetetrazole (PTZ. The administration of FLU (10 mg/kg, i.p., GABA A-benzodiazepine (GABA-BZD receptor antagonist, antagonized the effect of C. limon essential oil at higher dose. This C. limon essential oil was also capable to promote an increase of latency for development of convulsions induced by picrotoxin (PIC at higher dose. In the same way, the anticonvulsant effect of the EO was affected by pretreatment with flumazenil, a selective antagonist of benzodiazepine site of GABA A receptor. These results suggest a possible CNS depressant and anticonvulsant activities in mice that needs further investigation.

Protection against generalised seizured by Dalbergia saxatilis ...

African Journals Online (AJOL)

The aqueous root decoction of Dalbergia saxatilis (DS) is used to manage convulsive disorders in African herbal medicine practice. We had previously reported the anticonvulsant effects of the aqueous root extract of DS against strychnine and picrotoxin seizures. In this study, DS was tested against pentylenetetrazole (PTZ) ...

Two cases of glufosinate poisoning with late onset convulsions.

Science.gov (United States)

Tanaka, J; Yamashita, M; Yamashita, M; Matsuo, H; Yamamoto, T

1998-08-01

Glufosinate ammonium (GLA), the active ingredient in the non-selective herbicide BASTA (18.5% GLA), is a phosphinic acid analogue of glutamic acid. We report 2 cases of GLA poisoning with late onset convulsions and increased serum CK in spite of low blood concentrations of GLA after hemodialysis. A 69-y-old female was admitted to the emergency department after taking 500 ml of BASTA. On arrival she was conscious, and gut decontamination, hemodialysis and hemoperfusion were performed. However, 8 1/2 hours after ingestion, general convulsions occurred. Her serum OK increased to a peak of 24,900 IU/L on the third day of admission. An 87-y-old male was admitted to the emergency department 3 1/2 hours after taking 200 ml of BASTA and receiving gastric lavage at a local emergency room. On arrival he was conscious, and serial activated charcoal and hemodialysis was performed. Blood concentration of GLA after hemodialysis decreased from 1.56 micrograms/ml to 0.68 micrograms/ml. Thirty hours after admission he had general convulsions. GLA was not detected in the cerebrospinal fluid 6 h after the convulsions. His serum CK increased to a peak of 17,870 IU/L on the fifth day of admission.

Hypothermia for Neuroprotection in Convulsive Status Epilepticus.

Science.gov (United States)

Legriel, Stephane; Lemiale, Virginie; Schenck, Maleka; Chelly, Jonathan; Laurent, Virginie; Daviaud, Fabrice; Srairi, Mohamed; Hamdi, Aicha; Geri, Guillaume; Rossignol, Thomas; Hilly-Ginoux, Julia; Boisramé-Helms, Julie; Louart, Benjamin; Malissin, Isabelle; Mongardon, Nicolas; Planquette, Benjamin; Thirion, Marina; Merceron, Sybille; Canet, Emmanuel; Pico, Fernando; Tran-Dinh, Yves-Roger; Bedos, Jean-Pierre; Azoulay, Elie; Resche-Rigon, Matthieu; Cariou, Alain

2016-12-22

Convulsive status epilepticus often results in permanent neurologic impairment. We evaluated the effect of induced hypothermia on neurologic outcomes in patients with convulsive status epilepticus. In a multicenter trial, we randomly assigned 270 critically ill patients with convulsive status epilepticus who were receiving mechanical ventilation to hypothermia (32 to 34°C for 24 hours) in addition to standard care or to standard care alone; 268 patients were included in the analysis. The primary outcome was a good functional outcome at 90 days, defined as a Glasgow Outcome Scale (GOS) score of 5 (range, 1 to 5, with 1 representing death and 5 representing no or minimal neurologic deficit). The main secondary outcomes were mortality at 90 days, progression to electroencephalographically (EEG) confirmed status epilepticus, refractory status epilepticus on day 1, "super-refractory" status epilepticus (resistant to general anesthesia), and functional sequelae on day 90. A GOS score of 5 occurred in 67 of 138 patients (49%) in the hypothermia group and in 56 of 130 (43%) in the control group (adjusted common odds ratio, 1.22; 95% confidence interval [CI], 0.75 to 1.99; P=0.43). The rate of progression to EEG-confirmed status epilepticus on the first day was lower in the hypothermia group than in the control group (11% vs. 22%; odds ratio, 0.40; 95% CI, 0.20 to 0.79; P=0.009), but there were no significant differences between groups in the other secondary outcomes. Adverse events were more frequent in the hypothermia group than in the control group. In this trial, induced hypothermia added to standard care was not associated with significantly better 90-day outcomes than standard care alone in patients with convulsive status epilepticus. (Funded by the French Ministry of Health; HYBERNATUS ClinicalTrials.gov number, NCT01359332 .).

Analgesic and anticonvulsant effects of extracts from the leaves of Kalanchoe crenata (Andrews) Haworth (Crassulaceae).

Science.gov (United States)

Nguelefack, T B; Nana, P; Atsamo, A D; Dimo, T; Watcho, P; Dongmo, A B; Tapondjou, L A; Njamen, D; Wansi, S L; Kamanyi, A

2006-06-15

Kalanchoe crenata Andr. (Crassulaceae) is a fleshy herbaceous plant used in the African traditional medicine as remedies against otitis, headache, inflammations, convulsions and general debility. In the present work, the analgesic effects of methylene chloride/methanol (1:1) (CH(2)Cl(2)/CH(3)OH) extract and its hexane, methylene chloride (CH(2)Cl(2)), ethyl acetate, n-butanol fractions and aqueous residue have been evaluated using acetic acid, formalin and pressure test. The anticonvulsant effects of the CH(2)Cl(2)/CH(3)OH extract were also investigated on seizures induced by pentylenetetrazol (PTZ 70 mg/kg), strychnine sulphate (STN 2.5 mg/kg) and thiosemicarbazide (TSC 50 mg/kg). CH(2)Cl(2)/CH(3)OH extract and its fractions, administered orally at the doses of 150 and 300 mg/kg, exhibited protective effect of at least 30% on the pain induced by acetic acid. The CH(2)Cl(2) fraction at 300 mg/kg showed a maximal effect of 78.49%. The CH(2)Cl(2)/CH(3)OH extract and its CH(2)Cl(2) fraction at the doses of 150 and 300 mg/kg significantly reduced the first phase of pain induced by formalin while the second phase was completely inhibited. The CH(2)Cl(2) fraction produced more than 45% reduction in the sensitivity to pain induced by pressure. The CH(2)Cl(2)/CH(3)OH extract of Kalanchoe crenata significantly increased the latency period in seizures induced by PTZ and significantly reduced the duration of seizures induced by the three convulsant agents. The extract protected 20% of animals against death in seizures induced by TSC and STN. These results suggest a peripheral and central analgesic activities as well as an anticonvulsant effect of the leaves of Kalanchoe crenata.

Pharmacological screening of Malian medicinal plants used against epilepsy and convulsions

DEFF Research Database (Denmark)

Pedersen, Mikael E; Vestergaard, Henrik T; Hansen, Suzanne L

2009-01-01

Several medicinal plants are used in Mali to treat epilepsy and convulsions. So far, no studies have investigated the pharmacological effect of these plants.......Several medicinal plants are used in Mali to treat epilepsy and convulsions. So far, no studies have investigated the pharmacological effect of these plants....

Predictors of Outcome of Convulsive Status Epilepticus Among an Egyptian Pediatric Tertiary Hospital.

Science.gov (United States)

Halawa, Eman F; Draz, Iman; Ahmed, Dalia; Shaheen, Hala A

2015-11-01

Convulsive status epilepticus is a common neurologic emergency in pediatrics. We aimed to study the etiology, clinical features, and prognostic factors among pediatric patients with convulsive status epilepticus. Seventy patients were included in this cohort study from pediatric emergency department of the specialized Children Hospital of Cairo University. The outcome was evaluated using the Glasgow Outcome Score. Acute symptomatic etiology was the most common cause of convulsive status epilepticus. Refractory convulsive status epilepticus was observed more significantly in cases caused by acute symptomatic etiologies. The outcome was mortality in 26 (37.1%) patients, severe disability in 15 (21.4%), moderate disability in 17 (24.3%), and good recovery in 12 (17.1%) patients. The significant predictor of mortality was lower modified Glasgow Coma Scale score on admission, whereas lower modified Glasgow Coma Scale score on admission and refractory convulsive status epilepticus were the significant predictors for disability and mortality. © The Author(s) 2015.

Acute Systemic Complications of Convulsive Status Epilepticus-A Systematic Review.

Science.gov (United States)

Sutter, Raoul; Dittrich, Tolga; Semmlack, Saskia; Rüegg, Stephan; Marsch, Stephan; Kaplan, Peter W

2018-01-01

Status epilepticus is a neurologic emergency with high morbidity and mortality requiring neurointensive care and treatment of systemic complications. This systematic review compiles the current literature on acute systemic complications of generalized convulsive status epilepticus in adults and their immediate clinical impact along with recommendations for optimal neurointensive care. We searched PubMed, Medline, Embase, and the Cochrane library for articles published between 1960 and 2016 and reporting on systemic complications of convulsive status epilepticus. All identified studies were screened for eligibility by two independent reviewers. Key data were extracted using standardized data collection forms. Thirty-two of 3,046 screened articles were included. Acute manifestations and complications reported in association with generalized convulsive status epilepticus can affect all organ systems fueling complex cascades and multiple organ interactions. Most reported complications result from generalized excessive muscle contractions that increase body temperature and serum potassium levels and may interfere with proper and coordinated function of respiratory muscles followed by hypoxia and respiratory acidosis. Increased plasma catecholamines can cause a decay of skeletal muscle cells and cardiac function, including stress cardiomyopathy. Systemic complications are often underestimated or misinterpreted as they may mimic underlying causes of generalized convulsive status epilepticus or treatment-related adverse events. Management of generalized convulsive status epilepticus should center on the administration of antiseizure drugs, treatment of the underlying causes, and the attendant systemic consequences to prevent secondary seizure-related injuries. Heightened awareness, systematic clinical assessment, and diagnostic workup and management based on the proposed algorithm are advocated as they are keys to optimal outcome.

Attempt of differentiation acute encephalopathy with febrile convulsive status epilepticus from febrile convulsive status epilepticus induced by human herpesvirus 6 at early stage

International Nuclear Information System (INIS)

Ishikawa, Junichi; Yamamuro, Miho; Togawa, Masao; Shiomi, Masashi

2010-01-01

It is difficult for clinicians to predict the subsequent development of acute encephalopathy with febrile convulsive status epilepticus (AEFCSE), when febrile convulsive status epilepticus (FCSE) develops. Comparing clinical and laboratory characteristics between patients with AEFCSE and those with FCSE, we investigated the factors which predict the later development of febrile convulsive status caused by human herpesvirus 6 (HHV6). The subjects of this study were patients treated for FCSE or AEFCSE due to HHV6 in our hospital between April 2004 and January 2008. The AEFCSE group included 5 patients, and the FCSE group included 6 patients. There were few differences in clinical characteristics or brain images on admission between the 2 groups. Disturbance of consciousness persisted for 24 hours or more in all patients in the AEFCSE group and in 2 patients in the FCSE group. The serum creatinine concentration was significantly higher in the AEFCSE group. Serum creatinine concentration could be a good indicator for the prediction of AEFCSE in patients with FCSE. (author)

Attempt of differentiation acute encephalopathy with febrile convulsive status epilepticus from febrile convulsive status epilepticus induced by human herpesvirus 6 at early stage

Energy Technology Data Exchange (ETDEWEB)

Ishikawa, Junichi; Yamamuro, Miho; Togawa, Masao; Shiomi, Masashi [Osaka City General Hospital, Osaka, Osaka (Japan)

2010-07-15

It is difficult for clinicians to predict the subsequent development of acute encephalopathy with febrile convulsive status epilepticus (AEFCSE), when febrile convulsive status epilepticus (FCSE) develops. Comparing clinical and laboratory characteristics between patients with AEFCSE and those with FCSE, we investigated the factors which predict the later development of febrile convulsive status caused by human herpesvirus 6 (HHV6). The subjects of this study were patients treated for FCSE or AEFCSE due to HHV6 in our hospital between April 2004 and January 2008. The AEFCSE group included 5 patients, and the FCSE group included 6 patients. There were few differences in clinical characteristics or brain images on admission between the 2 groups. Disturbance of consciousness persisted for 24 hours or more in all patients in the AEFCSE group and in 2 patients in the FCSE group. The serum creatinine concentration was significantly higher in the AEFCSE group. Serum creatinine concentration could be a good indicator for the prediction of AEFCSE in patients with FCSE. (author)

Cardiac Arrest in Patients Managed for Convulsive Status Epilepticus: Characteristics, Predictors, and Outcome.

Science.gov (United States)

Legriel, Stephane; Bresson, Edouard; Deye, Nicolas; Grimaldi, David; Sauneuf, Bertrand; Lesieur, Olivier; Lascarrou, Jean-Baptiste; Argaud, Laurent; Chelly, Jonathan; Beuret, Pascal; Schnell, David; Chateauneuf, Anne-Laure; Holleville, Mathilde; Perier, François; Lemiale, Virginie; Bruel, Cedric; Cronier, Pierrick; Pichon, Nicolas; Mongardon, Nicolas; de-Prost, Nicolas; Dumas, Florence; Cariou, Alain

2018-05-08

Cardiac arrest is a catastrophic event that may arise during the management of convulsive status epilepticus. We aimed to report the clinical characteristics, outcomes, and early predictors of convulsive status epilepticus-related cardiac arrest. Retrospective multicenter study. Seventeen university or university affiliated participating ICUs in France and Belgium. Consecutive patients admitted to the participating ICUs for management of successfully resuscitated out-of-hospital cardiac arrest complicating the initial management of convulsive status epilepticus between 2000 and 2015. Patients were compared with controls without cardiac arrest identified in a single-center registry of convulsive status epilepticus patients, regarding characteristics, management, and outcome. None. We included 49 cases with convulsive status epilepticus-cardiac arrest and 235 controls. In the cases, median time from medical team arrival to cardiac arrest was 25 minutes (interquartile range, 5-85 min). First recorded rhythm was asystole in 25 patients (51%) and pulseless electrical activity in 13 patients (27%). A significantly larger proportion of patients had a favorable 1-year outcome (Glasgow Outcome Scale score of 5) among controls (90/235; 38%) than among cases (10/49; 21%; p = 0.02). By multivariate analysis, independent predictors of cardiac arrest were pulse oximetry less than 97% on scene (odds ratio, 2.66; 95% CI, 1.03-7.26; p = 0.04), drug poisoning as the cause of convulsive status epilepticus (odds ratio, 4.13; 95% CI, 1.27-13.53; p = 0.02), and complications during early management (odds ratio, 11.98; 95% CI, 4.67-34.69; p status epilepticus, relative hypoxemia, on-scene management complications, and drug poisoning as the cause of convulsive status epilepticus were strong early predictors of cardiac arrest, suggesting areas for improvement.

The novel δ opioid receptor agonist KNT-127 produces antidepressant-like and antinociceptive effects in mice without producing convulsions.

Science.gov (United States)

Saitoh, Akiyoshi; Sugiyama, Azusa; Nemoto, Toru; Fujii, Hideaki; Wada, Keiji; Oka, Jun-Ichiro; Nagase, Hiroshi; Yamada, Mitsuhiko

2011-10-01

We previously reported that the δ opioid receptor (DOP) agonists SNC80 and TAN-67 produce potent antidepressant-like and antinociceptive effects in rodents. However, SNC80 produced convulsive effects. Recently, we succeeded in synthesizing a novel DOP agonist called KNT-127. The present study examined the convulsive, antidepressant-like, and antinociceptive effects of KNT-127 in mice. In contrast to SNC80, KNT-127 produced no convulsions at doses of up to 100mg/kg. In mice subjected to the forced swim test, a screening model for antidepressants, KNT-127 (1mg/kg, s.c.) significantly decreased the duration of immobility and increased the duration of swimming without influencing spontaneous locomotor activity. These behavioral changes were similar to that observed for the tricyclic antidepressant imipramine (6mg/kg). The antidepressant-like effect of KNT-127 in mice was antagonized by pretreatment with naltrindole (NTI), a selective DOP antagonist, or naltriben, a putative DOP(2) subtype antagonist. In addition, KNT-127 (3mg/kg, s.c.) significantly reduced the number of acetic acid-induced abdominal constrictions and the duration of licking time, respectively, in mice subjected to a writhing test and a formalin test. These antinociceptive effects were antagonized by pretreatment with either NTI or 7-benzylidenenaltrexone, a putative DOP(1) subtype antagonist. We propose that KNT-127 should be considered as a candidate compound for the development of DOP-based antidepressants and/or analgesics that lack convulsive effects. Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.

Inhibition of CD38/Cyclic ADP-ribose Pathway Protects Rats against Ropivacaine-induced Convulsion

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Yu Zou

2017-01-01

Conclusions: The CD38/cADPR pathway is activated in ropivacaine-induced convulsion. Inhibiting this pathway alleviates ropivacaine-induced convulsion and protects the brain from apoptosis and oxidative stress.

Alcoholic epilepsy. A definition and a description of other convulsions related to alcoholism.

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Yamane, H; Katoh, N

1981-01-01

The role of alcohol intake and withdrawal in so-called alcoholic epilepsy is discussed and illustrated by case reports. A classification is made which includes definitions of withdrawal convulsions, tetany-like withdrawal convulsions and alcohol-induced epileptic fits, with or without predisposing features.

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

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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.

[3H]Ethynylbicycloorthobenzoate ([3H]EBOB) binding in recombinant GABAA receptors.

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Yagle, Monica A; Martin, Michael W; de Fiebre, Christopher M; de Fiebre, NancyEllen C; Drewe, John A; Dillon, Glenn H

2003-12-01

Ethynylbicycloorthobenzoate (EBOB) is a recently developed ligand that binds to the convulsant site of the GABAA receptor. While a few studies have examined the binding of [3H]EBOB in vertebrate brain tissue and insect preparations, none have examined [3H]EBOB binding in preparations that express known configurations of the GABAA receptor. We have thus examined [3H]EBOB binding in HEK293 cells stably expressing human alpha1beta2gamma2 and alpha2beta2gamma2 GABAA receptors, and the effects of CNS convulsants on its binding. The ability of the CNS convulsants to displace the prototypical convulsant site ligand, [35S]TBPS, was also assessed. Saturation analysis revealed [3H]EBOB binding at a single site, with a K(d) of approximately 9 nM in alpha1beta2gamma2 and alpha2beta2gamma2 receptors. Binding of both [3H]EBOB and [35S]TBPS was inhibited by dieldrin, lindane, tert-butylbicycloorthobenzoate (TBOB), PTX, TBPS, and pentylenetetrazol (PTZ) at one site in a concentration-dependent fashion. Affinities were in the high nM to low microM range for all compounds except PTZ (low mM range), and the rank order of potency for these convulsants to displace [3H]EBOB and [35S]TBPS was the same. Low [GABA] stimulated [3H]EBOB binding, while higher [GABA] (greater than 10 microM) inhibited [3H]EBOB binding. Overall, our data demonstrate that [3H]EBOB binds to a single, high affinity site in alpha1beta2gamma2 and alpha2beta2gamma2 GABAA receptors, and modulation of its binding is similar to that seen with [35S]TBPS. [3H]EBOB has a number of desirable traits that may make it preferable to [35S]TBPS for analysis of the convulsant site of the GABAA receptor.

Electro-Convulsive Therapy (ECT): an Egyptian perspective

African Journals Online (AJOL)

Adele

that has stood the test of time for over six decades like ECT. ... safety of ECT in the treatment of psychiatric disorders as well as determining its ... which needs to be changed since shock and convulsion are absent when giving modified ECT.

Anticonvulsant activity of the fractionated extract of Crinum jagus bulbs in experimental animals

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Azikiwe CCA

2012-05-01

Full Text Available Objective: To investigate the anticonvulsant activity of the bulbs of Crinum jagus in experimental animals. Methods: The uprooted bulbs were air dried for a week and ground into creamy-paste. 200g of paste was macerated each in 2 litres of water, ethanol and petroleum ether and filtered after 48 h. The obtained filtrates were each evaporated at the appropriate temperature to solid residue. The residues were further fractionated with successive changes of petroleum ether, ethyl acetate and n-butanol into a pooled filtrate which was further evaporated to dry solid brown-paste. Phytochemistry was carried out based on Treas and Evans method of 1987. The acute toxicity study (LD50 was carried based on Lorke ’s 1983 method. Convulsion was induced using maximum electric shock (MEST, pentylenetetrazole(PTZ, strychnine and Picrotoxin in the appropriate animal models. Seizures onset time and death time were used as successful induction of convulsion while prolongations of these features were taken as anticonvulsant activity. Results where possible, were statistically analyzed using SPSS-16.0 version. Results: The LD 50 was got at 1118.003mg/kg (IP in mice using Lorke ’s 1983 method. Fractionated extract of Crinum jagus exhibited dose dependent antiseizure against MEST induced seizure (P<0.001 and comparable to that of phenytoin, a standard anti generalized tonic-clonic seizure. There were also observable antiseizure activity of the fractionated extracts against PTZ, strychnine and Picrotoxin induced seizure and comparable to their standard corresponding antiseizures. Conclusions: We conclude that the bulbs of Crinum jagus possess proven broad spectrum antiseizure and perhaps antiepileptogenic activity thus justifies its use in traditional medicine. Clinical trial in man is recommended.

Lifelong consumption of sodium selenite: gender differences on blood-brain barrier permeability in convulsive, hypoglycemic rats.

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Seker, F Burcu; Akgul, Sibel; Oztas, Baria

2008-07-01

The aim of this study was to compare the effects of hypoglycemia and induced convulsions on the blood-brain barrier permeability in rats with or without lifelong administration of sodium selenite. There is a significant decrease of the blood-brain barrier permeability in three brain regions of convulsive, hypoglycemic male rats treated with sodium selenite when compared to sex-matched untreated rats (p0.05). The blood-brain barrier permeability of the left and right hemispheres of untreated, moderately hypoglycemic convulsive rats of both genders was better than their untreated counterparts (peffect against blood-brain barrier permeability during convulsions and that the effects of sodium selenite are gender-dependent.

Hippocampal Abnormalities after Prolonged Febrile Convulsions

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J Gordon Millichap

2003-11-01

Full Text Available Hippocampal volume and T2 relaxation times were determined in an MRI study of 14 children with prolonged febrile convulsions (PFC who were investigated, 1 within 5 days of a PFC, and 2 at follow-up 4-8 months after the acute study, at the Institute of Child Health, University College, and Great Ormond Street Hospital, London, UK.

The effect of PTZ-induced epileptic seizures on hippocampal expression of PSA-NCAM in offspring born to kindled rats

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Rajabzadeh Aliakbar

2012-05-01

Full Text Available Abstract Background Maternal epileptic seizures during pregnancy can affect the hippocampal neurons in the offspring. The polysialylated neural cell adhesion molecule (PSA-NCAM, which is expressed in the developing central nervous system, may play important roles in neuronal migration, synaptogenesis, and axonal outgrowth. This study was designed to assess the effects of kindling either with or without maternal seizures on hippocampal PSA-NCAM expression in rat offspring. Methods Forty timed-pregnant Wistar rats were divided into four groups: A Kind+/Seiz+, pregnant kindled (induced two weeks prior to pregnancy rats that received repeated intraperitoneal (i.p. pentylenetetrazol, PTZ injections on gestational days (GD 14-19; B Kind-/Seiz+, pregnant non-kindled rats that received PTZ injections on GD14-GD19; C Kind+/Seiz-, pregnant kindled rats that did not receive any PTZ injections; and D Kind-/Seiz-, the sham controls. Following birth, the pups were sacrificed on PD1 and PD14, and PSA-NCAM expression and localization in neonates’ hippocampi were analyzed by Western blots and immunohistochemistry. Results Our data show a significant down regulation of hippocampal PSA-NCAM expression in the offspring of Kind+/Seiz+ (p = 0.001 and Kind-/Seiz+ (p = 0.001 groups compared to the sham control group. The PSA-NCAM immunoreactivity was markedly decreased in all parts of the hippocampus, especially in the CA3 region, in Kind+/Seiz+ (p = 0.007 and Kind-/Seiz+ (p = 0.007 group’s newborns on both PD1 and 14. Conclusion Our findings demonstrate that maternal seizures but not kindling influence the expression of PSA-NCAM in the offspring’s hippocampi, which may be considered as a factor for learning/memory and cognitive impairments reported in children born to epileptic mothers.

OmniBird: a miniature PTZ NIR sensor system for UCAV day/night autonomous operations

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Yi, Steven; Li, Hui

2007-04-01

Through a SBIR funding from NAVAIR, we have successfully developed an innovative, miniaturized, and lightweight PTZ UCAV imager called OmniBird for UCAV taxiing. The proposed OmniBird will be able to fit in a small space. The designed zoom capability allows it to acquire focused images for targets ranging from 10 to 250 feet. The innovative panning mechanism also allows the system to have a field of view of +/- 100 degrees within the provided limited spacing (6 cubic inches). The integrated optics, camera sensor, and mechanics solution will allow the OmniBird to stay optically aligned and shock-proof under harsh environments.

Perioperative anaesthetic adverse events in Thailand (PAAd THAI) study: Incident report of perioperative convulsion.

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Eiamcharoenwit, Jatuporn; Akavipat, Phuping; Ariyanuchitkul, Thidarat; Wirachpisit, Nichawan; Pulnitiporn, Aksorn; Pongraweewan, Orawan

2018-01-01

The aim of this study was to identify the characteristics of perioperative convulsion and to suggest possible correcting strategies. The multi-centre study was conducted prospectively in 22 hospitals across Thailand in 2015. The occurrences of perioperative adverse events were collected. The data was collated by site manager and forwarded to the data management unit. All perioperative convulsion incidences were enrolled and analysed. The consensus was documented for the relevant factors and the corrective strategies. Descriptive statistics were used. From 2,000 incident reports, perioperative convulsions were found in 16 patients. Six episodes (37.5%) were related to anaesthesia, 31.3% to patients, 18.8% to surgery, and 12.5% to systemic processes. The contributing factor was an inexperienced anaesthesia performer (25%), while the corrective strategy was improvements to supervision (43.8%). Incidents of perioperative convulsion were found to be higher than during the last decade. The initiation and maintenance of safe anaesthesia should be continued.

Gammabenzene hexachloride-induced convulsions in an HIV positive individual

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Panvelkar V

1996-01-01

Full Text Available A case report of chancroid with scabies with HIV positivity is being presented. The individual was treated with 1% gamma benzene hexachloride for scabies and developed convulsions.

Automatic detection of non-convulsive seizures: A reduced complexity approach

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Tazeem Fatma

2016-10-01

Full Text Available Detection of non-convulsive seizures (NCSz is a challenging task because they lack convulsions, meaning no physical visible symptoms are there to detect the presence of a seizure activity. Hence their diagnosis is not easy, also continuous observation of full length EEG for the detection of non-convulsive seizures (NCSz by an expert or a technician is a very exhaustive, time consuming job. A technique for the automatic detection of NCSz is proposed in this paper. The database used in this research was recorded at the All India Institute of Medical Sciences (AIIMS, New Delhi. 13 EEG recordings of 9 subjects consisting of a total 23 seizures of 29.42 min duration were used for analysis. Normalized modified Wilson amplitude is used as a key feature to classify between normal and seizure activity. The main advantage of this study lies in the fact that no classifier is used here and hence algorithm is very simple and computationally fast. With the use of only one feature, all of the seizures under test were detected correctly, and hence the median sensitivity and specificity of 100% and 99.21% were achieved respectively.

Protection against soman-induced seizures in rats: relationship among doses of prophylactics, soman, and adjuncts

International Nuclear Information System (INIS)

Myhrer, Trond; Nguyen, Nga H.T.; Andersen, Jannike M.; Aas, Paal

2004-01-01

The combined effects of physostigmine and procyclidine (antagonizing muscarinic, nicotinic, and NMDA receptors) were tested against various doses of soman. Physostigmine (0.1 mg/kg) in combination with procyclidine doses of 1, 3, or 6 mg/kg effectively prevented the development of convulsions and hippocampally monitored seizures when the doses of soman were 1.3, 1.6, or 2 x LD50, respectively. Results from [ 3 H]MK-801-binding experiments showed that procyclidine inhibits the phencyclidine site at the NMDA receptor in a concentration-dependent manner. Physostigmine (0.1 mg/kg) and procyclidine in a dose of 1 mg/kg did not prevent convulsions or seizures when the soman dose was 1.6 x LD50. Subsequent treatment with scopolamine in doses of 0.5 or 1 mg/kg immediately after (3 min) seizure onset showed that only the highest dose produced a reliable termination. When scopolamine (1 mg/kg) was given later (10 min) after onset of seizures, no effect was obtained. The sustained seizures were subsequently treated with diazepam (10 mg/kg) and pentobarbital (30 mg/kg) and finally terminated 25 min after onset. In rats given inadequate prophylaxis, both modified convulsions and seizures were seen. It is suggested that moderate doses of prophylactics should be preferred to avoid adverse effects on cognitive functions because insufficient prophylaxis can be compensated for by adjunct treatment

Time-Dependent Decline in Serum Phenytoin Concentration with Heightened Convulsive Seizure Risk by Prolonged Administration of Fosphenytoin in Japanese: A Retrospective Study.

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Ohno, Yuta; Niwa, Takashi; Hirai, Keita; Suzuki, Keiko; Yamada, Yuto; Hayashi, Yuichi; Hayashi, Hideki; Suzuki, Akio; Itoh, Yoshinori

2018-04-20

Because clinical data to confirm the safety and effectiveness of fosphenytoin, a prodrug of phenytoin, are insufficient, the length of administration of fosphenytoin is restricted. Nevertheless, some cases require fosphenytoin administration for more than a few days. The aim of this study was to retrospectively investigate the serum concentration of phenytoin in adult Japanese patients who received intravenous fosphenytoin therapy for more than 3 days. Patients injected with intravenous fosphenytoin for more than 3 days at Gifu University Hospital between January 2012 and September 2014 were enrolled. Individual pharmacokinetic parameters were predicted by Bayesian estimation using NONMEM software, and the maintenance dose of fosphenytoin required to maintain the therapeutic trough concentration (10-20 μg/mL) was calculated from the parameters. Among a total of 8 patients, the serum trough concentration of phenytoin decreased with each day after repeated injection of fosphenytoin. The incidence rate of significant convulsive seizures was increased time-dependently (0% on day 1, 12.5% on day 2, 25% on day 3, and 66.7% on day 4 and after). Phenytoin clearance showed a time-dependent increase. The maintenance dose of fosphenytoin required to maintain the therapeutic trough concentration was simulated to be 779.8 ± 316.8 mg/day, a dose that was markedly higher than the actual maintenance dose (414.1 ± 55.7 mg/day). Prolonged use of fosphenytoin for such patients as those with autoimmune-mediated encephalopathy accompanied with reflux disease and/or ileus time-dependently decreased the serum concentration of phenytoin and increased the risk of convulsion. Therefore, the maintenance dose should be increased to maintain the therapeutic serum concentration.

Anticonvulsant Effect of the Aqueous Extract and Essential Oil of Carum Carvi L. Seeds in a Pentylenetetrazol Model of Seizure in Mice

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Showraki, Alireza; Emamghoreishi, Masoumeh; Oftadegan, Somayeh

2016-01-01

Background: Carum carvi L. (caraway), known as black zeera in Iran, has been indicated for the treatment of epilepsy in Iranian folk medicine. This study evaluated whether the aqueous extract and essential oil of caraway seeds have anticonvulsant effects in mice. Methods: The anticonvulsant effects of the aqueous extract (200, 400, 800, 1600, and 3200 mg/kg, i.p.) and essential oil (25, 50, 100, 200, and 400 mg/kg, i.p.) of caraway were assessed using pentylenetetrazol (PTZ; 95 mg/kg i.p.) induced convulsions. Diazepam (3 mg/kg) was used as positive control. The latency time before the onset of myoclonic, clonic, and tonic convulsions and the percentage of mortality were recorded. In addition, the effect of caraway on neuromuscular coordination was evaluated using the rotarod performance test. Results: The extract and essential oil dose-dependently increased the latency time to the onset of myoclonic (ED50, 1257 and 62.2 mg/kg, respectively) and clonic (ED50, 929 and 42.3 mg/kg, respectively) seizures. The extract and essential oil of caraway prevented the animals from tonic seizure with ED50s of 2142.4 and 97.6 mg/kg, respectively. The extract and essential oil of caraway protected 28.6 and 71.4% of the animals from PTZ-induced death, respectively, and had no significant effect on neuromuscular coordination. Conclusion: This study showed that the aqueous extract and essential oil of caraway had anticonvulsant properties. However, the essential oil was more potent and effective than was the aqueous extract as an anticonvulsant. Additionally, the anticonvulsant effect of caraway was not due to a muscle relaxant activity. These findings support the acclaimed antiepileptic effect of caraway in folk medicine and propose its potential use in petit mal seizure in humans. PMID:27217604

Inhibitor effect of dexketoprofen in rat model of pentylenetetrazol-induced seizures.

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Erbaş, Oytun; Solmaz, Volkan; Aksoy, Dürdane

2015-01-01

The relationship between epilepsy and inflammation is known, and it has been reported that there is an increase in cyclooxygenase (COX) levels in epilepsy. We aim to reveal the anticonvulsant effects of dexketoprofen in pentylenetetrazol (PTZ)-induced seizures in rats. Forty-eight male Sprague-Dawley rats, 24 of them for EEG recording and 24 of them are for behavioral studies, were randomly divided in two groups: Group A for EEG recordings and Group B for behavioral assessment. A weight of 70 mg/kg PTZ was used for behavioral studies after dexketoprofen administration. Thirty-five milligrams per kilogram PTZ were used for EEG recording after dexketoprofen administration. The electrodes were implanted on dura over the left frontal cortex and the reference electrode was implanted over the cerebellum for EEG recording. The Racine convulsion scale (RCS), first myoclonic jerk (FMJ) onset time, and spike percentages were evaluated between the two groups. There was a significant (PDexketoprofen has an antiepileptic feature and this effect increases as the dosage increases, however it is currently unknown through which mechanism this drug shows its anticonvulsant effect. Dexketoprofen, in the group of NSAIDs, shows an anticonvulsant effect on PTZ-induced epilepsy model. This study suggests that dexketoprofen can preferably be used with NSAIDs for epileptic patients in clinical practice.

Behavioral and electroencephalographic evaluation of the anticonvulsive activity of Moringa oleifera leaf non-polar extracts and one metabolite in PTZ-induced seizures.

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González-Trujano, María Eva; Martínez-González, Claudia Lizbeth; Flores-Carrillo, Maricela; Luna-Nophal, Sara Ibeth; Contreras-Murillo, Gerardo; Magdaleno-Madrigal, Víctor Manuel

2018-01-15

Moringa oleifera Lamarck is a species that has long been used in high demand in folk medicine, including for the treatment of epilepsy. Nevertheless, scientific studies demonstrating its anticonvulsant properties and the nature of the bioactive constituents are lacking. The aim of this study was to evaluate the anticonvulsant activities of the Moringa oleifera leaves in non-polar vs. polar extracts using behavioral and electroencephalographic (EEG) analyses in rodents. First, PTZ (80 mg/kg, i.p.)-induced tonic-clonic seizures were assayed via a dose-response (100, 200 and 300 mg/kg, i.p.) evaluation in mice. Then, a dosage of the extracts (100 or 300 mg/kg) and one metabolite (30 mg/kg, i.p.) was selected to evaluate its effect on PTZ (35 mg/kg, i.p.)-induced EEG paroxystic activities in rats compared to the effects of ethosuximide (reference anticonvulsant drug, 100 mg/kg, i.p.). Latent onset of the first paroxystic spike, first seizure and frequency as well as seizure severity, were determined using Racine's scale. Moringa oleifera ethanol and hexane extracts produced a delay in the seizure latency in mice and rats; this effect was improved in the presence of the hexane extract containing the active metabolite hexadecanoic acid. The anticonvulsant effects were corroborated in the spectral analysis by the potency of the EEG due to a reduction in the spike frequency and amplitude, as well as in the duration and severity of the seizures. The effects of the hexane extract resembled those observed in the reference antiepileptic drug ethosuximide. Moringa oleifera leaves possess anticonvulsant activities due to the complementary of the non-polar and polar constituents. However, the non-polar constituents appear to exert an important influence via the partial participation of fatty acids, providing evidence of the effects of this plant in epilepsy therapy. Copyright © 2017. Published by Elsevier GmbH.

Serum zinc and copper levels in children with febrile convulsion

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Mohammad Shokrzadeh

2016-09-01

Full Text Available Febrile convulsions (FC are the most common neurologic disorder in children 6-60 months of age. Zinc (Zn and copper (Cu play role as cofactors in more than 300 enzymatic activities significantly. The aim of this study was to evaluate the relationship serum levels of Zn and Cu with seizure occurrence in febrile children. In this case-control study, 270 children with 6 month to 6 years were evaluated. The patients were enrolled in three groups: a children with febrile convulsion, b febrile children without convulsion and c healthy ones. After recording of all patients’ characteristics, 5 mL blood was taken from peripheral vessels at the first 12 hours of hospitalization. Absorption of all samples was read by BRAIC (Rayleigh instrument company, WFX-130 model with calibration diagram, considering samples dilution levels. The mean of serum Zn levels in children with FC were significantly lower than other two groups. Mean serum Cu levels in children with FC and non-FC patients were significantly higher than healthy children. No meaningful differences were observed in serum levels of Zn and Cu among the girl or boy cases. This study showed significant lower serum zinc level in children with febrile seizure and meaningful higher serum copper level than control group cases. There was no significant difference in level of serum zinc and copper in term of sex.

Evidence for involvement of the astrocytic benzodiazepine receptor in the mechanism of action of convulsant and anticonvulsant drugs

International Nuclear Information System (INIS)

Bender, A.S.; Hertz, L.

1988-01-01

The anticonvulsant drugs carbamazepine, phenobarbital, trimethadione, valproic acid and ethosuximide at pharmacologically relevant concentrations inhibit [ 3 H]diazepam binding to astrocytes in primary cultures but have much less effect on a corresponding preparation of neurons. Phenytoin as well as pentobarbital (which is not used chronically as an anticonvulsant) are equipotent in the two cell types. The convulsants picrotoxinin and pentylenetetrazol, the convulsant benzodiazepine RO 5-3663 and the two convulsant barbiturates DMBB and CHEB similarly inhibit diazepam binding to astrocytes but have little effect on neurons. On the basis of these findings it is suggested that these convulsants and anticonvulsants owe at least part of their effect to an interaction with the astrocytic benzodiazepine receptor, perhaps by interference with a calcium channel

Multicenter clinical assessment of improved wearable multimodal convulsive seizure detectors.

Science.gov (United States)

Onorati, Francesco; Regalia, Giulia; Caborni, Chiara; Migliorini, Matteo; Bender, Daniel; Poh, Ming-Zher; Frazier, Cherise; Kovitch Thropp, Eliana; Mynatt, Elizabeth D; Bidwell, Jonathan; Mai, Roberto; LaFrance, W Curt; Blum, Andrew S; Friedman, Daniel; Loddenkemper, Tobias; Mohammadpour-Touserkani, Fatemeh; Reinsberger, Claus; Tognetti, Simone; Picard, Rosalind W

2017-11-01

New devices are needed for monitoring seizures, especially those associated with sudden unexpected death in epilepsy (SUDEP). They must be unobtrusive and automated, and provide false alarm rates (FARs) bearable in everyday life. This study quantifies the performance of new multimodal wrist-worn convulsive seizure detectors. Hand-annotated video-electroencephalographic seizure events were collected from 69 patients at six clinical sites. Three different wristbands were used to record electrodermal activity (EDA) and accelerometer (ACM) signals, obtaining 5,928 h of data, including 55 convulsive epileptic seizures (six focal tonic-clonic seizures and 49 focal to bilateral tonic-clonic seizures) from 22 patients. Recordings were analyzed offline to train and test two new machine learning classifiers and a published classifier based on EDA and ACM. Moreover, wristband data were analyzed to estimate seizure-motion duration and autonomic responses. The two novel classifiers consistently outperformed the previous detector. The most efficient (Classifier III) yielded sensitivity of 94.55%, and an FAR of 0.2 events/day. No nocturnal seizures were missed. Most patients had seizure frequency. When increasing the sensitivity to 100% (no missed seizures), the FAR is up to 13 times lower than with the previous detector. Furthermore, all detections occurred before the seizure ended, providing reasonable latency (median = 29.3 s, range = 14.8-151 s). Automatically estimated seizure durations were correlated with true durations, enabling reliable annotations. Finally, EDA measurements confirmed the presence of postictal autonomic dysfunction, exhibiting a significant rise in 73% of the convulsive seizures. The proposed multimodal wrist-worn convulsive seizure detectors provide seizure counts that are more accurate than previous automated detectors and typical patient self-reports, while maintaining a tolerable FAR for ambulatory monitoring. Furthermore, the multimodal system

Unconstrained Iris Acquisition and Recognition Using COTS PTZ Camera

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Venugopalan Shreyas

2010-01-01

Full Text Available Abstract Uniqueness of iris patterns among individuals has resulted in the ubiquity of iris recognition systems in virtual and physical spaces, at high security facilities around the globe. Traditional methods of acquiring iris patterns in commercial systems scan the iris when an individual is at a predetermined location in front of the scanner. Most state-of-the-art techniques for unconstrained iris acquisition in literature use expensive custom equipment and are composed of a multicamera setup, which is bulky, expensive, and requires calibration. This paper investigates a method of unconstrained iris acquisition and recognition using a single commercial off-the-shelf (COTS pan-tilt-zoom (PTZ camera, that is compact and that reduces the cost of the final system, compared to other proposed hierarchical multicomponent systems. We employ state-of-the-art techniques for face detection and a robust eye detection scheme using active shape models for accurate landmark localization. Additionally, our system alleviates the need for any calibration stage prior to its use. We present results using a database of iris images captured using our system, while operating in an unconstrained acquisition mode at 1.5 m standoff, yielding an iris diameter in the 150–200 pixels range.

Anticonvulsant properties of the total alkaloid fraction of Rauvolfia ligustrina Roem. et Schult. in male mice

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Lucindo J. Quintans-Júnior

Full Text Available Rauvolfia ligustrina Roem et. Schult (Apocynaceae, commonly known as "paratudo" and "arrebenta-boi" is a small tree found in Brazilian Northeastern. Previous studies have demonstrated depressant and anticonvulsant properties of the ethanol extract of Rauvolfia ligustrina. The aim of the present study was the determination of the lethal dose 50% (LD50 and the effects of total alkaloid fraction (TAF of the aerial parts of R. ligustrina in animal models of convulsion. It was found that the acute toxicity of TAF was 127.8 (112.5-145.2 mg/kg (i.p. in mice. TAF (20 mg/kg, ip significantly increased (p < 0.05 the latencies of clonic seizures induced by pentylenetetrazol (PTZ and picrotoxin (PIC. However, TAF did not protect the animals in maximal electroshock (MES induced seizures. These results suggest that TAF of R. ligustrina possesses anticonvulsant properties.

Anticonvulsant, neuroprotective and behavioral effects of organic and conventional yerba mate (Ilex paraguariensis St. Hil.) on pentylenetetrazol-induced seizures in Wistar rats.

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Branco, Cátia Dos Santos; Scola, Gustavo; Rodrigues, Adriana Dalpicolli; Cesio, Verónica; Laprovitera, Mariajosé; Heinzen, Horacio; Dos Santos, Maitê Telles; Fank, Bruna; de Freitas, Suzana Cesa Vieira; Coitinho, Adriana Simon; Salvador, Mirian

2013-03-01

Epilepsy, which is one of the most common neurological disorders, involves the occurrence of spontaneous and recurrent seizures that alter the performance of the brain and affect several sensory and behavioral functions. Oxidative damage has been associated with post-seizure neuronal injury, thereby increasing an individual's susceptibility to the occurrence of neurodegenerative disorders. The present study investigated the possible anticonvulsive and neuroprotective effects of organic and conventional yerba mate (Ilex paraguariensis), a plant rich in polyphenols, on pentylenetetrazol (PTZ)-induced seizures in Wistar rats. The behavioral and polyphenolic profiles of the yerba mate samples were also evaluated. Infusions of yerba mate (50mg/kg) or distilled water were given to rats for fifteen days by oral gavage. On the 15th day the animals were subjected to open field test, and exploratory behavior was assessed. Subsequently, 60mg/kg PTZ (i.p.) was administered, and animals were observed for the appearance of convulsions for 30min. Latency for the first seizure, tonic-clonic and generalized seizures time, frequency of seizures and mortality induced by PTZ were recorded. The animals were then sacrificed, and the cerebellum, cerebral cortex and hippocampus were quickly removed and frozen to study the neuroprotective effects of yerba mate. The oxidative damage in lipids and proteins, nitric oxide levels, the activities of the antioxidant enzymes superoxide dismutase (Sod) and catalase (Cat) and non-enzymatic cellular defense (sulfhydryl protein) were quantified in all the tissues. The results showed that organic and conventional yerba mate infusions were able to reduce the frequency of seizures when compared to the PTZ group. Besides, organic yerba mate infusion decreases the tonic-clonic seizures time in relation to the PTZ group. It was also shown that organic and conventional yerba mate infusions reduced the oxidative damage in lipids and proteins and nitric oxide

Prevalence and risk factors for Active Convulsive Epilepsy in ...

African Journals Online (AJOL)

Introduction: epilepsy is common in sub-Saharan Africa, but there is little data in West Africa, to develop public health measures for epilepsy in this region. Methods: we conducted a three-stage cross-sectional survey to determine the prevalence and risk factors for active convulsive epilepsy (ACE), and estimated the ...

Cerebral edema induced in mice by a convulsive dose of soman. Evaluation through diffusion-weighted magnetic resonance imaging and histology

International Nuclear Information System (INIS)

Testylier, Guy; Lahrech, Hana; Montigon, Olivier; Foquin, Annie; Delacour, Claire; Bernabe, Denis; Segebarth, Christoph; Dorandeu, Frederic; Carpentier, Pierre

2007-01-01

Purpose: In the present study, diffusion-weighted magnetic resonance imaging (DW-MRI) and histology were used to assess cerebral edema and lesions in mice intoxicated by a convulsive dose of soman, an organophosphate compound acting as an irreversible cholinesterase inhibitor. Methods: Three hours and 24 h after the intoxication with soman (172 μg/kg), the mice were anesthetized with an isoflurane/N 2 O mixture and their brain examined with DW-MRI. After the imaging sessions, the mice were sacrificed for histological analysis of their brain. Results: A decrease in the apparent diffusion coefficient (ADC) was detected as soon as 3 h after the intoxication and was found strongly enhanced at 24 h. A correlation was obtained between the ADC change and the severity of the overall brain damage (edema and cellular degeneration): the more severe the damage, the stronger the ADC drop. Anesthesia was shown to interrupt soman-induced seizures and to attenuate edema and cell change in certain sensitive brain areas. Finally, brain water content was assessed using the traditional dry/wet weight method. A significant increase of brain water was observed following the intoxication. Conclusions: The ADC decrease observed in the present study suggests that brain edema in soman poisoning is mainly intracellular and cytotoxic. Since entry of water into Brain was also evidenced, this type of edema is certainly mixed with others (vasogenic, hydrostatic, osmotic). The present study confirms the potential of DW-MRI as a non-invasive tool for monitoring the acute neuropathological consequences (edema and neurodegeneration) of soman-induced seizures

Short-term outcomes and major barriers in the management of convulsive status epilepticus in children: a study in Georgia.

Science.gov (United States)

Shatirishvili, Teona; Kipiani, Tamar; Lomidze, Giorgi; Gabunia, Maia; Tatishvili, Nino

2015-09-01

Convulsive status epilepticus is the most common childhood neurological emergency in developing countries, where poor healthcare organisation could play a negative role in the management of the condition. Unavailability of second-line injectable anticonvulsants is an additional hindering factor in Georgia. This report reflects the results of the first study aimed at evaluating the epidemiological features of convulsive status epilepticus, as well as identifying obstacles influencing the management of patients with convulsive status epilepticus in Georgia. A prospective, hospital-based study was performed. Paediatric patients with convulsive status epilepticus, admitted to the emergency department of a referral academic hospital from 2007 to 2012, were included in the study. Forty-eight paediatric patients admitted to hospital met the criteria for convulsive status epilepticus. Seizure duration was significantly shorter among the group with adequate and timely pre-hospital intervention. Moreover, patients with appropriate pre-hospital treatment less frequently required mechanical ventilation (p=0.039). Four deaths were detected during the follow-up period, thus the case fatality rate was 8%. Only 31% of patients received treatment with intravenous phenytoin. The study results show that adequate and timely intervention could improve outcome of convulsive status epilepticus and decrease the need for mechanical ventilation. Mortality parameters were comparable to the results from other resource-limited countries. More than one third of patients did not receive appropriate treatment due to unavailability of phenytoin.

Binding interactions of convulsant and anticonvulsant gamma-butyrolactones and gamma-thiobutyrolactones with the picrotoxin receptor

International Nuclear Information System (INIS)

Holland, K.D.; McKeon, A.C.; Covey, D.F.; Ferrendelli, J.A.

1990-01-01

Alkyl-substituted gamma-butyrolactones (GBLs) and gamma-thiobutyrolactones (TBLs) are neuroactive chemicals. beta-Substituted compounds are convulsant, whereas alpha-alkyl substituted GBLs and TBLs are anticonvulsant. The structural similarities between beta-alkyl GBLs and the convulsant picrotoxinin suggested that alkyl substituted GBLs and TBLs act at the picrotoxin receptor. To test this hypothesis we examined the interactions of convulsant and anticonvulsant GBLs and TBLs with the picrotoxin, benzodiazepine and gamma-aminobutyric acid (GABA) binding sites of the GABA receptor complex. All of these convulsants and anticonvulsants studied competitively displaced 35S-t-butylbicyclophosphorothionate (35S-TBPS), a ligand that binds to the picrotoxin receptor. This inhibition of 35S-TBPS binding was not blocked by the GABA antagonist bicuculline methobromide. The convulsant GBLs and TBLs also partially inhibited [3H]muscimol binding to the GABA site and [3H]flunitrazepam binding to the benzodiazepine site, but they did so at concentrations substantially greater than those that inhibited 35S-TBPS binding. The anticonvulsant GBLs and TBLs had no effect on either [3H]muscimol or [3H]flunitrazepam binding. In contrast to the GBLs and TBLs, pentobarbital inhibited TBPS binding in a manner that was blocked by bicuculline methobromide, and it enhanced both [3H]flunitrazepam and [3H]muscimol binding. Both ethosuximide and tetramethylsuccinimide, neuroactive compounds structurally similar to GBLs, competitively displaced 35S-TBPS from the picrotoxin receptor and both compounds were weak inhibitors of [3H] muscimol binding. In addition, ethosuximide also partially diminished [3H]flunitrazepam binding. These data demonstrate that the site of action of alkyl-substituted GBLs and TBLs is different from that of GABA, barbiturates and benzodiazepines

Evaluation of the anticonvulsant activity of the essential oil of Myrothamnus moschatus in convulsion induced by pentylenetetrazole and picrotoxin

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Emmanuel Randrianarivo

2016-06-01

Conclusions: The results confirmed at least partly the traditional uses of the smoke of M. moschatus for the management of convulsion, and implied that the essential oil may inhibit the convulsion by GABAergic neuromodulation.

Epilepsy is associated with ventricular alterations following convulsive status epilepticus in children.

Science.gov (United States)

Ali, Wail; Bubolz, Beth A; Nguyen, Linh; Castro, Danny; Coss-Bu, Jorge; Quach, Michael M; Kennedy, Curtis E; Anderson, Anne E; Lai, Yi-Chen

2017-12-01

Convulsive status epilepticus can exert profound cardiovascular effects in adults including ventricular depolarization-repolarization abnormalities. Whether status epilepticus adversely affects ventricular electrical properties in children is less understood. Therefore, we sought to characterize ventricular alterations and the associated clinical factors in children following convulsive status epilepticus. We conducted a 2-year retrospective, case-control study. Children between 1 month and 21 years of age were included if they were admitted to the pediatric intensive care unit with primary diagnosis of convulsive status epilepticus and had 12-lead electrocardiogram (ECG) within 24 hours of admission. Children with heart disease, ion channelopathy, or on vasoactive medications were excluded. Age-matched control subjects had no history of seizures or epilepsy. The primary outcome was ventricular abnormalities represented by ST segment changes, abnormal T wave, QRS axis deviation, and corrected QT (QTc) interval prolongation. The secondary outcomes included QT/RR relationship, beat-to-beat QTc interval variability, ECG interval measurement between groups, and clinical factors associated with ECG abnormalities. Of 317 eligible children, 59 met the inclusion criteria. History of epilepsy was present in 31 children (epileptic) and absent in 28 children (non-epileptic). Compared with the control subjects (n = 31), the status epilepticus groups were more likely to have an abnormal ECG with overall odds ratio of 3.8 and 7.0 for the non-epileptic and the epileptic groups respectively. Simple linear regression analysis demonstrated that children with epilepsy exhibited impaired dependence and adaptation of the QT interval on heart rate. Beat-to-beat QTc interval variability, a marker of ventricular repolarization instability, was increased in children with epilepsy. Convulsive status epilepticus can adversely affect ventricular electrical properties and stability in children

Preliminary Screening of a Classical Ayurvedic Formulation for Anticonvulsant Activity.

Science.gov (United States)

Dhar, Arnab; Maurya, Santosh Kumar; Mishra, Ashish; Singh, Gireesh Kumar; Singh, Manoj Kumar; Seth, Ankit

2016-01-01

Epilepsy is a serious and complex central nervous system disorder associated with recurrent episodes of convulsive seizures due to the imbalance between excitatory (glutamatergic) and inhibitory (GABAergic) neurotransmitters level in the brain. The available treatments are neither competent to control the seizures nor prevent progress of disease. Since ages, Herbal medicines have remained important sources of medicines in many parts of world which is evidenced through their uses in traditional systems of medicine i.e. Ayurveda, Siddha, Unani, Homeopathy and Chinese etc. A polyherbal formulation (containing Terminalia chebula Retz., Asparagus racemosus Willd., Embelia ribes Burm. F, Acorus calamus L., Tinospora cordifolia (Willd.) Miers, Convolvulus pluricaulis Choisy, Saussurea lappa C.B.Clarke, Achyranthes aspera L.) is mentioned in Ayurvedic classics Bhaiṣajya Ratnāvali . The aim of the study was to evaluate the anticonvulsant activity of the formulation in Maximum electroshock and Pentylenetetrazole induced convulsions in rats. In the present study, a polyherbal formulation was developed as directed by classical text and evaluated for the anticonvulsant activity using Maximal Electroshock Shock (MES) and Pentylenetetrazole (PTZ) induced convulsions in rats. Statistical comparison was done by one way ANOVA followed by the Tukey's multiple comparison test. The obtained results showed that the PHF had a protective role on epilepsy. Treatment with PHF significantly improves antioxidant enzymes activities of superoxide dismutase (SOD) and glutathione (GSH) levels significantly as compared to controls. PHF also significantly decreased malonaldialdehyde (MDA) levels in the brain. Moreover, it also attenuated the PTZ-induced increase in the activity of GABA-T in the rat brain. These findings suggest that PHF might have possible efficacy in the treatment of epilepsy.

Epidemiology of Pediatric Convulsive Status Epilepticus With Fever in the Emergency Department: A Cohort Study of 381 Consecutive Cases.

Science.gov (United States)

Hayakawa, Itaru; Miyama, Sahoko; Inoue, Nobuaki; Sakakibara, Hiroshi; Hataya, Hiroshi; Terakawa, Toshiro

2016-09-01

Pediatric convulsive status epilepticus with fever is common in the emergency setting but leads to severe neurological sequelae in some patients. To explore the epidemiology of convulsive status epilepticus with fever, a retrospective cohort covering all convulsive status epilepticus cases with fever seen in the emergency department of a tertiary care children's hospital were consecutively collected. Of the 381 consecutive cases gathered, 81.6% were due to prolonged febrile seizure, 6.6% to encephalopathy/encephalitis, 0.8% to meningitis, and 7.6% to epilepsy. In addition, seizures were significantly longer in encephalopathy/encephalitis cases than in prolonged febrile seizure cases (log rank test, P status epilepticus with fever in the emergency setting, and will help optimize the management of pediatric patients presenting to the emergency department with convulsive status epilepticus with fever. © The Author(s) 2016.

Effectiveness of ketogenic diet in pentylenetetrazol-induced and kindling rats as well as its potential mechanisms.

Science.gov (United States)

Wang, Shan; Ding, Yao; Ding, Xiao-Yan; Liu, Zhi-Rong; Shen, Chun-Hong; Jin, Bo; Guo, Yi; Wang, Shuang; Ding, Mei-Ping

2016-02-12

The effects and mechanisms of ketogenic diets (KD) are unclear. In this study, we aimed to reveal electrographic and behavioral thresholds in responses to the KD in pentylenetetrazol (PTZ)-induced seizures, as well as its antiepileptogenic effects on PTZ-kindling rats. Additionally, we investigated the potential link between KD and expression levels of two cation chloride co-transporters: K(+)-Cl(-) co-transporter 2 (KCC2) and Na(+)-K(+)-Cl(-) co-transporter 1 (NKCC1). The KD group had significantly higher electrographic thresholds than the control (ND) group for the first spike-and-wave, subcontinuous spike-and-wave, high amplitude spike-and-wave, and polyspikes both in the cortex and hippocampus. Compared to the ND group, the KD group had higher behavioral thresholds for behavioral absence, first jerk, first overt myoclonia, and generalized seizures. In the PTZ-kindling model, KD not only prolonged the latency of myoclonic and clonic convulsions, but shortened clonic and generalized duration. In addition, KD rats had higher KCC2 protein expression before kindling, during myoclonic jerks, and GTCS compared with ND rats. There were no significant differences in NKCC1 protein levels between both groups following the four-week dietary intervention without PTZ exposure (before kindling). Moreover, KD inhibited the upregulation of NKCC1 expression induced by kindling in myoclonic jerks and GTCS. Therefore, our findings demonstrated that KD had antiepileptic features in elevating thresholds to most electrographic and behavioral seizure patterns in PTZ-induced rats, as well as delaying the progression and alleviating the severity of seizure in PTZ-kindling model. The antiepileptogenic effects of KD may be attributed to its regulatory properties on KCC2 and NKCC1 protein expression. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Orthosiphon stamineus Leaf Extract Affects TNF-α and Seizures in a Zebrafish Model

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Brandon Kar Meng Choo

2018-02-01

Full Text Available Epileptic seizures result from abnormal brain activity and can affect motor, autonomic and sensory function; as well as, memory, cognition, behavior, or emotional state. Effective anti-epileptic drugs (AEDs are available but have tolerability issues due to their side effects. The Malaysian herb Orthosiphon stamineus, is a traditional epilepsy remedy and possesses anti-inflammatory, anti-oxidant and free-radical scavenging abilities, all of which are known to protect against seizures. This experiment thus aimed to explore if an ethanolic leaf extract of O. stamineus has the potential to be a novel symptomatic treatment for epileptic seizures in a zebrafish model; and the effects of the extract on the expression levels of several genes in the zebrafish brain which are associated with seizures. The results of this study indicate that O. stamineus has the potential to be a novel symptomatic treatment for epileptic seizures as it is pharmacologically active against seizures in a zebrafish model. The anti-convulsive effect of this extract is also comparable to that of diazepam at higher doses and can surpass diazepam in certain cases. Treatment with the extract also counteracts the upregulation of NF-κB, NPY and TNF-α as a result of a Pentylenetetrazol (PTZ treated seizure. The anti-convulsive action for this extract could be at least partially due to its downregulation of TNF-α. Future work could include the discovery of the active anti-convulsive compound, as well as determine if the extract does not cause cognitive impairment in zebrafish.

A role for endocannabinoids in viral-induced dyskinetic and convulsive phenomena.

Science.gov (United States)

Solbrig, Marylou V; Adrian, Russell; Baratta, Janie; Piomelli, Daniele; Giuffrida, Andrea

2005-08-01

Dyskinesias and seizures are both medically refractory disorders for which cannabinoid-based treatments have shown early promise as primary or adjunctive therapy. Using the Borna disease (BD) virus rat, an animal model of viral encephalopathy with spontaneous hyperkinetic movements and seizure susceptibility, we identified a key role for endocannabinoids in the maintenance of a balanced tone of activity in extrapyramidal and limbic circuits. BD rats showed significant elevations of the endocannabinoid anandamide in subthalamic nucleus, a relay nucleus compromised in hyperkinetic disorders. While direct and indirect cannabinoid agonists had limited motor effects in BD rats, abrupt reductions of endocannabinoid tone by the CB1 antagonist SR141716A (0.3 mg/kg, i.p.) caused seizures characterized by myoclonic jerks time-locked to periodic spike/sharp wave discharges on hippocampal electroencephalography. The general opiate antagonist naloxone (NLX) (1 mg/kg, s.c.), another pharmacologic treatment with potential efficacy in dyskinesias or L-DOPA motor complications, produced similar seizures. No changes in anandamide levels in hippocampus and amygdala were found in convulsing NLX-treated BD rats. In contrast, NLX significantly increased anandamide levels in the same areas of normal uninfected animals, possibly protecting against seizures. Pretreatment with the anandamide transport blocker AM404 (20 mg/kg, i.p.) prevented NLX-induced seizures. These findings are consistent with an anticonvulsant role for endocannabinoids, counteracting aberrant firing produced by convulsive agents, and with a functional or reciprocal relation between opioid and cannabinoid tone with respect to limbic convulsive phenomena.

Experimental study of neuropharmacological profile of Euphorbia pulcherrima in mice and rats

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Kundan Kr Singh

2012-01-01

Full Text Available Context: Euphorbia pulcherrima (EP belongs to the family: Euphorbiaceae and Genus: Euphorbia. Many species of Euphorbia have been reported as having beneficial properties like anticonvulsive effect, central analgesic properties, antipyretic action, central depressant action and strong sedative effect. However, little study has been done and published on EP. Aims: To observe and evaluate various neuropharmacological effects like antinociceptive effect, anticonvulsant effect, motor in-coordination, pentobarbital induced sleeping time and behavioral responses of EP in mice and rats. Setting and Design: Quantitative experimental study in mice and rats by various experimental models. Materials and Methods: Different experimental models were used to assess the antinociceptive effect (hotplate, tail flick and acetic acid induced writhing test, anticonvulsant effect (Maximal Electroshock Seizure test [MES] and Pentylenetetrazole induced seizures [PTZ], motor in-coordination effect (Rota rod test, pentobarbital induced sleeping time and behavioral responses of EP in mice and rats after oral administration of EP crude dried extracts in three different doses (250, 500 and 1000 mg/kg. Statistical Analysis Used: The significance of difference with respect to control was evaluated using the Mann-Whitney U test. A probability (P-value level less than 0.05 was considered as significant. Results: In MES test model, duration of tonic hind limb extension in mice treated with EP was significantly less as compared to vehicle treated group. EP was most effective in a dose of 1000 mg/kg. There was also significant increase in the latency and decrease in the incidence of convulsions with the use of EP in three different doses in PTZ induced seizure model. Conclusions: This study showed EP (crude dried extracts to possess anticonvulsant properties but no effect on motor co-ordination and anxiety.

Discovery of recurrent multiple brain states in non-convulsive status epilepticus

NARCIS (Netherlands)

van Putten, Michel Johannes Antonius Maria; van Putten, Maurice H.P.M.

2007-01-01

Objective We study burst-like patterns of epileptiform discharges in non-convulsive status epilepticus (SE). Methods Epileptiform burst-like transients were identified by estimating the amplitude envelope of the EEG signal, and recurrence and similarities were identified by pairwise matching in the

Risk factors associated with death in in-hospital pediatric convulsive status epilepticus.

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Tobias Loddenkemper

Full Text Available To evaluate in-patient mortality and predictors of death associated with convulsive status epilepticus (SE in a large, multi-center, pediatric cohort.We identified our cohort from the KID Inpatient Database for the years 1997, 2000, 2003 and 2006. We queried the database for convulsive SE, associated diagnoses, and for inpatient death. Univariate logistic testing was used to screen for potential risk factors. These risk factors were then entered into a stepwise backwards conditional multivariable logistic regression procedure. P-values less than 0.05 were taken as significant.We identified 12,365 (5,541 female patients with convulsive SE aged 0-20 years (mean age 6.2 years, standard deviation 5.5 years, median 5 years among 14,965,571 pediatric inpatients (0.08%. Of these, 117 died while in the hospital (0.9%. The most frequent additional admission ICD-9 code diagnoses in addition to SE were cerebral palsy, pneumonia, and respiratory failure. Independent risk factors for death in patients with SE, assessed by multivariate calculation, included near drowning (Odds ratio [OR] 43.2; Confidence Interval [CI] 4.4-426.8, hemorrhagic shock (OR 17.83; CI 6.5-49.1, sepsis (OR 10.14; CI 4.0-25.6, massive aspiration (OR 9.1; CI 1.8-47, mechanical ventilation >96 hours (OR9; 5.6-14.6, transfusion (OR 8.25; CI 4.3-15.8, structural brain lesion (OR7.0; CI 3.1-16, hypoglycemia (OR5.8; CI 1.75-19.2, sepsis with liver failure (OR 14.4; CI 5-41.9, and admission in December (OR3.4; CI 1.6-4.1. African American ethnicity (OR 0.4; CI 0.2-0.8 was associated with a decreased risk of death in SE.Pediatric convulsive SE occurs in up to 0.08% of pediatric inpatient admissions with a mortality of up to 1%. There appear to be several risk factors that can predict mortality. These may warrant additional monitoring and aggressive management.

A screening questionnaire for convulsive seizures: A three-stage field-validation in rural Bolivia.

Science.gov (United States)

Giuliano, Loretta; Cicero, Calogero Edoardo; Crespo Gómez, Elizabeth Blanca; Padilla, Sandra; Bruno, Elisa; Camargo, Mario; Marin, Benoit; Sofia, Vito; Preux, Pierre-Marie; Strohmeyer, Marianne; Bartoloni, Alessandro; Nicoletti, Alessandra

2017-01-01

Epilepsy is one of the most common neurological diseases in Latin American Countries (LAC) and epilepsy associated with convulsive seizures is the most frequent type. Therefore, the detection of convulsive seizures is a priority, but a validated Spanish-language screening tool to detect convulsive seizures is not available. We performed a field validation to evaluate the accuracy of a Spanish-language questionnaire to detect convulsive seizures in rural Bolivia using a three-stage design. The questionnaire was also administered face-to-face, using a two-stage design, to evaluate the difference in accuracy. The study was carried out in the rural communities of the Gran Chaco region. The questionnaire consists of a single screening question directed toward the householders and a confirmatory section administered face-to-face to the index case. Positive subjects underwent a neurological examination to detect false positive and true positive subjects. To estimate the proportion of false negative, a random sample of about 20% of the screened negative underwent a neurological evaluation. 792 householders have been interviewed representing a population of 3,562 subjects (52.2% men; mean age 24.5 ± 19.7 years). We found a sensitivity of 76.3% (95% CI 59.8-88.6) with a specificity of 99.6% (95% CI 99.4-99.8). The two-stage design showed only a slightly higher sensitivity respect to the three-stage design. Our screening tool shows a good accuracy and can be easily used by trained health workers to quickly screen the population of the rural communities of LAC through the householders using a three-stage design.

Preliminary Screening of a Classical Ayurvedic Formulation for Anticonvulsant Activity

Directory of Open Access Journals (Sweden)

Arnab Dhar

2016-01-01

Full Text Available Background: Epilepsy is a serious and complex central nervous system disorder associated with recurrent episodes of convulsive seizures due to the imbalance between excitatory (glutamatergic and inhibitory (GABAergic neurotransmitters level in the brain. The available treatments are neither competent to control the seizures nor prevent progress of disease. Since ages, Herbal medicines have remained important sources of medicines in many parts of world which is evidenced through their uses in traditional systems of medicine i.e. Ayurveda, Siddha, Unani, Homeopathy and Chinese etc. Aim: A polyherbal formulation (containing Terminalia chebula Retz., Asparagus racemosus Willd., Embelia ribes Burm. F, Acorus calamus L., Tinospora cordifolia (Willd. Miers, Convolvulus pluricaulis Choisy, Saussurea lappa C.B.Clarke, Achyranthes aspera L. is mentioned in Ayurvedic classics Bhaiṣajya Ratnāvali. The aim of the study was to evaluate the anticonvulsant activity of the formulation in Maximum electroshock and Pentylenetetrazole induced convulsions in rats. Materials and Methods: In the present study, a polyherbal formulation was developed as directed by classical text and evaluated for the anticonvulsant activity using Maximal Electroshock Shock (MES and Pentylenetetrazole (PTZ induced convulsions in rats. Statistical comparison was done by one way ANOVA followed by the Tukey's multiple comparison test. Results: The obtained results showed that the PHF had a protective role on epilepsy. Treatment with PHF significantly improves antioxidant enzymes activities of superoxide dismutase (SOD and glutathione (GSH levels significantly as compared to controls. PHF also significantly decreased malonaldialdehyde (MDA levels in the brain. Moreover, it also attenuated the PTZ-induced increase in the activity of GABA-T in the rat brain. Conclusion: These findings suggest that PHF might have possible efficacy in the treatment of epilepsy.

Neuropharmacological screening of essential oil from oleo gum resin of Gardenia lucida Roxb.

Science.gov (United States)

Shareef, Mohammad Zubair; Yellu, Narsimha Reddy; Achanta, Venkata Narsimha Appa Rao

2013-10-07

The oleo gum resin of Gardenia lucida is commonly employed in traditional medicine to treat multiple ailments, including epilepsy and mania. The essential oil isolated from it was screened for CNS activities to check if it is responsible for the claims made regarding the traditional use of the oleo gum resin. The hypnotic and anticonvulsant activity was assessed by pentobarbitone induced hypnosis and convulsant models-Maximum electroshock (MES) and Pentylene tetrazole (PTZ) respectively. Effect on motor activity was evaluated using an actophotometer, rotarod and grip strength methods. The oil significantly potentiated the barbitone induced hypnosis and offered significant protection against the intensity and frequency of convulsions and mortality rate in both the convulsant models. A significant decrease in locomotion, motor impairment and loss of gripping reflex was also observed. The essential oil of the oleo gum resin of Gardenia lucida is a CNS depressant and anticonvulsant with central muscle relaxant properties. This justifies the claims made regarding the use of the oleo gum resin of Gardenia lucida in CNS disorders. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Distribution of risk factors among children with febrile convulsions in ...

African Journals Online (AJOL)

The proximal risk factors are male gender, age < 2 years, 2nd birth order and positive family nd history. The social status of families is a distal risk factor. The second year of life and 2 birth order are the strongest predisposing factors to the development of FC. Key words: Febrile convulsions, Risk factors, Benin City, Nigeria ...

Influence of dietary zinc on convulsive seizures and hippocampal NADPH diaphorase-positive neurons in seizure susceptible EL mouse.

Science.gov (United States)

Nagatomo, I; Akasaki, Y; Uchida, M; Kuchiiwa, S; Nakagawa, S; Takigawa, M

1998-04-13

Adequate, high and deficient dietary levels of zinc (Zn) were compared in seizure-susceptible EL mice with respect to convulsions and to nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase-positive hippocampal neurons. Diaphorase positivity is associated with nitric oxide (NO) production. Convulsive seizures in the EL mice given the various diets did not differ over 1-4 weeks, but convulsions in EL mice given the Zn-deficient diet for 4 weeks were more effectively suppressed by injection of zonisamide (ZNS) (75 mg/kg intraperitoneally) than in mice receiving high- or adequate-Zn diet for the same period. Numbers of NADPH diaphorase-positive neurons in the CA1/CA2 region of the hippocampal formation were significantly higher in mice given the Zn-deficient diet for 4 weeks than in mice fed adequate Zn. Mice receiving the high-Zn diet for the same period had significantly fewer NADPH diaphorase-positive neurons in the subiculum than mice with adequate Zn. These results suggest that Zn deficiency inhibits convulsive seizures of EL mice, and that dietary Zn influences numbers of NO producing neurons in the hippocampal formation. Copyright 1998 Elsevier Science B.V.

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

NARCIS (Netherlands)

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).

Anticonvulsant and Antioxidant Effects of Pitavastatin Against Pentylenetetrazol-Induced Kindling in Mice.

Science.gov (United States)

Faghihi, Nastaran; Mohammadi, Mohammad Taghi

2017-06-01

Purpose: The pleiotropic effects of statins (antioxidant and anti-inflammation) have been reported by previous studies. Therefore, we aimed to determine whether pitavastatin has protective effects against pentylenetetrazol (PTZ)-induced kindling in mice and also whether pitavastatin improves the brain antioxidant capacity and attenuates the oxidative injuries in kindled mice. Methods: Twenty-four mice were randomly divided into four groups (each group n=6); control, PTZ-kindling and PTZ-kindled rats treated with pitavastatin (1&4 mg/kg). PTZ kindling seizures were induced by repetitive intraperitoneal injections of PTZ (65 mg/kg) every 48 hours till day twenty-one. Animals received daily oral pitavastatin for twenty-one days. Latency, score and duration of the seizures were recorded. The activities of catalase (CAT) ad superoxide dismutase (SOD), and likewise the contents of malondialdehyde (MDA) and nitrate were assessed in the brains of all rats. Results: There was a progressive reduction in latency of the kindled rats in the next injections of PTZ. Pitavastatin reduced this value (latency) particularly at higher dose. Seizures duration and score also decreased in treatment groups. SOD and CAT activities significantly decreased in PTZ-kindling group by 62% and 64%, respectively, but pitavastatin did not significantly change the SOD and CAT activities. Brain MDA and nitrate significantly increased in PTZ-kindling group by 53% and 30%, respectively. Pitavastatin at higher dose significantly decreased the MDA and nitrate contents of PTZ-kindling rats by 45% and 32%, respectively. Conclusion: Our findings revealed that pitavastatin can improve the behavioral expression of the PTZ-kindling rats and attenuate the seizure-induced oxidative/nitrosative damage.

Evidence-Based Guideline: Treatment of Convulsive Status Epilepticus in Children and Adults: Report of the Guideline Committee of the American Epilepsy Society

Science.gov (United States)

Shinnar, Shlomo; Gloss, David; Alldredge, Brian; Arya, Ravindra; Bainbridge, Jacquelyn; Bare, Mary; Bleck, Thomas; Dodson, W. Edwin; Garrity, Lisa; Jagoda, Andy; Lowenstein, Daniel; Pellock, John; Riviello, James; Sloan, Edward; Treiman, David M.

2016-01-01

CONTEXT: The optimal pharmacologic treatment for early convulsive status epilepticus is unclear. OBJECTIVE: To analyze efficacy, tolerability and safety data for anticonvulsant treatment of children and adults with convulsive status epilepticus and use this analysis to develop an evidence-based treatment algorithm. DATA SOURCES: Structured literature review using MEDLINE, Embase, Current Contents, and Cochrane library supplemented with article reference lists. STUDY SELECTION: Randomized controlled trials of anticonvulsant treatment for seizures lasting longer than 5 minutes. DATA EXTRACTION: Individual studies were rated using predefined criteria and these results were used to form recommendations, conclusions, and an evidence-based treatment algorithm. RESULTS: A total of 38 randomized controlled trials were identified, rated and contributed to the assessment. Only four trials were considered to have class I evidence of efficacy. Two studies were rated as class II and the remaining 32 were judged to have class III evidence. In adults with convulsive status epilepticus, intramuscular midazolam, intravenous lorazepam, intravenous diazepam and intravenous phenobarbital are established as efficacious as initial therapy (Level A). Intramuscular midazolam has superior effectiveness compared to intravenous lorazepam in adults with convulsive status epilepticus without established intravenous access (Level A). In children, intravenous lorazepam and intravenous diazepam are established as efficacious at stopping seizures lasting at least 5 minutes (Level A) while rectal diazepam, intramuscular midazolam, intranasal midazolam, and buccal midazolam are probably effective (Level B). No significant difference in effectiveness has been demonstrated between intravenous lorazepam and intravenous diazepam in adults or children with convulsive status epilepticus (Level A). Respiratory and cardiac symptoms are the most commonly encountered treatment-emergent adverse events

Characteristic phasic evolution of convulsive seizure in PCDH19-related epilepsy.

Science.gov (United States)

Ikeda, Hiroko; Imai, Katsumi; Ikeda, Hitoshi; Shigematsu, Hideo; Takahashi, Yukitoshi; Inoue, Yushi; Higurashi, Norimichi; Hirose, Shinichi

2016-03-01

PCDH19-related epilepsy is a genetic disorder that was first described in 1971, then referred to as "epilepsy and mental retardation limited to females". PCDH19 has recently been identified as the responsible gene, but a detailed characterization of the seizure manifestation based on video-EEG recording is still limited. The purpose of this study was to elucidate features of the seizure semiology in children with PCDH19-related epilepsy. To do this, ictal video-EEG recordings of 26 convulsive seizures in three girls with PCDH19-related epilepsy were analysed. All seizures occurred in clusters, mainly during sleep accompanied by fever. The motor manifestations consisted of six sequential phases: "jerk", "reactive", "mild tonic", "fluttering", "mild clonic", and "postictal". Some phases were brief or lacking in some seizures, whereas others were long or pronounced. In the reactive phase, the patients looked fearful or startled with sudden jerks and turned over reactively. The tonic and clonic components were less intense compared with those of typical tonic-clonic seizures in other types of epilepsy. The fluttering phase was characterised initially by asymmetric, less rhythmic, and less synchronous tremulous movement and was then followed by the subtle clonic phase. Subtle oral automatism was observed in the postictal phase. The reactive, mild tonic, fluttering and mild clonic phases were most characteristic of seizures of PCDH19-related epilepsy. Ictal EEG started bilaterally and was symmetric in some patients but asymmetric in others. It showed asymmetric rhythmic discharges in some seizures at later phases. The electroclinical pattern of the phasic evolution of convulsive seizure suggests a focal onset seizure with secondary generalisation. Based on our findings, we propose that the six unique sequential phases in convulsive seizures suggest the diagnosis of PCDH19-related epilepsy when occurring in clusters with or without high fever in girls. [Published with

A subconvulsive dose of kainate selectively compromises astrocytic metabolism in the mouse brain in vivo.

Science.gov (United States)

Walls, Anne B; Eyjolfsson, Elvar M; Schousboe, Arne; Sonnewald, Ursula; Waagepetersen, Helle S

2014-08-01

Despite the well-established use of kainate as a model for seizure activity and temporal lobe epilepsy, most studies have been performed at doses giving rise to general limbic seizures and have mainly focused on neuronal function. Little is known about the effect of lower doses of kainate on cerebral metabolism and particularly that associated with astrocytes. We investigated astrocytic and neuronal metabolism in the cerebral cortex of adult mice after treatment with saline (controls), a subconvulsive or a mildly convulsive dose of kainate. A combination of [1,2-(13)C]acetate and [1-(13)C]glucose was injected and subsequent nuclear magnetic resonance spectroscopy of cortical extracts was employed to distinctively map astrocytic and neuronal metabolism. The subconvulsive dose of kainate led to an instantaneous increase in the cortical lactate content, a subsequent reduction in the amount of [4,5-(13)C]glutamine and an increase in the calculated astrocytic TCA cycle activity. In contrast, the convulsive dose led to decrements in the cortical content and (13)C labeling of glutamate, glutamine, GABA, and aspartate. Evidence is provided that astrocytic metabolism is affected by a subconvulsive dose of kainate, whereas a higher dose is required to affect neuronal metabolism. The cerebral glycogen content was dose-dependently reduced by kainate supporting a role for glycogen during seizure activity.

Treatment of Generalized Convulsive Status Epilepticus in Pediatric Patients

Science.gov (United States)

Alford, Elizabeth L.; Wheless, James W.

2015-01-01

Generalized convulsive status epilepticus (GCSE) is one of the most common neurologic emergencies and can be associated with significant morbidity and mortality if not treated promptly and aggressively. Management of GCSE is staged and generally involves the use of life support measures, identification and management of underlying causes, and rapid initiation of anticonvulsants. The purpose of this article is to review and evaluate published reports regarding the treatment of impending, established, refractory, and super-refractory GCSE in pediatric patients. PMID:26380568

Unilateral Thalamic Infarct Presenting as a Convulsive Seizure.

Science.gov (United States)

Kumar, Rajesh; Brohi, Hazim; Mughul, Afshan

2017-09-01

Lesions of the thalamus and those extending into midbrain can cause various types of movement disorders such as dystonia, asterixis and ballism-chorea. Seizures are rare manifestation of thalamic disorder. Occurrence of seizures in bilateral thalamic infarct has been reported; but seizures in unilateral thalamic infarct have been reported very rarely. Literature review showed only single case of perinatal unilateral thalamic infarct presenting with seizures. We are reporting a unique case of convulsive seizure at the onset of unilateral thalamic infarct in an adult male, which has never been reported to the best of our knowledge.

Bilateral recurrent anterior fracture dislocation of shoulder joint due to grand mal epileptic convulsions

Directory of Open Access Journals (Sweden)

Chandrashekara Chowdipalya Maliyappa

2013-01-01

Full Text Available Bilateral shoulder dislocation is very much common with convulsions of different etiology. Often, these dislocations are associated with fractures due to violent muscle contractions. The typical lesion is bilateral posterior dislocation or fracture dislocations. The recurrent shoulder dislocations are common with traumatic etiology. The lack of asymmetry of the shoulders is stressed as a potential pitfall in the clinical evaluation of patients with this condition. We present a rare case of bilateral recurrent anterior fracture dislocation of the shoulder sustained due to repetitive episodes of convulsive seizures. Patient was treated by close reductions and immobilization on each episode. In epilepsy although posterior dislocations are common, the rare possibility of bilateral anterior fracture dislocation should be kept in mind. Often these patients are vulnerable for recurrence, similar to traumatic cases.

Treatment of prolonged convulsive seizures in children; a single centre, retrospective, observational study

NARCIS (Netherlands)

Vlaskamp, Danique R. M.; Brouwer, Oebele F.; Callenbach, Petra M. C.

2014-01-01

Objectives: To evaluate treatment of children with Prolonged Convulsive Seizures (PCS) at the University Medical Centre Groningen (UMCG). Material and methods: PCS were identified from an UMCG database of children with epilepsy aged = 10 mm and occurred between January 2000 and October 2012 in

Non-convulsive status epilepticus and consciousness disturbance after star fruit (Averrhoa carambola) ingestion in a dialysis patient.

Science.gov (United States)

Chang, Chung-Hsin; Yeh, Jiann-Horng

2004-12-01

Star fruit ingestion may induce severe neurological complications in chronic renal failure patients. We present a case on maintenance dialysis therapy who developed a consciousness disturbance without convulsion after eating star fruit. The symptoms became aggravated after haemodialysis. The brain computed tomography scan showed no abnormal findings, but the electroencephalogram found active focal sharp waves in the left central regions and diffusion-weighted magnetic resonance imaging also showed hyperintense lesions in the left central regions that were compatible with non-convulsive status epilepticus. His condition improved dramatically after anticonvulsant therapy and regular haemodialysis. The patient was discharged 20 days later without neurological sequela.

[The genotype-based haplotype relative risk and transmission disequilibrium test analyses of familial febrile convulsions].

Science.gov (United States)

Qi, Y; Wu, X; Guo, Z; Zhang, J; Pan, H; Li, M; Bao, X; Peng, J; Zou, L; Lin, Q

1999-10-01

To confirm the linkage of familial febrile convulsions to the short arm of chromosome 6(6p) or the long arm of chromosome 8(8q). The authors finished genotyping of Pst I locus on the coding region of heat shock protein (HSP) 70, 5'untranslated region of HSP70-1, 3' untranslated region of HSP70-2, D8S84 and D8S85. The data were processed by the genotype-based haplotype relative risk(GHRR) and transmission disequilibrium test(TDT) methods in PPAP. Some signs of association and disequilibrium between D8S85 and FC were shown by GHRR and TDT. A suspect linkage of familial febrile convulsions to the long arm of chromosome 8 has been proposed.

Incidence, Remission and Mortality of Convulsive Epilepsy in Rural Northeast South Africa.

Science.gov (United States)

Wagner, Ryan G; Bottomley, Christian; Ngugi, Anthony K; Ibinda, Fredrick; Gómez-Olivé, F Xavier; Kahn, Kathleen; Tollman, Stephen; Newton, Charles R; Wagner, Ryan; Twine, Rhian; Connor, Myles; Collinson, Mark; Masanja, Honratio; Mathew, Alexander; Kakooza, Angelina; Pariyo, George; Peterson, Stefan; Ndyo-mughenyi, Donald; Odhiambo, Rachael; Chengo, Eddie; Chabi, Martin; Bauni, Evasius; Kamuyu, Gathoni; Odera, Victor Mung'ala; Mageto, James O; Ae-Ngibise, Ken; Akpalu, Bright; Akpalu, Albert; Agbokey, Francis; Adjei, Patrick; Owusu-Agyei, Seth; Kleinschmidt, Immo; Doku, Victor C K; Odermatt, Peter; Neville, Brian; Sander, Josemir W; White, Steve; Nutman, Thomas; Wilkins, Patricia; Noh, John

2015-01-01

Epilepsy is one of the most common neurological conditions globally, estimated to constitute 0.75% of the global burden of disease, with the majority of this burden found in low- and middle- income countries (LMICs). Few studies from LMICs, including much of sub-Saharan Africa, have described the incidence, remission or mortality rates due to epilepsy, which are needed to quantify the burden and inform policy. This study investigates the epidemiological parameters of convulsive epilepsy within a context of high HIV prevalence and an emerging burden of cardiovascular disease. A cross-sectional population survey of 82,818 individuals, in the Agincourt Health and Socio-demographic Surveillance Site (HDSS) in rural northeast South Africa was conducted in 2008, from which 296 people were identified with active convulsive epilepsy. A follow-up survey was conducted in 2012. Incidence and mortality rates were estimated, with duration and remission rates calculated using the DISMOD II software package. The crude incidence for convulsive epilepsy was 17.4/100,000 per year (95%CI: 13.1-23.0). Remission was 4.6% and 3.9% per year for males and females, respectively. The standardized mortality ratio was 2.6 (95%CI: 1.7-3.5), with 33.3% of deaths directly related to epilepsy. Mortality was higher in men than women (adjusted rate ratio (aRR) 2.6 (95%CI: 1.2-5.4)), and was significantly associated with older ages (50+ years versus those 0-5 years old (RR 4.8 (95%CI: 0.6-36.4)). The crude incidence was lower whilst mortality rates were similar to other African studies; however, this study found higher mortality amongst older males. Efforts aimed at further understanding what causes epilepsy in older people and developing interventions to reduce prolonged seizures are likely to reduce the overall burden of ACE in rural South Africa.

Incidence, Remission and Mortality of Convulsive Epilepsy in Rural Northeast South Africa.

Directory of Open Access Journals (Sweden)

Ryan G Wagner

Full Text Available Epilepsy is one of the most common neurological conditions globally, estimated to constitute 0.75% of the global burden of disease, with the majority of this burden found in low- and middle- income countries (LMICs. Few studies from LMICs, including much of sub-Saharan Africa, have described the incidence, remission or mortality rates due to epilepsy, which are needed to quantify the burden and inform policy. This study investigates the epidemiological parameters of convulsive epilepsy within a context of high HIV prevalence and an emerging burden of cardiovascular disease.A cross-sectional population survey of 82,818 individuals, in the Agincourt Health and Socio-demographic Surveillance Site (HDSS in rural northeast South Africa was conducted in 2008, from which 296 people were identified with active convulsive epilepsy. A follow-up survey was conducted in 2012. Incidence and mortality rates were estimated, with duration and remission rates calculated using the DISMOD II software package.The crude incidence for convulsive epilepsy was 17.4/100,000 per year (95%CI: 13.1-23.0. Remission was 4.6% and 3.9% per year for males and females, respectively. The standardized mortality ratio was 2.6 (95%CI: 1.7-3.5, with 33.3% of deaths directly related to epilepsy. Mortality was higher in men than women (adjusted rate ratio (aRR 2.6 (95%CI: 1.2-5.4, and was significantly associated with older ages (50+ years versus those 0-5 years old (RR 4.8 (95%CI: 0.6-36.4.The crude incidence was lower whilst mortality rates were similar to other African studies; however, this study found higher mortality amongst older males. Efforts aimed at further understanding what causes epilepsy in older people and developing interventions to reduce prolonged seizures are likely to reduce the overall burden of ACE in rural South Africa.

Challenges in the treatment of convulsive status epilepticus.

Science.gov (United States)

Zaccara, Gaetano; Giannasi, Gianfranco; Oggioni, Roberto; Rosati, Eleonora; Tramacere, Luciana; Palumbo, Pasquale

2017-04-01

Convulsive status epilepticus (CSE) is a medical emergency associated with high mortality and morbidity. The most recent definition of CSE is a convulsive seizure lasting more than 5min or consecutive seizures without recovery of consciousness. In adults, for the treatment of the early stages of CSE, diazepam, lorazepam or midazolam are the most common treatments, although the choice of agent seems less important than rapid treatment. Midazolam, when administered intramuscularly (best evidence), buccally, or nasally, is effective and safe in the pre-hospital setting. The antiepileptic drugs, phenytoin, valproate, levetiracetam and, more recently lacosamide, are used in CSE that persists after first-line treatments (established CSE). Phenytoin is more difficult to administer and is less well tolerated. Evidence of the efficacy of lacosamide is scarce. Anaesthetics are the drugs of choice for the treatment of refractory CSE (not responding to second-line drugs). Midazolam seems to be the best tolerated and is the most often used drug, followed by propofol and thiopental (pentobarbital in the USA). A few studies indicate that ketamine is effective with the possible advantage that it can be co-administered with other anaesthetics, such as midazolam or propofol. CSE becomes super-refractory after more than 24h of appropriate treatments and may last weeks. Several anaesthetics have been proposed but evidence is scarce. Autoimmune refractory CSE has been recently identified, and early treatment with immuno-modulatory agents (corticosteroids and IV immunoglobulins and also second-line agents such as cyclophosphamide and rituximab followed by chronic immunosuppressive treatment) is now recommended by many experts. Copyright © 2017. Published by Elsevier Ltd.

'Infantile convulsions' in the early nineteenth century. Abnormal brain blood flow and leeches, teething and gums' scarification and food and purgatives: the historical contribution of John Clarke (1760-1815).

Science.gov (United States)

Brigo, Francesco; Lattanzi, Simona; Trinka, Eugen; Nardone, Raffaele; Bragazzi, Nicola Luigi; Ruggieri, Martino; Vecchio, Ignazio; Martini, Mariano

2018-03-20

In this article, we discuss on the role of the British physician and midwifery practitioner John Clarke (1760-1815) in the characterisation of the various types of seizures and epilepsy and related phenomena ('convulsions') occurring in children. In his unfinished work Commentaries on Some of the Most Important Diseases of Children (1815), Clarke discussed the pathophysiology of convulsions and was the first to describe, 12 years before the French neurologist Louis Francois Bravais (1801-1843) and more than 30 years before the Irish-born physician Robert Bentley Todd (1809-1860), the postictal paresis. He believed that convulsions originated from changes in pressure within the ventricles as a consequence of abnormal blood flow to the cerebral vessels. In keeping with the theories of his time (e.g. Baumes 1789, 1805; Brachet 1824), Clarke believed that teething was a major cause of 'infantile convulsions'. His proposed remedies ranged from scarification of the gums to ammonia, application of leeches, cold water, and purgatives. The use of antispasmodics, quite popular at the time, was instead questioned. In his Practical Observations on the Convulsions of Infants (1826), the London practitioner and midwifery John North (1790-1873) deeply criticised Clarke's view that convulsions arise inevitably as a consequence of organic brain lesions. North inferred that the results of autopsies of children who had died of convulsions revealed no brain damages, and claimed that cerebral irritation could also occur as the effect of distant lesions. Other Clarke's contemporaries (e.g. Jean Baptiste Timothée Baumes-1756-1828) inferred that all convulsions reflected a hereditary diathesis, which rendered children (especially those with softer and limper nervous and muscular tissues!) extremely sensitive to all sorts of provocation that could trigger convulsions, including bad digestion (more pronounced at the time of teething), loud noise, and bright light. Although almost every

Spreading convulsions, spreading depolarization and epileptogenesis in human cerebral cortex

DEFF Research Database (Denmark)

Dreier, Jens P; Major, Sebastian; Pannek, Heinz-Wolfgang

2012-01-01

Spreading depolarization of cells in cerebral grey matter is characterized by massive ion translocation, neuronal swelling and large changes in direct current-coupled voltage recording. The near-complete sustained depolarization above the inactivation threshold for action potential generating...... stimulations. Eventually, epileptic field potentials were recorded during the period that had originally seen spreading depression of activity. Such spreading convulsions are characterized by epileptic field potentials on the final shoulder of the large slow potential change of spreading depolarization. We...

Telemetry video-electroencephalography (EEG) in rats, dogs and non-human primates: methods in follow-up safety pharmacology seizure liability assessments.

Science.gov (United States)

Bassett, Leanne; Troncy, Eric; Pouliot, Mylene; Paquette, Dominique; Ascah, Alexis; Authier, Simon

2014-01-01

Non-clinical seizure liability studies typically aim to: 1) confirm the nature of EEG activity during abnormal clinical signs, 2) identify premonitory clinical signs, 3) measure plasma levels at seizure onset, 4) demonstrate that drug-induced seizures are self-limiting, 5) confirm that conventional drugs (e.g. diazepam) can treat drug-induced seizures and 6) confirm the no observed adverse effect level (NOAEL) at EEG. Our aim was to originally characterize several of these items in a three species comparative study. Cynomolgus monkey, Beagle dog and Sprague-Dawley rat with EEG telemetry transmitters were used to obtain EEG using the 10-20 system. Pentylenetetrazol (PTZ) was used to determine seizure threshold or as a positive seizurogenic agent. Clinical signs were recorded and premonitory signs were evaluated. In complement, other pharmacological agents were used to illustrate various safety testing strategies. Intravenous PTZ doses required to induce clonic convulsions were 36.1 (3.8), 56.1 (12.7) and 49.4 (11.7) mg/kg, in Beagle dogs, cynomolgus monkeys and Sprague-Dawley rats, respectively. Premonitory clinical signs typically included decreased physical activity, enhanced physiological tremors, hypersalivation, ataxia, emesis (except in rats) and myoclonus. In Sprague-Dawley rats, amphetamine (PO) increased high (approximately 40-120Hz), and decreased low (1-14Hz) frequencies. In cynomolgus monkeys, caffeine (IM) increased power in high (14-127Hz), and attenuated power in low (1-13Hz) frequencies. In the rat PTZ infusion seizure threshold model, yohimbine (SC and IV) and phenobarbital (IP) confirmed to be reliable positive controls as pro- and anticonvulsants, respectively. Telemetry video-EEG for seizure liability investigations was characterized in three species. Rats represent a first-line model in seizure liability assessments. Beagle dogs are often associated with overt susceptibility to seizure and are typically used in seizure liability studies only if

Involvement of ATP-sensitive potassium channels and the opioid system in the anticonvulsive effect of zolpidem in mice.

Science.gov (United States)

Sheikhi, Mehdi; Shirzadian, Armin; Dehdashtian, Amir; Amiri, Shayan; Ostadhadi, Sattar; Ghasemi, Mehdi; Dehpour, Ahmad Reza

2016-09-01

Zolpidem is a hypnotic medication that mainly exerts its function through activating γ-aminobutyric acid (GABA)A receptors. There is some evidence that zolpidem may have anticonvulsive effects. However, the mechanisms underlying this effect have not been elucidated yet. In the present study, we used the pentylentetrazole (PTZ)-induced generalized seizure model in mice to investigate whether zolpidem can affect seizure threshold. We also further evaluated the roles of ATP-sensitive potassium (KATP) channels as well as μ-opioid receptors in the effects of zolpidem on seizure threshold. Our data showed that zolpidem in a dose-dependent manner increased the PTZ-induced seizure threshold. The noneffective (i.e., did not significantly alter the PTZ-induced seizure threshold by itself) doses of KATP channel blocker (glibenclamide) and nonselective opioid receptor antagonist (naloxone) were able to inhibit the anticonvulsive effect of zolpidem. Additionally, noneffective doses of either KATP channel opener (cromakalim) or nonselective μ-opioid receptor agonist (morphine) in combination with a noneffective dose of zolpidem exerted a significant anticonvulsive effect on PTZ-induced seizures in mice. A combination of noneffective doses of naloxone and glibenclamide, which separately did not affect zolpidem effect on seizure threshold, inhibited the anticonvulsive effects of zolpidem. These results suggest a role for KATP channels and the opioid system, alone or in combination, in the anticonvulsive effects of zolpidem. Copyright © 2016 Elsevier Inc. All rights reserved.

Crise convulsive chez les abuseurs de Tramadol et caféine: à ...

African Journals Online (AJOL)

Nous rapportons Huit cas de crises convulsives diagnostiquées comme maladie épileptique après ingestion de Tramadol et d'autres substances psychotropes dont la Caféine dans une région ou maladie épileptique et addiction au café sont fréquentes. L'objectif de ce travail était d'informer les praticiens sur le risque de ...

Incidence, Remission and Mortality of Convulsive Epilepsy in Rural Northeast South Africa

Science.gov (United States)

Wagner, Ryan G.; Bottomley, Christian; Ngugi, Anthony K.; Ibinda, Fredrick; Gómez-Olivé, F. Xavier; Kahn, Kathleen; Tollman, Stephen; Newton, Charles R.

2015-01-01

Background Epilepsy is one of the most common neurological conditions globally, estimated to constitute 0.75% of the global burden of disease, with the majority of this burden found in low- and middle- income countries (LMICs). Few studies from LMICs, including much of sub-Saharan Africa, have described the incidence, remission or mortality rates due to epilepsy, which are needed to quantify the burden and inform policy. This study investigates the epidemiological parameters of convulsive epilepsy within a context of high HIV prevalence and an emerging burden of cardiovascular disease. Methods A cross-sectional population survey of 82,818 individuals, in the Agincourt Health and Socio-demographic Surveillance Site (HDSS) in rural northeast South Africa was conducted in 2008, from which 296 people were identified with active convulsive epilepsy. A follow-up survey was conducted in 2012. Incidence and mortality rates were estimated, with duration and remission rates calculated using the DISMOD II software package. Results The crude incidence for convulsive epilepsy was 17.4/100,000 per year (95%CI: 13.1-23.0). Remission was 4.6% and 3.9% per year for males and females, respectively. The standardized mortality ratio was 2.6 (95%CI: 1.7-3.5), with 33.3% of deaths directly related to epilepsy. Mortality was higher in men than women (adjusted rate ratio (aRR) 2.6 (95%CI: 1.2-5.4)), and was significantly associated with older ages (50+ years versus those 0-5 years old (RR 4.8 (95%CI: 0.6-36.4)). Conclusions The crude incidence was lower whilst mortality rates were similar to other African studies; however, this study found higher mortality amongst older males. Efforts aimed at further understanding what causes epilepsy in older people and developing interventions to reduce prolonged seizures are likely to reduce the overall burden of ACE in rural South Africa. PMID:26053071

Anticonvulsant and neuroprotective effects of Rosa damascena hydro-alcoholic extract on rat hippocampus

Directory of Open Access Journals (Sweden)

Mansour Homayoun

2015-04-01

Full Text Available Objective: Previously, analgesic, hypnotic, and anticonvulsant effects have been suggested for Rosa damascena (R. damascena. In the present study, possible anti-seizure and neuro-protective effects of hydro-alcoholic extract of R. damascena has been investigated after inducing seizures in rats by pentylenetetrazole (PTZ. Materials and Methods: The rats were divided to five groups: (1 Control: received saline, (2 PTZ: 100 mg/kg, i.p., (3 PTZ-Extract 50 mg/kg(PTZ-Ext 50, (4 PTZ- Extract 100 mg/kg(PTZ-Ext 100, and (5 PTZ- Extract 200 mg/kg(PTZ-Ext 200 groups which were treated with 50, 100, and 200 mg/kg respectively of hydro-alcoholic extract of R. damascena for one week before PTZ injection. The animals were examined for electrocorticography (ECoG recording and finally, the brains were removed for histological study. Results: The hydro-alcoholic extract of R. damascena significantly prolonged the latency of seizure attacks and reduced the frequency and amplitude of epileptiform burst discharges induced by PTZ injection. Moreover, all three doses of the extract significantly inhibited production of dark neurons in different regions of the hippocampus in the mentioned animal model. Conclusion: The present study showed that the hydro-alcoholic extract of R. damascena has anticonvulsant and neuroprotective effects. More investigations are needed to be done in order to better understand the responsible compound(s as well as the possible mechanism(s.

Electronic and structural aspects of spin transitions observed by optical microscopy. The case of [Fe(ptz)6](BF4)2.

Science.gov (United States)

Chong, Christian; Mishra, Haritosh; Boukheddaden, Kamel; Denise, Stéphane; Bouchez, Guillaume; Collet, Eric; Ameline, Jean-Claude; Naik, Anil D; Garcia, Yann; Varret, François

2010-02-11

The colorimetric analysis of images recorded with an optical microscope during the onset of the spin crossover transformation allows monitoring separately the involved electronic and structural aspects, through the separation of resonant absorption and scattering effects. Complementary information can also be obtained by using the polarized modes of the microscope. These potentialities are illustrated by the observation of [Fe(ptz)(6)](BF(4))(2) single crystals during the onset of the thermal transitions in the 110-140 K range. We characterized the interplay between the electronic (HS LS) and structural (order disorder) transformations. Elastic stresses and mechanical effects (hopping, self-cleavage) generated by the volume change upon electronic transition are also illustrated, with their impact on the photoswitching properties of the crystals.

Effect of NAD on binding and liberation of 14C-GABA in administration of the convulsion producing drug

International Nuclear Information System (INIS)

Fomenko, A.I.; Stepanenko, S.P.; Parkhomets, P.K.; Donchenko, G.V.

1993-01-01

Administration of corazole into animals led to a decrease in content of NAD and gamma-aminobutyric acid (GABA) in brain. Under these conditions, binding of 14 C-GABA was increased and its liberation was inhibited in the synaptosomes of the brain cortex. Additional administration of incotinamide, accompanied by considerable increase in content of NAD and GABA, caused a decrease in accumulation of exogenous GABA in the synaptosomes and removed the effects produced by the convulsant agent. Kinetics of 14 C-GABA binding in the presence of NAD demonstrated that the more effective inhibition of the binding occurred in the animals treated with the convulsant drug. NAD appears to affect the GABA-ergic transmission at the postsynaptic level

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

LENUS (Irish Health Repository)

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.

Diagnosis and interpretation of EEG on non-convulsive status epilepticus

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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

Unexpected Maternal Convulsion: An Idiopathic Case of Posterior Reversible Encephalopathy Syndrome after Delivery

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Jila Agah

2016-01-01

Full Text Available Posterior reversible encephalopathy syndrome (PRES is associated with various clinical manifestations such as headache, blurred vision, confusion and tonic-clonic convulsion. Some of the predisposing factors for PRES include hypertensive encephalopathy, preeclampsia and eclampsia, lupus erythematosus, thrombotic thrombocytopenic purpura and long-term use of immunosuppressive drugs. This condition rarely occurs after normotensive and uneventful pregnancies. Several theories have been proposed on the etiology of PRES. For instance, endothelial injury and brain edema have been reported as possible causes of PRES. Although PRES is a temporary condition, proper and timely management of the disorder in the acute phase is critical for the prevention of permanent neurological complications. During pregnancy, PRES is normally accompanied with hypertension. In this paper, we present a rare case of PRES in a normotensive pregnancy in a 25-year-old parturient woman (Gravida 2, Ab 1. The patient unexpectedly manifested symptoms of tonic-clonic convulsion one hour after an uneventful vaginal delivery, which were successfully managed. According to our observations, PRES has various clinical manifestations with unexpected occurrence in some cases. Therefore, it is recommended that maternity centers be well-equipped with resuscitation tools, emergency drugs and expert staff so as to manage unforeseen PRES efficiently and prevent permanent maternal neurological complications and mortality.

Anticonvulsant effect of ethanolic extract of Cyperus articulatus L. leaves on pentylenetetrazol induced seizure in mice

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Oscar Herrera-Calderon

2018-01-01

Full Text Available Cyperus articulatus (CA rhizomes have demonstrated different properties on nervous system. However, the leaves still have not studied to treat epilepsy. The aim of this study was to determine the effect of CA ethanolic extract on pentylenetetrazol (PTZ induced seizures in mice as well as measuring its antioxidant activity in vivo and in vitro. Mice were divided into five groups: (1 control (PTZ 80 mg/kg; i.p., (2 PTZ-Diazepam (1 mg/kg; i.p., (3–5 PTZ-CA 50, PTZ-CA 150 and PTZ-CA 300 (50, 150 and 300 mg/kg of CA extract, 30 min prior to each PTZ injection. The PTZ-CA 150 group showed lower seizure scores (P < 0.01, latency (P < 0.01, frequency (P < 0.01 and duration (P < 0.01 than control group. The antioxidant activity of CA extract scavenged DPPH radical showed IC 50 = 16.9 ± 0.1 μg/mL and TEAC = 2.28 ± 0.08, mmol trolox/g of extract, the content of gamma amino butyric acid (GABA and malondialdehyde (MDA were significantly high (P < 0.01 at dose of 150 mg/kg (82 ± 1.2 ng/g tissue; 1.0 ± 2.2 mol/g tissue, respectively. The present research demonstrated that CA extract possesses a potential effect to prevent PTZ induced seizures, antioxidant activity in addition to increase GABA levels.

A positioning system for forest diseases and pests based on GIS and PTZ camera

International Nuclear Information System (INIS)

Wang, Z B; Zhao, F F; Wang, C B; Wang, L L

2014-01-01

Forest diseases and pests cause enormous economic losses and ecological damage every year in China. To prevent and control forest diseases and pests, the key is to get accurate information timely. In order to improve monitoring coverage rate and economize on manpower, a cooperative investigation model for forest diseases and pests is put forward. It is composed of video positioning system and manual labor reconnaissance with mobile GIS embedded in PDA. Video system is used to scan the disaster area, and is particularly effective on where trees are withered. Forest diseases prevention and control workers can check disaster area with PDA system. To support this investigation model, we developed a positioning algorithm and a positioning system. The positioning algorithm is based on DEM and PTZ camera. Moreover, the algorithm accuracy is validated. The software consists of 3D GIS subsystem, 2D GIS subsystem, video control subsystem and disaster positioning subsystem. 3D GIS subsystem makes positioning visual, and practically easy to operate. 2D GIS subsystem can output disaster thematic map. Video control subsystem can change Pan/Tilt/Zoom of a digital camera remotely, to focus on the suspected area. Disaster positioning subsystem implements the positioning algorithm. It is proved that the positioning system can observe forest diseases and pests in practical application for forest departments

Update on causes of premature death in people with convulsive epilepsy in rural West China.

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Si, Yang; Chen, Deng; Tian, Linyu; Mu, Jie; Chen, Tao; Liu, Ling; Deng, Ying; He, Jun; Li, You; He, Li; Zhou, Dong

2016-06-01

This longitudinal prospective study updated a previous report on premature mortality and focused on the risk factors among patients with convulsive epilepsy in resource-poor settings. The present cohort size (7,231) and follow-up (mean 33.4 months) were expanded. The basic epidemiologic aspects of this cohort were similar to the original report (case fatality: 3.26% vs. 2.97%, respectively; injury contributed more than half of the deaths). Cox regression analysis suggested that male patients, late ages of onset (>45 years old), short duration of epilepsy (2 per month) were independent risk factors for overall premature death. Male patients with late ages of onset and high seizure frequency had a higher risk of injury-specific death. This study emphasizes the preventable nature of injuries that are leading putative causes of death among people with convulsive epilepsy in rural West China. Education on specific populations and efficient seizure control are of paramount importance in reducing the risk of premature mortality. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

Effects of thioperamide on seizure development and memory impairment induced by pentylenetetrazole-kindling epilepsy in rats

Institute of Scientific and Technical Information of China (English)

ZHANG Li-san; CHEN Jie-fang; CHEN Guan-feng; HU Xing-yue; DING Mei-ping

2013-01-01

Background Histamine H3 receptor antagonists have been considered as potential drugs to treat central nervous system diseases.However,whether these drugs can inhibit epileptogenesis remains unclear.This study aimed to investigate the effects of thioperamide,a selective and potent histamine H3 receptor antagonist,on the seizure development and memory impairment induced by pentylenetetrazole (PTZ)-kindling epilepsy in rats.Methods Chemical kindling was elicited by repeated intraperitoneal (ip) injections of a subconvulsant dose of PTZ (35 mg/kg) once every 48 hours for 12 times,and seizure activity of kindling was recorded for 30 minutes.Control rats were ip injected with saline instead of PTZ.Morris water maze was used to evaluate the spatial memory.Phosphorylated cyclic adenosine monophosphate response element binding protein (p-CREB) was tested by Western blotting in hippocampus.Results Intracerebroventricular (icv) injections with thioperamide (10 μg,20 μg) 30 minutes before every PTZ injections,significantly prolonged the onset of PTZ-kindling and inhibited the seizure stages.PTZ-kindling seizures led to the impairment of spatial memory in rats,and thioperamide ameliorated the impairment of spatial learning and memory.Compared to non-kindling rats,there was a significant decrease in p-CREB level in hippocampus of the PTZ-kindling rats,which was reversed by thioperamide.Conclusions Thioperamide plays a protective role in seizure development and cognitive impairment of PTZ-induced kindling in rats.The protection of thioperamide in cognitive impairment is possibly associated with the enhancement of CREB-dependent transcription.

Diagnostic accuracy of the Salzburg EEG criteria for non-convulsive status epilepticus

DEFF Research Database (Denmark)

Leitinger, Markus; Trinka, Eugen; Gardella, Elena

2016-01-01

Background Several EEG criteria have been proposed for diagnosis of non-convulsive status epilepticus (NCSE), but none have been clinically validated. We aimed to assess the diagnostic accuracy of the EEG criteria proposed by a panel of experts at the fourth London–Innsbruck Colloquium on Status...... Epilepticus in Salzburg, 2013 (henceforth called the Salzburg criteria). Methods We did a retrospective, diagnostic accuracy study using EEG recordings from patients admitted for neurological symptoms or signs to three centres in two countries (Danish Epilepsy Centre, Dianalund, Denmark; Aarhus University...

Post-transfusion hypertension, convulsion and intracranial haemorrhage in beta-thalassemia major

International Nuclear Information System (INIS)

Masood, S.A.; Zaidi, A.

2012-01-01

The haematologic disorder b-thalassemia major is common in Pakistan. We describe a patient with undiagnosed thalassemia presenting with hypertension and convulsions and found to have cerebral haemorrhage on neuro-imaging. He had been transfused 2 weeks before this illness. Our experience is similar to a few case reports described in literature that were found to have cerebral haemorrhages post-mortem after a similar clinical presentation. All patients had a blood transfusion within 2 weeks prior to the presentation so association with transfusion has been proposed. We have reviewed the several mechanisms presented and discussed the findings. (author)

Assessment of the Level of GABA and Some Trace Elements in Blood in Children who Suffer from Familial Febrile Convulsions

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Osama N. Salah

2014-03-01

Full Text Available Febrile seizure is one of the most common neurological problems during childhood. The etiology and pathogenesis of febrile seizure remain unknown. However, several factors such as vitamin B6 deficiency, electrolyte disturbances, and reduction in serum zinc, selenium, magnesium levels, and low gamma - aminobutyric acid (GABA levels are thought to play a role in the pathogenesis of febrile seizure. The present study included twenty children from 10 families, 11 were male and 9 were female. Each family has at least 2 members with a history of febrile convulsion. All cases were subjected to the following: Determination of serum levels of copper, zinc, magnesium, selenium level in serum, and plasma level of γ-aminobytaric acid (GABA. Serum levels of selenium and GABA were statistically significantly low in comparison with controls. Serum copper was statistically significantly higher in cases than controls, while serum zinc showed no significant changes in the cases of febrile convulsion compared with the control group. The mean Zn level in the serum of febrile convulsion was found to be at lower level than in the control group. The serum magnesium was significantly low in cases than controls. The logistic regression model in our study shows that Selenium and Magnesium have protective effects, while Copper has causative effect.

Enhancement of inhibitory neurotransmission and inhibition of excitatory mechanisms underlie the anticonvulsant effects of Mallotus oppositifolius

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Kennedy Kwami Edem Kukuia

2016-01-01

Full Text Available Context: Mallotus oppositifolius is a shrub that is used traditionally to treat epilepsy, but its potential has not been scientifically validated. Aims: This study investigated the anticonvulsant properties and possible mechanism of action of the 70% v/v hydroalcoholic extract of the leaves of M. oppositifolius.Materials and Methods: Inprinting control region (ICR mice (25–30 g were pretreated with the M. oppositifolius leaf extract (10–100 mg/kg before administering the respective convulsants (pentylenetetrazole [PTZ], picrotoxin [PTX], strychnine [STR], 4-aminopyridine [4-AP], and pilocarpine. The effect of the extract in maximal electroshock seizure (MES model was investigated also. Statistical Analysis: Data were presented as mean ± standard error of the mean and were analyzed with one-way analysis of variance (ANOVA or two-way ANOVA where appropriate with Newman–Keuls or Bonferroni post hoc test respectively. P< 0.05 was considered significant. Results: In both PTX and PTZ test, extract delayed the onset of seizures and reduced the frequency and duration of seizures. In the STR-induced seizure test, the extract significantly delayed the onset of seizures and reduced the duration of seizures. The extract also delayed the onset of clonic and tonic seizures as well as increasing the survival of mice in the 4-AP-induced seizure test. It further reduced the duration of tonic limb extensions in the MES test. In the pilocarpine-induced status epilepticus, the extract significantly delayed the onset of clonic convulsions and reduced the frequency and duration of seizures. Moreover, the anticonvulsant effect of the extract was attenuated by flumazenil, a benzodiazepine/gamma-aminobutyric acid (GABA receptor antagonist. Conclusion: These findings show that the extract has anticonvulsant effect possible mediated by GABAergic, glycinergic neurotransmission, and potassium channel conductions. It may also be acting by antagonizing muscarinic

Pentylenetetrazol modulates redox system by inducing addicsin translocation from endoplasmic reticulum to plasma membrane in NG108-15 cells

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Mitsushi J. Ikemoto

2017-09-01

Full Text Available Addicsin (Arl6ip5 is a multifunctional physiological and pathophysiological regulator that exerts its effects by readily forming homo- and hetero-complexes with various functional factors. In particular, addicsin acts as a negative modulator of neural glutamate transporter excitatory amino acid carrier 1 (EAAC1 and participates in the regulation of intracellular glutathione (GSH content by negatively modulating EAAC1-mediated cysteine and glutamate uptake. Addicsin is considered to play a crucial role in the onset of neurodegenerative diseases including epilepsy. However, the molecular dynamics of addicsin remains largely unknown. Here, we report the dynamics of addicsin in NG108-15 cells upon exposure to pentylenetetrazol (PTZ, a representative epileptogenic agent acting on the gamma-Aminobutyric acid A (GABAA receptor. Fluorescent immunostaining analysis demonstrated that addicsin drastically changed its localization from the endoplasmic reticulum (ER to the plasma membrane within 1 h of PTZ exposure in a dose-dependent manner. Moreover, addicsin was co-localized with the plasma membrane markers EAAC1 and Na+/K+ ATPase alpha-3 upon PTZ stimulation. This translocation was significantly inhibited by a non-competitive GABAA receptor antagonist, picrotoxin, but not by a competitive GABAA receptor antagonist, bicuculline. Furthermore, lactate dehydrogenase (LDH assay and 2,2-diphenyl-1-picrylhydrazyl (DPPH radical-scavenging assay showed that PTZ-induced addicsin translocation was accompanied by a decrease of radical-scavenging activity and an increase of cytotoxicity in a PTZ dose-dependent manner. These findings suggest that PTZ induces the translocation of addicsin from the ER to the plasma membrane and modulates the redox system by regulating EAAC1-mediated GSH synthesis, which leads to the activation of cell death signaling.

Effect of Pentylenetetrazol on Morphine State-Dependent Memory in Rat

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Marziyeh Tavassoli

2017-09-01

Full Text Available Abstract Background: Learning and memory are among the higher functions of the brain. State-dependent memory (STM is a type of memory in which the recall of a learned behavior is happend only in the same sensory and physiologic condition in which the behavior is encoded. The STM is seen with some drugs, e.g. the morphine. The pentylenetetrazol (PTZ is a durg which is used for the induction of seizure in experimental models. Some studies have been revealed different effects of the PTZ on brain higher function (learning, memory …. The aim of present study was to explore the effect of PTZ on morphine-induced STM. Materials and Methods: In this study, male adult Wistar rats (190-220 g were used. Animals in 3 groups (n=8 during 3 sessions (learning/memory, STM and interaction were studied. During 48 hour (training and test the learning and memory of animals were studied in inhibitory avoidance apparatus. The step-through latency in the test day was used as a criterion for memory. Post-training injection of saline or morphine (2.5, 5 and 7.5 mg/kg-ip in different groups was carried out. In addition, the pre-test injection of morphine at the same doses was made to study the STM. Moreover, the interaction of pre-test single-dose PTZ (60 mg/kg-ip on STM was studied. The locomotion of the animals was measured using the open field. Results: The post-training injection of morphine (2.5, 5 and 7.5 mg/kg-ip impaired the inhibitory memory of rats compared to control group (p<0.001. The post-training and pre-test injections of the same dose of morphine (7.5 mg/kg-ip reversed the impaired memory compared to morphine (2.5 and 5 mg/kg-ip, (p<0.001. The pre-test PTZ (60 mg/kg-ip maintained the morphine (7.5 mg/kg-ip STM (p<0.001. Conclusion: The present study revealed that the post-training ip injection of different doses of morphine results in the impairment of inhibitory avoidance memory in rat. In addition, the pre-test injection of the same doses of morphine

Vertebral Artery Dissection Associated with Generalized Convulsive Seizures: A Case Report

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Faisal Mohammad Amin

2013-07-01

Full Text Available A 46-year-old male with juvenile myoclonic epilepsy was admitted to the neurological department for convulsive seizures just after lamotrigine was discontinued. On admission he was awake but had a right-sided hemiparesis with Babinski sign and ataxic finger-nose test on the left side. An MR scan showed a left-sided pontine infarction, an infarct in the left cerebellar hemisphere and a right vertebral artery dissection (VAD. The patient was treated with heparin and an oral anticoagulant for 6 months. Recovery of neurologic function was excellent. In patients with symptoms of disturbances of posterior circulation after epileptic seizures, VAD should be considered.

Electro convulsive therapy in a pre-pubertal child with severe depression.

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Russell P

2002-10-01

Full Text Available Electro Convulsive Therapy (ECT in pre-pubertal children is a controversial and underreported treatment. Even though the effectiveness and side effects of ECT in adolescents are comparable with those in adults, there is a pervasive reluctance to use ECT in children and adolescents. We report the case of a pre-pubertal child in an episode of severe depression with catatonic features, where a protracted course of ECT proved life-saving in spite of prolonged duration of seizures and delayed response to treatment. The case illustrates the safety and efficacy of ECT in children. Relevant literature is also reviewed along with the case report.

Differentiation between eclampsia and cerebrovascular disorders by brain CT scan in pregnant patients with convulsive seizures

International Nuclear Information System (INIS)

Eguchi, Katsuto; Lin, Yaw-Tyng; Noda, Kiyofumi; Saeki, Kazuhiko; Yonezawa, Masaru; Sekiba, Kaoru; Ochiai, Youji

1987-01-01

Six pregnant women with convulsions between 25 to 40 weeks of gestation were experienced. Among them, 4 patients were diagnosed as having intracranial hemorrhage and two as simple eclampsia. With the aid of brain CT scan, one case of arteriovenous malformation was detected and treated surgically with good prognosis for both the mother and the fetus. Two patients were diagnosed to have cerebral hemorrhage with subsequent penetration into the lateral ventricles and were treated conservatively. Their fetuses were delivered alive by cesarean section, but the mothers expired. The other patient with cerebral hemorrhage was treated surgically, and both the mother and the fetus survived. One of the simple eclampsia patients was noted to have a growth retarded fetus at 32 weeks of pregnancy with subsequent intra-uterine death, but the mother recovered after conservative treatment. Another patient at 40 weeks of pregnancy was also treated conservatively and both the fetus and the mother survived. Brain CT scan findings differed between these two eclampsia patients; local brain edema for the second patient and generalized brain edema for the first patient. Thus more active application of brain CT scan is recommended in managing pregnant patients with convulsions. (author)

Differentiation between eclampsia and cerebrovascular disorders by brain CT scan in pregnant patients with convulsive seizures

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Eguchi, Katsuto; Lin, Yaw-Tyng; Noda, Kiyofumi; Saeki, Kazuhiko; Yonezawa, Masaru; Sekiba, Kaoru; Ochiai, Youji

1987-06-01

Six pregnant women with convulsions between 25 to 40 weeks of gestation were experienced. Among them, 4 patients were diagnosed as having intracranial hemorrhage and two as simple eclampsia. With the aid of brain CT scan, one case of arteriovenous malformation was detected and treated surgically with good prognosis for both the mother and the fetus. Two patients were diagnosed to have cerebral hemorrhage with subsequent penetration into the lateral ventricles and were treated conservatively. Their fetuses were delivered alive by cesarean section, but the mothers expired. The other patient with cerebral hemorrhage was treated surgically, and both the mother and the fetus survived. One of the simple eclampsia patients was noted to have a growth retarded fetus at 32 weeks of pregnancy with subsequent intra-uterine death, but the mother recovered after conservative treatment. Another patient at 40 weeks of pregnancy was also treated conservatively and both the fetus and the mother survived. Brain CT scan findings differed between these two eclampsia patients; local brain edema for the second patient and generalized brain edema for the first patient. Thus more active application of brain CT scan is recommended in managing pregnant patients with convulsions.

Rocuronium and sugammadex: An alternative to succinylcholine for electro convulsive therapy in patients with suspected neuroleptic malignant syndrome.

LENUS (Irish Health Repository)

Ramamoorthy, Karthik G

2012-01-31

We report a case of presumptive neuroleptic malignant syndrome requiring muscle relaxation for electro-convulsive therapy. short acting muscle relaxation without the use of succinylcholine was achieved using rocvronivm reversed with the novel reversal agent sugammadex. We suggest that this combination is a safe and effective alternative to succinylcholine in such cases.

Rocuronium and sugammadex: An alternative to succinylcholine for electro convulsive therapy in patients with suspected neuroleptic malignant syndrome

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Karthik G Ramamoorthy

2011-01-01

Full Text Available We report a case of presumptive neuroleptic malignant syndrome requiring muscle relaxation for electro-convulsive therapy. short acting muscle relaxation without the use of succinylcholine was achieved using rocvronivm reversed with the novel reversal agent sugammadex. We suggest that this combination is a safe and effective alternative to succinylcholine in such cases.

Anticonvulsant activity of DNS II fraction in the acute seizure models.

Science.gov (United States)

Raza, Muhammad Liaquat; Zeeshan, Mohammad; Ahmad, Manzoor; Shaheen, Farzana; Simjee, Shabana U

2010-04-21

Delphinium nordhagenii belongs to family Ranunculaceae, it is widely found in tropical areas of Pakistan. Other species of Delphinium are reported as anticonvulsant and are traditionally used in the treatment of epilepsy. Delphinium nordhagenii is used by local healer in Pakistan but never used for scientific investigation as anticonvulsant. Thus, Delphinium nordhagenii was subjected to bioassay-guided fractionation and the most active fraction, i.e. DNS II acetone was chosen for further testing in the acute seizure models of epilepsy to study the antiepileptic potential in male mice. Different doses (60, 65 and 70mg/kg, i.p.) of DNS II acetone fraction of Delphinium nordhagenii was administered 30min prior the chemoconvulsant's injection in the male mice. Convulsive doses of chemoconvulsants (pentylenetetrazole 90mg/kg, s.c. and picrotoxin 3.15mg/kg, s.c.) were used. The mice were observed 45-90min for the presence of seizures. Moreover, four different doses of DNS II (60, 65, 70 and 100mg/kg, i.p.) were tested in the MES test. The DNS II acetone fraction of Delphinium nordhagenii has exhibited the anticonvulsant actions by preventing the seizures against PTZ- and picrotoxin-induced seizure as well as 100% seizure protection in MES test. The results are comparable with standard AEDs (diazepam 7.5mg/kg, i.p. and phenytoin 20mg/kg, i.p.). These findings suggest that the Delphinium nordhagenii possesses the anticonvulsant activity. Further analysis is needed to confirm the structure and target the extended activity profile. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

The Emperor Dom Pedro II: his convulsive seizures when a boy O imperador Dom Pedro II: as suas crises convulsivas quando menino

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Marleide da Mota Gomes

2007-12-01

Full Text Available INTRODUCTION: Dom Pedro II, the Prince Heir and Emperor under regency, in a delicate period of the construction of the Brazilian nation, had convulsive seizures. OBJECTIVE: To investigate the convulsive seizures and related syndromes of Dom Pedro II and his family, besides the physicians in charge of the health care. METHOD: Narrative review based on primary and secondary sources. CONCLUSION: The scattered and self-limited convulsive seizures associated with physical and mental integrity favored a benign prognosis. Dom Pedro and his family presented rich history of epileptic seizures and febrile convulsion. This variety resembles the diagnosis of generalized epilepsy with febrile seizures plus that seems to be a combination of several syndromes with shared genetic susceptibility.INTRODUÇÃO: Dom Pedro, o príncipe herdeiro e imperador sob regência, em período delicado da formação da nação brasileira, apresentou crises convulsivas que geraram preocupação para o país. OBJETIVO: Investigar a história da epilepsia de Dom Pedro II e da sua família e procurar identificar quais tipos de crises epilépticas estavam presentes, além dos médicos envolvidos com os cuidados de saúde. MÉTODO: Revisão narrativa baseada em fontes primárias e secundárias. CONCLUSÃO: As crises convulsivas esparsas e auto-limitadas associadas a higidez física e mental de Dom Pedro II sugerem um prognóstico benigno. A história de epilepsia idiopática e convulsões febris no imperador e em outros membros da sua família aponta para o diagnóstico mais provável de Epilepsia Generalizada com Convulsões Febris Plus que é determinada por uma combinação de alguns tipos de manifestações epilépticas com suscetibilidade genética compartilhada.

Hemi-convulsion-hemiplegia syndrome revisited: longitudinal MRI findings in 10 children

International Nuclear Information System (INIS)

Barcia; Giulia; Chemaly, Nicole; Dulac, Olivier; Nabbout, Rima; Desguerre, Isabelle; Carmona, Orietta; Barnerias, Christine; Gitiaux, Cyril; Brunelle, Francis; Boddaert, Nathalie

2013-01-01

Hemi-convulsion-hemiplegia syndrome (HHS) is a rare severe epilepsy of infancy consisting of unilateral convulsive status epilepticus immediately followed by transient or lasting ipsilateral hemiplegia. HHS may occur either in patients with previous brain pathology or without any identified cause, so-called 'idiopathic HHS'. We retrospectively analysed clinical and MRI longitudinal findings of a series of 10 patients (six females, four males) presenting with HHS. Age at the study inclusion ranged from 2 years 6 months to 15 years (mean of 5 y 10 mo, median 4 y 2 mo). After defining magnetic resonance imaging (MRI) features as 'typical', i.e. strictly unilateral involvement, and 'atypical', i.e. bilateral, we compared clinical data from both groups. Cognitive level was assessed using Brunet-Lezine or Wechsler scales. HHS occurred at a mean age of 20.5 months (range 8-48 mo). In all cases, status epilepticus lasted for more than 1 hour and was characterised by unilateral clonic seizures followed by ipsilateral hemiplegia (persistent in five patients). Two patients in this series died: the first from multi-organ failure 2 weeks after the status epilepticus and the other from a second episode of ipsilateral intractable febrile status epilepticus 3 years after the first episode. Early MRI (days 1-7 from status epilepticus) showed hemispheric cytotoxic oedema in all, extending to the contralateral side for one. T2 hyperintensity in the basal ganglia was disclosed in 70% of patients and in the hippocampus in 60%. After 1 month (in intermediate and chronic phases), all surviving patients but one showed hemispheric cortical atrophy corresponding to the regions involved during the early stage. Comparing clinical features of patients presenting with 'typical' features, to those with 'atypical' findings, the second group presented psychomotor delay before status epilepticus. This series underlines the major value of early MRI

Hemi-convulsion-hemiplegia syndrome revisited: longitudinal MRI findings in 10 children

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Barcia,; Giulia,; Chemaly, Nicole; Dulac, Olivier; Nabbout, Rima [Reference Centre for Rare Epilepsies, Department of Paediatric Neurology, Hopital Necker-Enfants malades, APHP, Paris (France); Inserm U663, Paris [France; University Paris Descartes, CEA, Gif sur Yvette (France); Desguerre, Isabelle; Carmona, Orietta; Barnerias, Christine; Gitiaux, Cyril [Reference Centre for Rare Epilepsies, Department of Paediatric Neurology, Hopital Necker-Enfants malades, APHP, Paris (France); Brunelle, Francis; Boddaert, Nathalie [Paediatric Radiology Department, Hopital Necker-Enfants malades, APHP, Paris, (France)

2013-07-01

Hemi-convulsion-hemiplegia syndrome (HHS) is a rare severe epilepsy of infancy consisting of unilateral convulsive status epilepticus immediately followed by transient or lasting ipsilateral hemiplegia. HHS may occur either in patients with previous brain pathology or without any identified cause, so-called 'idiopathic HHS'. We retrospectively analysed clinical and MRI longitudinal findings of a series of 10 patients (six females, four males) presenting with HHS. Age at the study inclusion ranged from 2 years 6 months to 15 years (mean of 5 y 10 mo, median 4 y 2 mo). After defining magnetic resonance imaging (MRI) features as 'typical', i.e. strictly unilateral involvement, and 'atypical', i.e. bilateral, we compared clinical data from both groups. Cognitive level was assessed using Brunet-Lezine or Wechsler scales. HHS occurred at a mean age of 20.5 months (range 8-48 mo). In all cases, status epilepticus lasted for more than 1 hour and was characterised by unilateral clonic seizures followed by ipsilateral hemiplegia (persistent in five patients). Two patients in this series died: the first from multi-organ failure 2 weeks after the status epilepticus and the other from a second episode of ipsilateral intractable febrile status epilepticus 3 years after the first episode. Early MRI (days 1-7 from status epilepticus) showed hemispheric cytotoxic oedema in all, extending to the contralateral side for one. T2 hyperintensity in the basal ganglia was disclosed in 70% of patients and in the hippocampus in 60%. After 1 month (in intermediate and chronic phases), all surviving patients but one showed hemispheric cortical atrophy corresponding to the regions involved during the early stage. Comparing clinical features of patients presenting with 'typical' features, to those with 'atypical' findings, the second group presented psychomotor delay before status epilepticus. This series underlines the major value of early MRI for the prompt diagnosis of HHS, and shows that

Anti-kindling Effect of Bezafibrate, a Peroxisome Proliferator-activated Receptors Alpha Agonist, in Pentylenetetrazole Induced Kindling Seizure Model.

Science.gov (United States)

Saha, Lekha; Bhandari, Swati; Bhatia, Alka; Banerjee, Dibyajyoti; Chakrabarti, Amitava

2014-12-01

Studies in the animals suggested that Peroxisome proliferators activated receptors (PPARs) may be involved in seizure control and selective agonists of PPAR α or PPAR γ raise seizure thresholds. The present study was contemplated with the aim of evaluating the anti kindling effects and the mechanism of bezafibrate, a Peroxisome proliferator-activated receptors α (PPAR-α) agonist in pentylenetetrazole (PTZ) induced kindling model of seizures in rats. In a PTZ kindled Wistar rat model, different doses of bezafibrate (100 mg/kg, 200 mg/kg and 300 mg/kg) were administered intraperitoneally 30 minutes before the PTZ injection. The PTZ injection was given on alternate day till the animal became fully kindled or till 10 weeks. The parameters measured were the latency to develop kindling and incidence of kindling, histopathological study of hippocampus, hippocampal lipid peroxidation studies, serum neuron specific enolase, and hippocampal DNA fragmentation study. In this study, bezafibrate significantly reduced the incidence of kindling in PTZ treated rats and exhibited a marked prolongation in the latencies to seizures. In the present study bezafibrate decreased the thiobarbituric acid-reactive substance i.e. Malondialdehyde levels, increased the reduced glutathione levels, catalase and superoxide dismutase activity in the brain. This added to its additional neuroprotective effects. Bezafibrate also reduced the neuronal damage and apoptosis in hippocampal area of the brain. Therefore bezafibrate exerted anticonvulsant properties in PTZ induced kindling model in rats. These findings may provide insights into the understanding of the mechanism of bezafibrate as an anti kindling agent and could offer a useful support to the basic antiepileptic therapy in preventing the development of PTZ induced seizures, suggesting its potential for therapeutic applications in temporal lobe epilepsy.

Toxic cocaine- and convulsant-induced modification of forced swimming behaviors and their interaction with ethanol: comparison with immobilization stress

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Hayase, Tamaki; Yamamoto, Yoshiko; Yamamoto, Keiichi

2002-01-01

Background Swimming behaviors in the forced swimming test have been reported to be depressed by stressors. Since toxic convulsion-inducing drugs related to dopamine [cocaine (COC)], benzodiazepine [methyl 6,7-dimethoxy-4-ethyl-β-carboline-carboxylate (DMCM)], γ-aminobutyric acid (GABA) [bicuculline (BIC)], and glutamate [N-methyl-D-aspartate (NMDA)] receptors can function as stressors, the present study compared their effects on the forced swimming behaviors with the effects of immobilization stress (IM) in rats. Their interactions with ethanol (EtOH), the most frequently coabused drug with COC which also induces convulsions as withdrawal symptoms but interferes with the convulsions caused by other drugs, were also investigated. Results Similar to the IM (10 min) group, depressed swimming behaviors (attenuated time until immobility and activity counts) were observed in the BIC (5 mg/kg IP) and DMCM (10 mg/kg IP) groups at the 5 h time point, after which no toxic behavioral symptoms were observed. However, they were normalized to the control levels at the 12 h point, with or without EtOH (1.5 g/kg IP). In the COC (60 mg/kg IP) and NMDA (200 mg/kg IP) groups, the depression occurred late (12 h point), and was normalized by the EtOH cotreatment. At the 5 h point, the COC treatment enhanced the swimming behaviors above the control level. Conclusions Although the physiological stress (IM), BIC, and DMCM also depressed the swimming behaviors, a delayed occurrence and EtOH-induced recovery of depressed swimming were observed only in the COC and NMDA groups. This might be correlated with the previously-reported delayed responses of DA and NMDA neurons rather than direct effects of the drugs, which could be suppressed by EtOH. Furthermore, the characteristic psychostimulant effects of COC seemed to be correlated with an early enhancement of swimming behaviors. PMID:12425723

Loss of consciousness and convulsion induced by a ventricular tachycardia mimicking epilepsy in a patient with noncompaction cardiomyopathy : a case report

NARCIS (Netherlands)

Dello, S. A. W. G.; Kievit, C.; Dunselman, P. H.; Alings, M.

Convulsions and loss of consciousness can be caused by, among other things, arrhythmias, conduction disorders or epilepsy. In clinical practice it can be difficult to distinguish between these causes of syncope, even for well-trained specialists. Patients with cardiac syncope have a substantial risk

Dentate gyrus mossy cells control spontaneous convulsive seizures and spatial memory.

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Bui, Anh D; Nguyen, Theresa M; Limouse, Charles; Kim, Hannah K; Szabo, Gergely G; Felong, Sylwia; Maroso, Mattia; Soltesz, Ivan

2018-02-16

Temporal lobe epilepsy (TLE) is characterized by debilitating, recurring seizures and an increased risk for cognitive deficits. Mossy cells (MCs) are key neurons in the hippocampal excitatory circuit, and the partial loss of MCs is a major hallmark of TLE. We investigated how MCs contribute to spontaneous ictal activity and to spatial contextual memory in a mouse model of TLE with hippocampal sclerosis, using a combination of optogenetic, electrophysiological, and behavioral approaches. In chronically epileptic mice, real-time optogenetic modulation of MCs during spontaneous hippocampal seizures controlled the progression of activity from an electrographic to convulsive seizure. Decreased MC activity is sufficient to impede encoding of spatial context, recapitulating observed cognitive deficits in chronically epileptic mice. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Central nervous system activity of an aqueous acetonic extract of Ficus carica L. in mice

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Mittal M Bhanushali

2014-01-01

Full Text Available Background: Ficus carica Linn. is reported to possess variety of activities, but its potential in CNS disorders is still to be explored. Objective: The present study was carried out to evaluate the CNS depressant activity of aqueous acetonic extract of Ficus carica Linn on different models in mice. Materials and Methods: The aerial parts of the plant Ficus carica L. were extracted with aqueous acetone and the solvent was removed by rotary vacuum evaporator under reduced pressure. A crude extract was given orally and its effects were tested on ketamine-induced sleeping time, muscle-coordination, anxiety (elevated-plus maze and Staircase test, convulsions [maximal electroshock (MES and pentylenetetrazole (PTZ-induced seizures], and nociception. In addition, we determined the levels of neurotransmitters, norepinephrine (NE and 5-hydroxytryptamine (5-HT. Results: Results from the experimental models tested showed: (1 a delay on onset and prolongation of sleep of ketamine-induced sleeping time; (2 significant muscle relaxant activity; (3 a significant attenuation in the anxiety-response (4 a delay in the onset of seizures and reduction in duration of seizures and mortality induced by MES and PTZ; (5 a reduction in the licking time in nociception test and (6 increased levels of NE and 5-HT. Conclusion: This suggests that Ficus carica L. exerts its CNS depressive effect by modulating the neurotransmitters NE and 5-HT in the brain.

Neuropharmacological and neuroprotective activities of some metabolites produced by cell suspension culture of Waltheria americana Linn.

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Mundo, Jorge; Villeda-Hernández, Juana; Herrera-Ruiz, Maribel; Gutiérrez, María Del Carmen; Arellano-García, Jesús; León-Rivera, Ismael; Perea-Arango, Irene

2017-10-01

Waltheria americana is a plant used in Mexican traditional medicine to treat some nervous system disorders. The aims of the present study were to isolate and determine the neuropharmacological and neurprotective activities of metabolites produced by a cell suspension culture of Waltheria americana. Submerged cultivation of W. americana cells provided biomass. A methanol-soluble extract (WAsc) was obtained from biomass. WAsc was fractionated yielding the chromatographic fractions 4WAsc-H 2 O and WAsc-CH 2 Cl 2 . For the determination of anticonvulsant activity in vivo, seizures were induced in mice by pentylenetetrazol (PTZ). Neuropharmacological activities (release of gamma amino butyric acid (GABA) and neuroprotection) of chromatographic fractions were determined by in vitro histological analysis of brain sections of mice post mortem. Fraction 4WAsc-H 2 O (containing saccharides) did not produce neuronal damage, neurodegeneration, interstitial tissue edema, astrocytic activation, nor cell death. Pretreatment of animals with 4WAsc-H 2 O and WAsc-CH 2 Cl 2 from W. americana cell suspensions induced an increase in: GABA release, seizure latency, survival time, neuroprotection, and a decrease in the degree of severity of tonic/tonic-clonic convulsions, preventing PTZ-induced death of up to 100% of animals of study. Bioactive compounds produced in suspension cell culture of W. americana produce neuroprotective and neuropharmacological activities associated with the GABAergic neurotransmission system. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Validation of the French national health insurance information system as a tool in vaccine safety assessment: application to febrile convulsions after pediatric measles/mumps/rubella immunization.

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Hanf, Matthieu; Quantin, Catherine; Farrington, Paddy; Benzenine, Eric; Hocine, N Mounia; Velten, Michel; Tubert-Bitter, Pascale; Escolano, Sylvie

2013-12-02

In the French national health insurance information system (SNIIR-AM), routine records of health claimed reimbursements are linked to hospital admissions for the whole French population. The main focus of this work is the usability of this system for vaccine safety assessment programme. Self-controlled case series analyses were performed using an exhaustive SNIIR-AM extraction of French children aged less than 3 years, to investigate the relationship between MMR immunization and children hospitalizations for febrile convulsions, a well-documented rare adverse event, over 2009-2010. The results suggest a significant increase of febrile convulsions during the 6-11 days period following any MMR immunization (IRR=1.49, 95% CI=1.22, 1.83; p=0.0001) and no increase 15-35 days post any MMR immunization (IRR=1.03, 95% CI=0.89, 1.18; p=0.72). These results are in accordance with other results obtained from large epidemiologic studies, which suggest the usability of the SNIIR-AM as a relevant database to study the occurrence of adverse events associated with immunization. For future use, results associated with risk of convulsion during the day of vaccination should nevertheless be considered with particular caution. Copyright © 2013 Elsevier Ltd. All rights reserved.

De betekenis van consulieachtige verschijnselen in de eerste twee levensjaren [mportance of convulsion-like signs during the first two years of life

NARCIS (Netherlands)

Reerink, J.D.; Herngreen, W.P.; Peters, A.C.B.; Ouden, A.L. den; Verloove-Vanhorick, S.P.; Ruys, J.H.

1994-01-01

Objective. Assessment of the prevalence of convulsion-like symptoms in 1854 children of Dutch-speaking mothers of a population-based birth cohort. Method. At each child health clinic (CHC) visit mothers were asked whether they had noted any of the following signs: loss of consciousness, involuntary

[Prehospital management of febrile convulsions by the Mobile Emergency Care Unit in the Capital Region of Denmark

DEFF Research Database (Denmark)

Lindekaer, A.L.; Nielsen, S.L.; Pedersen, Ulf Gøttrup

2008-01-01

INTRODUCTION: We conducted a quality assurance project of The Mobile Emergency Care Unit (MECU) in the Capital Region of Denmark when dispatched to febrile convulsions. The study focuses on prehospital treatment, comparison between prehospital and in-hospital diagnoses and parents' perceptions......% of cases, the prehospital and in-hospital diagnosis were identical. CONCLUSION: In general, parents appreciate the service provided by the MECU. Reasons of dissatisfaction are described. On several occasions, the prehospital physician administered intravenous anticonvulsants, but we discuss if the MECU...

Acute administration of ginger (Zingiber officinale rhizomes) extract on timed intravenous pentylenetetrazol infusion seizure model in mice.

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Hosseini, Abdolkarim; Mirazi, Naser

2014-03-01

Zingiber officinale (Zingiberaceae) or ginger, which is used in traditional medicine has antioxidant activity and neuroprotective effects. The effects of this plant on clonic seizure have not yet been studied. The present study evaluated the anticonvulsant effect of ginger in a model of clonic seizures induced with pentylenetetrazole (PTZ) in male mice. The anticonvulsant effect of Z. officinale was investigated using i.v. PTZ-induced seizure models in mice. Different doses of the hydroethanolic extract of Z. officinale (25, 50, and 100mg/kg) were administered intraperitonal (i.p.), 2 and 24h before induction of PTZ. Phenobarbital sodium (30mg/kg), a reference standard, was also tested for comparison. The effect of ginger on to the appearance of three separate seizure endpoints (myoclonic, generalized clonus and forelimb tonic extension phase) was recorded. The results showed that the ginger extract has anticonvulsant effects in all the experimental treatment groups of seizure tested as it significantly increased the seizure threshold. Hydroethanolic extract of Z. officinale significantly increased the onset time of myoclonic seizure at doses of 25-100mg/kg (p<0.001) and significantly prevented generalized clonic (p<0.001) and increased the threshold for the forelimb tonic extension (p<0.01) seizure 2 and 24h before induction of PTZ compared with control group. Based on the results the hydroethanolic extract of ginger has anticonvulsant effects, possibly through an interaction with inhibitory and excitatory system, antioxidant mechanisms, oxidative stress and calcium channel inhibition. Copyright © 2014 Elsevier B.V. All rights reserved.

Alteration of pentylenetetrazole-induced seizure threshold by chronic administration of ginger (Zingiber officinale) extract in male mice.

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Hosseini, Abdolkarim; Mirazi, Naser

2015-05-01

Zingiber officinale Roscoe (Zingiberaceae), or ginger, used in traditional Chinese medicine, has antioxidant activity and neuroprotective effects. The effects of this plant on clonic seizure have not yet been studied. The present study evaluated the anticonvulsant effect of ginger in a model of clonic seizures induced with pentylenetetrazole (PTZ) in male mice. The anticonvulsant effect of Z. officinale was investigated using i.v. PTZ-induced seizure models in mice. Different doses of the hydroethanolic extract of Z. officinale (25, 50, and 100 mg/kg) were administered intraperitonal (i.p.), daily for 1 week before induction of PTZ. Phenobarbital sodium (30 mg/kg), a reference standard, was also tested for comparison. The effect of ginger on to the appearance of three separate seizure endpoints, e.g., myoclonic, generalized clonic, and tonic extension phase, was recorded. Hydroethanolic extract of Z. officinale significantly increased the onset time of myoclonic seizure at doses of 25-100 mg/kg (55.33 ± 1.91 versus 24.47 ± 1.33 mg/kg, p < 0.001) and significantly prevented generalized clonic (74.64 ± 3.52 versus 47.72 ± 2.31 mg/kg, p < 0.001) and increased the threshold for the forelimb tonic extension (102.6 ± 5.39 versus 71.82 ± 7.82 mg/kg, p < 0.01) seizure induced by PTZ compared with the control group. Based on the results, the hydroethanolic extract of ginger has anticonvulsant effects, possibly through an interaction with inhibitory and excitatory systems, antioxidant mechanisms, and oxidative stress inhibition.

Vinpocetine inhibits glutamate release induced by the convulsive agent 4-aminopyridine more potently than several antiepileptic drugs.

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Sitges, M; Sanchez-Tafolla, B M; Chiu, L M; Aldana, B I; Guarneros, A

2011-10-01

4-Aminopyridine (4-AP) is a convulsing agent that in vivo preferentially releases Glu, the most important excitatory amino acid neurotransmitter in the brain. Here the ionic dependence of 4-AP-induced Glu release and the effects of several of the most common antiepileptic drugs (AEDs) and of the new potential AED, vinpocetine on 4-AP-induced Glu release were characterized in hippocampus isolated nerve endings pre-loaded with labelled Glu ([3H]Glu). 4-AP-induced [3H]Glu release was composed by a tetrodotoxin (TTX) sensitive and external Ca2+ dependent fraction and a TTX insensitive fraction that was sensitive to the excitatory amino acid transporter inhibitor, TBOA. The AEDs: carbamazepine, phenytoin, lamotrigine and oxcarbazepine at the highest dose tested only reduced [3H]Glu release to 4-AP between 50-60%, and topiramate was ineffective. Vinpocetine at a much lower concentration than the above AEDs, abolished [3H]Glu release to 4-AP. We conclude that the decrease in [3H]Glu release linked to the direct blockade of presynaptic Na+ channels, may importantly contribute to the anticonvulsant actions of all the drugs tested here (except topiramate); and that the significantly greater vinpocetine effect in magnitude and potency on [3H]Glu release when excitability is exacerbated like during seizures, may involve the increase additionally exerted by vinpocetine in some K+ channels permeability. Copyright © 2011 Elsevier B.V. All rights reserved.

Mutations in the Gene PRRT2 Cause Paroxysmal Kinesigenic Dyskinesia with Infantile Convulsions

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Hsien-Yang Lee

2012-01-01

Full Text Available Paroxysmal kinesigenic dyskinesia with infantile convulsions (PKD/IC is an episodic movement disorder with autosomal-dominant inheritance and high penetrance, but the causative genetic mutation is unknown. We have now identified four truncating mutations involving the gene PRRT2 in the vast majority (24/25 of well-characterized families with PKD/IC. PRRT2 truncating mutations were also detected in 28 of 78 additional families. PRRT2 encodes a proline-rich transmembrane protein of unknown function that has been reported to interact with the t-SNARE, SNAP25. PRRT2 localizes to axons but not to dendritic processes in primary neuronal culture, and mutants associated with PKD/IC lead to dramatically reduced PRRT2 levels, leading ultimately to neuronal hyperexcitability that manifests in vivo as PKD/IC.

Curcumin-loaded chitosan-alginate-STPP nanoparticles ameliorate memory deficits and reduce glial activation in pentylenetetrazol-induced kindling model of epilepsy.

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Hashemian, Mona; Anissian, Diana; Ghasemi-Kasman, Maryam; Akbari, Atefeh; Khalili-Fomeshi, Mohsen; Ghasemi, Shahram; Ahmadi, Fatemeh; Moghadamnia, Ali Akbar; Ebrahimpour, Anahita

2017-10-03

Despite several beneficial effects of curcumin, its medical application has been hampered due to low water solubility. To improve the aqueous solubility of curcumin, it has been loaded on chitosan (CS)-alginate (ALG) - sodium tripolyphosphate (STPP) nanoparticles (NPs). Then, the effect of curcumin NPs on memory improvement and glial activation was investigated in pentylenetetrazol (PTZ)-induced kindling model. Male NMRI mice have received the daily injection of curcumin NPs at dose of 12.5 or 25mg/kg. All interventions were injected intraperitoneally (i.p), 10days before PTZ administration and the injections were continued until 1h before each PTZ injection. Spatial learning and memory was evaluated using Morris water maze test after the 7th PTZ injection. Animals have received 10 injections of PTZ and then, brain tissues were removed for histological evaluation. Nissl staining was used to determine the level of cell death in hippocampus and immunostaining method was performed against NeuN and GFAP/Iba1 for assessment of neuronal density and glial activation respectively. Behavioral results showed that curcumin NPs exhibit anticonvulsant activity and prevent cognitive impairment in fully kindled animals. The level of cell death and glial activation reduced in animals which have received curcumin NPs compared to those received free curcumin. To conclude, these findings suggest that curcumin NPs effectively ameliorate memory impairment and attenuate the level of activated glial cells in a mice model of chronic epilepsy. Copyright © 2017. Published by Elsevier Inc.

A case of acute disseminated encephalomyelitis with convulsion, gait disturbance, facial palsy and with multifocal CT lesions

International Nuclear Information System (INIS)

Nagano, Tetsu; Kurihara, Eiji; Mizuno, Yoshihiko; Tamagawa, Kimiko; Komiya, Kazuhiko; Mizuguchi, Masashi.

1988-01-01

A case of acute disseminated encephalomyelitis (ADEM) was presented. The patient was a 4-year-old boy with convulsion, ataxic gait, facial palsy. It was postulated that the influenza vaccine might induce the disease in this case. Cranial CT showed a low density arease in the right temporal lobe, which disappeared afterwards when other low density areas appeared in the right cerebellar hemisphere and in inner portion of the body of the left lateral ventricle. All symptoms disappeared without therapy and the CT findings improved within three months after onset. (author)

Intermittent diazepam prophylaxis in febrile convulsions. Pros and cons.

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Knudsen, F U

1991-01-01

Major cohort studies document that the long-term prognosis for most children with febrile convulsions (FC) is excellent. The 2 main treatment alternatives so far have been long-term prophylaxis with phenobarbital or valproate or no prophylaxis at all. Phenobarbital at times of fever is ineffective and obsolete. Consensus has emerged that long-term prophylaxis with antiepileptic drugs is rarely justified in FC considering the side effects and the favourable prognosis. No treatment at all does not appear quite satisfactory either, as FC have a high recurrence rate, disrupt family life and may have emotional consequences for the family. Moreover, all FC children face a risk, although admittedly low, of subsequent long-lasting potentially central nervous system (CNS)-damaging seizures. However, 2 further options exist: treatment with rapid-acting benzodiazepines solely at times of greatest risk, i.e., at high fever or at renewed seizures. Several clinical trials have confirmed that intermittent diazepam prophylaxis by way of a few doses of the drug per year provides effective seizure control and reduces the recurrence rate by one half or two thirds. The treatment is feasible and cheap, well tolerated by the child and well accepted by the parents. Compliance problems are common and only partly abatable. Trivial side effects are frequent. Transient respiratory apnoea does occur, but 15 years' experience substantiates that serious side effects are remarkably rare. Acute anticonvulsant treatment with rectal diazepam in solution given by the parents to stop ongoing seizures and to prevent immediate recurrences is an attractive alternative. It is feasible, is probably effective and minimizes the use of drugs, but compliance problems are common and protracted seizures are not always controlled. The subsequent management should include a risk profile approach considering a combination of risk factors for new FC rather than a single factor. By means of a risk index, based on

Anticonvulsant potentials of ethanolic extract of Eleusine indica

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Ette Okon Ettebong

2016-11-01

Full Text Available Objective: To assess the anticonvulsant potentials of ethanolic extract of Eleusine indica. Methods: Albino Wistar mice were separated into five groups with six animals in each group and thereafter pretreated with distilled water, various doses of the extract (200–600 mg/kg and standard drug diazepam (0.5 mg/kg. Thirty minutes later, pentylenetetrazole (70 mg/kg, aminophylline (280 mg/kg and isoniazid (250 mg/kg were used to induce convulsions by intraperitoneal administration. These mice were then placed in plexiglas cages and monitored for the occurrence of seizures over a thirty-minute time period. The latency of convulsions, duration of tonic convulsions and mortality protection were recorded. Data obtained were analyzed using GraphPad InStat 3.10. Results: The results showed that the extract exhibited a dose-dependent increase in the latency of clonic convulsions and decrease in duration of tonic convulsions as compared to the control and these effects were statistically significant (P < 0.001. The extract also provided protection against the mortality which was similar to that produced by the standard drug diazepam. Conclusions: The significant increase in the latency of clonic convulsions and decrease in duration of tonic convulsions caused by the extract show anticonvulsant activity and corroborate with the claims of the traditional use of the plant as an anticonvulsant remedy.

Comparative Anticonvulsant Study of Epoxycarvone Stereoisomers

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Paula Regina Rodrigues Salgado

2015-10-01

Full Text Available Stereoisomers of the monoterpene epoxycarvone (EC, namely (+-cis-EC, (−-cis-EC, (+-trans-EC, and (−-trans-EC, were comparatively evaluated for anticonvulsant activity in specific methodologies. In the pentylenetetrazole (PTZ-induced anticonvulsant test, all of the stereoisomers (at 300 mg/kg increased the latency to seizure onset, and afforded 100% protection against the death of the animals. In the maximal electroshock-induced seizures (MES test, prevention of tonic seizures was also verified for all of the isomers tested. However, the isomeric forms (+ and (−-trans-EC showed 25% and 12.5% inhibition of convulsions, respectively. In the pilocarpine-induced seizures test, all stereoisomers demonstrated an anticonvulsant profile, yet the stereoisomers (+ and (−-trans-EC (at 300 mg/kg showed a more pronounced effect. A strychnine-induced anticonvulsant test was performed, and none of the stereoisomers significantly increased the latency to onset of convulsions; the stereoisomers probably do not act in this pathway. However, the stereoisomers (+-cis-EC and (+-trans-EC greatly increased the latency to death of the animals, thus presenting some protection. The four EC stereoisomers show promise for anticonvulsant activity, an effect emphasized in the isomers (+-cis-EC, (+-trans-EC, and (−-trans-EC for certain parameters of the tested methodologies. These results serve as support for further research and development of antiepileptic drugs from monoterpenes.

Caffeine and an adenosine A(2A) receptor antagonist prevent memory impairment and synaptotoxicity in adult rats triggered by a convulsive episode in early life.

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Cognato, Giana P; Agostinho, Paula M; Hockemeyer, Jörg; Müller, Christa E; Souza, Diogo O; Cunha, Rodrigo A

2010-01-01

Seizures early in life cause long-term behavioral modifications, namely long-term memory deficits in experimental animals. Since caffeine and adenosine A(2A) receptor (A(2A)R) antagonists prevent memory deficits in adult animals, we now investigated if they also prevented the long-term memory deficits caused by a convulsive period early in life. Administration of kainate (KA, 2 mg/kg) to 7-days-old (P7) rats caused a single period of self-extinguishable convulsions which lead to a poorer memory performance in the Y-maze only when rats were older than 90 days, without modification of locomotion or anxiety-like behavior in the elevated-plus maze. In accordance with the relationship between synaptotoxicity and memory dysfunction, the hippocampus of these adult rats treated with kainate at P7 displayed a lower density of synaptic proteins such as SNAP-25 and syntaxin (but not synaptophysin), as well as vesicular glutamate transporters type 1 (but not vesicular GABA transporters), with no changes in PSD-95, NMDA receptor subunits (NR1, NR2A, NR2B) or alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptor subunits (GluR1, GluR2) compared with controls. Caffeine (1 g/L) or the A(2A)R antagonist, KW6002 (3 mg/kg) applied in the drinking water from P21 onwards, prevented these memory deficits in P90 rats treated with KA at P7, as well as the accompanying synaptotoxicity. These results show that a single convulsive episode in early life causes a delayed memory deficit in adulthood accompanied by a glutamatergic synaptotoxicity that was prevented by caffeine or adenosine A(2A)R antagonists.

A preliminary observation of the adverse effects of phenobarbital among patients with convulsive epilepsy in rural West China.

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Si, Yang; Liu, Ling; Tian, Linyu; Mu, Jie; Chen, Deng; Chen, Tao; Deng, Ying; He, Jun; Li, You; He, Li; Zhou, Dong

2016-01-01

This study explored the adverse effect (AE) profile of phenobarbital (PB) among patients with active convulsive epilepsy (ACE) from resource-poor areas. Patients with ACE were enrolled into an epilepsy management project in rural West China. Information was obtained from monthly follow-up questionnaires. The demographic and clinical features of the patients with AE were firstly described. After that, the occurrence rate was estimated for each subtype of AE at three different severity levels (mild, moderate, and serious). Survival analysis was used to determine the potential risk factors of AEs. A total of 7231 patients (3780 men) were included in the present cohort. During the follow-up time period (average 33.4months), the most common AEs were drowsiness (moderate: 4.4%, serious: 0.68%), dizziness (moderate: 3.7%, serious: 0.5%), and headache (moderate: 2.9%, serious: 0.41%). In the confirmed AE groups (moderate and serious severity levels), the symptoms tended to be transient, with durations of less than 3months. Polytherapy was an independent risk factor for AEs and had an increasing risk when the severity of the AE increased (Hazard Ratio 1.12, 1.55, and 2.52 for mild AE, moderate AE, and serious AE, respectively). Receiving a high dosage of PB (>180mg/day) indicated a slightly elevated risk (Hazard Ratio 1.22 and 1.27 for mild AE and moderate AE, respectively). Phenobarbital demonstrates overall tolerability, and serious AEs were not common. Patients receiving a high dose of PB or polytherapy are at increased risk of developing AEs. Copyright © 2015 Elsevier Inc. All rights reserved.

Premature mortality in active convulsive epilepsy in rural Kenya

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Bottomley, Christian; Fegan, Gregory; Chengo, Eddie; Odhiambo, Rachael; Bauni, Evasius; Neville, Brian; Kleinschmidt, Immo; Sander, Josemir W.; Newton, Charles R.

2014-01-01

Objective: We estimated premature mortality and identified causes of death and associated factors in people with active convulsive epilepsy (ACE) in rural Kenya. Methods: In this prospective population-based study, people with ACE were identified in a cross-sectional survey and followed up regularly for 3 years, during which information on deaths and associated factors was collected. We used a validated verbal autopsy tool to establish putative causes of death. Age-specific rate ratios and standardized mortality ratios were estimated. Poisson regression was used to identify mortality risk factors. Results: There were 61 deaths among 754 people with ACE, yielding a rate of 33.3/1,000 persons/year. Overall standardized mortality ratio was 6.5. Mortality was higher across all ACE age groups. Nonadherence to antiepileptic drugs (adjusted rate ratio [aRR] 3.37), cognitive impairment (aRR 4.55), and age (50+ years) (rate ratio 4.56) were risk factors for premature mortality. Most deaths (56%) were directly related to epilepsy, with prolonged seizures/possible status epilepticus (38%) most frequently associated with death; some of these may have been due to sudden unexpected death in epilepsy (SUDEP). Possible SUDEP was the likely cause in another 7%. Conclusion: Mortality in people with ACE was more than 6-fold greater than expected. This may be reduced by improving treatment adherence and prompt management of prolonged seizures and supporting those with cognitive impairment. PMID:24443454

Consensus guidelines on management of childhood convulsive status epilepticus.

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Mishra, Devendra; Sharma, Suvasini; Sankhyan, Naveen; Konanki, Ramesh; Kamate, Mahesh; Kanhere, Sujata; Aneja, Satinder

2014-12-01

Status epilepticus has a wide etiological spectrum, and significant morbidity and mortality. Management using a pre-determined uniform protocol leads to better outcomes. Multiple protocols for management of childhood status epilepticus are available, without much consensus. A 'Multi-disciplinary Consensus Development Workshop on Management of Status Epilepticus in Children in India' was organized. The invited experts included Pediatricians, Pediatric neurologists, Neurologists, Epileptologists, and Pediatric intensive care specialists from India, with experience in the relevant field. Experts had previously been divided into focus groups and had interacted on telephone and e-mail regarding their group recommendations, and developed consensus on the topic. During the meeting, each group presented their recommendations, which were deliberated upon by the house and a consensus was reached on various issues; the document was finalized after incorporating suggestions of experts on the draft document. To provide consensus guidelines on evaluation and management of convulsive status epilepticus in children in India (excluding neonatal and super-refractory status epilepticus). Each institution should use a pre-determined protocol for management of status epilepticus; pre-hospital management and early stabilization is the key to a satisfactory outcome of status epilepticus. Pharmacotherapy should not be delayed for any investigations; the initial management should consist of a parenteral benzodiazepine by any route feasible. Subsequent management has been detailed. The group also felt the need for more epidemiological research on status epilepticus from India, and identified certain research areas for the purpose.

Combination of Continuous Dexmedetomidine Infusion with Titrated Ultra-Low-Dose Propofol-Fentanyl for an Awake Craniotomy

Science.gov (United States)

Das, Samaresh; Al-Mashani, Ali; Suri, Neelam; Salhotra, Neeraj; Chatterjee, Nilay

2016-01-01

An awake craniotomy is a continuously evolving technique used for the resection of brain tumours from the eloquent cortex. We report a 29-year-old male patient who presented to the Khoula Hospital, Muscat, Oman, in 2016 with a two month history of headaches and convulsions due to a space-occupying brain lesion in close proximity with the left motor cortex. An awake craniotomy was conducted using a scalp block, continuous dexmedetomidine infusion and a titrated ultra-low-dose of propofolfentanyl. The patient remained comfortable throughout the procedure and the intraoperative neuropsychological tests, brain mapping and tumour resection were successful. This case report suggests that dexmedetomidine in combination with titrated ultra-low-dose propofolfentanyl are effective options during an awake craniotomy, ensuring optimum sedation, minimal disinhibition and a rapid recovery. To the best of the authors’ knowledge, this is the first awake craniotomy conducted successfully in Oman. PMID:27606116

Differential antagonism of tetramethylenedisulfotetramine-induced seizures by agents acting at NMDA and GABAA receptors

International Nuclear Information System (INIS)

Shakarjian, Michael P.; Velíšková, Jana; Stanton, Patric K.; Velíšek, Libor

2012-01-01

Tetramethylenedisulfotetramine (TMDT) is a highly lethal neuroactive rodenticide responsible for many accidental and intentional poisonings in mainland China. Ease of synthesis, water solubility, potency, and difficulty to treat make TMDT a potential weapon for terrorist activity. We characterized TMDT-induced convulsions and mortality in male C57BL/6 mice. TMDT (ip) produced a continuum of twitches, clonic, and tonic–clonic seizures decreasing in onset latency and increasing in severity with increasing dose; 0.4 mg/kg was 100% lethal. The NMDA antagonist, ketamine (35 mg/kg) injected ip immediately after the first TMDT-induced seizure, did not change number of tonic–clonic seizures or lethality, but increased the number of clonic seizures. Doubling the ketamine dose decreased tonic–clonic seizures and eliminated lethality through a 60 min observation period. Treating mice with another NMDA antagonist, MK-801, 0.5 or 1 mg/kg ip, showed similar effects as low and high doses of ketamine, respectively, and prevented lethality, converting status epilepticus EEG activity to isolated interictal discharges. Treatment with these agents 15 min prior to TMDT administration did not increase their effectiveness. Post-treatment with the GABA A receptor allosteric enhancer diazepam (5 mg/kg) greatly reduced seizure manifestations and prevented lethality 60 min post-TMDT, but ictal events were evident in EEG recordings and, hours post-treatment, mice experienced status epilepticus and died. Thus, TMDT is a highly potent and lethal convulsant for which single-dose benzodiazepine treatment is inadequate in managing electrographic seizures or lethality. Repeated benzodiazepine dosing or combined application of benzodiazepines and NMDA receptor antagonists is more likely to be effective in treating TMDT poisoning. -- Highlights: ► TMDT produces convulsions and lethality at low doses in mice. ► Diazepam pre- or post-treatments inhibit TMDT-induced convulsions and death. �

Differential antagonism of tetramethylenedisulfotetramine-induced seizures by agents acting at NMDA and GABA{sub A} receptors

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Shakarjian, Michael P., E-mail: michael_shakarjian@nymc.edu [Department of Environmental Health Science, School of Health Sciences and Practice, Institute of Public Health, New York Medical College, Valhalla, NY, 10595 (United States); Department of Medicine, Division of Pulmonary and Critical Care Medicine, UMDNJ–Robert Wood Johnson Medical School, Piscataway, NJ 08854 (United States); Velíšková, Jana [Department of Cell Biology and Anatomy, New York Medical College, Valhalla, NY 10595 (United States); Department of Obstetrics and Gynecology, New York Medical College, Valhalla, NY 10595 (United States); Department of Neurology, New York Medical College, Valhalla, NY 10595 (United States); Stanton, Patric K., E-mail: patric_stanton@nymc.edu [Department of Cell Biology and Anatomy, New York Medical College, Valhalla, NY 10595 (United States); Department of Neurology, New York Medical College, Valhalla, NY 10595 (United States); Velíšek, Libor [Department of Cell Biology and Anatomy, New York Medical College, Valhalla, NY 10595 (United States); Department of Neurology, New York Medical College, Valhalla, NY 10595 (United States); Department of Pediatrics, New York Medical College, Valhalla, NY 10595 (United States)

2012-11-15

Tetramethylenedisulfotetramine (TMDT) is a highly lethal neuroactive rodenticide responsible for many accidental and intentional poisonings in mainland China. Ease of synthesis, water solubility, potency, and difficulty to treat make TMDT a potential weapon for terrorist activity. We characterized TMDT-induced convulsions and mortality in male C57BL/6 mice. TMDT (ip) produced a continuum of twitches, clonic, and tonic–clonic seizures decreasing in onset latency and increasing in severity with increasing dose; 0.4 mg/kg was 100% lethal. The NMDA antagonist, ketamine (35 mg/kg) injected ip immediately after the first TMDT-induced seizure, did not change number of tonic–clonic seizures or lethality, but increased the number of clonic seizures. Doubling the ketamine dose decreased tonic–clonic seizures and eliminated lethality through a 60 min observation period. Treating mice with another NMDA antagonist, MK-801, 0.5 or 1 mg/kg ip, showed similar effects as low and high doses of ketamine, respectively, and prevented lethality, converting status epilepticus EEG activity to isolated interictal discharges. Treatment with these agents 15 min prior to TMDT administration did not increase their effectiveness. Post-treatment with the GABA{sub A} receptor allosteric enhancer diazepam (5 mg/kg) greatly reduced seizure manifestations and prevented lethality 60 min post-TMDT, but ictal events were evident in EEG recordings and, hours post-treatment, mice experienced status epilepticus and died. Thus, TMDT is a highly potent and lethal convulsant for which single-dose benzodiazepine treatment is inadequate in managing electrographic seizures or lethality. Repeated benzodiazepine dosing or combined application of benzodiazepines and NMDA receptor antagonists is more likely to be effective in treating TMDT poisoning. -- Highlights: ► TMDT produces convulsions and lethality at low doses in mice. ► Diazepam pre- or post-treatments inhibit TMDT-induced convulsions and death

Can we safely administer the recommended dose of phenobarbital in very low birth weight infants?

Science.gov (United States)

Oztekin, Osman; Kalay, Salih; Tezel, Gonul; Akcakus, Mustafa; Oygur, Nihal

2013-08-01

We investigated whether the recommended phenobarbital loading dose of 15-20 mg/kg with maintenance of 3-4 mg/kg/day can safely be administered to very low birth weight preterm newborns with seizures. Twenty-four convulsive preterms of Phenobarbital was administered intravenously with a loading dose of 15 mg/kg in approximately 10-15 min. After 24 h, the maintenance dose of 3 mg/kg/day was administered as a single injection. Blood samples were obtained 2, 24, 48, 72, and 96 h after the phenobarbital loading dose was administered, immediately before the next phenobarbital dose was injected. None of the cases had plasma phenobarbital concentrations above the therapeutic upper limit of 40 μg/mL on the 2nd hour; one case (4.7%), on the 24th; 11 cases (45.8%), on the 48th; 15 cases (62.5%), on the 72nd; and 17 cases (70.8%), on the 96th hour. A negative correlation was detected between the serum concentrations of phenobarbital and gestational age on the 72th (p, 0.036; r, -0.608) and 96th hour (p, 0.043; r, -0.769). We suggest that particular attention should be done while administering phenobarbital in preterms, as blood levels of phenobarbital are higher than the reference ranges that those are often reached with the recommended doses in these groups of babies.

Modulation of c-Fos and BDNF Protein Expression in Pentylenetetrazole-Kindled Mice following the Treatment with Novel Antiepileptic Compound HHL-6

Directory of Open Access Journals (Sweden)

Saima Mahmood Malhi

2014-01-01

Full Text Available Brain-derived neurotrophic factor (BDNF and c-Fos are shown to promote epileptogenesis and are taken as a marker of neuronal activity. The present study investigated the expression of BDNF and c-Fos in mice brain with pentylenetetrazol- (PTZ- induced generalized seizure and evaluated the effect of novel tryptamine derivative HHL-6 on the expression of these two markers. The subconvulsive dose of PTZ (50 mg/kg was administered on alternate days in the experimental groups until the seizure scores 4-5 developed in the PTZ-control group. At the end of each experiment, animals were sacrificed, brain samples were collected and cryosectioned, and immunohistochemical analysis of BDNF and c-Fos protein was performed. Data obtained from two sections per mouse (n=12 animals/group is presented as means ± S.E.M. The test compound HHL-6 demonstrated a potent anticonvulsant activity in the PTZ-induced seizure in mice. Significant reduction in the BDNF (P<0.003 and c-Fos (P<0.01 protein expression was observed in the HHL-6 treated group. Based on these results we suggest that one of the possible mechanisms of HHL-6 to inhibit epileptogenesis might be due to its controlling effect on the cellular and molecular expression of the factors that contribute to the development of epileptogenic plasticity in the CNS.

Anticonvulsant effect of the ethanol extract of Caesalpiniapulcherrima (L. Sw., Fabaceae, leaves

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Dinesh Kumar

2010-08-01

Full Text Available In this study, ethanol extract of Caesalpinia pulcherrima (L. Sw., Fabaceae, leaves (CPEE was investigated for anticonvulsant effect against maximal electroshock (MES and pentylenetetrazole (PTZ induced seizures in rats and mice at dose levels 200 and 400 mg/kg, i.p. respectively. Diazepam (3 mg/kg, i.p. was used as a standard anticonvulsant drug for comparison. CPEE was found to be safe up to the dose of 4000 mg/kg in mice, when administered intraperitoneally. The extract at 400 mg/kg dose produced significant (p<0.01 anticonvulsant effect w.r.t. control against PTZ-induced clonic seizures. In MES-induced seizure model, there were no significant alterations in the onset as well as duration of hind limb extension seizures as compared to control at a dose of 200 mg/kg when administered intraperitoneally. However, the extract (CPEE, 400 mg/kg i.p. significantly (p<0.01 delayed the onset as well as decreased the duration of hind limb extension seizures (HLES as compared to control. However, the extract, CPEE, percentage protection of the animals was increased at higher dose (200 mg/kg in both the models. The results of the study suggest that ethanol extract of Caesalpinia pulcherrima (L. Sw. leaves possess anticonvulsant effect.

Triazole incorporated thiazoles as a new class of anticonvulsants: design, synthesis and in vivo screening.

Science.gov (United States)

Siddiqui, Nadeem; Ahsan, Waquar

2010-04-01

Various 3-[4-(substituted phenyl)-1,3-thiazol-2-ylamino]-4-(substituted phenyl)-4,5-dihydro-1H-1,2,4-triazole-5-thiones (7a-t) were designed keeping in view the structural requirements suggested in the pharmacophore model for anticonvulsant activity. Thiazole and triazole moieties being anticonvulsants were clubbed together to get the titled compounds and their in vivo anticonvulsant screening were performed by two most adopted seizure models, maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole (scPTZ). Two compounds 7d and 7f showed significant anticonvulsant activity in both the screens with ED(50) values 23.9 mg/kg and 13.4 mg/kg respectively in MES screen and 178.6 mg/kg and 81.6 mg/kg respectively in scPTZ test. They displayed a wide margin of safety with Protective index (PI), median hypnotic dose (HD(50)) and median lethal dose (LD(50)) much higher than the standard drugs. Copyright (c) 2010 Elsevier Masson SAS. All rights reserved.

Combination of Continuous Dexmedetomidine Infusion with Titrated Ultra-Low-Dose Propofol-Fentanyl for an Awake Craniotomy; Case report

Directory of Open Access Journals (Sweden)

Samaresh Das

2016-08-01

Full Text Available An awake craniotomy is a continuously evolving technique used for the resection of brain tumours from the eloquent cortex. We report a 29-year-old male patient who presented to the Khoula Hospital, Muscat, Oman, in 2016 with a two month history of headaches and convulsions due to a space-occupying brain lesion in close proximity with the left motor cortex. An awake craniotomy was conducted using a scalp block, continuous dexmedetomidine infusion and a titrated ultra-low-dose of propofol-fentanyl. The patient remained comfortable throughout the procedure and the intraoperative neuropsychological tests, brain mapping and tumour resection were successful. This case report suggests that dexmedetomidine in combination with titrated ultra-low-dose propofolfentanyl are effective options during an awake craniotomy, ensuring optimum sedation, minimal disinhibition and a rapid recovery. To the best of the authors’ knowledge, this is the first awake craniotomy conducted successfully in Oman.

Convulsive status epilepticus and health-related quality of life in children with epilepsy.

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Ferro, Mark A; Chin, Richard F M; Camfield, Carol S; Wiebe, Samuel; Levin, Simon D; Speechley, Kathy N

2014-08-19

The objective of this study was to examine the association between convulsive status epilepticus (CSE) and health-related quality of life (HRQL) during a 24-month follow-up in a multisite incident cohort of children with epilepsy. Data were collected in the Health-Related Quality of Life Study in Children with Epilepsy Study from 374 families of children with newly diagnosed epilepsy. The Quality of Life in Childhood Epilepsy (QOLCE) Questionnaire was used to evaluate parent-reported child HRQL. Hierarchical linear regression was used to examine the relationship between CSE and HRQL at 24 months postepilepsy. A total of 359 families completed the 24-month assessment. Twenty-two children (6.1%) had experienced CSE during the follow-up. Children with and without CSE were similar, except a larger proportion of children with CSE had partial seizures (p QOLCE scores. The findings suggested that not only do children with CSE have significantly poorer HRQL compared with their non-CSE counterparts, but that this factor is independent of the effects of demographic and clinical features known to affect HRQL. © 2014 American Academy of Neurology.

Convulsive status epilepticus and health-related quality of life in children with epilepsy

Science.gov (United States)

Chin, Richard F.M.; Camfield, Carol S.; Wiebe, Samuel; Levin, Simon D.; Speechley, Kathy N.

2014-01-01

Objectives: The objective of this study was to examine the association between convulsive status epilepticus (CSE) and health-related quality of life (HRQL) during a 24-month follow-up in a multisite incident cohort of children with epilepsy. Methods: Data were collected in the Health-Related Quality of Life Study in Children with Epilepsy Study from 374 families of children with newly diagnosed epilepsy. The Quality of Life in Childhood Epilepsy (QOLCE) Questionnaire was used to evaluate parent-reported child HRQL. Hierarchical linear regression was used to examine the relationship between CSE and HRQL at 24 months postepilepsy. A total of 359 families completed the 24-month assessment. Results: Twenty-two children (6.1%) had experienced CSE during the follow-up. Children with and without CSE were similar, except a larger proportion of children with CSE had partial seizures (p children with CSE have significantly poorer HRQL compared with their non-CSE counterparts, but that this factor is independent of the effects of demographic and clinical features known to affect HRQL. PMID:25037204

Nonconvulsive status epilepticus after cessation of convulsive status epilepticus in pediatric intensive care unit patients.

Science.gov (United States)

Chen, Jin; Xie, Lingling; Hu, Yue; Lan, Xinghui; Jiang, Li

2018-05-01

Little is known about pediatric patients suffering from nonconvulsive status epilepticus (NCSE) after convulsive status epilepticus (CSE) cessation. The aim of this study was to identify in pediatric patients the clinical characteristics of NCSE after CSE cessation and the factors that contribute to patient outcomes. Data from clinical features, electroencephalography (EEG) characteristics, neuroimaging findings, treatments, and prognosis were systematically summarized, and the associations between clinical characteristics and prognosis were quantified. Thirty-eight children aged 51days-14years, 2months were identified in the Chongqing Medical University pediatric intensive care unit as having experienced NCSE after CSE cessation between October 1, 2014 and April 1, 2017. All patients were comatose, 15 of whom presented subtle motor signs. The most common underlying etiology was acute central nervous system (CNS) infection. Electroencephalography (EEG) data showed that, during the NCSE period, all patients had several discrete episodes (lasting from 30s to 6h long), and the most common duration was 1-5min. The ictal onset locations were classified as focal (16 patients, 42.1%), multiregional independent (10 patients, 26.3%), and generalized (12 patients, 31.6%). Wave morphologies varied during the ictal and interictal periods. Neuroimaging detected signal abnormalities in the cerebral cortex or subcortex of 33 patients with NCSE (87%), which were classified as either multifocal and consistent with extensive cortical edema (21 patients, 55.3%) or focal (12 patients, 31.6%). Twelve patients were on continuous intravenous phenobarbital, and 31 were on continuous infusion of either midazolam (27 patients) or propofol (4 patients). At least one other antiepileptic drug was prescribed for 32 patients. Three patients were on mild hypothermia therapy. The duration of NCSE lasted 24h for 18 patients. The mortality rate was 21.1%, and half of the surviving patients had

Modulation of benzodiazepine by lysine and pipecolic acid on pentylenetetrazol-induced seizures

International Nuclear Information System (INIS)

Chang, Y.F.; Hargest, V.; Chen, J.S.

1988-01-01

L-lysine and its metabolite pipecolic acid (PA) have been studied for their effects on pentylenetetrazol (PTZ)-induced seizures in mice. L-Lysine of L-Pa i.p. significantly increased clonic and tonic latencies in a dose-dependent manner against 90 mg/kg PTZ-induced seizures. L-Lysine but not L-Pa enhanced the anticonvulsant effect of diazepam (DZ). L-Pa i.c.v. showed a slight decrease in clonic latency; it did not enhance the antiseizure activity of DZ; it caused seizures at 0.6 mmol/kg. D-PA i.c.v. displayed an opposite effect compared to its L-isomer. The anticonvulsant effect of L-lysine in terms of increase in seizure latency and survival was even more amplified when tested with a submaximal PTZ concentration. L-Lysine showed an enhancement of specific 3 H-flunitrazepam(FZ) binding to mouse brain membranes both in vitro an din vivo. The possibility of L-lysine acting as a modulator for the GABA/benzodiazepine receptors was demonstrated. Since L-PA showed enhancement of 3 H-FZ binding only in vitro but not in vivo, the anticonvulsant effect of L-PA may not be linked to the GABA/benzodiazepine receptor

Synthesis and anticonvulsant activity of some 2-pyrazolines derived from chalcones

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Nagihan Beyhan

2017-05-01

All compounds were tested for their anticonvulsant activity using pentylenetetrazole induced seizure (PTZ and maximal electroshock seizure (MES tests in mice at a dose level of 50 mg/kg. Among the 2-pyrazoline-1-carbothioamide derivatives, 5-(2,6-dichlorophenyl-3-(thiophen-2-yl-4,5-dihydro-1H-pyrazole-1-carbothioamide (2e reduced grade-5 seizure activity and also increased survival rate in PTZ test. In MES test, 5-(4-methoxyphenyl-3-[4-(methylsulphonylphenyl]-4,5-dihydro-1H-pyrazole-1-carbothioamide(2g has not only decreased seizure severity, but also increased survival rate. Among the 2-pyrazoline-1-carboxamide derivatives, 3-(5-bromothiophen-2-yl-N-(4-chlorophenyl-5-(2,6-dichlorophenyl-4,5-dihydro-1H-pyrazole-1-carboxamide (3d having 5-bromothiophen and 2,6-dichlorophenyl moieties and N-(4-chlorophenyl-5-(2,6-dichlorophenyl-3-(5-chlorothiophen-2-yl-4,5-dihydro-1H-pyrazole-1-carboxamide (3e having 5-chlorothiophen and 2,6-dichlorophenyl moieties showed remarkable activities in PTZ test. Among all tested derivatives, compound 3d was found to be the most active one and reduced grade-5 seizure severity and also increased survival rate.

A novel model for NSAID induced gastroenteropathy in rats.

Science.gov (United States)

Singh, Devendra Pratap; Borse, Swapnil P; Nivsarkar, Manish

2016-01-01

Progress in management of Nonsteroidal anti-inflammatory drug (NSAID) induced gastrointestinal toxicity requires the availability of appropriate experimental animal models that are as close to humans as feasible. Our objective was to develop a rat model for NSAID-induced gastroenteropathy and also to simulate the common clinical scenario of co-administration of NSAID and proton pump inhibitor (PPI) to explore if PPI contribute to exacerbation of NSAID-enteropathy. Rats were treated twice daily with pantoprazole sodium (PTZ; 10mg/kg peroral) or vehicle for a total of 10days. In some experiments, Diclofenac sodium (DCF; 9mg/kg) or vehicle was administered orally twice daily for the final 5days of PTZ/vehicle administration. After the last dose on 9th day, rats in all the groups were fasted but water was provided ad libitum. 12h after the last dose on 10th day, rats in all the groups were euthanized and their gastrointestinal tracts were assessed for haemorrhagic lesions, lipid peroxidation, intestinal permeability and gastrointestinal luminal pH alterations. Changes in haemoglobin, haematocrit and serum levels of albumin, total protein, ALT and bilirubin were calculated. The macroscopic and histological evidence suggested that administration of DCF resulted in significant gastroenteropathic damage and co-administration of PTZ resulted in significant exacerbation of NSAID enteropathy, while attenuation of NSAID induced gastropathy was observed. Our results were further supported by the significant decrease in haemoglobin and haematocrit levels and serum levels of albumin and total proteins, an increase in oxidative stress and intestinal permeability with the use of DCF either alone or in combination with PTZ. This model was developed to simulate the human clinical situation during NSAID therapy and indeed the present DCF regimen caused both gastric and small bowel alterations, such as multiple erosive lesions, together with a decrease in haemoglobin, haematocrit

Effect of an Early Dose of Measles Vaccine on Morbidity Between 18 Weeks and 9 Months of Age: A Randomized, Controlled Trial in Guinea-Bissau

DEFF Research Database (Denmark)

Do, Vu An; Biering-Sorensen, Sofie; Fisker, Ane Bærent

2017-01-01

with a higher risk of the well-known adverse events of fever, rash, and convulsions within the first 14 days. From 15 days after randomization to age 9 months, early measles vaccination was associated with reductions in maternally reported diarrhea (hazard ratio [HR], 0.89; 95% confidence interval [CI],.82-. 97......Background: Children in Guinea-Bissau receive measles vaccine (MV) at 9 months of age, but studies have shown that an additional dose before 9 months of age might have beneficial nonspecific effects. Within a randomized trial designed to examine nonspecific effects of early MV receipt on mortality......, we conducted a substudy to investigate the effect of early MV receipt on morbidity. Methods: Children were randomly assigned at a ratio of 2: 1 to receive 2 doses of MVat 18 weeks and age 9 months (intervention group) or 1 dose of MV at age 9 months, in accordance with current practice (control group...

Brain levels of N-acylethanolamine phospholipids in mice during pentylenetetrazol-induced seizure

DEFF Research Database (Denmark)

Moesgaard, B.; Hansen, H.H.; Petersen, G.

2003-01-01

occur in response to seizure activity. Therefore, we investigated the effect of pentylenetetrazol (PTZ)-induced seizures in PTZ-kindled mice on the level of NAPE in the brain. Male NMRI mice were kindled with PTZ injections 3 times/wk, thereby developing clonic seizures in response to PTZ. Mice were...... killed within 30 min after the clonic seizure on the test day (12th injection) and the brains were collected. Eight species of NAPE were analyzed as the glycerophospho-N-acylethanolamines by high-performance liquid chromatography-coupled electrospray ionization mass spectrometry. No effect of the PTZ...... accumulate during seizure....

The antiepileptic and neuroprotective effect of the Buxus hyrcana Pojark hydroethanolic extract against the pentylentetrazol induced model of the seizures in the male rats.

Science.gov (United States)

Azizi, Vahid; Allahyari, Farzin; Hosseini, Abdolkarim

2018-03-06

The genus Buxus grows up widespread in Europe and Western Asia. It is an important traditional plant that has been used in the treatment of many illnesses. In the present study, the effect of hydroethanolic extract of Buxus hyrcana Pojark (BHP) on the animal model of seizure was studied. In this experimental study, 42 male Wistar rats weighing 220-250 g were randomly selected and were divided into experimental and control groups (six rats per group). The experimental groups were treated by the intraperitoneal (i.p.) single injection of 150, 300, 450, 600 and 750 mg kg -1 of hydroalcoholic extracts of BHP. The control negative group received normal saline (0.9%) and the control positive group received phenobarbital (30 mg kg -1 , i.p.) pre-treatment. Thirty minutes after the treatments, the seizure behaviors were evaluated by the pentylenetetrazole (PTZ) (70 mg kg -1 , i.p.) challenge. In addition, after the experiment, the rats were put to death and their brains were removed for the histological study. The ANOVA demonstrated that compared to the control group, all the BHP doses delayed the initiation and duration of the tonic, colonic and tonic-colonic seizures and significantly reduced the tonic and colonic seizures (p < 0.001). Furthermore, the administration of all five doses of the extract significantly prevented the production of the dark neurons (p < 0.001) in different areas of the hippocampus compared to PTZ group. We can conclude that the BHP extract has beneficial effects for the prevention of the PTZ induced seizure.

Effects of pentylenetetrazole and glutamate on metabolism of [U-(13)C]glucose in cultured cerebellar granule neurons.

Science.gov (United States)

Eloqayli, Haytham; Qu, Hong; Unsgård, Geirmund; Sletvold, Olav; Hadidi, Hakam; Sonnewald, Ursula

2002-02-01

This study was performed to analyze the effects of glutamate and the epileptogenic agent pentylenetetrazole (PTZ) on neuronal glucose metabolism. Cerebellar granule neurons were incubated for 2 h in medium containing 3 mM [U-(13)C]glucose, with and without 0.25 mM glutamate and/or 10 mM PTZ. In the presence of PTZ, decreased glucose consumption with unchanged lactate release was observed, indicating decreased glucose oxidation. PTZ also slowed down tricarboxylic acid (TCA) cycle activity as evidenced by the decreased amounts of labeled aspartate and [1,2-(13)C]glutamate. When glutamate was present, glucose consumption was also decreased. However, the amount of glutamate, derived from [U-(13)C]glucose via the first turn of the TCA cycle, was increased. The decreased amount of [1,2-(13)C]glutamate, derived from the second turn in the TCA cycle, and increased amount of aspartate indicated the dilution of label due to the entrance of unlabeled glutamate into TCA cycle. In the presence of glutamate plus PTZ, the effect of PTZ was enhanced by glutamate. Labeled alanine was detected only in the presence of glutamate plus PTZ, which indicated that oxaloacetate was a better amino acid acceptor than pyruvate. Furthermore, there was also evidence for intracellular compartmentation of oxaloacetate metabolism. Glutamate and PTZ caused similar metabolic changes, however, via different mechanisms. Glutamate substituted for glucose as energy substrate in the TCA cycle, whereas, PTZ appeared to decrease mitochondrial activity.

Photophysical and photoprototropic characteristics of phenothiazine in aqueous and β-cyclodextrin media

Energy Technology Data Exchange (ETDEWEB)

Rajamohan, Rajaram, E-mail: rajmohanau@gmail.com [Department of Chemistry, S.K.P Institute of Technology, Tiruvannamalai 606611 (India); Nayaki, Sundararajulu Kothai [Chemistry Section, FEAT, Annamalai University, Annamalainagar 608002 (India); Sivakumar, Krishnamoorthy [Department of Chemistry, SCSV University, Enathur, Kanchipuram 631561 (India); Swaminathan, Meenakshisundaram [Department of Chemistry, Annamalai University, Annamalainagar 608002 (India)

2015-12-15

The photophysical and photoprototropic characteristics of phenothiazine (PTZ) in aqueous and β-cyclodextrin (β-CD) media have been investigated using absorption, steady state and time resolved fluorescence measurements. The absorbance and fluorescence intensities of the neutral and monocationic forms of PTZ are enhanced by the addition of β-cyclodextrin and it is due to the formation of 1:1 inclusion complex. The formation of complex is confirmed by the decay analysis and Job's continuous variation method in the liquid state while FT-IR spectral study and SEM image analysis in the solid state. The peak and pK{sub a}* values of PTZ in aqueous media are higher than in β-CD medium, which reveals that the >NH group of PTZ lies in the β-CD cavity. - Highlights: • Increase in the absorbance and fluorescence intensity of PTZ by the addition of β-CDx is confirmed the complex formation. • Biexponential decay is noticed for PTZ by the addition of β-CDx is due to the formation of inclusion complex. • FT-IR and SEM images analysis confirms complex between PTZ and β-CDx in solid state. • The pK{sub a} and pK{sub a}* values of PTZ in aqueous medium is higher than in β-CDx medium, which reveals that the >NH group of PTZ lies in the β-CDx cavity. • The orientation of the inclusion complex is proposed by PatchDock server.

Assessment of coverage levels of single dose measles vaccine

International Nuclear Information System (INIS)

Tariq, P.

2003-01-01

Objective: To study the consequences of low coverage levels of a single dose of measles vaccine. Results: mean age observed in measles cases was 2 years and 8 months with a range from 3 months to 8 years. Maximum number of cases reported were <1 year of age (n=22,32%). Fifty percent of cases were seen among vaccinated children. Seventy-five percent (n=51) had history of contact with a measles case. Pneumonia was the commonest complication followed by acute gastroenteritis, encephalitis, febrile convulsions, oral ulcers, oral thrush, eye changes of vitamin-A deficiency and pulmonary tuberculosis (T.B.) in descending order of frequency. Fifty four cases were successfully treated for complications of measles and discharged. Nine cases left against medical advice. Five patients died all of them had encephalitis either alone (n=1) or in combination with pneumonia and acute gastroenteritis (n=4). Conclusion: There is a dire need to increase the immunization coverage to reduce the rate of vaccine failure and achieve effective control of measles.(author)

Phenobarbital Versus Valproate for Generalized Convulsive Status Epilepticus in Adults: A Prospective Randomized Controlled Trial in China.

Science.gov (United States)

Su, Yingying; Liu, Gang; Tian, Fei; Ren, Guoping; Jiang, Mengdi; Chun, Brian; Zhang, Yunzhou; Zhang, Yan; Ye, Hong; Gao, Daiquan; Chen, Weibi

2016-12-01

Although generalized convulsive status epilepticus (GCSE) is a life-threatening emergency, evidence-based data to guide initial drug treatment choices are lacking in the Chinese population. We conducted this prospective, randomized, controlled trial to evaluate the relative efficacy and safety of intravenous phenobarbital and valproate in patients with GCSE. After the failure of first-line diazepam treatment, Chinese adult patients with GCSE were randomized to receive either intravenous phenobarbital (standard doses, low rate) or valproate (standard). Successful treatment was considered when clinical and electroencephalographic seizure activity ceased. Adverse events following treatment, as well as the neurological outcomes at discharge and 3 months later, were also evaluated. Overall, 73 cases were enrolled in the study. Intravenous phenobarbital was successful in 81.1% of patients, and intravenous valproate was successful in 44.4% of patients (p phenobarbital (6.7%) was significantly lower than that in patients receiving valproate (31.3%), and the total number of adverse events did not differ significantly between the two groups (p > 0.05). In the phenobarbital group, two patients (5.4%) required ventilation and two patients (5.4%) developed serious hypotension. The neurological outcomes of the phenobarbital group were generally better than those of the valproate group; however, no significant differences were observed between phenobarbital and valproate with respect to mortality (8.1 vs. 16.6%) at discharge, or mortality (16.2 vs. 30.5%) and post-symptomatic epilepsy (26.3 vs. 42.8%) at 3-month follow-up. Intravenous phenobarbital appears to be more effective than intravenous valproate for Chinese adult patients with GCSE. The occurrence of serious respiratory depression and hypotension caused by phenobarbital was reduced by decreasing the intravenous infusion rate; however, even at a lower infusion rate than typically used in other institutions, intravenous

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

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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.

Synthesis and Pharmacological Evaluation of Novel Benzenesulfonamide Derivatives as Potential Anticonvulsant Agents

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Zhiming Wang

2015-09-01

Full Text Available A novel series of benzenesulfonamide derivatives containing 4-aminobenzenesul-fonamide and α-amides branched valproic acid or 2,2-dimethylcyclopropanecarboxylic acid moieties were synthesized and screened for their anticonvulsant activities in mice maximal electroshock seizure (MES and subcutaneous pentylenetetrazole (scPTZ test. The activity experimental study showed that 2,2-dipropyl-N1-(4-sulfamoylphenylmalonamide (18b had the lowest median effective dose (ED50 of 16.36 mg/kg in MES test, and 2,2-dimethyl-N-(4-sulfamoylphenylcyclopropane-1,1-dicarboxamide (12c had the lowest ED50 of 22.50 mg/kg in scPTZ test, which resulted in the protective indexe (PI of 24.8 and 20.4, respectively. These promising data suggest the new compounds have good potential as new class of anticonvulsant agents with high effectiveness and low toxicity for the treatment of epilepsy.

Piperacillin-tazobactam vs. imipenem-cilastatin as empirical therapy in hematopoietic stem cell transplantation recipients with febrile neutropenia.

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Jing, Yu; Li, Jian; Yuan, Lei; Zhao, Xiaoli; Wang, Quanshun; Yu, Li; Zhou, Daobin; Huang, Wenrong

2016-03-01

This randomized, dual-center study compared the efficacy and safety of piperacillin-tazobactam (PTZ) and imipenem-cilastatin (IMP) in hematopoietic stem cell transplantation (HSCT) recipients with febrile neutropenia. HSCT recipients with febrile neutropenia were randomized into two groups receiving either PTZ or IMP as initial empiric antibiotic. Endpoints were defervescence rate after empiric antibiotic for 48 h, success at end of therapy, and side effects. Defervescence within 48 h after empiric antibiotic was observed in 46 patients with PTZ (75.4%) and 59 patients with IMP (95.2%) (p = 0.002). Ten patients (10/46) in the PTZ group and two patients (2/59) in the IMP group switched empiric antibiotics due to recurrent fever (p = 0.005). Success of initial antibiotic with modification was achieved in 34 patients with PTZ (55.7%) and 53 patients with IMP (85.5%) at the end of therapy (p = 0.001). To treat the bacteremia, seven of 10 patients in the PTZ group and one of eight patients in the IMP group needed to switch the empiric antibiotic (p = 0.025). Compared with PTZ, IMP had more gastrointestinal adverse events (p = 0.045). This study demonstrates that IMP had better efficacy than PTZ as an empiric antibiotic for febrile neutropenia in the HSCT setting, but with more gastrointestinal side reactions. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A bacterial cocaine esterase protects against cocaine-induced epileptogenic activity and lethality.

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Jutkiewicz, Emily M; Baladi, Michelle G; Cooper, Ziva D; Narasimhan, Diwahar; Sunahara, Roger K; Woods, James H

2009-09-01

Cocaine toxicity results in cardiovascular complications, seizures, and death and accounts for approximately 20% of drug-related emergency department visits every year. Presently, there are no treatments to eliminate the toxic effects of cocaine. The present study hypothesizes that a bacterial cocaine esterase with high catalytic efficiency would provide rapid and robust protection from cocaine-induced convulsions, epileptogenic activity, and lethality. Cocaine-induced paroxysmal activity and convulsions were evaluated in rats surgically implanted with radiotelemetry devices (N=6 per treatment group). Cocaine esterase was administered 1 minute after a lethal dose of cocaine or after cocaine-induced convulsions to determine the ability of the enzyme to prevent or reverse, respectively, the effects of cocaine. The cocaine esterase prevented all cocaine-induced electroencephalographic changes and lethality. This effect was specific for cocaine because the esterase did not prevent convulsions and death induced by a cocaine analog, (-)-2beta-carbomethoxy-3beta-phenyltropane. The esterase prevented lethality even after cocaine-induced convulsions occurred. In contrast, the short-acting benzodiazepine, midazolam, prevented cocaine-induced convulsions but not the lethal effects of cocaine. The data showed that cocaine esterase successfully degraded circulating cocaine to prevent lethality and that cocaine-induced convulsions alone are not responsible for the lethal effects of cocaine in this model. Therefore, further investigation into the use of cocaine esterase for treating cocaine overdose and its toxic effects is warranted.

PRRT2 links infantile convulsions and paroxysmal dyskinesia with migraine

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Cloarec, Robin; Bruneau, Nadine; Rudolf, Gabrielle; Massacrier, Annick; Salmi, Manal; Bataillard, Marc; Boulay, Clotilde; Caraballo, Roberto; Fejerman, Natalio; Genton, Pierre; Hirsch, Edouard; Hunter, Alasdair; Lesca, Gaetan; Motte, Jacques; Roubertie, Agathe; Sanlaville, Damien; Wong, Sau-Wei; Fu, Ying-Hui; Rochette, Jacques; Ptáček, Louis J.

2012-01-01

ABSTRACT Objective: Whole genome sequencing and the screening of 103 families recently led us to identify PRRT2 (proline-rich-transmembrane protein) as the gene causing infantile convulsions (IC) with paroxysmal kinesigenic dyskinesia (PKD) (PKD/IC syndrome, formerly ICCA). There is interfamilial and intrafamilial variability and the patients may have IC or PKD. Association of IC with hemiplegic migraine (HM) has also been reported. In order to explore the mutational and clinical spectra, we analyzed 34 additional families with either typical PKD/IC or PKD/IC with migraine. Methods: We performed Sanger sequencing of all PRRT2 coding exons and of exon-intron boundaries in the probands and in their relatives whenever appropriate. Results: Two known and 2 novel PRRT2 mutations were detected in 18 families. The p.R217Pfs*8 recurrent mutation was found in ≈50% of typical PKD/IC, and the unreported p.R145Gfs*31 in one more typical family. PRRT2 mutations were also found in PKD/IC with migraine: p.R217Pfs*8 cosegregated with PKD associated with HM in one family, and was also detected in one IC patient having migraine with aura, in related PKD/IC familial patients having migraine without aura, and in one sporadic migraineur with abnormal MRI. Previously reported p.R240X was found in one patient with PKD with migraine without aura. The novel frameshift p.S248Afs*65 was identified in a PKD/IC family member with IC and migraine with aura. Conclusions: We extend the spectrum of PRRT2 mutations and phenotypes to HM and to other types of migraine in the context of PKD/IC, and emphasize the phenotypic pleiotropy seen in patients with PRRT2 mutations. PMID:23077017

COMPARISON OF EFFICACY AND FETOMATERNAL OUTCOME WITH LOW DOSE AND STANDARD PRITCHARD’S REGIMEN OF MAGNESIUM SULPHATE IN ECLAMPSIA

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Nirmala Chamakuri

2017-11-01

Full Text Available BACKGROUND Eclampsia, a hypertensive disorder of pregnancy is a common obstetric emergency, which leads to significant maternal morbidity, perinatal morbidity and mortality. The Pritchard’s regimen of magnesium sulphate remains as the standard regimen worldwide. The aim of this study is to compare the effectiveness, side effects and fetomaternal outcome using low-dose magnesium sulphate with the results of Pritchard regime. MATERIALS AND METHODS A comparative prospective study including 120 eclampsia patients designed into group I and group II treated with low-dose magnesium sulphate and Pritchard’s regimen was conducted in the Department of Obstetrics and Gynaecology for a period of 18 months between January 2015 to June 2016. RESULTS In the present study, there was 100% control of seizures in both the groups. No recurrence of seizures were seen in 57 (95% of cases in group II (low-dose regimen and 3 (5% cases showed recurrence, which were controlled by giving additional doses. In group II, loss of patellar reflexes was seen in 6 (10%, reduced urine output was seen in 3 (5% of cases, mild PPH was observed in 3 (5% cases and perinatal mortality in 18 (30% cases, which were lower than that of group I (Pritchard’s regimen. CONCLUSION Low-dose magnesium sulphate is effective in controlling convulsions in eclampsia. This regimen is highly suitable for use in Indian women who are known to have low body mass index

Adaptation of Lorke's method to determine and compare ED50 values: the cases of two anticonvulsants drugs.

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Garrido-Acosta, Osvaldo; Meza-Toledo, Sergio Enrique; Anguiano-Robledo, Liliana; Valencia-Hernández, Ignacio; Chamorro-Cevallos, Germán

2014-01-01

We determined the median effective dose (ED50) values for the anticonvulsants phenobarbital and sodium valproate using a modification of Lorke's method. This modification allowed appropriate statistical analysis and the use of a smaller number of mice per compound tested. The anticonvulsant activities of phenobarbital and sodium valproate were evaluated in male CD1 mice by maximal electroshock (MES) and intraperitoneal administration of pentylenetetrazole (PTZ). The anticonvulsant ED50 values were obtained through modifications of Lorke's method that involved changes in the selection of the three first doses in the initial test and the fourth dose in the second test. Furthermore, a test was added to evaluate the ED50 calculated by the modified Lorke's method, allowing statistical analysis of the data and determination of the confidence limits for ED50. The ED50 for phenobarbital against MES- and PTZ-induced seizures was 16.3mg/kg and 12.7mg/kg, respectively. The sodium valproate values were 261.2mg/kg and 159.7mg/kg, respectively. These results are similar to those found using the traditional methods of finding ED50, suggesting that the modifications made to Lorke's method generate equal results using fewer mice while increasing confidence in the statistical analysis. This adaptation of Lorke's method can be used to determine median letal dose (LD50) or ED50 for compounds with other pharmacological activities. Copyright © 2014 Elsevier Inc. All rights reserved.

Comparison of Rates of Nephrotoxicity Associated with Vancomycin in Combination with Piperacillin-Tazobactam Administered as an Extended versus Standard Infusion.

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Mousavi, Mariam; Zapolskaya, Tanya; Scipione, Marco R; Louie, Eddie; Papadopoulos, John; Dubrovskaya, Yanina

2017-03-01

Despite recent reports of relatively high rates (16-37%) of acute kidney injury (AKI) in patients receiving the combination of intravenous piperacillin-tazobactam (PTZ) and vancomycin, data are limited evaluating the impact of PTZ infusion strategy on the occurrence of nephrotoxicity. The objective of this study was to compare the rates of nephrotoxicity in patients receiving vancomycin in combination with PTZ administered as an extended infusion (EI) versus a standard infusion (SI). Single-center, retrospective, matched-cohort study. Large academic tertiary care hospital. Two hundred eighty adults with a creatinine clearance (CrCl) of 40 ml/minute or higher who received at least 96 hours of vancomycin plus PTZ EI (140 patients) or vancomycin plus PTZ SI (140 patients) between January 1, 2009, and December 31, 2011, and between January 1, 2013, and December 31, 2014 (year 2012 was skipped due the closure of inpatient units following Superstorm Sandy); 48 patients in each group were admitted to the intensive care unit. The median age of all patients was 67 (interquartile range [IQR] 54-77) years, and CrCl was 75 (IQR 55-107) ml/minute. Nephrotoxicity was assessed by the risk, injury, failure, loss, and end-stage kidney disease (RIFLE) and Acute Kidney Injury Network (AKIN) criteria. Rates of AKI, according to these criteria, were similar between groups: 17.9% versus 17.1% (p=1) and 32.9% versus 29.3% (p=0.596) for the PTZ EI and PTZ SI groups, respectively. When controlling for residual differences between groups in a conditional logistic regression analysis, no association was observed between receipt of PTZ EI and RIFLE-defined AKI (odds ratio 0.522, 95% confidence interval 0.043-6.295, p=0.609). Time to onset of nephrotoxicity was 4 (IQR 3-6) days, with no significant difference noted between groups (p=0.887). Our findings suggest a similar rate of nephrotoxicity between patients who received vancomycin in combination with PTZ EI versus PTZ SI. These results need

Premature mortality in active convulsive epilepsy in rural Kenya: causes and associated factors.

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Ngugi, Anthony K; Bottomley, Christian; Fegan, Gregory; Chengo, Eddie; Odhiambo, Rachael; Bauni, Evasius; Neville, Brian; Kleinschmidt, Immo; Sander, Josemir W; Newton, Charles R

2014-02-18

We estimated premature mortality and identified causes of death and associated factors in people with active convulsive epilepsy (ACE) in rural Kenya. In this prospective population-based study, people with ACE were identified in a cross-sectional survey and followed up regularly for 3 years, during which information on deaths and associated factors was collected. We used a validated verbal autopsy tool to establish putative causes of death. Age-specific rate ratios and standardized mortality ratios were estimated. Poisson regression was used to identify mortality risk factors. There were 61 deaths among 754 people with ACE, yielding a rate of 33.3/1,000 persons/year. Overall standardized mortality ratio was 6.5. Mortality was higher across all ACE age groups. Nonadherence to antiepileptic drugs (adjusted rate ratio [aRR] 3.37), cognitive impairment (aRR 4.55), and age (50+ years) (rate ratio 4.56) were risk factors for premature mortality. Most deaths (56%) were directly related to epilepsy, with prolonged seizures/possible status epilepticus (38%) most frequently associated with death; some of these may have been due to sudden unexpected death in epilepsy (SUDEP). Possible SUDEP was the likely cause in another 7%. Mortality in people with ACE was more than 6-fold greater than expected. This may be reduced by improving treatment adherence and prompt management of prolonged seizures and supporting those with cognitive impairment.

A single subconvulsant dose of domoic acid at mid-gestation does not cause temporal lobe epilepsy in mice.

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Demars, Fanny; Clark, Kristen; Wyeth, Megan S; Abrams, Emily; Buckmaster, Paul S

2018-05-01

Harmful blooms of domoic acid (DA)-producing algae are a problem in oceans worldwide. DA is a potent glutamate receptor agonist that can cause status epilepticus and in survivors, temporal lobe epilepsy. In mice, one-time low-dose in utero exposure to DA was reported to cause hippocampal damage and epileptiform activity, leading to the hypothesis that unrecognized exposure to DA from contaminated seafood in pregnant women can damage the fetal hippocampus and initiate temporal lobe epileptogenesis. However, development of epilepsy (i.e., spontaneous recurrent seizures) has not been tested. In the present study, long-term seizure monitoring and histology was used to test for temporal lobe epilepsy following prenatal exposure to DA. In Experiment One, the previous study's in utero DA treatment protocol was replicated, including use of the CD-1 mouse strain. Afterward, mice were video-monitored for convulsive seizures from 2 to 6 months old. None of the CD-1 mice treated in utero with vehicle or DA was observed to experience spontaneous convulsive seizures. After seizure monitoring, mice were evaluated for pathological evidence of temporal lobe epilepsy. None of the mice treated in utero with DA displayed the hilar neuron loss that occurs in patients with temporal lobe epilepsy and in the mouse pilocarpine model of temporal lobe epilepsy. In Experiment Two, a higher dose of DA was administered to pregnant FVB mice. FVB mice were tested as a potentially more sensitive strain, because they have a lower seizure threshold, and some females spontaneously develop epilepsy. Female offspring were monitored with continuous video and telemetric bilateral hippocampal local field potential recording at 1-11 months old. A similar proportion of vehicle- and DA-treated female FVB mice spontaneously developed epilepsy, beginning in the fourth month of life. Average seizure frequency and duration were similar in both groups. Seizure frequency was lower than that of positive

Long-term effects on biotransformation of labelled choline in different parts of the rat brain induced by single choline injections

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Nordberg, A.; Wahlstroem, G.

1988-01-01

The long-term effects of single choline (Ch) injections on the uptake and metabolism of a tracer dose of /sup 3/H-Ch were studied in male rats. Choline was administered as a threshold infusion to obtain convulsions 10 and 4 weeks before sacrific (group 1). At a single threshold infusion of choline 4 weeks before sacrifice no convulsions were induced in 50% of the animals in a second group (group 2-) whereas convulsions were induced in the remainder of the animals in this group (group 2+). Group 3 contained control animals. One min. after administration of a tracer dose of /sup 3/H-Ch the animals were sacrificed and examined for /sup 3/H-total activity, /sup 3/H-Ch, /sup 3/H-acetylcholine (/sup 3/H-ACh) and /sup 3/H-phosphorylcholine (/sup 3/-H-PhCh). These activities were determined in three parts of the brain (cortex, striatum, midbrain + medulla oblongata). In the cortex a significant negative correlation between brain weight and /sup 3/H-ACh synthesis was seen in group 1. A comparison between group 2+ and group 2- indicated that induced convulsions were not critical for this effect. In the striatum there was a significant reduction in the total uptake of radioactivity in group 1 and group 2- when values were compared to the control group. Furthermore a significant positive correlation was detected between the concentration of radiolabel and /sup 3/H-ACh synthesis and a negative relationship with the level of /sup 3/H-Ch. In the midbrain preparation the synthesis of /sup 3/H-ACh was reduced in group 1 where a significant negative correlation was found between the average threshold dose of choline and both /sup 3/H-Ach and /sup 3/H-PhCh synthesis. Thus the Ch threshold doses given several weeks before testing seem to have long term effects on the uptake and utilization of a tracer dose of /sup 3/H-Ch in the cortex and striatum.

Anti-epileptogenic and antioxidant effect of Lavandula officinalis aerial part extract against pentylenetetrazol-induced kindling in male mice.

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Rahmati, Batool; Khalili, Mohsen; Roghani, Mehrdad; Ahghari, Parisa

2013-06-21

Repeated application of Lavandula officinalis (L. officinalis) has been recommended for a long time in Iranian traditional medicine for some of nervous disorders like epilepsy and dementia. However, there is no available report for the effect of chronic administration of Lavandula extract in development (acquisition) of epilepsy. Therefore, this study was designed to investigate the anti-epileptogenic and antioxidant activity of repeated administration of Lavandula officinalis extract on pentylenetetrazol (PTZ) kindling seizures in mice model. Lavandula officinalis was tested for its ability (i) to suppress the seizure intensity and lethal effects of PTZ in kindled mice (anti-epileptogenic effect), (ii) to attenuate the PTZ-induced oxidative injury in the brain tissue (antioxidant effect) when given as a pretreatment prior to each PTZ injection during kindling development. Valproate (Val), a major antiepileptic drug, was also tested for comparison. Val and Lavandula officinalis extract showed anti-epileptogenic properties as they reduced seizure score of kindled mice and PTZ-induced mortality. In this regard, Lavandula officinalis was more effective than Val. Both Lavandula officinalis and Val suppressed brain nitric oxide (NO) level of kindled mice in comparison with the control and PTZ group. Meanwhile, Lavandula officinalis suppressed NO level more than Val and Lavandula officinalis also decreased brain MDA level relative to PTZ group. This is the first report to demonstrate NO suppressing and anti-epileptogenic effect of chronic administration of Lavandula officinalis extract on acquisition of epilepsy in PTZ kindling mice model. In this regard, Lavandula officinalis extract was more effective than Val, possibly and in part via brain NO suppression. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

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

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Kaminski, Rafal M [Department of Toxicology, Institute of Agricultural Medicine, Jaczewskiego 2, 20-950 Lublin (Poland); Blaszczak, Piotr [Department of Toxicology, Institute of Agricultural Medicine, Jaczewskiego 2, 20-950 Lublin (Poland); Dekundy, Andrzej [Department of Toxicology, Institute of Agricultural Medicine, Jaczewskiego 2, 20-950 Lublin (Poland); Parada-Turska, Jolanta [Department of Rheumatology and Connective Tissue Diseases, Medical University, Jaczewskiego 8, 20-090 Lublin (Poland); Calderazzo, Lineu [Department of Neurology and Neurosurgery, Laboratory of Experimental Neurology, Escola Paulista de Medicina, R. Botucatu 862, BR-04023 Sao Paulo, S.P. (Brazil); Cavalheiro, Esper A [Department of Neurology and Neurosurgery, Laboratory of Experimental Neurology, Escola Paulista de Medicina, R. Botucatu 862, BR-04023 Sao Paulo, S.P. (Brazil); Turski, Waldemar A [Department of Toxicology, Institute of Agricultural Medicine, Jaczewskiego 2, 20-950 Lublin (Poland); Department of Experimental and Clinical Pharmacology, Medical University, Jaczewskiego 8, 20-090 Lublin (Poland)

2007-03-15

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.

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

International Nuclear Information System (INIS)

Kaminski, Rafal M.; Blaszczak, Piotr; Dekundy, Andrzej; Parada-Turska, Jolanta; Calderazzo, Lineu; Cavalheiro, Esper A.; Turski, Waldemar A.

2007-01-01

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

Design, synthesis and biological evaluation of new hybrid anticonvulsants derived from N-benzyl-2-(2,5-dioxopyrrolidin-1-yl)propanamide and 2-(2,5-dioxopyrrolidin-1-yl)butanamide derivatives.

Science.gov (United States)

Kamiński, Krzysztof; Rapacz, Anna; Łuszczki, Jarogniew J; Latacz, Gniewomir; Obniska, Jolanta; Kieć-Kononowicz, Katarzyna; Filipek, Barbara

2015-05-15

The purpose of this study was to synthesize the library of 33 new N-benzyl-2-(2,5-dioxopyrrolidin-1-yl)propanamides, 2-(3-methyl-2,5-dioxopyrrolidin-1-yl)propanamides, and 2-(2,5-dioxopyrrolidin-1-yl)butanamides as potential new hybrid anticonvulsant agents. These hybrid molecules join the chemical fragments of well-known antiepileptic drugs (AEDs) such as ethosuximide, levetiracetam, and lacosamide. The coupling reaction of the 2-(2,5-dioxopyrrolidin-1-yl)propanoic acid, 2-(3-methyl-2,5-dioxopyrrolidin-1-yl)propanoic acid, or 2-(2,5-dioxopyrrolidin-1-yl)butanoic acid with the appropriately substituted benzylamines in the presence of the coupling reagent, N,N-carbonyldiimidazole (CDI) generated the final compounds 4-36. Spectral data acquired via (1)H NMR, (13)C NMR, and LC-MS confirmed the chemical structures of the newly prepared compounds. The initial anticonvulsant screening was performed in mice intraperitoneally (ip), using the maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole (scPTZ) seizure tests. The rotarod test determined the acute neurological toxicity (NT). The results of preliminary pharmacological screening revealed that 25 compounds showed protection in half or more of the animals tested in the MES and/or scPTZ seizure models at the fixed dose of 100mg/kg. The broad spectra of activity across the preclinical seizure models displayed compounds 4, 7, 8, 13, 15-18, 24, and 26. The quantitative pharmacological studies in mice demonstrated the highest protection for compounds 4 (ED50 MES=67.65 mg/kg, ED50scPTZ=42.83 mg/kg); 8 (ED50 MES=54.90 mg/kg, ED50scPTZ=50.29 mg/kg); and 20 (ED50scPTZ=47.39 mg/kg). These compounds were distinctly more potent and provided better safety profiles in the rotarod test compared to valproic acid or ethosuximide, which were used as model AEDs. Compound 8 underwent only a slight metabolic change by the human liver microsomes (HLMs), and also did not affect the activity of human cytochrome P450 isoform

Construction and characterization on composite electrospinning fibers doped with iridium complex owing fluorine atoms in its auxiliary ligand.

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Gao, Yu-Qian; Zhang, Shimin; Wang, Pengju; Xu, Shuxia; Wu, Kun; Mou, Wanzhi

2014-10-15

The authors synthesized a fluorine-containing Ir(III) complex Ir(PTZ)2(HFD) and the corresponding composite electrospinning fibers PVP@Ir(PTZ)2(HFD), where PTZ, HFD and PVP stood for 2-phenylbenzo[d]thiazole, 1,1,1,5,5,5-hexafluoropentane-2,4-dione and poly(vinylpyrrolidone), respectively. The molecular structure of the Ir(III) complex was confirmed by its single crystal analysis, which suggested that Ir(PTZ)2(HFD) molecules crystallized as monoclinic system with two molecules in each unit cell. Density functional theory calculation on the crystal revealed that the onset electronic transitions possessed a mixed character of metal-to-ligand-charge-transfer (MLCT) and ligand-to-ligand-charge-transfer (LLCT). Ir(PTZ)2(HFD) was then doped into electrospinning fibers so that the photophysical comparison between bulk Ir(PTZ)2(HFD) and composite samples could be performed. It was found that both face-to-face π-π attraction in crystal and the immobilization in PVP host could improve photoluminescence performance by restraining the geometric relaxation of MLCT excited state, showing emission blue shift, longer excited state lifetime and improved photostability. Copyright © 2014 Elsevier B.V. All rights reserved.

PSEUDOTUMORAL FORM OF MULTIPLE SCLEROSIS WITH SYMPTOMATIC CONVULSIVE SEIZURES (A CLINICAL CASE

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Yu. A. Belova

2015-01-01

Full Text Available Multiple sclerosis (MS is prominent among central nervous system diseases. It affects chiefly young people and almost inevitably results in disability. In the past decade, there has been an upward trend for the prevalence of MS worldwide; in particular, the higher prevalence of this disease has been registered in the Moscow Region, which is associated with both an objective increase in its morbidity and improvement of specialized care to the population in the region. MS is characterized by a variety of clinical manifestations. However, paroxysmal disturbances are referred to as the rare symptoms of MS: the incidence of epileptic seizures in this condition is 0.89 to 7.5% according to the literature data. In addition to the clinical form of MS, there are its rare malignant atypical forms that also include its pseudotumoral form characterized by intrinsic neuroimaging and clinical signs that are different from the classical form of MS and another abnormality of the central nervous system. The pseudotumoral form of MS is characterized by the development of acute focal demyelination that appears as a large focus of an increased magnetic resonance signal with perifocal edema as evidenced by magnetic resonance imaging. A pseudotumoral focus of demyelination can occur both at the onset of MS and during its recurrent course. The atypical onset of MS is a special challenge because of diagnostic problems, which may lead to erroneous therapeutic policy and have a negative impact on the late prognosis of the disease. The authors provide a clinical case of the pseudotumoral form of MS with convulsive seizures at the onset of demyelinating disease. The problems of diagnosis and therapeutic approaches are discussed.

Efek Electro Convulsive Therapy (ECT terhadap Daya Ingat Pasien Skizofrenia di RSJ Prof. HB. Sa’anin Padang

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Ikky Nabila Nandinanti

2015-09-01

Full Text Available Abstrak  ECT merupakan terapi kejang listrik dengan menghantarkan arus listrik pada elektroda dan dipasang pada kepala sehingga menyebabkan konvulsi. ECT terbukti dapat memperbaiki gejala skizofrenia, namun ECT juga memiliki efek samping terutama pada daya ingat. Tujuan  penelitian ini adalah mengetahui efek ECT terhadap daya ingat pasien skizofrenia. Metode : Penelitian ini menggunakan desain analitik dengan jumlah sampel 15 orang penderita skizofrenia di Rumah Sakit Jiwa (RSJ Prof. HB. Sa’anin Padang dengan teknik pengambilan consecutive sampling.Pemeriksaan daya ingat menggunakan Tes Memori Indonesia, dilakukan sehari sebelum ECT dan 2 jam sesudah ECT. Analisis data dengan uji T berpasangan. Gangguan daya ingat sebelum ECT terjadi pada 90% sampel dengan terganggu sedang pada kemampuan immediate memory, terganggu ringan pada kemampuan recent memory, dan terganggu berat pada remote memory. Gangguan daya ingat sesudah ECT terjadi pada seluruh sampel (100% dengan terganggu sedang pada immediate memory, terganggu berat pada recent memory, dan terganggu berat padaremote memory. Uji hipotesis pada nilai kemampuan immediate dan recent memory menghasilkan nilai p 0,018 dan 0,031 (p < 0,05, berarti Ho ditolak, sedangkan nilai p remote memory 0,678 (p > 0,05, berarti Ho diterima. Kesimpulan adalah perbedaan daya ingat immediate dan recent memory pada pasien skizofrenia sebelum dan sesudah ECT, sedangkan kemampuan remote memory tidak mengalami perubahan.Kata kunci: skizofrenia, ECT, daya ingat Abstract ECT is an electric convulsive therapy by delivering electrical current to electrodes and mounted on the head causing convulsions. ECT shown to improve schizophrenia symptoms, but ECT also has side effects especially on memory. The objective of this study was to determine the effects of ECT on memory schizophrenic patients. Current study was conducted with analytic design with sample size was 15 schizophrenia people at RSJ Prof. HB. Sa'anin Padang

Baicalein administration protects against pentylenetetrazole ...

African Journals Online (AJOL)

normal control, model (untreated epilepsy) and four treatment groups that received separately, intraperitoneal ... pentylenetetrazole-induced convulsions by baicalein treatment at a dose of 50 mg/kg. .... baicalein groups vs. model group ...

Anticonvulsant and antipunishment effects of toluene.

Science.gov (United States)

Wood, R W; Coleman, J B; Schuler, R; Cox, C

1984-08-01

Toluene can have striking acute behavioral effects and is subject to abuse by inhalation. To determine if its actions resemble those of drugs used in the treatment of anxiety ("anxiolytics"), two sets of experiments were undertaken. Inasmuch as prevention of pentylenetetrazol-induced convulsions is an identifying property of this class of agents, we first demonstrated that pretreatment with injections of toluene delayed the onset of convulsive signs and prevented the tonic extension phase of the convulsant activity in a dose-related manner. Injections of another alkyl benzene, m-xylene, were of comparable potency to toluene. Inhalation of toluene delayed the time to death after pentylenetetrazol injection in a manner related to the duration and concentration of exposure; at lower convulsant doses, inhalation of moderate concentrations (EC50, 1311 ppm) prevented death. Treatment with a benzodiazepine receptor antagonist (Ro 15-1788) failed to reduce the anticonvulsant activity of inhaled toluene. Anxiolytics also attenuate the reduction in response rate produced by punishment with electric shock. Toluene increased rates of responding suppressed by punishment when responding was maintained under a multiple fixed-interval fixed-interval punishment schedule of reinforcement. Distinct antipunishment effects were observed after 2 hr of exposure to 1780 and 3000 ppm of toluene; the rate-increasing effects of toluene were related to concentration and to time after the termination of exposure. Thus, toluene and m-xylene resemble in several respects clinically useful drugs such as the benzodiazepines.

Anticonvulsant effect of minocycline on pentylenetetrazole-induced seizure in mice: involvement of nitric oxide and N-methyl-D-aspartate receptor.

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Amini-Khoei, Hossein; Kordjazy, Nastaran; Haj-Mirzaian, Arya; Amiri, Shayan; Haj-Mirzaian, Arvin; Shirzadian, Armin; Hasanvand, Amin; Balali-Dehkordi, Shima; Hassanipoor, Mahsa; Dehpour, Ahmad Reza

2018-03-20

Anticonvulsant effects of minocycline have been explored recently. This study was designed to examine the anticonvulsant effect of acute administration of minocycline on pentylenetetrazole (PTZ)-induced seizures in mouse considering the possible role of nitric oxide (NO)/NMDA pathway. We induced seizure using intravenous administration of PTZ. Our results showed that acute administration of minocycline increased the seizure threshold. Furthermore, co-administration of sub-effective doses of the non-selective nitric oxide synthase (NOS) inhibitor, L-NAME (10 mg/kg) and the neuronal NOS inhibitor, 7-nitroindazole (40 mg/kg) enhanced the anticonvulsant effect of sub-effective dose of minocycline (40 mg/kg). We found that inducible NOS inhibitor, aminoguanidine (100 mg/kg), had no effect on the anti-seizure effect of minocycline. Moreover, L-arginine (60 mg/kg), as a NOS substrate, reduced the anticonvulsant effect of minocycline. We also demonstrated that pretreatment with NMDA receptor antagonists, ketamine (0.5 mg/kg) and MK-801 (0.05 mg/kg) increased the anticonvulsant effect of sub-effective dose of minocycline. Results showed that minocycline significantly decreased the hippocampal nitrite level. Furthermore, co-administration of nNOS inhibitor like NMDA receptor antagonists augmented the effect of minocycline on the hippocampal nitrite level. In conclusion, we revealed that anticonvulsant effect of minocycline might be, at least in part, due to decline in constitutive hippocampal nitric oxide activity as well as inhibition of NMDA receptors.

Effects of different doses of glucose and insulin on morphine state-dependent memory of passive avoidance in mice.

Science.gov (United States)

Jafari, M R; Zarrindast, M R; Djahanguiri, B

2004-10-01

Behavioral effects of morphine, including its effect on memory, have been demonstrated to be influenced by glucose pretreatment. The measurement of step-down latency in passive avoidance has been used to study memory in laboratory animals. The pre-training injection of 5 mg/kg morphine impaired memory, which was restored when 24 h later the same dose of the drug was administered. To investigate the effects of glucose and insulin alone or in combination with morphine, on pre-test day, on memory recall in mice. The effects of different doses of glucose (50, 100, and 200 mg/kg, IP) and insulin (5, 10, and 20 IU/kg, IP) alone or in combination with morphine, have been studied in mice. The blood glucose level and locomotor activity of the animals were also measured. Although the administration of glucose alone showed no effect on morphine-induced memory impairment, its co-administration with morphine resulted in a significant and dose-dependent memory enhancement compared with the effects of morphine administration alone. Like glucose, the administration of different doses of insulin alone produced no change in the memory, but when the drug was co-administered with morphine, it significantly reduced morphine-induced memory retrieval. The effect of insulin was the opposite of glucose. None of the animals subjected to insulin treatment showed convulsions. Glucose is suggested to increase, on the test day, the morphine-induced memory enhancement by three different mechanisms: cholinergic or opioidergic modulations, or regulation of the ATP-dependent potassium channels.

Ultraviolet A photosensitivity profile of dexchlorpheniramine maleate and promethazine-based creams: Anti-inflammatory, antihistaminic, and skin barrier protection properties.

Science.gov (United States)

Facchini, Gustavo; Eberlin, Samara; Clerici, Stefano Piatto; Alves Pinheiro, Ana Lucia Tabarini; Costa, Adilson

2017-12-01

Unwanted side effects such as dryness, hypersensitivity, and cutaneous photosensitivity are challenge for adherence and therapeutical success for patients using treatments for inflammatory and allergic skin response. In this study, we compared the effects of two dermatological formulations, which are used in inflammatory and/or allergic skin conditions: dexchlorpheniramine maleate (DCP; 10 mg/g) and promethazine (PTZ; 20 mg/g). We evaluated both formulations for phototoxicity potential, skin irritation, anti-inflammatory and antihistaminic abilities, and skin barrier repair in vitro and ex vivo using the standard OECD test guideline n° 432, the ECVAM protocol n° 78, and cultured skin explants from a healthy patient. Ultraviolet A was chosen as exogenous agent to induce allergic and inflammatory response. Both PTZ and DCP promoted increases in interleukin-1 (IL-1) synthesis in response to ultraviolet A (UVA) radiation compared to control. However, the increase observed with PTZ was significantly greater than the DCP, indicating that the latter has a lower irritant potential. DCP also demonstrated a protective effect on UVA-induced leukotriene B4 and nuclear factor kappa B (NF-κB) synthesis. Conversely, PTZ demonstrates more robust UVA antihistaminic activity. Likewise, PTZ promoted a significantly greater increase in the production of involucrin and keratin 14, both associated with protective skin barrier property. In conclusion, these data suggest possible diverging UVA response mechanisms of DCP and PTZ, which gives greater insight into the contrasting photosensitizing potential between DCP and PTZ observed in the patients. © 2017 Wiley Periodicals, Inc.

A Drosophila systems model of pentylenetetrazole induced locomotor plasticity responsive to antiepileptic drugs

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Singh Priyanka

2009-01-01

Full Text Available Abstract Background Rodent kindling induced by PTZ is a widely used model of epileptogenesis and AED testing. Overlapping pathophysiological mechanisms may underlie epileptogenesis and other neuropsychiatric conditions. Besides epilepsy, AEDs are widely used in treating various neuropsychiatric disorders. Mechanisms of AEDs' long term action in these disorders are poorly understood. We describe here a Drosophila systems model of PTZ induced locomotor plasticity that is responsive to AEDs. Results We empirically determined a regime in which seven days of PTZ treatment and seven days of subsequent PTZ discontinuation respectively cause a decrease and an increase in climbing speed of Drosophila adults. Concomitant treatment with NaVP and LEV, not ETH, GBP and VGB, suppressed the development of locomotor deficit at the end of chronic PTZ phase. Concomitant LEV also ameliorated locomotor alteration that develops after PTZ withdrawal. Time series of microarray expression profiles of heads of flies treated with PTZ for 12 hrs (beginning phase, two days (latent phase and seven days (behaviorally expressive phase showed only down-, not up-, regulation of genes; expression of 23, 2439 and 265 genes were downregulated, in that order. GO biological process enrichment analysis showed downregulation of transcription, neuron morphogenesis during differentiation, synaptic transmission, regulation of neurotransmitter levels, neurogenesis, axonogenesis, protein modification, axon guidance, actin filament organization etc. in the latent phase and of glutamate metabolism, cell communication etc. in the expressive phase. Proteomic interactome based analysis provided further directionality to these events. Pathway overrepresentation analysis showed enrichment of Wnt signaling and other associated pathways in genes downregulated by PTZ. Mining of available transcriptomic and proteomic data pertaining to established rodent models of epilepsy and human epileptic

Perencanaan Enterprise Architecture Pada Perusahaan Manufaktur PT. Z

OpenAIRE

Hartedja, Odwin Viator; Santoso, Leo Willyanto; Rostianingsih, Silvia

2015-01-01

PT.Z is a well-known producer and manufacturer of paint in Indonesia with years of experience in paint industry which produce many varieties of paint such as Decorative Coating (water and solvent based), automotive coating, Industrial Coating and Heavy Duty Coating. PT.Z has several subsidiaries all over Indonesia to elevate its product distribution. In the business process, PT.Z applies Information System to support and enhance the overall business. But, the current Information System applie...

Neuropharmacological effects of the aqueous leaf extract and fractions of Pavetta crassipes (K. Schum Rubiaceae in mice

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Moses W. Bariweni

2017-10-01

Full Text Available Context: In Northern Nigeria, Pavetta crassipes (K. Schum Rubiaceae leaf extracts are used in the treatment of convulsion, pain and mental illness; however, there is paucity of information on its neuropharmacological effects. Aims: To evaluate the neuropharmacological effects of the aqueous leaf extract and fractions of Pavetta crassipes. Methods: Pavetta crassipes leaves were harvested, dried and powdered using an electric mill. Hot aqueous extraction was done with 250 g powdered leaf in 1000 mL distilled water. The dry extract was partitioned in various solvents with only the aqueous fraction (AF, and butanol fraction (BF giving significant yields. Neuropharmacological effects including anticonvulsant, behavioural, antipsychotic, muscle relaxant and sedative effects were evaluated in the extract and fractions at doses of 100, 200 and 400 mg/kg, using standard methods. Results: The onset of strychnine induced convulsions was significantly (p<0.01 delayed by doses of AE and BF. Pentylenetetrazol induced convulsions were significantly (p<0.01 delayed by doses of AF and BF while AE at 400 mg/kg offered 100% protection. The duration of maximum electroshock induced tonic hind limb extension was reduced significantly (p<0.01 by AE, AF and BF. There were also significant reductions in motor coordination (p<0.01, rearing (p<0.05, locomotor activity (p<0.01, grooming (p<0.01, time of sleep onset (p<0.01, and an increase in sleeping time (p<0.01 by doses of AE, AF and BF. Conclusions: The extract and fractions of P. crassipes possess anxiolytic, sedative, anticonvulsant, antipsychotic and muscle relaxant effects to varying degrees.

l-Carnitine Modulates Epileptic Seizures in Pentylenetetrazole-Kindled Rats via Suppression of Apoptosis and Autophagy and Upregulation of Hsp70.

Science.gov (United States)

Hussein, Abdelaziz M; Adel, Mohamed; El-Mesery, Mohamed; Abbas, Khaled M; Ali, Amr N; Abulseoud, Osama A

2018-03-14

l-Carnitine is a unique nutritional supplement for athletes that has been recently studied as a potential treatment for certain neuropsychiatric disorders. However, its efficacy in seizure control has not been investigated. Sprague Dawley rats were randomly assigned to receive either saline (Sal) (negative control) or pentylenetetrazole (PTZ) 40 mg/kg i.p. × 3 times/week × 3 weeks. The PTZ group was further subdivided into two groups, the first received oral l-carnitine (l-Car) (100 mg/kg/day × 4 weeks) (PTZ + l-Car), while the second group received saline (PTZ + Sal). Daily identification and quantification of seizure scores, time to the first seizure and the duration of seizures were performed in each animal. Molecular oxidative markers were examined in the animal brains. l-Car treatment was associated with marked reduction in seizure score ( p = 0.0002) that was indicated as early as Day 2 of treatment and continued throughout treatment duration. Furthermore, l-Car significantly prolonged the time to the first seizure ( p l-Car administration for four weeks attenuated PTZ-induced increase in the level of oxidative stress marker malondialdehyde (MDA) ( p l-Car significantly reduced PTZ-induced elevation in protein expression of caspase-3 ( p l-Car in seizure control and call for testing these preclinical results in a proof of concept pilot clinical study.

Anticonvulsant mechanism of saponins fraction from adventitious roots of Ficus religiosa: possible modulation of GABAergic, calcium and sodium channel functions

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Damanpreet Singh

Full Text Available ABSTRACT In our previous studies, quantified saponins-rich fraction from adventitious root extract of Ficus religiosa L., Moraceae, showed anticonvulsant effect in acute, as well as chronic mice models of epilepsy. The present study was designed to reveal putative anticonvulsant mechanism of quantified saponins-rich fraction using target specific animal models. The anticonvulsant effect of quantified saponins-rich fraction was initially studied in maximal electroshock and pentylenetetrazol test at 1, 2 and 4 mg/kg; i.p. doses. Based on the results of initial anticonvulsant testing, different groups of mice were injected with vehicle or quantified saponins-rich fraction (4 mg/kg; i.p., 30 min prior to an injection of N-methyl-D-aspartic acid (100 mg/kg; s.c., bicuculline (5 mg/kg; i.p., strychnine hydrochloride (2 mg/kg; i.p., BAY k-8644 (37.5 µg; i.c.v., veratridine (500 µg/kg; i.p. and the convulsive episodes were studied. Treatment with the extract (1, 2 and 4 mg/kg showed significant protection in maximal electroshock and pentylenetetrazol-induced convulsion tests, in a dose-dependent manner. Moreover, quantified saponins-rich fraction at 4 mg/kg dose showed significant increase in latency to clonic convulsions, decrease in seizure severity and increase in average wave amplitude in bicuculline, BAY k-8644 and veratridine tests, respectively, as compared to vehicle control. However, SRF treatment failed to abolish N-methyl-D-aspartic acid and strychnine-induced convulsions, indicated by insignificant change in the appearance of turning behavior and onset of tonic extension, respectively, as compared to vehicle control. From the results of present study, it is concluded that quantified saponins-rich fraction suppress maximal electroshock, pentylenetetrazol, bicuculline, BAY k-8644 and veratridine-induced convulsions, indicating its GABAergic, Na+ and Ca2+ channel modulatory effects. Further it can be correlated that quantified saponins

Electromagnetic radiation (Wi-Fi) and epilepsy induce calcium entry and apoptosis through activation of TRPV1 channel in hippocampus and dorsal root ganglion of rats.

Science.gov (United States)

Ghazizadeh, Vahid; Nazıroğlu, Mustafa

2014-09-01

Incidence rates of epilepsy and use of Wi-Fi worldwide have been increasing. TRPV1 is a Ca(2+) permeable and non-selective channel, gated by noxious heat, oxidative stress and capsaicin (CAP). The hyperthermia and oxidant effects of Wi-Fi may induce apoptosis and Ca(2+) entry through activation of TRPV1 channel in epilepsy. Therefore, we tested the effects of Wi-Fi (2.45 GHz) exposure on Ca(2+) influx, oxidative stress and apoptosis through TRPV1 channel in the murine dorsal root ganglion (DRG) and hippocampus of pentylentetrazol (PTZ)-induced epileptic rats. Rats in the present study were divided into two groups as controls and PTZ. The PTZ groups were divided into two subgroups namely PTZ + Wi-Fi and PTZ + Wi-Fi + capsazepine (CPZ). The hippocampal and DRG neurons were freshly isolated from the rats. The DRG and hippocampus in PTZ + Wi-Fi and PTZ + Wi-Fi + CPZ groups were exposed to Wi-Fi for 1 hour before CAP stimulation. The cytosolic free Ca(2+), reactive oxygen species production, apoptosis, mitochondrial membrane depolarization, caspase-3 and -9 values in hippocampus were higher in the PTZ group than in the control although cell viability values decreased. The Wi-Fi exposure induced additional effects on the cytosolic Ca(2+) increase. However, pretreatment of the neurons with CPZ, results in a protection against epilepsy-induced Ca(2+) influx, apoptosis and oxidative damages. In results of whole cell patch-clamp experiments, treatment of DRG with Ca(2+) channel antagonists [thapsigargin, verapamil + diltiazem, 2-APB, MK-801] indicated that Wi-Fi exposure induced Ca(2+) influx via the TRPV1 channels. In conclusion, epilepsy and Wi-Fi in our experimental model is involved in Ca(2+) influx and oxidative stress-induced hippocampal and DRG death through activation of TRPV1 channels, and negative modulation of this channel activity by CPZ pretreatment may account for the neuroprotective activity against oxidative stress.

Oxadiazole-Based Highly Efficient Bipolar Fluorescent Emitters for Organic Light-Emitting Diodes

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Qiong Wu

2018-04-01

Full Text Available In this study, a series of bipolar fluorescence emitters named 2DPAc-OXD, DPAc-OXD, 2PTZ-OXD and PTZ-OXD were designed and synthesized with excellent yields. The characterization of materials was investigated by using nuclear magnetic resonance (NMR (1H, 13C, mass spectrometry and thermogravimetric analysis (TGA. To investigate device efficiencies, two different OLED devices (Device 1, Device 2 were fabricated with two different host materials (Bepp2, DPEPO. The Device 2 with 2PTZ-OXD as fluorescent emitter exhibited excellent power and current efficiencies of 6.88 Lm/W and 10.10 cd/A, respectively. The external quantum efficiency of 2PTZ-OXD was around 3.99% for Device 2. The overall device properties of phenothiazine donor were better than acridine derivatives.

[Toxicity studies of landiolol hydrochloride (ONO-1101) (2). 4-week repeated dose intravenous toxicity study in rats with 4-week recovery test].

Science.gov (United States)

Yamaguchi, K; Yanagi, H; Shimizu, K; Sakai, M; Nishibata, K; Oida, H; Shinomiya, K; Suzuki, Y; Yonezawa, H; Fujita, T

1997-12-01

4-week repeated dose toxicity study with 4-week recovery test of landiolol hydrochloride (ONO-1101), a novel ultra short acting beta-blocker, was conducted in Sprague-Dawley (SD) rats. ONO-1101 was administered intravenously to rats of both sexes at a dose level of 0 (control), 12.5, 25, 50 or 100 mg/kg/day. In the 100 mg/kg/day group, bradypnea or dyspnea was seen in all animals, pale in ear, eye and foot, tremor, reddish lacrimation and loss of righting reflex were also observed in some animals right after administration, and then those signs disappeared within 1 min after administration. During the treatment period, 3/20 animals of each sex in the 100 mg/kg/day showed clonic convulsion and died within 2 min after administration. No clinical changes were seen in the 50 mg/kg/day group or lower. Histopathological findings showed atrophy of the submaxillary gland in females and vessel-wall thickening and perivascular fibrosis of the injection site (tail) in both sexes at 100 mg/kg/day, however those changes were reversible. ONO-1101 did not effect on body weight, food consumption, ophthalmology, urinalysis, hematology, blood chemistry, organ weights or necropsy at any doses. These results indicate that the no-adverse-effect level of ONO-1101 in rats is 50 mg/kg/day for both sexes in this study.

[Familial febrile convulsions is supposed to link to human chromosome 19p13.3].

Science.gov (United States)

Qi, Y; Lü, J; Wu, X

2001-01-10

To localize the familial febrile convulsion (FC) genes on human chromosomes. For 63 FC pedigrees, tetranucleotide repeat markers D19S253 D19S395 and D19S591 on the short arm of chromosome 19, as well as dinucleotide repeat markers D8S84 and D8S85 on the long arm of chromosome 8 were genotyped. Transmission disequilibrium test (TDT) and Lod score calculation were carried out. The data were processed by PPAP software package. All the alleles in every locus of FC probands and normal controls were in Hardy-Weinburg balance. Transmission disequilibrium was found on D8S84, D19S395 and D19S591 in FC families. chi(2) values were 4.0, 5.124 and 7.364 separately. Each P value was < 0.05, and significantly meaningful. The two-point Lod scores between D8S84 and FC, D8S85 and FC, D19S253 and FC, D19S395 and FC, D19S591 and FC are 0.00002, 0.000017, 0.58, 1.53 and 1.42 respectively. The multi-point Lod score among markers on chromosome 8q and FC was 0.88, while Lod score among markers on chromosome 19p and FC reached 2.78. The results by both the non-parameter (TDT) and parameter (Lod score) methods were consistant on a whole. FC is linked with chromosome region 19p13.3, but not with chromosome 8q.

Adenosine receptor modulation of seizure susceptibility in rats

International Nuclear Information System (INIS)

Szot, P.

1987-01-01

Adenosine is considered to be a neuromodulator or cotransmitter in the periphery and CNS. This neuromodulatory action of adenosine may be observed as an anticonvulsant effect. Dose-response curves for R-phenylisopropyladenosine (PIA), cycohexyladenosine (CHA), 2-chloroadenosine (2-ClAdo), N-ethylcarboxamidoadenosine (NECA) and S-PIA were generated against PTZ seizure thresholds in the rat. The rank order of potency for adenosine agonists to elevate PTZ seizure threshold was R-PIA > 2-ClAdo > NECA > CHA > S-PIA. R-PIA was approximately 80-fold more potent than S-PIA. This 80-fold difference in potency between the diasteriomers of PIA was consistent with an A 1 adenoise receptor-mediated response. The anticonvulsant action of 2-ClAdo was reversed by pretreatment with theoplylline. Chronic administration of theophylline significantly increased the specific binding of 3 H-cyclohexyladenosine in membranes of the cerebral cortex and cerebellum of the rat. Chronic exposure to theophylline produced a significant increase in the densities of both the high- and low-affinity forms of A 1 adenosine receptors in the cerebral cortex

Ameliorative effect of Asparagus racemosus root extract against pentylenetetrazol-induced kindling and associated depression and memory deficit.

Science.gov (United States)

Pahwa, Priyanka; Goel, Rajesh Kumar

2016-04-01

Asparagus racemosus (A. racemosus) roots are extensively used in traditional medicine for the management of epilepsy. The aim of the present study was to investigate the ameliorative effect of A. racemosus root extract (ARE) against pentylenetetrazol-induced kindling and associated depression and memory deficit. Kindling was successfully induced by repeated administration of a subconvulsant dose of PTZ (35 mg/kg; i.p.) at an interval of 48 ± 2 h in 43 days (21 injections). Pretreatment with valproate (300 mg/kg; i.p.), a major antiepileptic drug as well as ARE significantly suppressed the progression of kindling. Moreover, ARE also ameliorated the kindling-associated depression and memory deficit as indicated by decreased immobility time and increased step-down latency, respectively, as compared to vehicle control animals. Further, these behavioral observations were complemented with analogous neurochemical changes. In conclusion, the results of the present study showed that ARE treatment has an ameliorative effect against PTZ-induced kindling and associated behavioral comorbidities. Copyright © 2016 Elsevier Inc. All rights reserved.

Adaptation Computing Parameters of Pan-Tilt-Zoom Cameras for Traffic Monitoring

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Ya Lin WU

2014-01-01

Full Text Available The Closed- CIRCUIT television (CCTV cameras have been widely used in recent years for traffic monitoring and surveillance applications. We can use CCTV cameras to extract automatically real-time traffic parameters according to the image processing and tracking technologies. Especially, the pan-tilt-zoom (PTZ cameras can provide flexible view selection as well as a wider observation range, and this makes the traffic parameters can be accurately calculated. Therefore, that the parameters of PTZ cameras are calibrated plays an important role in vision-based traffic applications. However, in the specific traffic environment, which is that the license plate number of the illegal parking is located, the parameters of PTZ cameras have to be updated according to the position and distance of illegal parking. In proposed traffic monitoring systems, we use the ordinary webcam and PTZ camera. We get vanishing-point of traffic lane lines in the pixel-based coordinate system by fixed webcam. The parameters of PTZ camera can be initialized by distance of the traffic monitoring and specific objectives and vanishing-point. And then we can use the coordinate position of the illegally parked car to update the parameters of PTZ camera and then get the real word coordinate position of the illegally parked car and use it to compute the distance. The result shows the error of the tested distance and real distance is only 0.2064 meter.

Evaluating acute effects of Electro Convulsive Therapy (ECT) on brain perfusion with Tc-99m HMPAO brain SPECT

International Nuclear Information System (INIS)

Ozguven, M.; Ozturk, E.; Gunalp, B.; Ozgen, F.; Bayhan, H.

1992-01-01

Regional cerebral blood flow (rCBF) was measured by Tc-99m HMPAO brain perfusion SPECT in 10 schizophrenes (8 male, 2 female) undergoing electro convulsive therapy (ECT) and the results were compared to those of baseline studies performed 3 days prior to the ECT application to evaluate its acute effect on brain perfusion. ECT caused a redistribution in the tracers uptake. There was a global increase in the rCBF and the uptake became more pronounced in the basal ganglia (left: 44.4+-1.9%, right: 43.1+-19%) and to a degree in the parietal (left: 26.5+-4.1%, right: 25+-3.4%) and temporal (left: 22.9+-4.3%, right: 22.3+-3.6%) cortices. When evaluating the effects of ECT on rCBF, factors like the used perfusion agent, the injection and rCBF measurement times, clinical status of the patient, duration of the illness, used therapeutic agents and variations in the ECT application should be taken into consideration because the obtained data may reflect either the ictal or post-ictal changes on rCBF and is specific to the group of patients undergoing the study

Treatment of Established Status Epilepticus.

Science.gov (United States)

Falco-Walter, Jessica J; Bleck, Thomas

2016-04-25

Status epilepticus is the most severe form of epilepsy, with a high mortality rate and high health care costs. Status epilepticus is divided into four stages: early, established, refractory, and super-refractory. While initial treatment with benzodiazepines has become standard of care for early status epilepticus, treatment after benzodiazepine failure (established status epilepticus (ESE)) is incompletely studied. Effective treatment of ESE is critical as morbidity and mortality increases dramatically the longer convulsive status epilepticus persists. Phenytoin/fosphenytoin, valproic acid, levetiracetam, phenobarbital, and lacosamide are the most frequently prescribed antiseizure medications for treatment of ESE. To date there are no class 1 data to support pharmacologic recommendations of one agent over another. We review each of these medications, their pharmacology, the scientific evidence in support and against each in the available literature, adverse effects and safety profiles, dosing recommendations, and limitations of the available evidence. We also discuss future directions including the established status epilepticus treatment trial (ESETT). Substantial further research is urgently needed to identify these patients (particularly those with non-convulsive status epilepticus), elucidate the most efficacious antiseizure treatment with head-to-head randomized prospective trials, and determine whether this differs for convulsive vs. non-convulsive ESE.

Berberidaceae

African Journals Online (AJOL)

drug-induced convulsions and provided 100 % protection to animals at both doses. They also showed .... according to method with minor modifications as described by ... well was transferred to the next well and mixed with 50 µL of broth.

Synthesis and anticonvulsant activity of certain chalcone based pyrazoline compounds

Directory of Open Access Journals (Sweden)

Sudhakara Rao Gerapati

2015-09-01

Full Text Available Convulsions are involuntary, violent, spasmodic and prolonged contractions of skeletal muscles. That means a patient may have epilepsy without convulsions and vice versa. Epilepsy is a common neurological abnormality affecting about 1% of the world population. The primary objectives of these synthesized compounds are to suppress seizures and provide neuroprotection by minimizing the effects from seizure attacks. Here some of the chalcones and chalcone based various pyrazolines were evaluated for anticonvulsant activity. Their structures have been elucidated on the basis of elemental analyses and spectroscopic studies (IR, 1H-NMR & Mass spectroscopy. A preliminary evaluation of the prepared compounds has indicated that some of them exhibit moderate to significant anticonvulsant activity compared to a diazepam standard1-3.  All compounds were tested for their anticonvulsant activity using maximal electroshock induced convulsions (MES in mice at a dose level of 4 mg/kg.b.w. The compounds  Ph1, Ph2 , Py2 ,Py3 and Py4 have shown  to  good anticonvulsant activity when doses are administered as 25mg/ kg.b.w  , reduced the phases of seizures severity and  found to be active and also  increased survival rate. Remaining compounds are less efficacious.

Quantitative analysis of neurological effects induced by cranio-caudal gamma-irradiation of rats

International Nuclear Information System (INIS)

Davydov, B.I.; Ushakov, I.B.; Karpov, V.N.

1987-01-01

A study was made of the frequency and duration of neurological disorders after cranio-caudal irradiation of rats with doses of 7.5-500 Gy delivered to the head. As the mean effective dose increased the neurological disorders occurred in the following order: tremor, rotatory movements hyperkinesia, opisthotonos, and convulsions. The europhysiological disorders observed were subjected to a pathophysiological analysis

High-dose phenobarbital with intermittent short-acting barbiturates for acute encephalitis with refractory, repetitive partial seizures.

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Uchida, Takashi; Takayanagi, Masaru; Kitamura, Taro; Nishio, Toshiyuki; Numata, Yurika; Endo, Wakaba; Haginoya, Kazuhiro; Ohura, Toshihiro

2016-08-01

Acute encephalitis with refractory, repetitive partial seizures (AERRPS) is characterized by repetitive seizures during the acute and chronic phases and has a poor neurological outcome. Burst-suppression coma via continuous i.v. infusion of a short-acting barbiturate is used to terminate refractory seizures, but the severe side-effects of short-acting barbiturates are problematic. We report on a 9-year-old boy with AERRPS who was effectively treated with very-high-dose phenobarbital (VHDPB) combined with intermittent short-acting barbiturates. VHDPB side-effects were mild, especially compared with those associated with continuous i.v. infusion of short-acting barbiturates (dosage, 40-75 mg/kg/day; maximum blood level, 290 μg/mL). Using VHDPB as the main treatment, short-acting barbiturates were used intermittently and in small amounts. This is the first report to show that VHDPB, combined with intermittent short-acting barbiturates, can effectively treat AERRPS. After treatment, convulsions were suppressed and daily life continued, but intellectual impairment and high-level dysfunction remained. © 2016 Japan Pediatric Society.

Clinical and neuroradiological study on adult cases of familial microcephaly associated with mental retardation and convulsive seizure

International Nuclear Information System (INIS)

Murakami, Nobuyuki; Kitabayashi, Toshiko.

1987-01-01

Microcephaly results from various causes, some genetic and some non-genetic. Recently, we encountered two families with microcephaly, mental retardation and convulsive seizure. These conform to an autosomal recessive mode of inheritance. All adult cases were analyzed to describe the characteristic neuroradiographic findings. Although each presented a similar neurologic outlook, two cases secondarily resulting from infection or injuries to the developing brain during postnatal periods showed a specific variation. Skull X-P and CT scan of these two cases showed thickening of the carvarium, predominantly fronto-parietal lobe atrophy of the cerebrum, enlargement of the ventricle, and compensatory hypertrophy of sinuses. Magnetic resonance imaging (MRI) showed severe micropolygyria and hypogenesis of corpus callosum. Abnormalities such as skull X-P, CT scan and MRI were severer in the secondary than in the primary microcephalics. Although brain volume was reduced, the volume ratio of cortex to white watter was similar to that of normal brain. MRI on severe cases of microcephaly revealed a high signal intensity in inversion-recovery images on the brain stem where markedly atrophy was noted. In adult microcephaly, the extent of cerebral development was thought to be reflected in the corpus callosum and brain stem where neuron fibers were densely gathered. (author)

The SAFARI Score to Assess the Risk of Convulsive Seizure During Admission for Aneurysmal Subarachnoid Hemorrhage.

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Jaja, Blessing N R; Schweizer, Tom A; Claassen, Jan; Le Roux, Peter; Mayer, Stephan A; Macdonald, R Loch

2018-06-01

Seizure is a significant complication in patients under acute admission for aneurysmal SAH and could result in poor outcomes. Treatment strategies to optimize management will benefit from methods to better identify at-risk patients. To develop and validate a risk score for convulsive seizure during acute admission for SAH. A risk score was developed in 1500 patients from a single tertiary hospital and externally validated in 852 patients. Candidate predictors were identified by systematic review of the literature and were included in a backward stepwise logistic regression model with in-hospital seizure as a dependent variable. The risk score was assessed for discrimination using the area under the receiver operator characteristics curve (AUC) and for calibration using a goodness-of-fit test. The SAFARI score, based on 4 items (age ≥ 60 yr, seizure occurrence before hospitalization, ruptured aneurysm in the anterior circulation, and hydrocephalus requiring cerebrospinal fluid diversion), had AUC = 0.77, 95% confidence interval (CI): 0.73-0.82 in the development cohort. The validation cohort had AUC = 0.65, 95% CI 0.56-0.73. A calibrated increase in the risk of seizure was noted with increasing SAFARI score points. The SAFARI score is a simple tool that adequately stratified SAH patients according to their risk for seizure using a few readily derived predictor items. It may contribute to a more individualized management of seizure following SAH.

Effect of an Early Dose of Measles Vaccine on Morbidity Between 18 Weeks and 9 Months of Age: A Randomized, Controlled Trial in Guinea-Bissau

DEFF Research Database (Denmark)

Do, Vu An; Biering-Sorensen, Sofie; Fisker, Ane Bærent

2017-01-01

Background: Children in Guinea-Bissau receive measles vaccine (MV) at 9 months of age, but studies have shown that an additional dose before 9 months of age might have beneficial nonspecific effects. Within a randomized trial designed to examine nonspecific effects of early MV receipt on mortality......). Children were visited weekly from enrollment to age 9 months; the mother reported morbidity, and the field assistants examined the children. Using Cox and binomial regression models, we compared the 2 randomization groups. Results: Among the 1592 children, early measles vaccination was not associated...... with a higher risk of the well-known adverse events of fever, rash, and convulsions within the first 14 days. From 15 days after randomization to age 9 months, early measles vaccination was associated with reductions in maternally reported diarrhea (hazard ratio [HR], 0.89; 95% confidence interval [CI],.82-. 97...

Clinical features, proximate causes, and consequences of active convulsive epilepsy in Africa

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Kariuki, Symon M; Matuja, William; Akpalu, Albert; Kakooza-Mwesige, Angelina; Chabi, Martin; Wagner, Ryan G; Connor, Myles; Chengo, Eddie; Ngugi, Anthony K; Odhiambo, Rachael; Bottomley, Christian; White, Steven; Sander, Josemir W; Neville, Brian G R; Newton, Charles R J C

2014-01-01

Purpose Epilepsy is common in sub-Saharan Africa (SSA), but the clinical features and consequences are poorly characterized. Most studies are hospital-based, and few studies have compared different ecological sites in SSA. We described active convulsive epilepsy (ACE) identified in cross-sectional community-based surveys in SSA, to understand the proximate causes, features, and consequences. Methods We performed a detailed clinical and neurophysiologic description of ACE cases identified from a community survey of 584,586 people using medical history, neurologic examination, and electroencephalography (EEG) data from five sites in Africa: South Africa; Tanzania; Uganda; Kenya; and Ghana. The cases were examined by clinicians to discover risk factors, clinical features, and consequences of epilepsy. We used logistic regression to determine the epilepsy factors associated with medical comorbidities. Key Findings Half (51%) of the 2,170 people with ACE were children and 69% of seizures began in childhood. Focal features (EEG, seizure types, and neurologic deficits) were present in 58% of ACE cases, and these varied significantly with site. Status epilepticus occurred in 25% of people with ACE. Only 36% received antiepileptic drugs (phenobarbital was the most common drug [95%]), and the proportion varied significantly with the site. Proximate causes of ACE were adverse perinatal events (11%) for onset of seizures before 18 years; and acute encephalopathy (10%) and head injury prior to seizure onset (3%). Important comorbidities were malnutrition (15%), cognitive impairment (23%), and neurologic deficits (15%). The consequences of ACE were burns (16%), head injuries (postseizure) (1%), lack of education (43%), and being unmarried (67%) or unemployed (57%) in adults, all significantly more common than in those without epilepsy. Significance There were significant differences in the comorbidities across sites. Focal features are common in ACE, suggesting identifiable and

Salzburg Consensus Criteria for Non-Convulsive Status Epilepticus--approach to clinical application.

Science.gov (United States)

Leitinger, M; Beniczky, S; Rohracher, A; Gardella, E; Kalss, G; Qerama, E; Höfler, J; Hess Lindberg-Larsen, A; Kuchukhidze, G; Dobesberger, J; Langthaler, P B; Trinka, E

2015-08-01

Salzburg Consensus Criteria for diagnosis of Non-Convulsive Status Epilepticus (SCNC) were proposed at the 4th London-Innsbruck Colloquium on status epilepticus in Salzburg (2013). We retrospectively analyzed the EEGs of 50 consecutive nonhypoxic patients with diagnoses of nonconvulsive status epilepticus (NCSE) at discharge and 50 consecutive controls with abnormal EEGs in a large university hospital in Austria. We implemented the American Clinical Neurophysiology Society's Standardized Critical Care EEG Terminology, 2012 version (ACNS criteria) to increase the test performance of SCNC. In patients without preexisting epileptic encephalopathy, the following criteria were applied: (1) more than 25 epileptiform discharges (ED) per 10-second epoch, i.e., >2.5/s and (2) patients with EDs ≤ 2.5/s or rhythmic delta/theta activity (RDT) exceeding 0.5/s AND at least one of the additional criteria: (2a) clinical and EEG improvements from antiepileptic drugs (AEDs), (2b) subtle clinical phenomena, or (2c) typical spatiotemporal evolution. In case of fluctuation without evolution or EEG improvement without clinical improvement, "possible NCSE" was diagnosed. For identification of RDT, the following criteria were compared: (test condition A) continuous delta-theta activity without further rules, (B) ACNS criterion for rhythmic delta activity (RDA), and (C) ACNS criteria for RDA and fluctuation. False positive rate in controls dropped from 28% (condition A) to 2% (B) (p = 0.00039) and finally to 0% (C) (p = 0.000042). Application of test condition C in the group with NCSE gives one false negative (2%). Various EEG patterns were found in patients with NCSE: (1) 8.2%, (2a) 2%, (2b) 12.2%, and (2c) 32.7%. Possible NCSE was diagnosed based on fluctuations in 57.1% and EEG improvement without clinical improvement in 14.2%. The modified SCNC with refined definitions including the ACNS terminology leads to clinically relevant and statistically significant reduction of false

The epileptogenic spectrum of opiate agonists.

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Snead, O C; Bearden, L J

1982-11-01

The present authors gave mu, delta, kappa, epsilon and sigma opiate receptor agonists intracerebroventricularly to rats both singly and in combination while monitoring the electroencephalogram from cortical and depth electrodes. Dose-response curves were plotted with naloxone against the changes produced by each agonist, and the effect of a number of anticonvulsant drugs on agonist-induced seizures was ascertained. Each opiate agonist produced a different seizure pattern with a different naloxone dose-response curve and anticonvulsant profile. The order of convulsive potency was epsilon greater than delta greater than mu greater than sigma much greater than kappa. Petit mal-like seizure activity was unique to the delta agonist, leucine-enkephalin, while only the mu agonist, morphine produced generalized convulsive seizures. These experiments raise the possibility that opiate systems in the brain may be involved in the pathogenesis of a wide spectrum of seizure disorders.

Synthesis and enantiopharmacology of new AMPA-kainate receptor agonists

DEFF Research Database (Denmark)

Conti, P; De Amici, M; De Sarro, G

1999-01-01

. The convulsant properties of all the compounds were evaluated in vivo on DBA/2 mice after icv injection. CIP-A showed a convulsant activity, measured as tonus and clonus seizures, 18-65 times higher than that produced by AMPA. It was also quite active after ip administration, since it induced seizures in mice...... at doses as low as 3.2 nmol/mouse. On the basis of the above-reported results we prepared and tested the enantiomers of CIP-A and CIP-B, obtained by reacting (S)-3,4-didehydroproline and (R)-3,4-didehydroproline, respectively, with ethoxycarbonylformonitrile oxide. In all the tests the S-form, CIP...

Protection against cocaine toxicity in mice by the dopamine D-3/D-2 agonist R-(+)-trans-3,4a,10b-Tetrahydro-4-propyl-2H,5H[1]benzopyrano[4,3-b]-1,4-oxazin-9-ol[(+)-PD 128,907

NARCIS (Netherlands)

Witkin, JM; Dijkstra, D; Levant, B; Akunne, HC; Zapata, A; Peters, S; Shannon, HE; Gasior, M

2004-01-01

Cocaine abuse is a public health concern with seizures and death being one consequence of overdose. In the present study, dopamine D-3/D-2 receptor agonists dose dependently and completely prevented the convulsant and lethal effects of cocaine. The D-3-preferring agonists

Neurotoxicity of cholinesterase inhibitors: Mechanism, prophylaxis, and therapy (organophosphates). Midterm report, 1 December 1991-30 June 1993

Energy Technology Data Exchange (ETDEWEB)

De Groot, D.M.; Bierman, E.P.; Van Huygevoort, A.H.; Bruijnzeel, P.L.

1993-09-30

The effects of the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist N-L(2-thienyl)cyclohexylpiperidine (TCP) on soman-induced convulsions and brain damage were studied in rats. For comparison, the effects of another non-competitive NMDA receptor antagonist MK801 were investigated in a pilot study. We were unable to provide hard evidence that TCP without additional drug treatment has therapeutic effects on soman-induced convulsions and/or brain damage, either when injected intracerebrally, or when injected systemically. In contrast, MK801 was effective, but only when an additional dose of MK801 was administered 5 minutes prior to the soman injection and not when seizures had been going on for 30 minutes. The results suggest that interference with the mechanisms leading to brain damage after soman at the level of the NMDA receptor only, is not sufficient to prevent this damage. However, in combination with drugs that interfere at an earlier stage in the sequence of events leading to convulsions and brain damage after soman, TCP and analogues appear as promising drugs for further treatment of soman-intoxicated individuals. Non-Competitive NMDA antagonists, TCP, MK801, Convulsions, Neuropathology, Intracerebral injections, NMDA receptors, RA V, Lab animals, Rats, Amino acids.

Treatment of Established Status Epilepticus

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Falco-Walter, Jessica J.; Bleck, Thomas

2016-01-01

Status epilepticus is the most severe form of epilepsy, with a high mortality rate and high health care costs. Status epilepticus is divided into four stages: early, established, refractory, and super-refractory. While initial treatment with benzodiazepines has become standard of care for early status epilepticus, treatment after benzodiazepine failure (established status epilepticus (ESE)) is incompletely studied. Effective treatment of ESE is critical as morbidity and mortality increases dramatically the longer convulsive status epilepticus persists. Phenytoin/fosphenytoin, valproic acid, levetiracetam, phenobarbital, and lacosamide are the most frequently prescribed antiseizure medications for treatment of ESE. To date there are no class 1 data to support pharmacologic recommendations of one agent over another. We review each of these medications, their pharmacology, the scientific evidence in support and against each in the available literature, adverse effects and safety profiles, dosing recommendations, and limitations of the available evidence. We also discuss future directions including the established status epilepticus treatment trial (ESETT). Substantial further research is urgently needed to identify these patients (particularly those with non-convulsive status epilepticus), elucidate the most efficacious antiseizure treatment with head-to-head randomized prospective trials, and determine whether this differs for convulsive vs. non-convulsive ESE. PMID:27120626

Role of nitric oxide in additive anticonvulsant effects of agmatine and morphine.

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Payandemehr, Borna; Rahimian, Reza; Bahremand, Arash; Ebrahimi, Ali; Saadat, Seyedehpariya; Moghaddas, Peiman; Fadakar, Kaveh; Derakhshanian, Hoda; Dehpour, Ahmad Reza

2013-06-13

The anticonvulsant effects of agmatine, an endogenous polyamine and a metabolite of l-arginine, have been shown in various experimental seizure models. Agmatine also potentiates the anti-seizure activity of morphine. The present study aimed to investigate a possible involvement of nitric oxide (NO) pathway in the protection by agmatine and morphine co-administration against pentylenetetrazole (PTZ) -induced seizure in male mice. To this end, the thresholds for the clonic seizures induced by the intravenous administration of PTZ, a GABA antagonist, were assessed. Intraperitoneal administration of morphine at lower dose (1mg/kg) increased the seizure threshold. Also intraperitoneal administration of agmatine (5 and 10mg/kg) increased the seizure threshold significantly. Combination of subeffective doses of morphine and agmatine led to potent anticonvulsant effects. Non-effective doses of morphine (0.1 and 0.5mg/kg) were able to induce anticonvulsant effects in mice pretreated with agmatine (3mg/kg). Concomitant administration of either the non-selective nitric oxide synthase (NOS) inhibitor L-NAME (1, 5mg/kg, i.p.) or the selective NOS inhibitor 7-NI (15, 30mg/kg, i.p.), with an ineffective combination of morphine (0.1mg/kg) plus agmatine (1mg/kg) produced significant anticonvulsant impacts. Moreover, the NO precursor, l-arginine (30, 60mg/kg, i.p.), inhibited the anticonvulsant action of agmatine (3mg/kg) plus morphine (0.5mg/kg) co-administration. Our results indicate that pretreatment of animals with agmatine enhances the anticonvulsant effects of morphine via a mechanism which may involve the NO pathway. Copyright © 2013 Elsevier Inc. All rights reserved.

l-Carnitine Modulates Epileptic Seizures in Pentylenetetrazole-Kindled Rats via Suppression of Apoptosis and Autophagy and Upregulation of Hsp70

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Abdelaziz M. Hussein

2018-03-01

Full Text Available l-Carnitine is a unique nutritional supplement for athletes that has been recently studied as a potential treatment for certain neuropsychiatric disorders. However, its efficacy in seizure control has not been investigated. Sprague Dawley rats were randomly assigned to receive either saline (Sal (negative control or pentylenetetrazole (PTZ 40 mg/kg i.p. × 3 times/week × 3 weeks. The PTZ group was further subdivided into two groups, the first received oral l-carnitine (l-Car (100 mg/kg/day × 4 weeks (PTZ + l-Car, while the second group received saline (PTZ + Sal. Daily identification and quantification of seizure scores, time to the first seizure and the duration of seizures were performed in each animal. Molecular oxidative markers were examined in the animal brains. l-Car treatment was associated with marked reduction in seizure score (p = 0.0002 that was indicated as early as Day 2 of treatment and continued throughout treatment duration. Furthermore, l-Car significantly prolonged the time to the first seizure (p < 0.0001 and shortened seizure duration (p = 0.028. In addition, l-Car administration for four weeks attenuated PTZ-induced increase in the level of oxidative stress marker malondialdehyde (MDA (p < 0.0001 and reduced the activity of catalase enzyme (p = 0.0006 and increased antioxidant GSH activity (p < 0.0001. Moreover, l-Car significantly reduced PTZ-induced elevation in protein expression of caspase-3 (p < 0.0001 and β-catenin (p < 0.0001. Overall, our results suggest a potential therapeutic role of l-Car in seizure control and call for testing these preclinical results in a proof of concept pilot clinical study.

Involvement of over-expressed BMP4 in pentylenetetrazol kindling-induced cell proliferation in the dentate gyrus of adult rats

International Nuclear Information System (INIS)

Yin Jinbo; Ma Yuxin; Yin Qing; Xu Haiwei; An Ning; Liu Shiyong; Fan Xiaotang; Yang Hui

2007-01-01

The dentate gyrus (DG) of the hippocampus is one of a few regions in the adult mammalian brain characterized by ongoing neurogenesis. Proliferation of neural precursors in the granule cell layer of the DG has been identified in pentylenetetrazol (PTZ) kindling epilepsy model, however, little is known about the molecular mechanism. We previously reported that the expression pattern of bone morphogenetic proteins-4 (BMP4) mRNA in the hippocampus was developmentally regulated and mainly localized in the DG of the adult. To explore the role of BMP4 in epileptic activity, we detected BMP4 expression in the DG during PTZ kindling process and explore its correlation with cell proliferation combined with bromodeoxyuridine (BrdU) labeling technique. We found that dynamic changes in BMP4 level and BrdU labeled cells dependent on the kindling stage of PTZ induced seizure-prone state. The number of BMP4 mRNA-positive cells and BrdU labeled cells reached the top level 1 day after PTZ kindled, then declined to base level 2 months later. Furthermore, there was a significant correlation between increased BMP4 mRNA expression and increased number of BrdU labeled cells. After effectively blocked expression of BMP4 with antisense oligodeoxynucleotides(ASODN), the BrdU labeled cells in the dentate gyrus subgranular zone(DG-SGZ) and hilus were significantly decreased 16d after First PTZ injection and 1, 3, 7, 14d after kindled respectively. These findings suggest that increased proliferation in the DG of the hippocampus resulted from kindling epilepsy elicited by PTZ maybe be modulated by BMP4 over-expression

Insights from zebrafish and mouse models on the activity and safety of ar-turmerone as a potential drug candidate for the treatment of epilepsy.

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Adriana Monserrath Orellana-Paucar

Full Text Available In a previous study, we uncovered the anticonvulsant properties of turmeric oil and its sesquiterpenoids (ar-turmerone, α-, β-turmerone and α-atlantone in both zebrafish and mouse models of chemically-induced seizures using pentylenetetrazole (PTZ. In this follow-up study, we aimed at evaluating the anticonvulsant activity of ar-turmerone further. A more in-depth anticonvulsant evaluation of ar-turmerone was therefore carried out in the i.v. PTZ and 6-Hz mouse models. The potential toxic effects of ar-turmerone were evaluated using the beam walking test to assess mouse motor function and balance. In addition, determination of the concentration-time profile of ar-turmerone was carried out for a more extended evaluation of its bioavailability in the mouse brain. Ar-turmerone displayed anticonvulsant properties in both acute seizure models in mice and modulated the expression patterns of two seizure-related genes (c-fos and brain-derived neurotrophic factor [bdnf] in zebrafish. Importantly, no effects on motor function and balance were observed in mice after treatment with ar-turmerone even after administering a dose 500-fold higher than the effective dose in the 6-Hz model. In addition, quantification of its concentration in mouse brains revealed rapid absorption after i.p. administration, capacity to cross the BBB and long-term brain residence. Hence, our results provide additional information on the anticonvulsant properties of ar-turmerone and support further evaluation towards elucidating its mechanism of action, bioavailability, toxicity and potential clinical application.

Insights from zebrafish and mouse models on the activity and safety of ar-turmerone as a potential drug candidate for the treatment of epilepsy.

Science.gov (United States)

Orellana-Paucar, Adriana Monserrath; Afrikanova, Tatiana; Thomas, Joice; Aibuldinov, Yelaman K; Dehaen, Wim; de Witte, Peter A M; Esguerra, Camila V

2013-01-01

In a previous study, we uncovered the anticonvulsant properties of turmeric oil and its sesquiterpenoids (ar-turmerone, α-, β-turmerone and α-atlantone) in both zebrafish and mouse models of chemically-induced seizures using pentylenetetrazole (PTZ). In this follow-up study, we aimed at evaluating the anticonvulsant activity of ar-turmerone further. A more in-depth anticonvulsant evaluation of ar-turmerone was therefore carried out in the i.v. PTZ and 6-Hz mouse models. The potential toxic effects of ar-turmerone were evaluated using the beam walking test to assess mouse motor function and balance. In addition, determination of the concentration-time profile of ar-turmerone was carried out for a more extended evaluation of its bioavailability in the mouse brain. Ar-turmerone displayed anticonvulsant properties in both acute seizure models in mice and modulated the expression patterns of two seizure-related genes (c-fos and brain-derived neurotrophic factor [bdnf]) in zebrafish. Importantly, no effects on motor function and balance were observed in mice after treatment with ar-turmerone even after administering a dose 500-fold higher than the effective dose in the 6-Hz model. In addition, quantification of its concentration in mouse brains revealed rapid absorption after i.p. administration, capacity to cross the BBB and long-term brain residence. Hence, our results provide additional information on the anticonvulsant properties of ar-turmerone and support further evaluation towards elucidating its mechanism of action, bioavailability, toxicity and potential clinical application.

Moving Target Detection and Active Tracking with a Multicamera Network

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Long Zhao

2014-01-01

Full Text Available We propose a systematic framework for Intelligence Video Surveillance System (IVSS with a multicamera network. The proposed framework consists of low-cost static and PTZ cameras, target detection and tracking algorithms, and a low-cost PTZ camera feedback control algorithm based on target information. The target detection and tracking is realized by fixed cameras using a moving target detection and tracking algorithm; the PTZ camera is manoeuvred to actively track the target from the tracking results of the static camera. The experiments are carried out using practical surveillance system data, and the experimental results show that the systematic framework and algorithms presented in this paper are efficient.

Evaluation of Analgesic, Anticonvulsant and Hypnotic activities of ...

African Journals Online (AJOL)

AqPs (100-400mg/kg i.p.) also demonstrated a protective effect against strychnine-induced convulsion. The extract potentiated the hypnotic effect of hexobarbitone following i.p. injection at the dose levels studied. The results suggested that AqPs possesses potential analgesic, anticonvulsive and hypnotic properties.

CNS Depressant and Antiepileptic Activities of the Methanol Extract of the Leaves of Ipomoea Aquatica Forsk

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Dhanasekaran Sivaraman

2010-01-01

Full Text Available The central nervous system (CNS depressant and antiepileptic activities of the methanol extract of the leaves of Ipomoea aquatica Forsk (IAF were investigated on various animal models including pentobarbitone sleeping time and hole-board exploratory behavior for sedation tests and strychnine, picrotoxin and pentylenetetrazole-induced convulsions in mice. IAF (200 and 400 mg/kg, p.o., like chlorpromazine HCl (1 mg/kg, i.m., produced a dose-dependent prolongation of pentobarbitone sleeping time and suppression of exploratory behavior. IAF (200 and 400 mg/kg produced dose-dependent and significant increases in onset to clonic and tonic convulsions and at 400 mg/kg, showed complete protection against seizures induced by strychnine and picrotoxin but not with pentylenetetrazole. Acute oral toxicity test, up to 14 days, did not produce any visible signs of toxicity. These results suggest that potentially antiepileptic compounds are present in leaf extract of IAF that deserve the study of their identity and mechanism of action.

Clinical features, proximate causes, and consequences of active convulsive epilepsy in Africa.

Science.gov (United States)

Kariuki, Symon M; Matuja, William; Akpalu, Albert; Kakooza-Mwesige, Angelina; Chabi, Martin; Wagner, Ryan G; Connor, Myles; Chengo, Eddie; Ngugi, Anthony K; Odhiambo, Rachael; Bottomley, Christian; White, Steven; Sander, Josemir W; Neville, Brian G R; Newton, Charles R J C; Twine, Rhian; Gómez Olivé, F Xavier; Collinson, Mark; Kahn, Kathleen; Tollman, Stephen; Masanja, Honratio; Mathew, Alexander; Pariyo, George; Peterson, Stefan; Ndyomughenyi, Donald; Bauni, Evasius; Kamuyu, Gathoni; Odera, Victor Mung'ala; Mageto, James O; Ae-Ngibise, Ken; Akpalu, Bright; Agbokey, Francis; Adjei, Patrick; Owusu-Agyei, Seth; Kleinschmidt, Immo; Doku, Victor C K; Odermatt, Peter; Nutman, Thomas; Wilkins, Patricia; Noh, John

2014-01-01

Epilepsy is common in sub-Saharan Africa (SSA), but the clinical features and consequences are poorly characterized. Most studies are hospital-based, and few studies have compared different ecological sites in SSA. We described active convulsive epilepsy (ACE) identified in cross-sectional community-based surveys in SSA, to understand the proximate causes, features, and consequences. We performed a detailed clinical and neurophysiologic description of ACE cases identified from a community survey of 584,586 people using medical history, neurologic examination, and electroencephalography (EEG) data from five sites in Africa: South Africa; Tanzania; Uganda; Kenya; and Ghana. The cases were examined by clinicians to discover risk factors, clinical features, and consequences of epilepsy. We used logistic regression to determine the epilepsy factors associated with medical comorbidities. Half (51%) of the 2,170 people with ACE were children and 69% of seizures began in childhood. Focal features (EEG, seizure types, and neurologic deficits) were present in 58% of ACE cases, and these varied significantly with site. Status epilepticus occurred in 25% of people with ACE. Only 36% received antiepileptic drugs (phenobarbital was the most common drug [95%]), and the proportion varied significantly with the site. Proximate causes of ACE were adverse perinatal events (11%) for onset of seizures before 18 years; and acute encephalopathy (10%) and head injury prior to seizure onset (3%). Important comorbidities were malnutrition (15%), cognitive impairment (23%), and neurologic deficits (15%). The consequences of ACE were burns (16%), head injuries (postseizure) (1%), lack of education (43%), and being unmarried (67%) or unemployed (57%) in adults, all significantly more common than in those without epilepsy. There were significant differences in the comorbidities across sites. Focal features are common in ACE, suggesting identifiable and preventable causes. Malnutrition and

Anticonvulsant Potencies of the Enantiomers of the Neurosteroids Androsterone and Etiocholanolone Exceed those of the Natural Forms

Science.gov (United States)

Zolkowska, Dorota; Dhir, Ashish; Krishnan, Kathiresan; Covey, Douglas F.; Rogawski, Michael A.

2014-01-01

Rationale Androsterone [(3α,5α)-3-hydroxyandrostan-17-one; 5α,3α-A] and its 5β-epimer etiocholanolone [(3α,5β)-3-hydroxyandrostan-17-one; 5β,3α-A)], the major excreted metabolites of testosterone, are neurosteroid positive modulators of GABAA receptors. Such neurosteroids typically show enantioselectivity in which the natural form is more potent than the corresponding unnatural enantiomer. For 5α,3α-A and 5β,3α-A, the unnatural enantiomers are more potent at GABAA receptors than the natural forms. Objectives The aim of this study was to compare the anticonvulsant potencies and time courses of 5α,3α-A and 5β,3α-A with their enantiomers in mouse seizure models. Methods Steroids were administered intraperitoneally to male NIH Swiss mice 15 min (or up to 6 h in time course experiments) prior to administration of an electrical stimulus in the 6-Hz or maximal electroshock (MES) seizure tests or the convulsant pentylenetetrazol (PTZ). Results In the 6-Hz test, the ED50 values of ent-5α,3α-A was 5.0 mg/kg whereas the value for 5α,3α-A was 12.1 mg/kg; the corresponding values in the PTZ seizure test were 22.8 and 51.8 mg/kg. Neurosteroid GABAA receptor positive allosteric modulators are generally weak in the MES test and this was confirmed in the present study. However, the atypical relative potency relationship was maintained with ED50 values of 140 and 223 mg/kg for ent-5α,3α- A and 5α,3α-A, respectively. Similar relationships were obtained for the 5β-isomers, except that the enantioselectivity was accentuated. In the 6-Hz and PTZ tests, the ED50 values of ent-5β,3α-A were 11.8 and 20.4 mg/kg whereas the values for 5β,3α-A were 57.6 and 109.1 mg/kg. Protective activity in the 6-Hz test of ent-5α,3α-A persisted for somewhat longer (~5 h) than for 5α,3α-A (~4 h); protection by ent-5β,3α-A also persisted longer (~3 h) than for 5β,3α-A (~2 h). Conclusions The unnatural enantiomers of 17-keto androgen class neurosteroids have greater in

Development of Toxicity Data for Munition Compounds to Support Toxicity Reference Value Derivations for Wildlife

Science.gov (United States)

2010-06-01

kilogram (cmol kg -1 ), with soil pH 5.9. Compound was then dissolved in high purity acetone, and dispersed into deionized water. The solution was...acute and subacute studies. (2) Rabbits orally dosed at greater than 256 mg/kg experienced clonic convulsion to include salivation roughly 21

March 2010 Final for Publicat...

African Journals Online (AJOL)

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dose of quinine she lapsed in to coma. This necessitated referral to the nearby Federal Medical. Centre for further management. Following a rapid assessment, she had the quinine changed to intravenous rate-controlled infusion. GB began to convulse and had three episodes of generalized tonic clonic seizures with ...

Hydrothermal syntheses and anion-induced structural transformation of three Cadmium phosphonates

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Hu, Han; Zhai, Fupeng; Liu, Xiaofeng; Ling, Yun; Chen, Zhenxia; Zhou, Yaming

2018-05-01

Three cadmium phosphonate coordinated polymers, namely as [Cd5(ptz)3(SO4)2(5H2O)]·6H2O (Cdptz-1), [Cd3(ptz)2(Cl)2(4H2O)]·2H2O (Cdptz-2) and [Cd4(ptz)2(SO4)(Cl)(OH)H2O]·H2O (Cdptz-3) have been hydrothermally synthesized using 4-(1,2,4-triazol-4-yl)phenylphosphonic acid (H2ptz) as ligand. Single crystal X-ray analyses revealed Cdptz-2 as layered structure and Cdptz-1,3 as pillar-layered structures with Cl- or SO42- as bridging anions. Due to the weak bonding between metal and anions, Cdptz-1 and 2 can reversibly convert into each other by simple immersing in the corresponding solution at room temperature. While the transformations between Cdptz-1,2 and Cdptz-3 can only happen under hydrothermal condition. The causes for the transformation involve the metal-ligand bond breaking/formation, replacement of anions and enhancement/decrement of the network dimensionality.

[The role of the opiate mechanisms of the hippocampus and substantia nigra in the behavioral and convulsive disorders in picrotoxin-induced kindling].

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Kryzhanovskiĭ, G N; Shandra, A A; Godlevskiĭ, L S; Mazarati, A M; Nguyen, T T

1991-03-01

It was shown in the experiments on rats that the repeated picrotoxin administration resulted in the kindling of generalized seizures. Generalized convulsions were followed by the development of either postictal depression or explosiveness. The injection of mu-opiate agonist met-enkephalin into hippocampus of kindled rats resulted in the increase in the severity of seizure reactions which were induced by picrotoxin and also in the increase in the number of animals with postictal explosiveness. The injection of dynorphin-A-1-13 (kappa-opiate agonist) into substantia nigra reticulata induced the locomotor depression which was like one in postictal period and resulted in the decrease of picrotoxin-induced seizures severity. It was concluded that mu-opiate system of hippocampus took part in the formation of generator of pathologically enhanced excitation in the structure during kindling and the development of seizure syndrome, providing also the postictal explosiveness. Kappa-opiate system of substantia nigra plays an important role in the activation of the antiepileptic system, limitation of seizures and the development of postictal depression.

Accidental administration of Syntometrine in adult dosage to the newborn.

OpenAIRE

Whitfield, M F; Salfield, S A

1980-01-01

The clinical course is described of an infant who accidentally received an adult dose of Syntometrine (synthetic oxytocin + ergometrine) at delivery. The infant soon became ill with convulsions and ventilatory failure, and later with water intoxication. Similar reported cases are reviewed and recommendations are given for the management of future cases.

Prelimilary experimental study of manganese enhanced-functional MR imaging on cat model about acute epilepsy caused by pentylenetetrazol

International Nuclear Information System (INIS)

Huang Jingbai; Xu Haibo; Kong Xiangquan; Liu Dingxi; Kong Qingxia; Sun Shenggang

2007-01-01

Objective: To explore the activated brain region of acute epilepsy in cat model induced by pentylenetetrazol (PTZ) with manganese enhanced-functional MR imaging (ME-fMRI), and evaluate the application of ME-fMRI on localization of the activated brain. Methods: Forty cats were divided into 4 groups by random number table method as epileptic A and B groups as well as control A and B groups. Cats of epileptic groups were injected with PTZ (55 mg/kg) intramuscularly, and those of control groups were injected with the saline at same dose. The behavior change in the epileptic and control group A was observed and electroencephalogram (EEG) was also undertaken. Cats of epileptic and control group B were performed ME-fMRI, and the percentage of the enhanced signal intensity was then calculated. Results: After injection with PTZ (55 mg/kg) intramuscularly, epileptic seizure was all evoked, and then EEG recording showed spike-wave and polyspike-wave complexes. The neocortex of cats of epileptic group B was diffusely phanero-enhanced on ME-fMRI. The percent enhancement of signal intensity in cortex of frontal lobe, parietal lobe and occipital lobe was (34.6 ± 5.7)% and that in cortex of temporal lobe with (22.9 ± 6.5)%, whereas those of control group B with (14.9 ± 4.5)% and (11.6 ± 3.2)% respectively. And there was significant difference between the above different localization of the brain in the two groups (t= -10.43, -5.46 respectively, P<0.05). There was no significant difference between the two groups in the percentage of the enhancement at the hippocampus, brain ventricle, cerebral white matter, basal nuclei and facial muscles. Conclusion: As an in vivo sensitive method, ME-fMRI can document the brain activation directly, and show great potential ability on the exploration of the brain function. (authors)

Inhibitory Effect of High Dose of the Flavonoid Quercetin on Amygdala Electrical Kindling in Rats

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Tourandokht Baluchnejadmojarad

2010-05-01

Full Text Available A B S T R A C T Introduction: Epilepsy is a chronic neurological disorder in which patients experience spontaneous recurrent seizures. Although the most commonly recommended therapy is drug treatment, some patients do not achieve adequate control of their seizures on existing drugs. New medications with novel mechanisms of action are needed to help those patients whose seizures are resistant to currently-available drugs. Therefore, the anti-convulsant effect of a high dose of quercetin was evaluated in amygdala kindling model in male rats. Methods: Rats were divided into sham-operated group, quercetintreated SH, kindled, and quercetin-treated kindled rats. Quercetin was administered i.p. one day before amygdale kindling for 3 weeks (40 mg/kg/day. The parameters seizure stage, AD duration, the latency to the onset of stage 4, and the duration of stage 5 were analyzed. Results: The results showed that quercetin pretreatment causes a lower seizure intensity in treated kindled rats (p<0.05-0.01, a lower after-discharge duration (p<0.05-0.01, and a higher latency to stage IV (p<0.05 as compared to untreated kindled ones. Discussion: To conclude, chronic administration of quercetin inhibits amygdala electrical kindling and more studies are warranted to clarify its underlying mechanisms.

Novel Hybrid Anticonvulsants Derived from Pyrrolidine-2,5-dione Scaffold with Broad Spectrum of Activity in the Preclinical Studies.

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Kaminski, Krzysztof

2017-01-01

The multifunctional ligands application is an emerging approach in drug delivery, mainly in the treatment of diseases with complex pathology, such as Alzheimer's, cancer, and epilepsy. Using this method many biomolecules with different properties are combined to form a single unit that can provide a complex broad spectrum activity. Thus, a new type of hybrid anticonvulsants based on the pyrrolidine-2,5-dione frame are detailed with the aim of acquiring more effective antiepileptic drugs (AED) that could suppress various human convulsions. These hybrid molecules attach to the chemical particles of clinically relevant AEDs such as ethosuximide, levetiracetam, and lacosamide. As a result of this hybridization process the compounds obtained were effective in three most important animal epilepsy models, namely the maximal electroshock seizure (MES) test, the subcutaneous pentylenetetrazole (scPTZ) test, and the six-Hertz (6 Hz) model in mice. These substances displayed wider spectrum of protection, more potent efficacy, and better safety profile than the aforementioned AEDs. Several compounds were also active in the formalin model of persistent pain in mice. The in vitro ligand binding studies have proved that the most conceivable molecular mechanism of anticonvulsant and antinociceptive action was the influence on the neuronal voltage-sensitive sodium and L-type calcium channels. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Prospective study evaluating the radiosensitizing effect of reduced doses of temozolomide in the treatment of Egyptian patients with glioblastoma multiforme

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Gaber M

2013-10-01

Full Text Available May Gaber, Hanan Selim, Tamer El-NahasDepartment of Clinical Oncology, Cairo University, Cairo, EgyptPurpose: In view of the documented toxicity of continuous daily radiosensitizer doses of temozolomide concomitant with radiation in the treatment of glioblastoma multiforme, we aimed to compare it with a different schedule of abbreviated radiosensitizer dosing.Patients and methods: This was a randomized prospective study comparing toxicity and survival in 60 Egyptian patients with glioblastoma multiforme. Patients in arm I received temozolomide at a dose of 75 mg/m2 daily with radiotherapy for 42 days, starting 4 weeks after surgery and reaching to a total radiation dose of 60 Gy/30 Fractions/6 weeks, while patients in arm II received temozolomide at a dose of 75 mg/m2 concomitantly with the same radiotherapy schedule daily in the first and last weeks of the same radiotherapy program.Results: Common grade 1–2 adverse events were malaise in 28 patients (46.7%, followed by alopecia (40% and nausea (26.7%. Grade 3–4 convulsion and decreased level of consciousness was seen in only four patients who were all from arm I. The median progression-free survival (PFS for the entire study population was 10.6 months (95% confidence interval [CI] 7.3–14, and PFS at 12 months was 32%. The median PFS in arm I was 8.8 months (95% CI 5.9–11.7 and in arm II 11.5 months (95% CI 8.9–14.2, and PFS at 12 months for both arms was 32% and 30% respectively (P=0.571. The median overall survival (OS of the whole group of patients was 14.2 months (95% CI 13–15.5, and OS was 70% at 12 months and 25% at 18 months. The median OS for patients in arm I was 12.3 months (95% CI 7.7–16.9, whereas in arm II it was 14.3 months (95% CI 14–14.7 (P=0.83.Conclusion: Reduced radiosensitizer dosing of temozolomide concomitant with radiotherapy in glioblastoma multiforme exhibited comparable efficacy with a classic continuous daily schedule, though with better tolerability

Journal of Chemical Sciences | Indian Academy of Sciences

Indian Academy of Sciences (India)

In this study the preparation and characterization of a zinc MOF which gives blue luminescence and photocatalytic activity have been described The reaction of 2cyanopyridine, Zn(NO3)2·4H2O and NaN3 yielded a new 3D Zn(II) coordination polymer {(2PTZ)2Zn}n (1), where 2PTZ=5(2pyridyl)tetrazolate via in situ [2+3] ...

Randomized controlled trial of piperacillin-tazobactam, cefepime and ertapenem for the treatment of urinary tract infection caused by extended-spectrum beta-lactamase-producing Escherichia coli.

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Seo, Yu Bin; Lee, Jacob; Kim, Young Keun; Lee, Seung Soon; Lee, Jeong-A; Kim, Hyo Youl; Uh, Young; Kim, Han-Sung; Song, Wonkeun

2017-06-07

Due to limited therapeutic options, the spread of extended-spectrum beta-lactamases (ESBLs) have become a major public health concern. We conducted a prospective, randomized, open-label comparison of the therapeutic efficacy of piperacillin-tazobactam (PTZ), cefepime, and ertapenem in febrile nosocomial urinary tract infection with ESBL-producing Escherichia coli (ESBL-EC). This study was conducted at three university hospitals between January 2013 and August 2015. Hospitalized adult patients presenting with fever were screened for healthcare-associated urinary tract infection (HA-UTI). When ESBL-EC was solely detected and susceptible to a randomized antibiotic in vitro, the case was included in the final analysis. Participants were treated for 10-14 days with PTZ, cefepime, or ertapenem. A total of 66 participants were evenly assigned to the PTZ and ertapenem treatment groups. After the recruitment of six participants, assignment to the cefepime treatment group was stopped because of an unexpectedly high treatment failure rate. The baseline characteristics of these participants did not differ from participants in other treatment groups. The clinical and microbiological response to PTZ treatment was estimated to be 94% and was similar to the response to ertapenem treatment. The efficacy of cefepime was 33.3%. In the cefepime group, age, Charlson comorbidity index, genotype, and minimal inhibitory concentration (MIC) did not significantly affect the success of treatment. Similarly, genotype seemed to be irrelevant with respect to clinical outcome in the PTZ group. Expired cases tended to involve septic shock with a high Charlson comorbidity index and high MIC. Results from this study suggest that PTZ is effective in the treatment of urinary tract infection caused by ESBL-EC when the in vitro test indicates susceptibility. In addition, cefepime should not be used as an alternative treatment for urinary tract infection caused by ESBL-EC. The trial was registered with

Carbapenem therapy is associated with improved survival compared with piperacillin-tazobactam for patients with extended-spectrum β-lactamase bacteremia.

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Tamma, Pranita D; Han, Jennifer H; Rock, Clare; Harris, Anthony D; Lautenbach, Ebbing; Hsu, Alice J; Avdic, Edina; Cosgrove, Sara E

2015-05-01

The effectiveness of piperacillin-tazobactam (PTZ) for the treatment of extended-spectrum β-lactamase (ESBL) bacteremia is controversial. We compared 14-day mortality of PTZ vs carbapenems as empiric therapy in a cohort of patients with ESBL bacteremia who all received definitive therapy with a carbapenem. Patients hospitalized between January 2007 and April 2014 with monomicrobial ESBL bacteremia were included. A decrease of >3 doubling dilutions in the minimum inhibitory concentration for third-generation cephalosporins tested in combination with 4 µg/mL of clavulanic acid was used to confirm ESBL status. The primary exposure was empiric therapy, defined as antibiotic therapy administered to a patient before ESBL status was known. Patients were excluded if they did not receive a carbapenem after ESBL production was identified. The primary outcome was time to death from the first day of bacteremia. Propensity scores using inverse probability of exposure weighting (IPW) were used to estimate the probability that a patient would receive PTZ vs carbapenems empirically. We calculated overall hazard ratios for mortality censored at 14 days using Cox proportional hazards models on an IPW-adjusted cohort. A total of 331 unique patients with ESBL bacteremia were identified. One hundred three (48%) patients received PTZ empirically and 110 (52%) received carbapenems empirically. The adjusted risk of death was 1.92 times higher for patients receiving empiric PTZ compared with empiric carbapenem therapy (95% confidence interval, 1.07-3.45). PTZ appears inferior to carbapenems for the treatment of ESBL bacteremia. For patients at high risk of invasive ESBL infections, early carbapenem therapy should be considered. Our findings should not be extended to β-lactam/β-lactamase inhibitor combinations in development, as limited clinical data are available for these agents. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of

Assessment of Potential Long Term Health Effects on Army Human Test Subjects of Relevant Biological and Chemical Agents, Drugs, Medications and Substances

Science.gov (United States)

2016-02-29

status epilepticus , contributing to profound brain damage. The exposure of experimental ani- mals to tabun in convulsion-inducing doses may result in...Basolateral Amygdala after Soman-Induced Status Epilepticus : Relation to Anxiety-Like Be...to Nerve Agents: From Status Epilepticus to Neuroinflammation, Brain Damage, Neuro- genesis and Epilepsy." Neurotoxicology 33, no. 6 (2012): 1476-1490

Pro- and anticonvulsant actions of morphine and the endogenous opioids: involvement and interactions of multiple opiate and non-opiate systems.

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Frenk, H

1983-10-01

The proconvulsant actions of high doses of systemic morphine are probably mediated by 3 different systems. One of them produces non-convulsant electrographic seizures and can be activated separately from the others both by intracerebroventricular injections as well as microinjections into discrete subcortical areas. The enkephalins and beta-endorphin, when administered to the same loci, produce similar effects. Pharmacological evidence suggests that specific opiate receptors of the delta-subtype mediate the epileptiform effects produced by this system. The second system mediating proconvulsant effects of systemic morphine is not mediated by stereo-specific opiate receptors. It produces behavioral convulsions, and the GABA-ergic system has been implicated in its action. A third proconvulsant action of systemic morphine can be activated separately from the other two systems by administering this compound with other convulsive agents or manipulations. Specific mu-type opiate receptors are implicated in this effect. In addition to potent proconvulsant effects, systemic morphine also has anticonvulsant properties which are mediated by specific opiate mu-receptors. The conditions under which morphine acts as a proconvulsant rather than an anticonvulsant agent are, as yet, not understood.

Dose specification for radiation therapy: dose to water or dose to medium?

International Nuclear Information System (INIS)

Ma, C-M; Li Jinsheng

2011-01-01

The Monte Carlo method enables accurate dose calculation for radiation therapy treatment planning and has been implemented in some commercial treatment planning systems. Unlike conventional dose calculation algorithms that provide patient dose information in terms of dose to water with variable electron density, the Monte Carlo method calculates the energy deposition in different media and expresses dose to a medium. This paper discusses the differences in dose calculated using water with different electron densities and that calculated for different biological media and the clinical issues on dose specification including dose prescription and plan evaluation using dose to water and dose to medium. We will demonstrate that conventional photon dose calculation algorithms compute doses similar to those simulated by Monte Carlo using water with different electron densities, which are close (<4% differences) to doses to media but significantly different (up to 11%) from doses to water converted from doses to media following American Association of Physicists in Medicine (AAPM) Task Group 105 recommendations. Our results suggest that for consistency with previous radiation therapy experience Monte Carlo photon algorithms report dose to medium for radiotherapy dose prescription, treatment plan evaluation and treatment outcome analysis.

Effect of dexmedetomidine on rats with convulsive status epilepticus and association with activation of cholinergic anti-inflammatory pathway.

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Xu, Kai-Liang; Liu, Xin-Qiu; Yao, Yu-Long; Ye, Ming-Rong; Han, Yao-Guo; Zhang, Tao; Chen, Gang; Lei, Ming

2018-01-01

Convulsive status epilepticus (CSE) is a neurological disease with contraction and extension of limbs, leading to damage of hippocampus and cognition. This study aimed to explore the effects of dexmedetomidine (DEX) on the cognitive function and neuroinflammation in CSE rats. All rats were divided into control group, CSE group and DEX group. Morris water maze test was used to measure cognitive function. Acute hippocampal slices were made to detect long-term potentiation (LTP). Immunohistochemistry was used to determine the expression of α7-nicotinic acetylcholine receptor (α7-nAChR) and interleukin-1β (IL-1β). Enzyme-linked immunosorbent assay (ELISA) was used to measure serum levels of IL-1β, tumor necrosis factor-α (TNF-α), S-100β and brain-derived neurotrophic factor (BDNF). Our results showed that DEX improved the memory damage caused by CSE. DEX reduced seizure severity and increased the amplitudes and sustainable time of LTP, and also inhibited the hippocampal expression of α7-nAChR and IL-1β in CSE rats. DEX treatment decreased serum IL-1β, TNF-α and S-100β levels and increased BDNF levels. The effects of DEX on seizure severity and LTP could be simulated by nicotine or attenuated by concurrent α-bungarotoxin (α-BGT) treatment. In conclusions, DEX significantly improved spatial cognitive dysfunction, reduced seizure severity and increased LTP in CSE rats. Improvements by DEX were closely related to enhancement of cholinergic anti-inflammatory pathway. Copyright © 2017 Elsevier Inc. All rights reserved.

The effects of different fractions of Coriandrum sativum on pentylenetetrazole-induced seizures and brain tissues oxidative damage in rats

Directory of Open Access Journals (Sweden)

Akbar Anaeigoudari

2016-03-01

Full Text Available Objective: In the present work, the effects of different fractions of Coriandrum sativum (C. sativum, on pentylenetetrazole (PTZ-induced seizures and brain tissues oxidative damage were investigated in rats. Materials and Methods: The rats were divided into the following groups: (1 vehicle, (2 PTZ (90 mg/kg, (3 water fraction (WF of C. sativum (25 and 100 mg/kg, (4 n-butanol fraction (NBF of C. sativum (25 and 100 mg/kg, and (5 ethyl acetate fraction (EAF of C. sativum (25 and 100 mg/kg. Results: The first generalized tonic-clonic seizures (GTCS latency in groups treated with 100 mg /kg of WF or EAF was significantly higher than that of PTZ group (p< 0.01. In contrast to WF, the EAF and NBF were not effective in increasing the first minimal clonic seizure (MCS latency. Malondialdehyde (MDA levels in both cortical and hippocampal tissues of PTZ group were significantly higher than those of control animals (p< 0.001. Pretreatment with WF, NBF, or EAF resulted in a significant reduction in the MDA levels of hippocampi (pConclusion: The present study showed that different fractions of C. sativum possess antioxidant activity in the brain and WF and EAF of this plant have anticonvulsant effects.

Design and synthesis of bipyridine platinum(II) bisalkynyl fullerene donor-chromophore-acceptor triads with ultrafast charge separation.

Science.gov (United States)

Lee, Sai-Ho; Chan, Chris Tsz-Leung; Wong, Keith Man-Chung; Lam, Wai Han; Kwok, Wai-Ming; Yam, Vivian Wing-Wah

2014-07-16

Donor-chromophore-acceptor triads, (PTZ)2-Pt(bpy)-C60 and ((t)BuPTZ)2-Pt(bpy)-C60, along with their model compound, (Ph)2-Pt(bpy)-C60, have been synthesized and characterized; their photophysical and electrochemical properties have been studied, and the origin of the absorption and emission properties has been supported by computational studies. The photoinduced electron transfer reactions have been investigated using the femtosecond and nanosecond transient absorption spectroscopy. In dichloromethane, (Ph)2-Pt(bpy)-C60 shows ultrafast triplet-triplet energy transfer from the (3)MLCT/LLCT excited state within 4 ps to give the (3)C60* state, while in (PTZ)2-Pt(bpy)-C60 and ((t)BuPTZ)2-Pt(bpy)-C60, charge-separated state forms within 400 fs from the (3)MLCT/LLCT excited state with efficiency of over 0.90, and the total efficiency with the contribution of (3)C60* is estimated to be 0.99. Although the forward electron transfer reactions are very rapid, the charge-separated state recombines to the singlet ground state at a time of hundreds of nanoseconds because of the difference in spin multiplicity between the charge-separated state and the ground state.

Solvent-Induced Change of Electronic Spectra and Magnetic Susceptibility of Co(II) Coordination Polymer with 2,4,6-Tris(4-pyridyl)-1,3,5-triazine.

Science.gov (United States)

Polunin, Ruslan A; Burkovskaya, Nataliya P; Satska, Juliya A; Kolotilov, Sergey V; Kiskin, Mikhail A; Aleksandrov, Grigory G; Cador, Olivier; Ouahab, Lahcène; Eremenko, Igor L; Pavlishchuk, Vitaly V

2015-06-01

One-dimensional coordination polymer [Co(Piv)2(4-ptz)(C2H5OH)2]n (compound 1, Piv(-) = pivalate, 4-ptz = 2,4,6-tris(4-pyridyl)-1,3,5-triazine) was synthesized by interaction of Co(II) pivalate with 4-ptz. Desolvation of 1 led to formation of [Co(Piv)2(4-ptz)]n (compound 2), which adsorbed N2 and H2 at 78 K as a typical microporous sorbent. In contrast, absorption of methanol and ethanol by 2 at 295 K led to structural transformation probably connected with coordination of these alcohols to Co(II). Formation of 2 from 1 was accompanied by change of color of sample from orange to brown and more than 2-fold decrease of molar magnetic susceptibility (χM) in the temperature range from 2 to 300 K. Resolvation of 2 by ethanol or water resulted in restoration of spectral characteristics and χM values almost to the level of that of 1. χMT versus T curves for 1 and samples, obtained by resolvation of 2 by H2O or C2H5OH, were fitted using a model for Co(II) complex with zero-field splitting of this ion.

Tolerance and withdrawal to anticonvulsant action of clonazepam: role of nitric oxide.

Science.gov (United States)

Gupta, N; Bhargava, V K; Pandhi, P

2000-05-01

The use of clonazepam in the long-term treatment of epilepsy is greatly inhibited by its capacity to induce tolerance and dependence. A means of preventing or minimizing the tolerance and dependence inducing properties is required. Here the role of nitric oxide in preventing the development of tolerance and withdrawal hyperexcitability was studied. In Wistar rats, clonazepam at a dose of 0.25 mg/kg i.p. twice daily produced tolerance to its anticonvulsant action in 28 days. After sudden cessation of therapy it produced hyperexcitability. Tolerance was shown by a decrease in seizure threshold to near control value while withdrawal hyperexcitability was evidenced by a significant decrease in seizure threshold below the control value. L-Arginine (a donor of nitric oxide) and N omega-nitro-L-arginine (an inhibitor of nitric oxide synthase) were given in doses of 150 mg/kg and 8 mg/kg, respectively on day 1, 3, 7, 14, 21 and 28 with clonazepam. Withdrawal hyperexcitability was seen on day 1, 2 and 4 after cessation of drug therapy. Electroshock was used as a model of epilepsy and seizure thresholds were determined by an up and down method of Kimball et al. L-Arginine was found to inhibit the development tolerance as well as withdrawal hyperexcitability when administered with clonazepam while N omega-L-arginine did not prevent either the development of tolerance or withdrawal hyperexcitability in the electroshock model. In the PTZ model, however, L-arginine had no effect on the anticonvulsant action and withdrawal hyperexcitability while inhibition of nitric oxide synthesis prevented withdrawal hyperexcitability in PTZ-induced seizures.

Search for new potential anticonvulsants with anxiolytic and antidepressant properties among derivatives of 4,4-diphenylpyrrolidin-2-one.

Science.gov (United States)

Malawska, Katarzyna; Rak, Aleksandra; Gryzło, Beata; Sałat, Kinga; Michałowska, Małgorzata; Żmudzka, Elżbieta; Lodarski, Krzysztof; Malawska, Barbara; Kulig, Katarzyna

2017-02-01

The aim of this study was to synthesize a series of new N-Mannich bases derived from 4,4-diphenylpyrrolidin-2-one having differently substituted 4-phenylpiperazines as potential anticonvulsant agents with additional (beneficial) pharmacological properties. The target compounds 8-12 were prepared in one step from the 4-substituted phenylpiperazines, paraformaldehyde, and synthesized 4,4-diphenylpyrrolodin-2-one (7) by a Mannich-type reaction. The obtained compounds were assessed and tested for their anticonvulsant activity in two screening mouse models of seizures, i.e., the maximal electroshock (MES) test and in the subcutaneous pentylenetetrazole (scPTZ) test. The effect of these compounds on animals' motor coordination was measured in the rotarod test. A selected 4,4-diphenyl-1-((4-phenylpiperazin-1-yl)methyl)pyrrolidin-2-one (8) was evaluated in vivo for its anxiolytic- and antidepressant-like properties. Its impact on animals' locomotor activity was also evaluated. Compound 8 showed protection (25%) in the MES and in the scPTZ tests at the dose of 100mg/kg and was not neurotoxic. In the four-plate test, compound 8 at the dose of 30mg/kg showed a statistically significant (p<0.05) anxiolytic-like activity. In the forced swim test, it reduced the immobility time by 24.3% (significant at p<0.05), which indicates its potential antidepressant-like properties. In the locomotor activity test, compound 8 significantly reduced animals' locomotor activity by 79.9%. The results obtained make a new derivative of 4,4-diphenyl-1-((4-phenylpiperazin-1-yl)methyl)pyrrolidin-2-one (8) a promising lead structure for further development. Copyright © 2016. Published by Elsevier Urban & Partner Sp. z o.o.

The safety of seasonal influenza vaccines in Australian children in 2013.

Science.gov (United States)

Wood, Nicholas J; Blyth, Chris C; Willis, Gabriela A; Richmond, Peter; Gold, Michael S; Buttery, Jim P; Crawford, Nigel; Crampton, Michael; Yin, J Kevin; Chow, Maria Yui Kwan; Macartney, Kristine

2014-11-17

To examine influenza vaccine safety in Australian children aged under 10 years in 2013. Active prospective surveillance study conducted with parents or carers of children who received influenza vaccine in outpatient clinics at six tertiary paediatric hospitals or from selected primary health care providers between 18 March and 19 July 2013. Parental-reported frequency of systemic reactions (fever, headache, nausea, abdominal symptoms, convulsions, rash, rigors and fatigue), injection site reactions (erythema, swelling and/or pain at the injection site), use of antipyretics or analgesics, and medical attendance or advice within 72 hours after vaccination. Of 981 children enrolled in the surveillance, 893 children aged 6 months to children received 1052 influenza vaccine doses. Fever was reported in 5.5% (95% CI, 4.1%-7.3%) and 6.5% (95% CI, 3.5%-10.9%) of children after Doses 1 and 2, respectively. One febrile convulsion occurred in a child with a known seizure disorder. Injection site reactions occurred in 21.2% (95% CI, 18.5%-24.1%) and 6.0% (95% CI, 3.1%-10.2%) after Doses 1 and 2, respectively; most were mild. Very few parents sought medical follow-up for their child's reaction: 22 (2.6%; 95% CI, 1.6%-3.9%) after Dose 1, and 11 (5.5%; 95% CI, 2.8%-9.6%) after Dose 2. These results are consistent with clinical trials and other observational studies of influenza vaccines currently registered for use in young children in Australia and can reassure parents and health care providers that influenza vaccination is safe and well tolerated.

Dose tracking and dose auditing in a comprehensive computed tomography dose-reduction program.

Science.gov (United States)

Duong, Phuong-Anh; Little, Brent P

2014-08-01

Implementation of a comprehensive computed tomography (CT) radiation dose-reduction program is a complex undertaking, requiring an assessment of baseline doses, an understanding of dose-saving techniques, and an ongoing appraisal of results. We describe the role of dose tracking in planning and executing a dose-reduction program and discuss the use of the American College of Radiology CT Dose Index Registry at our institution. We review the basics of dose-related CT scan parameters, the components of the dose report, and the dose-reduction techniques, showing how an understanding of each technique is important in effective auditing of "outlier" doses identified by dose tracking. Copyright © 2014 Elsevier Inc. All rights reserved.

Indomethacin treatment prior to pentylenetetrazole-induced seizures downregulates the expression of il1b and cox2 and decreases seizure-like behavior in zebrafish larvae.

Science.gov (United States)

Barbalho, Patrícia Gonçalves; Lopes-Cendes, Iscia; Maurer-Morelli, Claudia Vianna

2016-03-09

It has been demonstrated that the zebrafish model of pentylenetetrazole (PTZ)-evoked seizures and the well-established rodent models of epilepsy are similar pertaining to behavior, electrographic features, and c-fos expression. Although this zebrafish model is suitable for studying seizures, to date, inflammatory response after seizures has not been investigated using this model. Because a relationship between epilepsy and inflammation has been established, in the present study we investigated the transcript levels of the proinflammatory cytokines interleukin-1 beta (il1b) and cyclooxygenase-2 (cox2a and cox2b) after PTZ-induced seizures in the brain of zebrafish 7 days post fertilization. Furthermore, we exposed the fish to the nonsteroidal anti-inflammatory drug indomethacin prior to PTZ, and we measured its effect on seizure latency, number of seizure behaviors, and mRNA expression of il1b, cox2b, and c-fos. We used quantitative real-time PCR to assess the mRNA expression of il1b, cox2a, cox2b, and c-fos, and visual inspection was used to monitor seizure latency and the number of seizure-like behaviors. We found a short-term upregulation of il1b, and we revealed that cox2b, but not cox2a, was induced after seizures. Indomethacin treatment prior to PTZ-induced seizures downregulated the mRNA expression of il1b, cox2b, and c-fos. Moreover, we observed that in larvae exposed to indomethacin, seizure latency increased and the number of seizure-like behaviors decreased. This is the first study showing that il1b and cox-2 transcripts are upregulated following PTZ-induced seizures in zebrafish. In addition, we demonstrated the anticonvulsant effect of indomethacin based on (1) the inhibition of PTZ-induced c-fos transcription, (2) increase in seizure latency, and (3) decrease in the number of seizure-like behaviors. Furthermore, anti-inflammatory effect of indomethacin is clearly demonstrated by the downregulation of the mRNA expression of il1b and cox2b. Our results

Insights from Zebrafish and Mouse Models on the Activity and Safety of Ar-Turmerone as a Potential Drug Candidate for the Treatment of Epilepsy

OpenAIRE

Orellana-Paucar, Adriana Monserrath; Afrikanova, Tatiana; Thomas, Joice; Aibuldinov, Yelaman K; Dehaen, Wim; de Witte, Peter; Esguerra, Camila

2013-01-01

In a previous study, we uncovered the anticonvulsant properties of turmeric oil and its sesquiterpenoids (ar-turmerone, ?-, ?-turmerone and ?-atlantone) in both zebrafish and mouse models of chemically-induced seizures using pentylenetetrazole (PTZ). In this follow-up study, we aimed at evaluating the anticonvulsant activity of ar-turmerone further. A more in-depth anticonvulsant evaluation of ar-turmerone was therefore carried out in the i.v. PTZ and 6-Hz mouse models. The potential toxic ef...

[Clinical investigation and mutation analysis of a child with citrin deficiency complicated with purpura, convulsive seizures and methioninemia].

Science.gov (United States)

Wen, Peng-qiang; Wang, Guo-bing; Chen, Zhan-ling; Liu, Xiao-hong; Cui, Dong; Shang, Yue; Li, Cheng-rong

2013-12-01

To analyze the clinical features and SLC25A13 gene mutations of a child with citrin deficiency complicated with purpura, convulsive seizures and methioninemia. The patient was subjected to physical examination and routine laboratory tests. Blood amino acids and acylcarnitines, and urine organic acids and galactose were analyzed respectively with tandem mass spectrometry and gas chromatographic mass spectrometry. SLC25A13 gene mutation screening was conducted by high resolution melt (HRM) analysis. The petechiae on the patient's face and platelet count (27×10(9)/L, reference range 100×10(9)/L-300×10(9)/L) supported the diagnosis of immunologic thrombocytopenic purpura (ITP). Laboratory tests found that the patient have abnormal coagulation, cardiac enzyme, liver function and liver enzymes dysfunction. Tandem mass spectrometry also found methionine to be increased (286 μmol/L, reference ranges 8-35 μmol/L). The patient did not manifest any galactosemia, citrullinemia and tyrosinemia. Analysis of SLC25A13 gene mutation found that the patient has carried IVS16ins3kb, in addition with abnormal HRM result for exon 6. Direct sequencing of exon 6 revealed a novel mutation c.495delA. The same mutation was not detected in 100 unrelated healthy controls. Further analysis of her family has confirmed that the c.495delA mutation has derived from her farther, and that the IVS16ins3kb was derived from her mother. The clinical features and metabolic spectrum of citrin deficiency can be variable. The poor prognosis and severity of clinical symptoms of the patient may be attributed to the novel c.495delA mutation.

Svær D-vitamin-mangel hos børn født i Danmark af kvinder med mørk hud

DEFF Research Database (Denmark)

Brok, Jesper; Huusom, Lene; Cortes, Dina

2011-01-01

Rickets due to malnutrition is rare in Denmark. The Danish Board of Health recommend that: pregnant women are treated with a daily dose of vitamin D daily (10 micrograms); emigrants with coloured skin have their vitamin D level assessed during pregnancy; all children receive a daily dose of vitamin...... D (10 micrograms) until two years old. Despite of these recommendations two cases of severe nutritional rickets among children of emigrants were discovered upon hospital admission. The symptoms were heterogeneous: delayed walking skills and convulsions. We conclude that nutritional rickets...

Modulating effect of cerulein on benzodlazepine receptors

International Nuclear Information System (INIS)

Vasar, E.E.; Marmets, M.O.; Nurk, A.M.; Rego, L.K.; Soosar, A.H.

1986-01-01

This paper studies the role of benzodiazepine receptors in the anticonvulsant action of cerulein. Parallel with the study of the behavioral reactions, the effect of cerulein binding of tritium-flunitrazepam was investtigated in vitro and in vivo. It was shown that preliminary subcutaneous injection of relatively high doses of cerulein (over 100 micro/kg) delayed the development of picrotoxin seizures; the latent period of clonic and tonic convulsions and the survival of the mice were lengthened. In doses inhibiting picrotoxen seizures, cerulein significantly inhibited binding of tritium-flunitrazepam in vitro

Transcriptomic analysis in a Drosophila model identifies previously implicated and novel pathways in the therapeutic mechanism in neuropsychiatric disorders

Directory of Open Access Journals (Sweden)

Priyanka eSingh

2011-03-01

Full Text Available We have taken advantage of a newly described Drosophila model to gain insights into the potential mechanism of antiepileptic drugs (AEDs, a group of drugs that are widely used in the treatment of several neurological and psychiatric conditions besides epilepsy. In the recently described Drosophila model that is inspired by pentylenetetrazole (PTZ induced kindling epileptogenesis in rodents, chronic PTZ treatment for seven days causes a decreased climbing speed and an altered CNS transcriptome, with the latter mimicking gene expression alterations reported in epileptogenesis. In the model, an increased climbing speed is further observed seven days after withdrawal from chronic PTZ. We used this post-PTZ withdrawal regime to identify potential AED mechanism. In this regime, treatment with each of the five AEDs tested, namely, ethosuximide (ETH, gabapentin (GBP, vigabatrin (VGB, sodium valproate (NaVP and levetiracetam (LEV, resulted in rescuing of the altered climbing behavior. The AEDs also normalized PTZ withdrawal induced transcriptomic perturbation in fly heads; whereas AED untreated flies showed a large number of up- and down-regulated genes which were enriched in several processes including gene expression and cell communication, the AED treated flies showed differential expression of only a small number of genes that did not enrich gene expression and cell communication processes. Gene expression and cell communication related upregulated genes in AED untreated flies overrepresented several pathways - spliceosome, RNA degradation, and ribosome in the former category, and inositol phosphate metabolism, phosphatidylinositol signaling, endocytosis and hedgehog signaling in the latter. Transcriptome remodeling effect of AEDs was overall confirmed by microarray clustering that clearly separated the profiles of AED treated and untreated flies. Besides being consistent with previously implicated pathways, our results provide evidence for a role of

A BARBITURATE ANTIDOTE—Use of Methylethylglutarimide in Barbiturate Intoxication and in Terminating Barbiturate Anesthesia

Science.gov (United States)

Marmer, Milton J.

1959-01-01

Methylethylglutarimide was administered to 488 patients ranging in age from 7 to 89 years, in a study on sleep-reversal after harbiturate anesthesia. Sodium surital or sodium pentothal were the barbiturates used. The drug was administered intravenously in doses varying from 25 to 200 mg. Dosage below 25 mg. was found to be ineffective. Almost all patients showed signs of awakening as evidenced by the return of corneal and conjunctival reflexes, the opening of the eyes, and stirring or moving about. Many responded to questioning. Almost all showed evidence of greater responsiveness within five minutes. No untoward reactions were noted. No convulsions were produced. Five patients ranging in age from 24 to 70 years were treated for barbiturate poisoning with Mikedimide® given intravenously in doses varying from 550 mg. to 1950 mg. All recovered consciousness within 30 minutes to an hour. No convulsions were produced. While it is not known whether Mikedimide is a direct barbiturate antagonist, or whether it is an analeptic, it appears to be a useful drug in reversing the respiratory depression and the cerebral depression produced by harbiturate intoxication and barbiturate anesthesia. PMID:14421358

Evaluation of antiepileptic activity of the methanol extract of Trachyspermum ammi (L.

Directory of Open Access Journals (Sweden)

Rajput Muhammad Ali

2013-01-01

Full Text Available This study aims to investigate the effect of a methanol extract of Trachyspermum ammi (L. as an antiepileptic agent. Tests were conducted with a single- and multiple-dosing schedule of Trachyspermum ammi (L., using a strychnine-induced seizure model for epilepsy. Twenty-one animals were divided into three groups; control (vehicle, standard (diazepam and test (Trachyspermum ammi (L. extract. Trachyspermum ammi (L. demonstrated antiepileptic effects, since there was a highly significant delay in the onset of convulsions as compared to the control, whereas the percentage of animals that survived or ignored seizure was also greater compared to the control. However, the duration of convulsions was significantly increased with both Trachyspermum ammi (L. and diazepam as compared to the control. The methanol extract of Trachyspermum ammi (L. showed antiepileptic activity, which may be due to the presence of thymol.

Dose rate constants for new dose quantities

International Nuclear Information System (INIS)

Tschurlovits, M.; Daverda, G.; Leitner, A.

1992-01-01

Conceptual changes and new quantities made is necessary to reassess dose rate quantities. Calculations of the dose rate constant were done for air kerma, ambient dose equivalent and directional dose equivalent. The number of radionuclides is more than 200. The threshold energy is selected as 20 keV for the dose equivalent constants. The dose rate constant for the photon equivalent dose as used mainly in German speaking countries as a temporary quantity is also included. (Author)

A Validated HPLC-DAD Method for Simultaneous Determination of Etodolac and Pantoprazole in Rat Plasma

Directory of Open Access Journals (Sweden)

Ali S. Abdelhameed

2014-01-01

Full Text Available A simple, sensitive, and accurate HPLC-DAD method has been developed and validated for the simultaneous determination of pantoprazole and etodolac in rat plasma as a tool for therapeutic drug monitoring. Optimal chromatographic separation of the analytes was achieved on a Waters Symmetry C18 column using a mobile phase that consisted of phosphate buffer pH~4.0 as eluent A and acetonitrile as eluent B in a ratio of A : B, 55 : 45 v/v for 6 min, pumped isocratically at a flow rate of 0.8 mL min−1. The eluted analytes were monitored using photodiode array detector set to quantify samples at 254 nm. The method was linear with r2=0.9999 for PTZ and r2=0.9995 for ETD at a concentration range of 0.1–15 and 5–50 μgmL−1 for PTZ and ETD, respectively. The limits of detection were found to be 0.033 and 0.918 μgmL−1 for PTZ and ETD, respectively. The method was statistically validated for linearity, accuracy, precision, and selectivity following the International Conference for Harmonization (ICH guidelines. The reproducibility of the method was reliable with the intra- and interday precision (% RSD <7.76% for PTZ and <7.58 % for ETD.

Geological Structures Appearances and Its Relation to Mechanism of Arc-Continent Collision Northen Alor-Wetar Islands

Directory of Open Access Journals (Sweden)

Subarsyah Subarsyah

2017-02-01

Full Text Available Study area is located in South Banda Basin near the triple junction between Eurasian, Pacific and Indo-Australian Plates. This area is part of back-arc thrusting zone that evolved to compensate convergence between Australia Continent and Banda Arc. Based on seismic section in this area, geological structure analysis is characterized into three distinctive zones. There are Thrust Zone (TZ, Proto Thrust Zone (PTZ and Normal Fault Zone (NFZ. TZ is defined by distribution of numerous of thrust fault, PTZ contains a blind zone or folds instead of thrust fault, and NFZ defined by distribution of numerous normal fault in the upper portion of seismic section. PTZ identified at several seismic section along the bending zone of oceanic crust. The appearances of bending zone will be easily understood by comprehend the driving mechanism of Australia Continent to the Northeast. The bending zone also related to geometry and tectonic stress of collision. Based on this mechanism it was clearly understood why the western end of study area was not identified the bending zone but it probably the initial process of bending. Contradictive to the western end, the eastern part was clearly shown the bending zone that assumed to have the biggest tectonic stress at this moment. Map of structural analysis also explain that PTZ getting narrow towards the west as the indicator of less of tectonic stress.

Effect of combined treatment with diuretics and gabapentin on convulsive threshold in mice.

Science.gov (United States)

Łukawski, Krzysztof; Swiderska, Grajyna; Czuczwar, Stanisław J

2013-01-01

Research data show that diuretics can have anticonvulsant properties. This study examined effects of ethacrynic acid, a loop diuretic, and hydrochlorothiazide, a thiazide-type diuretic, on the anticonvulsant activity of gabapentin, a newer antiepileptic drug, in the maximal electroshock seizure threshold test in mice. Diuretics were administered intraperitoneally (ip.) both acutely (single dose) and chronically (once daily for seven days). Electroconvulsions were produced by an alternating current (50 Hz, 500 V, 0.2 s stimulus duration) delivered via ear-clip electrodes by a generator. Additionally, the influence of combined treatment with the diuretics and gabapentin on motor performance in the chimney test has been assessed. In the current study, ethacrynic acid at the chronic dose of 12.5 mg/kg and the single dose of 100 mg/kg did not affect the anticonvulsant activity of gabapentin. Similarly, hydrochlorothiazide (100 mg/kg), both in acute and chronic experiments, had no effect on the gabapentin action. On the other hand, in the chimney test, the combined treatment with ethacrynic acid (100 mg/kg) and gabapentin (50 mg/kg) significantly impaired motor performance in mice. Based on the current preclinical findings, it can be suggested that the diuretics should not affect the anticonvulsant action of gabapentin in epileptic patients. However, the combination of ethacrynic acid with gabapentin may cause neurotoxicity.

[Evaluation of Organ Dose Estimation from Indices of CT Dose Using Dose Index Registry].

Science.gov (United States)

Iriuchijima, Akiko; Fukushima, Yasuhiro; Ogura, Akio

Direct measurement of each patient organ dose from computed tomography (CT) is not possible. Most methods to estimate patient organ dose is using Monte Carlo simulation with dedicated software. However, dedicated software is too expensive for small scale hospitals. Not every hospital can estimate organ dose with dedicated software. The purpose of this study was to evaluate the simple method of organ dose estimation using some common indices of CT dose. The Monte Carlo simulation software Radimetrics (Bayer) was used for calculating organ dose and analysis relationship between indices of CT dose and organ dose. Multidetector CT scanners were compared with those from two manufactures (LightSpeed VCT, GE Healthcare; SOMATOM Definition Flash, Siemens Healthcare). Using stored patient data from Radimetrics, the relationships between indices of CT dose and organ dose were indicated as each formula for estimating organ dose. The accuracy of estimation method of organ dose was compared with the results of Monte Carlo simulation using the Bland-Altman plots. In the results, SSDE was the feasible index for estimation organ dose in almost organs because it reflected each patient size. The differences of organ dose between estimation and simulation were within 23%. In conclusion, our estimation method of organ dose using indices of CT dose is convenient for clinical with accuracy.

Comparative systemic toxicity of ropivacaine and bupivacaine in nonpregnant and pregnant ewes.

Science.gov (United States)

Santos, A C; Arthur, G R; Wlody, D; De Armas, P; Morishima, H O; Finster, M

1995-03-01

Ropivacaine is a new amide local anesthetic, having therapeutic properties similar to those of bupivacaine but with a wider margin of safety. Bupivacaine is probably the most commonly used drug in obstetric epidural analgesia, even though laboratory studies have suggested that pregnancy increases the cardiotoxicity of bupivacaine but not of other local anesthetics. The current study was designed to reevaluate, in a random and blinded fashion, the systemic toxicity of bupivacaine and ropivacaine in nonpregnant and pregnant sheep. Chronically prepared nonpregnant and pregnant ewes were randomized to receive an intravenous infusion of ropivacaine or bupivacaine at a constant rate of 0.5 mg.kg-1.min-1 until circulatory collapse. The investigators were blinded to the identity of local anesthetic. Heart rate, arterial blood pressure, and cardiac rhythm were monitored throughout the study. Arterial blood samples were obtained before infusion and at the onset of toxic manifestations, which appeared in the following sequence: convulsions, hypotension, apnea, and circulatory collapse. Serum drug concentrations and protein binding were determined. Blood pH and gas tensions were measured. There were no significant differences between non-pregnant and pregnant animals in the doses or serum concentrations of either drug required to elicit toxic manifestations. In nonpregnant animals, similar doses and serum concentrations of ropivacaine and bupivacaine were associated with the onset of convulsions and circulatory collapse. In pregnant ewes, greater doses of ropivacaine as compared to bupivacaine were required to produce convulsions (7.5 +/- 0.5 vs. 5.0 +/- 0.6 mg.kg-1) and circulatory collapse (12.9 +/- 0.8 vs. 8.5 +/- 1.2 mg.kg-1). The corresponding serum concentrations of ropivacaine were similar to those of bupivacaine. Pregnancy did not affect the serum protein binding of either drug. The proportion of animals manifesting a malignant ventricular arrhythmia as the terminal

Responsiveness of cerebral and hepatic cytochrome P450s in rat offspring prenatally exposed to lindane

International Nuclear Information System (INIS)

Johri, Ashu; Yadav, Sanjay; Dhawan, Alok; Parmar, Devendra

2008-01-01

ABSTRACT: Prenatal exposure to low doses of lindane has been shown to affect the ontogeny of xenobiotic metabolizing cytochrome P450s (CYPs), involved in the metabolism and neurobehavioral toxicity of lindane. Attempts were made in the present study to investigate the responsiveness of CYPs in offspring prenatally exposed to lindane (0.25 mg/kg b. wt.; 1/350th of LD 50 ; p. o. to mother) when challenged with 3-methylcholanthrene (MC) or phenobarbital (PB), inducers of CYP1A and 2B families or a sub-convulsant dose of lindane (30 mg/kg b. wt., p. o.) later in life. Prenatal exposure to lindane was found to produce an increase in the mRNA and protein expression of CYP1A1, 1A2, 2B1, 2B2 isoforms in brain and liver of the offspring at postnatal day 50. The increased expression of the CYPs in the offspring suggests the sensitivity of the CYPs during postnatal development, possibly, to low levels of lindane, which may partition into mother's milk. A higher increase in expression of CYP1A and 2B isoenzymes and their catalytic activity was observed in animals pretreated prenatally with lindane and challenged with MC (30 mg/kg, i. p. x 5 days) or PB (80 mg/kg, i. p. x 5 days) when young at age (approx. 7 weeks) compared to animals exposed to MC or PB alone. Further, challenge of the control and prenatally exposed offspring with a single sub-convulsant dose of lindane resulted in an earlier onset and increased incidence of convulsions in the offspring prenatally exposed to lindane have demonstrated sensitivity of the CYPs in the prenatally exposed offspring. Our data assume significance as the subtle changes in the expression profiles of hepatic and cerebral CYPs in rat offspring during postnatal development could modify the adult response to a later exposure to xenobiotics

Dose sculpting with generalized equivalent uniform dose

International Nuclear Information System (INIS)

Wu Qiuwen; Djajaputra, David; Liu, Helen H.; Dong Lei; Mohan, Radhe; Wu, Yan

2005-01-01

With intensity-modulated radiotherapy (IMRT), a variety of user-defined dose distribution can be produced using inverse planning. The generalized equivalent uniform dose (gEUD) has been used in IMRT optimization as an alternative objective function to the conventional dose-volume-based criteria. The purpose of this study was to investigate the effectiveness of gEUD optimization to fine tune the dose distributions of IMRT plans. We analyzed the effect of gEUD-based optimization parameters on plan quality. The objective was to determine whether dose distribution to selected structures could be improved using gEUD optimization without adversely altering the doses delivered to other structures, as in sculpting. We hypothesized that by carefully defining gEUD parameters (EUD 0 and n) based on the current dose distributions, the optimization system could be instructed to search for alternative solutions in the neighborhood, and we could maintain the dose distributions for structures already satisfactory and improve dose for structures that need enhancement. We started with an already acceptable IMRT plan optimized with any objective function. The dose distribution was analyzed first. For structures that dose should not be changed, a higher value of n was used and EUD 0 was set slightly higher/lower than the EUD value at the current dose distribution for critical structures/targets. For structures that needed improvement in dose, a higher to medium value of n was used, and EUD 0 was set to the EUD value or slightly lower/higher for the critical structure/target at the current dose distribution. We evaluated this method in one clinical case each of head and neck, lung and prostate cancer. Dose volume histograms, isodose distributions, and relevant tolerance doses for critical structures were used for the assessment. We found that by adjusting gEUD optimization parameters, the dose distribution could be improved with only a few iterations. A larger value of n could lead to

From personnel dose to personal dose

International Nuclear Information System (INIS)

Hoefert, M.; Raffnsoe, R.C.; Tuyn, J.W.N.; Wittekind, D.

1985-01-01

From following the development of personnel doses at CERN over the past six years it has become evident that work in areas of induced radioactivity is the principal cause of exposure. The results of photon dose measurements free-in-air and around a phantom are presented and discussed in the light of new quantities in individual monitoring. The importance of these results, with respect to the practical situation, is discussed and the problem of phantom size is mentioned. Finally, the results of dose measurements in the phantom are presented, since such information is important in cases where it becomes necessary to transform personnel doses into personal doses. (author)

Effects of proton radiation dose, dose rate and dose fractionation on hematopoietic cells in mice

International Nuclear Information System (INIS)

Ware, J.H.; Rusek, A.; Sanzari, J.; Avery, S.; Sayers, C.; Krigsfeld, G.; Nuth, M.; Wan, X.S.; Kennedy, A.R.

2010-01-01

The present study evaluated the acute effects of radiation dose, dose rate and fractionation as well as the energy of protons in hematopoietic cells of irradiated mice. The mice were irradiated with a single dose of 51.24 MeV protons at a dose of 2 Gy and a dose rate of 0.05-0.07 Gy/min or 1 GeV protons at doses of 0.1, 0.2, 0.5, 1, 1.5 and 2 Gy delivered in a single dose at dose rates of 0.05 or 0.5 Gy/min or in five daily dose fractions at a dose rate of 0.05 Gy/min. Sham-irradiated animals were used as controls. The results demonstrate a dose-dependent loss of white blood cells (WBCs) and lymphocytes by up to 61% and 72%, respectively, in mice irradiated with protons at doses up to 2 Gy. The results also demonstrate that the dose rate, fractionation pattern and energy of the proton radiation did not have significant effects on WBC and lymphocyte counts in the irradiated animals. These results suggest that the acute effects of proton radiation on WBC and lymphocyte counts are determined mainly by the radiation dose, with very little contribution from the dose rate (over the range of dose rates evaluated), fractionation and energy of the protons.

Effects of proton radiation dose, dose rate and dose fractionation on hematopoietic cells in mice.

Science.gov (United States)

Ware, J H; Sanzari, J; Avery, S; Sayers, C; Krigsfeld, G; Nuth, M; Wan, X S; Rusek, A; Kennedy, A R

2010-09-01

The present study evaluated the acute effects of radiation dose, dose rate and fractionation as well as the energy of protons in hematopoietic cells of irradiated mice. The mice were irradiated with a single dose of 51.24 MeV protons at a dose of 2 Gy and a dose rate of 0.05-0.07 Gy/min or 1 GeV protons at doses of 0.1, 0.2, 0.5, 1, 1.5 and 2 Gy delivered in a single dose at dose rates of 0.05 or 0.5 Gy/min or in five daily dose fractions at a dose rate of 0.05 Gy/min. Sham-irradiated animals were used as controls. The results demonstrate a dose-dependent loss of white blood cells (WBCs) and lymphocytes by up to 61% and 72%, respectively, in mice irradiated with protons at doses up to 2 Gy. The results also demonstrate that the dose rate, fractionation pattern and energy of the proton radiation did not have significant effects on WBC and lymphocyte counts in the irradiated animals. These results suggest that the acute effects of proton radiation on WBC and lymphocyte counts are determined mainly by the radiation dose, with very little contribution from the dose rate (over the range of dose rates evaluated), fractionation and energy of the protons.

Modulation of seizure activity in mice by metabotropic glutamate receptor ligands

DEFF Research Database (Denmark)

Dalby, Nils Ole; Thomsen, C

1996-01-01

The anticonvulsant properties of ligands at metabotropic glutamate receptors (mGluRs) were examined in different seizure models by use of intracerebroventricular infusion. The mGluR1a antagonist/mGluR2 agonist, (S)-4-carboxy-3-hydroxyphenylglycine [(S)-4C3HPG] dose-dependently antagonized...... pentylenetetrazol- and methyl-6,7-dimethoxy-4-ethyl-beta-carboline-2-carboxylate (DMCM)-induced clonic convulsions in mice with ED50 values of 400 and 180 nmol/mice, respectively. A modest increase in electrical seizure threshold was observed in mice injected with (S)-4C3HPG. No effect on seizures induced...... by systemic administration of N-methyl-D-aspartate was observed by prior intracerebroventricular infusion of (S)-4C3HPG. The more selective (but less potent) mGluR1a antagonist, (S)-4-carboxyphenylglycine, was a weak anticonvulsant in similar seizure models with the exception of convulsions induced...

Effects of transcranial focal electrical stimulation via tripolar concentric ring electrodes on pentylenetetrazole-induced seizures in rats.

Science.gov (United States)

Besio, W G; Makeyev, O; Medvedev, A; Gale, K

2013-07-01

To study the effects of noninvasive transcranial focal electrical stimulation (TFS) via tripolar concentric ring electrodes (TCRE) on the electrographic and behavioral activity from pentylenetetrazole (PTZ)-induced seizures in rats. The TCREs were attached to the rat scalp. PTZ was administered and, after the first myoclonic jerk was observed, TFS was applied to the TFS treated group. The electroencephalogram (EEG) and behavioral activity were recorded and studied. In the case of the TFS treated group, after TFS, there was a significant (p=0.001) decrease in power compared to the control group in delta, theta, and alpha frequency bands. The number of myoclonic jerks was significantly different (p=0.002) with median of 22 and 4.5 for the control group and the TFS treated groups, respectively. The duration of myoclonic activity was also significantly different (p=0.031) with median of 17.56 min for the control group versus 8.63 min for the TFS treated group. At the same time there was no significant difference in seizure onset latency and maximal behavioral seizure activity score between control and TFS treated groups. TFS via TCREs interrupted PTZ-induced seizures and electrographic activity was reduced toward the "baseline." The significantly reduced electrographic power, number of myoclonic jerks, and duration of myoclonic activity of PTZ-induced seizures suggests that TFS may have an anticonvulsant effect. Copyright © 2012 Elsevier B.V. All rights reserved.

Increased seizure susceptibility and other toxicity symptoms following acute sulforaphane treatment in mice

International Nuclear Information System (INIS)

Socała, Katarzyna; Nieoczym, Dorota; Kowalczuk-Vasilev, Edyta; Wyska, Elżbieta; Wlaź, Piotr

2017-01-01

Activation of Nrf2 with sulforaphane has recently gained attention as a new therapeutic approach in the treatment of many diseases, including epilepsy. As a plant-derived compound, sulforaphane is considered to be safe and well-tolerated. It is widely consumed, also by patients suffering from seizure and taking antiepileptic drugs, but no toxicity profile of sulforaphane exists. Since many natural remedies and dietary supplements may increase seizure risk and potentially interact with antiepileptic drugs, the aim of our study was to investigate the acute effects of sulforaphane on seizure thresholds and activity of some first- and second-generation antiepileptic drugs in mice. In addition, some preliminary toxicity profile of sulforaphane in mice after intraperitoneal injection was evaluated. The LD 50 value of sulforaphane in mice was estimated at 212.67 mg/kg, while the TD 50 value – at 191.58 mg/kg. In seizure tests, sulforaphane at the highest dose tested (200 mg/kg) significantly decreased the thresholds for the onset of the first myoclonic twitch and generalized clonic seizure in the iv PTZ test as well as the threshold for the 6 Hz-induced psychomotor seizure. At doses of 10–200 mg/kg, sulforaphane did not affect the threshold for the iv PTZ-induced forelimb tonus or the threshold for maximal electroshock-induced hindlimb tonus. Interestingly, sulforaphane (at 100 mg/kg) potentiated the anticonvulsant efficacy of carbamazepine in the maximal electroshock seizure test. This interaction could have been pharmacokinetic in nature, as sulforaphane increased concentrations of carbamazepine in both serum and brain tissue. The toxicity study showed that high doses of sulforaphane produced marked sedation (at 150–300 mg/kg), hypothermia (at 150–300 mg/kg), impairment of motor coordination (at 200–300 mg/kg), decrease in skeletal muscle strength (at 250–300 mg/kg), and deaths (at 200–300 mg/kg). Moreover, blood analysis showed leucopenia in mice injected

Anticonvulsive evaluation of THIP in the murine pentylenetetrazole kindling model

DEFF Research Database (Denmark)

Simonsen, Charlotte; Boddum, Kim; von Schoubye, Nadia L

2017-01-01

. Evaluation of THIP as a potential anticonvulsant has given contradictory results in different animal models and for this reason, we reevaluated the anticonvulsive properties of THIP in the murine pentylenetetrazole (PTZ) kindling model. As loss of δ-GABAA R in the dentate gyrus has been associated...... the observed upregulation of δ-GABAA Rs. Even in the demonstrated presence of functional δ-GABAA Rs, THIP (0.5-4 mg/kg) showed no anticonvulsive effect in the PTZ kindling model using a comprehensive in vivo evaluation of the anticonvulsive properties....

Shenfu injection reduces toxicity of bupivacaine in rats

Institute of Scientific and Technical Information of China (English)

王强; 刘艳红; 雷毅; 杨静; 陈绍洋; 陈敏; 熊利泽

2003-01-01

Objective To investigate the effects of injecting Shenfu, an extract of traditional Chinese herbal medicines, on the central nervous system (CNS) and the cardiac toxicity of bupivacaine in rats. Methods Sixteen male Sprague-Dawley rats, weighing form 280 to 320 g, were randomly assigned to two groups (n=8 in each group). Animals in the control group received a saline injection 10 ml/kg while animals in the Shenfu group received an injection of Shenfu 10 ml/kg intraperitoneally 30 minutes before intravenous infusion of bupivacaine. Lead Ⅱ of an electrocardiogram (EEG) was continuously monitored after 3 needles were inserted into the skin of both forelimbs and the left hind-leg of each rat. The femoral artery was cannulated for measurement of arterial blood pressure and blood sampling. The femoral vein was cannulated for the infusion of bupivacaine. After baseline measurement (arterial blood pressure, heart rate and arterial blood gas), 0.5% bupivacaine was infused intravenously at a rate of 2 mg*kg-1*min-1 to all animals until asystole occurred. The time of bupivacaine-induced convulsions, arrhythmia and asystole were determined. The dose of bupivacaine was then calculated at the corresponding time point. Results The doses of bupivacaine that induced convulsions, arrhythmia and cardiac arrest were remarkably larger in Shenfu injection-treated animals than in saline-treated rats ［convulsions, (10.5±1.9) mg/kg vs (7.2±1.5) mg/kg; arrhythmia (10.5±2.0) mg/kg vs (7.2±1.9) mg/kg; asystole, (32.8±8.5) mg/kg vs (25.0±5.0) mg/kg; P=0.006, 0.009 and 0.044, respectively］. Conclusion The Shenfu injection is able to reduce the toxicity of bupiralaine to CNS and cardiac system in rats.

Detection of transgenerational spermatogenic inheritance of adult male acquired CNS gene expression characteristics using a Drosophila systems model.

Directory of Open Access Journals (Sweden)

Abhay Sharma

Full Text Available Available instances of inheritance of epigenetic transgenerational phenotype are limited to environmental exposures during embryonic and adult gonadal development. Adult exposures can also affect gametogenesis and thereby potentially result in reprogramming of the germline. Although examples of epigenetic effects on gametogenesis exist, it is notable that transgenerational inheritance of environment-induced adult phenotype has not yet been reported. Epigenetic codes are considered to be critical in neural plasticity. A Drosophila systems model of pentylenetetrazole (PTZ induced long-term brain plasticity has recently been described. In this model, chronic PTZ treatment of adult males causes alterations in CNS transcriptome. Here, we describe our search for transgenerational spermatogenic inheritance of PTZ induced gene expression phenotype acquired by adult Drosophila males. We generated CNS transcriptomic profiles of F(1 adults after treating F(0 adult males with PTZ and of F(2 adults resulting from a cross between F(1 males and normal females. Surprisingly, microarray clustering showed F(1 male profile as closest to F(1 female and F(0 male profile closest to F(2 male. Differentially expressed genes in F(1 males, F(1 females and F(2 males showed significant overlap with those caused by PTZ. Interestingly, microarray evidence also led to the identification of upregulated rRNA in F(2 males. Next, we generated microarray expression profiles of adult testis from F(0 and F(1 males. Further surprising, clustering of CNS and testis profiles and matching of differentially expressed genes in them provided evidence of a spermatogenic mechanism in the transgenerational effect observed. To our knowledge, we report for the first time detection of transgenerational spermatogenic inheritance of adult acquired somatic gene expression characteristic. The Drosophila systems model offers an excellent opportunity to understand the epigenetic mechanisms underlying

Detection of transgenerational spermatogenic inheritance of adult male acquired CNS gene expression characteristics using a Drosophila systems model.

Science.gov (United States)

Sharma, Abhay; Singh, Priyanka

2009-06-02

Available instances of inheritance of epigenetic transgenerational phenotype are limited to environmental exposures during embryonic and adult gonadal development. Adult exposures can also affect gametogenesis and thereby potentially result in reprogramming of the germline. Although examples of epigenetic effects on gametogenesis exist, it is notable that transgenerational inheritance of environment-induced adult phenotype has not yet been reported. Epigenetic codes are considered to be critical in neural plasticity. A Drosophila systems model of pentylenetetrazole (PTZ) induced long-term brain plasticity has recently been described. In this model, chronic PTZ treatment of adult males causes alterations in CNS transcriptome. Here, we describe our search for transgenerational spermatogenic inheritance of PTZ induced gene expression phenotype acquired by adult Drosophila males. We generated CNS transcriptomic profiles of F(1) adults after treating F(0) adult males with PTZ and of F(2) adults resulting from a cross between F(1) males and normal females. Surprisingly, microarray clustering showed F(1) male profile as closest to F(1) female and F(0) male profile closest to F(2) male. Differentially expressed genes in F(1) males, F(1) females and F(2) males showed significant overlap with those caused by PTZ. Interestingly, microarray evidence also led to the identification of upregulated rRNA in F(2) males. Next, we generated microarray expression profiles of adult testis from F(0) and F(1) males. Further surprising, clustering of CNS and testis profiles and matching of differentially expressed genes in them provided evidence of a spermatogenic mechanism in the transgenerational effect observed. To our knowledge, we report for the first time detection of transgenerational spermatogenic inheritance of adult acquired somatic gene expression characteristic. The Drosophila systems model offers an excellent opportunity to understand the epigenetic mechanisms underlying the

Evaluation of Anticonvulsant, Sedative, Anxiolytic, and Phytochemical Profile of the Methanol Extract from the Aerial Parts of Swertia corymbosa (Griseb. Wight ex C.B. Clarke

Directory of Open Access Journals (Sweden)

G. Mahendran

2014-01-01

Full Text Available The objective of the present study was to evaluate the anxiolytic, antidepressant, and anticonvulsant activity of the methanolic extract of Swertia corymbosa (SCMeOH. After acute toxicity test, oral treatment with SCMeOH at doses of 125, 250, and 500 mg/kg behavioral models of open field, elevated-plus-maze, actophotometer, rotarod, pentylenetetrazole, isoniazid, and maximal electroshock induced seizure models were utilized. In open field test, SCMeOH (125, 250, and 500 mg/kg (P<0.01, P<0.001 increased the number of rearings. However, the number of central motor and ambulation (P<0.01, P<0.001 were reduced. Likewise, the number of entries and the time spent in open arm were increased while the number of locomotion was decreased (P<0.001 in elevated-plus-maze and actophotometer test, respectively. SCMeOH (125–500 mg/kg protected the mice against the pentylenetetrazole and isoniazid induced convulsions; it causes significant (P<0.01 and P<0.001 dose dependent increase in latency of convulsion. Treatment with SCMeOH reduced the duration of the tonic hind limb extension induced by electroshock. Two major compounds such as gentiopicroside and swertianin were analyzed by HPLC system.

Review of Post-Marketing Safety Data on Tapentadol, a Centrally Acting Analgesic.

Science.gov (United States)

Stollenwerk, Ariane; Sohns, Melanie; Heisig, Fabian; Elling, Christian; von Zabern, Detlef

2018-01-01

Tapentadol is a centrally acting analgesic that has been available for the management of acute and chronic pain in routine clinical practice since 2009. This is the first integrated descriptive analysis of post-marketing safety data following the use of tapentadol in a broad range of pain conditions relating to the topics overall safety, dose administration above approved dosages, administration during pregnancy, serotonin syndrome, respiratory depression, and convulsion. The data analyzed pertain to spontaneous reports from healthcare and non-healthcare professionals and were put in the context of safety information known from interventional and non-interventional trials. The first years of routine clinical practice experience with tapentadol have confirmed the tolerability profile that emerged from the clinical trials. Moreover, the reporting of expected side effects such as respiratory depression and convulsion was low and no major risks were identified. The evaluation of available post-marketing data did not confirm the theoretical risk of serotonin syndrome nor did it reveal unexpected side effects with administration of higher than recommended doses. More than 8 years after its first introduction, the favorable overall safety profile of tapentadol in the treatment of various pain conditions is maintained in the general population. Grünenthal GmbH.

Convulsive status epilepticus in a quaternary hospital paediatric intensive care unit (PICU) in South Africa: An 8 year review.

Science.gov (United States)

Reddy, Yavini; Balakrishna, Yusentha; Mubaiwa, Lawrence

2017-10-01

Convulsive status epilepticus (CSE) is associated with a high morbidity and mortality. This study aimed to describe the clinical profile, aetiology, neuroimaging and EEG findings as well as outcome of children with CSE in Sub-Saharan Africa. This was a retrospective analysis of electronic records of children with CSE admitted to the Paediatric Intensive Care Unit (PICU) over an 8-year period from January 2007 to December 2014. Seventy six patients were admitted to the PICU with CSE and 55(72%) had refractory status epilepticus. The median age at presentation was 15 months (IQR 6-37 months). The main aetiologies were meningoencephalitis and gastroenteritis in 33(43%) and 19(25%) patients respectively. The most frequently used antiepileptic drugs for CSE in PICU consisted of infusions of midazolam (96%) and thiopentone (22%). Neuroimaging findings were abnormal in 53(75%) patients with hypoxic changes in 17 patients. On multivariable regression, the predictors of poor outcome included the use of more than 3 antiepileptic drugs in PICU(RR-1.41(1.12-1.78), p=0.003), duration of mechanical ventilation for more than 3days (RR 1.98(1.22-3.20), p=0.005) and abnormal neuroimaging findings (RR 3.21(1.53-6.72), p=0.002). The mortality rate was 24%(n=18). Persistent seizures or a new neurological deficit occurred in 58%(n=44). The main cause of mortality was CSE related diffuse cortical and brainstem injury. Predominant neurological sequelae were cerebral palsy and persistent epilepsy. The high burden of infection related CSE is associated with high morbidity and mortality rates in contrast to the rates in developed countries. This highlights the need for early recognition and treatment of underlying conditions. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Dose planning and dose delivery in radiation therapy

International Nuclear Information System (INIS)

Knoeoes, T.

1991-01-01

A method has been developed for calibration of CT-numbers to volumetric electron density distributions using tissue substitutes of known elemental composition and experimentally determined electron density. This information have been used in a dose calculation method based on photon and electron interaction processes. The method utilizes a convolution integral between the photon fluence matrix and dose distribution kernels. Inhomogeneous media are accounted for using the theorems of Fano and O'Connor for scaling dose distribution kernels in proportion to electron density. For clinical application of a calculated dose plan, a method for prediction of accelerator output have been developed. The methods gives the number of monitor units that has to be given to obtain a certain absorbed dose to a point inside an irregular, inhomogeneous object. The method for verification of dose distributions outlined in this study makes it possible to exclude the treatment related variance contributions, making an objective evaluation of dose calculations with experiments feasible. The methods for electron density determination, dose calculation and prediction of accelerator output discussed in this study will all contribute to an increased accuracy in the mean absorbed dose to the target volume. However, a substantial gain in the accuracy for the spatial absorbed dose distribution will also follow, especially using CT for mapping of electron density together with the dose calculation algorithm. (au)

Normal tissue dose-effect models in biological dose optimisation

International Nuclear Information System (INIS)

Alber, M.

2008-01-01

Sophisticated radiotherapy techniques like intensity modulated radiotherapy with photons and protons rely on numerical dose optimisation. The evaluation of normal tissue dose distributions that deviate significantly from the common clinical routine and also the mathematical expression of desirable properties of a dose distribution is difficult. In essence, a dose evaluation model for normal tissues has to express the tissue specific volume effect. A formalism of local dose effect measures is presented, which can be applied to serial and parallel responding tissues as well as target volumes and physical dose penalties. These models allow a transparent description of the volume effect and an efficient control over the optimum dose distribution. They can be linked to normal tissue complication probability models and the equivalent uniform dose concept. In clinical applications, they provide a means to standardize normal tissue doses in the face of inevitable anatomical differences between patients and a vastly increased freedom to shape the dose, without being overly limiting like sets of dose-volume constraints. (orig.)

Study of jet quenching with Z+jet correlations in PbPb and pp collisions at $\\sqrt{s_{NN}}$ = 5.02 TeV

Energy Technology Data Exchange (ETDEWEB)

Sirunyan, Albert M; et al.

2017-02-03

The production of jets in association with Z bosons, reconstructed via the mu+mu- and e+e- decay channels, is studied in pp and, for the first time, in PbPb collisions. Both data samples were collected by the CMS experiment at the LHC, at a center-of-mass energy of 5.02 TeV. The PbPb collisions were analyzed in the 0-30% centrality range. The back-to-back azimuthal alignment was studied in both pp and PbPb collisions for Z bosons with transverse momentum ptz > 60 GeV/c and a recoiling jet with ptj > 30 GeV/c. The pt imbalance, xjz= ptj/ptz, as well as the average number of jet partners per Z, rjz, were studied in intervals of ptz, in both pp and PbPb collisions. The rjz is found to be smaller in PbPb than in pp collisions, which suggests that in PbPb collisions a larger fraction of partons, associated with the Z bosons, lose energy and fall below the 30 GeV/c ptj threshold.

Dose and dose rate monitor

International Nuclear Information System (INIS)

Novakova, O.; Ryba, J.; Slezak, V.; Svobodova, B.; Viererbl, L.

1984-10-01

The methods are discussea of measuring dose rate or dose using a scintillation counte. A plastic scintillator based on polystyrene with PBD and POPOP activators and coated with ZnS(Ag) was chosen for the projected monitor. The scintillators were cylindrical and spherical in shape and of different sizes; black polypropylene tubes were chosen as the best case for the probs. For the counter with different plastic scintillators, the statistical error 2σ for natural background was determined. For determining the suitable thickness of the ZnS(Ag) layer the energy dependence of the counter was measured. Radioisotopes 137 Cs, 241 Am and 109 Cd were chosen as radiation sources. The best suited ZnS(Ag) thickness was found to be 0.5 μm. Experiments were carried out to determine the directional dependence of the detector response and the signal to noise ratio. The temperature dependence of the detector response and its compensation were studied, as were the time stability and fatigue manifestations of the photomultiplier. The design of a laboratory prototype of a dose rate and dose monitor is described. Block diagrams are given of the various functional parts of the instrument. The designed instrument is easiiy portable, battery powered, measures dose rates from natural background in the range of five orders, i.e., 10 -2 to 10 3 nGy/s, and allows to determine a dose of up to 10 mGy. Accouracy of measurement in the energy range of 50 keV to 1 MeV is better than +-20%. (E.S.)

Determination of organ doses and effective doses in radiooncology

International Nuclear Information System (INIS)

Roth, J.; Martinez, A.E.

2007-01-01

Background and Purpose: With an increasing chance of success in radiooncology, it is necessary to estimate the risk from radiation scatter to areas outside the target volume. The cancer risk from a radiation treatment can be estimated from the organ doses, allowing a somewhat limited effective dose to be estimated and compared. Material and Methods: The doses of the radiation-sensitive organs outside the target volume can be estimated with the aid of the PC program PERIDOSE developed by van der Giessen. The effective doses are determined according to the concept of ICRP, whereby the target volume and the associated organs related to it are not taken into consideration. Results: Organ doses outside the target volume are generally < 1% of the dose in the target volume. In some cases, however, they can be as high as 3%. The effective doses during radiotherapy are between 60 and 900 mSv, depending upon the specific target volume, the applied treatment technique, and the given dose in the ICRU point. Conclusion: For the estimation of the radiation risk, organ doses in radiooncology can be calculated with the aid of the PC program PERIDOSE. While evaluating the radiation risk after ICRP, for the calculation of the effective dose, the advanced age of many patients has to be considered to prevent that, e.g., the high gonad doses do not overestimate the effective dose. (orig.)

Prevalence and Incidence of Epilepsy Associated with Convulsive Seizures in Rural Bolivia. A Global Campaign against Epilepsy Project.

Science.gov (United States)

Bruno, Elisa; Quattrocchi, Graziella; Crespo Gómes, Elizabeth Blanca; Sofia, Vito; Padilla, Sandra; Camargo, Mario; Zappia, Mario; Bartoloni, Alessandro; Nicoletti, Alessandra

2015-01-01

we performed a three-stages door-to-door survey to estimate incidence and prevalence of epilepsy associated with convulsive seizures (EACS) in a rural area of Bolivia. the study was carried out in the Cordillera Province, southern-eastern Bolivia. One hundred fourteen rural communities with a total population of 18,907 inhabitants were included in the survey. In order to identify subjects with EACS, trained fieldworkers administered a validated single screening question to the householders (stage I). A second face-to-face questionnaire was administered to each positive subject (stage II) that, in case of positive answer, underwent a complete neurological examination to confirm the diagnosis (stage III). We estimated age and sex specific life-time and active EACS prevalence at the prevalence day (30th June 2010). Incidence risk was evaluated for the 10-year period between January 2000 and December 2010. on prevalence day we identified 136 subjects with EACS, 124 of whom had active epilepsy. The life-time prevalence of EACS was 7.2/1,000 (7.6/1,000 age-adjusted to the world standard population) while the prevalence of active EACS was 6.6/1,000 (6.7/1,000 age-adjusted to the world standard population). Both life-time and active prevalence showed a peak (10.3/1,000) in the 15-24 years age group and, overall, were higher among women. During the incidence study period, 105 patients living in the study area had the onset of EACS. The crude incidence risk was 55.4/100,000 (49.5/100,000 age-adjusted to the world standard population). Incidence was slightly but not significantly higher among women (58.9/100,000 versus 51.9/100,000). the present study demonstrated a considerable burden of EACS in the Bolivian Chaco, showing prevalence and incidence estimates close to those reported for low and middle- income countries and underlying the need of treatment programs.

Prevalence and Incidence of Epilepsy Associated with Convulsive Seizures in Rural Bolivia. A Global Campaign against Epilepsy Project

Science.gov (United States)

Crespo Gómes, Elizabeth Blanca; Sofia, Vito; Padilla, Sandra; Camargo, Mario; Zappia, Mario; Bartoloni, Alessandro; Nicoletti, Alessandra

2015-01-01

Objective we performed a three-stages door-to-door survey to estimate incidence and prevalence of epilepsy associated with convulsive seizures (EACS) in a rural area of Bolivia. Methods the study was carried out in the Cordillera Province, southern-eastern Bolivia. One hundred fourteen rural communities with a total population of 18,907 inhabitants were included in the survey. In order to identify subjects with EACS, trained fieldworkers administered a validated single screening question to the householders (stage I). A second face-to-face questionnaire was administered to each positive subject (stage II) that, in case of positive answer, underwent a complete neurological examination to confirm the diagnosis (stage III). We estimated age and sex specific life-time and active EACS prevalence at the prevalence day (30th June 2010). Incidence risk was evaluated for the 10-year period between January 2000 and December 2010. Results on prevalence day we identified 136 subjects with EACS, 124 of whom had active epilepsy. The life-time prevalence of EACS was 7.2/1,000 (7.6/1,000 age-adjusted to the world standard population) while the prevalence of active EACS was 6.6/1,000 (6.7/1,000 age-adjusted to the world standard population). Both life-time and active prevalence showed a peak (10.3/1,000) in the 15–24 years age group and, overall, were higher among women. During the incidence study period, 105 patients living in the study area had the onset of EACS. The crude incidence risk was 55.4/100,000 (49.5/100,000 age-adjusted to the world standard population). Incidence was slightly but not significantly higher among women (58.9/100,000 versus 51.9/100,000). Conclusions the present study demonstrated a considerable burden of EACS in the Bolivian Chaco, showing prevalence and incidence estimates close to those reported for low and middle- income countries and underlying the need of treatment programs. PMID:26427017

Organ or tissue doses, effective dose and collective effective dose from X-ray diagnosis, in Japan

International Nuclear Information System (INIS)

Murayama, Takashi; Nishizawa, Kanae; Noda, Yutaka; Kumamoto, Yoshikazu; Iwai, Kazuo.

1996-01-01

Effective doses and collective effective doses from X-ray diagnostic examinations were calculated on the basis of the frequency of examinations estimated by a nationwide survey and the organ or tissue doses experimentally determined. The average organ or tissue doses were determined with thermoluminescence dosimeters put at various sites of organs or tissues in an adult and a child phantom. Effective doses (effective dose equivalents) were calculated as the sum of the weighted equivalent doses in all the organs or tissues of the body. As the examples of results, the effective doses per radiographic examination were approximately 7 mGy for male, and 9 mGy for female angiocardiography, and about 3 mGy for barium meal. Annual collective effective dose from X-ray diagnostic examinations in 1986 were about 104 x 10 3 person Sv from radiography and 118 x 10 3 person Sv from fluoroscopy, with the total of 222 x 10 3 person Sv. (author)

Dosimetric systems of high dose, dose rate and dose uniformity in food and medical products

International Nuclear Information System (INIS)

Vargas, J.; Vivanco, M.; Castro, E.

2014-08-01

In the Instituto Peruano de Energia Nuclear (IPEN) we use the chemical dosimetry Astm-E-1026 Fricke as a standard dosimetric system of reference and different routine dosimetric systems of high doses, according to the applied doses to obtain the desired effects in the treated products and the doses range determined for each type of dosimeter. Fricke dosimetry is a chemical dosimeter in aqueous solution indicating the absorbed dose by means an increase in absorbance at a specific wavelength. A calibrated spectrophotometer with controlled temperature is used to measure absorbance. The adsorbed dose range should cover from 20 to 400 Gy, the Fricke solution is extremely sensitive to organic impurities, to traces of metal ions, in preparing chemical products of reactive grade must be used and the water purity is very important. Using the referential standard dosimetric system Fricke, was determined to March 5, 2013, using the referential standard dosimetric system Astm-1026 Fricke, were irradiated in triplicate Fricke dosimeters, to 5 irradiation times (20; 30; 40; 50 and 60 seconds) and by linear regression, the dose rate of 5.400648 kGy /h was determined in the central point of the irradiation chamber (irradiator Gamma cell 220 Excel), applying the decay formula, was compared with the obtained results by manufacturers by means the same dosimetric system in the year of its manufacture, being this to the date 5.44691 kGy /h, with an error rate of 0.85. After considering that the dosimetric solution responds to the results, we proceeded to the irradiation of a sample of 200 g of cereal instant food, 2 dosimeters were placed at the lateral ends of the central position to maximum dose and 2 dosimeters in upper and lower ends as minimum dose, they were applied same irradiation times; for statistical analysis, the maximum dose rate was 6.1006 kGy /h and the minimum dose rate of 5.2185 kGy /h; with a dose uniformity of 1.16. In medical material of micro pulverized bone for

Glutamate receptor antibodies directed against AMPA receptors subunit 3 peptide B (GluR3B) can be produced in DBA/2J mice, lower seizure threshold and induce abnormal behavior.

Science.gov (United States)

Ganor, Yonatan; Goldberg-Stern, Hadassa; Cohen, Ran; Teichberg, Vivian; Levite, Mia

2014-04-01

Anti-GluR3B antibodies (GluR3B Ab's), directed against peptide B/aa372-395 of GluR3 subunit of glutamate/AMPA receptors, are found in ∼35% of epilepsy patients, activate glutamate/AMPA receptors, evoke ion currents, kill neurons and damage the brain. We recently found that GluR3B Ab's also associate with neurological/psychiatric/behavioral abnormalities in epilepsy patients. Here we asked if GluR3B Ab's could be produced in DBA/2J mice, and also modulate seizure threshold and/or cause behavioral/motor impairments in these mice. DBA/2J mice were immunized with the GluR3B peptide in Complete Freund's Adjuvant (CFA), or with controls: ovalbumin (OVA), CFA, or phosphate-buffer saline (PBS). GluR3B Ab's and OVA Ab's were tested. Seizures were induced in all mice by the chemoconvulsant pentylenetetrazole (PTZ) at three time points, each time with less PTZ to avoid non-specific death. Behavior was examined in Open-Field, RotaRod and Grip tests. GluR3B Ab's were produced only in GluR3B-immunized mice, while OVA Ab's were produced only in OVA-immunized mice, showing high Ab's specificity. In GluR3B Ab's negative mice, seizure severity scores and percentages of animals developing generalized seizures declined in response to decreasing PTZ doses. In contrast, both parameters remained unchanged/high in the GluR3B Ab's positive mice, showing that these mice were more susceptible to seizures. The seizure scores associated significantly with the GluR3B Ab's levels. GluR3B Ab's positive mice were also more anxious in Open-Field test, fell faster in RotaRod test, and fell more in Grip test, compared to all the control mice. GluR3B Ab's are produced in DBA/2J mice, facilitate seizures and induce behavioral/motor impairments. This animal model can therefore serve for studying autoimmune epilepsy and abnormal behavior mediated by pathogenic anti-GluR3B Ab's. Copyright © 2014 Elsevier Ltd. All rights reserved.

Evaluation of the dose uniformity for double-plane high dose rate interstitial breast implants with the use of dose reference points and dose non-uniformity ratio

International Nuclear Information System (INIS)

MAjor, T.; Polgar, C.; Somogyi, A.; Nemeth, G.

2000-01-01

This study investigated the influence of dwell time optimizations on dose uniformity characterized by dose values in dose points and dose non-uniformity ratio (DNR) and analyzed which implant parameters have influence on the DNR. Double-plane breast implants with catheters arranged in triangular pattern were used for the calculations. At a typical breast implant, dose values in dose reference points inside the target volume and volumes enclosed by given isodose surfaces were calculated and compared for non-optimized and optimized implants. The same 6-cm treatment length was used for the comparisons. Using different optimizations plots of dose non-uniformity ratio as a function of catheter separation, source step size, number of catheters, length of active sections were drawn and the minimum DNR values were determined. Optimization resulted in less variation in dose values over dose points through the whole volume and in the central plane only compared to the non-optimized case. At implant configurations consisting of seven catheters with 15-mm separation, 5-mm source step size and various active lengths adapted according to the type of optimization, the no optimization, geometrical (volume mode) and dose point (on dose points and geometry) optimization resulted in similar treatment volumes, but an increased high dose volume was observed due to the optimization. The dose non-uniformity ratio always had the minimum at average dose over dose normalization points, defined in the midpoints between the catheters through the implant volume. The minimum value of DNR depended on catheter separation, source step size, active length and number of catheters. The optimization had only a small influence on DNR. In addition to the reference points in the central plane only, dose points positioned in the whole implant volume can be used for evaluating the dose uniformity of interstitial implants. The dose optimization increases not only the dose uniformity within the implant but

Dose gradient curve: A new tool for evaluating dose gradient.

Science.gov (United States)

Sung, KiHoon; Choi, Young Eun

2018-01-01

Stereotactic radiotherapy, which delivers an ablative high radiation dose to a target volume for maximum local tumor control, requires a rapid dose fall-off outside the target volume to prevent extensive damage to nearby normal tissue. Currently, there is no tool to comprehensively evaluate the dose gradient near the target volume. We propose the dose gradient curve (DGC) as a new tool to evaluate the quality of a treatment plan with respect to the dose fall-off characteristics. The average distance between two isodose surfaces was represented by the dose gradient index (DGI) estimated by a simple equation using the volume and surface area of isodose levels. The surface area was calculated by mesh generation and surface triangulation. The DGC was defined as a plot of the DGI of each dose interval as a function of the dose. Two types of DGCs, differential and cumulative, were generated. The performance of the DGC was evaluated using stereotactic radiosurgery plans for virtual targets. Over the range of dose distributions, the dose gradient of each dose interval was well-characterized by the DGC in an easily understandable graph format. Significant changes in the DGC were observed reflecting the differences in planning situations and various prescription doses. The DGC is a rational method for visualizing the dose gradient as the average distance between two isodose surfaces; the shorter the distance, the steeper the dose gradient. By combining the DGC with the dose-volume histogram (DVH) in a single plot, the DGC can be utilized to evaluate not only the dose gradient but also the target coverage in routine clinical practice.

Optimized dose distribution of a high dose rate vaginal cylinder

International Nuclear Information System (INIS)

Li Zuofeng; Liu, Chihray; Palta, Jatinder R.

1998-01-01

Purpose: To present a comparison of optimized dose distributions for a set of high-dose-rate (HDR) vaginal cylinders calculated by a commercial treatment-planning system with benchmark calculations using Monte-Carlo-calculated dosimetry data. Methods and Materials: Optimized dose distributions using both an isotropic and an anisotropic dose calculation model were obtained for a set of HDR vaginal cylinders. Mathematical optimization techniques available in the computer treatment-planning system were used to calculate dwell times and positions. These dose distributions were compared with benchmark calculations with TG43 formalism and using Monte-Carlo-calculated data. The same dwell times and positions were used for a quantitative comparison of dose calculated with three dose models. Results: The isotropic dose calculation model can result in discrepancies as high as 50%. The anisotropic dose calculation model compared better with benchmark calculations. The differences were more significant at the apex of the vaginal cylinder, which is typically used as the prescription point. Conclusion: Dose calculation models available in a computer treatment-planning system must be evaluated carefully to ensure their correct application. It should also be noted that when optimized dose distribution at a distance from the cylinder surface is calculated using an accurate dose calculation model, the vaginal mucosa dose becomes significantly higher, and therefore should be carefully monitored

Review

African Journals Online (AJOL)

abp

29 févr. 2016 ... convulsions n'ont pu être stoppées 10 minutes après administration du DZP intrarectal contre 30,3% après MZM buccal [57]. A part le. DZP et le MZM, le lorazépam (LZP) et paraldéhyde ont étaient aussi objets d'essais cliniques en ASS. Chez les enfants présentant la malaria sévère, une dose (0,1 mg/kg) ...

Dynamically accumulated dose and 4D accumulated dose for moving tumors

International Nuclear Information System (INIS)

Li Heng; Li Yupeng; Zhang Xiaodong; Li Xiaoqiang; Liu Wei; Gillin, Michael T.; Zhu, X. Ronald

2012-01-01

Purpose: The purpose of this work was to investigate the relationship between dynamically accumulated dose (dynamic dose) and 4D accumulated dose (4D dose) for irradiation of moving tumors, and to quantify the dose uncertainty induced by tumor motion. Methods: The authors established that regardless of treatment modality and delivery properties, the dynamic dose will converge to the 4D dose, instead of the 3D static dose, after multiple deliveries. The bounds of dynamic dose, or the maximum estimation error using 4D or static dose, were established for the 4D and static doses, respectively. Numerical simulations were performed (1) to prove the principle that for each phase, after multiple deliveries, the average number of deliveries for any given time converges to the total number of fractions (K) over the number of phases (N); (2) to investigate the dose difference between the 4D and dynamic doses as a function of the number of deliveries for deliveries of a “pulsed beam”; and (3) to investigate the dose difference between 4D dose and dynamic doses as a function of delivery time for deliveries of a “continuous beam.” A Poisson model was developed to estimate the mean dose error as a function of number of deliveries or delivered time for both pulsed beam and continuous beam. Results: The numerical simulations confirmed that the number of deliveries for each phase converges to K/N, assuming a random starting phase. Simulations for the pulsed beam and continuous beam also suggested that the dose error is a strong function of the number of deliveries and/or total deliver time and could be a function of the breathing cycle, depending on the mode of delivery. The Poisson model agrees well with the simulation. Conclusions: Dynamically accumulated dose will converge to the 4D accumulated dose after multiple deliveries, regardless of treatment modality. Bounds of the dynamic dose could be determined using quantities derived from 4D doses, and the mean dose

A review of radiology staff doses and dose monitoring requirements

International Nuclear Information System (INIS)

Martin, C. J.

2009-01-01

Studies of radiation doses received during X-ray procedures by radiology, cardiology and other clinical staff have been reviewed. Data for effective dose (E), and doses to the eyes, thyroid, hands and legs have been analysed. These data have been supplemented with local measurements to determine the most exposed part of the hand for monitoring purposes. There are ranges of 60-100 in doses to individual tissues reported in the literature for similar procedures at different centres. While ranges in the doses per unit dose-area product (DAP) are between 10 and 25, large variations in dose result from differences in the sensitivity of the X-ray equipment, the type of procedure and the operator technique, but protection factors are important in maintaining dose levels as low as possible. The influence of shielding devices is significant for determining the dose to the eyes and thyroid, and the position of the operator, which depends on the procedure, is the most significant factor determining doses to the hands. A second body dosemeter worn at the level of the collar is recommended for operators with high workloads for use in assessment of effective dose and the dose to the eye. It is proposed that the third quartile values from the distributions of dose per unit DAP identified in the review might be employed in predicting the orders of magnitude of doses to the eye, thyroid and hands, based on interventional operator workloads. Such dose estimates could be employed in risk assessments when reviewing protection and monitoring requirements. A dosemeter worn on the little finger of the hand nearest to the X-ray tube is recommended for monitoring the hand. (authors)

''Low dose'' and/or ''high dose'' in radiation protection: A need to setting criteria for dose classification

International Nuclear Information System (INIS)

Sohrabi, M.

1997-01-01

The ''low dose'' and/or ''high dose'' of ionizing radiation are common terms widely used in radiation applications, radiation protection and radiobiology, and natural radiation environment. Reading the title, the papers of this interesting and highly important conference and the related literature, one can simply raise the question; ''What are the levels and/or criteria for defining a low dose or a high dose of ionizing radiation?''. This is due to the fact that the criteria for these terms and for dose levels between these two extreme quantities have not yet been set, so that the terms relatively lower doses or higher doses are usually applied. Therefore, setting criteria for classification of radiation doses in the above mentioned areas seems a vital need. The author while realizing the existing problems to achieve this important task, has made efforts in this paper to justify this need and has proposed some criteria, in particular for the classification of natural radiation areas, based on a system of dose limitation. (author)

Quantitative analysis of biological responses to low dose-rate γ-radiation, including dose, irradiation time, and dose-rate

International Nuclear Information System (INIS)

Magae, J.; Furukawa, C.; Kawakami, Y.; Hoshi, Y.; Ogata, H.

2003-01-01

Full text: Because biological responses to radiation are complex processes dependent on irradiation time as well as total dose, it is necessary to include dose, dose-rate and irradiation time simultaneously to predict the risk of low dose-rate irradiation. In this study, we analyzed quantitative relationship among dose, irradiation time and dose-rate, using chromosomal breakage and proliferation inhibition of human cells. For evaluation of chromosome breakage we assessed micronuclei induced by radiation. U2OS cells, a human osteosarcoma cell line, were exposed to gamma-ray in irradiation room bearing 50,000 Ci 60 Co. After the irradiation, they were cultured for 24 h in the presence of cytochalasin B to block cytokinesis, cytoplasm and nucleus were stained with DAPI and propidium iodide, and the number of binuclear cells bearing micronuclei was determined by fluorescent microscopy. For proliferation inhibition, cells were cultured for 48 h after the irradiation and [3H] thymidine was pulsed for 4 h before harvesting. Dose-rate in the irradiation room was measured with photoluminescence dosimeter. While irradiation time less than 24 h did not affect dose-response curves for both biological responses, they were remarkably attenuated as exposure time increased to more than 7 days. These biological responses were dependent on dose-rate rather than dose when cells were irradiated for 30 days. Moreover, percentage of micronucleus-forming cells cultured continuously for more than 60 days at the constant dose-rate, was gradually decreased in spite of the total dose accumulation. These results suggest that biological responses at low dose-rate, are remarkably affected by exposure time, that they are dependent on dose-rate rather than total dose in the case of long-term irradiation, and that cells are getting resistant to radiation after the continuous irradiation for 2 months. It is necessary to include effect of irradiation time and dose-rate sufficiently to evaluate risk

Calculation of dose conversion factors for doses in the fingernails to organ doses at external gamma irradiation in air

International Nuclear Information System (INIS)

Khailov, A.M.; Ivannikov, A.I.; Skvortsov, V.G.; Stepanenko, V.F.; Orlenko, S.P.; Flood, A.B.; Williams, B.B.; Swartz, H.M.

2015-01-01

Absorbed doses to fingernails and organs were calculated for a set of homogenous external gamma-ray irradiation geometries in air. The doses were obtained by stochastic modeling of the ionizing particle transport (Monte Carlo method) for a mathematical human phantom with arms and hands placed loosely along the sides of the body. The resulting dose conversion factors for absorbed doses in fingernails can be used to assess the dose distribution and magnitude in practical dose reconstruction problems. For purposes of estimating dose in a large population exposed to radiation in order to triage people for treatment of acute radiation syndrome, the calculated data for a range of energies having a width of from 0.05 to 3.5 MeV were used to convert absorbed doses in fingernails to corresponding doses in organs and the whole body as well as the effective dose. Doses were assessed based on assumed rates of radioactive fallout at different time periods following a nuclear explosion. - Highlights: • Elemental composition and density of nails were determined. • MIRD-type mathematical human phantom with arms and hands was created. • Organ doses and doses to nails were calculated for external photon exposure in air. • Effective dose and nail doses values are close for rotational and soil surface exposures.

Dose/dose-rate responses of shrimp larvae to UV-B radiation

International Nuclear Information System (INIS)

Damkaer, D.M.

1981-01-01

Previous work indicated dose-rate thresholds in the effects of UV-B on the near-surface larvae of three shrimp species. Additional observations suggest that the total dose response varies with dose-rate. Below 0.002 Wm -2 sub([DNA]) irradiance no significant effect is noted in activity, development, or survival. Beyond that dose-rate threshold, shrimp larvae are significantly affected if the total dose exceeds about 85 Jm -2 sub([DNA]). Predictions cannot be made without both the dose-rate and the dose. These dose/dose-rate thresholds are compared to four-year mean dose/dose-rate solar UV-B irradiances at the experimental site, measured at the surface and calculated for 1 m depth. The probability that the shrimp larvae would receive lethal irradiance is low for the first half of the season of surface occurrence, even with a 44% increase in damaging UV radiation. (orig.)

Dose/dose-rate responses of shrimp larvae to UV-B radiation

Energy Technology Data Exchange (ETDEWEB)

Damkaer, D.M.; Dey, D.B.; Heron, G.A.

1981-01-01

Previous work indicated dose-rate thresholds in the effects of UV-B on the near-surface larvae of three shrimp species. Additional observations suggest that the total dose response varies with dose-rate. Below 0.002 Wm/sup -2/sub((DNA)) irradiance no significant effect is noted in activity, development, or survival. Beyond that dose-rate threshold, shrimp larvae are significantly affected if the total dose exceeds about 85 Jm/sup -2/sub((DNA)). Predictions cannot be made without both the dose-rate and the dose. These dose/dose-rate thresholds are compared to four-year mean dose/dose-rate solar UV-B irradiances at the experimental site, measured at the surface and calculated for 1 m depth. The probability that the shrimp larvae would receive lethal irradiance is low for the first half of the season of surface occurrence, even with a 44% increase in damaging UV radiation.

Use of electronic immunization registry in the surveillance of adverse events following immunization

Directory of Open Access Journals (Sweden)

Ana Paula Sayuri Sato

2018-02-01

Full Text Available ABSTRACT OBJECTIVE To describe adverse events following vaccination (AEFV of children under two years old and analyze trend of this events from 2000 to 2013, in the city of Araraquara (SP, Brazil. METHODS This is a descriptive study conducted with data of the passive surveillance system of AEFV that is available in the electronic immunization registry (EIR of the computerized medical record of the municipal health service (Juarez System. The study variables were: age, gender, vaccine, dose, clinical manifestations and hospitalization. We estimated rates using AEFV as numerator and administered doses of vaccines as denominator. The surveillance sensitivity was estimated by applying the method proposed by the Centers for Disease Control and Prevention. We used Prais-Winsten regression with a significance level of 5.0%. RESULTS The average annual rate of AEFV was 11.3/10,000 administered doses, however without a trend in the study period (p=0.491. Most cases occurred after the first dose (41.7% and among children under one year of age (72.6%. Vaccines with pertussis component, yellow fever and measles-mumps-rubella were the most reactogenic. We highlighted the rates of hypotonic-hyporesponsive episodes and convulsion that were 4.1/10,000 and 1.5/10,000 doses of vaccines with pertussis component, respectively, most frequently in the first dose; 60,0% of cases presented symptoms in the first 24 hours after vaccination, however, 18.6% showed after 96 hours. The sensitivity of surveillance was 71.9% and 78.9% for hypotonic-hyporesponsive episodes and convulsion, respectively. CONCLUSIONS The EIR-based AEFV surveillance system proved to be useful and highly sensitive to describe the safety profile of vaccines in a medium-sized city. It was also shown that the significant increase of the vaccines included in the basic vaccination schedule in childhood in the last decade did not alter the high safety standard of the National Immunization Program.

Neutrons in active proton therapy. Parameterization of dose and dose equivalent

Energy Technology Data Exchange (ETDEWEB)

Schneider, Uwe; Haelg, Roger A. [Univ. of Zurich (Switzerland). Dept. of Physics; Radiotherapy Hirslanden AG, Aarau (Switzerland); Lomax, Tony [Paul Scherrer Institute, Villigen (Switzerland). Center for Proton Therapy

2017-08-01

One of the essential elements of an epidemiological study to decide if proton therapy may be associated with increased or decreased subsequent malignancies compared to photon therapy is an ability to estimate all doses to non-target tissues, including neutron dose. This work therefore aims to predict for patients using proton pencil beam scanning the spatially localized neutron doses and dose equivalents. The proton pencil beam of Gantry 1 at the Paul Scherrer Institute (PSI) was Monte Carlo simulated using GEANT. Based on the simulated neutron dose and neutron spectra an analytical mechanistic dose model was developed. The pencil beam algorithm used for treatment planning at PSI has been extended using the developed model in order to calculate the neutron component of the delivered dose distribution for each treated patient. The neutron dose was estimated for two patient example cases. The analytical neutron dose model represents the three-dimensional Monte Carlo simulated dose distribution up to 85 cm from the proton pencil beam with a satisfying precision. The root mean square error between Monte Carlo simulation and model is largest for 138 MeV protons and is 19% and 20% for dose and dose equivalent, respectively. The model was successfully integrated into the PSI treatment planning system. In average the neutron dose is increased by 10% or 65% when using 160 MeV or 177 MeV instead of 138 MeV. For the neutron dose equivalent the increase is 8% and 57%. The presented neutron dose calculations allow for estimates of dose that can be used in subsequent epidemiological studies or, should the need arise, to estimate the neutron dose at any point where a subsequent secondary tumour may occur. It was found that the neutron dose to the patient is heavily increased with proton energy.

Absorbed dose in CT. Comparison by CT dose index

International Nuclear Information System (INIS)

Yamamoto, Kenji; Akazawa, Hiroshi; Andou, Takashi

2002-01-01

Few reports have discussed the absorbed dose on CT units with increased scanning capacity even with the current widespread adoption of multi-slice CT units. To compare and investigate the dose indexes among CT units, we measured the absorbed dose on CT units operating in Nagano Prefecture Japan. The measurements showed proportionality between phantom absorbed dose and the exposured mAs values in conventional scanning operation. Further, the measurements showed that the absorbed dose in the center of the phantom differed by about 2.1-fold between the highest and lowest levels on individual CT units. Within a single company, multi-slice CT units of the same company gave absorbed doses of about 1.3 to 1.5 times those of conventional single-slice CT units under the same exposured conditions of conventional scanning. When the scanning pitch was reduced in helical scanning, the absorbed dose at the center of the phantom increased. (author)

Occupational dose assessment and national dose registry system in Iran

International Nuclear Information System (INIS)

Jafari-Zadeh, M.; Nazeri, F.; Hosseini-Pooya, S. M.; Taheri, M.; Gheshlaghi, F.; Kardan, M. R.; Babakhani, A.; Rastkhah, N.; Yousefi-Nejad, F.; Darabi, M.; Oruji, T.; Gholamali-Zadeh, Z.; Karimi-Diba, J.; Kazemi-Movahed, A. A.; Dashti-Pour, M. R.; Enferadi, A.; Jahanbakhshian, M. H.; Sadegh-Khani, M. R.

2011-01-01

This report presents status of external and internal dose assessment of workers and introducing the structure of National Dose Registry System of Iran (NDRSI). As well as types of individual dosemeters in use, techniques for internal dose assessment are presented. Results obtained from the International Atomic Energy Agency intercomparison programme on measurement of personal dose equivalent H p (10) and consistency of the measured doses with the delivered doses are shown. Also, implementation of dosimetry standards, establishment of quality management system, authorisation and approval procedure of dosimetry service providers are discussed. (authors)

NMDA antagonists exert distinct effects in experimental organophosphate or carbamate poisoning in mice

International Nuclear Information System (INIS)

Dekundy, Andrzej; Kaminski, Rafal M.; Zielinska, Elzbieta; Turski, Waldemar A.

2007-01-01

Organophosphate (OP) and carbamate acetylcholinesterase (AChE) inhibitors produce seizures and lethality in mammals. Anticonvulsant and neuroprotective properties of N-methyl-D-aspartate (NMDA) antagonists encourage the investigation of their effects in AChE inhibitor-induced poisonings. In the present study, the effects of dizocilpine (MK-801, 1 mg/kg) or 3-((RS)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP, 10 mg/kg), alone or combined with muscarinic antagonist atropine (1.8 mg/kg), on convulsant and lethal properties of an OP pesticide dichlorvos or a carbamate drug physostigmine, were studied in mice. Both dichlorvos and physostigmine induced dose-dependent seizure activity and lethality. Atropine did not prevent the occurrence of convulsions but decreased the lethal effects of both dichlorvos and physostigmine. MK-801 or CPP blocked or attenuated, respectively, dichlorvos-induced convulsions. Contrariwise, NMDA antagonists had no effect in physostigmine-induced seizures or lethality produced by dichlorvos or physostigmine. Concurrent pretreatment with atropine and either MK-801 or CPP blocked or alleviated seizures produced by dichlorvos, but not by physostigmine. Both MK-801 and CPP co-administered with atropine enhanced its antilethal effects in both dichlorvos and physostigmine poisoning. In both saline- and AChE inhibitor-treated mice, no interaction of the investigated antidotes with brain cholinesterase was found. The data indicate that both muscarinic ACh and NMDA receptor-mediated mechanisms contribute to the acute toxicity of AChE inhibitors, and NMDA receptors seem critical to OP-induced seizures

What is correct: equivalent dose or dose equivalent

International Nuclear Information System (INIS)

Franic, Z.

1994-01-01

In Croatian language some physical quantities in radiation protection dosimetry have not precise names. Consequently, in practice either terms in English or mathematical formulas are used. The situation is even worse since the Croatian language only a limited number of textbooks, reference books and other papers are available. This paper compares the concept of ''dose equivalent'' as outlined in International Commission on Radiological Protection (ICRP) recommendations No. 26 and newest, conceptually different concept of ''equivalent dose'' which is introduced in ICRP 60. It was found out that Croatian terminology is both not uniform and unprecise. For the term ''dose equivalent'' was, under influence of Russian and Serbian languages, often used as term ''equivalent dose'' even from the point of view of ICRP 26 recommendations, which was not justified. Unfortunately, even now, in Croatia the legal unit still ''dose equivalent'' defined as in ICRP 26, but the term used for it is ''equivalent dose''. Therefore, in Croatian legislation a modified set of quantities introduced in ICRP 60, should be incorporated as soon as possible

Seizures induced by carbachol, morphine, and leucine-enkephalin: a comparison.

Science.gov (United States)

Snead, O C

1983-04-01

The electrical, behavioral, and pharmacological properties of seizures induced by morphine, leucine-enkephalin, and the muscarinic cholinergic agonist carbachol were examined and compared. Low-dose carbachol given intracerebroventricularly (ICV) produced seizures similar electrically to those produced by ICV morphine and leucine-enkephalin, although there was some difference in site of subcortical origin of onset. Carbachol and morphine were similar in that they had the same anticonvulsant profile, produced similar behavioral changes, caused generalized absence seizures in low doses and generalized convulsive seizures in high doses, and were capable of chemical kindling. However, opiate-induced seizures were not overcome by cholinergic antagonists, nor were carbachol seizures blocked by opiate antagonists. These data suggest that there may be a common noncholinergic, nonopiatergic system involved in mediating carbachol- and morphine-induced seizures but not enkephalin seizures.

Dose volume assessment of high dose rate 192IR endobronchial implants

International Nuclear Information System (INIS)

Cheng, B. Saw; Korb, Leroy J.; Pawlicki, Todd; Wu, Andrew

1996-01-01

Purpose: To study the dose distributions of high dose rate (HDR) endobronchial implants using the dose nonuniformity ratio (DNR) and three volumetric irradiation indices. Methods and Materials: Multiple implants were configured by allowing a single HDR 192 Ir source to step through a length of 6 cm along an endobronchial catheter. Dwell times were computed to deliver a dose of 5 Gy to points 1 cm away from the catheter axis. Five sets of source configurations, each with different dwell position spacings from 0.5 to 3.0 cm, were evaluated. Three-dimensional (3D) dose distributions were then generated for each source configuration. Differential and cumulative dose-volume curves were generated to quantify the degree of target volume coverage, dose nonuniformity within the target volume, and irradiation of tissues outside the target volume. Evaluation of the implants were made using the DNR and three volumetric irradiation indices. Results: The observed isodose distributions were not able to satisfy all the dose constraints. The ability to optimally satisfy the dose constraints depended on the choice of dwell position spacing and the specification of the dose constraint points. The DNR and irradiation indices suggest that small dwell position spacing does not result in a more homogeneous dose distribution for the implant. This study supports the existence of a relationship between the dwell position spacing and the distance from the catheter axis to the reference dose or dose constraint points. Better dose homogeneity for an implant can be obtained if the spacing of the dwell positions are about twice the distance from the catheter axis to the reference dose or dose constraint points

Increased seizure susceptibility and other toxicity symptoms following acute sulforaphane treatment in mice

Energy Technology Data Exchange (ETDEWEB)

Socała, Katarzyna, E-mail: ksocala@op.pl [Department of Animal Physiology, Institute of Biology and Biochemistry, Maria Curie-Skłodowska University, Lublin (Poland); Nieoczym, Dorota [Department of Animal Physiology, Institute of Biology and Biochemistry, Maria Curie-Skłodowska University, Lublin (Poland); Kowalczuk-Vasilev, Edyta [Institute of Animal Nutrition and Bromatology, University of Life Sciences, Lublin (Poland); Wyska, Elżbieta [Department of Pharmacokinetics and Physical Pharmacy, Jagiellonian University Medical College, Kraków (Poland); Wlaź, Piotr [Department of Animal Physiology, Institute of Biology and Biochemistry, Maria Curie-Skłodowska University, Lublin (Poland)

2017-07-01

Activation of Nrf2 with sulforaphane has recently gained attention as a new therapeutic approach in the treatment of many diseases, including epilepsy. As a plant-derived compound, sulforaphane is considered to be safe and well-tolerated. It is widely consumed, also by patients suffering from seizure and taking antiepileptic drugs, but no toxicity profile of sulforaphane exists. Since many natural remedies and dietary supplements may increase seizure risk and potentially interact with antiepileptic drugs, the aim of our study was to investigate the acute effects of sulforaphane on seizure thresholds and activity of some first- and second-generation antiepileptic drugs in mice. In addition, some preliminary toxicity profile of sulforaphane in mice after intraperitoneal injection was evaluated. The LD{sub 50} value of sulforaphane in mice was estimated at 212.67 mg/kg, while the TD{sub 50} value – at 191.58 mg/kg. In seizure tests, sulforaphane at the highest dose tested (200 mg/kg) significantly decreased the thresholds for the onset of the first myoclonic twitch and generalized clonic seizure in the iv PTZ test as well as the threshold for the 6 Hz-induced psychomotor seizure. At doses of 10–200 mg/kg, sulforaphane did not affect the threshold for the iv PTZ-induced forelimb tonus or the threshold for maximal electroshock-induced hindlimb tonus. Interestingly, sulforaphane (at 100 mg/kg) potentiated the anticonvulsant efficacy of carbamazepine in the maximal electroshock seizure test. This interaction could have been pharmacokinetic in nature, as sulforaphane increased concentrations of carbamazepine in both serum and brain tissue. The toxicity study showed that high doses of sulforaphane produced marked sedation (at 150–300 mg/kg), hypothermia (at 150–300 mg/kg), impairment of motor coordination (at 200–300 mg/kg), decrease in skeletal muscle strength (at 250–300 mg/kg), and deaths (at 200–300 mg/kg). Moreover, blood analysis showed leucopenia in

A novel dose uncertainty model and its application for dose verification

International Nuclear Information System (INIS)

Jin Hosang; Chung Heetaek; Liu Chihray; Palta, Jatinder; Suh, Tae-Suk; Kim, Siyong

2005-01-01

Based on statistical approach, a novel dose uncertainty model was introduced considering both nonspatial and spatial dose deviations. Non-space-oriented uncertainty is mainly caused by dosimetric uncertainties, and space-oriented dose uncertainty is the uncertainty caused by all spatial displacements. Assuming these two parts are independent, dose difference between measurement and calculation is a linear combination of nonspatial and spatial dose uncertainties. Two assumptions were made: (1) the relative standard deviation of nonspatial dose uncertainty is inversely proportional to the dose standard deviation σ, and (2) the spatial dose uncertainty is proportional to the gradient of dose. The total dose uncertainty is a quadratic sum of the nonspatial and spatial uncertainties. The uncertainty model provides the tolerance dose bound for comparison between calculation and measurement. In the statistical uncertainty model based on a Gaussian distribution, a confidence level of 3σ theoretically confines 99.74% of measurements within the bound. By setting the confidence limit, the tolerance bound for dose comparison can be made analogous to that of existing dose comparison methods (e.g., a composite distribution analysis, a γ test, a χ evaluation, and a normalized agreement test method). However, the model considers the inherent dose uncertainty characteristics of the test points by taking into account the space-specific history of dose accumulation, while the previous methods apply a single tolerance criterion to the points, although dose uncertainty at each point is significantly different from others. Three types of one-dimensional test dose distributions (a single large field, a composite flat field made by two identical beams, and three-beam intensity-modulated fields) were made to verify the robustness of the model. For each test distribution, the dose bound predicted by the uncertainty model was compared with simulated measurements. The simulated

Evaluation of the pentylenetetrazole seizure threshold test in epileptic mice as surrogate model for drug testing against pharmacoresistant seizures.

Science.gov (United States)

Töllner, Kathrin; Twele, Friederike; Löscher, Wolfgang

2016-04-01

Resistance to antiepileptic drugs (AEDs) is a major problem in epilepsy therapy, so that development of more effective AEDs is an unmet clinical need. Several rat and mouse models of epilepsy with spontaneous difficult-to-treat seizures exist, but because testing of antiseizure drug efficacy is extremely laborious in such models, they are only rarely used in the development of novel AEDs. Recently, the use of acute seizure tests in epileptic rats or mice has been proposed as a novel strategy for evaluating novel AEDs for increased antiseizure efficacy. In the present study, we compared the effects of five AEDs (valproate, phenobarbital, diazepam, lamotrigine, levetiracetam) on the pentylenetetrazole (PTZ) seizure threshold in mice that were made epileptic by pilocarpine. Experiments were started 6 weeks after a pilocarpine-induced status epilepticus. At this time, control seizure threshold was significantly lower in epileptic than in nonepileptic animals. Unexpectedly, only one AED (valproate) was less effective to increase seizure threshold in epileptic vs. nonepileptic mice, and this difference was restricted to doses of 200 and 300 mg/kg, whereas the difference disappeared at 400mg/kg. All other AEDs exerted similar seizure threshold increases in epileptic and nonepileptic mice. Thus, induction of acute seizures with PTZ in mice pretreated with pilocarpine does not provide an effective and valuable surrogate method to screen drugs for antiseizure efficacy in a model of difficult-to-treat chronic epilepsy as previously suggested from experiments with this approach in rats. Copyright © 2016 Elsevier Inc. All rights reserved.

A dose error evaluation study for 4D dose calculations

Science.gov (United States)

Milz, Stefan; Wilkens, Jan J.; Ullrich, Wolfgang

2014-10-01

Previous studies have shown that respiration induced motion is not negligible for Stereotactic Body Radiation Therapy. The intrafractional breathing induced motion influences the delivered dose distribution on the underlying patient geometry such as the lung or the abdomen. If a static geometry is used, a planning process for these indications does not represent the entire dynamic process. The quality of a full 4D dose calculation approach depends on the dose coordinate transformation process between deformable geometries. This article provides an evaluation study that introduces an advanced method to verify the quality of numerical dose transformation generated by four different algorithms. The used transformation metric value is based on the deviation of the dose mass histogram (DMH) and the mean dose throughout dose transformation. The study compares the results of four algorithms. In general, two elementary approaches are used: dose mapping and energy transformation. Dose interpolation (DIM) and an advanced concept, so called divergent dose mapping model (dDMM), are used for dose mapping. The algorithms are compared to the basic energy transformation model (bETM) and the energy mass congruent mapping (EMCM). For evaluation 900 small sample regions of interest (ROI) are generated inside an exemplary lung geometry (4DCT). A homogeneous fluence distribution is assumed for dose calculation inside the ROIs. The dose transformations are performed with the four different algorithms. The study investigates the DMH-metric and the mean dose metric for different scenarios (voxel sizes: 8 mm, 4 mm, 2 mm, 1 mm 9 different breathing phases). dDMM achieves the best transformation accuracy in all measured test cases with 3-5% lower errors than the other models. The results of dDMM are reasonable and most efficient in this study, although the model is simple and easy to implement. The EMCM model also achieved suitable results, but the approach requires a more complex

Standardization of high-dose measurement of electron and gamma ray absorbed doses and dose rates

International Nuclear Information System (INIS)

McLaughlin, W.L.

1985-01-01

Intense electron beams and gamma radiation fields are used for sterilizing medical devices, treating municipal wastes, processing industrial goods, controlling parasites and pathogens, and extending the shelf-life of foods. Quality control of such radiation processes depends largely on maintaining measurement quality assurance through sound dosimetry procedures in the research leading to each process, in the commissioning of that process, and in the routine dose monitoring practices. This affords documentation as to whether satisfactory dose uniformity is maintained throughout the product and throughout the process. Therefore, dosimetry at high doses and dose rates must in many radiation processes be standardized carefully, so that 'dosimetry release' of a product is verified. This standardization is initiated through preliminary dosimetry intercomparison studies such as those sponsored recently by the IAEA. This is followed by establishing periodic exercises in traceability to national or international standards of absorbed dose and dose rate. Traceability is achieved by careful selection of dosimetry methods and proven reference dosimeters capable of giving sufficiently accurate and precise 'transfer' dose assessments: (1) they must be calibrated or have well-established radiation-yield indices; (2) their radiation response characteristics must be reproducible and cover the dose range of interest; (3) they must withstand the rigours of back-and-forth mailing between a central standardizing laboratory and radiation processing facilities, without excessive errors arising due to instabilities, dosimeter batch non-uniformities, and environmental and handling stresses. (author)

Biological influence from low dose and low-dose rate radiation

International Nuclear Information System (INIS)

Magae, Junji

2007-01-01

Although living organisms have defense mechanisms for radioadaptive response, the influence is considered to vary qualitatively and quantitatively for low dose and high dose, as well as for low-dose rate and high-dose rate. This article describes the bioresponse to low dose and low-dose rate. Among various biomolecules, DNA is the most sensitive to radiation, and accurate replication of DNA is an essential requirement for the survival of living organisms. Also, the influence of active enzymes resulted from the effect of radiation on enzymes in the body is larger than the direct influence of radiation on the body. After this, the article describes the carcinogenic risk by low-dose radiation, and then so-called Hormesis effect to create cancer inhibition effect by stimulating active physiology. (S.K.)

Anticonvulsant activity of bioflavonoid gossypin

Directory of Open Access Journals (Sweden)

Srinivasan Duraisamy

2009-06-01

Full Text Available The anticonvulsant activity of gossypin was investigated by studying the effects on seizures induced by pentelentetrazole, strychnine and maximal electroshock convulsive methods in mice. Gossypin (10 and 20 mg/kg significantly reduced the duration of convulsion in tonic seizure induced by pentelenetetrazole (95 mg/kg, intraperitoneally. Gossypin (20 mg/kg p.o significantly reduced the tonic extensor convulsion induced by strychnine and maximum electroshock-induced convulsions. The data obtained suggest that gossypin have anticonvulsant property and may probably be affecting both GABA aminergic and glycine inhibitory mechanism.

Anticonvulsant activity of bioflavonoid gossypin

Directory of Open Access Journals (Sweden)

Duraisami Rasilingam

2009-03-01

Full Text Available The anticonvulsant activity of gossypin was investigated by studying the effects on seizures induced by pentelentetrazole, strychnine and maximal electroshock convulsive methods in mice. Gossypin (10 and 20 mg/kg significantly reduced the duration of convulsion in tonic seizure induced by pentelenetetrazole (95 mg/kg, intraperitoneally. Gossypin (20 mg/kg p.o significantly reduced the tonic extensor convulsion induced by strychnine and maximum electroshock-induced convulsions. The data obtained suggest that gossypin have anticonvulsant property and may probably be affecting both GABA aminergic and glycine inhibitory mechanism.

Superficial dose evaluation of four dose calculation algorithms

Science.gov (United States)

Cao, Ying; Yang, Xiaoyu; Yang, Zhen; Qiu, Xiaoping; Lv, Zhiping; Lei, Mingjun; Liu, Gui; Zhang, Zijian; Hu, Yongmei

2017-08-01

Accurate superficial dose calculation is of major importance because of the skin toxicity in radiotherapy, especially within the initial 2 mm depth being considered more clinically relevant. The aim of this study is to evaluate superficial dose calculation accuracy of four commonly used algorithms in commercially available treatment planning systems (TPS) by Monte Carlo (MC) simulation and film measurements. The superficial dose in a simple geometrical phantom with size of 30 cm×30 cm×30 cm was calculated by PBC (Pencil Beam Convolution), AAA (Analytical Anisotropic Algorithm), AXB (Acuros XB) in Eclipse system and CCC (Collapsed Cone Convolution) in Raystation system under the conditions of source to surface distance (SSD) of 100 cm and field size (FS) of 10×10 cm2. EGSnrc (BEAMnrc/DOSXYZnrc) program was performed to simulate the central axis dose distribution of Varian Trilogy accelerator, combined with measurements of superficial dose distribution by an extrapolation method of multilayer radiochromic films, to estimate the dose calculation accuracy of four algorithms in the superficial region which was recommended in detail by the ICRU (International Commission on Radiation Units and Measurement) and the ICRP (International Commission on Radiological Protection). In superficial region, good agreement was achieved between MC simulation and film extrapolation method, with the mean differences less than 1%, 2% and 5% for 0°, 30° and 60°, respectively. The relative skin dose errors were 0.84%, 1.88% and 3.90%; the mean dose discrepancies (0°, 30° and 60°) between each of four algorithms and MC simulation were (2.41±1.55%, 3.11±2.40%, and 1.53±1.05%), (3.09±3.00%, 3.10±3.01%, and 3.77±3.59%), (3.16±1.50%, 8.70±2.84%, and 18.20±4.10%) and (14.45±4.66%, 10.74±4.54%, and 3.34±3.26%) for AXB, CCC, AAA and PBC respectively. Monte Carlo simulation verified the feasibility of the superficial dose measurements by multilayer Gafchromic films. And the rank

Biological dose estimation for accidental supra-high dose gamma-ray exposure

International Nuclear Information System (INIS)

Chen, Y.; Yan, X.K.; Du, J.; Wang, Z.D.; Zhang, X.Q.; Zeng, F.G.; Zhou, P.K.

2011-01-01

To correctly estimate the biological dose of victims accidentally exposed to a very high dose of 60 Co gamma-ray, a new dose-effect curve of chromosomal dicentrics/multicentrics and rings in the supra-high dose range was established. Peripheral blood from two healthy men was irradiated in vitro with doses of 60 Co gamma-rays ranging from 6 to 22 Gy at a dose rate of 2.0 Gy/min. Lymphocytes were concentrated, cultured and harvested at 52 h, 68 h and 72 h. The numbers of dic + r were counted. The dose-effect curves were established and validated using comparisons with doses from the Tokai-mura accident and were then applied to two victims of supra-high dose exposure accident. The results indicated that there were no significant differences in chromosome aberration frequency among the different culture times from 52 h to 72 h. The 6-22 Gy dose-effect curve was fitted to a linear quadratic model Y = -2.269 + 0.776D - 7.868 x l0 -3 D 2 . Using this mathematic model, the dose estimates were similar to data from Tokai-mura which were estimated by PCC ring. Whole body average doses of 9.7 Gy and 18.1 Gy for two victims in the Jining accident were satisfactorily given. We established and successfully applied a new dose-effect curve of chromosomal dicentrics plus ring (dic + r) after 6-22 Gy γ-irradiation from a supra-high dose 60 Co gamma-ray accident.

Reducing the radiation dose to the eye lens region during CT brain examination: the potential beneficial effect of the combined use of bolus and a bismuth shield

International Nuclear Information System (INIS)

Lai, C.W.K.; Chan, T.P.; Cheung, H.Y.; Wong, T.H.

2015-01-01

Objective: Computed Tomography (CT) is the leading contributor to medical exposure to ionizing radiation. Although the use of CT brain scans for patients with head injuries and convulsions has shown a tremendous growth, it has raised substantial concerns in the general public because of the risk of radiation-induced cataracts: the current available strategies to reduce the radiation dose to the eye lens region are limited. Therefore, the present research project was initiated with the aim of evaluating the potential benefit of the combined use of bolus and a bismuth shield on reducing the radiation dose to the eye lens region during CT brain examination. Materials and methods: We conducted a series of phantom studies to measure the entrance surface dose (ESD) that is delivered to the eye lens region during CT brain examination under the effect of different scanning and shielding setups. Results: Our results indicated, during CT brain examination: (1) a drastic reduction of 92.5% in the ESD to the eye lens region was found when the CT gantry was tilted from 0 deg. (overall ESD = 30.7 mGy) to 30 deg. cranially (overall ESD = 2.4 mGy), and (2) when the CT gantry was positioned at 0 deg. (the common practice in the clinical setting), the setups with the application of a) a bismuth shield, b) a bismuth shield with a face shield (air gap), c) a bismuth shield with bolus, and d) a bismuth shield with bolus and an air gap can result in an acceptable level of image quality with a smaller overall ESD delivered to the eye lens region (overall ESD = 23.2 mGy, 24 mGy, 21 mGy and 19.9 mGy, respectively) than the setup without the bismuth shield applied (overall ESD = 30.7 mGy). Conclusion: When the primary beam scanning through the eye lens region is unavoidable during CT brain examination, the combined use of a bismuth shield with bolus and a face shield is an easy-to-use and inexpensive shielding setup to reduce the radiation dose delivered to the eye lens region while

Fast in vivo volume dose reconstruction via reference dose perturbation

International Nuclear Information System (INIS)

Lu, Weiguo; Chen, Mingli; Mo, Xiaohu; Parnell, Donald; Olivera, Gustavo; Galmarini, Daniel

2014-01-01

Purpose: Accurate on-line reconstruction of in-vivo volume dose that accounts for both machine and patient discrepancy is not clinically available. We present a simple reference-dose-perturbation algorithm that reconstructs in-vivo volume dose fast and accurately. Methods: We modelled the volume dose as a function of the fluence map and density image. Machine (output variation, jaw/leaf position errors, etc.) and patient (setup error, weight loss, etc.) discrepancies between the plan and delivery were modelled as perturbation of the fluence map and density image, respectively. Delivered dose is modelled as perturbation of the reference dose due to change of the fluence map and density image. We used both simulated and clinical data to validate the algorithm. The planned dose was used as the reference. The reconstruction was perturbed from the reference and accounted for output-variations and the registered daily image. The reconstruction was compared with the ground truth via isodose lines and the Gamma Index. Results: For various plans and geometries, the volume doses were reconstructed in few seconds. The reconstruction generally matched well with the ground truth. For the 3%/3mm criteria, the Gamma pass rates were 98% for simulations and 95% for clinical data. The differences mainly appeared on the surface of the phantom/patient. Conclusions: A novel reference-dose-perturbation dose reconstruction model is presented. The model accounts for machine and patient discrepancy from planning. The algorithm is simple, fast, yet accurate, which makes online in-vivo 3D dose reconstruction clinically feasible.

Estimation of the transit dose component in high dose rate brachytherapy

International Nuclear Information System (INIS)

Garcia Romero, A.; Millan Cebrian, E.; Lozano Flores, F.J.; Lope Lope, R.; Canellas Anoz, M.

2001-01-01

Current high dose rate brachytherapy (HDR) treatment planning systems usually calculate dose only from source stopping positions (stationary component), but fails to account for the administered dose when the source is moving (dynamic component or transit dose). Numerical values of this transit dose depends upon the source velocity, implant geometry, source activity and prescribed dose. In some HDR treatments using particular geometry the transit dose cannot be ignored because it increases the dose at the prescriptions points and also could increase potential late tissue complications as predicted by the linear quadratic model. International protocols recommend to verify this parameter. The aim of this paper has been to establish a procedure for the transit dose calculation for the Gammamed 12i equipment at the RT Department in the Clinical University Hospital (Zaragoza-Spain). A numeric algorithm was implemented based on a dynamic point approximation for the moving HDR source and the calculated results for the entrance-exit transit dose was compared with TLD measurements made in some discrete points. (author) [es

The effect of exogenous GM1 ganglioside on kindled-amygdaloid seizures.

Science.gov (United States)

Albertson, T E; Walby, W F

1987-01-01

The effects of 12 daily doses of 30 mg/kg GM1 ganglioside i.p. on the acquisition of kindled-amygdaloid seizures in the rat was studied. No modification in the rate of kindling or the expression of the elicited seizures was noted during the acquisition phase. Further studies with additional fully amygdaloid kindled rats failed to show significant modification of suprathreshold or threshold elicited seizures after single 30-60 mg/kg i.p. doses of GM1 ganglioside. Despite previous studies which have shown antibodies to GM1 ganglioside to be convulsive, no anticonvulsant activity was demonstrated in this study with exogenous GM1 ganglioside using a battery of kindled-amygdaloid seizure tests in the rat.

Effective dose and dose to crystalline lens during angiographic procedures

International Nuclear Information System (INIS)

Pages, J.

1998-01-01

The highest radiation doses levels received by radiologists are observed during interventional procedures. Doses to forehead and neck received by a radiologist executing angiographic examinations at the department of radiology at the academic hospital (AZ-VUB) have been measured for a group of 34 examinations. The doses to crystalline lens and the effective doses for a period of one year have been estimated. For the crystalline lens the maximum dose approaches the ICRP limit, that indicates the necessity for the radiologist to use leaded glasses. (N.C.)

Studies on neuropharmacological profile of ethanol extract of Moringa oleifera leaves in mice.

Science.gov (United States)

Bakre, Adewale G; Aderibigbe, Adegbuyi O; Ademowo, Olusegun G

2013-10-07

Moringa oleifera (family Moringaceae), commonly called Horseradish or tree of life, is traditionally used for the treatment of epilepsy and neurologic conditions. The objective of this study is to investigate the neurobehavioural and anticonvulsant properties of the ethanol extract from the leaves of Moringa oleifera. Neurobehavioural properties were evaluated using the open field, hole board, Y-maze, elevated plus maze (EPM) and pentobarbitone-induced hypnosis. Pentylenetetrazole (leptazol), picrotoxin and strychnine induced convulsion tests were used to investigate the anti-convulsive actions of Moringa oleifera. The result showed that the extract (250-2000mg/kg) caused a significant dose-dependent decrease in rearing, grooming, head dips and locomotion (P6.4g/kg. The findings from this study suggest that the ethanol extract of Moringa oleifera leaves possesses CNS depressant and anticonvulsant activities possibly mediated through the enhancement of central inhibitory mechanism involving release γ-amino butyric acid (GABA). The results partially justified the traditional use of the extract for the treatment of epilepsy. © 2013 Elsevier Ireland Ltd. All rights reserved.

Induration at Injection or Infusion Site May Reduce Bioavailability of Parenteral Phenobarbital Administration.

Science.gov (United States)

Nakayama, Hirokazu; Echizen, Hirotoshi; Ogawa, Ryuichi; Akabane, Atsuya; Kato, Toshiaki; Orii, Takao

2017-06-01

Phenobarbital is well tolerated and effective for controlling agitation or preventing convulsion at the end of life. No information is available concerning parenteral bioavailability of phenobarbital when induration develops at the injection or infusion site. We investigated whether induration at injection or infusion site is related to phenobarbital bioavailability via parenteral routes of continuous subcutaneous infusion and intermittent subcutaneous or intramuscular injection. A retrospective analysis was conducted on the medical data obtained from 18 patients who received chronic subcutaneous or intramuscular injections of phenobarbital for the prevention of convulsions and underwent plasma concentration monitoring of the drug. Patients whose concomitant medications were altered during the observation periods were excluded from the analysis. Comparisons were performed for concentration/dose (C/D) ratios obtained from patients with induration at injection or infusion sites (induration group, n = 6) and those without induration (noninduration group, n = 12). P phenobarbital may be reduced when induration develops at the injection or infusion site in patients treated parenterally by continuous subcutaneous infusion or intramuscular injection.

Prescribing and evaluating target dose in dose-painting treatment plans

DEFF Research Database (Denmark)

Håkansson, Katrin; Specht, Lena; Aznar, Marianne C

2014-01-01

BACKGROUND: Assessment of target dose conformity in multi-dose-level treatment plans is challenging due to inevitable over/underdosage at the border zone between dose levels. Here, we evaluate different target dose prescription planning aims and approaches to evaluate the relative merit of such p......-painting and multi-dose-level plans. The tool can be useful for quality assurance of multi-center trials, and for visualizing the development of treatment planning in routine clinical practice....... of such plans. A quality volume histogram (QVH) tool for history-based evaluation is proposed. MATERIAL AND METHODS: Twenty head and neck cancer dose-painting plans with five prescription levels were evaluated, as well as clinically delivered simultaneous integrated boost (SIB) plans from 2010 and 2012. The QVH...

Structural and Functional Elucidation of Yeast Lanosterol 14α-Demethylase in Complex with Agrochemical Antifungals

Science.gov (United States)

Sagatova, Alia A.; Keniya, Mikhail V.; Negroni, Jacopo; Wilson, Rajni K.; Woods, Matthew A.; Monk, Brian C.

2016-01-01

Azole antifungals, known as demethylase inhibitors (DMIs), target sterol 14α-demethylase (CYP51) in the ergosterol biosynthetic pathway of fungal pathogens of both plants and humans. DMIs remain the treatment of choice in crop protection against a wide range of fungal phytopathogens that have the potential to reduce crop yields and threaten food security. We used a yeast membrane protein expression system to overexpress recombinant hexahistidine-tagged S. cerevisiae lanosterol 14α-demethylase and the Y140F or Y140H mutants of this enzyme as surrogates in order characterize interactions with DMIs. The whole-cell antifungal activity (MIC50 values) of both the R- and S-enantiomers of tebuconazole, prothioconazole (PTZ), prothioconazole-desthio, and oxo-prothioconazole (oxo-PTZ) as well as for fluquinconazole, prochloraz and a racemic mixture of difenoconazole were determined. In vitro binding studies with the affinity purified enzyme were used to show tight type II binding to the yeast enzyme for all compounds tested except PTZ and oxo-PTZ. High resolution X-ray crystal structures of ScErg11p6×His in complex with seven DMIs, including four enantiomers, reveal triazole-mediated coordination of all compounds and the specific orientation of compounds within the relatively hydrophobic binding site. Comparison with CYP51 structures from fungal pathogens including Candida albicans, Candida glabrata and Aspergillus fumigatus provides strong evidence for a highly conserved CYP51 structure including the drug binding site. The structures obtained using S. cerevisiae lanosterol 14α-demethylase in complex with these agrochemicals provide the basis for understanding the impact of mutations on azole susceptibility and a platform for the structure-directed design of the next-generation of DMIs. PMID:27907120

Isobio software: biological dose distribution and biological dose volume histogram from physical dose conversion using linear-quadratic-linear model.

Science.gov (United States)

Jaikuna, Tanwiwat; Khadsiri, Phatchareewan; Chawapun, Nisa; Saekho, Suwit; Tharavichitkul, Ekkasit

2017-02-01

To develop an in-house software program that is able to calculate and generate the biological dose distribution and biological dose volume histogram by physical dose conversion using the linear-quadratic-linear (LQL) model. The Isobio software was developed using MATLAB version 2014b to calculate and generate the biological dose distribution and biological dose volume histograms. The physical dose from each voxel in treatment planning was extracted through Computational Environment for Radiotherapy Research (CERR), and the accuracy was verified by the differentiation between the dose volume histogram from CERR and the treatment planning system. An equivalent dose in 2 Gy fraction (EQD 2 ) was calculated using biological effective dose (BED) based on the LQL model. The software calculation and the manual calculation were compared for EQD 2 verification with pair t -test statistical analysis using IBM SPSS Statistics version 22 (64-bit). Two and three-dimensional biological dose distribution and biological dose volume histogram were displayed correctly by the Isobio software. Different physical doses were found between CERR and treatment planning system (TPS) in Oncentra, with 3.33% in high-risk clinical target volume (HR-CTV) determined by D 90% , 0.56% in the bladder, 1.74% in the rectum when determined by D 2cc , and less than 1% in Pinnacle. The difference in the EQD 2 between the software calculation and the manual calculation was not significantly different with 0.00% at p -values 0.820, 0.095, and 0.593 for external beam radiation therapy (EBRT) and 0.240, 0.320, and 0.849 for brachytherapy (BT) in HR-CTV, bladder, and rectum, respectively. The Isobio software is a feasible tool to generate the biological dose distribution and biological dose volume histogram for treatment plan evaluation in both EBRT and BT.

Patient dose measurement and dose reduction in chest radiography

Directory of Open Access Journals (Sweden)

Milatović Aleksandra A.

2014-01-01

Full Text Available Investigations presented in this paper represent the first estimation of patient doses in chest radiography in Montenegro. In the initial stage of our study, we measured the entrance surface air kerma and kerma area product for chest radiography in five major health institutions in the country. A total of 214 patients were observed. We reported the mean value, minimum and third quartile values, as well as maximum values of surface air kerma and kerma area product of patient doses. In the second stage, the possibilities for dose reduction were investigated. Mean kerma area product values were 0.8 ± 0.5 Gycm2 for the posterior-anterior projection and 1.6 ± 0.9 Gycm2 for the lateral projection. The max/min ratio for the entrance surface air kerma was found to be 53 for the posterior-anterior projection and 88 for the lateral projection. Comparing the results obtained in Montenegro with results from other countries, we concluded that patient doses in our medical centres are significantly higher. Changes in exposure parameters and increased filtration contributed to a dose reduction of up to 36% for posterior-anterior chest examinations. The variability of the estimated dose values points to a significant space for dose reduction throughout the process of radiological practice optimisation.

Experimental evaluation of neutron dose in radiotherapy patients: Which dose?

Energy Technology Data Exchange (ETDEWEB)

Romero-Expósito, M., E-mail: mariateresa.romero@uab.cat; Domingo, C.; Ortega-Gelabert, O.; Gallego, S. [Grup de Recerca en Radiacions Ionizants (GRRI), Departament de Física, Universitat Autònoma de Barcelona, Bellaterra 08193 (Spain); Sánchez-Doblado, F. [Departamento de Fisiología Médica y Biofísica, Universidad de Sevilla, Sevilla 41009 (Spain); Servicio de Radiofísica, Hospital Universitario Virgen Macarena, Sevilla 41009 (Spain)

2016-01-15

Purpose: The evaluation of peripheral dose has become a relevant issue recently, in particular, the contribution of secondary neutrons. However, after the revision of the Recommendations of the International Commission on Radiological Protection, there has been a lack of experimental procedure for its evaluation. Specifically, the problem comes from the replacement of organ dose equivalent by the organ-equivalent dose, being the latter “immeasurable” by definition. Therefore, dose equivalent has to be still used although it needs the calculation of the radiation quality factor Q, which depends on the unrestricted linear energy transfer, for the specific neutron irradiation conditions. On the other hand, equivalent dose is computed through the radiation weighting factor w{sub R}, which can be easily calculated using the continuous function provided by the recommendations. The aim of the paper is to compare the dose equivalent evaluated following the definition, that is, using Q, with the values obtained by replacing the quality factor with w{sub R}. Methods: Dose equivalents were estimated in selected points inside a phantom. Two types of medical environments were chosen for the irradiations: a photon- and a proton-therapy facility. For the estimation of dose equivalent, a poly-allyl-diglicol-carbonate-based neutron dosimeter was used for neutron fluence measurements and, additionally, Monte Carlo simulations were performed to obtain the energy spectrum of the fluence in each point. Results: The main contribution to dose equivalent comes from neutrons with energy higher than 0.1 MeV, even when they represent the smallest contribution in fluence. For this range of energy, the radiation quality factor and the radiation weighting factor are approximately equal. Then, dose equivalents evaluated using both factors are compatible, with differences below 12%. Conclusions: Quality factor can be replaced by the radiation weighting factor in the evaluation of dose

Health effect of low dose/low dose rate radiation

International Nuclear Information System (INIS)

Kodama, Seiji

2012-01-01

The clarified and non-clarified scientific knowledge is discussed to consider the cause of confusion of explanation of the title subject. The low dose is defined roughly lower than 200 mGy and low dose rate, 0.05 mGy/min. The health effect is evaluated from 2 aspects of clinical symptom/radiation hazard protection. In the clinical aspect, the effect is classified in physical (early and late) and genetic ones, and is classified in stochastic (no threshold value, TV) and deterministic (with TV) ones from the radioprotection aspect. Although the absence of TV in the carcinogenic and genetic effects has not been proved, ICRP employs the stochastic standpoint from the safety aspect for radioprotection. The lowest human TV known now is 100 mGy, meaning that human deterministic effect would not be generated below this dose. Genetic deterministic effect can be observable only in animal experiments. These facts suggest that the practical risk of exposure to <100 mGy in human is the carcinogenesis. The relationship between carcinogenic risk in A-bomb survivors and their exposed dose are found fitted to the linear no TV model, but the epidemiologic data, because of restriction of subject number analyzed, do not always mean that the model is applicable even below the dose <100 mGy. This would be one of confusing causes in explanation: no carcinogenic risk at <100 mGy or risk linear to dose even at <100 mGy, neither of which is scientifically conclusive at present. Also mentioned is the scarce risk of cancer in residents living in the high background radiation regions in the world in comparison with that in the A-bomb survivors exposed to the chronic or acute low dose/dose rate. Molecular events are explained for the low-dose radiation-induced DNA damage and its repair, gene mutation and chromosome aberration, hypothesis of carcinogenesis by mutation, and non-targeting effect of radiation (bystander effect and gene instability). Further researches to elucidate the low dose

Analysis of Cumulative Dose to Implanted Pacemaker According to Various IMRT Delivery Methods: Optimal Dose Delivery Versus Dose Reduction Strategy

Energy Technology Data Exchange (ETDEWEB)

Lee, Jeong Woo; Hong, Se Mie [Dept. of Radiation Oncology, Konkuk University Medical Center, Seoul (Korea, Republic of)

2011-11-15

Cancer patients with implanted cardiac pacemaker occasionally require radiotherapy. Pacemaker may be damaged or malfunction during radiotherapy due to ionizing radiation or electromagnetic interference. Although radiotherapy should be planned to keep the dose to pacemaker as low as possible not to malfunction ideally, current radiation treatment planning (RTP) system does not accurately calculate deposited dose to adjacent field border or area beyond irradiated fields. In terms of beam delivery techniques using multiple intensity modulated fields, dosimetric effect of scattered radiation in high energy photon beams is required to be detailed analyzed based on measurement data. The aim of this study is to evaluate dose discrepancies of pacemaker in a RTP system as compared to measured doses. We also designed dose reduction strategy limited value of 2 Gy for radiation treatment patients with cardiac implanted pacemaker. Total accumulated dose of 145 cGy based on in-vivo dosimetry was satisfied with the recommendation criteria to prevent malfunction of pacemaker in SS technique. However, the 2 mm lead shielder enabled the scattered doses to reduce up to 60% and 40% in the patient and the phantom, respectively. The SS technique with the lead shielding could reduce the accumulated scattered doses less than 100 cGy. Calculated and measured doses were not greatly affected by the beam delivery techniques. In-vivo and measured doses on pacemaker position showed critical dose discrepancies reaching up to 4 times as compared to planned doses in RTP. The current SS technique could deliver lower scattered doses than recommendation criteria, but use of 2 mm lead shielder contributed to reduce scattered doses by 60%. The tertiary lead shielder can be useful to prevent malfunction or electrical damage of implanted pacemakers during radiotherapy. It is required to estimate more accurate scattered doses of the patient or medical device in RTP to design proper dose reduction strategy.

Analysis of Cumulative Dose to Implanted Pacemaker According to Various IMRT Delivery Methods: Optimal Dose Delivery Versus Dose Reduction Strategy

International Nuclear Information System (INIS)

Lee, Jeong Woo; Hong, Se Mie

2011-01-01

Cancer patients with implanted cardiac pacemaker occasionally require radiotherapy. Pacemaker may be damaged or malfunction during radiotherapy due to ionizing radiation or electromagnetic interference. Although radiotherapy should be planned to keep the dose to pacemaker as low as possible not to malfunction ideally, current radiation treatment planning (RTP) system does not accurately calculate deposited dose to adjacent field border or area beyond irradiated fields. In terms of beam delivery techniques using multiple intensity modulated fields, dosimetric effect of scattered radiation in high energy photon beams is required to be detailed analyzed based on measurement data. The aim of this study is to evaluate dose discrepancies of pacemaker in a RTP system as compared to measured doses. We also designed dose reduction strategy limited value of 2 Gy for radiation treatment patients with cardiac implanted pacemaker. Total accumulated dose of 145 cGy based on in-vivo dosimetry was satisfied with the recommendation criteria to prevent malfunction of pacemaker in SS technique. However, the 2 mm lead shielder enabled the scattered doses to reduce up to 60% and 40% in the patient and the phantom, respectively. The SS technique with the lead shielding could reduce the accumulated scattered doses less than 100 cGy. Calculated and measured doses were not greatly affected by the beam delivery techniques. In-vivo and measured doses on pacemaker position showed critical dose discrepancies reaching up to 4 times as compared to planned doses in RTP. The current SS technique could deliver lower scattered doses than recommendation criteria, but use of 2 mm lead shielder contributed to reduce scattered doses by 60%. The tertiary lead shielder can be useful to prevent malfunction or electrical damage of implanted pacemakers during radiotherapy. It is required to estimate more accurate scattered doses of the patient or medical device in RTP to design proper dose reduction strategy.

Dose-reduction techniques for high-dose worker groups in nuclear power plants

International Nuclear Information System (INIS)

Khan, T.A.; Baum, J.W.; Dionne, B.J.

1991-03-01

This report summarizes the main findings of a study of the extent of radiation dose received by special work groups in the nuclear power industry. Work groups which chronically get large doses were investigated, using information provided by the industry. The tasks that give high doses to these work groups were examined and techniques described that were found to be particularly successful in reducing dose. Quantitative information on the extent of radiation doses to various work groups shows that significant numbers of workers in several critical groups receive doses greater than 1 and even 2 rem per year, particularly contract personnel and workers at BWR-type plants. The number of radiation workers whose lifetime dose is greater than their age is much less. Although the techniques presented would go some way in reducing dose, it is likely that a sizeable reduction to the high-dose work groups may require development of new dose-reduction techniques as well as major changes in procedures. 10 refs., 26 tabs

Analysis of workers' dose records from the Greek Dose Registry Information System

International Nuclear Information System (INIS)

Kamenopoulou, V.; Dimitriou, P.; Proukakis, Ch.

1995-01-01

The object of this work is the study of the individual film badge annual dose information of classified workers in Greece, monitored and assessed by the central dosimetry service of the Greek Atomic Energy Commission. Dose summaries were recorded and processed by the Dose Registry Information System. The statistical analysis refers to the years 1989-93 and deals with the distribution of individuals in the occupational groups, the mean annual dose, the collective dose, the distribution of the dose over the different specialties and the number of workers that have exceeded any of the established dose limits. Results concerning the annual dose summaries, demonstrate a year-by-year reduction in the mean individual dose to workers in the health sector. Conversely, exposures in the industrial sector did not show any decreasing tendency during the period under consideration. (Author)

Neurotoxic lesions of the pedunculopontine tegmental nucleus impair the elaboration of postictal antinociception.

Science.gov (United States)

de Oliveira, Rithiele Cristina; de Oliveira, Ricardo; Falconi-Sobrinho, Luiz Luciano; Biagioni, Audrey Franceschi; Almada, Rafael Carvalho; Dos Anjos-Garcia, Tayllon; Bazaglia-de-Sousa, Guilherme; Khan, Asmat Ullah; Coimbra, Norberto Cysne

2018-05-12

Generalised tonic-clonic seizures, generated by abnormal neuronal hyper-activity, cause a significant and long-lasting increase in the nociceptive threshold. The pedunculopontine tegmental nucleus (PPTN) plays a crucial role in the regulation of seizures as well as the modulation of pain, but its role in postictal antinociceptive processes remains unclear. In the present study, we aimed to investigate the involvement of PPTN neurons in the postictal antinociception. Wistar rats had their tail-flick baseline recorded and were injected with ibotenic acid (1.0 μg/0.2 μL) into the PPTN, aiming to promote a local neurotoxic lesion. Five days after the neuronal damage, pentylenetetrazole (PTZ; 64 mg/kg) was intraperitoneally administered to induce tonic-clonic seizures. The tail-withdrawal latency was measured immediately after the seizures (0 min) and subsequently at 10-min intervals until 130 min after the seizures were induced pharmacologically. Ibotenic acid microinjected into the PPTN did not reduce the PTZ-induced seizure duration and severity, but it diminished the postictal antinociception from 0 to 130 min after the end of the PTZ-induced tonic-clonic seizures. These results suggest that the postictal antinociception depends on the PPTN neuronal cells integrity. Copyright © 2018 Elsevier Inc. All rights reserved.

Agmatine reduces extracellular glutamate during pentylenetetrazole-induced seizures in rat brain: A potential mechanism for the anticonvulsive effects

Science.gov (United States)

Feng, Yangzheng; LeBlanc, Michael H.; Regunathan, Soundar

2010-01-01

Glutamate has been implicated in the initiation and spread of seizure activity. Agmatine, an endogenous neuromodulator, is an antagonist of NMDA receptors and has anticonvulsive effects. Whether agmatine regulate glutamate release, as measured by in vivo microdialysis, is not known. In this study, we used pentylenetetrazole (PTZ)-induced seizure model to determine the effect of agmatine on extracellular glutamate in rat brain. We also determined the time course and the amount of agmatine that reached brain after peripheral injection. After i.p. injection of agmatine (50 mg/kg), increase of agmatine in rat cortex and hippocampus was observed in 15 min with levels returning to baseline in one hour. Rats, naïve and implanted with microdialysis cannula into the cortex, were administered PTZ (60 mg/kg, i.p.) with prior injection of agmatine (100 mg/kg, i.p.) or saline. Seizure grades were recorded and microdialysis samples were collected every 15 min for 75 min. Agmatine pre-treatment significantly reduced the seizure grade and increased the onset time. The levels of extracellular glutamate in frontal cortex rose two- to three-fold after PTZ injection and agmatine significantly inhibited this increase. In conclusion, the present data suggest that the anticonvulsant activity of agmatine, in part, could be related to the inhibition glutamate release. PMID:16125317

Dose from radiological examinations

International Nuclear Information System (INIS)

Imamura, Keiko; Uji, Teruyuki; Sakuyama, Keiko; Fujikawa, Mitsuhiro; Fujii, Masamichi

1976-01-01

Relatively high gonad doses, several hundred to one thousand mR, have been observed in case of pelvis, hip-joint, coccyx, lower abdomen and lumber examination. Dose to the ovary is especially high in barium enema and I.V.P. examinations. About 12 per cent of the 4-ray examination are high-dose. The gonad dose is relatively high in examination of abdomen and lower extremities, in infants. The dose to the eyes is especially high, 1.0 to 2.5R per exposure, in temporal bone and nasal sinuses tomography. X-ray doses have been compared with dose limits recommended by ICRP and with the gonad dose from natural radiations. The gonad dose in lumbar examination, barium enema, I.V.P. etc. is as high as the maximum permissible dose per year recommended by ICRP. Several devices have been made for dose reduction in the daily examinations: (1) separating the radiation field from the gonad by one centimeter decreases the gonad dose about one-half. (2) using sensitive screens and films. In pelvimetry and in infant hip-joint examination, the most sensitive screen and film are used. In the I.V.P. examination of adult, use of MS screen in place of FS screen decreases the dose to one-third, in combination with careful setting of radiation field, (3) use of grid increases the dose about 50 percent and the lead rubber protection (0.1mm lead equivalent) decreases the gonad dose to one-thirtieth in the spinal column examination of infant, (4) A lead protector, 1mm thickness and 2.5cm in diameter, on the eyes decreases the dose to about one-eighth in the face and nead examinations. These simple and effective methods for dose reduction. Should be carried out in as many examinations as possible in addition to observing dose limits recommended by ICRP. (Evans, J.)

Body friendly, safe and effective regimen of MgSO4 for eclampsia

Directory of Open Access Journals (Sweden)

Gautam S. Aher, Urmila Gavali

2013-01-01

Full Text Available Pre-eclampsia and eclampsia are major health problems in developing countries. MgSO4 is the standard drug in the control of convulsions in eclampsia. Our study carried out at PDVVPF’s hospital is based on the low dose regimen than Pritchard, which is suitable for Indian women who are of smaller built thanwomen in western world. This prospective study included 50 eclampsia patients receiving low dose MgSO4 therapy. The loading dose of MgSO4 was 9gm. Following this 2.5 gm was given intramuscularly every 6 hourly for 24 hours after administration of the loading dose. Patients were monitored hourly by observing their respiratory rate, knee jerk and urine output. Out of 50, two patients required Pritchard regimen, rest completely recovered from eclampsia. The maternal and perinatal morbidity and mortality were comparable to those of the standard Pritchard regime. The study did not find a single case of magnesium related toxicity with low dose MgSO4 regime. Low dose magnesium sulphate regime was found to be safe and effective in eclampsia

Dose conversion factors

International Nuclear Information System (INIS)

Kocher, D.C.; Eckerman, K.F.

1992-01-01

The following is discussed in this report: concepts and quantities used in calculating radiation dose from internal and external exposure. Tabulations of dose conversion factor for internal and external exposure to radionuclides. Dose conversion factors give dose per unit intake (internal) or dose per unit concentration in environment (external). Intakes of radionuclides for internal exposure and concentrations of radionuclides in environment for external exposure are assumed to be known. Intakes and concentrations are obtained, e.g., from analyses of environmental transport and exposure pathways. differences between dosimetry methods for radionuclides and hazardous chemicals are highlighted

Changes in mouse brain metabolism following a convulsive dose of soman: A proton HRMAS NMR study

Energy Technology Data Exchange (ETDEWEB)

Fauvelle, F. [Unite de Biophysique Cellulaire et Moleculaire, Institut de Recherche Biomedicale des Armees, Centre de Recherches du Service Sante des Armees, BP87, 38 702 La Tronche Cedex (France); Dorandeu, F.; Carpentier, P.; Foquin, A. [Departement de Toxicologie, Institut de Recherche Biomedicale des Armees, Centre de Recherches du Service Sante des Armees, 24 avenue des Maquis du Gresivaudan, BP87, 38 702 La Tronche Cedex (France); Rabeson, H.; Graveron-Demilly, D. [Universite Lyon 1, Laboratoire Creatis-LRMN, CNRS UMR 5220, INSERM U630, INSA de Lyon (France); Arvers, P. [Unite de Biophysique Cellulaire et Moleculaire, Institut de Recherche Biomedicale des Armees, Centre de Recherches du Service Sante des Armees, BP87, 38 702 La Tronche Cedex (France); Testylier, G., E-mail: guytestylier@crssa.net [Departement de Toxicologie, Institut de Recherche Biomedicale des Armees, Centre de Recherches du Service Sante des Armees, 24 avenue des Maquis du Gresivaudan, BP87, 38 702 La Tronche Cedex (France)

2010-01-12

Soman, an irreversible organophosphorus cholinesterase inhibitor, induces status epilepticus and, in sensitive brain areas, seizure-related brain damage (e.g. brain edema and neuronal loss). The brain metabolic disturbances associated with these events are ill known. In the present study, we thus evaluated these changes in a murine model of soman-induced status epilepticus up to 7 days after intoxication. Mice, protected by HI-6 and atropine methyl nitrate, were poisoned with soman (172 μg/kg) and then sacrificed at set time points, from 1 h to 7 days. Brain biopsies from the piriform cortex (Pir) and cerebellum (Cer) were analyzed by {sup 1}H HRMAS NMR spectroscopy. Spectra were then analyzed using both a supervised multivariate analysis and the QUEST procedure of jMRUI for the quantification of 17 metabolites. The multivariate analysis clearly showed the metabolic differences between a damaged structure (Pir) and a structure with less prominent changes (cerebellum) and helped to globally assess the time course of metabolic changes. Analysis of the individual metabolites showed that the major changes took place in the piriform cortex but that cerebellum was not change-free. The most prominent changes in the former were an early (1-4 h) increase in alanine and acetate, a delayed increase in lactate, glycerophosphocholine and glutamine as well as a delayed decrease in myo-inositol and N-acetylaspartate. A week after poisoning, some metabolic disturbances were still present. Further research will be necessary to clarify what could be the involvement of these metabolites in physiological processes and how they might become useful surrogate markers of brain damage and repair.

Changes in mouse brain metabolism following a convulsive dose of soman: A proton HRMAS NMR study

International Nuclear Information System (INIS)

Fauvelle, F.; Dorandeu, F.; Carpentier, P.; Foquin, A.; Rabeson, H.; Graveron-Demilly, D.; Arvers, P.; Testylier, G.

2010-01-01

Soman, an irreversible organophosphorus cholinesterase inhibitor, induces status epilepticus and, in sensitive brain areas, seizure-related brain damage (e.g. brain edema and neuronal loss). The brain metabolic disturbances associated with these events are ill known. In the present study, we thus evaluated these changes in a murine model of soman-induced status epilepticus up to 7 days after intoxication. Mice, protected by HI-6 and atropine methyl nitrate, were poisoned with soman (172 μg/kg) and then sacrificed at set time points, from 1 h to 7 days. Brain biopsies from the piriform cortex (Pir) and cerebellum (Cer) were analyzed by 1 H HRMAS NMR spectroscopy. Spectra were then analyzed using both a supervised multivariate analysis and the QUEST procedure of jMRUI for the quantification of 17 metabolites. The multivariate analysis clearly showed the metabolic differences between a damaged structure (Pir) and a structure with less prominent changes (cerebellum) and helped to globally assess the time course of metabolic changes. Analysis of the individual metabolites showed that the major changes took place in the piriform cortex but that cerebellum was not change-free. The most prominent changes in the former were an early (1-4 h) increase in alanine and acetate, a delayed increase in lactate, glycerophosphocholine and glutamine as well as a delayed decrease in myo-inositol and N-acetylaspartate. A week after poisoning, some metabolic disturbances were still present. Further research will be necessary to clarify what could be the involvement of these metabolites in physiological processes and how they might become useful surrogate markers of brain damage and repair.

Radiation dose in cardiac SPECT/CT: An estimation of SSDE and effective dose

International Nuclear Information System (INIS)

Abdollahi, Hamid; Shiri, Isaac; Salimi, Yazdan; Sarebani, Maghsoud; Mehdinia, Reza; Deevband, Mohammad Reza; Mahdavi, Seied Rabi; Sohrabi, Ahmad; Bitarafan-Rajabi, Ahmad

2016-01-01

Aims: The dose levels for Computed Tomography (CT) localization and attenuation correction of Single Photon Emission Computed Tomography (SPECT) are limited and reported as Volume Computed Tomography Dose Index (CTDIvol) and Dose-Length Product (DLP). This work presents CT dose estimation from Cardiac SPECT/CT based on new American Association of Physicists in Medicine (AAPM) Size Specific Dose Estimation (SSDE) parameter, effective dose, organ doses and also emission dose from nuclear issue. Material and methods: Myocardial perfusion SPECT/CT for 509 patients was included in the study. SSDE, effective dose and organ dose were calculated using AAPM guideline and Impact-Dose software. Data were analyzed using R and SPSS statistical software. Spearman-Pearson correlation test and linear regression models were used for finding correlations and relationships among parameters. Results: The mean CTDIvol was 1.34 mGy ± 0.19 and the mean SSDE was 1.7 mGy ± 0.16. The mean ± SD of effective dose from emission, CT and total dose were 11.5 ± 1.4, 0.49 ± 0.11 and 12.67 ± 1.73 (mSv) respectively. The mean ± SD of effective dose from emission, CT and total dose were 11.5 ± 1.4, 0.49 ± 0.11 and 12.67 ± 1.73 (mSv) respectively. The spearman test showed that correlation between body size and organ doses is significant except thyroid and red bone marrow. CTDIvol was strongly dependent on patient size, but SSDE was not. Emission dose was strongly dependent on patient weight, but its dependency was lower to effective diameter. Conclusion: The dose parameters including CTDIvol, DLP, SSDE, effective dose values reported here are very low and below the reference level. This data suggest that appropriate CT acquisition parameters in SPECT/CT localization and attenuation correction are very beneficial for patients and lowering cancer risks.

Radiation dose in cardiac SPECT/CT: An estimation of SSDE and effective dose

Energy Technology Data Exchange (ETDEWEB)

Abdollahi, Hamid, E-mail: Hamid_rbp@yahoo.com [Department of Medical Physics, School of Medicine, Iran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Shiri, Isaac [Department of Medical Physics, School of Medicine, Iran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Salimi, Yazdan [Biomedical Engineering and Medical Physics Department, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran (Iran, Islamic Republic of); Sarebani, Maghsoud; Mehdinia, Reza [Department of Medical Physics, School of Medicine, Iran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Deevband, Mohammad Reza [Biomedical Engineering and Medical Physics Department, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran (Iran, Islamic Republic of); Mahdavi, Seied Rabi [Department of Medical Physics, School of Medicine, Iran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Radiation Biology Research Center, Iran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Sohrabi, Ahmad [Department of Biostatistics, School of Public Health, Iran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Bitarafan-Rajabi, Ahmad, E-mail: bitarafan@hotmail.com [Department of Medical Physics, School of Medicine, Iran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Department of Nuclear Medicine, Rajaei Cardiovascular, Medical and Research Center, Iran University of Medical Sciences, Tehran (Iran, Islamic Republic of)

2016-12-15

Aims: The dose levels for Computed Tomography (CT) localization and attenuation correction of Single Photon Emission Computed Tomography (SPECT) are limited and reported as Volume Computed Tomography Dose Index (CTDIvol) and Dose-Length Product (DLP). This work presents CT dose estimation from Cardiac SPECT/CT based on new American Association of Physicists in Medicine (AAPM) Size Specific Dose Estimation (SSDE) parameter, effective dose, organ doses and also emission dose from nuclear issue. Material and methods: Myocardial perfusion SPECT/CT for 509 patients was included in the study. SSDE, effective dose and organ dose were calculated using AAPM guideline and Impact-Dose software. Data were analyzed using R and SPSS statistical software. Spearman-Pearson correlation test and linear regression models were used for finding correlations and relationships among parameters. Results: The mean CTDIvol was 1.34 mGy ± 0.19 and the mean SSDE was 1.7 mGy ± 0.16. The mean ± SD of effective dose from emission, CT and total dose were 11.5 ± 1.4, 0.49 ± 0.11 and 12.67 ± 1.73 (mSv) respectively. The mean ± SD of effective dose from emission, CT and total dose were 11.5 ± 1.4, 0.49 ± 0.11 and 12.67 ± 1.73 (mSv) respectively. The spearman test showed that correlation between body size and organ doses is significant except thyroid and red bone marrow. CTDIvol was strongly dependent on patient size, but SSDE was not. Emission dose was strongly dependent on patient weight, but its dependency was lower to effective diameter. Conclusion: The dose parameters including CTDIvol, DLP, SSDE, effective dose values reported here are very low and below the reference level. This data suggest that appropriate CT acquisition parameters in SPECT/CT localization and attenuation correction are very beneficial for patients and lowering cancer risks.

On dose distribution comparison

International Nuclear Information System (INIS)

Jiang, Steve B; Sharp, Greg C; Neicu, Toni; Berbeco, Ross I; Flampouri, Stella; Bortfeld, Thomas

2006-01-01

In radiotherapy practice, one often needs to compare two dose distributions. Especially with the wide clinical implementation of intensity-modulated radiation therapy, software tools for quantitative dose (or fluence) distribution comparison are required for patient-specific quality assurance. Dose distribution comparison is not a trivial task since it has to be performed in both dose and spatial domains in order to be clinically relevant. Each of the existing comparison methods has its own strengths and weaknesses and there is room for improvement. In this work, we developed a general framework for comparing dose distributions. Using a new concept called maximum allowed dose difference (MADD), the comparison in both dose and spatial domains can be performed entirely in the dose domain. Formulae for calculating MADD values for various comparison methods, such as composite analysis and gamma index, have been derived. For convenience in clinical practice, a new measure called normalized dose difference (NDD) has also been proposed, which is the dose difference at a point scaled by the ratio of MADD to the predetermined dose acceptance tolerance. Unlike the simple dose difference test, NDD works in both low and high dose gradient regions because it considers both dose and spatial acceptance tolerances through MADD. The new method has been applied to a test case and a clinical example. It was found that the new method combines the merits of the existing methods (accurate, simple, clinically intuitive and insensitive to dose grid size) and can easily be implemented into any dose/intensity comparison tool

Cancer risk of low dose/low dose rate radiation: a meta-analysis of cancer data of mammals exposed to low doses of radiation

International Nuclear Information System (INIS)

Ogata, Hiromitsu; Magae, Junji

2008-01-01

Full text: Linear No Threshold (LNT) model is a basic theory for radioprotection, but the adaptability of this hypothesis to biological responses at low doses or at low dose rates is not sufficiently investigated. Simultaneous consideration of the cumulative dose and the dose rate is necessary for evaluating the risk of long-term exposure to ionizing radiation at low dose. This study intends to examine several numerical relationships between doses and dose rates in biological responses to gamma radiation. Collected datasets on the relationship between dose and the incidence of cancer in mammals exposed to low doses of radiation were analysed using meta-regression models and modified exponential (MOE) model, which we previously published, that predicts irradiation time-dependent biological response at low dose rate ionizing radiation. Minimum doses of observable risk and effective doses with a variety of dose rates were calculated using parameters estimated by fitting meta-regression models to the data and compared them with other statistical models that find values corresponding to 'threshold limits'. By fitting a weighted regression model (fixed-effects meta-regression model) to the data on risk of all cancers, it was found that the log relative risk [log(RR)] increased as the total exposure dose increased. The intersection of this regression line with the x-axis denotes the minimum dose of observable risk. These estimated minimum doses and effective doses increased with decrease of dose rate. The goodness of fits of MOE-model depended on cancer types, but the total cancer risk is reduced when dose rates are very low. The results suggest that dose response curve for cancer risk is remarkably affected by dose rate and that dose rate effect changes as a function of dose rate. For scientific discussion on the low dose exposure risk and its uncertainty, the term 'threshold' should be statistically defined, and dose rate effects should be included in the risk

Dose rate effect on low-dose hyper-radiosensitivity with cells in vitro

Energy Technology Data Exchange (ETDEWEB)

Kim, Geon-Min; Kim, Eun-Hee [Seoul National University, Seoul (Korea, Republic of)

2016-10-15

Low-dose hyper-radiosensitivity (HRS) is the phenomenon that mammalian cells exhibit higher sensitivity to radiation at low doses (< 0.5 Gy) than expected by the linear-quadratic model. At doses above 0.5Gy, the cellular response is recovered to the level expected by the linear-quadratic model. This transition is called the increased radio-resistance (IRR). HRS was first verified using Chinese hamster V79 cells in vitro by Marples and has been confirmed in studies with other cell lines including human normal and tumor cells. HRS is known to be induced by inactivation of ataxia telangiectasia-mutated (ATM), which plays a key role in repairing DNA damages. Considering the connection between ATM and HRS, one can infer that dose rate may affect cellular response regarding HRS at low doses. In this study, we quantitated the effect of dose rate on HRS by clonogenic assay with normal and tumor cells. The HRS of cells at low dose exposures is a phenomenon already known. In this study, we observed HRS of rat normal diencephalon cells and rat gliosarcoma cells at doses below 1 Gy. In addition, we found that dose rate mattered. HRS occurred at low doses, but only when total dose was delivered at a rate below certain level.

Long-term outcome of phenobarbital treatment for epilepsy in rural China: a prospective cohort study.

Science.gov (United States)

Kwan, Patrick; Wang, Wenzhi; Wu, Jianzhong; Li, Shichuo; Yang, Hongchao; Ding, Ding; Hong, Zhen; Dai, Xiuying; Yang, Bing; Wang, Taiping; Yuan, Chenglin; Ma, Guangyu; de Boer, Hanneke M; Sander, Josemir W

2013-03-01

To evaluate the long-term outcome of phenobarbital treatment for convulsive epilepsy in rural China, and to explore factors associated with overall seizure outcomes. We carried out follow-up assessments of people who took part in an epilepsy community management program conducted in rural counties of six provinces in China. People with convulsive epilepsy who were previously untreated (or on irregular treatment) were commenced on regular treatment with phenobarbital. Information was collected using a standardized questionnaire by face-to-face interviews of the individuals (and their families where necessary). Information collected included treatment status, medication change, seizure frequency, and mortality. Among the 2,455 people who participated in the original program, outcomes were successfully ascertained during the follow-up assessment in 1986. Among them, 206 had died. Information on treatment response was obtained in 1,780 (56% male; mean age 33.9 years, range 3-84; mean duration of follow-up 6.4 years). Among them, 939 (53%) were still taking phenobarbital. The most common reasons for stopping phenobarbital were seizure freedom or substantial seizure reduction, socioeconomic reasons, and personal preference. Four hundred fifty-three individuals (25%) became seizure-free for at least 1 year while taking phenobarbital, 88% of whom did so at daily doses of 120 mg or below. Four hundred six (23%) reported adverse events, which led to withdrawal of phenobarbital in phenobarbital for convulsive epilepsy in rural China. One hundred years after the discovery of its antiepileptic effect, phenobarbital is still playing an important role in the management of epilepsy. Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.

Vancomycin Dosing in Obese Patients: Special Considerations and Novel Dosing Strategies.

Science.gov (United States)

Durand, Cheryl; Bylo, Mary; Howard, Brian; Belliveau, Paul

2018-06-01

To review the literature regarding vancomycin pharmacokinetics in obese patients and strategies used to improve dosing in this population. PubMed, EMBASE (1974 to November 2017), and Google Scholar searches were conducted using the search terms vancomycin, obese, obesity, pharmacokinetics, strategy, and dosing. Additional articles were selected from reference lists of selected studies. Included articles were those published in English with a primary focus on vancomycin pharmacokinetic parameters in obese patients and practical vancomycin dosing strategies, clinical experiences, or challenges of dosing vancomycin in this population. Volume of distribution and clearance are the pharmacokinetic parameters that most often affect vancomycin dosing in obese patients; both are increased in this population. Challenges with dosing in obese patients include inconsistent and inadequate dosing, observations that the obese population may not be homogeneous, and reports of an increased likelihood of supratherapeutic trough concentrations. Investigators have revised and developed dosing and monitoring protocols to address these challenges. These approaches improved target trough attainment to varying degrees. Some of the vancomycin dosing approaches provided promising results in obese patients, but there were notable differences in methods used to develop these approaches, and sample sizes were small. Although some approaches can be considered for validation in individual institutions, further research is warranted. This may include validating approaches in larger populations with narrower obesity severity ranges, investigating target attainment in indication-specific target ranges, and evaluating the impact of different dosing weights and methods of creatinine clearance calculation.

Patient dose measurement and dose reduction in East Anglia (UK)

International Nuclear Information System (INIS)

Wade, J.P.; Goldstone, K.E.; Dendy, P.P.

1995-01-01

At the end of 1990 a programme of patient dose measurements was introduced as part of the quality assurance service already provided for X ray departments throughout the East Anglian Health Region (UK). Thermoluminescence dosemeters (TLDs) were used to measure over 1200 skin entrance surface doses for four common radiographic views in 33 hospitals in both the NHS and private sector. The four views were chosen to cover a wide range of equipment and techniques. The data collected have enabled Regional reference doses to be set which, for all views considered, fall below the National Radiological Protection Board (NRPB) Reference levels. In departments which exceeded reference levels, techniques were reviewed, improvements suggested and doses re-measured, in accordance with the recommended procedure for patient dose audit. A significant finding was that, given appropriate controls, X ray departments in the private sector could achieve the same acceptably low doses as NHS departments. (Author)

Dependence of total dose response of bipolar linear microcircuits on applied dose rate

International Nuclear Information System (INIS)

McClure, S.; Will, W.; Perry, G.; Pease, R.L.

1994-01-01

The effect of dose rate on the total dose radiation hardness of three commercial bipolar linear microcircuits is investigated. Total dose tests of linear bipolar microcircuits show larger degradation at 0.167 rad/s than at 90 rad/s even after the high dose rate test is followed by a room temperature plus a 100 C anneal. No systematic correlation could be found for degradation at low dose rate versus high dose rate and anneal. Comparison of the low dose rate with the high dose rate anneal data indicates that MIL-STD-883, method 1019.4 is not a worst-case test method when applied to bipolar microcircuits for low dose rate space applications

Safety Evaluation of EXPAREL (DepoFoam Bupivacaine Administered by Repeated Subcutaneous Injection in Rabbits and Dogs: Species Comparison

Directory of Open Access Journals (Sweden)

Brigitte M. Richard

2011-01-01

Full Text Available EXPAREL (bupivacaine extended-release liposome injection, DepoFoam bupivacaine, is in development for prolonged postsurgical analgesia. Repeat-dose toxicity studies were conducted in rabbits and dogs to compare the potential local and systemic toxicities of EXPAREL and bupivacaine HCl (Bsol, and the reversibility of any effects. Dogs tolerated much larger doses than rabbits. EXPAREL-related minimal-to-moderate granulomatous inflammation was noted at the injection sites. In recovery animals, the granulomatous inflammation was observed less frequently and was characterized by an increased number of multinucleated giant cells. These effects were considered a normal response to liposomes and nonadverse. Rabbits are more sensitive than dogs. In rabbits, convulsions were noted with EXPAREL and more frequently with Bsol; a NOAEL was not identified. In dogs, EXPAREL was well tolerated (NOAEL > 30 mg/kg/dose. The cumulative exposure of EXPAREL in these studies is well in excess of the proposed maximum single-dose exposure that is intended in humans.

Insignificant levels of dose

International Nuclear Information System (INIS)

Webb, G.A.M.; McLean, A.S.

1977-01-01

The procedures recommended by the International Commission on Radiological Protection (ICRP) for making decisions concerning controllable sources of radiation exposure of the public include 'justification' and 'optimisation'. The tool recommended by the ICRP for reaching these decisions is collective dose or dose commitment supplemented by consideration of doses to individuals. In both these considerations the practical problem arises of whether very small doses to large numbers of people should contribute to the final decision-making process. It may be that at levels of dose which are small increments on natural background, the relationship between dose and effect is linear even though the slope may be close to zero. If so, collective dose is a meaningful concept and the calculation of total detriment for the purpose of justification could legitimately include all doses. In the calculation of collective doses for the purpose of optimisation, which involves decisions on how much money or resource should be allocated to dose reduction, it is necessary to appraise radiation detriment realistically. At low levels of dose to the individual such as those small by comparison with variations in natural background within the UK, the risk to the individual is such that his well-being will not be significantly changed by the presence or absence of the radiation dose. These small doses, which are well below the point at which an individual attaches significance, should not carry a societal significance. Societal acceptance of risk is analysed with a view to assessing a level of possible risk, and hence dose, below which resources should not in general be diverted to secure further reduction. A formulation for collective dose commitment is proposed incorporating a cut-off to exclude insignificant doses. The implications of this formulation in practical situations are discussed

Case Example of Dose Optimization Using Data From Bortezomib Dose-Finding Clinical Trials.

Science.gov (United States)

Lee, Shing M; Backenroth, Daniel; Cheung, Ying Kuen Ken; Hershman, Dawn L; Vulih, Diana; Anderson, Barry; Ivy, Percy; Minasian, Lori

2016-04-20

The current dose-finding methodology for estimating the maximum tolerated dose of investigational anticancer agents is based on the cytotoxic chemotherapy paradigm. Molecularly targeted agents (MTAs) have different toxicity profiles, which may lead to more long-lasting mild or moderate toxicities as well as to late-onset and cumulative toxicities. Several approved MTAs have been poorly tolerated during long-term administration, leading to postmarketing dose optimization studies to re-evaluate the optimal treatment dose. Using data from completed bortezomib dose-finding trials, we explore its toxicity profile, optimize its dose, and examine the appropriateness of current designs for identifying an optimal dose. We classified the toxicities captured from 481 patients in 14 bortezomib dose-finding studies conducted through the National Cancer Institute Cancer Therapy Evaluation Program, computed the incidence of late-onset toxicities, and compared the incidence of dose-limiting toxicities (DLTs) among groups of patients receiving different doses of bortezomib. A total of 13,008 toxicities were captured: 46% of patients' first DLTs and 88% of dose reductions or discontinuations of treatment because of toxicity were observed after the first cycle. Moreover, for the approved dose of 1.3 mg/m(2), the estimated cumulative incidence of DLT was > 50%, and the estimated cumulative incidence of dose reduction or treatment discontinuation because of toxicity was nearly 40%. When considering the entire course of treatment, the approved bortezomib dose exceeds the conventional ceiling DLT rate of 20% to 33%. Retrospective analysis of trial data provides an opportunity for dose optimization of MTAs. Future dose-finding studies of MTAs should take into account late-onset toxicities to ensure that a tolerable dose is identified for future efficacy and comparative trials. © 2016 by American Society of Clinical Oncology.

Involvement of adrenergic and serotonergic nervous mechanisms in allethrin-induced tremors in mice.

Science.gov (United States)

Nishimura, M; Obana, N; Yagasaki, O; Yanagiya, I

1984-05-01

Oral or intravenous administration of allethrin, a synthetic derivative of the pirethrin-based insecticides, produces neurotoxic symptoms consisting of mild salivation, hyperexcitability, tremors and convulsions which result in death. Intracerebroventricular injection of allethrin to mouse at about one-nineth the dose of intravenous administration, produced qualitatively identical but less prominent symptoms, indicating that at least some of the symptoms may be originated in the central nervous system. To investigate the mechanism of action of the compound, we studied the ability of agents which alter neurotransmission to prevent or potentiate the effect of convulsive doses of technical grade (15.5% cis, 84.5% trans) allethrin. Intraperitoneal pretreatment with drugs which block noradrenergic receptors or norepinephrine synthesis, such as pentobarbital, chlorpromazine, phentolamine, phenoxybenzamine and reserpine, depressed the tremor induced by allethrin. The inhibitory effect of reserpine was reversed by phenylephrine. Both the serotonergic blocker, methysergide, and the serotonin depletor, rho-chlorphenylalanine, potentiated the effect of allethrin. The potentiating effect of methysergide was antagonized by 5-hydroxytryptamine. However, intracerebroventricular administration of methysergide was ineffective in potentiating the effect of allethrin. alpha 2- and beta-adrenoceptor blockers, muscarinic antagonists, GABA mimenergics and morphine had no effect. These results suggest that allethrin produces its neurotoxic responses in mice by acting on the brain and spinal levels. Furthermore, adrenergic excitatory and serotonergic inhibitory mechanisms may be involved in the neural pathway through which the allethrin-induced tremor is evoked.

Occupational Doses and the Contribution to the Population Dose in Korea

Energy Technology Data Exchange (ETDEWEB)

Han, Seung Jae; Kyu, Hwan Jeong [KINS, Daejeon (Korea, Republic of)

2016-05-15

The purpose of this study is to evaluate the occupational exposure records in terms of the control of exposure for radiation workers and dose reduction. The study includes the estimates of the number of people exposed occupationally, the effective collective doses and mean doses to those exposed. In addition, the study includes an estimate of the contribution of occupational exposure to the Korean population dose. The exposure of radiation workers in occupational field includes medical radiology, industrial applications such as radiography, nuclear power, and some research activities. Occupational exposure from medical radiology practices includes the contributions from diagnostic x-ray procedures, dental radiography, nuclear medicine and radiation therapy. The control of exposure for radiation workers, and the measures necessary to maintain radiation exposure as low as reasonably achievable (ALARA) are specified in Subparagraph 3 and Subparagraph 4 of Article 91 (1) of the Korea Nuclear Safety Act (KNSA), respectively. Therefore, from a regulatory perspective, the exposure data of the workers are primarily for verification of the adequacy of the control of exposure, radiation protection and implementation of ALARA. The number of people exposed occupationally, the effective collective doses and mean doses to those exposed, and average effective doses from occupational exposure during the period of 2009 to 2013 have been evaluated. In general, radiation workers were increasing in number annually, but the mean doses for those exposed each year showed the control of exposures were mostly considered met within the dose limit in KNSA. Nevertheless, it was shown that the continuous efforts would be needed to reduce doses and thus to implement ALARA regulatory requirements. In radiation occupations, the application of ICRP radiation protection principles will ensure good practice and decreasing exposures. Over the period of 5 years, the contributions of the annual

Occupational Doses and the Contribution to the Population Dose in Korea

International Nuclear Information System (INIS)

Han, Seung Jae; Kyu, Hwan Jeong

2016-01-01

The purpose of this study is to evaluate the occupational exposure records in terms of the control of exposure for radiation workers and dose reduction. The study includes the estimates of the number of people exposed occupationally, the effective collective doses and mean doses to those exposed. In addition, the study includes an estimate of the contribution of occupational exposure to the Korean population dose. The exposure of radiation workers in occupational field includes medical radiology, industrial applications such as radiography, nuclear power, and some research activities. Occupational exposure from medical radiology practices includes the contributions from diagnostic x-ray procedures, dental radiography, nuclear medicine and radiation therapy. The control of exposure for radiation workers, and the measures necessary to maintain radiation exposure as low as reasonably achievable (ALARA) are specified in Subparagraph 3 and Subparagraph 4 of Article 91 (1) of the Korea Nuclear Safety Act (KNSA), respectively. Therefore, from a regulatory perspective, the exposure data of the workers are primarily for verification of the adequacy of the control of exposure, radiation protection and implementation of ALARA. The number of people exposed occupationally, the effective collective doses and mean doses to those exposed, and average effective doses from occupational exposure during the period of 2009 to 2013 have been evaluated. In general, radiation workers were increasing in number annually, but the mean doses for those exposed each year showed the control of exposures were mostly considered met within the dose limit in KNSA. Nevertheless, it was shown that the continuous efforts would be needed to reduce doses and thus to implement ALARA regulatory requirements. In radiation occupations, the application of ICRP radiation protection principles will ensure good practice and decreasing exposures. Over the period of 5 years, the contributions of the annual

Estudo histológico e computadorizado das áreas com células parietais e principais no estômago de ratos Wistar tratados com pantoprazol e "N-Nitroso-N-Methylurea"(NMU Histological and computer-assisted analysis of parietal and chief cells stomach areas in Wistar rats treated with pantoprazole and N-Nitroso-N-Methylurea (NMU

Directory of Open Access Journals (Sweden)

Iure Kalinine Ferraz de Souza

2002-08-01

Full Text Available O uso prolongado dos inibidores da bomba de prótons tem sido considerado uma condição de risco para o desenvolvimento de gastrite atrófica e tumores gástricos. Objetivo: Estudar o efeito do uso de pantoprazol (PTZ e carcinogênese pela "N-Nitroso-N-Methylurea" (NMU, por 15 semanas, sobre o estômago glandular de ratos Wistar, pela análise histológica e computadorizada das áreas com células parietais (AP, principais (AZ e da mucosa não oxíntica (ANO, além do estudo das alterações histopatológicas identificadas. Métodos: Quarenta ratos Wistar machos foram distribuídos em 4 grupos: G1 (controle, G2 (NMU+PTZ, G3 (PTZ e G4 (NMU. O pantoprazol foi administrado 2x/semana (14mg/kg de peso, i.p. e a NMU oferecida, ad libitum, diluída na água de beber (100mig/ml. Após o estudo histológico AP, AZ e ANO foram determinadas por análise computadorizada das imagens dos estômagos, utilizando o programa "ImageJ 1.19z". Resultados: Mostraram redução da AP e aumento da ANO, em G2, G3 e G4 (pThe long-term use of proton bomb inhibitors has been considered a risk condition for the development of atrophic gastritis and gastric tumors. Objective: The aim of this study was to investigate the effects of pantoprazole (PTZ treatment and N-Nitroso-N-Methylurea (NMU carcinogenesis, for 15 weeks, in the glandular stomach of rats by histological and computer-assisted analysis of parietal cells area (PA, chief cells area (CP and non-oxintic mucosal area (ANO, as well as by histopathological study. Methods: A total of 40 male Wistar rats were divided into four groups on the basis of the treatment: G1 (control, G2 (NMU+PTZ, G3 (PTZ and G4 (NMU. Pantoprazole was administered twice a week (14mg/kg body wt., i.p. and NMU was given in the drinking water (100ppm ad libitum. After histological examination AP, AZ and ANO were investigated by computer-assisted analysis of the stomach image using the program ImageJ1.19z. Results: Showed a reduction of AP and

Low-dose computed tomography image restoration using previous normal-dose scan

International Nuclear Information System (INIS)

Ma, Jianhua; Huang, Jing; Feng, Qianjin; Zhang, Hua; Lu, Hongbing; Liang, Zhengrong; Chen, Wufan

2011-01-01

Purpose: In current computed tomography (CT) examinations, the associated x-ray radiation dose is of a significant concern to patients and operators. A simple and cost-effective means to perform the examinations is to lower the milliampere-seconds (mAs) or kVp parameter (or delivering less x-ray energy to the body) as low as reasonably achievable in data acquisition. However, lowering the mAs parameter will unavoidably increase data noise and the noise would propagate into the CT image if no adequate noise control is applied during image reconstruction. Since a normal-dose high diagnostic CT image scanned previously may be available in some clinical applications, such as CT perfusion imaging and CT angiography (CTA), this paper presents an innovative way to utilize the normal-dose scan as a priori information to induce signal restoration of the current low-dose CT image series. Methods: Unlike conventional local operations on neighboring image voxels, nonlocal means (NLM) algorithm utilizes the redundancy of information across the whole image. This paper adapts the NLM to utilize the redundancy of information in the previous normal-dose scan and further exploits ways to optimize the nonlocal weights for low-dose image restoration in the NLM framework. The resulting algorithm is called the previous normal-dose scan induced nonlocal means (ndiNLM). Because of the optimized nature of nonlocal weights calculation, the ndiNLM algorithm does not depend heavily on image registration between the current low-dose and the previous normal-dose CT scans. Furthermore, the smoothing parameter involved in the ndiNLM algorithm can be adaptively estimated based on the image noise relationship between the current low-dose and the previous normal-dose scanning protocols. Results: Qualitative and quantitative evaluations were carried out on a physical phantom as well as clinical abdominal and brain perfusion CT scans in terms of accuracy and resolution properties. The gain by the use

Conversion from tooth enamel dose to organ doses for electron spin resonance dosimetry

International Nuclear Information System (INIS)

Takahashi, Fumiaki; Yamaguchi, Yasuhiro; Saito, Kimiaki; Hamada, Tatsuji

2002-01-01

Conversion from tooth enamel dose to organ doses was analyzed to establish a method of retrospective individual dose assessment against external photon exposure by electron spin resonance (ESR) dosimetry. Dose to tooth enamel was obtained by Monte Carlo calculations using a modified MIRD-type phantom with a teeth part. The calculated tooth enamel doses were verified by measurements with thermo-luminescence dosimeters inserted in a physical head phantom. Energy and angular dependences of tooth enamel dose were compared with those of other organ doses. Additional Monte Carlo calculations were performed to study the effect of human model on the tooth enamel dose with a voxel-type phantom, which was based on computed tomography images of the physical phantom. The data derived with the modified MIRD-type phantom were applied to convert from tooth enamel dose to organ doses against external photon exposure in a hypothesized field, where scattered radiation was taken into account. The results indicated that energy distribution of photons incident to a human body is required to evaluate precisely an individual dose based on ESR dosimetry for teeth. (author)

When is a dose not a dose?

International Nuclear Information System (INIS)

Green, Patrick

1992-01-01

There is confusion over radiation dose limits between the International Commission on Radiological Protection, the National Radiological Protection Board and the Ministry of Agriculture, Fisheries and Food (MAFF), reports a Friends of the Earth's radiation campaigner. MAFF is suggesting the inadequate ICRP public dose limit does not apply to public exposures which arise from environmental contamination from past radioactive discharges. (author)

Determination of Entrance Skin Doses and Organ Doses for Medical X Ray Examinations

International Nuclear Information System (INIS)

Tung, C.J.; Cheng, C.Y.; Chao, T.C.; Tsai, H.Y.

1999-01-01

A national survey of patient doses for diagnostic X ray radiographs is planned in Taiwan. Entrance skin doses and organ doses for all installed X ray machines will be investigated. A pilot study has been carried out for the national survey to develop a protocol for the dose assessment. Entrance skin doses and organ doses were measured by thermoluminescence dosemeters and calculated by Monte Carlo simulations for several X ray examinations. The conversion factor from free air entrance absorbed dose to entrance skin dose was derived. A formula for the computation of entrance skin doses from inputs of kV p , mA.s, source to skin distance, aluminium filtration, and generator rectifying was constructed. Organ doses were measured using a RANDO phantom and calculated using a mathematical phantom. All data will be passed to the Atomic Energy Council for developing a programme of national survey and regulatory controls for diagnostic X ray examinations. (author)

Benzodiazepine antagonism by harmane and other beta-carbolines in vitro and in vivo.

Science.gov (United States)

Rommelspacher, H; Nanz, C; Borbe, H O; Fehske, K J; Müller, W E; Wollert, U

1981-03-26

Harmane and other related beta-carbolines are putative endogenous ligands of the benzodiazepine receptor. Since the compounds are potent convulsants they may have agonist activities at the benzodiazepine receptor while the benzodiazepines may be antagonists. This hypothesis was proved by comparing the in vivo and in vitro antagonism of benzodiazepines by harmane and other beta-carbolines. Harmane is clearly a competitive inhibitor of benzodiazepine receptor binding in vitro. Moreover, harmane-induced convulsions can be inhibited reversibly by diazepam in a manner which is consistent with the assumption of competitive antagonism in vivo. For some beta-carboline derivatives a correlation was found between the affinity for the benzodiazepine receptor in vitro and the convulsive potency in vivo. Thus, the data reported suggest that harmane or other related beta-carbolines are putative endogenous agonists of the benzodiazepine receptor. This suggestion is further supported by the observation that diazepam is equally potent in inhibiting harmane- or picrotoxin-induced convulsions, indicating a convulsive mechanism within the GABA receptor-benzodiazepine receptor system.

Screening of the anticonvulsant activity of some plants from Fabaceae family in experimental seizure models in mice

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S Sardari

2011-10-01

Full Text Available "n  Background and purpose of the study: Fabaceae is the third largest family of flowering plants. Lack of essential oils in the plants of this family can be an advantage in search for safe and effective medicines. In this study the anticonvulsant effect of the leaves of Albizzia julibrissin, Acacia juliflora, Acacia nubica and aerial parts of Astragalus obtusifolius was evaluated in pentylenetetrazole (PTZ and maximal electroshock (MES seizure tests. "n  Methods: The hydroalcoholic extracts of the plants were obtained by percolation. Different doses of the extracts were injected to the mice intraperitoneally (i.p. and occurrence of clonic seizures induced by PTZ (60 mg/kg, i.p. or tonic seizures induced by MES (50 mA, 50Hz, 1sec were monitored up to 30 min after administration. Acute toxicity of the extracts was also assessed. The safe and effective extract was then fractionated by dichloromethane and anticonvulsant activity of the fractions was determined. Finally, the constituents of the extract and the fractions were screened by thin layer chromatography. "n  Results: Among the extracts, only A. obtusifolius extract showed low toxicity and protective effect against clonic seizures with ED50 value of 3.97 g/kg. Fractionation of the extract led to increase in anticonvulsant activity and ED50 value of 2.86 g/kg was obtained for the aqueous fraction. Phytochemical screening revealed the presence of alkaloids, flavonoids, anthrones and saponins in the aqueous fraction. "n  Major conclusion: The presence of anticonvulsant compounds in A. obtusifolius suggests further activity-guided fractionation and analytical studies to find out the potential of this plant as a source of anticonvulsant agent.

Zebrafish-Based Discovery of Antiseizure Compounds from the Red Sea: Pseurotin A2 and Azaspirofuran A.

Science.gov (United States)

Copmans, Daniëlle; Rateb, Mostafa; Tabudravu, Jioji N; Pérez-Bonilla, Mercedes; Dirkx, Nina; Vallorani, Riccardo; Diaz, Caridad; Pérez Del Palacio, José; Smith, Alan J; Ebel, Rainer; Reyes, Fernando; Jaspars, Marcel; de Witte, Peter A M

2018-04-19

In search for novel antiseizure drugs (ASDs), the European FP7-funded PharmaSea project used zebrafish embryos and larvae as a drug discovery platform to screen marine natural products to identify promising antiseizure hits in vivo for further development. Within the framework of this project, seven known heterospirocyclic γ-lactams, namely, pseurotin A, pseurotin A 2 , pseurotin F1, 11- O-methylpseurotin A, pseurotin D, azaspirofuran A, and azaspirofuran B, were isolated from the bioactive marine fungus Aspergillus fumigatus, and their antiseizure activity was evaluated in the larval zebrafish pentylenetetrazole (PTZ) seizure model. Pseurotin A 2 and azaspirofuran A were identified as antiseizure hits, while their close chemical analogues were inactive. Besides, electrophysiological analysis from the zebrafish midbrain demonstrated that pseurotin A 2 and azaspirofuran A also ameliorate PTZ-induced epileptiform discharges. Next, to determine whether these findings translate to mammalians, both compounds were analyzed in the mouse 6 Hz (44 mA) psychomotor seizure model. They lowered the seizure duration dose-dependently, thereby confirming their antiseizure properties and suggesting activity against drug-resistant seizures. Finally, in a thorough ADMET assessment, pseurotin A 2 and azaspirofuran A were found to be drug-like. Based on the prominent antiseizure activity in both species and the drug-likeness, we propose pseurotin A 2 and azaspirofuran A as lead compounds that are worth further investigation for the treatment of epileptic seizures. This study not only provides the first evidence of antiseizure activity of pseurotins and azaspirofurans, but also demonstrates the value of the zebrafish model in (marine) natural product drug discovery in general, and for ASD discovery in particular.

Occupational dose constraint

International Nuclear Information System (INIS)

Heilbron Filho, Paulo Fernando Lavalle; Xavier, Ana Maria

2005-01-01

The revision process of the international radiological protection regulations has resulted in the adoption of new concepts, such as practice, intervention, avoidable and restriction of dose (dose constraint). The latter deserving of special mention since it may involve reducing a priori of the dose limits established both for the public and to individuals occupationally exposed, values that can be further reduced, depending on the application of the principle of optimization. This article aims to present, with clarity, from the criteria adopted to define dose constraint values to the public, a methodology to establish the dose constraint values for occupationally exposed individuals, as well as an example of the application of this methodology to the practice of industrial radiography

Automated size-specific CT dose monitoring program: Assessing variability in CT dose

International Nuclear Information System (INIS)

Christianson, Olav; Li Xiang; Frush, Donald; Samei, Ehsan

2012-01-01

Purpose: The potential health risks associated with low levels of ionizing radiation have created a movement in the radiology community to optimize computed tomography (CT) imaging protocols to use the lowest radiation dose possible without compromising the diagnostic usefulness of the images. Despite efforts to use appropriate and consistent radiation doses, studies suggest that a great deal of variability in radiation dose exists both within and between institutions for CT imaging. In this context, the authors have developed an automated size-specific radiation dose monitoring program for CT and used this program to assess variability in size-adjusted effective dose from CT imaging. Methods: The authors radiation dose monitoring program operates on an independent health insurance portability and accountability act compliant dosimetry server. Digital imaging and communication in medicine routing software is used to isolate dose report screen captures and scout images for all incoming CT studies. Effective dose conversion factors (k-factors) are determined based on the protocol and optical character recognition is used to extract the CT dose index and dose-length product. The patient's thickness is obtained by applying an adaptive thresholding algorithm to the scout images and is used to calculate the size-adjusted effective dose (ED adj ). The radiation dose monitoring program was used to collect data on 6351 CT studies from three scanner models (GE Lightspeed Pro 16, GE Lightspeed VCT, and GE Definition CT750 HD) and two institutions over a one-month period and to analyze the variability in ED adj between scanner models and across institutions. Results: No significant difference was found between computer measurements of patient thickness and observer measurements (p= 0.17), and the average difference between the two methods was less than 4%. Applying the size correction resulted in ED adj that differed by up to 44% from effective dose estimates that were not

In Vivo Reactivation by Oximes of Inhibited Blood, Brain and Peripheral Tissue Cholinesterase Activity Following Exposure to Nerve Agents in Guinea Pigs

Science.gov (United States)

2010-01-01

nerve agent intoxication ( salivation , rhinorrhea, tremors,muscle asciculations, convulsions) at 60min following the 1.0× LD50 dose f GB, GF, VR or VX...reactivation of GF-, soman-, or VR-inhibited enzyme byHI-6 andHLö7. However, these in vitro experiments [24,25] were conducted with a pH of 8.0 at 25 ◦C...data. Even the study of Worek et al. [23] that was performed at a pH of 7.4 at 37 ◦C, whose in vitro kinetic data obtained from guinea pig RBC ghosts

Dose reconstruction in deforming lung anatomy: Dose grid size effects and clinical implications

International Nuclear Information System (INIS)

Rosu, Mihaela; Chetty, Indrin J.; Balter, James M.; Kessler, Marc L.; McShan, Daniel L.; Ten Haken, Randall K.

2005-01-01

In this study we investigated the accumulation of dose to a deforming anatomy (such as lung) based on voxel tracking and by using time weighting factors derived from a breathing probability distribution function (p.d.f.). A mutual information registration scheme (using thin-plate spline warping) provided a transformation that allows the tracking of points between exhale and inhale treatment planning datasets (and/or intermediate state scans). The dose distributions were computed at the same resolution on each dataset using the Dose Planning Method (DPM) Monte Carlo code. Two accumulation/interpolation approaches were assessed. The first maps exhale dose grid points onto the inhale scan, estimates the doses at the 'tracked' locations by trilinear interpolation and scores the accumulated doses (via the p.d.f.) on the original exhale data set. In the second approach, the 'volume' associated with each exhale dose grid point (exhale dose voxel) is first subdivided into octants, the center of each octant is mapped to locations on the inhale dose grid and doses are estimated by trilinear interpolation. The octant doses are then averaged to form the inhale voxel dose and scored at the original exhale dose grid point location. Differences between the interpolation schemes are voxel size and tissue density dependent, but in general appear primarily only in regions with steep dose gradients (e.g., penumbra). Their magnitude (small regions of few percent differences) is less than the alterations in dose due to positional and shape changes from breathing in the first place. Thus, for sufficiently small dose grid point spacing, and relative to organ motion and deformation, differences due solely to the interpolation are unlikely to result in clinically significant differences to volume-based evaluation metrics such as mean lung dose (MLD) and tumor equivalent uniform dose (gEUD). The overall effects of deformation vary among patients. They depend on the tumor location, field

Radon Exposure and the Definition of Low Doses-The Problem of Spatial Dose Distribution.

Science.gov (United States)

Madas, Balázs G

2016-07-01

Investigating the health effects of low doses of ionizing radiation is considered to be one of the most important fields in radiological protection research. Although the definition of low dose given by a dose range seems to be clear, it leaves some open questions. For example, the time frame and the target volume in which absorbed dose is measured have to be defined. While dose rate is considered in the current system of radiological protection, the same cancer risk is associated with all exposures, resulting in a given amount of energy absorbed by a single target cell or distributed among all the target cells of a given organ. However, the biological effects and so the health consequences of these extreme exposure scenarios are unlikely to be the same. Due to the heterogeneous deposition of radon progeny within the lungs, heterogeneous radiation exposure becomes a practical issue in radiological protection. While the macroscopic dose is still within the low dose range, local tissue doses on the order of Grays can be reached in the most exposed parts of the bronchial airways. It can be concluded that progress in low dose research needs not only low dose but also high dose experiments where small parts of a biological sample receive doses on the order of Grays, while the average dose over the whole sample remains low. A narrow interpretation of low dose research might exclude investigations with high relevance to radiological protection. Therefore, studies important to radiological protection should be performed in the frame of low dose research even if the applied doses do not fit in the dose range used for the definition of low doses.

Physiological and immunological changes following exposure to low versus high-dose ionizing irradiation; comparative analysis with dose rate and cumulative dose

International Nuclear Information System (INIS)

Heesun, Kim; Heewon, Jang; Soungyeon, Song; Shinhye, Oh; Cukcheul, Shin; Meeseon, Jeong; Chasoon, Kim; Kwnaghee, Yang; Seonyoung, Nam; Jiyoung, Kim; Youngwoo, Jin; Changyoung, Cha

2008-01-01

Full text: While high-dose of ionizing radiation is generally harmful and causes damage to living organisms some reports suggest low-dose of radiation may not be as damaging as previously thought. Despite increasing evidence regarding the protective effect of low-dose radiation, no studies have directly compared the exact dose-response pattern by high- and low-dose of radiation exposed at high-and low-dose rate. This study aims to explore the cellular and molecular changes in mice exposed to low- and high-dose of radiation exposed at low- and high-dose rate. When C57BL/6 mice (Female, 6 weeks) were exposed at high-dose rate, 0.8 Gy/min, no significant change on the level of WBC, RBC, or platelets was observed up to total dose of 0.5 Gy. However, 2 Gy of radiation caused dramatic reduction in the level of white blood cells (WBC) and platelets. This reduction was accompanied by increased DNA damage in hematopoietic environments. The reduction of WBC was mainly due to the reduction in the number of CD4+ T cells and CD19+ B cells. CD8+ T cells and NK cells appeared to be relatively resistant to high-dose of radiation. This change was also accompanied by the reduction of T- and B- progenitor cells in the bone marrow. In contrast, no significant changes of the number of CD4+ T, CD8+ T, NK, and B cells were observed in the spleen of mice exposed at low-dose-rate (0.7 m Gy/h or 3.95 mGy/h) for up to 2 Gy, suggesting that low-dose radiation does not alter cellular distribution in the spleen. Nevertheless, mice exposed to low-dose radiation exhibited elevation of VEGF, MCP-1, IL-4, Leptin, IL-3, and Tpo in the peripheral blood and slight increases in MIP-2, RANTES, and IL-2 in the spleen. This suggests that chronic γ-radiation can stimulate immune function without causing damage to the immune components of the body. Taken together, these data indicate hormesis of low-dose radiation, which could be attributed to the stimulation of immune function. Dose rate rather than total

Dose rate correction in medium dose rate brachytherapy for carcinoma cervix

International Nuclear Information System (INIS)

Patel, F.D.; Negi, P.S.; Sharma, S.C.; Kapoor, R.; Singh, D.P.; Ghoshal, S.

1998-01-01

Purpose: To establish the magnitude of brachytherapy dose reduction required for stage IIB and III carcinoma cervix patients treated by external radiation and medium dose rate (MDR) brachytherapy at a dose rate of 220±10 cGy/h at point A.Materials and methods: In study-I, at the time of MDR brachytherapy application at a dose rate of 220±10 cGy/h at point A, patients received either 3060 cGy, a 12.5% dose reduction (MDR-12.5), or 2450 cGy, a 30% dose reduction (MDR-30), to point A and they were compared to a group of previously treated LDR patients who received 3500 cGy to point A at a dose rate of 55-65 cGy/h. Study-II was a prospective randomized trial and patients received either 2450 cGy, a 30% dose reduction (MDR-II (30)) or 2800 cGy, a 20% dose reduction (MDR-II (20)), at point A. Patients were evaluated for local control of disease and morbidity. Results: In study-I the 5-year actuarial local control rate in the MDR-30 and MDR-12.5 groups was 71.7±10% and 70.5±10%, respectively, compared to 63.4±10% in the LDR group. However, the actuarial morbidity (all grades) in the MDR-12.5 group was 58.5±14% as against 34.9±9% in the LDR group (P 3 developed complication as against 62.5% of those receiving a rectal BED of (140 3 (χ 2 =46.43; P<0.001). Conclusion: We suggest that at a dose rate of 220±10 cGy/h at point A the brachytherapy dose reduction factor should be around 30%, as suggested by radiobiological data, to keep the morbidity as low as possible without compromising the local control rates. (Copyright (c) 1998 Elsevier Science B.V., Amsterdam. All rights reserved.)

Controllable dose

International Nuclear Information System (INIS)

Alvarez R, J.T.; Anaya M, R.A.

2004-01-01

With the purpose of eliminating the controversy about the lineal hypothesis without threshold which found the systems of dose limitation of the recommendations of ICRP 26 and 60, at the end of last decade R. Clarke president of the ICRP proposed the concept of Controllable Dose: as the dose or dose sum that an individual receives from a particular source which can be reasonably controllable by means of any means; said concept proposes a change in the philosophy of the radiological protection of its concern by social approaches to an individual focus. In this work a panorama of the foundations is presented, convenient and inconveniences that this proposal has loosened in the international community of the radiological protection, with the purpose of to familiarize to our Mexican community in radiological protection with these new concepts. (Author)

Application of biological dose concept in dose optimization for conformal radiotherapy of prostate carcinoma

International Nuclear Information System (INIS)

Li Yunhai; Liao Yuan; Zhou Lijun; Pan Ziqiang; Feng Yan

2003-01-01

Objective: On basis of physical dose optimization, LQ model was used to investigate the difference between the curves of biological effective dose and physical isodose. The influence of applying the biological dose concept on three dimensional conformal radiotherapy of prostate carcinoma was discussed. Methods: Four treatment plannings were designed for physical dose optimization: three fields, four-box fields, five fields and six fields. Target dose uniformity and protection of the critical tissue-rectum were used as the principal standard for designing the treatment planning. Biological effective dose (BED) was calculated by LQ model. The difference between the BED curve drawn in the central layer and the physical isodose curve was studied. The difference between the adjusted physical dose (APD) and the physical dose was also studied. Results: Five field planning was the best in target dose uniformity and protection of the critical tissue-rectum. The physical dose was uniform in the target, but the biological effective doses revealed great discrepancy in the biological model. Adjusted physical dose distribution also displayed larger discrepancy than the physical dose unadjusted. Conclusions: Intensified Modulated Radiotherapy (IMRT) technique with inversion planning using biological dose concept may be much more advantageous to reach a high tumor control probability and low normal tissue complication probability

Measurements of dose on build-up region, surface dose and outlet dose by a 10 MeV Linear accelerator

International Nuclear Information System (INIS)

Souza, C.N. de; Khoury, H.J.

1987-01-01

The dose on buildup region and the surface dose for a 10 MeV photon beam from a linear acelerator (Mevatrom-74, Siemens) is studied. The influence of the tray of polycarbonate on the surface dose is determined. (M.A.C.) [pt

Paediatric dose display

International Nuclear Information System (INIS)

Griffin, D.W.; Derges, S.; Hesslewood, S.

1984-01-01

A compact, inexpensive unit, based on an 8085 microprocessor, has been designed for calculating doses of intravenous radioactive injections for children. It has been used successfully for over a year. The dose is calculated from the body surface area and the result displayed in MBq. The operator can obtain the required dose on a twelve character alphanumeric display by entering the age of the patient and the adult dose using a hexadecimal keyboard. Circuit description, memory map and input/output, and firmware are dealt with. (U.K.)

Research on low radiation doses - A better understanding of low doses

International Nuclear Information System (INIS)

2016-01-01

Radiation doses below 100 mSv are called low doses. Epidemiological research on the health hazards of low doses are difficult to do because numerous pathologies, particularly cancer, appear lifelong for genetical or environmental causes without any link with irradiation and it is very difficult to identify the real cause of a cancer. Another concern is that the impact on human health is weak and are observed only after a long period after irradiation. These features make epidemiological studies cumbersome to implement since they require vast cohorts and a very long-term follow-up. The extrapolation of the effects of higher doses to the domain of low doses does not meet reality and it is why the European Union takes part into the financing of such research. In order to gain efficiency, scientists work together through various European networks among them: HLEG (High Level Expert Group On European Low Dose Risk Research) or MELODI (Multidisciplinary European Low Dose Initiative). Several programs are underway or have been recently launched: -) the impact of Cesium contamination on children's health (Epice program), -) the study of the impact of medical imaging on children, -) the study of the health of children living near nuclear facilities, -) the relationship between radon and lung cancer, -) the effect of occupational low radiation doses, -) the effect of uranium dissolved in water on living organisms (Envirhom program). (A.C.)

Dose Response Model of Biological Reaction to Low Dose Rate Gamma Radiation

International Nuclear Information System (INIS)

Magae, J.; Furikawa, C.; Hoshi, Y.; Kawakami, Y.; Ogata, H.

2004-01-01

It is necessary to use reproducible and stable indicators to evaluate biological responses to long term irradiation at low dose-rate. They should be simple and quantitative enough to produce the results statistically accurate, because we have to analyze the subtle changes of biological responses around background level at low dose. For these purposes we chose micronucleus formation of U2OS, a human osteosarcoma cell line, as indicators of biological responses. Cells were exposed to gamma ray in irradiation rom bearing 50,000 Ci 60Co. After irradiation, they were cultured for 24 h in the presence of cytochalasin B to block cytokinesis, and cytoplasm and nucleus were stained with DAPI and prospidium iodide, respectively. the number of binuclear cells bearing micronuclei was counted under a fluorescence microscope. Dose rate in the irradiation room was measured with PLD. Dose response of PLD is linear between 1 mGy to 10 Gy, and standard deviation of triplicate count was several percent of mean value. We fitted statistically dose response curves to the data, and they were plotted on the coordinate of linearly scale response and dose. The results followed to the straight line passing through the origin of the coordinate axes between 0.1-5 Gy, and dose and does rate effectiveness factor (DDREF) was less than 2 when cells were irradiated for 1-10 min. Difference of the percent binuclear cells bearing micronucleus between irradiated cells and control cells was not statistically significant at the dose above 0.1 Gy when 5,000 binuclear cells were analyzed. In contrast, dose response curves never followed LNT, when cells were irradiated for 7 to 124 days. Difference of the percent binuclear cells bearing micronucleus between irradiated cells and control cells was not statistically significant at the dose below 6 Gy, when cells were continuously irradiated for 124 days. These results suggest that dose response curve of biological reaction is remarkably affected by exposure

Doses from portable gauges

International Nuclear Information System (INIS)

Linauskas, S.H.

1988-08-01

Field studies to measure actual radiation exposures of operators of commercial moisture-density gauges were undertaken in several regions of Canada. Newly developed bubble detector dosimeter technology and conventional dosimetry such as thermoluminescent dosimeters (TLDs), integrating electronic dosimeters (DRDs), and CR-39 neutron track-etch detectors were used to estimate the doses received by 23 moisture-density gauge operators and maintenance staff. These radiation dose estimates were supported by mapping radiation fields and accounting for the time an operator was near a gauge. Major findings indicate that gauge maintenance and servicing workers were more likely than gauge operators to receive exposures above the level of 5 mSv, and that neutron doses were roughly the same as gamma doses. Gauge operators receive approximately 75% of their dose when transporting and carrying the gauge. Dose to their hands is similar to the dose to their trunks, but the dose to their feet area is 6 to 30 times higher. Gamma radiation is the primary source of radiation contributing to operator dose

Automated size-specific CT dose monitoring program: Assessing variability in CT dose

Energy Technology Data Exchange (ETDEWEB)

Christianson, Olav; Li Xiang; Frush, Donald; Samei, Ehsan [Clinical Imaging Physics Group, Department of Radiology, Duke University Medical Center, Durham, North Carolina 27705 and Department of Radiology, Duke University Medical Center, Durham, North Carolina 27705 (United States); Clinical Imaging Physics Group, Department of Radiology, Duke University Medical Center, Durham, North Carolina 27705 (United States); Department of Radiology, Duke University Medical Center, Durham, North Carolina 27705 (United States) and Carl E. Ravin Advanced Imaging Laboratories, Department of Radiology, Duke University Medical Center, Durham, North Carolina 27705 (United States); Department of Radiology, Duke University Medical Center, Durham, North Carolina 27705 (United States); Clinical Imaging Physics Group, Department of Radiology, Duke University Medical Center, Durham, North Carolina 27705 (United States); Department of Radiology, Duke University Medical Center, Durham, North Carolina 27705 (United States); Carl E. Ravin Advanced Imaging Laboratories, Department of Radiology, Duke University Medical Center, Durham, North Carolina 27705 (United States); Medical Physics Graduate Program, Duke University, Durham, North Carolina 27705 (United States); Department of Physics, Duke University, Durham, North Carolina 27710 (United States); and Department of Biomedical Engineering, Duke University, Durham, North Carolina 27708 (United States)

2012-11-15

Purpose: The potential health risks associated with low levels of ionizing radiation have created a movement in the radiology community to optimize computed tomography (CT) imaging protocols to use the lowest radiation dose possible without compromising the diagnostic usefulness of the images. Despite efforts to use appropriate and consistent radiation doses, studies suggest that a great deal of variability in radiation dose exists both within and between institutions for CT imaging. In this context, the authors have developed an automated size-specific radiation dose monitoring program for CT and used this program to assess variability in size-adjusted effective dose from CT imaging. Methods: The authors radiation dose monitoring program operates on an independent health insurance portability and accountability act compliant dosimetry server. Digital imaging and communication in medicine routing software is used to isolate dose report screen captures and scout images for all incoming CT studies. Effective dose conversion factors (k-factors) are determined based on the protocol and optical character recognition is used to extract the CT dose index and dose-length product. The patient's thickness is obtained by applying an adaptive thresholding algorithm to the scout images and is used to calculate the size-adjusted effective dose (ED{sub adj}). The radiation dose monitoring program was used to collect data on 6351 CT studies from three scanner models (GE Lightspeed Pro 16, GE Lightspeed VCT, and GE Definition CT750 HD) and two institutions over a one-month period and to analyze the variability in ED{sub adj} between scanner models and across institutions. Results: No significant difference was found between computer measurements of patient thickness and observer measurements (p= 0.17), and the average difference between the two methods was less than 4%. Applying the size correction resulted in ED{sub adj} that differed by up to 44% from effective dose

Comparative study of eye dose and chest dose received during radiopharmaceutical production processes

International Nuclear Information System (INIS)

Chindarkar, A.S.; Chavan, S.V.; Sawant, D.K.; Sahoo, L.; Gopalakrishnan, R.K.; Sneha, C.; Sachdev, S.S.; Dey, A.C.

2018-01-01

Radiopharmaceutical laboratory, BRIT, Vashi produces different radiopharmaceuticals of 131 I, 153 Sm, 99 Mo/ 99m Tc and 177 Lu. Principle gamma energies of these isotopes vary from 103 to 740 KeV and their maximum beta energies vary from 384 to 1214 KeV. In the light of the revised eye lens dose limit recommended in IAEA Basic Safety Standard Interim Edition No. GSR Part 3 (IAEA-2011), the study of radiation dose for eye lens was carried out using CaSO 4 : Dy based Thermo luminescence dosimeter (TLD). This TLD was worn at center of the forehead to measure eye lens dose. This TLD dose was then compared with chest TLD dose to deduce any correlation between these TLD doses. These TLD doses were assessed on quarterly basis. Eight quarter data of these TLD doses were compared

Organ dose and effective dose with the EOS scanner in spine deformity surgery

DEFF Research Database (Denmark)

Heide Pedersen, Peter; Petersen, Asger Greval; Eiskjær, Søren Peter

2016-01-01

Organ dose and effective dose with the EOS scanner in spine deformity surgery. A study on anthropomorphic phantoms describing patient radiation exposure in full spine examinations. Authors: Peter Heide Pedersen, Asger Greval Petersen, Søren Peter Eiskjær. Background: Ionizing radiation potentially...... quality images while at the same time reducing radiation dose. At our institution we use the EOS for pre- and postoperative full spine examinations. Purpose: The purpose of the study is to make first time organ dose and effective dose evaluations with micro-dose settings in full spine examinations. Our...... hypothesis is that organ dose and effective doses can be reduced 5-10 times compared to standard settings, without too high image-quality trade off, resulting in a theoretical reduction of radiation induced cancer. Methods: Patient dosimetry is performed on anthropomorphic child phantoms, representing a 5...

Mobile-Dose: A Dose-Meter Designed for Use in Automatic Machineries for Dose Manipulation in Nuclear Medicine

Science.gov (United States)

de Asmundis, Riccardo; Boiano, Alfonso; Ramaglia, Antonio

2008-06-01

Mobile-Dose has been designed for a very innovative use: the integration in a robotic machinery for automatic preparation of radioactive doses, to be injected to patients in Nuclear Medicine Departments, with real time measurement of the activity under preparation. Mobile-Dose gives a constant measurement of the dose during the filling of vials or syringes, triggering the end of the filling process based on a predefined dose limit. Several applications of Mobile-Dose have been delivered worldwide, from Italian hospitals and clinics to European and Japanese ones. The design of such an instrument and its integration in robotic machineries, was required by an Italian company specialised in radiation protection tools for nuclear applications, in the period 2001-2003. At the time of its design, apparently no commercial instruments with a suitable interfacing capability to the external world existed: we designed it in order to satisfy all the strict requirements coming from the medical aspects (precision within 10%, repeatability, stability, time response) and from the industrial conceiving principles that are mandatory to ensure a good reliability in such a complicated environment. The instrument is suitable to be used in standalone mode too, thanks to its portability and compactness and to the intelligent operator panel programmed for this purpose.

Quality control of 192Ir high dose rate after loading brachytherapy dose veracity

International Nuclear Information System (INIS)

Feng Zhongsu; Xu Xiao; Liu Fen

2008-01-01

Recently, 192 Ir high dose rate (HDR) afterloading are widely used in brachytherapy. The advantage of using HDR systems over low dose rate systems are shorter treatment time and higher fraction dose. To guarantee the veracity of the delivery dose, several quality control methods are deseribed in this work. With these we can improve the position precision, time precision and dose precision of the brachytherapy. (authors)

Repair and dose-response at low doses

International Nuclear Information System (INIS)

Totter, J.R.; Weinberg, A.M.

1977-04-01

The DNA of each individual is subject to formation of some 2-4 x 10 14 ion pairs during the first 30 years of life from background radiation. If a single hit is sufficient to cause cancer, as is implicit in the linear, no-threshold theories, it is unclear why all individuals do not succumb to cancer, unless repair mechanisms operate to remove the damage. We describe a simple model in which the exposed population displays a distribution of repair thresholds. The dose-response at low dose is shown to depend on the shape of the threshold distribution at low thresholds. If the probability of zero threshold is zero, the response at low dose is quadratic. The model is used to resolve a longstanding discrepancy between observed incidence of leukemia at Nagasaki and the predictions of the usual linear hypothesis

Automated extraction of radiation dose information from CT dose report images.

Science.gov (United States)

Li, Xinhua; Zhang, Da; Liu, Bob

2011-06-01

The purpose of this article is to describe the development of an automated tool for retrieving texts from CT dose report images. Optical character recognition was adopted to perform text recognitions of CT dose report images. The developed tool is able to automate the process of analyzing multiple CT examinations, including text recognition, parsing, error correction, and exporting data to spreadsheets. The results were precise for total dose-length product (DLP) and were about 95% accurate for CT dose index and DLP of scanned series.

The patient dose survey and dose reduction in diagnostic radiology

International Nuclear Information System (INIS)

Dang Thanh Luong; Duong Van Vinh; Ha Ngoc Thach

2000-01-01

This paper presented the results of the patient dose survey in some hospitals in Hanoi from 1995 to 1997. The main investigated types of the X-ray examination were: Chest PA, LAT; Skull PA/AP, LAT; Lumbar spine AP, LAT; and Pelvis AP. The fluctuation of the entrance surface doses (ESD) was too large, even in the same type of X-ray examination and X-ray facility. It was found that the ratio of maximum and minimum ESD were ranged from 1.5 to 18. The mean values of ESD for chest and skull were higher than CEC recommended values, while the mean values of lumbar spine and pelvis were smaller than that of CEC recommended values. The result of dose intercomparison was also reported. Some methods of dose reduction were applied for improving the patient dose in X-ray departments such as a high kV technique, high sensitive screen-film combination. (author)

From physical dose constraints to equivalent uniform dose constraints in inverse radiotherapy planning

International Nuclear Information System (INIS)

Thieke, Christian; Bortfeld, Thomas; Niemierko, Andrzej; Nill, Simeon

2003-01-01

Optimization algorithms in inverse radiotherapy planning need information about the desired dose distribution. Usually the planner defines physical dose constraints for each structure of the treatment plan, either in form of minimum and maximum doses or as dose-volume constraints. The concept of equivalent uniform dose (EUD) was designed to describe dose distributions with a higher clinical relevance. In this paper, we present a method to consider the EUD as an optimization constraint by using the method of projections onto convex sets (POCS). In each iteration of the optimization loop, for the actual dose distribution of an organ that violates an EUD constraint a new dose distribution is calculated that satisfies the EUD constraint, leading to voxel-based physical dose constraints. The new dose distribution is found by projecting the current one onto the convex set of all dose distributions fulfilling the EUD constraint. The algorithm is easy to integrate into existing inverse planning systems, and it allows the planner to choose between physical and EUD constraints separately for each structure. A clinical case of a head and neck tumor is optimized using three different sets of constraints: physical constraints for all structures, physical constraints for the target and EUD constraints for the organs at risk, and EUD constraints for all structures. The results show that the POCS method converges stable and given EUD constraints are reached closely

Dose Reduction and Dose Management in Computed Tomography - State of the Art.

Science.gov (United States)

Zinsser, Dominik; Marcus, Roy; Othman, Ahmed E; Bamberg, Fabian; Nikolaou, Konstantin; Flohr, Thomas; Notohamiprodjo, Mike

2018-03-13

 For years, the number of performed CT examinations has been rising. At the same time, computed tomography became more dose efficient. The aim of this article is to give an overview about the state of the art in dose reduction in CT and to highlight currently available tools in dose management.  By performing a literature research on Pubmed regarding dose reduction in CT, relevant articles were identified and analyzed.  Technical innovations with individual adaptation of tube current and voltage as well as iterative image reconstruction enable a considerable dose reduction with preserved image quality. At the same time, dedicated software tools are able to handle huge amounts of data and allow to optimize existing examination protocols.   · CT examinations are increasingly performed and contribute considerably to non-natural radiation exposure.. · A correct indication is crucial for each CT examination.. · The examination protocol has to be tailored to the medical question and patient.. · Multiple technical innovations enable considerable dose reduction with constant image quality.. · Dose management with dedicated software tools gains importance.. · Zinsser D, Marcus R, Othman AE et al. Dose reduction and dose management in computed tomography - State of the art. Fortschr Röntgenstr 2018; DOI: 10.1055/s-0044-101261. © Georg Thieme Verlag KG Stuttgart · New York.

[Clinical applications of dosing algorithm in the predication of warfarin maintenance dose].

Science.gov (United States)

Huang, Sheng-wen; Xiang, Dao-kang; An, Bang-quan; Li, Gui-fang; Huang, Ling; Wu, Hai-li

2011-12-27

To evaluate the feasibility of clinical application for genetic based dosing algorithm in the predication of warfarin maintenance dose in Chinese population. The clinical data were collected and blood samples harvested from a total of 126 patients undergoing heart valve replacement. The genotypes of VKORC1 and CYP2C9 were determined by melting curve analysis after PCR. They were divided randomly into the study and control groups. In the study group, the first three doses of warfarin were prescribed according to the predicted warfarin maintenance dose while warfarin was initiated at 2.5 mg/d in the control group. The warfarin doses were adjusted according to the measured international normalized ratio (INR) values. And all subjects were followed for 50 days after an initiation of warfarin therapy. At the end of a 50-day follow-up period, the proportions of the patients on a stable dose were 82.4% (42/51) and 62.5% (30/48) for the study and control groups respectively. The mean durations of reaching a stable dose of warfarin were (27.5 ± 1.8) and (34.7 ± 1.8) days and the median durations were (24.0 ± 1.7) and (33.0 ± 4.5) days in the study and control groups respectively. Significant differences existed in the durations of reaching a stable dose between the two groups (P = 0.012). Compared with the control group, the hazard ratio (HR) for the duration of reaching a stable dose was 1.786 in the study group (95%CI 1.088 - 2.875, P = 0.026). The predicted dosing algorithm incorporating genetic and non-genetic factors may shorten the duration of achieving efficiently a stable dose of warfarin. And the present study validates the feasibility of its clinical application.

External dose-rate conversion factors for calculation of dose to the public

Energy Technology Data Exchange (ETDEWEB)

1988-07-01

This report presents a tabulation of dose-rate conversion factors for external exposure to photons and electrons emitted by radionuclides in the environment. This report was prepared in conjunction with criteria for limiting dose equivalents to members of the public from operations of the US Department of Energy (DOE). The dose-rate conversion factors are provided for use by the DOE and its contractors in performing calculations of external dose equivalents to members of the public. The dose-rate conversion factors for external exposure to photons and electrons presented in this report are based on a methodology developed at Oak Ridge National Laboratory. However, some adjustments of the previously documented methodology have been made in obtaining the dose-rate conversion factors in this report. 42 refs., 1 fig., 4 tabs.

Enjebi Island dose assessment

International Nuclear Information System (INIS)

Robison, W.L.; Conrado, C.L.; Phillips, W.A.

1987-07-01

We have updeated the radiological dose assessment for Enjebi Island at Enewetak Atoll using data derived from analysis of food crops grown on Enjebi. This is a much more precise assessment of potential doses to people resettling Enjebi Island than the 1980 assessment in which there were no data available from food crops on Enjebi. Details of the methods and data used to evaluate each exposure pathway are presented. The terrestrial food chain is the most significant potential exposure pathway and 137 Cs is the radionuclide responsible for most of the estimated dose over the next 50 y. The doses are calculated assuming a resettlement date of 1990. The average wholebody maximum annual estimated dose equivalent derived using our diet model is 166 mremy;the effective dose equivalent is 169 mremy. The estimated 30-, 50-, and 70-y integral whole-body dose equivalents are 3.5 rem, 5.1 rem, and 6.2 rem, respectively. Bone-marrow dose equivalents are only slightly higher than the whole-body estimates in each case. The bone-surface cells (endosteal cells) receive the highest dose, but they are a less sensitive cell population and are less sensitive to fatal cancer induction than whole body and bone marrow. The effective dose equivalents for 30, 50, and 70 y are 3.6 rem, 5.3 rem, and 6.6 rem, respectively. 79 refs., 17 figs., 24 tabs

Trends in doses to radiation workers recorded on the Central Index of Dose Information

International Nuclear Information System (INIS)

Greenslade, E.; Kendall, G.M.; Fillary, K.; Bines, W.P.

1991-01-01

This paper presents a preliminary analysis of the doses stored on the Central Index of Dose Information for the calendar years 1986, 1987 and 1988. Mean doses are low, and both mean doses and the proportion of workers exceeding 15 mSv in a year are decreasing with time. Underground miners are the occupational group receiving the highest doses, though in this and other relatively high dose groups the exposures are falling with time. Only 6% of workers are female and their average individual dose is about half that of men. Patterns of employment are different for women and men but there is a tendency for women to receive lower doses than men even within the same occupation. (author)

Prediction of midline dose from entrance ad exit dose using OSLD measurements for total irradiation

Energy Technology Data Exchange (ETDEWEB)

Choi, Chang Heon; Park, Jong Min; Park, So Yeon; Chun, Min Soo; Han, Ji Hye; Cho, Jin Dong; Kim, Jung In [Dept. of Radiation Oncology, Seoul National University Hospital, Seoul (Korea, Republic of)

2017-06-15

This study aims to predict the midline dose based on the entrance and exit doses from optically stimulated luminescence detector (OSLD) measurements for total body irradiation (TBI). For TBI treatment, beam data sets were measured for 6 MV and 15 MV beams. To evaluate the tissue lateral effect of various thicknesses, the midline dose and peak dose were measured using a solid water phantom (SWP) and ion chamber. The entrance and exit doses were measured using OSLDs. OSLDs were attached onto the central beam axis at the entrance and exit surfaces of the phantom. The predicted midline dose was evaluated as the sum of the entrance and exit doses by OSLD measurement. The ratio of the entrance dose to the exit dose was evaluated at various thicknesses. The ratio of the peak dose to the midline dose was 1.12 for a 30 cm thick SWP at both energies. When the patient thickness is greater than 30 cm, the 15 MV should be used to ensure dose homogeneity. The ratio of the entrance dose to the exit dose was less than 1.0 for thicknesses of less than 30 cm and 40 cm at 6 MV and 15 MV, respectively. Therefore, the predicted midline dose can be underestimated for thinner body. At 15 MV, the ratios were approximately 1.06 for a thickness of 50 cm. In cases where adult patients are treated with the 15 MV photon beam, it is possible for the predicted midline dose to be overestimated for parts of the body with a thickness of 50 cm or greater. The predicted midline dose and OSLD-measured midline dose depend on the phantom thickness. For in-vivo dosimetry of TBI, the measurement dose should be corrected in order to accurately predict the midline dose.

Dose concentration and dose verification for radiotherapy of cancer

International Nuclear Information System (INIS)

Maruyama, Koichi

2005-01-01

The number of cancer treatments using radiation therapy is increasing. The background of this increase is the accumulated fact that the number of successful cases is comparative to or even better than surgery for some types of cancer due to the improvement in irradiation technology and radiation planning technology. This review describes the principles and technology of radiation therapy, its characteristics, particle therapy that improves the dose concentration, its historical background, the importance of dose concentration, present situation and future possibilities. There are serious problems that hinder the superior dose concentration of particle therapy. Recent programs and our efforts to solve these problems are described. A new concept is required to satisfy the notion of evidence based medicine, i.e., one has to develop a method of dose verification, which is not yet available. This review is for researchers, medical doctors and radiation technologists who are developing this field. (author)

Post-marketing safety surveillance for inactivated and live-attenuated Japanese encephalitis vaccines in China, 2008-2013.

Science.gov (United States)

Wu, Wendi; Liu, Dawei; Li, Keli; Nuorti, J Pekka; Nohynek, Hanna M; Xu, Disha; Ye, Jiakai; Zheng, Jingshan; Wang, Huaqing

2017-06-22

Two types of Japanese encephalitis (JE) vaccines, inactivated JE vaccine (JE-I) and live-attenuated JE vaccine (JE-L), are available and used in China. In particular, one JE-L, produced by a domestic manufacturer in China, was prequalified by WHO in 2013. We assessed the safety of JE vaccines in China during 2008-2013 using the Chinese National Adverse Events Following Immunization Information System (CNAEFIS) data. We retrieved AEFI reporting data about JE vaccines from CNAEFIS, 2008-2013, examined demographic characteristics of AEFI cases, and used administrative data on vaccine doses as denominator to calculate and compare crude reporting rates. We also used disproportionality reporting analysis between JE-I and JE-L to assess potential safety signals. A total of 34,879 AEFIs related with JE-I and JE-L were reported, with a ratio of male to female as 1.3:1; 361 (1.0%) cases were classified as serious. JE vaccines were administered concurrently with one or more other vaccines in 13,592 (39.0%) of cases. The overall AEFI reporting rates were 214.4 per million vaccination doses for JE-L and 176.9 for JE-I (rate ratio [RR]: 1.2, 95% confidence interval [CI]: 1.1-1.3) in 2010-2013. Febrile convulsions (FC) following JE-I was found as a signal of disproportionate reporting (SDR). However, there was no significant difference between the reporting rates of FC of JE-I and JE-L (0.3 per million vaccination doses for JE-L, 0.4 for JE-I, p=0.05). While our analysis did not find apparent safety concern of JE vaccines in China, further study should consider JE-I vaccines and febrile convulsion, and taking more sensitive methods to detect signals. Copyright © 2017. Published by Elsevier Ltd.

Absorbed dose to mice in prolonged irradiation by low-dose rate ionizing radiation

Energy Technology Data Exchange (ETDEWEB)

Shiragai, Akihiro [National Inst. of Radiological Sciences, Chiba (Japan); Saitou, Mikio; Kudo, Iwao [and others

2000-07-01

In this paper, the dose absorbed by mice was evaluated as a preliminary study of the late effects of prolonged continuous irradiation of mice with low-dose rate ionizing radiation. Eight-week-old male and female SPF C3H/HeN mice in three irradiation rooms were exposed to irradiation at 8000, 400, and 20 mGy, respectively, using a {sup 137}Cs {gamma}-source. Nine racks were arranged in a circle approximately 2.5 m from the source in each room, and 10 cages were arranged on the 4 shelves of each rack. Dose distributions, such as in air at the source level, in the three rooms were estimated by using ionization chambers, and the absorbed dose distributions in the room and relative dose distributions in the cages in relation to the distance of the cage center were examined. The mean abdomen doses of the mice measured by TLD were compared with the absorbed doses in the cages. The absorbed dose distributions showed not only inverse-inverse-square-law behavior with distance from the source, but geometric symmetry in every room. The inherent scattering and absorption in each room are responsible for such behavior and asymmetry. Comparison of relative dose distributions revealed cage positions that are not suitable for experiments with high precision doses, but all positions can be used for prolonged continuous irradiation experiments if the position of the cages is rotated regularly. The mean abdomen doses of the mice were similar in each cage. The mean abdomen doses of the mice and the absorbed doses in a cage were almost the same in all cages. Except for errors concerning the positions of the racks and cages, the uncertainties in the exposure doses were estimated to be about {+-}12% for 8000 mGy group, 17% for 400 mGy group, and 35% for 20 mGy group. (K.H.)

Dose specification for 192Ir high dose rate brachytherapy in terms of dose-to-water-in-medium and dose-to-medium-in-medium

International Nuclear Information System (INIS)

Fonseca, Gabriel Paiva; Yoriyaz, Hélio; Tedgren, Åsa Carlsson; Nilsson, Josef; Persson, Maria; Reniers, Brigitte; Verhaegen, Frank

2015-01-01

Dose calculation in high dose rate brachytherapy with 192 Ir is usually based on the TG-43U1 protocol where all media are considered to be water. Several dose calculation algorithms have been developed that are capable of handling heterogeneities with two possibilities to report dose: dose-to-medium-in-medium (D m,m ) and dose-to-water-in-medium (D w,m ). The relation between D m,m and D w,m for 192 Ir is the main goal of this study, in particular the dependence of D w,m on the dose calculation approach using either large cavity theory (LCT) or small cavity theory (SCT). A head and neck case was selected due to the presence of media with a large range of atomic numbers relevant to tissues and mass densities such as air, soft tissues and bone interfaces. This case was simulated using a Monte Carlo (MC) code to score: D m,m, D w,m (LCT), mean photon energy and photon fluence. D w,m (SCT) was derived from MC simulations using the ratio between the unrestricted collisional stopping power of the actual medium and water. Differences between D m,m and D w,m (SCT or LCT) can be negligible (<1%) for some tissues e.g. muscle and significant for other tissues with differences of up to 14% for bone. Using SCT or LCT approaches leads to differences between D w,m (SCT) and D w,m (LCT) up to 29% for bone and 36% for teeth. The mean photon energy distribution ranges from 222 keV up to 356 keV. However, results obtained using mean photon energies are not equivalent to the ones obtained using the full, local photon spectrum. This work concludes that it is essential that brachytherapy studies clearly report the dose quantity. It further shows that while differences between D m,m and D w,m (SCT) mainly depend on tissue type, differences between D m,m and D w,m (LCT) are, in addition, significantly dependent on the local photon energy fluence spectrum which varies with distance to implanted sources. (paper)

Collective effective dose equivalent, population doses and risk estimates from occupational exposures in Japan