Anticonvulsant property of celecoxib in maximal electroshock seizure: Correlating the role of inflammation in pathophysiology of epileptic seizures

Background: Epilepsy is an abnormal excessive electric neuronal activity and always represents by recurrent seizures. There is positive feedback cycle between epileptogenesis and brain inflammation. It has been proved that an inflammatory enzyme, cyclooxygenase (COX) (especially isoform-2, a constitutive enzyme), expressed in some important parts of the central nervous system and is responsible to induced inflammation locally and having seizurogenic property. Aim and Objective: The goal of this study was to see if celecoxib (a selective COX-2 inhibitor) could reduce the maximal electroshock seizure (MES)-induced seizures in mice. Materials and Methods: Celecoxib injected intraperitoneally in two different doses 5 mg/kgb/w and 10 mg/kg b/w, in albino Swiss mice and in two different phases. MES was elicited and length of different phases was noted. Length of tonic hindlimb extension was considered as indicator of anti-epileptic activity. Results: Celecoxib, when given intraperitoneally, exert significant reduction in the duration of THLE. This action of celecoxib strongly suggests the involvement of inflammation in the pathophysiology of epilepsy. Conclusion: The findings are suggestive of the therapeutic significance of celecoxib, as a future antiepileptic agent for seizure management.

Correlation between 95% spectral edge frequency and depth of anesthesia in patients with schizophrenia / 中国基层医药

Objective:To investigate the value of 95% spectral edge frequency (SEF) in identifying the depth of anesthesia in patients with schizophrenia subjected to modified electroconvulsive therapy center.Methods:A total of 195 patients with schizophrenia who received treatment in The Affiliated Kangning Hospital of Wenzhou Medical University in April to December 2020 were included in this study. They were randomly divided into three groups with 65 patients each. Three groups of patients received different doses of anesthesia before undergoing MECT as follows: group A: propofol 1.5 mg/kg, atropine 0.5 mg/kg, succinylcholine chloride 1.0 mg/kg; group B: propofol 2.0 mg/kg, atropine 0.5 mg/kg, succinylcholine chloride 1.0 mg/kg; group C: propofol 2.5 mg/kg, atropine 0.5 mg/kg, succinylcholine chloride 1.0 mg/kg. 95% SEF and bispectral index (BIS) were measured when patients were awake before treatment (T 1), when eyelash reflex disappeared (T 2), at the beginning of electrical stimulation (T 3), at 3 minutes after electrical stimulation (T 4), and when patients were completely awake (T 5) and compared between groups. The incidence of adverse reaction was recorded at 1 day after treatment. Results:At T 1-T 5, 95% SEF in the group A was (28.50 ± 0.87) Hz, (21.49 ± 0.91) Hz, (21.99 ± 0.92) Hz, (28.42 ± 1.29) Hz, (28.40 ± 1.15) Hz respectively, and it was (28.34 ± 0.91) Hz, (18.93 ± 0.86) Hz, (19.05 ± 0.83) Hz, (27.54 ± 0.73) Hz, (28.42 ± 1.21) Hz respectively in group B and (28.26 ± 0.90) Hz, (16.41 ± 0.75) Hz, (16.36 ± 0.75) Hz, (26.58 ± 0.64) Hz, (28.48 ± 1.19) Hz respectively in group C. 95% SEF measured at T 2 ( t = 24.49, 48.60, both P < 0.05), T 3 ( t = 28.47, 54.51, both P < 0.05), and T 4 ( t = 7.61, 15.91, both P < 0.05) in groups B and C were significantly lower than those in group A. 95% SEF measured at T 2 ( t = 24.11, P < 0.05), T 3 ( t = 26.04, P < 0.05) and T 4 ( t = 8.30, P < 0.05) in group C were significantly lower than those in group B. At T 1-T 5, BIS in group A was (94.16 ± 2.07), (55.34 ± 1.93), (56.61 ± 1.84), (76.29 ± 1.94) and (93.84 ± 2.39) respectively, and it was (94.51 ± 2.25), (52.39 ± 1.58), (52.45 ± 1.94), (73.58 ± 2.19), (93.28 ± 2.52) respectively in group B and (93.97 ± 2.16), (50.57 ± 1.96), (51.60 ± 2.03), (69.51 ± 2.12), (93.57 ± 2.66) respectively in group C. BIS values measured at T 2 ( t = 24.49, 48.60, both P < 0.05), T 3 ( t = 28.34, 54.28, both P < 0.05), and T 4 ( t = 7.61, 15.91, both P < 0.05) in groups B and C were significantly lower than those in group A. BIS measured at T 2 ( t = 24.11, P < 0.05), T 3 ( t = 25.93, P < 0.05), and T 4 ( t = 8.30, P < 0.05) in group C were significantly lower than those in group B. Correlation analysis showed that 95% SEF measured at T 2 ( r = 0.65, P < 0.05), T 3 ( r = 0.68, P < 0.05) and T 4 ( r = 0.49, P < 0.05) were positively correlated with BIS measured at corresponding time points. There were no significant differences in duration of electrical stimulation [(61.25 ± 4.32) seconds, (45.19 ± 3.68) seconds, and (27.54 ± 2.54) seconds, F = 1 434.14, P < 0.05], post-onset inhibition index [(87.68 ± 5.82)%, (81.59 ± 5.35)%, (75.27 ± 4.87)%, F = 87.09, P < 0.05], and average seizure energy index [(5 668.38 ± 1 264.01) μV2, (4 555.61 ± 1 058.96) μV2, (3 642.25 ± 792.68) μV2, F = 59.97, P < 0.05] among the three groups. Duration of electrical stimulation ( t = 36.07, 75.71, both P < 0.05), post-onset inhibition index ( t = 9.15, 18.66, both P < 0.05), and average seizure energy index ( t = 8.49, 15.46, both P < 0.05) in groups B and C were significantly lower than those in group A. Duration of electrical stimulation, post-onset inhibition index and average seizure energy index in group C were significantly lower than those in group B ( t = 39.64, 9.50, 6.97, all P < 0.05). BIS was positively correlated with duration of electrical stimulation ( r = 0.68, P < 0.05), post-onset inhibition index ( r = 0.55, P < 0.05) and average seizure energy index ( r = 0.42, P < 0.05). There were no significant differences in the incidences of headache, myalgia, nausea and vomiting among the three groups ( P > 0.05). Conclusion:95% SEF was positively correlated with BIS in patients with schizophrenia. BIS measured at T 2 was positively correlated with effect of modified electroconvulsive therapy center.

Effect of ethanolic extract of Centella asiatica on maximal electroshock seizure in albino mice

Background: Animal models had always served as integral part in introducing newer drugs for epilepsy. India has long tradition of using herbal medicines. Centella asiatica is an ingredient of various ayurvedic preparations to treat brain related disorders like insanity, memory loss and epilepsy. This research is done to find out the usefulness of Centella asiatica in epilepsy.  Methods: Ethanolic extract of the plant is prepared using Soxhlet apparatus. Experimental seizure is induced in albino mice by maximal electroshock method. Resulting seizure goes through different phases. Duration of the phase of hind limb extension was the measured data. Clinically used anti epileptic drugs can abolish hind limb extension. Effect is compared to that of standard drug phenytoin. Four different doses of the plant extract; 100mg, 200mg, 500mg and 1000mg per kilogram bodyweight was given orally. Statistical analysis of data was done by one way ANOVA and Dunnett test.Results: Ethanolic extract of Centella asiatica exhibited statistically significant protection from maximal electroshock seizures. All given doses of the extract had p<0.05 when compared to control.Conclusions: Centella asiatica is potential source of anti-epileptic drug. Detailed phytochemical studies and animal experiments are recommended.

Design and Synthesis of New Derivatives of (E)-3-(5-((phenylamino)methyl)-1,3,4-thiadiazol-2-yl)-2-styrylquinazolin-4(3H)-one for their Anticonvulsant Potential

Objective: The objective of the paper was to design and synthesize new derivatives of ((E)-3-(5-((substitutedphenylamino)methyl)-1,3,4-thiadiazol-2-yl)-2-styrylquinazolin-4(3H)-one and evaluated for their anticonvulsant potential. Materials and Methods: Various synthesis of (E)-3-(5-(substitutedaminomethyl)-1,3,4-thiadiazol-2-yl)-2-styrylquinazolin-4(3H)-one derivatives has been synthesized by reacting 2-substituted benzoxazin-4-one with (E)-2-(4-Substituedstyryl)-4H-benzo[d] [1,3]oxazin-4-one. All synthesized compounds have been characterized by the infrared, 1HNMR, and mass spectral analysis. Proposed compounds have been evaluated for anticonvulsant potential by subcutaneous pentylenetetrazole and maximal electroshock seizure model and compared with the reference drug phenytoin and carbamazepine. Neurotoxicity study of the synthesized compounds was also performed. Results and Discussion: The anticonvulsant evaluation of synthesized compound QNM-1, QNM-2, QNM-4, QNM-6, QNM-9, QNM-11, QNM-13, and QNM-15 has shown seizure protection at 100 mg/kg dose after 30 min and 4 h, so they have good onset of action as quickly reach brain and have prolonged action reveal that compound metabolized slowly. Whereas compound QNM-7, QNM-8, and QNM-12 were moderate active and reveal that their high concentration is required to cross blood brain barrier. Compounds QNM-3, QNM-5, QNM-10, and QNM-14 were less active. Compounds having chlorine, bromine, fluorine, and nitro in the phenyl moiety have shown good activity when attached to para group but the addition of meta and ortho group of the same may provide least active compounds and in last fluorine compounds have shown comparative less active compounds. Conclusion:The Pharmacological evaluation suggest that eight synthesized compounds have shown promising anticonvulsant potential and bulkier compounds can easily penetrate BBB to exert their effect.

Anticonvulsant activity of nicardipine in experimentally induced seizures in wistar albino rats.

Background: The objective of the study was to evaluate the anticonvulsant activity of nicardipine in wistar albino rats.Methods: Anticonvulsant activity of nicardipine in a dose 10 mg/kg, and its effect with the standard drug lamotrigine (5 mg/kg) was studied in a maximal electroshock seizures (MES) experimental animal model.Results: Nicardipine in dose of 10 mg/kg showed significant anticonvulsant effect (p<0.001) and combination with standard drug lamotrigine (p<0.001) also showed more significant anticonvulsant effect in MES model.Conclusions: Nicardipine is having anticonvulsant activity and it also potentiates the anticonvulsant effect of lamotrigine in MES model.

Assessment of efficacy of promethazine on seizure activity and its interactions with antiepileptic drugs lorazepam and sodium valproate in rats

Background: Presently available antiepileptic drugs are effective in controlling seizures in more than half of patients of all epilepsy but use is often limited by adverse effects. H1 receptor antagonists, have a controversial status in patients of epilepsy. Both pro and antiepileptic effect has been documented in various animal studies. Hence, this study was designed to see the effect of promethazine, an H1 antihistaminic drug and its interactions with antiepileptic drugs lorazepam and sodium valproate in rats.Methods: The effect of promethazine (10 mg/kg) and its interactions with antiepileptic drugs lorazepam and sodium valproate was assessed by using maximal electroshock seizures (MES) and chemoshock pentylenetetrazol (PTZ) method.Results: Promethazine along with lorazepam and sodium valproate in subtherapeutic doses exerted significant protection against MES induced seizures whereas no such protection was observed with PTZ method rather the seizure threshold was reduced.Conclusions: Subtherapeutic doses of promethazine alone and in combination with lorazepam and sodium valproate showed protection against seizures in MES method. However, proconvulsant effect was seen with PTZ method. This shows dual behavior of promethazine on MES and PTZ induced seizures.

Study of anticonvulsant activity of acetazolamide on albino rats and its influence on anticonvulsant activity of sodium valproate

Background: Epilepsy is a common neurological disorder. 30-40% of patients will continue to have seizures despite the use of antiepileptic drugs either alone or in combination. The present study is undertaken to evaluate the anticonvulsant activity of Acetazolamide (ACZ) in albino rats and its influence on anticonvulsant activity of sodium valproate.Methods: Albino rats (150-200gms) of male sex were randomly selected, from central animal facility, MMCRI, Mysore. They were divided into 6groups (per model) of 6 rats each, control group-normal saline 0.5ml, standard group-sodium valproate (300mg/kg), dose 1-ACZ (8.75mg/kg), dose 2-ACZ (17.5mg/kg) and dose 3-ACZ (35mg/kg), dose 4-ACZ (8.75mg/kg) with sodium valproate (150mg/kg). The anti-convulsant activity was screened using MES model and PTZ model.Results: Results were analysed by ANOVA followed by post hoc Fisher’s LSD test. The ACZ has shown anticonvulsant activity at the dose of 17.5mg/kg and 35mg/kg body weight and combination of ACZ 8.75mg/kg with sodium valproate 150mg/kg both in MES model and PTZ model. The anticonvulsant activity of ACZ was less when compared to Sodium Valproate in both MES model and PTZ model. The anticonvulsant activity of combination, ACZ 8.75mg/kg with Sodium valproate 150mg/kg was comparable and more significant when compared to standard drug alone in MES model and PTZ model.Conclusions: The ACZ has shown anticonvulsant activity in MES model and PTZ induced seizure model of epilepsy. This study has shown that ACZ potentiated the effect of sodium valproate and can be used as add on drug with sodium valproate in epilepsy.

Fluoxetine enhances maximal electroshock seizure threshold in Albino rat model when compared to phenytoin

Background: Individuals with epilepsy have a higher incidence of psychiatric disorders than person without epilepsy. Epidemiological studies have shown that the co-morbidity of epilepsy and depression to be high as 50%. The conventional anti-depressants are believed to lower the seizure threshold making it difficult to treat the co-morbid depression, but animal studies have shown SSRIs, a common anti-depressant, to have anti-convulsant properties. So, we propose to study the anticonvulsant effects of fluoxetine, a SSRI, in albino rats against maximal electroshock seizure and to compare against a standard antiepileptic drug phenytoin.Methods: The anticonvulsant effect of fluoxetine was observed in model of maximal electroconvulsive seizure threshold in albino rats. The animals were divided into 3 groups having 6 animals each, receiving distilled water, fluoxetine and phenytoin respectively. The drugs were given orally, and the effect was observed on day 7, 14 and 21. Tonic hind-limb extension was taken as the parameter of electroshock seizure. The effects were compared against a standard anti-seizure drug phenytoin.Results: Fluoxetine showed significant elevation of the seizure threshold following 14 days of administration (P value 0.031). The effect was comparable to phenytoin with no significant difference after 7, 14 and 21 days of treatment (P-value 0.485, 0.699 and 0.818 respectively) though phenytoin showed significant anti-seizure effect since day 7 of treatment.Conclusions: Fluoxetine showed significant anti-seizure activity against electroconvulsive seizure in albino rats.

Acidentes de trabalho e os religadores automáticos no setor elétrico: para além das causas imediatas / Work accidents and automatic circuit reclosers in the electricity sector: beyond the immediate causes / Accidentes de trabajo y reconectadores automáticos en el sector eléctrico: más allá de las causas inmediatas

Resumo: O setor elétrico brasileiro registra elevados índices de mortalidade por acidentes de trabalho que vêm sendo associados à terceirização, introduzida como forma de rebaixamento de custos. Para diminuir o tempo de interrupção do fornecimento de energia aos consumidores, o setor adotou, como solução tecnológica, o religador automático. Essa medida apresenta características perversas para os trabalhadores de manutenção. O objetivo deste estudo é analisar origens e consequências de acidentes de trabalho em sistemas elétricos dotados de religador automático utilizando o Modelo de Análise e Prevenção de Acidentes (MAPA). O MAPA foi usado na investigação de dois acidentes de trabalho visando a explorar as origens organizacionais dos eventos. Caso 1 - ao trocar linha secundária desenergizada, um trabalhador foi atingido por cabo primário energizado (13,8kV). O sistema foi religado três vezes, agravando as lesões (amputação de membro inferior). Caso 2 - acidente de trabalho fatal ocorrido durante instalação de cruzeta nova, em linha energizada, parcialmente isolada. A extremidade de uma mão francesa metálica encostou na linha secundária energizada e eletrocutou o operador de manutenção. O componente desligador do religador automático não funcionou. As análises contribuem para desvelar como a lógica de gestão de negócios pode participar nas origens de acidentes de trabalho via falhas da gestão de manutenção, da gestão de força de trabalho de terceiras e, em especial, da gestão de segurança em sistemas dotados de religadores. As decisões pela automação para garantir a distribuição de energia não podem negligenciar os riscos aos trabalhadores da rede elétrica e, tampouco, deixar de reconhecer a importância do controle sobre as condições de segurança.

Abstract: The Brazilian electricity sector has recorded high work-related mortality rates that have been associated with outsourcing, used to cut costs. In order to decrease the power outage time for consumers, the industry adopted the automatic circuit recloser as the technical solution. The device has hazardous implications for maintenance workers. The aim of this study was to analyze the origins and consequences of work accidents in power systems with automatic circuit recloser, using the Accident Analysis and Prevention (AAP) model. The AAP model was used to investigate two work accidents, aimed to explore the events' organizational origins. Case 1 - when changing a deenergized secondary line, a worker received a shock from the energized primary cable (13.8kV). The system reclosed three times, causing severe injury to the worker (amputation of a lower limb). Case 2 - a fatal work accident occurred during installation of a new crosshead on a partially insulated energized line. The tip of a metal cross arm section strap touched the energized secondary line and electrocuted the maintenance operator. The circuit breaker component of the automatic circuit recloser failed. The analyses revealed how business management logic can participate in the root causes of work accidents through failures in maintenance management, outsourced workforce management, and especially safety management in systems with reclosers. Decisions to adopt automation to guarantee power distribution should not overlook the risks to workers in overhead power lines or fail to acknowledge the importance of ensuring safe conditions.

Resumen: El sector eléctrico brasileño registra elevados índices de mortalidad por accidentes de trabajo, que están siendo asociados a la tercerización, introducida como forma de reducción de costes. Para disminuir el tiempo de interrupción de la energía a los consumidores, el sector adoptó como solución tecnológica, el reconectador automático. Esta medida presenta características perversas para los trabajadores del sector de mantenimiento. El objetivo de este estudio es analizar los orígenes y consecuencias de los accidentes de trabajo en sistemas eléctricos dotados de reconectador automático, utilizando el Modelo de Análisis y Prevención de Accidentes (MAPA). El MAPA se usó en la investigación de dos accidentes de trabajo, con el objetivo de explorar las causas organizativas de los eventos. Caso 1 - al cambiar la línea secundaria sin energía, un trabajador fue alcanzado por un cable primario con energía (13,8kV). El sistema se reconectó tres veces, agravando las lesiones (amputación de miembro inferior). Caso 2 - accidente de trabajo fatal ocurrido durante la instalación de una cruceta nueva, en una línea con energía, parcialmente aislada. La extremidad de una cruceta metálica cayó en la línea secundaria con energía y electrocutó al obrero de mantenimiento. El componente que desconectaba el reconectador automático no funcionó. Los análisis contribuyen a desvelar cómo la lógica de gestión de negocios puede ser partícipe en las causas de accidentes de trabajo, vía fallos en la gestión del mantenimiento, de la gestión de fuerza de trabajo de terceras personas y, en especial, de la gestión de seguridad en sistemas dotados de reconectadores. Las decisiones de la automatización para garantizar la distribución de energía no pueden obviar los riesgos para los trabajadores de la red eléctrica y tampoco dejar de reconocer la importancia del control sobre las condiciones de seguridad.

Analysis of the effect of modified electroconvulsive therapy on cognitive function and therapeutic effect in patients with depression / 中国基层医药

Objective To observe the effect of modified electroconvulsive therapy combined with venlafaxine on cognitive function and its efficacy in patients with depression.Methods 60 patients with depressive disorder were selected,and they were randomly divided into study group and control group according to the random number table method,30 cases in each group.The patients in the study group accepted modified electroconvulsive therapy for 10 times combined with venlafaxine sustained-release tablets treatment,while the patients in the control group were only treated with venlafaxine.Both two groups were treated for 6 weeks.The cognitive function was assessed by the Repeat able Battery for the Assessment of Neuropsycholgical Status (RBANS) and the therapeutic effect was evaluated by Hamilton Depression(HAMD) Scale before and after treatment.Results The scores of immediate memory,delayed memory,speech function,visual breadth and attention of both two groups after treatment were significantly higher than those before treatment(all P ＜ 0.05),and the attention score of the study group was (109.96 ± 19.01) points,which was higher than (100.32 ± 17.13)points of the control group (t =2.062,P ＜ 0.05).The HAMD scores after treatment in both two groups were significantly lower compared with those before treatment (all P ＜ 0.05),and the HAMD score of the study group was (7.23 ± 4.19)points,which was lower than (10.27 ± 5.99)points of the control group (t =2.273,P ＜ 0.05).The total effective rate of the study group(96.7％) was significantly higher than that of the control group (86.7 ％) (x2 =6.546,P ＜ 0.05),and the cure rate of the study group (60.0％) was also higher than that of the control group (36.7％) (x2 =10.901,P ＜ 0.05).Conclusion Modified electroconvulsive therapy combined with venlafaxine treatment can effectively improve the cognitive function of depressive patients,and its effect is significantly better than monotherapy.

Protection Against Electroshock- and Pentylenetetrazol-induced Seizures by the Water Extract of Rehmannia glutinous can be Mediated through GABA Receptor-chloride Channel Complexes

Epilepsy is a brain disorder that affects millions of people worldwide. It is characterized by recurrent and unpredictable seizures that are usually controlled with antiepileptic/anticonvulsive drugs. However, most antiepileptic drugs produce various side effects such as tolerance and sedation. Thus, there is a growing interest for alternative anticonvulsive drugs, preferably from natural or herbal sources. In this study, we evaluated the anticonvulsive effects of Rehmannia glutinosa (RG). The anticonvulsive effect of RG extract was evaluated using electroshock- and chemical-induced seizure tests in mice. To identify its probable mechanism of action, the effects of RG extract on Cl− influx was measured in vitro. We found that RG extract has anticonvulsive effects against electroshock-induced seizures, as indicated by an increased seizure threshold in mice. The RG extract also decreased the percentage of seizure responses induced by the GABAergic antagonist, pentylenetetrazole. These results suggest that the anticonvulsive effects of RG extract are mediated through a GABAergic mechanism. In support of this mechanism, our in vitro test showed that RG extract increases intracellular Cl− influx. Furthermore, RG extract did not show sedative and/or muscle relaxant effects in the open-field and rota-rod tests. Altogether, these results confirm that RG extract could be a herbal anticonvulsant and a potential alternative for clinical use.

Effect of electroconvulsive therapy on p-GluR1 and p-CaMK Ⅱ α expression under small dose ketamine combined with propofol anesthesia in depressed rats / 中华麻醉学杂志

Objective To evaluate the effect of electroconvulsive therapy (ECT) on the expression of phosphorylated glutamate receptor 1 (p-GluR1) and Ca2+/calmodulin-dependent protein kinase Ⅱ α (p-CaMK Ⅱ α) under small dose ketamine combined with propofol anesthesia in the depressed rats.Methods Forty healthy adult male Sprague-Dawley rats,weighing 200-250 g,aged 2-3 months,were used in this study.Mental depression was induced by exposing the animals to chronic unpredictable mild stress (CUMS).Forty mentally depressed rats were divided randomly into 5 groups (n =8 each) using a random number table:M0-4 groups.Propofol 80 mg/kg and ketamine 10 mg/kg were injected intraperitoneally in M0-4 groups.After disappearance of righting reflex,M1-4 groups received ECT of 60,120,180 and 240 mC once a day for 7 consecutive days,respectively,by means of a current (frequency 50 Hz,sine-wave,pulse width 0.7 ms,1-s duration) delivered via ear-clip electrodes,while group M0 received ECT of no quantity of electric charge via ear-clip electrodes.Before CUMS,at 1 day after CUMS and at 1 day after ECT,sucrose preference test was applied to evaluate the depressive behavior.The sucrose preference percentage (SPP) was calculated.At 4 days after CUMS and 4 days after ECT,the learning and memory function was assessed using Morris water maze test.The rats were then sacrificed,and hippocampi were isolated to detect the expression of GluR1,p-GluRl,CaMK Ⅱ α and p-CaMK Ⅱ α by Western blot.Results The SPP was significantly lower after CUMS than before CUMS in M0-4 groups (P＜0.05).Compared with that after CUMS,the SPP was significantly increased,the escape latency was shortened,and the space exploration time was prolonged after ECT in M1-4 groups (P＜0.05).There was no significant difference in SPP after ECT between M1-4 groups (P＞0.05).Compared with group M0,the SPP was significantly increased,and the expression of pGluR1 and p-CaMK Ⅱ α was up-regulated in M1-4groups (P＜0.05).Compared with group M2,the escape latency was significantly prolonged,the space exploration time was shortened,and the expression of pGluR1 and p-CaMK Ⅱ α was down-regulated after ECT in the other groups (P＜0.05).There was no significant difference in GluR1 and CaMK Ⅱ α expression after ECT between the five groups (P＞ 0.05).Conclusion ECT can induce cognitive decline when applied for anti-depression under small dose ketamine combined with propofol anesthesia,and the mechanism is related to increased phosphorylation of GluR1 and CaMK Ⅱ α expression in rats.

Anticonvulsant activity of nitrendipine in albino mice.

Background: The objective is to evaluate the anticonvulsant activity of nitrendipine in seizure-induced mice. Methods: Albino mice (25-30 g) of either sex were randomly selected and divided into four groups of six mice each. After overnight fasting, Group I received 0.25 ml of propylene glycol and served as the control, Group II received valproic acid (110 mg/kg orally) as standard, Groups III received 5 mg/kg of nitrendipine and 100 mg/kg of valproic acid, Group IV received 5 mg/kg of nitrendipine and 75 mg/kg of valproic acid, and Group V received 5 mg/kg of nitrendipine and 50 mg/kg of valproic acid all of which were administered orally 60 mins prior to the test in this acute study. The anticonvulsant activity was screened using maximal electroshock (MES) model and pentylenetetrazole (PTZ) model. Results: The nitrendipine showed a considerable reduction in the duration of hindlimb extensor phase in MES model and also delayed the latency of seizures induced by PTZ when compared with control group. The probable mechanism of anticonvulsant action of nitrendipine could be due to its interference with the gamma amino butyric acid type aminergic mechanism, modulation of nicotinic, and N-methyl-D-aspartate receptors. Conclusion: Nitrendipine possesses the anticonvulsant activity and has a beneficial role in epilepsy.

Pro-Convulsant Effect of Olanzapine, an Atypical Antipsychotic on Maximal Electro Shock Induced Seizures in Wistar Albino Rats.

Objectives: The aim of the study was to investigate the chronic effect of Olanzapine; an atypical antipsychotic drug on maximal electroshock (MES) induced seizures in Wistar albino rats. Methods: Olanzapine (2mg/kg, 10 days orally) was used to study its effect on MES induced seizures in Wistar albino rats. Duration of the tonic hind limb extension was noted. Results: Olanzapine (2mg/kg) significantly (p<0.001) increased the duration of hind limb extension induced by MES. Conclusions: The data suggests that Olanzapine, the atypical antipsychotic drug has a proconvulsant action.

Anticonvulsant Activity of Moringa Oleifera in Swiss Albino Mice.

Objectives: The aim of the study was to investigate anticonvulsant effect of Moringa oleifera on maximal electroshock (MES), pentylenetetrazole (PTZ) and pilocarpine induced seizures. Methods: The ethanolic extract of Moringa oleifera leaves (200mg/ Kg) was used to study its anticonvulsant effect on MES, PTZ and pilocarpine induced seizures in Swiss albino mice. Suppression of the tonic hind limb extension, duration of convulsion, abolition of convulsions was noted respectively for the above tests. Results: The ethanolic extracts of Moringa oleifera leaves (200mg/ Kg) significantly (p<0.001) abolished the hind limb extension induced by MES. The same dose also significantly (p<0.001) protected the animals from PTZ induced tonic convulsions. None of the animals treated with same dose of plant extract reached the status epilepticus state in pilocarpine induced seizures. Conclusions: The data suggests that the ethanolic extracts Moringa oleifera leaves may produce its anticonvulsant effect via different mechanisms since it prevented the hind limb extension induced by MES, decreased the duration of convulsions produced by PTZ and abolished status epilepticus in pilocarpine induced seizures.

Study of potential drug-drug interactions between benzodiazepines and four commonly used antiepileptic drugs in mice.

Background: Benzodiazepines (BZD) is one of the commonly used drug groups for certain neurological diseases. As sometimes, the anti-epileptic drugs (AEDs) may be used concomitantly with BZD there is a potential for drug-drug interactions. Study aimed to study potential drug-drug interactions between four commonly used AEDs (phenytoin, carbamazepine (CBZ), phenobarbitone, sodium valproate) and BZD (diazepam, clonazepam) in mice using maximal electroshock seizure (MES) method and pentylenetetrazole (PTZ) method. Methods: Adult male albino mice were divided into four different groups of six animals each and anti-epileptic activity was assessed using MES method and PTZ method. Group I acted as a control, Group II received any one of the four AEDs (phenytoin, CBZ, phenobarbitone or sodium valproate) in sub-effective doses, Group III received diazepam or clonazepam alone, Group IV received a combination of diazepam or clonazepam with any one of the AEDs. Results: In MES method, the groups receiving combination of diazepam with phenytoin and CBZ showed significant protection compared to the control group (p<0.01 and p<0.02), respectively. However, diazepam in combination with sodium valproate and phenobarbitone did not show any significant protection compared to the control group and individual antiepileptic group. All the four antiepileptic showed significant protection against MES seizure in combination with clonazepam when compared to control group. In PTZ method, combination of sodium valproate with clonazepam showed significant protection compared to control group (p<0.02). However, this was not observed with diazepam-valproate combination. Conclusion: Clonazepam potentiates the action of all the four anti-epileptics while diazepam potentiates only phenytoin and CBZ against MES seizures. Clonazepam but not diazepam potentiates the action of sodium valproate against PTZ seizures.

Assessment of the anticonvulsant activity of pyrazolo[1,5-a][1,3,5]triazines obtained by synthesis / Evaluación de la actividad anticonvulsiva de pirazolo [1,5-a] [1,3,5] triazinas obtenidos por síntesis

Giving that the pyrazolo[1,5-a][1,3,5]triazine system is a potential source of pharmacological agents for treatment of central nervous system disorders this work was aimed to asses anticonvulsant and acute neurotoxic effects of six molecules obtained by synthesis, using experimental models in mice. A series of six pyrazolo[1,5-a][1,3,5]triazines (EAC-21, EAC-31, EAC-33, MH4a, MH4b1 and MH4c) obtained by one-step reaction from S,S-diethyl aroyl-/hetaroylimidodithiocarbonates and 5-aminopyrazoles were screened in vivo (300 mg/kg, v.o.) for their anticonvulsant activity in the maximal electroshock (MES) test in ICR mice and for acute toxicity in the rota-rod and wiring test. The structures of the obtained compounds were unambiguously established by IR, 1H and 13C-NMR spectroscopic techniques, COSY 1H-1H, HSQC and HMBC experiments, mass spectrometry and elemental analyses. Results shown that only MH4b1 showed protection against MES (p<0.05) and was devoid of gross neurotoxicity signs. Therefore, MH4b1 was chosen for additional anticonvulsant screening against MES, pentilenetetrazole, picrotoxin, strychnine and 6 Hz psychomotor seizure model, in a dose dependent manner (50, 150, 300 mg/kg, v.o.). MH4b1 also protected against 6 Hz seizure test (>150 mg/kg, v.o.). These data suggest that MH4b1 could be a source for anticonvulsant pyrazolo[1,5-a][1,3,5]triazine analogs potentially useful against tonic clonic and refractory seizures.

Dado el interés que el sistema pirazolo[1,5-a][1,3,5]triazina tiene como fuente potencial para la obtención de agentes farmacológicos para el tratamiento de trastornos del sistema nervioso central, en este trabajo se efectuó el cribado anticonvulsivante y el efecto neurotóxico agudo de seis moléculas derivadas de este sistema, en ratones ICR. La serie de compuestos denominados EAC-21, EAC-31, EAC-33, MH4a, MH4b1 y MH4c, obtenidas por la reacción de S,S-dietil aroil-/heteroilimidoditiocarbonatos y 5-aminopirazoles se evaluó in vivo (300 mg/kg, v.o.) en la prueba de convulsiones inducidas por electrochoque y en las pruebas de actividad neurotóxica aguda del eje rodante y del alambre. La estructura de estos compuestos se determinó por técnicas de infrarrojo, espectroscopia de 1H, 13C-NMR, COSY 1H-1H, experimentos de HSQC y HMBC, espectrometría de masas y análisis elemental. Los resultados mostraron que el compuesto MH4b1 confirió protección frente a las convulsiones inducidas por electrochoque (p<0.05) sin producir signos de neurotoxicidad aguda. Por consiguiente, MH4b1 se escogió para las siguientes pruebas de actividad anticonvulsivante, dosis - respuesta (50, 150, 300 mg/kg, v.o.): electrochoque, pentilenetetrazol, picrotoxin, estricnina y el modelo de convulsión psicomotora de 6 Hz. MH4b1 mostró efectos protectores en función de la dosis frente a las pruebas de convulsión por electrochoque (>150 mg/kg) y convulsión de 6 Hz (300 mg/kg, v.o.). Estos resultados sugieren que MH4b1 podría constituirse en fuente anticonvulsivante del sistema pirazolo[1,5-a][1,3,5]triazina eventualmente útil para el tratamiento de las crisis tónicas clónicas generalizadas y las crisis refractarias.

The Cause Analysis and Countermeasures of Frequent Shocks in Patients with Implantable Cardioverter Defibrillator / 天津医药

Objective To investigate the cause and countermeasures of frequent shocks in patients with implantable cardioverter defibrillators (ICD). Methods Eighty ICD patients with heart failure and malignant ventricular arrhythmias were followed up, including sixty-two male and eighteen female patients. There were 35 patients with single-chamber ICD, 23 with dual-chamber ICD and 22 with three-chamber ICD. Patients in this study were followed up for 1-6 years to analyze the reasons for ICD discharge. According to the specific circumstances, patients were treated. Results Twenty-three pa-tients in 80 patients suffered from shock treatment. Ten patients (12.5%) experienced frequent shocks. The causes of fre-quent shock included repeated episodes of ventricular tachycardia, invalid shock due to increased defibrillation threshold (DF) and false identification of the frequent episodes of paroxysmal ventricular tachycardia or arrhythmias. The management included the identification process adjustment of ventricular tachycardia and supraventricular tachycardia, increased num-bers of beats of ventricular tachycardia judgment and increase the basic pacing rate. The anti-arrhythmic drugs should be combinedly used, especially metoprolol and amiodarone. The ICD shock was significantly reduced after parameter optimiza-tion and anti-arrhythmic therapy. Conclusion The ICD shocks were effectively reduced with rational use of anti-arrhyth-mic drugs and valid ICD programming.

Effect of Acute and Chronic Electroconvulsive Shock on 5-Hydroxytrypamine 6 Receptor Immunoreactivity in Rat Hippocampus

Electroconvulsive shock (ECS) induces not only an antidepressant effect but also adverse effects such as amnesia. One potential mechanism underlying both the antidepressant and amnesia effect of ECS may involve the regulation of serotonin (5-hydroxytryptamine) 6 (5-HT6) receptor, but less is known about the effects of acute ECS on the changes in 5-HT6 receptor expression in the hippocampus. In addition, as regulation of 5-HT receptor expression is influenced by the number of ECS treatment and by interval between ECS treatment and sacrifice, it is probable that magnitude and time-dependent changes in 5-HT6 receptor expression could be influenced by repeated ECS exposure. To explore this possibility, we observed and compared the changes of 5-HT6 receptor immunoreactivity (5-HT6 IR) in rat hippocampus at 1, 8, 24, or 72 h after the treatment with either a single ECS (acute ECS) or daily ECS for 10 days (chronic ECS). We found that acute ECS increased 5-HT6 IR in the CA1, CA3, and granule cell layer of hippocampus, reaching peak levels at 8 h and returning to basal levels 72 h later. The magnitude and time-dependent changes in 5-HT6 IR observed after acute ECS were not affected by chronic ECS. These results demonstrate that both acute and chronic ECS transiently increase the 5-HT6 IR in rat hippocampus, and suggest that the magnitude and time-dependent changes in 5-HT6 IR in the hippocampus appear not to be influenced by repeated ECS treatment.