Open-label comparative study of the efficacy of sodium valproate and topiramate as prophylactic therapy for migraine in adults

Background: Migraine is a most common and highly prevalent neurologic disorder characterized by recurrent moderate-to-severe headaches often in association with a number of autonomic nervous system symptoms. Sodium valproate and topiramate are the two newer antiepileptic agents which are commonly prescribed for the migraine prophylaxis in India. Aims and Objectives: The aims of the study were as follows: (1) To compare the efficacy of sodium valproate 15–30 mg/kg/day and topiramate 2–3 mg/kg/day as prophylactic therapy for migraine in adults and (2) to study cost-effectiveness and safety profile of sodium valproate and topiramate. Materials and Methods: It is an open-label comparative study; 100 migraine patients of age group between 20 years and 50 years of both sexes were enrolled in the present study according to the inclusion criteria. Patients were diagnosed as migraine as per the International Criteria For Headache Disorders-3. Before starting treatment and after diagnosis, investigations have done, that is, complete blood picture, liver function test, renal function test, random blood sugar, and thyroid profile. Randomization was done by choosing every alternate patient and study drugs were prescribed. One hundred patients were divided into two groups, Group-A: 50 patients administered Tab. sodium valproate 500 mg twice daily orally and Group-B: 50 patients administered Tab. topiramate 150 mg once daily orally for a period of 6 months. Results: In Group-A, the severity of pain value before starting treatment was 6.440 ± 2.130 which is reduced to 1.820 ± 1.024 at the end of the treatment which was statistically significant (P < 0.0001) and the frequency of headache value before starting treatment was 4.220 ± 1.298 which is reduced to 1.320 ± 0.7407 at the end of the treatment, P < 0.0001 which was statistically significant. In Group-B, the severity of pain value before starting treatment was 6.200 ± 2.119 which is reduced to 1.840 ± 0.9765 after starting treatment which was statistically significant (P < 0.0001) and the frequency of headache value before starting treatment was 4.300 ± 1.199 which is reduced to 1.340 ± 0.6884 after starting treatment, P < 0.0001 which was statistically significant. In between the two groups severity of migraine pain and headache frequencies the P value was statistically significant. Conclusion: The results of the present study demonstrated that both sodium valproate and topiramate were well tolerated, having similar efficacy in reducing the severity of the pain, headache frequencies, and improving the quality of life. Sodium valproate is preferred because of cost-effectiveness.

Expression and effect of roundabout guidance receptor 1 during valproate induced neural stem cells differentiation / 解剖学报

Objective To investigate the expression and role of roundabout guidance receptor 1 (Robo1) in the neuronal differentiation of neural stem cells (NSCs) induced by valproate (VPA). Methods The hippocampus NSCs of SD rats were isolated and cultured. Normal NSCs and VPA-treated NSCs were extracted from 10 SD rats. After VPA treatment, the proportion of neuron-specific marker β-tubulin III (Tuj1) positive neurons differentiated from NSCs were detected by immunofluorescence. The differentially expressed mRNA in normal NSCs and VPA-induced NSCs were detected by gene chip technology. After VPA treatment, the expression levels of Robo1 mRNA and protein were detected by Real-time PCR and Western blotting. The dynamic changes of Robo1 mRNA were detected by Real-time PCR after the differentiation of NSCs. After the expression of Robo1 was down-regulated in NSCs by small interfering RNA, the expression of Robo1 protein was detected by Western blotting, and the expression levels of neuron-specific markers Tuj1 and microtubule associated protein-2 (MAP-2) were detected by Real-time PCR and immunofluorescence. Results VPA induced NSCs to differentiate into neurons. Compared with the control group, the expression levels of Robo1 mRNA and protein in the differentiation of NSCs were significantly up-regulated during valproate treatment. After interference of Robo1 expression, not only Robo1 upregulation was inhibited during the differentiation of NSCs induced by VPA, but also the proportion of NSCs differentiated into neurons decreased. Conclusion VPA may promote the differentiation of NSCs into neurons by up-regulating the expression of Robo1.

A pilot study on the effects of early use of valproate sodium on neuroinflammation after traumatic brain injury / 中国当代儿科杂志

OBJECTIVES@#To study the effect of early use of sodium valproate on neuroinflammation after traumatic brain injury (TBI).@*METHODS@#A total of 45 children who visited in Xuzhou Children's Hospital Affiliated to Xuzhou Medical University from August 2021 to August 2022 were enrolled in this prospective study, among whom 15 healthy children served as the healthy control group, and 30 children with TBI were divided into a sodium valproate treatment group and a conventional treatment group using a random number table (n=15 each). The children in the sodium valproate treatment group were given sodium valproate in addition to conventional treatment, and those in the conventional group were given an equal volume of 5% glucose solution in addition to conventional treatment. The serum concentrations of nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3), high-mobility group box 1 (HMGB1), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) were measured in the healthy control group on the day of physical examination and in the children with TBI on days 1, 3, and 5 after admission. Glasgow Outcome Scale-Extended (GOS-E) score was evaluated for the children with TBI 2 months after discharge.@*RESULTS@#Compared with the healthy control group, the children with TBI had significantly higher serum concentrations of NLRP3, HMGB1, TNF-α, and IL-1β on day 1 after admission (P<0.017). The concentration of NLRP3 on day 5 after admission was significantly higher than that on days 1 and 3 after admission in the children with TBI (P<0.017). On days 3 and 5 after admission, the sodium valproate treatment group had a significantly lower concentration of NLRP3 than the conventional treatment group (P<0.05). For the conventional treatment group, there was no significant difference in the concentration of HMGB1 on days 1, 3, and 5 after admission (P>0.017), while for the sodium valproate treatment group, the concentration of HMGB1 on day 5 after admission was significantly lower than that on days 1 and 3 after admission (P<0.017). On day 5 after admission, the sodium valproate treatment group had a significantly lower concentration of HMGB1 than the conventional treatment group (P<0.05). For the children with TBI, the concentration of TNF-α on day 1 after admission was significantly lower than that on days 3 and 5 after admission (P<0.017). On days 3 and 5 after admission, the sodium valproate treatment group had a significantly lower concentration of TNF-α than the conventional treatment group (P<0.05). The concentration of IL-1β on day 3 after admission was significantly lower than that on days 1 and 5 after admission (P<0.017) in the children with TBI. On days 3 and 5 after admission, the sodium valproate treatment group had a significantly lower concentration of IL-1β than the conventional treatment group (P<0.05). The GOS-E score was significantly higher in the sodium valproate treatment group than that in the conventional treatment group 2 months after discharge (P<0.05).@*CONCLUSIONS@#Early use of sodium valproate can reduce the release of neuroinflammatory factors and improve the prognosis of children with TBI.

O uso do canabidiol em crianças com epilepsia resistente a medicamento e a diminuição na frequência das crises: revisão rápida / The use of cannabidiol in children with drug-resistant epilepsy and the decrease in the frequency of seizures: quick review

Uso de canabidiol (CDB) medicinal presente no óleo de canabis. Indicação: Tratamento de crianças portadoras de epilepsia refratária resistente a medicação e síndromes graves decorrentes. Pergunta: O uso do canabidiol em crianças com epilepsia resistente a medicamentos apresentaria diminuição na frequência de crises convulsivas? Objetivo: Investigar a eficácia e a segurança do canabidiol, em comparação a placebo, na manutenção da remissão em crianças com epilepsia refratária. Métodos: Revisão rápida de revisões sistemáticas, por meio de buscas bibliográficas realizadas nas bases PUBMED, SCOPUS, BVS, Cochrane Library. Foram utilizadas estratégias de buscas com vocabulário padronizado e avaliação da qualidade metodológica usando o checklist AMSTAR 2. Resultados: Foram selecionadas duas revisões sistemáticas que atendiam aos critérios de elegibilidade. O CDB quando comparado ao placebo reduziu 50% das convulsões para epilepsia refrataria (RR 1.69 [1.20 ­ 2.36]), para a síndrome de Lennox-Gastaut o RR foi 2.98 (IC 95%, 1.83 - 4.85) e para a síndrome de Dravet o RR foi 2.26 (IC 95% ,1.38 - 3.70). O CDB pode resultar em uma diminuição no apetite em dosagens maiores (RR = 2,10, IC 95% [0,96­4,62], embora não apresente diferença de efeito dos grupos comparadores. Conclusão: Duas revisões sistemáticas recentes o CDB quando comparado ao placebo reduziu 50% das convulsões para epilepsia refrataria e síndromes graves. Entretanto, existem poucos ensaios clínicos publicados na área

: Use of cannabidiol (CBD) present in cannabis oil. Indication: Treatment of children with drug-resistant refractory epilepsy and severe syndromes resulting. Question: Would the use of cannabidiol in children with drug-resistant epilepsy lead to a decrease in seizure frequency? Objective: to investigate the efficacy and safety of cannabidiol, compared to placebos, in maintaining remission in children with refractory epilepsy. Methods: Rapid review of systematic reviews, through a bibliographical search carried out in the PUBMED, SCOPUS, BVS, Cochrane Library databases. Predefined search strategies were followed, and the methodological quality of the included studies was evaluated using the AMSTAR 2 tool. Results: Two systematic reviews were selected, which met the eligibility criteria. CBD when compared to placebo reduce 50% of seizures for refractory epilepsy (RR 1.69, IC 95% [1.20 ­ 2.36]), for Lennox-Gastaut Syndrome the RR was foi 2.98 (IC 95%, 1.83 - 4.85) and for Dravet Syndrome o RR FOI 2.26 (IC 95% ,1.38 - 3.70). CBD may result in appetite decrease using high doses (RR = 2.10, 95% IC [0.96­ 4.62], with no statistical difference. Conclusion: Two recent systematics, CBD, when compared to placebo, presented 50% of seizures for refractory epilepsy and severe syndromes. However, there are few clinical trials published in the area

Efectos adversos severos de los estabilizadores del ánimo: revisión de la literatura

Introducción: El trastorno bipolar TB es una enfermedad crónica y recurrente, según el DSM 5 se clasifica en los subtipos: trastorno bipolar I, trastorno bipolar II, ciclotimia y categorías residuales de formas atípicas que no encajan en los subtipos antes mencionados. La prevalencia del TB tipo I es similar entre hombres y mujeres, mientras que el TB tipo II ocurre con mayor frecuencia en mujeres. Según la Encuesta nacional de salud mental la prevalencia estimada del trastorno bipolar tipo I en Colombia es del 1,9% en los hombres y del 0,6% en las mujeres, para un porcentaje total de 1,3%. La etiología de TB incluye factores genéticos, neuro bioquímicos, neuro anatómicos, así como médicos y ambientales. El tratamiento del trastorno bipolar se puede dividir en dos fases distintas: manejo de un episodio inicial y tratamiento a largo plazo para prevenir recaídas, los fármacos utilizados comúnmente son: litio, antipsicóticos y anticonvulsivantes. Los estabilizadores del estado del ánimo aceptados por la FDA son: litio, carbamazepina, divalproato, y lamotrigina. Una reacción adversa a medicamentos (RAM) se define como cualquier respuesta nociva y no intencionada a un medicamento, constituye una importante causa de morbimortalidad y de aumento de los costes sanitarios. Los sistemas de farmaco-vigilancia permiten la identificación y prevención de los riesgos asociados al uso de medicamentos. Metodología: Se realizó una búsqueda bibliográfica mediante la base de datos PubMed, utilizando términos MeSH. Los criterios de inclusión utilizados fueron: a) Artículos publicados entre el año 2016 y 2021, b) Idioma inglés o español, c) Población a estudio: pacientes con diagnóstico de trastorno bipolar según criterios del DSM. Resultados: Se encontró que los efectos adversos severos de los estabilizadores del estado del ánimo como la carbamazepina y el ácido valproico son variados, se pueden presentar manifestaciones cutáneas como el síndrome de Stevens-Johnson, necrólisis epidérmica tóxica; manifestaciones hematológicas como anemia aplásica y manifestaciones hepáticas como lo son la hepatotoxicidad e hiperamonemia.

SUMMARY Introduction: Bipolar disorder TB is a chronic and recurrent disease, according to DSM 5 it is classified into subtypes: bipolar I disorder, bipolar II disorder, cyclothymia and residual categories of atypical forms that do not fit into aforementioned subtypes. Prevalence of type I TB is similar between men and women, while type II TB occurs more frequently in women. According to the National Mental Health Survey, estimated prevalence of type I bipolar disorder in Colombia is 1.9% in men and 0.6% in women, for a total percentage of 1.3%. Etiology of TB includes genetic, neuro biochemical, neuro anatomical, as well as medical and environmental factors. Treatment of bipolar disorder can be divided into two phases: management of an initial episode and long-term treatment to prevent relapses, drugs normally used are: Lithium, antipsychotics and anticonvulsants. Mood stabilizers accepted by FDA are: Lithium, carbamazepine, divalproex, and lamotrigine. An adverse drug reaction (ADR) is defined as any harmful and unintended response to a drug, it constitutes a major cause of morbidity and mortality and increased healthcare costs. Pharma-covigilance systems allow identification and prevention of risks associated with use of drugs. Methodology: A graphic search was performed using PubMed database, using MeSH terms. Inclusion criteria used were: a) Articles published between 2016 and 2021, b) English or Spanish language, c) Study population: Patients with a diagnosis of Bipolar Disorder according to DSM criteria. Results: It was found that severe adverse effects of mood stabilizers such as carbamazepine and valproic acid are varied, skin manifestations such as Stevens-Johnson's syndrome, toxic epidermal necrolysis can occur; Hematological manifestations such as aplastic anemia and hepatic manifestations such as hepatotoxicity and hyperammonemia.

Introdução: O transtorno bipolar TB é uma doença crônica e recorrente, segundo o DSM 5 é classificada em subtipos: transtorno bipolar I, transtorno bipolar II, ciclo-timia e categorias residuais de formas atípicas que não se enquadram nos subtipos mencionados. A prevalência de TB tipo I é semelhante entre homens e mulheres, enquanto a TB tipo II ocorre com mais frequência em mulheres. De acordo com a Pesquisa Nacional de Saúde Mental, a prevalência estimada de transtorno bipolar tipo I na Colômbia é de 1,9% nos homens e 0,6% nas mulheres, para um percentual total de 1,3%. A etiologia da TB inclui fatores genéticos, neuro-bioquímicos, neuro-anatômicos, médicos e ambientais. O tratamento do transtorno bipolar pode ser dividido em duas fases distintas: manejo de um episódio inicial e tratamento de longo prazo para prevenção de recidivas, os medicamentos comumente utilizados são: lítio, antipsicóticos e anticonvulsivantes. Os estabilizadores de humor aceitos pela FDA são: lítio, carbamazepina, divalproex e lamotrigina. Uma reação adversa a medicamento (ADR) é definida como qualquer resposta prejudicial e não intencional a um medicamento, é uma das principais causas de morbidade e mortalidade e aumento dos custos de saúde. Os sistemas de farmacovigilância permitem a identificação e prevenção dos riscos associados ao uso de medicamentos. Metodologia: Foi realizada pesquisa bibliográfica na base de dados PubMed, utilizando termos MeSH. Os critérios de inclusão utilizados foram: a) Artigos publicados entre 2016 e 2021, b) Língua inglesa ou espanhola, c) População do estudo: Pacientes com diagnóstico de Bipolar Desordem de acordo com os critérios do DSM. Resultados: Verificou-se que os efeitos adversos graves dos estabilizadores do humor como a carbamazepina e o ácido valpróico são variados, podendo ocorrer manifestações cutâneas como a síndrome de Stevens-Johnson, podendo ocorrer necrólise epidérmica tóxica; Manifestações hematológicas como anemia aplástica e manifestações hepáticas como hepatotoxicidade e hiperamonemia.

Association of Child Neurology (AOCN) Consensus Statement on the Diagnosis and Management of Febrile Seizures

Justification: Febrile seizures are quite common in children but there are controversies in many aspects of their diagnosis and management. Methods: An expert group consisting of pediatric neurologists and pediatricians was constituted. The modified Delphi method was used to develop consensus on the issues of definitions and investigations. The writing group members reviewed the literature and identified the contentious issues under these subheadings. The questions were framed, pruned, and discussed among the writing group members. The final questions were circulated to all experts during the first round of Delphi consensus. The results of the first round were considered to have arrived at a consensus if more than 75% experts agreed. Contentious issues that reached a 50- 75% agreement was discussed further in online meetings and subsequently voting was done over an online platform to arrive at a consensus. Three rounds of Delphi were conducted to arrive at final statements. Results: The expert group arrived at a consensus on 52 statements. These statements pertain to definitions of febrile seizures, role of blood investigations, urine investigations, neuroimaging, electroencephalography (EEG), cerebrospinal fluid analysis and screening for micronutrient deficiency. In addition, role of rescue medications, intermittent anti-seizure medication and continuous prophylaxis, antipyretic medication and micronutrient supplementation have been covered. Conclusion: This consensus statement addresses various contentious issues pertaining to the diagnosis and management of febrile seizures. Adoption of these statements in office practice will improve and standardize the care of children with this disorder.

The role and mechanism of sodium valproate in alleviating cardiac and cerebral injuries after cardiopulmonary resuscitation in pigs / 中华急诊医学杂志

Objective:To investigate the role and mechanism of sodium valproate (VPA) in cardiac and cerebral injuries after cardiopulmonary resuscitation (CPR) in pigs.Methods:Twenty-five healthy male domestic pigs, weighing (37±3) kg, were randomly divided into the sham group ( n=6), CPR group ( n=10), and CPR+VPA group ( n=9). Cardiac arrest was induced by alternating current delivered via a pacing catheter in the right ventricle and untreated for 9 min, and then CPR was performed for 6 min, in which this procedure was used to establish the animal model of cardiac arrest and CPR. At 5 min after resuscitation, a dose of 150 mg/kg of VPA was infused with a pump via the femoral vein in 1 h in the CPR+VAP group. At 1 h, 2 h, 4 h and 24 h after resuscitation, blood samples were drawn from the femoral vein, and then used to measure the serum concentrations of cardiac troponin I (cTnI), creatine kinase MB (CKMB), neuron specific enolase (NSE), and S100B protein (S100B) by ELISA. At 24 h after resuscitation, the animals were euthanized, and then tissue specimens in the left myocardium and brain cortex were rapidly harvested to detect the expression levels of C/EBP homologous protein (CHOP), caspase 12, and caspase 3 by Western blot, and the rate of apoptotic cells was detected by TUNEL. Continuous variables were compared with one way analysis of variance among the three groups. Results:(1) After resuscitation, cardiac and cerebral injury biomarkers including cTnI, CKMB, NSE, and S100B in serum were significantly increased in the CPR and CPR+VPA groups compared with the Sham group (all P<0.05). The serum concentrations of cTnI and NSE starting 1 h after resuscitation and the serum concentrations of CKMB and S100B starting 2 h after resuscitation were significantly decreased in the CPR+VPA group compared to the CPR group (all P<0.05). (2) Those proteins related to cell apoptosis mediated by endoplasmic reticulum stress, including CHOP, caspase 12, and caspase 3, were significantly increased, and meanwhile apoptosis index was markedly elevated after resuscitation in the CPR and CPR+VPA groups compared with the Sham group (all P<0.05). Nevertheless, the expression levels of CHOP, caspase 12, and caspase 3 were significantly decreased, and cell apoptosis was markedly reduced in the heart and brain after resuscitation in the CPR+VPA group compared to the CPR group (all P<0.05). Conclusions:VPA can alleviate cardiac and cerebral injuries after CPR in pigs, and its mechanism may be possibly related to the inhibition of cell apoptosis mediated by endoplasmic reticulum stress.

Determination of sodium valproate and vancomycin in human serum by HPLC-MS/MS / 药学实践杂志

Objective To establish a high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for simultaneous determination of sodium valproate and vancomycin in human serum. Methods Valproic acid-d6 and kanamycin B were used as the internal standard of sodium valproate and vancomycin, the serum samples were treated by acetonitrile precipitation protein method. The mobile phase was 0.1% formic acid aqueous solution-acetonitrile for gradient elution. The flow rate was 0.5 ml/min, with column temperature at 25 ℃. The sample volume was 4 μl and total analysis time was 12 min. The positive and negative ion mode was monitored by electrospray ion source and the multiple reaction monitoring mode was used for quantitative analysis. The specificity, standard curve, lower limit of quantification, precision, recovery, matrix effect, and stability of the method were examined. Results Sodium valproate and vancomycin had good linear relationships in the range of 1 - 200 μg/ml and 0.5 - 100 μg/ml, respectively. The quantitative lower limits were 1 μg/ml and 0.5 μg/ml, respectively. The extraction recoveries were above 70%. The inter- and intra-batch precision RSD values were less than 10%. The stability was good and there was no obvious matrix effect. Conclusion This method is simple, quick, sensitive, specific and accurate, which could be used to simultaneously determine the concentration of sodium valproate and vancomycin in human serum.

Clinical study on the treatment of QingxinWendan decoction in bipolar disorder manic episode patients / 中国医师杂志

Objective:To study the clinical effects of QingxinWendan decoction in the treatment of bipolar disorder (BD) manic episode.Methods:60 patients with BD manic episode treated in Hunan Brain Hospital from February 2020 to December 2020 were prospectively selected. They were included in the control group and the observation group according to the random alphabet method, with 30 cases in each group. The control group was treated with magnesium valproate sustained-release tablets, and the observation group was treated with Qingxin Wendan decoction combined with magnesium valproate sustained-release tablets. The curative effect was evaluated after 4 weeks of continuous treatment. The degree of mania before and after treatment was evaluated by Beck-Rafaelsen mania scale (BRMS); the cognitive function before and after treatment was evaluated by Wechsler Adult Intelligence Scale (WAIS-RC) and Wechsler Memory Scale (WMS); The levels of interleukin (IL)-1β, tumor necrosis factor-α (TNF-α), neuron specific enolase (NSE) and amyloid β protein (Aβ) levels were measured by enzyme linked immunosorbent assay (ELISA) before and after treatment. Spearman correlation analysis was used to analyze the correlation between serum NSE and Aβ levels and WAIS-RC and WMS scores in the two groups.Results:The curative effect of the observation group was better than that of the control group, with statistically significant difference ( P<0.05). After treatment, the BRMS scores of the control group and the observation group decreased (all P<0.05), and the BRMS scores of the observation group were lower than those of the control group ( P<0.05); After treatment, the WAIS-RC and WMS scores of the control group and the observation group increased (all P<0.05), and the WAIS-RC and WMS scores of the observation group were higher than those of the control group (all P<0.05). After treatment, the serum levels of IL-1β, TNF-α, NSE and Aβ in two groups were decreased (all P<0.05), and the levels of IL-1β, TNF-α, NSE and Aβ in the observation group were lower than those in the control group (all P<0.05). NSE and Aβ levels were negatively correlated with WAIS-RC and WMS scores (all P<0.05). Conclusions:Magnesium valproate sustained-release tablets combined with Qingxin Wendan decoction in the treatment of patients with BD manic episode were superior to magnesium valproate sustained-release tablets alone in reducing manic score, IL-1β, TNF-α, NSE and Aβ levels, and improving the cognitive function of patients. The use of QingxinWendan decoction on top of valproate extended-release tablet treatment for BD manic episode was superior to treatment with valproate extended-release tablets alone in reducing mania scores, IL-1β, TNF-α, NSE and Aβ levels, as well as improving patients' cognitive function.

Efficacy of maintenance electroconvulsive therapy combined with quetiapine treatment for manic episode of bipolar disorder / 中国基层医药

Objective:To investigate the efficacy of maintenance electroconvulsive therapy (MECT) combined with quetiapine treatment for manic episodes of bipolar disorder.Methods:A total of 103 patients with manic episodes of bipolar disorder received treatment in Kangci Hospital of Jiaxing from January 2019 to August 2020 and were included in this study. They were randomly divided into observation ( n = 46) and control groups ( n = 57). The observation group was given MECT combined with quetiapine treatment and the control group was treated with magnesium valproate sustained-release tablets combined with quetiapine. All patients received 4 weeks of treatment. Clinical efficacy, total hospital cost, drug cost during hospitalization, drug proportion, adverse reactions, and scores of the Bech-Rafaelsdn Mania Rating Scale and the Wisconsin Card Sorting Test pre- and post-treatment were compared between the two groups. Results:After 4 weeks of treatment, total response rate was significantly higher in the observation group than in the control group [76.09% (35/46) vs. 56.14% (32/57), χ2 = 4.45, P < 0.05]. In the observation group, total hospital cost, drug cost during hospitalization, and drug proportion were (16074.52 ± 1019.81) yuan, (1374.52 ± 619.81) yuan, and 8.70% respectively, which were not significantly different from those in the control group [(15618.14 ± 1550.34) yuan, (1261.14 ± 750.34) yuan, 10.53%, t = 1.71, 0.82, χ2 = 0.09, all P > 0.05]. After 4 weeks of treatment, Bech-Rafaelsdn Mania Rating score was significantly lower in the observation group than in the control group [(7.36 ± 3.04) points vs. (10.23 ± 2.37) points, t = 5.38, P < 0.001]. The number of wrong responses and the number of perseverative errors in the Wisconsin Card Sorting Test in the observation group were (40.45 ± 3.61) counts and (9.56 ± 1.39) counts, respectively, which were significantly lower than those in the control group [(48.59 ± 4.51) counts, (12.08 ± 1.25) counts, t = 10.17, 9.56, both P < 0.001]. The number of perseverative errors in the Wisconsin Card Sorting Test was significantly higher in the observation group than in the control group [(33.85 ± 2.50) counts vs. (29.71 ± 2.14) counts, t = 8.90, P < 0.001]. There was no significant difference in total incidence of adverse reactions between observation and control groups (21.74% vs. 22.81%, χ2 = 0.01, P > 0.05). Conclusion:MECT combined with quetiapine treatment is highly effective on the manic episodes of bipolar disorder. The combined therapy is worthy of clinical application.

Magnesium valproate for the treatment of bipolar disorder in 40 patients / 中国基层医药

Objective:To investigate the efficacy of magnesium valproate versus lithium carbonate in the treatment of bipolar disorder and their effects on serum indexes and quality of life. Methods:80 patients with bipolar disorder treated in the Fifth People's Hospital of Zhuji City from March 2017 to May 2020 were included in this study. They were randomly assigned to receive either lithium carbonate (control group, n = 40) or magnesium valproate (treatment group, n = 40) for 3 months. Efficacy,serum indexes, and quality of life were compared between the two groups. Results:Total effective rate was significantly higher in the observation group than in the control group [95.0% (38/40) vs. 75.0% (30/40), χ2 = 6.28, P = 0.012]. There were no significant differences in tumor necrosis factor-α, uric acid, total bilirubin, and albumin levels between the two groups (all P > 0.05). Tumor necrosis factor-α and uric acid levels in each group were decreased after treatment compared with before treatment (both P < 0.001). Total bilirubin and albumin levels in each group were increased after treatment compared with before treatment (both P < 0.001). Tumor necrosis factor-2 and uric acid levels measured after treatment were (136.5 ± 6.2) ng/L and (307.9 ± 15.2) μmol/L, respectively in the observation group, which were significantly lower than those in the control group [(148.9 ± 7.5) ng/L, (335.6 ± 18.9) μmol/L in the control group, t = 12.20, 7.22, both P < 0.001]. Total bilirubin and albumin levels measured after treatment were (11.0 ± 2.3) μmol/L and (45.5 ± 3.6) g/L, respectively in the observation group, which were significantly higher than those in the control group [(8.4 ± 2.1) μmol/L, (42.8 ± 3.0) g/L, t = 5.28, 3.64, both P < 0.001). There were no significant differences in scores of all dimensions of quality of life between the two groups before treatment (all P > 0.05). Scores of all dimensions of quality of life in each group increased after treatment compared with befor treatment (all P < 0.001). Scores of physical functioning, physical role functioning, bodily pain, vitality, social role functioning, emotional role functioning, and mental health measured after treatment were (75.2 ± 4.4) points, (71.9 ± 4.6) points, (76.2 ± 4.7) points, (71.8 ± 3.9) points, (66.8 ± 4.0) points, (75.9 ± 4.4) points, (70.5 ± 3.9) points, and (69.9 ± 4.0) points respectively in the observation group, which were significantly higher than those in the control group [(68.0 ± 4.0) points, (65.5 ± 4.3) points, (69.8 ± 4.0) points, (66.5 ± 3.5) points, (61.8 ± 3.5) points, (68.1 ± 4.0) points, (64.1 ± 3.6) points, (63.3 ± 3.9) points, t = 7.66, 6.43, 6.56, 6.40, 5.95, 8.30, 7.63, 7.47, all P < 0.001]. Conclusion:Magnesium valproate for the treatment of bipolar disorder can improve the antioxidant capacity, inhibit immune-inflammatory injury, improve abnormal metabolism, effectively control the symptoms of depression and mania,and improve the quality of life. Magnesium valproate is more effective than lithium carbonate in the treatment of bipolar disease.

Identification of hub genes in response to valproate treatment in patients with epilepsy / 中国药理学通报

Aim To investigate the hub genes associated with response to valproate treatment in patients with epilepsy by using weighted gene co-expression network analysis.Methods We downloaded data from the GEO database and constructed the gene co-expression network.Pearson correlation test was used to calculate the correlation between module genes and clinical traits, to screen gene modules significantly associated with response to valproate treatment, and to screen hub genes according to the connectivity within modules.GO functional enrichment analysis and KEGG pathway analysis were used to annotate the functions of the modules.Results A total of 12 gene co-expression modules were constructed from the correlations of gene expression, in which the yellow module was significantly correlated with the drug treatment(r=0.57, P<0.000 1)and the blue module was significantly correlated with the response to valproate(r=-0.53, P<0.000 1).We found that S1PR5, SARM1 and MAGED1, FBXO31 were in the hub of the co-expression network.The biological annotation function revealed that the genes in both modules were mainly enriched in immune response and MPAK pathways.Conclusions Our work delivers preliminary data that valproate treatment causes the changes of immune and metabolic pathways in patients, and the response to epilepsy may be related to the expression of MAGED1, FBXO31.

Effects of altitude hypoxia on cerebral blood distribution of sodium valproate in mice / 中国药理学通报

Aim To investigate the effects of altitude hypoxia on serum sodium valproate eoncentration and eerebral blood distribution.Methods Male mice were divided into control group and plateau group.Each group was given sodium valproate orally and intrave¬nously, respectively.UFLC-MS/MS was used to deter¬mine the concentration of sodium valproate in plasma and brain, and Western blot was used to detect the ex¬pression of P-gp in BBB.Results Compared with the control group, the ratio of brain/blood drug concentra¬tion in plateau group was up-regulated by 44.0% , 57.9% , 176.8% and 184.5% at 10, 30, 60 and 120 min, respectively.The ratio of brain/blood drug con-centration increased by 33.9% , 50.6% and 125.6% at 60 min, 120 min and 240 min in plateau group, re¬spectively.Compared with the control group, the ex¬pression of P-gp protein in BBB of mice in altitude group was significantly down-regulated by 58.46% (P < 0.05 ).Conclusions Compared with the control group, the brain/blood drug concentration ratio of val¬proic acid increases in high altitude hypoxia environ¬ment.Meanwhile, it is found that P-gp expression lev-el decreased in the brain mierovessels of mice under high altitude hypoxia environment, and the cerebral and blood distribution of valproic acid in mic increases in high altitude hypoxia environment.

Protective effects of valproic acid on cardiac and cerebral injury in rats subjected to severe scalding combined with seawater immersion injury with delayed fluid replacement / 中国药房

OBJECTIVE To study the protective effects o f valproic acid on cardiac and cerebral injury in rats subjected to severe scalding combined with seawater immersion injury with delayed fluid replacement. METHODS The rats were divided into scalding+delayed fluid replacement group （group S ），scalding+seawater immersion+delayed fluid replacement group （group SS ）， scalding+seawater immersion+valproic acid+delayed fluid replacement group （group SSV ）according to random number table ，with 60 rats in each group. All groups were subjected to 35％total body surface area third-degree full-thickness scalding with boiled water. Group SS and group SSV were immersed in artificial ；seawater（30 min）immediately after scalding ，and group SSV was subcutaneously injected with valproic acid 300 mg/kg immediately after out of water. Sodium lactate Ringer ’s 0314-2279277。E-mail：125467374@qq.com injection was injected intravenously within 30 minutes according to 1/2 Parkland formula at 2 h after scalding in each group for delayed fluid replacement. The death time of rats was recorded ，and the average survival time and 24 h survival rate of rats in each group were calculat ed. Mean arterial pressure （MAP），heart rate （HR），respiration rate （RR），rectal temperature （RT），arterial blood pH ，arterial partial pressure of oxygen （PaO2），arterial blood partial pressure of carbon dioxide （PaCO2），HCO3－，creatine kinase MB isoenzyme （CK-MB）and neuron specific enolase （NSE）were detected before scalding ，at 0，2，5 h after scalding. The pathological changes of cardiac and cerebral tissue were observed. RESULTS The 24 h survival rate of group SS （55％）was significantly lower than that of group S （90％）， while that of group SSV （75％）was increased significantly ，compared with group SS （P＜0.05）. Compared with group S ，the levels of MAP ，RT，HR，pH，PaO2 and HCO 3－ in group SS were significantly lowered ，while the levels of CK-MB and NSE were increased significantly at 0，2，5 h after scalding ；the levels of PaCO 2 were increased significantly at 2，5 h after scalding ， while the levels of RR were decreased significantly at 0，2 h after scalding （P＜0.05）. Compared with group SS ，the levels of MAP，RT，HR，pH，PaO2 and HCO 3－ in group SSV were significantly increased ，while the levels of PaCO 2，CK-MB and NSE were decreased significantly at 2，5 h after scalding ；the level of RR was increased significantly at 2 h after scalding （P＜0.05）. At 2，5 h after scalding ，cardiac and cerebral injury of rats in group SS were aggravated significantly than that in group S ；cardiac and cerebral injury of rats in group SSV were relieved significantly than that in group SS. CONCLUSIONS After severe scalding combined seawater immersion injury ，hypodermic injection of sodium valproate could protect cardiac and cerebral function of rats ， improve vital signs and blood gas index ，prolong survival time and improve survival rate in rats.

A description of sodium valproate, lamotrigine and levetiracetam consumption in the Western Cape public sector

The rational use of medicine is fundamental to ensure effective and safe patient medicine treatment, and hence, should be monitored. Undisputable evidence exists for the teratogenic risk factors associated with sodium valproate. Consequently, the Western Cape Department of Health introduced a policy (2019) recommending alternatives for valproate in women of childbearing age, including lamotrigine or levetiracetam as alternatives for patients on antiretrovirals. This study aimed to describe the change in the consumption of valproate, lamotrigine and levetiracetam after a policy implementation in public sector health facilities of the Western Cape, South Africa. Methods: This observational study followed a quasi-experimental design. Consumption data from the Cape Medical Depot over the period 01 April 2018 to 31 March 2020 were analysed retrospectively. Consumption was presented as a defined daily dose (DDD) per 1000 population per quarter for sodium valproate, levetiracetam and lamotrigine for the Western Cape province, urban and rural areas. Consumption 12 months before was compared with consumption 12 months after policy implementation. Results: Post-policy implementation, valproate consumption remained unchanged provincially (3.3%; p = 0.255), in urban (7.8%; p = 0.255) and rural (1.5%; p = 0.701) areas. Lamotrigine consumption increased significantly provincially (30.7%; p = 0.020) and in urban areas (54.5%; p = 0.002); however, rural (26.1%; p = 0.108) areas did not show significant change. Provincially, valproate consumption remained substantially higher (209 DDDs/1000 population per quarter) compared with lamotrigine consumption (32.22 DDDs/1000 population per quarter). Conclusion: In the Western Cape public sector, the consumption of sodium valproate remained unchanged 12 months after policy implementation. Although there were significant increases in lamotrigine and levetiracetam consumption, the consumption was considerably less compared with sodium valproate consumption.

Correlation between Breakthrough Seizures and Serum Level of Phenytoin and Valproate in Indian Patients

Objectives: To determine the optimum range of phenytoin (PHT) and valproate (VAP) levels and find out the critical drug levels below which chances of breakthrough seizures increase in North Indian population. Methodology: A cross-sectional, case-controlled, record-based study was conducted in a quaternary care hospital from September 2018–2019. The case group comprised epilepsy patients on monotherapy with PHT/VAP presenting with breakthrough seizures after at least 6 months of seizure control. Noncompliant, overdose, toxicity, no or partial response, any other psychiatric or neurological disorder, adverse effects, and patients taking two or more antiepileptic drugs were excluded. Results: Data of 100 patients in each group were analyzed. Significantly lower mean levels in cases were observed in PHT (5.74 ± 3.68 mg/L vs. 13.75 ± 4.27 mg/L control) and VAP (24.13 ± 27.39 mg/L vs. 76.37 ± 17.71 mg/L control). A negative correlation of drug levels was observed with age and weight in both the groups. The level/dose ratio in controls (0.05 ± 0.03; 0.09 ± 0.06) was significantly (P < 0.0001) higher than cases (0.02 ± 0.01; 0.02 ± 0.03) in PHT and VAP, respectively. Conclusions: This study identifies the critical levels and level/dose ratio at which the risk of breakthrough seizures increases. A wide level/dose ratio was found in controls, more so in the VAP group. A prospective study with larger group size along with genetic studies should be done to evaluate further.

Analysis of clinical pharmacists participating in the treatment of a case of sodium valproate poisoning / 药学实践杂志

Objective To explore the role of clinical pharmacists in the treatment of drug poisoning by analyzing the clinical pharmacist's participation in the treatment of a patient with sodium valproate poisoning. Methods Clinical pharmacists measured the plasma concentration of sodium valproate to inform the doctor to diagnose illnesses. At the initial stage when the concentration is high, to eliminate the free drug by continuous venous-venous hemodialysis-filtration (CVVHDF). Then, the combined drug was cleared by hemoperfusion (HP). Results The blood concentration dropped by half at the first CVVHDF and decreased obviously after two HPs. After stable observation in five days’ course of disease, the blood concentration was maintained at a low level and the patient was cured and discharged. Conclusion The implementation of the blood purification program under the monitoring of the blood drug concentration with the participation of pharmacists is helpful for the rescue of drug overdose and is worthy of promotion.

Expression and role of Huntingtin-associated protein 1 during valproate induced neural stem cells differentiation / 解剖学报

Objective To investigate the expression and role of Huntingtin-associated protein-1 (HAP-1) in the process of valproate acid (VP A) inducing neural stem cells (NSCs) into neurons. Methods The hippocampus NSCs of SD rats were isolated and cultured, Real-time PCR and Western blotting were used to detect HAP-1 mRNA and protein expression at day 0, day 1, day 3 and day 5 during the induction of VPA on NSCs differentiation into neurons ; Real-time PCR was used to detect the expression level of HAP-1 mRNA in multiple tissues of adult SD rats, as well as NSCs, neurons and astrocytes. After applying small interfering RNA technology to down-regulate the expression of HAP-1 mRNA in NSCs, Real-time PCR was used to detect the mRNA expression levels of neuron-specific molecules stathmin-2 ( Stmn-2), neuronal differentiation-1 (Neurod-1), microtubule-associated protein-2 (Map-2) and synapsin-1 (Syn-1), and Western blotting was used to detect the protein expression levels of neuron-specific marker β-tubulin III (Tuj-1). Immunofluorescence was used to detect the proportion of NSCs differentiated into Tuj-1 positive neurons, and to observe the development of neurons. Results At day 1 and day 3 after VPA treatment, the expression of HAP-1 mRNA and protein in the VPA group was significantly up-regulated; HAP-1 mRNA was predominantly expressed in the hippocampus, and its expression was higher in neurons, followed by NSCs, and minimally in astrocytes. After down-regulating HAP-1 with small interference technology, the proportion of NSCs differentiated into Tuj-1 positive neurons reduced, and neuron development became worse. Conclusion VPA may promote the differentiation of NSCs into neurons by up-regulating HAP-1 expression.

Investigation of Drug Storage Conditions of Sodium Valproate Granules Maintained by Pediatric Patients / 医薬品情報学

Objective: Sodium valproate granules (VPA granules) are extremely hygroscopic, deliquesce slowly in the air, and aggregate depending on temperature and humidity conditions. Although pharmacists are required to maintain drug storage conditions until the time of dispensing, they cannot keep track of the actual storage conditions maintained by the patients thereafter. Therefore, we investigated the actual temperature and humidity of the storage conditions maintained by the patients after delivery of the VPA granules.Methods: We conducted a prospective observational study at Kameda Medical Center on pediatric outpatients who were prescribed VPA granules from July 5, 2018 to February 20, 2019. A portable data logger capable of measuring temperature and humidity for 24 h was delivered at the time of dispensation. At the following visit, the data logger was collected, and data about temperature and humidity were obtained. We defined the suitable temperature as 1.0-30.0℃ and suitable humidity as 75.0% or less.Results: In this study, 13 patients were included. In total, 18 data loggers were distributed, and the return rate was 100.0%. The storage temperature was outside the suitable range in 0.8% of the total observation time whereas the humidity exceeded 75.0% in 1.7% of the total observation time.Conclusion: Storage of medications after dispensation was evaluated, and certain temperature and humidity deviations were observed. As storing a drug in an inappropriate environment changes the nature of the drug, affecting its efficacy and safety, it is necessary to educate patients on the proper methods to store oral medications.

Association of UGT1A6 gene polymorphism with clinical outcome in pediatric epileptic patients on sodium valproate monotherapy

Pediatric epilepsy comprises chronic neurological disorders characterized by recurrent seizures. Sodium valproate is one of the common antiseizure medications used for treatment. Glucuronide conjugation is the major metabolic pathway of sodium valproate, carried out by the enzyme uridine 5′-diphosphate (UDP) glucuronosyl transferase (UGT) whose gene polymorphisms may alter the clinical outcome. The objective of this study was to assess the association between UGT1A6 genetic polymorphism and clinical outcome in terms of efficacy and tolerability in pediatric epileptic patients on sodium valproate monotherapy. Pediatric epileptic patients (n=65) aged 2-18 years receiving sodium valproate monotherapy for the past one month were included. Genetic polymorphism patterns of UGT1A6 (T19G, A541G, A552C) were evaluated by PCR-RFLP. Clinical outcome was seizure control during the 6 months observation period. Tolerability was measured by estimating the hepatic, renal, and other lab parameters. Out of 65 patients, TT (40%), TG (57%), and GG (3%) patterns were observed in UGT1A6 (T19G) gene, AA (51%), AG (40%), and GG (9%) in (A541G) gene, and AA (43%), AC (43%), and CC (14%) in (A552C) gene. No statistical difference in clinical outcome was found for different UGT1A6 genetic polymorphism patterns. We concluded that different patterns of UGT1A6 genetic polymorphism were not associated with the clinical outcome of sodium valproate in terms of efficacy and tolerability. Sodium valproate was well-tolerated among pediatric patients with epilepsy and can be used as an effective antiseizure medication.