Correlation studies on pathological changes in brain with neurotransmitters and behavioural changes in Balb/c mice

Aim: To determine the plasma neurotransmitters simultaneously and to find any correlation with pathological changes in the hippocampus and Purkinje cells and their relation with behavioral changes in Balb/c mice. Methodology: In the present study, both sexes of Balb /C mice were divided into two groups (4 males and 4 females; n = 8): Both the groups were given a single dose of either saline or sodium valproate (400mg kg-1) respectively through subcutaneous injection on PND 14. Behavioural tests were conducted on mice pups on various postnatal days till 40th day. On PND 41, blood samples were collected from all the animals for quantification of the neurotransmitters (serotonin, dopamine, and noradrenalin) in plasma, animals were sacrificed by cervical dislocation and whole brain was isolated for histological examination of the Purkinje cells and hippocampus. Results: Sodium valproate exposed animals showed loss of motor skill development (delayed negative geotaxic response), increased locomotor activity, increased anxiety, and retardation in water maze performance, and lower social interaction. Histopathological evolutions of cerebellum purkinje cells and hippocampus showed 40-50% atrophic cells in sodium valproate animals compared to control animals. Interpretation: The results of the present study indicate that Sodium valproate changes specific brain cell population in Balb/C mice, which might be the reason for the altered neurotransmitter levels, leading to behavioural changes in these animals.

Sodium Valproate Combined With Topiramate vs. Sodium Valproate Alone for Refractory Epilepsy: A Systematic Review and Meta-Analysis

Background: Among antiepileptic drugs (AEDs), sodium valproate alone or in the combination of topiramate (TPM) for treating refractory epilepsy was controversial. This meta-analysis aimed to systematically evaluate the clinical effects of these two regimens in this population.Methods: Relevant studies up to August 2021 were identified through systematic searches of CNKI, Wanfang, PubMed, and Embase databases. We assessed the effectiveness and the frequency of absence seizures, atonic seizures, and tonic–clonic seizures. The included literature's risk of bias was evaluated using the Cochrane Collaboration's Risk of Bias tool. Sensitivity analysis was conducted to confirm the results' stability. STATA 15.0 was utilized for all pooled analyses in the included studies.Results: Totally 10 articles were determined for our meta-analysis, involving 976 patients with epilepsy in total (combined group, n = 488; monotherapy group, n = 488). The results of this meta-analysis indicated that the total effective rate of sodium valproate combined with TPM was higher than that of sodium valproate alone (random-effect model: OR = 3.52; 95% CI 1.47 to 8.47; p < 0.001; I2 = 73.8%). The frequency of absence seizures in the combined group was lower (fixed-effect model: WMD = −6.02; 95% CI −6.50 to −5.54; I2 = 0.0%) than that in the monotherapy group, with a statistical difference (p < 0.05). The combined group had lower frequency of atonic seizures (WMD = −4.56, 95% CI −6.02 to −3.10; I2 = 82.6%) and lower frequency of tonic–clonic seizures (WMD = −3.32; 95% CI −4.75 to −1.89; I2 = 96.4%). In addition, the distinct difference of adverse events was non-existent between two groups.Conclusions: Sodium valproate combined with TPM was more effective than sodium valproate alone for epilepsy therapy. This meta-analysis provides feasibility data for a larger-scale study on AED therapy of refractory epilepsy and may contribute to better therapy strategies for epilepsy clinically.

Sodium valproate is effective against Botrytis cinerea infection of tomato by enhancing histone H3 acetylation-directed gene transcription and triggering tomato fruits immune response

Botrytis cinerea causes grey mold resulting in enormous financial loss. Fungicide resistance of B. cinerea has become a serious issue in food safety and agricultural environmental protection. Sodium valproate (SV) has been used in clinical trials, thus it is excellent candidate for fungicide development considering its safety. However, the antifungal activity remains unclear. SV was effective against B. cinerea by enhancing acetylation of histone H3, including H3K9ac, H3K14ac, and H3K56ac. A transcriptomics analysis revealed that the expression of 1,557 genes changed significantly in response to SV. A pathway enrichment analysis identified 16 significant GO terms, in which molecular functions were mainly involved. In addition, the expression levels of 13 genes involved in B. cinerea virulence and 5 genes involved in tomato immune response were altered by the SV treatment. These results indicate that SV inhibits B. cinerea by enhancing acetylation of histone H3 and modifying gene transcription. Thus, SV is an effective, safe potential antifungal agent for control of both pre- and post-harvest losses caused by B. cinerea.

Evaluating Mirna-222 Expression Level and Its Association with AMH for Early Diagnosis of Pcos-Like Symptoms in Epileptic Patients Plasma Treated with Sodium Valproate: A Case – Control Study

Introduction: Epileptic neurological disorder, which is controlled with medications such as sodium valproate (one of the treatment priorities for the patients with epilepsy). Polycystic ovary syndrome (PCOS) is one of complication of sodium valproate. Ovulation in PCOs Patients is disrupted, resulting in serious complications, including endometrial hyperplasia with typical and atypical forms, increased the risk of endometrial endometrial cancer, diabetes mellitus, and decreased fertility rates. This study, in accordance with bioinformatics studies and other studies based on the association of miRNA-222 with genes involved in PCOs and hyperandrogenism, was designed to evaluate the association of PCOs in the patients treated with sodium valproate by simultaneously comparing the AMH factor and miRNA-222 marker at specific time periods. Methods: In this case-control study, 33 women with epilepsy before and after use the drug were selected based on inclusion and exclusion criteria. After blood sampling, their plasma was isolated. According to the instructions of the Total RNA extracted kit , cDNA synthesized and miRNA-222 expression was evaluated by RT-qPCR technique and statistical analysis was performed by SPSS 23 software, T-test and ANOVA tests. Results: The results of statistical tests such as T-test and ANOVA test (done with SPSS software) which showed a significant difference (p<0/01) between the mean expression of mir-222 and AMH in the patients before treatment compared to 3 month after treatment. The results of Pearson correlation test showed that the increase in AMH is directly related to the decrease in miRNA-222 expression (p<0/01). Conclusion: According to the results of the present study, in order to better control the possible side effects of the drug and possibly timely drug change and early diagnosis of PCOs (PCOs‌-like symptoms), evaluation of miRNA-222 expression changes can be used at the same time with AMH assay.

Effect of Sodium Valproate Treatment on the Cardiac Index in New Cases with Status Epilepticus

Background: Sodium valproate is an antiepileptic drug primarily used to treat status epilepticus [SE]; however, its effect on cardiac function is unclear. This study aimed to examine the effect of 6 months of sodium valproate treatment on the cardiac index in new cases with status epilepticus. Methods: In this cross-sectional study, 30 cases with status epilepticus [18 boys and 12 girls] who were admitted to the Pediatric Intensive Care Unit of Hazrat-e Rasool Hospital were enrolled. Information on basic demographic and clinical data of all children, such as age, weight, gender, blood pressures, and underlying diseases, was recorded. Echocardiography and electrocardiogram [ECG] were performed for all cases before and after the treatment. Results: There were no abnormalities in ECG parameters [including PR, QRS, and QT intervals] after 6 months of treatment with sodium valproate. No significant differences were found in echocardiographic parameters, including blood pressure, pulmonary artery pressure [PAP], right ventricular [RV] size, diastolic dysfunction,], Tie index, end-diastolic volume [EDV], ejection fraction [EF], and TAPSE before and after study [p>0.05]. Conclusion: Administration of sodium valproate over 6 months is not associated with a serious adverse effect on heart function in children with status epilepticus.

Neuroleptic Malignant Syndrome in an Elderly Patient with Bipolar Disorder

Neuroleptic malignant syndrome (NMS) is a well-known and potentially fatal complication of antipsychotic use. The elderly population, with multiple risk factors, are more vulnerable to this condition. We described a case of an 80-yearold man with bipolar disorder, previously on oral extended-release sodium valproate, aripiprazole and long-acting injectable paliperidone, who developed NMS. He presented with generalised muscle rigidity, fever, fluctuating blood pressure and elevated creatinine kinase during his hospitalisation for a manic episode. Contributing factors included old age, underlying vascular Parkinsonism, electrolyte imbalance, intercurrent lung infection with acute exacerbation of chronic obstructive pulmonary disease, hyperactive delirium, and repeated administration of parenteral typical antipsychotic. Antipsychotics were withheld promptly, and the patient was treated with dantrolene, bromocriptine and amantadine. His symptoms resolved after a week. He subsequently remained well with oral extended-release sodium valproate alone. Relevant clinical points are discussed. Clinical vigilance, close interdisciplinary cooperation, and prompt interventions are keys to successful to management of NMS in elderly patients.

Henoch-Schonlein purpura due to sodium valproate: A Case report

The etiology of Henoch-Schönlein purpura (HSP) has been frequently attributed to certain drugs. Anticonvulsive drugs are reported rarely in drug-induced HSP.We report a 5-year-old girl with a seizure treated with sodium valproate. we report a case of HSP due to the consumption of sodium valproate..