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      Effects of carbamazepine combined with vitamin B12 on levels of plasma homocysteine, hs-CRP and TNF-α in patients with epilepsy

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          Abstract

          The efficacy of carbamazepine combined with vitamin B12 in epilepsy treatment by comparing levels of plasma homocysteine (Hcy), serum TNF-α and hs-CRP in patients with epilepsy before and after treatment was investigated. Fifty-eight patients with epilepsy who were admitted and received treatment in The First People's Hospital of Xuzhou were recruited as subjects, and fifty-eight healthy volunteers were recruited as the control group. Patients were treated with carbamazepine combined with vitamin B12 for a period of three months. The mRNA and protein levels of TNF-α and hs-CRP in serum were measured before and after treatment using semi-quantitative RT-PCR and western blotting, respectively. The plasma Hcy levels were measured as well. Within one year after the 3-month treatment, the frequency and duration of seizure were tracked. After treatment with carbamazepine combined with vitamin B12 for patients with epilepsy, the Hcy level was significantly higher than that before treatment and that in the control group (P<0.01). The mRNA and protein levels of TNF-α and hs-CRP in serum were significantly higher in patients than that in healthy people (P<0.01). After treatment these levels were reduced (P<0.01), but still higher than those in healthy people (P<0.05, P<0.01). After treatment, the frequency and duration of seizures were all reduced (P<0.05, P<0.01). The results suggested that carbamazepine combined with vitamin B12 was effective in treatment of epilepsy by reducing levels of TNF-α and hs-CRP in the serum, but had a risk of increasing the Hcy level.

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          Epilepsy, Antiepileptic Drugs, and Aggression: An Evidence-Based Review

          Antiepileptic drugs (AEDs) have many benefits but also many side effects, including aggression, agitation, and irritability, in some patients with epilepsy. This article offers a comprehensive summary of current understanding of aggressive behaviors in patients with epilepsy, including an evidence-based review of aggression during AED treatment. Aggression is seen in a minority of people with epilepsy. It is rarely seizure related but is interictal, sometimes occurring as part of complex psychiatric and behavioral comorbidities, and it is sometimes associated with AED treatment. We review the common neurotransmitter systems and brain regions implicated in both epilepsy and aggression, including the GABA, glutamate, serotonin, dopamine, and noradrenaline systems and the hippocampus, amygdala, prefrontal cortex, anterior cingulate cortex, and temporal lobes. Few controlled clinical studies have used behavioral measures to specifically examine aggression with AEDs, and most evidence comes from adverse event reporting from clinical and observational studies. A systematic approach was used to identify relevant publications, and we present a comprehensive, evidence-based summary of available data surrounding aggression-related behaviors with each of the currently available AEDs in both adults and in children/adolescents with epilepsy. A psychiatric history and history of a propensity toward aggression/anger should routinely be sought from patients, family members, and carers; its presence does not preclude the use of any specific AEDs, but those most likely to be implicated in these behaviors should be used with caution in such cases.
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            Familial risk of epilepsy: a population-based study.

            Almost all previous studies of familial risk of epilepsy have had potentially serious methodological limitations. Our goal was to address these limitations and provide more rigorous estimates of familial risk in a population-based study. We used the unique resources of the Rochester Epidemiology Project to identify all 660 Rochester, Minnesota residents born in 1920 or later with incidence of epilepsy from 1935-94 (probands) and their 2439 first-degree relatives who resided in Olmsted County. We assessed incidence of epilepsy in relatives by comprehensive review of the relatives' medical records, and estimated age-specific cumulative incidence and standardized incidence ratios for epilepsy in relatives compared with the general population, according to proband and relative characteristics. Among relatives of all probands, cumulative incidence of epilepsy to age 40 was 4.7%, and risk was increased 3.3-fold (95% confidence interval 2.75-5.99) compared with population incidence. Risk was increased to the greatest extent in relatives of probands with idiopathic generalized epilepsies (standardized incidence ratio 6.0) and epilepsies associated with intellectual or motor disability presumed present from birth, which we denoted 'prenatal/developmental cause' (standardized incidence ratio 4.3). Among relatives of probands with epilepsy without identified cause (including epilepsies classified as 'idiopathic' or 'unknown cause'), risk was significantly increased for epilepsy of prenatal/developmental cause (standardized incidence ratio 4.1). Similarly, among relatives of probands with prenatal/developmental cause, risk was significantly increased for epilepsies without identified cause (standardized incidence ratio 3.8). In relatives of probands with generalized epilepsy, standardized incidence ratios were 8.3 (95% confidence interval 2.93-15.31) for generalized epilepsy and 2.5 (95% confidence interval 0.92-4.00) for focal epilepsy. In relatives of probands with focal epilepsy, standardized incidence ratios were 1.0 (95% confidence interval 0.00-2.19) for generalized epilepsy and 2.6 (95% confidence interval 1.19-4.26) for focal epilepsy. Epilepsy incidence was greater in offspring of female probands than in offspring of male probands, and this maternal effect was restricted to offspring of probands with focal epilepsy. The results suggest that risks for epilepsies of unknown and prenatal/developmental cause may be influenced by shared genetic mechanisms. They also suggest that some of the genetic influences on generalized and focal epilepsies are distinct. However, the similar increase in risk for focal epilepsy among relatives of probands with either generalized (2.5-fold) or focal epilepsy (2.6-fold) may reflect some coexisting shared genetic influences.
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              Association of carbamazepine major metabolism and transport pathway gene polymorphisms and pharmacokinetics in patients with epilepsy.

              The aim of this study was to evaluate the association of genetic variants in the major genes involved in carbamazepine (CBZ) metabolism and transport with its pharmacokinetics in epilepsy patients. Twenty-five SNPs within seven CBZ pathway genes, namely CYP3A4, CYP3A5, EPHX1, NR1I2, UGT2B7, ABCB1 and ABCC2, were analyzed for association with CBZ pharmacokinetics in 90 epilepsy patients. The CYP3A4*1B SNP was significantly associated with CBZ clearance. Significant association of EPHX1 SNPs was observed with greater carbamazepine-10,11-trans dihydrodiol:carbamazepine 10-11 epoxide ratios. Among drug transporters, ABCB1 and ABCC2 SNPs were significantly associated with altered CBZ clearance. SNPs within CBZ pathway genes contribute to interpatient variation in CBZ pharmacokinetics and might contribute to pharmacoresistant epilepsy. Although our results need further clinical validation in a larger patient cohort, they indicate that genetic variation in CBZ pathway genes could influence its pharmacokinetics, and hence would have clinical significance.
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                Author and article information

                Journal
                Exp Ther Med
                Exp Ther Med
                ETM
                Experimental and Therapeutic Medicine
                D.A. Spandidos
                1792-0981
                1792-1015
                March 2018
                04 January 2018
                04 January 2018
                : 15
                : 3
                : 2327-2332
                Affiliations
                [1 ]School of Clinical Medicine, Kangda College of Nanjing Medical University, Lianyungang, Jiangsu 222002, P.R. China
                [2 ]Department of Neurology, The First People's Hospital of Xuzhou, Xuzhou, Jiangsu 221000, P.R. China
                [3 ]Department of Pharmacy, The First People's Hospital of Xuzhou, Xuzhou, Jiangsu 221000, P.R. China
                Author notes
                Correspondence to: Dr Hao Zhou, Department of Neurology, The First People's Hospital of Xuzhou, 19 Zhongshanbei Road, Xuzhou, Jiangsu 221000, P.R. China, E-mail: hao_zhou9@ 123456163.com
                Article
                ETM-0-0-5698
                10.3892/etm.2018.5698
                5854944
                0351582f-f9b8-4cae-865c-ee69f3d94c88
                Copyright: © Zhou et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                : 18 August 2017
                : 11 December 2017
                Categories
                Articles

                Medicine
                epilepsy,carbamazepine,homocysteine,tnf-α
                Medicine
                epilepsy, carbamazepine, homocysteine, tnf-α

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