Experimental Studies to Define the Role of Calcium (Ca2+) and Voltage-Gated Calcium Channel Blockers (vCa-CCB) against Neurosteroid Induced Obesity

Introduction:Obesity is closely associated with various types of illness, primarily caused by more calorie intake than body burn. In adipocytes, Calcium (Ca2+) is an important second messenger involved in theregulation of many physiological functions which are essential for survival. In the present research, we have investigated the role of Ca2+ions in obesity by manipulating cytosolic Ca2+ion concentration by selective blocking/advancing the Ca2+ions through the voltage-gated calcium channels. Voltage-gated calcium channel (vCa) plays a key role in regulating intracellular and extracellular Ca2+concentration.Cytoplasmic level of Ca2+was manipulated by supplying calcium carbonateand by using vCa blockers i.e. nifedipine-(N-type-vCa-CCB) and ethosuximide (T-type, vCa-CCB).Methods:Obesity was induced by progesterone in female mice and test drugs were co-administered with progesterone whereas sibutramine was used as standard. The treatment was carried out for 28 days, during and afterthetreatment periodvarious parameters were studied viz food consumption, change in body weight and temperature, the effect on WAT (white adipose tissue, adiposity index, histology of fat pad) and fecal lipid content.Results:Calcium carbonate treated group has shown promising effects in the decrease in body weight by increasing fecal lipid content and lipolysis which was reflected by an increase in body temperature. Ethosuximide also offered significant protection by decreasing the food intake but has not shown any notable effect on fecal fat content, whereas nifedipine has not offered any protection against the obesity induced by neurosteroid.Conclusion:Calcium carbonate has significant anti-obesity activity by including thermogenesis, and increasing fecal lipid content

A Case of Ethosuximide-Induced Aplastic Anemia Successfully Treated with Methylprednisolone Pulse Therapy / 임상소아혈액종양

Aplastic anemia may develop secondary to environmental exposure to entities such as chemicals, medical drugs, and infectious agents. Fatal complications from antiepileptic medications may occur despite careful and appropriate use. We report the case of a 9-year-old girl with a presenting diagnosis of aplastic anemia following treatment with ethosuximide for absence seizures. Aplastic anemia can now be cured with stem cell transplantation or immunosuppressive therapy. In this case, however, because of the impossibility of bone marrow transplantation and the specific needs of the patient's parents, three courses of methylprednisolone pulse therapy were administered. Following the therapy, there was improvement in pancytopenia and complete remission in the bone marrow. No adverse side effects of therapy were observed. The authors suggest that methylprednisolone pulse therapy may be a treatment for acquired aplastic anemia.

Inhibitory effect of ethosuximide on sevoflurane-induced emergence delirium in neonatal rats / 临床麻醉学杂志

Objective To investigate the inhibitory effect of ethosuximide,an antiepileptic drug,on sevoflurane-induced emergence delirium in neonatal rats.Methods Twelve SD rats (17-23 g) at postnatal day 9-11 were randomly divided into ethosuximide group (4 mg/100 μl,intraperitoneal injection,n=6) and saline group (100 μ1,intraperitoneal injection,n =6).Then the pups were treated with 1％ sevoflurane for 10 minutes and agitated behaviors was observed using PAHBs scoring method for every 2 minutes.Ten more pups were randomly divided into two groups as previously described.Then the pups were treated with 1％ sevoflurane for 10 minutes and EEG power spectrum of frontal lobe was monitored for every 2 minutes.Results Both PAHBs scores and EEG power spectrum at 2 min,4 min,6 min,8 min and 10 min were significantly decreased in ethosuximide group when comparing with saline group under 1％ sevoflurane inhalation (P ＜ 0.05).Conclusion Ethosuximide can decrease frontal lobe EEG power spectrum in sevoflurane-induced agitated rats and inhibit sevoflurane-induced emergence delirium in neonatal rats.

Lamotrigine for absence seizures in children and adolescents：a systematic review / 药学实践杂志

Objective To assess the efficacy and safety of lamotrigine for absence seizures in children and adolescents . Methods Databases of PubMed ,the Cochrane Library ,EMbase ,CENTRAL ,VIP ,WanFang ,CBM and CNKI were electron-ically searched till August ,2014 for clinical trials on lamotrigine for absence seizures in children and adolescents .All literature were screened by two reviewers independently according to the inclusion and exclusion criteria .The data was extracted ,and the methodological quality was assessed .Then ,meta-analysis was performed using RevMan 5 .2 .Results Seven trials were in-cluded involving a total of 721 patients .The results of methodological qualities were two studies rated as A-class ,three studies rated as B-class and two studies rated as C-class .Meta-analysis results showed that the efficacy of lamotrigine monotherapy for absence seizure in children and adolescents was better than placebo ,but efficacy of lamotrigine was lower than valproic acid and ethosuximide .The adverse reaction rates of lamotrigine were with no significant difference compared with valproic acid and et-hosuximide .Conclusion Lamotrigine monotherapy was effective for absence seizures in children and adolescents and was well tolerated .Lamotrigine was a good choice for patients that are intolerable to valproic acid or ethosuximide .

Outcomes of the Monoconversion to Valproate or Lamotrigine for Absence Seizures / 대한소아신경학회지

PURPOSE: Ethosuximide (ESX) is currently not available due to various reasons in Korea. The aim of this study is to compare the efficacy of valproate (VPA) and lamotrigine (LTG) when ESX monotherapy was replaced by VPA or LTG. METHODS: A retrospective study was done for a total of 34 patients treated with ESX in 5 different hospitals affiliated with Catholic University of Korea from January, 2010 to December, 2012. They all were initially treated with ESX, but later switched to VPA or LTG. The subjects were selected based on clinical symptoms and electroencephalography findings. RESULTS: Among 34 patients, VPA was prescribed to 17 patients (50.0%) and LTG to 17 patients (50.0%). Twenty patients (58.8%) achieved the seizure freedom after 3 months of the treatments, 13 patients (76.5%) by VPA and 7 (41.2%) by LTG respectively. Four patients (23.5%) with VPA and 10 (58.8%) with LTG were replaced by other anticonvulsants due to ineffectiveness and/or side effects of medication. When we compare the efficacy of seizure reduction between VPA and LTG after 3 month period of the treatment, the efficacy of VPA was better than that of LTG (P=0.04). CONCLUSION: The results of this study suggest that the VPA is a better alternative anticonvulsant than LTG for the patients with absence epilepsy who are unable to continue ESX.

Antihyperalgesic Effects of Ethosuximide and Mibefradil, T-type Voltage Activated Calcium Channel Blockers, in a Rat Model of Postoperative Pain / 대한통증학회지

BACKGROUND: A correlation between a T-type voltage activated calcium channel (VACC) and pain mechanism has not yet been established. The purpose of this study is to find out the effect of ethosuximide and mibefradil, representative selective T-type VACC blockers on postoperative pain using an incisional pain model of rats. METHODS: After performing a plantar incision, rats were stabilized on plastic mesh for 2 hours. Then, the rats were injected with ethosuximide or mibefradil, intraperitoneally and intrathecally. The level of withdrawal threshold to the von Frey filament near the incision site was determined and the dose response curves were obtained. RESULTS: After an intraperitoneal ethosuximide or mibefradil injection, the dose-response curve showed a dose-dependent increase of the threshold in a withdrawal reaction. After an intrathecal injection of ethosuximide, the threshold of a withdrawal reaction to mechanical stimulation increased and the increase was dose-dependent. After an intrathecal injection of mibefradil, no change occurred in either the threshold of a withdrawal reaction to mechanical stimulation or a dose-response curve. CONCLUSIONS: The T-type VACC blockers in a rat model of postoperative pain showed the antihyperalgesic effect. This effect might be due to blockade of T-type VACC, which was distributed in the peripheral nociceptors or at the supraspinal level. Further studies of the effect of T-type VACC on a pain transmission mechanism at the spinal cord level would be needed.

Effects of Ethosuximide on the Pilocarpine Induced Seizure in Rat Model of Neuronal Migration Disorder

Cortical malformation-associated epileptic seizures are resistant to conventional anticonvulsant drugs. Relatively little research has been conducted on the effects of antiepileptic drugs (AEDs) on seizure activity in a rat model of dysplasia. We have used rats exposed to methylazoxymethanol acetate (MAM) in utero, an animal model featuring nodular heterotopia, to investigate the effects of ethosuximide (ETX) in the dysplastic brain. Pilocarpine was used to induce acute seizure in MAM-exposed and age-matched vehicle-injected control animals. Field potential recordings were used to monitor the amplitude and number of population spikes, and paired pulse inhibition in response to stimulation of the commissural pathway. Pharmaco-resistance was tested by measuring seizure latencies after pilocarpine administration (320 mg/kg, i.p.) with and without pre-treatment with ETX. Pre-treatment with 300 mg of ETX significantly prolonged the latency to the status epilepticus (SE) in both control and MAM-treated groups. Pre-treatment with ETX 100mg and ETX 200 mg had little effect in MAM-exposed rats. However, ETX 200 mg prolonged the latency to the SE in control groups. Spontaneous field potential and secondary after-discharges were higher for MAM-treated rat in comparison with control rats injects with ETX. The main findings of this study are that acute seizures initiated in MAM-exposed rats are relatively resistant to standard ETX assessed in vivo. These data suggest that ETX do not prolong seizure latencies in MAM-rats exposed to pilocarpine.