Lattice metamaterials based on three-period minimum surface(TPMS)are an effective means to achieve lightweight and high-strength materials which are widely used in various fields such as aerospace and ships.However,it...Lattice metamaterials based on three-period minimum surface(TPMS)are an effective means to achieve lightweight and high-strength materials which are widely used in various fields such as aerospace and ships.However,its vibration and noise reduction,and damping properties have not been fully studied.Therefore,in this study,the TPMS structures with parameterization were designed by the method of surface migration,and the TPMS structures with high forming quality was manufactured by laser powder bed fusion(LPBF).The mechanical properties and energy absorption characteristics of the beam and TPMS structures were studied and compared by quasi-static compression.The modal shapes of the beam lattice structures and TPMS structures were obtained by the free modal analysis,and the damping properties of two structures were obtained by modal tests.For the two structures after heat treatment with the same porosity of 70%,the yield strength of the beam lattice structure reaches 40.76 MPa,elastic modulus is 20.38 GPa,the energy absorption value is 32.23 MJ·m^(-3),the damping ratio is 0.52%.The yield strength,elastic modulus,energy absorption value,and damping ratio of the TPMS structure are 50.74 MPa,25.37 GPa,47.34 MJ·m^(-3),and 0.99%,respectively.The results show that TPMS structures exhibit more excellent mechanical properties and energy absorption,better damping performance,and obvious advantages in structural load and vibration and noise reduction compared with the beam lattice structures under the same porosity.展开更多
Objective:To explore protective effeet of topiramate(TPM) on hypoxic—ischemic brain injury.Methods:A total of 360 neonatal rats were seleeted then randomly divided into sham operation group,ischemia and hypoxia group...Objective:To explore protective effeet of topiramate(TPM) on hypoxic—ischemic brain injury.Methods:A total of 360 neonatal rats were seleeted then randomly divided into sham operation group,ischemia and hypoxia group,conventional treatment group and degradation therapy group(n=90).After surgical treatment,sham and ischemic hypoxia group were treat with normal saline:conventional treatment group was received Tl'M solution 100 mg/kg.2 times/d:degradation therapy group received TPM solution 150 mg/kg.2 times/d.per 3 d treatment each dosage was reduced 50 mg/kg.the lowest reduced to 50 mg/kg.Four groups received continuous treatment for 10 d.After treatment for 1 d.4 d.7 d.10 d the cercbral edema,neuron-specific enolase(NSE)and γ-aminobutyric acid(GABA) levels and cognitive abilities of four groups were observed.Results:After 1d.4d of treatment,the brain water conlenl and NSE levels in ischemia and hypoxia group,the conventional treatment group and the degradation therapy group were significantly higher than that in sham group(P<0.05),the brain water content and NSE levels of the conventional treatment group and the degradation therapy group were significantly lower than that in the ischemic hypoxia group(P<0.05).GABA levels and learning ability of the ischemia and hypoxia group,the conventional treatment group and degradation therapy group were significantly lower than the sham group(P<0.05).the GABA levels and learning ability of the conventional treatment group and degradation therapy group were significantly higher than the ischemia and hypoxia group(P<0.05).After 7d.10 d of treatment,the brain water content and NSE levels in the sham operation group,the conventional treatment group and degradation therapy group were significantly lower than the ischemia and hypoxia group(P<0.05).while the GABA levels and learning ability of these three groups were significantly higher than that in the ischemia and hypoxia group(P<0.05>.the GABA levels in the conventional treatment group were significantly higher than degradation therapy group(P<0.05);After 10 d of treatment,the GABA levels of the conventional treatment group were significantly higher than the sham group,the learning ability of the degradation therapy group and sham operation group were significantly higher than the conventional treatment group(P<0.05).Conclusions:The correct amount of short—term TPM has protective effect on hypoxic—ischemic brain injury,but long-term or excessive use may cause new damage to the brain and reduce the cognitive ability.展开更多
Drug-induced peripheral neuropathy had been rarely reported as an adverse effect of some antiepileptic drugs(AEDs) at high cumulative doses or even within the therapeutic drug doses or levels.We describe clinical and ...Drug-induced peripheral neuropathy had been rarely reported as an adverse effect of some antiepileptic drugs(AEDs) at high cumulative doses or even within the therapeutic drug doses or levels.We describe clinical and diagnostic features of a patient with peripheral neuropathy as an adverse effect of chronic topiramate(TPM) therapy.A 37-year-old woman was presented for the control of active epilepsy(2010).She was resistant to some AEDs as mono-or combined therapies(carbamazepine,sodium valproate,levetiracetam,oxcarbazepine and lamotrigine).She has the diagnosis of frontal lobe epilepsy with secondary generalization and has a brother,sister and son with active epilepsies.She became seizure free on TPM(2013-2017) but is complaining of persistent distal lower extremities paresthesia in a stocking distribution.Neurological examination revealed presence of diminished Achilles tendon reflexes,stocking hypesthesia and delayed distal latencies,reduced conduction velocities and amplitudes of action potentials of posterior tibial and sural nerves,indicating demyelinating and axonal peripheral neuropathy of the lower extremities.After exclusion of the possible causes of peripheral neuropathy,chronic TPM therapy is suggested as the most probable cause of patient's neuropathy.This is the first case report of topiramate induced peripheral neuropathy in the literature.展开更多
Topiramate（TPM） is a widely used antiepileptic and antimigraine agent which has been shown to exert neuroprotective effects in various experimental traumatic brain injury and stroke models. However, its utility in s...Topiramate（TPM） is a widely used antiepileptic and antimigraine agent which has been shown to exert neuroprotective effects in various experimental traumatic brain injury and stroke models. However, its utility in spinal cord injury has not been studied extensively. Thus, we evaluated effects of TPM on secondary cellular injury mechanisms in an experimental rat model of traumatic spinal cord injury（SCI）. After rat models of thoracic contusive SCI were established by free weight-drop method, TPM（40 mg/kg） was given at 12-hour intervals for four times orally. Post TPM treatment, malondialdehyde and protein carbonyl levels were significantly reduced and reduced glutathione levels were increased, while immunoreactivity for endothelial nitric oxide synthase, inducible nitric oxide synthase, and apoptotic peptidase activating factor 1 was diminished in SCI rats. In addition, TPM treatment improved the functional recovery of SCI rats. This study suggests that administration of TPM exerts neuroprotective effects on SCI.展开更多
BACKGROUND: It has been demonstrated that traditional antiepileptics, such as phenytoin, carbamazepine (CBZ), phenobarbital, etc., can result in the decrease of thyroid hormone of epileptic patients. However, there is...BACKGROUND: It has been demonstrated that traditional antiepileptics, such as phenytoin, carbamazepine (CBZ), phenobarbital, etc., can result in the decrease of thyroid hormone of epileptic patients. However, there is still no sufficient evidence for the studies about the effect of new-type antiepileptics, such as topiramate (TPM), on thyroid hormones. OBJECTIVE: To observe the effects of TPM and CBZ on the level of thyroid hormones in serum of adults with epilepsy. DESIGN: A comparative observation. SETTING: Department of Neurology, Sichuan Provincial People's Hospital. PARTICIPANTS: Totally 100 outpatients or inpatients newly diagnosed to have epilepsy were selected from the Department of Neurology, Sichuan Provincial People's Hospital from July 2003 to August 2005, including 60 males and 40 females, aged 18-70 years. All the patients were accorded with the standard for the classification of epilepsy set by International League Against Epilepsy (ILAE) in 1981; Had been Informed and agreed with the detection; Had no history of thyroid gland disease; Had not taken any drugs could affect the thyroid function. Meanwhile, 40 adult healthy examinees were selected from our hospital as the control group, including 24 males and 16 females, aged 18-65 years. METHODS: ① The 100 epileptic patients were randomly divided into TPM group (n =50) and CBZ group (n =50), and they were treated with TPM (Xian-Janssen Pharmaceutical, Ltd.; Batch number: 03AS032, Norm: 25 mg/tablet) and CBZ (Shanghai Sunve Pharmaceutical Co., Ltd.; Batch number: 030201, Norm: 100 mg/tablet) respectively. The initial dosage of TPM was 25 mg per day, increased by 25 mg every week, the objective dosage of 100-200 mg per day was maintained when the symptoms were satisfactorily controlled. The dosage of CBZ was 6-8 mg/kg per day. All the patients were administrated for 1 year. ② The serum levels of total thyroxine (TT4), free thyroxine (FT4), total triiodothyronine (TT3), free triiodothyronine (FT3) and thyroid stimulating hormone (TSH) in the epileptic patients were detected by means of chemiluminescence before treatment and at 3, 6 and 12 months after treatment respectively. ③Standards for judging curative effects: Controlled by without seizure, the frequency of seizure reduced by ≥ 75% was taken as significant effect, reduced by 50%-74% as effect, and reduced by < 49% as invalid, whereas increased by more than 20% was taken as aggravation. ④ The intergroup and intragroup differences of the measurement data were compared by the analysis of variance and paired t test respectively. MAIN OUTCOME MEASURES: Serum levels of thyroid hormones before treatment and at different time points after treatment of TPM and CBZ. RESULTS: All the 100 epileptic patients and 40 healthy subjects were involved in the analysis of results. ① Changes of serum levels of thyroid hormones: The serum levels of TT3, TT4, FT3, FT4 and TSH were close between the epileptic patients and normal subjects before treatment (P > 0.05). In the CBZ group, the serum levels of FT4 at 3, 6 and 12 months after treatment [(16.87±3.77), (16.34±3.98) , (16.97±3.95) pmol/L] were significantly decreased as compared with those before treatment [(18.00±3.54) pmol/L, t =2.74, 3.50, 2.26, P < 0.05]; The levels of TT3 at 3, 6 and 12 months [(2.09±0.54), (1.99±0.49), (1.84±0.47) nmol/L] were significantly decreased as compared with those before treatment [(2.22±0.63) nmol/L, t =2.73, 2.78, 5.18, P < 0.05]. The levels of TT3 at 6 and 12 months [(109.65±23.98), (107.72±23.90) nmol/L] were significantly decreased as compared with those before treatment [(118.98±28.48) nmol/L, t =3.11, 3.30, P < 0.05]. TT4 level in serum at 3 months and the levels of FT3 and TSH at each time point after CBZ treatment had no obvious changes as compared with those before treatment (P > 0.05). In the TPM group, the levels of thyroid hormones at each time point had no obvious changes as compared with those before treatment (P > 0.05). ② Curative effects: Of the 100 epileptic patients, it was controlled in 12 cases, significantly effective in 30 cases, effective in 39 cases and invalid in 19 cases, the total effective rate was 81% (81/100). CONCLUSION: CBZ treatment can lead to the decreases of thyroid hormones in adult epileptic patients. Epilepsy itself and TPM treatment cannot change the thyroid hormones in adult epileptic patients, which suggests that TPM treatment is safer for the thyroid function of adult epileptic patients.展开更多
OBJECTIVE：To evaluate the treatment effects and safety of topiramate in migraine prophylaxis. DATA RETRIEVAL：We searched the Medline database,EMbase,Cochrane Library and China National Knowledge Infrastructure datab...OBJECTIVE：To evaluate the treatment effects and safety of topiramate in migraine prophylaxis. DATA RETRIEVAL：We searched the Medline database,EMbase,Cochrane Library and China National Knowledge Infrastructure database for articles published between January 1995 and May 2011,using the key words＂migraine＂,＂topiramate＂,and＂prophylaxis＂. SELECTION CRITERIA：We selected randomized controlled trials of migraine patients,in which the experimental group was orally administered topiramate,and the control group was given placebo. Odds ratios（ORs）and mean differences（MDs）were calculated using a fixed effects model/random effects model.Quality evaluation and data extraction were performed independently by two researchers utilizing RevMan 5.0 software. MAIN OUTCOME MEASURES：Efficacy was recorded as the responder rate（response defined as at least a 50%reduction in average monthly migraine frequency）and change in mean monthly number of migraine days.Adverse events were recorded as the number of subjects exhibiting at least one adverse event. RESULTS：Eight randomized controlled trials were found to be appropriate,and had available data. The meta-analysis results revealed that topiramate（100 or 200 mg/d）was more effective than placebo in responder rate（OR=2.97,95%confidence interval（CI）：2.17-4.08,P〈0.01;OR=2.35, 95%CI：1.77-3.12,P〈0.01）.Topiramate（100 mg/d）was more effective than placebo in terms of the change in mean monthly migraine days（MD：-1.14,95%CI：-1.69 to-0.59,P〈0.01）.The total incidence rate of adverse events for topiramate was higher than in the placebo group（P〈0.01）,but most adverse events were mild to moderate. CONCLUSION：Overall,topiramate obtained good outcomes and safety in migraine prophylaxis.展开更多
BACKGROUND： Apoptosis plays an important role in brain injury after seizures and the formation of chronic epilepsy. It is important to investigate whether topiramate exhibits either antiepileptic and/or antiapoptotic...BACKGROUND： Apoptosis plays an important role in brain injury after seizures and the formation of chronic epilepsy. It is important to investigate whether topiramate exhibits either antiepileptic and/or antiapoptotic effects on hippocampal neurons. OBJECTIVE： To observe neuronal apoptosis in hippocampus of rat seizure models, and to investigate the antagonizing effect of topiramate on neuronal apoptosis after seizures. DESIGN： An animal experiment of comparative observation. SETTING： First Affiliated Hospital of Guangxi Medical University. MATERIALS： Sixty healthy male Sprague Dawley （SD） rats, 4-6 weeks old and weighing 160-220 g, were provided by the Experimental Animal Center of Guangxi Medical University. Main apparatus and reagents were as follows： Rat brain solid positioner （SR-6N, made in Japan）; kainic acid by Sigma （USA）; pathological image analyzer （DMR＋550） by Leica （Germany）; in situ apoptosis detection kit by Wuhan Boster Biological Technology Co., Ltd; topiramate by Xi＇an-Janssen Pharmaceutical, Ltd. The treatment on animals in the experiment was in accordance with the standards of animal ethics. METHODS： The experiments were performed at the Scientific Experimental Center of Guangxi Medical University from June to December 2006. The rats were randomly divided into a topiramate-treated group （n = 30） and a model group （n = 30）. ① After anesthesia, all rats were administered a kainic acid injection （0.2 μL, 2 g/L） into the right lateral ventricle. Grade Ⅲ and greater Racine standards were considered to be a successful model establishment. Thirty minutes after seizure , rats in the topiramate-treated group were treated with an intraperitoneal （i.p.） injection of topiramate every day （40 mg/kg/d） for 2 weeks. The rats in the model group were treated with an equal volume of saline for 2 weeks. ③ Six rats in the topiramate-treated group were sacrificed at 1 day, and 1, 2, 3, and 4 weeks after treatment, respectively. The model group animals were sacrificed at corresponding time points. The brain tissues of hippocampal dentate gyrus, CA1, CA2, and CA3 region were removed and prepared into sections. Neuronal apoptosis was detected with in situ terminal deoxynucleotidyl transferase dUTP nick-end labeling. MAIN OUTCOME MEASURES： Hippocampal neuronal apoptosis in various rat brain areas was detected in the two groups. RESULTS： All 60 rats were included in the final analysis of results. In the topiramate-treated group, the number of apoptotic cells in hippocampal dentate gyrus and CA3 region at 1 day, 1, and 4 weeks after seizures were significantly lower than the model group （P 〈 0.05-0.01）. The number of apoptotic cells in hippocampal CA1 and CA2 regions at 1 day and 4 weeks after seizures in the topiramate-treated group were significantly lower than the model group （P 〈 0.05）. CONCLUSION： Hippocampal apoptosis is closely associated with kainic acid-evoked seizures, and topiramate can alleviate early （1 day and 1 week） and delayed （4 weeks） hippocampal neuronal injury induced by kainic acid.展开更多
Paroxysmal kinesigenic dyskinesia(PKD)is presented as a short paroxysmal attack of focal or generalized involuntary movement.The most common treatments for PKD are carbamazepine and phenytoin.Though the cases of clini...Paroxysmal kinesigenic dyskinesia(PKD)is presented as a short paroxysmal attack of focal or generalized involuntary movement.The most common treatments for PKD are carbamazepine and phenytoin.Though the cases of clinically diagnosed PKD with a good response to topiramate have been already reported,this patient was unique in several ways.Here,we reported the case of a 24-year-old patient with PKD for one year,and described the pathogenesis of PKD.展开更多
The use of generic formulation of therapeutic agents may allow a significant reduction of costs for patients and the National Health Services. This is particularly true for drugs used in prolonged therapies such as to...The use of generic formulation of therapeutic agents may allow a significant reduction of costs for patients and the National Health Services. This is particularly true for drugs used in prolonged therapies such as topiramate which is effective in the treatment of epilepsy, migraine, alcohol abuse and psychiatric conditions. The purposes of this study were: 1) evaluate Topiramate (50 mg) release in vitro from a generic (Sincronil) and the reference formulation (Topamax);2) compare the above mentioned generic and reference formulations in bioavailability studies in healthy volunteers. Dissolution tests in vitro showed that more than 95% of the active principle was released within 15 minutes both from the reference and the generic formulation. No difference in release kinetics was found between the two topiramate preparations. In vivo pharmacokinetic data were obtained by administering 1 tablet containing 50 mg of topiramate of each of the two formulations to 28 healthy volunteers under fasting conditions, using a randomized, single-dose, open-label, 2-way crossover design. The treatment phases were separated by a washout period of 21 days. The maximum concentration reached in plasma (Cmax) for the reference and the generic formulation, were 946 ± 308 and 849 ± 247 (ng/mL) and the area under the curve (AUC0-t) were 35,900 ± 7800 and 34,300 ± 8100 (ng·h/mL) respectively. The data indicate that the rate and extent of absorption of the reference or generic 50 mg topiramate formulation are not significantly different and suggest that the therapeutic effects of the two preparations do not significantly differ.展开更多
基金financially supported by the Liaoning Province Applied Fundamental Research Program(No.2023JH2/101700039)Liaoning Province Natural Science Foundation(No.2023-MSLH-328)。
文摘Lattice metamaterials based on three-period minimum surface(TPMS)are an effective means to achieve lightweight and high-strength materials which are widely used in various fields such as aerospace and ships.However,its vibration and noise reduction,and damping properties have not been fully studied.Therefore,in this study,the TPMS structures with parameterization were designed by the method of surface migration,and the TPMS structures with high forming quality was manufactured by laser powder bed fusion(LPBF).The mechanical properties and energy absorption characteristics of the beam and TPMS structures were studied and compared by quasi-static compression.The modal shapes of the beam lattice structures and TPMS structures were obtained by the free modal analysis,and the damping properties of two structures were obtained by modal tests.For the two structures after heat treatment with the same porosity of 70%,the yield strength of the beam lattice structure reaches 40.76 MPa,elastic modulus is 20.38 GPa,the energy absorption value is 32.23 MJ·m^(-3),the damping ratio is 0.52%.The yield strength,elastic modulus,energy absorption value,and damping ratio of the TPMS structure are 50.74 MPa,25.37 GPa,47.34 MJ·m^(-3),and 0.99%,respectively.The results show that TPMS structures exhibit more excellent mechanical properties and energy absorption,better damping performance,and obvious advantages in structural load and vibration and noise reduction compared with the beam lattice structures under the same porosity.
基金supported by Social Development Science and Technology Research Projects of Shanxi Province(2011 ks-30)
文摘Objective:To explore protective effeet of topiramate(TPM) on hypoxic—ischemic brain injury.Methods:A total of 360 neonatal rats were seleeted then randomly divided into sham operation group,ischemia and hypoxia group,conventional treatment group and degradation therapy group(n=90).After surgical treatment,sham and ischemic hypoxia group were treat with normal saline:conventional treatment group was received Tl'M solution 100 mg/kg.2 times/d:degradation therapy group received TPM solution 150 mg/kg.2 times/d.per 3 d treatment each dosage was reduced 50 mg/kg.the lowest reduced to 50 mg/kg.Four groups received continuous treatment for 10 d.After treatment for 1 d.4 d.7 d.10 d the cercbral edema,neuron-specific enolase(NSE)and γ-aminobutyric acid(GABA) levels and cognitive abilities of four groups were observed.Results:After 1d.4d of treatment,the brain water conlenl and NSE levels in ischemia and hypoxia group,the conventional treatment group and the degradation therapy group were significantly higher than that in sham group(P<0.05),the brain water content and NSE levels of the conventional treatment group and the degradation therapy group were significantly lower than that in the ischemic hypoxia group(P<0.05).GABA levels and learning ability of the ischemia and hypoxia group,the conventional treatment group and degradation therapy group were significantly lower than the sham group(P<0.05).the GABA levels and learning ability of the conventional treatment group and degradation therapy group were significantly higher than the ischemia and hypoxia group(P<0.05).After 7d.10 d of treatment,the brain water content and NSE levels in the sham operation group,the conventional treatment group and degradation therapy group were significantly lower than the ischemia and hypoxia group(P<0.05).while the GABA levels and learning ability of these three groups were significantly higher than that in the ischemia and hypoxia group(P<0.05>.the GABA levels in the conventional treatment group were significantly higher than degradation therapy group(P<0.05);After 10 d of treatment,the GABA levels of the conventional treatment group were significantly higher than the sham group,the learning ability of the degradation therapy group and sham operation group were significantly higher than the conventional treatment group(P<0.05).Conclusions:The correct amount of short—term TPM has protective effect on hypoxic—ischemic brain injury,but long-term or excessive use may cause new damage to the brain and reduce the cognitive ability.
文摘Drug-induced peripheral neuropathy had been rarely reported as an adverse effect of some antiepileptic drugs(AEDs) at high cumulative doses or even within the therapeutic drug doses or levels.We describe clinical and diagnostic features of a patient with peripheral neuropathy as an adverse effect of chronic topiramate(TPM) therapy.A 37-year-old woman was presented for the control of active epilepsy(2010).She was resistant to some AEDs as mono-or combined therapies(carbamazepine,sodium valproate,levetiracetam,oxcarbazepine and lamotrigine).She has the diagnosis of frontal lobe epilepsy with secondary generalization and has a brother,sister and son with active epilepsies.She became seizure free on TPM(2013-2017) but is complaining of persistent distal lower extremities paresthesia in a stocking distribution.Neurological examination revealed presence of diminished Achilles tendon reflexes,stocking hypesthesia and delayed distal latencies,reduced conduction velocities and amplitudes of action potentials of posterior tibial and sural nerves,indicating demyelinating and axonal peripheral neuropathy of the lower extremities.After exclusion of the possible causes of peripheral neuropathy,chronic TPM therapy is suggested as the most probable cause of patient's neuropathy.This is the first case report of topiramate induced peripheral neuropathy in the literature.
基金partly supported by Turkish Neurosurgical Society
文摘Topiramate（TPM） is a widely used antiepileptic and antimigraine agent which has been shown to exert neuroprotective effects in various experimental traumatic brain injury and stroke models. However, its utility in spinal cord injury has not been studied extensively. Thus, we evaluated effects of TPM on secondary cellular injury mechanisms in an experimental rat model of traumatic spinal cord injury（SCI）. After rat models of thoracic contusive SCI were established by free weight-drop method, TPM（40 mg/kg） was given at 12-hour intervals for four times orally. Post TPM treatment, malondialdehyde and protein carbonyl levels were significantly reduced and reduced glutathione levels were increased, while immunoreactivity for endothelial nitric oxide synthase, inducible nitric oxide synthase, and apoptotic peptidase activating factor 1 was diminished in SCI rats. In addition, TPM treatment improved the functional recovery of SCI rats. This study suggests that administration of TPM exerts neuroprotective effects on SCI.
文摘BACKGROUND: It has been demonstrated that traditional antiepileptics, such as phenytoin, carbamazepine (CBZ), phenobarbital, etc., can result in the decrease of thyroid hormone of epileptic patients. However, there is still no sufficient evidence for the studies about the effect of new-type antiepileptics, such as topiramate (TPM), on thyroid hormones. OBJECTIVE: To observe the effects of TPM and CBZ on the level of thyroid hormones in serum of adults with epilepsy. DESIGN: A comparative observation. SETTING: Department of Neurology, Sichuan Provincial People's Hospital. PARTICIPANTS: Totally 100 outpatients or inpatients newly diagnosed to have epilepsy were selected from the Department of Neurology, Sichuan Provincial People's Hospital from July 2003 to August 2005, including 60 males and 40 females, aged 18-70 years. All the patients were accorded with the standard for the classification of epilepsy set by International League Against Epilepsy (ILAE) in 1981; Had been Informed and agreed with the detection; Had no history of thyroid gland disease; Had not taken any drugs could affect the thyroid function. Meanwhile, 40 adult healthy examinees were selected from our hospital as the control group, including 24 males and 16 females, aged 18-65 years. METHODS: ① The 100 epileptic patients were randomly divided into TPM group (n =50) and CBZ group (n =50), and they were treated with TPM (Xian-Janssen Pharmaceutical, Ltd.; Batch number: 03AS032, Norm: 25 mg/tablet) and CBZ (Shanghai Sunve Pharmaceutical Co., Ltd.; Batch number: 030201, Norm: 100 mg/tablet) respectively. The initial dosage of TPM was 25 mg per day, increased by 25 mg every week, the objective dosage of 100-200 mg per day was maintained when the symptoms were satisfactorily controlled. The dosage of CBZ was 6-8 mg/kg per day. All the patients were administrated for 1 year. ② The serum levels of total thyroxine (TT4), free thyroxine (FT4), total triiodothyronine (TT3), free triiodothyronine (FT3) and thyroid stimulating hormone (TSH) in the epileptic patients were detected by means of chemiluminescence before treatment and at 3, 6 and 12 months after treatment respectively. ③Standards for judging curative effects: Controlled by without seizure, the frequency of seizure reduced by ≥ 75% was taken as significant effect, reduced by 50%-74% as effect, and reduced by < 49% as invalid, whereas increased by more than 20% was taken as aggravation. ④ The intergroup and intragroup differences of the measurement data were compared by the analysis of variance and paired t test respectively. MAIN OUTCOME MEASURES: Serum levels of thyroid hormones before treatment and at different time points after treatment of TPM and CBZ. RESULTS: All the 100 epileptic patients and 40 healthy subjects were involved in the analysis of results. ① Changes of serum levels of thyroid hormones: The serum levels of TT3, TT4, FT3, FT4 and TSH were close between the epileptic patients and normal subjects before treatment (P > 0.05). In the CBZ group, the serum levels of FT4 at 3, 6 and 12 months after treatment [(16.87±3.77), (16.34±3.98) , (16.97±3.95) pmol/L] were significantly decreased as compared with those before treatment [(18.00±3.54) pmol/L, t =2.74, 3.50, 2.26, P < 0.05]; The levels of TT3 at 3, 6 and 12 months [(2.09±0.54), (1.99±0.49), (1.84±0.47) nmol/L] were significantly decreased as compared with those before treatment [(2.22±0.63) nmol/L, t =2.73, 2.78, 5.18, P < 0.05]. The levels of TT3 at 6 and 12 months [(109.65±23.98), (107.72±23.90) nmol/L] were significantly decreased as compared with those before treatment [(118.98±28.48) nmol/L, t =3.11, 3.30, P < 0.05]. TT4 level in serum at 3 months and the levels of FT3 and TSH at each time point after CBZ treatment had no obvious changes as compared with those before treatment (P > 0.05). In the TPM group, the levels of thyroid hormones at each time point had no obvious changes as compared with those before treatment (P > 0.05). ② Curative effects: Of the 100 epileptic patients, it was controlled in 12 cases, significantly effective in 30 cases, effective in 39 cases and invalid in 19 cases, the total effective rate was 81% (81/100). CONCLUSION: CBZ treatment can lead to the decreases of thyroid hormones in adult epileptic patients. Epilepsy itself and TPM treatment cannot change the thyroid hormones in adult epileptic patients, which suggests that TPM treatment is safer for the thyroid function of adult epileptic patients.
文摘OBJECTIVE：To evaluate the treatment effects and safety of topiramate in migraine prophylaxis. DATA RETRIEVAL：We searched the Medline database,EMbase,Cochrane Library and China National Knowledge Infrastructure database for articles published between January 1995 and May 2011,using the key words＂migraine＂,＂topiramate＂,and＂prophylaxis＂. SELECTION CRITERIA：We selected randomized controlled trials of migraine patients,in which the experimental group was orally administered topiramate,and the control group was given placebo. Odds ratios（ORs）and mean differences（MDs）were calculated using a fixed effects model/random effects model.Quality evaluation and data extraction were performed independently by two researchers utilizing RevMan 5.0 software. MAIN OUTCOME MEASURES：Efficacy was recorded as the responder rate（response defined as at least a 50%reduction in average monthly migraine frequency）and change in mean monthly number of migraine days.Adverse events were recorded as the number of subjects exhibiting at least one adverse event. RESULTS：Eight randomized controlled trials were found to be appropriate,and had available data. The meta-analysis results revealed that topiramate（100 or 200 mg/d）was more effective than placebo in responder rate（OR=2.97,95%confidence interval（CI）：2.17-4.08,P〈0.01;OR=2.35, 95%CI：1.77-3.12,P〈0.01）.Topiramate（100 mg/d）was more effective than placebo in terms of the change in mean monthly migraine days（MD：-1.14,95%CI：-1.69 to-0.59,P〈0.01）.The total incidence rate of adverse events for topiramate was higher than in the placebo group（P〈0.01）,but most adverse events were mild to moderate. CONCLUSION：Overall,topiramate obtained good outcomes and safety in migraine prophylaxis.
基金Foundation for the Returned Overseas Chinese Scholars, Guangxi Science and Technology Committee, No. 0342012
文摘BACKGROUND： Apoptosis plays an important role in brain injury after seizures and the formation of chronic epilepsy. It is important to investigate whether topiramate exhibits either antiepileptic and/or antiapoptotic effects on hippocampal neurons. OBJECTIVE： To observe neuronal apoptosis in hippocampus of rat seizure models, and to investigate the antagonizing effect of topiramate on neuronal apoptosis after seizures. DESIGN： An animal experiment of comparative observation. SETTING： First Affiliated Hospital of Guangxi Medical University. MATERIALS： Sixty healthy male Sprague Dawley （SD） rats, 4-6 weeks old and weighing 160-220 g, were provided by the Experimental Animal Center of Guangxi Medical University. Main apparatus and reagents were as follows： Rat brain solid positioner （SR-6N, made in Japan）; kainic acid by Sigma （USA）; pathological image analyzer （DMR＋550） by Leica （Germany）; in situ apoptosis detection kit by Wuhan Boster Biological Technology Co., Ltd; topiramate by Xi＇an-Janssen Pharmaceutical, Ltd. The treatment on animals in the experiment was in accordance with the standards of animal ethics. METHODS： The experiments were performed at the Scientific Experimental Center of Guangxi Medical University from June to December 2006. The rats were randomly divided into a topiramate-treated group （n = 30） and a model group （n = 30）. ① After anesthesia, all rats were administered a kainic acid injection （0.2 μL, 2 g/L） into the right lateral ventricle. Grade Ⅲ and greater Racine standards were considered to be a successful model establishment. Thirty minutes after seizure , rats in the topiramate-treated group were treated with an intraperitoneal （i.p.） injection of topiramate every day （40 mg/kg/d） for 2 weeks. The rats in the model group were treated with an equal volume of saline for 2 weeks. ③ Six rats in the topiramate-treated group were sacrificed at 1 day, and 1, 2, 3, and 4 weeks after treatment, respectively. The model group animals were sacrificed at corresponding time points. The brain tissues of hippocampal dentate gyrus, CA1, CA2, and CA3 region were removed and prepared into sections. Neuronal apoptosis was detected with in situ terminal deoxynucleotidyl transferase dUTP nick-end labeling. MAIN OUTCOME MEASURES： Hippocampal neuronal apoptosis in various rat brain areas was detected in the two groups. RESULTS： All 60 rats were included in the final analysis of results. In the topiramate-treated group, the number of apoptotic cells in hippocampal dentate gyrus and CA3 region at 1 day, 1, and 4 weeks after seizures were significantly lower than the model group （P 〈 0.05-0.01）. The number of apoptotic cells in hippocampal CA1 and CA2 regions at 1 day and 4 weeks after seizures in the topiramate-treated group were significantly lower than the model group （P 〈 0.05）. CONCLUSION： Hippocampal apoptosis is closely associated with kainic acid-evoked seizures, and topiramate can alleviate early （1 day and 1 week） and delayed （4 weeks） hippocampal neuronal injury induced by kainic acid.
基金the National Natural Science Foundation of China(81400957)
文摘Paroxysmal kinesigenic dyskinesia(PKD)is presented as a short paroxysmal attack of focal or generalized involuntary movement.The most common treatments for PKD are carbamazepine and phenytoin.Though the cases of clinically diagnosed PKD with a good response to topiramate have been already reported,this patient was unique in several ways.Here,we reported the case of a 24-year-old patient with PKD for one year,and described the pathogenesis of PKD.
文摘The use of generic formulation of therapeutic agents may allow a significant reduction of costs for patients and the National Health Services. This is particularly true for drugs used in prolonged therapies such as topiramate which is effective in the treatment of epilepsy, migraine, alcohol abuse and psychiatric conditions. The purposes of this study were: 1) evaluate Topiramate (50 mg) release in vitro from a generic (Sincronil) and the reference formulation (Topamax);2) compare the above mentioned generic and reference formulations in bioavailability studies in healthy volunteers. Dissolution tests in vitro showed that more than 95% of the active principle was released within 15 minutes both from the reference and the generic formulation. No difference in release kinetics was found between the two topiramate preparations. In vivo pharmacokinetic data were obtained by administering 1 tablet containing 50 mg of topiramate of each of the two formulations to 28 healthy volunteers under fasting conditions, using a randomized, single-dose, open-label, 2-way crossover design. The treatment phases were separated by a washout period of 21 days. The maximum concentration reached in plasma (Cmax) for the reference and the generic formulation, were 946 ± 308 and 849 ± 247 (ng/mL) and the area under the curve (AUC0-t) were 35,900 ± 7800 and 34,300 ± 8100 (ng·h/mL) respectively. The data indicate that the rate and extent of absorption of the reference or generic 50 mg topiramate formulation are not significantly different and suggest that the therapeutic effects of the two preparations do not significantly differ.
