BACKGROUND： Calcium antagonists may act as neuroprotectants, diminishing the influx of calcium ions through voltage-sensitive calcium channels. When administered prophylactically, they display neuroprotective effects...BACKGROUND： Calcium antagonists may act as neuroprotectants, diminishing the influx of calcium ions through voltage-sensitive calcium channels. When administered prophylactically, they display neuroprotective effects against hypoxic-ischemic brain damage in newborn rats. OBJECTIVE： To investigate the neuroprotective effects of flunarizine （FNZ）, lamotrigine （LTG） and the combination of both drugs, on hypoxic-ischemic brain damage in fetal rats. DESIGN AND SETTING： This randomized, complete block design was performed at the Department of Pediatrics, Shenzhen Fourth People＇s Hospital, Guangdong Medical College. MATERIALS： Forty pregnant Wistar rats, at gestational day 20, were selected for the experiment and were randomly divided into FNZ, LTG, FNZ ＋ LTG, and model groups, with 10 rats in each group. METHODS： Rats in the FNZ, LTG, and FNZ ＋ LTG groups received intragastric injections of FNZ （0.5 mg/kg/d）, LTG （10 mg/kg/d）, and FNZ （0.5 mg/kg/d） ＋ LTG （10 mg/kg/d）, respectively. Drugs were administered once a day for 3 days prior to induction of hypoxia-ischemia. Rats in the model group were not administered any drugs. Three hours after the final administration, eight pregnant rats from each group underwent model establishment hypoxia-ischemia brain damage to the fetal rats. Cesareans were performed at 6, 12, 24, and 48 hours later; and 5 fetal rats were removed from each mother and kept warm. Two fetuses without model establishment were removed by planned cesarean at the same time and served as controls. A total of 0.3 mL serum was collected from fetal rats at 6, 12, 24, and 48 hours, respectively, following birth. MAIN OUTCOME MEASURES： Serum protein concentrations of neuron-specific enolase and S-100 were measured by ELISA. Serum concentrations of brain-specific creatine kinase were measured using an electrogenerated chemiluminescence method. RESULTS： Serum concentrations of neuron-specific enolase, S-100, and brain-specific creatine kinase were significantly higher in the hypoxic-ischemic fetal rats, compared with the non-hypoxic-ischemic group. Serum concentrations of neuron-specific enolase, S-100, and brain-specific creatine kinase were significantly less in the FNZ, LTG, and FNZ ＋ LTG groups following ischemia, compared with the model group （P 〈 0.01）. However, these values were significantly greater in the FNZ and LTG groups, compared with the FNZ ＋ LTG group, following ischemia （P 〈 0.01）. CONCLUSION： Preventive antenatal use of oral FNZ and LTG has positive neuroprotective effects on intrauterine hypoxic-ischemic brain damage. The combined effect of these two drugs is superior.展开更多
A rapid selective method for the analysis of flunarizine and its associated impurities was developed and validated according to ICH guidelines. The separation was carried out using a Thermo Scientific Hypersil Gold C1...A rapid selective method for the analysis of flunarizine and its associated impurities was developed and validated according to ICH guidelines. The separation was carried out using a Thermo Scientific Hypersil Gold C18 column （50 mm × 4.6 mm i.d., 1.9 μm particle size） with a gradient mobile phase of acetonitrile-ammonium acetate-tetrabutylammoniumhydrogen sulfate buffer, at a flow rate of 1,8 mL/min and UV detection at 230 nm. Naturally aged samples were also tested to determine sample stability. A profile of sample and impurity breakdown was also presented.展开更多
Background Although flunarizine has been widely used for migraine prophylaxis with clear success, the mechanisms of its actions in migraine prophylaxis are not completely understood. The aim of this study was to inves...Background Although flunarizine has been widely used for migraine prophylaxis with clear success, the mechanisms of its actions in migraine prophylaxis are not completely understood. The aim of this study was to investigate the effects of flunarizine on tetrodotoxin-resistant Na＋ channels and high-voltage activated Ca2＋ channels of acutely isolated mouse trigeminal ganglion neurons. Methods Sodium currents and calcium currents in trigeminal ganglion neurons were monitored using whole-cell patch-clamp recordings. Paired Student＇s t test was used as appropriate to evaluate the statistical significance of differences between two group means. Results Both tetrodotoxin-resistant sodium currents and high-voltage activated calcium currents were blocked by flunarizine in a concentration-dependent manner with the concentration producing half-maximal current block values of 2.89 μmol/L and 2.73 μmol/L, respectively. The steady-state inactivation curves of tetrodotoxin-resistant sodium currents and high-voltage activated calcium currents were shifted towards more hyperpolarizing potentials after exposure to flunarizine. Furthermore, the actions of flunarizine in blocking tetrodotoxin-resistant sodium currents and high-voltage activated calcium currents were use-dependent, with effects enhanced at higher rates of channel activation. Conclusion Blockades of these currents might help explain the peripheral mechanism underlying the preventive effect of flunarizine on migraine attacks.展开更多
Background Alternating hemiplegia of childhood(AHC)is a rare pediatric syndrome characterized by recurring episodes of hemiplegia or quadriplegia,and frequently accompanied by dystonic posturing,choreoathetosis moveme...Background Alternating hemiplegia of childhood(AHC)is a rare pediatric syndrome characterized by recurring episodes of hemiplegia or quadriplegia,and frequently accompanied by dystonic posturing,choreoathetosis movements,anomalous ocular motions,and a gradual deterioration in cognitive function.The principal etiology of this disorder is traced back to mutations in the ATP1A3 gene.Case presentation Here,we report a 16-year-old girl with recurrent hemiplegia since her infancy.This patient has experienced paroxysmal limb weakness and aphasia for over 15 years,and has kept seeking medical attention but without receiving effective treatment.A misdiagnosis of hysteria persisted for over 4 years until the patient’s admission to our hospital.Whole-exome sequencing identified a known pathogenic heterozygous c.2270T>C(p.Leu757Pro)mutation in her ATP1A3 gene.Notably,her clinical manifestations,including pathological emotional responses and autonomic dysfunction,differed from the established profile associated with the same ATP1A3 mutation,which typically present with intellectual disability,a rostrocaudal symptom gradient,choreoathetosis,and dysarthria.The patient was finally diagnosed with AHC and treated with flunarizine thus significantly ameliorated hemiplegic episodes.Conclusions This case enhances our understanding of the intricate clinical manifestations of AHC,which require careful differentiation from various diseases such as epilepsy,hysteria,and paroxysmal dyskinesias.In the diagnosis of patients presenting with suspected symptoms,adhering to a systematic approach for localizing and diagnosing neurological disorders is crucial to prevent misdiagnosis and inappropriate treatments.Additionally,when AHC is suspected in a patient,genetic testing should be considered as part of the diagnostic approach.展开更多
Objective:To observe the clinical therapeutic effect on atlantoaxial instability treated with the combination of ulna-tibia needling therapy and"point-to-surface"tuina manipulation.Methods:A total of 64 outp...Objective:To observe the clinical therapeutic effect on atlantoaxial instability treated with the combination of ulna-tibia needling therapy and"point-to-surface"tuina manipulation.Methods:A total of 64 outpatients diagnosed as atlantoaxial instability were collected and randomized into a control group and an observation group,32 cases in each one.In the control group,flunarizine hydrochloride capsules were used for oral administration.In the observation group,the combined treatment of ulna-tibia needling therapy and"point-to-surface"tuina manipulation was adopted.The ulnatibia needling therapy was exerted at the cutaneous region of hand taiyang meridian on the ulnar region(from carpal joint to elbow joint)on both sides.The"point-to-surface"tuina manipulation included"onepoint and two-surface"technique,"upper-to-lower pressing"method and"lifting-trembling"method.The treatment was provided once daily,consecutively for 5 times.The scores of neck symptoms and physical signs,atlantoaxial axle separation degree and clinical therapeutic results were taken as the observation indicators to evaluate the treatment effect.Results:After treatment,the curative rate and the total effective rate in the observation group were all higher significantly than the control group(all P<0.01).The scores of clinical symptoms and physical signs were statistically different in the self-comparison of each group before and after treatment(all P<0.05).After treatment,the scores of clinical symptoms and physical signs,the excellence rate of atlantoaxial axle separation and the effective rate in the observation group were all significantly better than those of the control group(all P<0.01).Conclusion:The combination of ulna-tibia needling therapy and"point-to-surface"tuina manipulation achieves the better clinical therapeutic effect as compared with flunarizine hydrochloride.展开更多
基金Shenzhen Science and Technology Bureau, No.200405204
文摘BACKGROUND： Calcium antagonists may act as neuroprotectants, diminishing the influx of calcium ions through voltage-sensitive calcium channels. When administered prophylactically, they display neuroprotective effects against hypoxic-ischemic brain damage in newborn rats. OBJECTIVE： To investigate the neuroprotective effects of flunarizine （FNZ）, lamotrigine （LTG） and the combination of both drugs, on hypoxic-ischemic brain damage in fetal rats. DESIGN AND SETTING： This randomized, complete block design was performed at the Department of Pediatrics, Shenzhen Fourth People＇s Hospital, Guangdong Medical College. MATERIALS： Forty pregnant Wistar rats, at gestational day 20, were selected for the experiment and were randomly divided into FNZ, LTG, FNZ ＋ LTG, and model groups, with 10 rats in each group. METHODS： Rats in the FNZ, LTG, and FNZ ＋ LTG groups received intragastric injections of FNZ （0.5 mg/kg/d）, LTG （10 mg/kg/d）, and FNZ （0.5 mg/kg/d） ＋ LTG （10 mg/kg/d）, respectively. Drugs were administered once a day for 3 days prior to induction of hypoxia-ischemia. Rats in the model group were not administered any drugs. Three hours after the final administration, eight pregnant rats from each group underwent model establishment hypoxia-ischemia brain damage to the fetal rats. Cesareans were performed at 6, 12, 24, and 48 hours later; and 5 fetal rats were removed from each mother and kept warm. Two fetuses without model establishment were removed by planned cesarean at the same time and served as controls. A total of 0.3 mL serum was collected from fetal rats at 6, 12, 24, and 48 hours, respectively, following birth. MAIN OUTCOME MEASURES： Serum protein concentrations of neuron-specific enolase and S-100 were measured by ELISA. Serum concentrations of brain-specific creatine kinase were measured using an electrogenerated chemiluminescence method. RESULTS： Serum concentrations of neuron-specific enolase, S-100, and brain-specific creatine kinase were significantly higher in the hypoxic-ischemic fetal rats, compared with the non-hypoxic-ischemic group. Serum concentrations of neuron-specific enolase, S-100, and brain-specific creatine kinase were significantly less in the FNZ, LTG, and FNZ ＋ LTG groups following ischemia, compared with the model group （P 〈 0.01）. However, these values were significantly greater in the FNZ and LTG groups, compared with the FNZ ＋ LTG group, following ischemia （P 〈 0.01）. CONCLUSION： Preventive antenatal use of oral FNZ and LTG has positive neuroprotective effects on intrauterine hypoxic-ischemic brain damage. The combined effect of these two drugs is superior.
文摘A rapid selective method for the analysis of flunarizine and its associated impurities was developed and validated according to ICH guidelines. The separation was carried out using a Thermo Scientific Hypersil Gold C18 column （50 mm × 4.6 mm i.d., 1.9 μm particle size） with a gradient mobile phase of acetonitrile-ammonium acetate-tetrabutylammoniumhydrogen sulfate buffer, at a flow rate of 1,8 mL/min and UV detection at 230 nm. Naturally aged samples were also tested to determine sample stability. A profile of sample and impurity breakdown was also presented.
基金This work was supported by grants from the National Natural Science Foundation of China （No. 81070896） and a Yangsen Scienence Grant.
文摘Background Although flunarizine has been widely used for migraine prophylaxis with clear success, the mechanisms of its actions in migraine prophylaxis are not completely understood. The aim of this study was to investigate the effects of flunarizine on tetrodotoxin-resistant Na＋ channels and high-voltage activated Ca2＋ channels of acutely isolated mouse trigeminal ganglion neurons. Methods Sodium currents and calcium currents in trigeminal ganglion neurons were monitored using whole-cell patch-clamp recordings. Paired Student＇s t test was used as appropriate to evaluate the statistical significance of differences between two group means. Results Both tetrodotoxin-resistant sodium currents and high-voltage activated calcium currents were blocked by flunarizine in a concentration-dependent manner with the concentration producing half-maximal current block values of 2.89 μmol/L and 2.73 μmol/L, respectively. The steady-state inactivation curves of tetrodotoxin-resistant sodium currents and high-voltage activated calcium currents were shifted towards more hyperpolarizing potentials after exposure to flunarizine. Furthermore, the actions of flunarizine in blocking tetrodotoxin-resistant sodium currents and high-voltage activated calcium currents were use-dependent, with effects enhanced at higher rates of channel activation. Conclusion Blockades of these currents might help explain the peripheral mechanism underlying the preventive effect of flunarizine on migraine attacks.
文摘Background Alternating hemiplegia of childhood(AHC)is a rare pediatric syndrome characterized by recurring episodes of hemiplegia or quadriplegia,and frequently accompanied by dystonic posturing,choreoathetosis movements,anomalous ocular motions,and a gradual deterioration in cognitive function.The principal etiology of this disorder is traced back to mutations in the ATP1A3 gene.Case presentation Here,we report a 16-year-old girl with recurrent hemiplegia since her infancy.This patient has experienced paroxysmal limb weakness and aphasia for over 15 years,and has kept seeking medical attention but without receiving effective treatment.A misdiagnosis of hysteria persisted for over 4 years until the patient’s admission to our hospital.Whole-exome sequencing identified a known pathogenic heterozygous c.2270T>C(p.Leu757Pro)mutation in her ATP1A3 gene.Notably,her clinical manifestations,including pathological emotional responses and autonomic dysfunction,differed from the established profile associated with the same ATP1A3 mutation,which typically present with intellectual disability,a rostrocaudal symptom gradient,choreoathetosis,and dysarthria.The patient was finally diagnosed with AHC and treated with flunarizine thus significantly ameliorated hemiplegic episodes.Conclusions This case enhances our understanding of the intricate clinical manifestations of AHC,which require careful differentiation from various diseases such as epilepsy,hysteria,and paroxysmal dyskinesias.In the diagnosis of patients presenting with suspected symptoms,adhering to a systematic approach for localizing and diagnosing neurological disorders is crucial to prevent misdiagnosis and inappropriate treatments.Additionally,when AHC is suspected in a patient,genetic testing should be considered as part of the diagnostic approach.
基金Construction Project of Zhang Weihua Inheritance Studio in Shaanxi Province(2019.01 to 2021.12):2,019,022Academic School Inheritance Project of Shaanxi Provincial Administration of Traditional Chinese Medicine:Shaanxixi TCM[2018]NO.40。
文摘Objective:To observe the clinical therapeutic effect on atlantoaxial instability treated with the combination of ulna-tibia needling therapy and"point-to-surface"tuina manipulation.Methods:A total of 64 outpatients diagnosed as atlantoaxial instability were collected and randomized into a control group and an observation group,32 cases in each one.In the control group,flunarizine hydrochloride capsules were used for oral administration.In the observation group,the combined treatment of ulna-tibia needling therapy and"point-to-surface"tuina manipulation was adopted.The ulnatibia needling therapy was exerted at the cutaneous region of hand taiyang meridian on the ulnar region(from carpal joint to elbow joint)on both sides.The"point-to-surface"tuina manipulation included"onepoint and two-surface"technique,"upper-to-lower pressing"method and"lifting-trembling"method.The treatment was provided once daily,consecutively for 5 times.The scores of neck symptoms and physical signs,atlantoaxial axle separation degree and clinical therapeutic results were taken as the observation indicators to evaluate the treatment effect.Results:After treatment,the curative rate and the total effective rate in the observation group were all higher significantly than the control group(all P<0.01).The scores of clinical symptoms and physical signs were statistically different in the self-comparison of each group before and after treatment(all P<0.05).After treatment,the scores of clinical symptoms and physical signs,the excellence rate of atlantoaxial axle separation and the effective rate in the observation group were all significantly better than those of the control group(all P<0.01).Conclusion:The combination of ulna-tibia needling therapy and"point-to-surface"tuina manipulation achieves the better clinical therapeutic effect as compared with flunarizine hydrochloride.
