Safety and efficacy of botulinum toxin type A made in China for treatment of post-stroke upper limb spasticity: a randomized double-blind controlled trial / 中华神经科杂志

Objective To evaluate the safety and efficacy of botulinum toxin type A for injection in the treatment of post-stroke upper limb spasticity (dosage was 200 U,or 240 U if combined with thumb spasticity).Methods The study was a multi-center,stratified block randomized,double-blind,placebocontrolled trial.All the qualificd subjects were from 15 clinical centers from September 2014 to February 2016.They were randomized (2∶1) to injections of botulinum toxin type A made in China (200-240 U;n =118) or placebo (n =60) in pivotal phase after informed consent signed.The study was divided into two stages.The pivotal trial phase included a one-week screening,12-week double-blind treatment,followed by an expanded phase which included six-week open-label treatment.The tone of the wrist,finger,thumb flexors was assessed at baseline and at weeks 0,1,4,6,8,12,16 and 18 using Modified Ashworth Scale (MAS),disability in activities of daily living was rated using the Disability Assessment Scale and impaction on pain,muscle tone and deformity was assessed using the Global Assessment Scale.The primary endpoint was the score difference between botulinum toxin type A and placebo groups in the tone of the wrist flexor using MAS at six weeks compared to baseline.Results Muscle tone MAS score in the wrist flexor of botulinum toxin type A and placebo groups at six weeks changed-1.00 (-2.00,-1.00) and 0.00 (-0.50,0.00) respectively from baseline.Botulinum toxin type A was significantly superior to placebo for the primary endpoint (Z =6.618,P ＜ 0.01).The safety measurement showed 10 subjects who received botulinum toxin type A had 13 adverse reactions,with an incidence of 8.47％ (10/118),and three subjects who received placebo had three adverse reactions,with an incidence of 5.00％ (3/60) during the pivotal trial phase.All adverse reactions were mild to moderate,none serious.There was no significant difference in adverse reactions incidence between the botulinum toxin type A and the placebo groups.During the expanded phase three subjects had four adverse reactions and the incidence was 1.95％.All adverse reactions were mild,none serious.Conclusion Botulinum toxin type A was found to be safe and efficacious for the treatment of post-stroke upper limb spasticity.Clinical Trial Registration:China Drug Trials,CTR20131191

Study on the efficacy of breviscapine in the treatment of vascular cognitive impairment / 中国基层医药

Objective To investigate the efficacy of breviscapine in the treatment of vascular cognitive impairment.Methods A self-controlled trial was carried out in 36 patients with vascular cognitive impairment.36 cases were treated with breviscapine injection 50mg intravenous infusion daily for 3 weeks.At the same time,all cases were also given citicoline 0.75g/d and enteric-coated aspirin 100mg/d as routine treatment.The means of the evaluation on therapeutic effect included MMSE and ADL,and the adverse reactions were also observed.Results After the treatment,the MMSE scales increased from(18.75 ± 3.25)to(21.62 ± 3.58)(t=2.52,P＜0.05),Meanwhile,ADL scales declined from(45.65 ±3.36)to(42.33 ±4.18)(t=3.71,P＜0.05).There was significant difference on the MMSE and ADL between the pre and post therapy.No obvious side effects were found.Conclusion The results indicated that the breviscapine injection is an effective medicine in the treatment of vascular cognitive impairment,while the adverse reactions were few.

Effects of Rifampicin on Rotenone-induced Oxidative Stress in Differentiated PC12 Cells / 中山大学学报(医学科学版)

[Objective] To explore the effects of rifampicin on cell morphology,intracellular reactive oxygen species (ROS),reduced glutathione (GSH),and cell apoptosis in rotenone-induced differentiated pheochromocytoma (PC12) cells.[Methods] Rotenone was added in rat PC12 cells to develop a model of Parkinson's disease in vitro.Cell morphology was observed by microscope.Intracellular GSH was determined by a microplate reader.The intracellular ROS and the apoptosis rate were measured by flow cytometry.[Results] Compared with control group and rifampicin control group,GSH significantly decreased but ROS and apoptosis rate significantly increased in rotenone group.Compared with rotenone group,GSH significantly increased but ROS and apoptosis rate significantly decreased in a dose-dependent manner in rifampicin control group (100,200,and 300 μmol/L).[Conclusion] Rifampicin may reduce the damage of rotenone-induced differentiated PC12 cells through inhibiting oxidative injury in a dose-dependent manner.

Clinical and electrophysiological analysis of limb-girdle muscular dystrophy:A geneological report / 中华物理医学与康复杂志

Objective To analyze the clinical and electrophysiological features of one geneology with limbgirdle muscular dystrophy(LGMD). Methods Twenty-seven members of one family with limb-girdle muscular dystrophy(LGMD)were investigated.Fourteen of them were examined with electromyography(EMG)and their motor conduction velocities(MCV)and sensory conduction velocities(SCV)were measured.Among them,10 had no clinical manifestations,while 4 demonstrated symptoms and signs of LGMD. Results Three of the 4 patients had suffered from LGMD when young.They demonstrated the typical clinical features,including the progressive muscle weakness in the upper and lower extremities,positive Gower signs,duck gait,muscle atrophy distributed tO the proximal extremity,and no gastrocnemius hypertrophy.One subject presented atypical characteristics.The MCVs and SCVs of the 4 patients were normal,but neuropathic manifestations were found in the EMGS of 3 of them.and mixed neuropathic and myopathic manifestations were found in the EMG of the other.Conclusion LGMD patients in the same family can vary in their clinical characteristics.The longer the duration,the more severe the clinical features.Electrophysiological examination can reveal normal MCV and SCV but abnormal elctromyography.

Relationship between hereditary susceptibility of Parkinson disease and polymorphism of NAD (P) H: quinone oxidoreductase gene / 中国组织工程研究

BACKGROUND: Causes of Parkinson disease have not been mentioned clearly up to now yet. Theory of hereditary susceptibility is the main theory to explain Parkinson disease now. But there is no definite conclusion on which hereditary factors have relationship with it.OBJECTIVE: To study the relationship between gene polymorphism caused by point mutation C to T on cDNA609 basic group of reduced NAD(P) H:quinone oxidoreductase(NQO1) gene and hereditary susceptibility of Parkinson disease.DESIGN: A non-randomized synchronized control research based on patient and healthy people.SETTING: Neurology departments in two university hospitals and a senile disease research institute in a university hospital.PARTICIPANTS: Totally 126 patients(Parkinson disease group) diagnosed as Parkinson disease in Neurology Clinic of First Hospital Affiliated to Sun Yat-sen University from September 1994 to September 1997, aged 46 to 73 years, in which 74 were males and 52 were females. Totally 136 healthy adults (control group), in which 66 were males and 70 were females, who came to the clinic to do health examination at the same time, aged 40 to 72 years.METHODS: Polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) was used to analyze NQO1 gene polymorphism in Parkinson disease group and healthy adult control group.MAIN OUTCOME MEASURES: Mutation frequency and genotype of point mutation of basic group C to T on NQO1 gene cDNA609.RESULTS: T allele frequency in Parkinson disease group was 52% and that in control group was 43%. There was significant difference between two groups (P ＜ 0. 005) . There was significant difference on distribution of genotype in Parkinson disease group and control group( P ＜ 0.05). The risk incidence increased 3.8 times in individual with T allele.CONCLUSION: NQO1 gene cDNA609 mutation T allele may be a risk factor to Parkinson disease, which could be associated with the hereditary susceptibility of Parkinson disease.

An Ile93Met substitution in the UCH-L1 gene is not a disease-causing mutation for idiopathic Parkinson's disease / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To ascertain whether a coding mutation (Ile93Met) in ubiquitin carboxy-terminal hydrolase (UCH-L1) gene plays a role in idiopathic Parkinson's disease (IPD).</p><p><b>METHODS</b>Polymerase chain reaction-restriction fragment length polymorphism assay (PCR-RFLP) was used to distinguish the wild-type (two DNA fragments of 34 and 126 bp) from the variant allele (three fragments of 34, 60 and 66 bp) because the mutation created a new site for restriction endonuclease BsmF1. DNA was isolated from various blood samples using a phenolchloroform extraction.</p><p><b>RESULTS</b>Ile93Met substitution was found neither in PD patients nor in controls.</p><p><b>CONCLUSIONS</b>Our study suggested that Ile93Met of UCH-L1 gene did not influence risk of IPD.</p>

A new point mutation on exon 2 of parkin gene in Parkinson's disease / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To detect the relationship between point mutations on exon 2 of parkin gene and sporadic early-onset Parkinson's disease.</p><p><b>METHODS</b>The point mutations on exon 2 of parkin gene were detected using polymerase chain reaction(PCR), agarose electrophoresis, single strand conformation polymorphism(SSCP), DNA sequencing and analysis of restrict enzyme in DNA of 60 Parkinson's disease patients with an onset age under 50 and 120 normal controls.</p><p><b>RESULTS</b>One homozygous mutation (G(237)-->C) on exon 2 was found by sequencing and verified by analysis of restrict enzyme, whereas no mutation was found in normal controls.</p><p><b>CONCLUSION</b>Point mutations on exon 2 of parkin gene are likely to be related to sporadic early-onset Parkinson's disease.</p>

Mutation Detection on Exon 1 and 2 of Parkin Gene in Sporadic Early-onset Parkinson's Disease / 中山大学学报(医学科学版)

【Objective】To study the relationship between mutations on exon 1,2 of parkin gene and sporadic early-onset Parkinson's disease.【Methods】The deletion and single strand mobility shift on exon 1 and 2 of parkin gene in peripheral white blood cell DNA were detected by using PCR,agarose electrophoresis,and SSCP techniques in 52 patients with sporadic early-onset (onset age≤50) Parkinson's disease.The exons with mobility shift on SSCP were sequenced.【Results】One deletion（1.9%） of exon 2,2 cases with single strand mobility shift（3.8%）on exon 1 and exon 2 respectively,one heterozygous mutation (T103C) on exon 1 and one homozygous mutation (G237C) on exon 2 were found by sequencing.【Conclusion】Mutations on exon 1 and 2 of parkin gene are likely to be related to sporadic early-onset Parkinson's disease.

Rifampicin protects rats against rotenone-induced dopaminergic neurons damage / 中国病理生理杂志

AIM: To investigate the protective effect of rifampicin on rotenone-induced apoptosis of dopaminergic neurons and expression of ?-synuclein in rats.METHODS: Highly selective lesions and high expression of ?-synuclein in nigrostriatal dopaminergic neurons in rats were induced by chronic subcutaneous exposure to rotenone at dose of 1.5 mg?kg-1?d-1 for 3 weeks.At the same time,rifampicin was administered at dose of 30 mg?kg-1?d-1 by intragastric administration for 3 weeks.The changes of behavior,pathology and immunoreactivity of TH and ?-synuclein in SNc were observed.RESULTS: Obvious changes of behavior,pathology and TH immunoreactivity in SNc were observed in male SD rats injected subcutaneously with rotenone and rifampicin protected rats against these toxic effects induced by rotenone.CONCLUSION: Rifampicin has extensive protective effects against rotenone-induced neurotoxicity,which is related to inhibiting the expression and aggregation of ?-synuclein.