Parkinson's disease (PD) is one of the most frequent neurodegenerative disorders. ?-Synuclein was the first"PD gene"to be discovered. The involvement of ?-synuclein in PD was first suspected after two different ?-synuclein mutations were identified in two kindreds with autosomal-dominant PD. However,the discovery that ?-synuclein is the major component of Lewy bodies-pathological hallmarks of PD, confirmed its role in PD pathogenesis. Pathological aggregation of ?-synuclein might be responsible for neurodegeneration. Multiple factors have been shown to affect ?-synuclein aggregation in vitro or in vivo. In addition, soluble oligomers of ?-synuclein might be even more toxic than the insoluble fibrils found in degenerative diseases. So it is significant to investigate factors affecting ?-synuclein aggregation, especially their accurate effects on the aggregation process.

Objective To observe the efficacy and safety of pegylated interferon apha-2a combined with ribavirin in the treatment of chronic hepatitis C.Methods One hundred and six patients with chronic hepatitis C were divided into 2 groups randomly.Patients in the observation group were treated with pegylated interferon alpha-2a,and patients in the control group were treated with interferon alpha-1b.All patients were given ribavirin according to the weight,and the treatment course was 48 weeks.HCV-RNA was tested before treatment,4 weeks, 12weeks and 24 weeks after the start of treatment,end of treatment,24 weeks after the end of treatment.The adverse reactions were also observed.Results In the observation group,the rapid virological response (RVR) was 77.4%,the complete early virological response (cEVR) was 83.0%,the end treatment virological response (ETVR) was 90.6%, the sustained virological response (SVR) of 24 weeks after the end of treatment was 84.9%.and these rates were significantly higher than the control group.All patients received the whole course of treatment.Condusion Treatment of chronic hepatitis C with pegylated interferon apha-2a combined with ribavirin is effective and safe.

Objectiive:The present study was designed to explore whether overexpression of human wild ?-synuclein in rat brain caused selective dopaminergic neuron loss in substantia nigra and aimed to find out a new method to make a rat model of Parkinson's disease(PD).Methods:The human wild ?-synuclein gene was induced into the rat brain by Adeno-Associated Virus(AAV) vector.The overexpression of ?-synuclein was detected by realtime PCR.The behavior of rats were recorded every 4 weeks after the viral particle injection.TH immunohistochemistry were performed at 4,8,12 and 16 weeks post-injection as well as the dopamine(DA),3,4-dihydroxypheny-lacetic acid(DOPAC) of striatum were determined by high performance liquid chromatography coupled with electrochemical detection.Results:Realtime PCR results revealed a significant overexpression of ?-synuclein in the injected hemisphere.By 8 weeks post injection,a significant loss of the dopaminergic neurons was observed.34% of the dopaminergic neurons were lost after 12 weeks,and about 60% cells loss after 16 weeks.The DA and DOPAC levels in the striatum decreased about 15% 12 weeks after injecting viral particle carried ?-synuclein gene and 30% decreased after 16 weeks.The AAV-?-synuclein-treated rats developed a type of motor impairment,i.e.,head position bias,compatible with this magnitude of nigrostriatal damage.Conclusion:All the results showed that overexpression of human wild ?-synuclein caused selective dopaminergic neuron loss and mimic a symptom of human PD in rats.This may be a new methed to make rat PD model which can offer new opportunities for the study of pathogenetic mechanismsand exploration of new therapeutic targets of particular relevance to human PD.

Parkinson's disease(PD) is a common neurodegenerative disorder with no effective protective treatment,characterized by a massive degeneration of dopaminergic neurons in the substantia nigra(SNpc) and the subsequent loss of their projecting nerve fibers in the striatum.The major neurochemical manifestation of this disorder is the loss of the neurotransmitter dopamine(DA) in the striatum as a result of the progressive degeneration of the dopaminergic neurons in the substantia nigra.There have been significant progresses in recent years reporting on the use of mesenchymal stem cells(MSCs)in gene therapy,with specific application towards PD.MSCs,a kind of multipotent adult progenitor cells,are considered as a useful vehicle for cell and gene therapy because of their multiple differentiation potentiality and self-transplantation.The present study was focused on treating rat model of PD using human tyrosine hydroxylase gene(hTH),human aromatic L-amino acid decarboxylase gene(hAADC) and human GT Pcyclohydrolase I gene(hGCH-I) engineered MSCs,in order to provide a better understanding about the application of these cells in the therapeutic benifit of PD.The gene of hTH,hAADC and hGCH-I were introduced via recombinant adeno-associated virus(rAAV) infection into the MSCs in vitro.The genetically modified MSCs expressing hTH,hAADC and hGCH-I were transplanted into the striatum of PD rat models.The behavior,the nigra-striatal level of DA and its metabolite were detected.The results of present study were shown as follows:hTH,hAADC,hGCH-I and LacZ gene were transfected into MSCs with adeno-associated virus vectors.The HEK293 packaging cells(ATCC) were transfected with the plasmids of pAAV-hTH,pAAV-hAADC,pAAV-hGCH-I,pAAV-LacZ,pAAV-RC,pHelper by using calcium phosphate precipitation.Titer was detected using HT1080 cells.Viral particles were collected and used to infect MSCs.The purified modified MSCs expressing the three kinds of genes were selected separately and were grafted in the striatum of the PD model rats in the lesion side.The MSCs genetically modified suvived well 12 weeks after transplantation.The improvements of the behavior were observed every week after transplantation.Compared with the control group,the rounds of asymmetric rotation after apomorphine administration decreased in the groups double or triple genes engineered MSCs grafted(p

Objective:To identify the effect of ?-synuclein overexpression on mitochondrial membrane structure with atomic force microscopy. Methods:?-syn expression was mediated by AAV (adeno-associated viral vector) and Recombinant AAV/?-syn and AAV/LacZ viral particles were stereotaxically injected in the left side of rat substantia nigra (SN) for rat model of ?-synuclein overexpression. Mitochondria were isolated from rats SN of Brain. Mitochondria were analysis with JC-1 staining,atomic force microscopy and Western blot. Results:By 16 weeks post-infection of AAV-?-syn,the level of ?-syn increased about 2 times in mitochondrial fraction with Western blot and mitochondrial membrane potential (??) decreased with JC-1 staining. Furthermore,mitochondria swelling and porous like structure formed on the mitochondrial membrane with atomic force microscopy. Conclusion:The data suggested that ?-syn could accumulate in mitochondria,might form mitochondrial membrane pores and lead to ?? decreases. ?-syn might lead to mitochondrial dysfunction in Parkinson's disease.

Adult ; Congresses as Topic ; Hearing ; Hearing Tests ; Humans ; Mass Screening

Objective To observe the efficacy of antiviral therapy of pegylated interferon (Peg-IFN) α-2a combined with ribavirin for patients with hepatitis C cirrhosis and hypersplenism underwent splenectomy or partial splenic embolization. Methods Thirty-eight patients with hepatitis C cirrhosis (genotype Ⅰ HCV infection) hypersplenism failed to the anti-viral therapy were performed splenectomy or partial splenic embolization to improving hypersplenism. After 3 months,Peg-IFNα-2a 90μg or 135 μg was given subcutaneously once weekly, plus ribavirin 600-1 000 mg/d orally for 1 year of the treatment. During the treatment, patients were followed at four-week intervals, and then followed-up every month until the 24th week after stopping. Liver function, blood routine, renal function, HCV RNA, and adverse reaction of medication were observed during treatment and the follow-up period. Results Splenic function of patients with hepatitis C cirrhosis and hypersplenism was improved after hypersplenism splenectomy or partial splenic embolization. The sustained virologic response (SVR) rate was 63.88%after giving Peg-IFNα-2a combined with ribavirin anti-viral treatment. Conclusion After splenectomy or partial splenic embolization, patients with hepatitis C cirrhosis and hypersplenism showed the better SVR at the treatment of Peg-IFNα-2a combined with ribavirin. The treatment could delay the progress of the hepatitis C cirrhosis and reduce the incidence of liver failure and liver cancer.

Four methods were compared to purify Fo from porcine h ear t mitochondria. The best results were obtained by the following method: after re moving F1-ATPase with NaBr incubation from submitochondrial FoF1-ATPase, Fo was solubilized with CHAPS and purified by sucrose density gradient centri fugation. SDS-PAGE with silver staining showed about 85% purity of the isolated Fo and 9 different subunits including b, OSCP, d, a, e, F6, IF1, A6L and c. The purified Fo was then incorporated into asolectin liposomes, the reconst ituted Fo showed higher H+ translocation activity and after Fo was reconst ituted with F1-ATPase, the resulted FoF1-ATPase complex exhibited high A TP hydrolysis activity and high sensitivity to oligomycin. The results provide e vidence for successful purification, reconstitution of Fo with high H+ trans location activity and its relationship with phospholipids.

Humans ; Lipid Peroxidation ; Male ; Pneumoconiosis ; metabolism ; Superoxide Dismutase ; blood

OBJECTIVE: To study the effects of electroacupuncture and diet adjusting on insulin resistance in rats with nutrition obesity, and the role of electroacupuncture and diet adjusting in the treatment of obesity. METHODS: Obesity was induced in rats by high-fat diet. Rats with nutrition obesity were randomly divided into high-fat diet (HD) group, high-fat diet plus electroacupuncture (HA) group, normal diet (ND) group and normal diet plus electroacupuncture (NA) group, with another group of SD rats as normal control (NC). After 15 days, all the rats' body weight and length were measured, the Lee's index was calculated, and the levels of total cholesterol (TC), triglycerides (TG), free fatty acid (FFA), fasting plasma glucose (FPG), fasting insulin (FINS) and tumor necrosis factor-alpha (TNF-alpha) were detected. RESULTS: Compared with the HD group, food intake, body weight and viscera fat weight of the rats with nutrition obesity in the HA group and the NA group were markedly reduced (P<0.05). The levels of blood serum TC, FFA and IR index in the NA group were obviously lower than those in the HD group (P<0.01). The levels of TNF-alpha and FINS in the NA group were lower than those in the HD group (P<0.05). CONCLUSION: Electroacupuncture plus diet adjusting can decrease the levels of serum TNF-alpha and FINS of the obesity rats, and improve the state of insulin resistance.