BACKGROUND: 3-nitropropionic acid(3-NP) can inhibit the process of oxidative phosphorylation and injure the energy metabolism of the cell and thereby induce cell injury. However, small dose of 3-NP can excite intrinsic cellular protective factor to protect neurons and increase the tolerance of neurons to ischemic hypoxia through mild inhibiting the process of oxidative phosphorylation. It is unclear whether it also has the similar effect on dopaminergic neurons.OBJECTIVE: To investigate whether 3-NP preconditioning could enhance the tolerance of dopaminergic neurons to MPP+(1-methyl-4-phenylpyridine)toxicity.DESIGN: A randomized controlled exploring research based on neuroblastoma SH-SYSY cell that could secrete dopamine.SETTING: Department of neurology of a university hospital.MATERIALS: The study was conducted in the Laboratory of Pathophysiology of Tongji Medical College between March 2003 and November 2003. SH-SYSY cell was obtained from the Cell Center of Peking Union Medical University.INTERVENTIONS: Cells were randomly divided into 6 groups. MPP+ was added into the cultured dopaminergic neuron SH-SY5Y cells for the establishment of the cell model for Parkinson disease. Before the admission of MPP+ (0.25 mmol/L), 3-NP(0. 2 mmol/L) was added once or repetitive times to form preconditioning. Microculture tetrozolium(MTT) was used to detect cell survival rate, and[3H] DA uptake rate was used to test the anterior synaptic function of dopaminergic neurons.MAIN OUTCOME MEASURES: Major consequence: Cell survival rate;Minor consequence: [3H] DA uptake rate.RESULTS: Cell survival rate of MPP+ group was 54.3%, which was significantly lower than that of blank control group( P ＜ 0.01) . After 3-NP preconditioning, cell survival rate significantly elevated, which was 71.8%(single) or 85.2% (repetitive) . There was significant difference between single preconditioning and repetitive preconditioning( P ＜ 0.05 ). The results of[3H] DA uptake rate were similar to that of cell survival rate. [3H] DA uptake rate was 65.8% (single) or 80. 3% (repetitive), which was significantly higher than 50. 1% of MPP+ group. And moreover, repetitive preconditioning had more favorable effect than single preconditioning. Simple admission of 3-NP had no impact on cells.CONCLUSION: 3-NP preconditioning can significantly enhance the tolerance of dopaminergic neuron to MPP+ toxicity, which has significant protective effects on dopaminergic neuron. Repetitive preconditioning have more significant protective effects.

The objective of this study was to assess the clinical evidence for or against mood stabilizers as a treatment for Alzheimer's disease (AD). We searched 5 databases from their inception to January 2010. Five randomized clinical trials of mood stabilizers to treat human patients suffering from AD were included. These trials assessed the effectiveness of mood stabilizers as an adjunct treatment to conventional anti-dementia drugs on behavioral and psychological symptoms, especially on agitation. Methodological quality was assessed using the Jadad score. The results suggested a significant effect in favor of placebo on the Mini-Mental Status Examination [n=270, weight mean difference (WMD), -0.89; 95% confidence intervals (CIs) -1.69 to -0.09, P=0.03] and on the Neuropsychiatric Inventory total (NPI total) (n=51, WMD, 3.71; 95% CIs 0.15 to 7.26, P=0.04). There were no significant differences in change scores on total Brief Psychiatric Rating Scale (BPRS total), NPI/BPRS agitation, Cohen-Mansfield Agitation Inventory total and Physical Self Maintenance Scale between mood stabilizers and placebo. Only one of these studies was free of methodological limitations (Jadad score=5). In conclusion, based on the existing evidence, mood stabilizers are ineffective or even harmful as a treatment for AD.

Objective To study the clinicopathological characteristics of hepatobiliary cystic neoplasms(cystadenoma and cystadenocarcinoma)in order to improve its diagnostic and therapeutic accuracy.Methods A retrospective analysis was done on the clinical materials of 9 cases of cystic biliary tumors hospitalized in the People's Hospital of Rizhao City from May 1993 to May 2007.All cases were confirmed by operation and pathologic biopsy.Results Six cases were biliary cystadenoma with muhilocular cyst.The other three cases were biliary cystadenocarcinoma,two with single cyst and one with multilocular cyst.Of the three cystadenocarcinorna,two cases had mural nodules and one case had papillary excrescences and cystic wall thickening.Irregular thickening of internal sept.was shown in the multilocular cyst cases.Two had calcification.Enhancement of the wall.internal septa and nlasses were seen in all the malignant tumors on CT scans. Metastatic lymph node was found in one cage. Conclusion There were no special clinical characteristics in difierentiation between hiliary cystadenoma and cystadenocarcinoma. Single cyst, mural nodules and papillary excrescences,irregular thickening of cystic wall and internal septa,coarse calcification and metastatic lymph node increase the likelihood of the diagnosis of the malignant tumors.But the diagnostic differentiation between cystadenoma and cystadenocarcinoma depends on pathology.

Objective To investigate the efficacy and safety of pramipexole versus fluoxetine in the treatment of depression in Parkinson's disease ( PD). Methods A randomized, clinical trial of pramipexole versus fluoxetine treatment for 12 weeks in 50 patients suffering from combined PD and depression was accomplished. The efficacy and safety assessments of the treatments were performed at different time points. Results For the intent-to-treat (ITT) population, the Hamilton Depression Rating Scale (HAMD) scores decreased progressively in both the pramipexole and the fluoxetine group, and a between-time statistical analysis was significant for both groups. The efficacy proportion of patients who responded to the treatment, as defined by at least a 50% reduction in HAMD score, was 56. 0% in the pramipexole group versus 48. 0% in the fluoxetine group (χ~2 =0. 321, P>0. 05). Similarly, the proportion of patients who recovered, as defined by a final HAMD score ≤8, was 52. 0% in the pramipexole group versus 32. 0% in the fluoxetine group (χ~2 =2. 053, P>0. 05) , but the difference between the two treatments showed no statistical significance. At the endpoint, both the Unified Parkinson's Disease Rating Scale (UPDRS) part Ⅱ and part Ⅲ subscores improved in the pramipexole group, by a mean of 2. 9±3. 7 (t= 2.366, P<0.05) and7.2±5.1 (t=2.654, P< 0.05), respectively, and the latter was significantly different from the change in this variable of the fluoxetine group (P<0. 05). Spearman analysis showed that no relationship between HAMD score and UPDRS Part II or Part III subscore. The findings for the per-protocol (PP) population were consistent with the above results, except that the proportion of patients who recovered in the pramipexole group was significantly larger than that in the fluoxetine group. The adverse events in both groups were mild dizziness, nausea and anorexia. No significant difference was found in the frequencies of the adverse events between the pramipexole and fluoxetine group. Conclusions Pramipexole is effective and safe in the treatment of Chinese PD patients combined with depression.

BACKGROUND: Mainly pathological changes of Parkinson disease (PD)are related to irreversible degeneration and reduction of dopamine neurons of substantia nigra in midbrain; however, oxidative stress reaction plays an important role in onset of PD. 3-nitropropionie acid (3-NP) is an inhibitor of mitochondria compound I, and it can inhibit oxidative phosphorylation so as to restrain energy metabolism. However, professor Riepe from Germany found that small dose of 3-NP can increase the tolerance of neurons to ischemic hypoxia. It is unclear whether it can also strengthen the tolerance of dopamine neurons to neurotoxin.OBJECTIVE: To investigate the possible mechanism and prevention of repetitively preconditioning 3-NP for treating PD.DESIGN: Controlled observational animal study. SETTING: Department of Neurology, Union Hospital affiliated to TongjiMedical College, Huazhong University of Science and Technology. MATERIALS: The experiment was carried out at the Neurological Lab oratory, Union Hospital affiliated to Tongji Medical College, Huazhong U niversity of Science and Technology from March to July 2004. A total of48 C57BL mice, weighing 18-20 g, aged 2-3 months, of both genders, were randomly divided into 6 groups with 8 in each group. ① Blank con trol group: Mice were not medicated. ② 3-NP single administrationgroup: Mice were intraperitoneally injected with 3-NP once. ③ 3-NPrepetitively administrations group: Mice were intraperitoneally injectedwith 3-NP every 5 days for 5 times in total. ④ Neurotoxin group: Micewere intraperitoneally injected with neurotoxin once every day for 5 timesin total. ⑤ 3-NP single preconditioning group: Mice were intraperitoneal ly injected with 3-NP once, and 3 days later, they were intraperitoneallyinjected with neurotoxin once every day for 5 times in total. ⑥ 3-NPrepetitively preconditionings group: Mice were intraperitoneally injectedwith 3-NP and repetitively every 5 days for 5 times in total; 3 days later, mice were intraperitoneally injected with neurotoxin once every day for5 times in total. Dosages of 3-NP and neurotoxin were 20 mg/kg and30 mg/kg, respectively. METHODS: Motor coordination of mice was scored with pole test andtraction test before experiment and at 3 days after the last injection ofneurotoxin. Three days after complete injection, mice were sacrificed rapid ly to measure the contents of malondialdehyde (MDA) and reduced glu tathione (GSH) in the substantia nigra of midbrain. MAIN OUTCOME MEASURES: ① Motor and behavior scores; ② con tent of MDA; ③ content of GSH.~ULTS: All 48 mice were involved in the final analysis. ① Scores of pole test and traction test were decreased in neurotoxin group as compared with those in control group (P＜0.01); but the scores were increased after 3-NP single/repetitively preconditionings, and there were significant difference (P＜0.05, P＜0.01). Meanwhile, there was also significant differencebetween 3-NP repetitively preconditionings group and 3-NP single preconditioning group (P＜0.05). ② Content of MDA was increased in neurotoxin group as compared with that in control group, and there was significant difference (P＜0.01); content of MDA was decreased after 3-NP single preconditioning as compared with that in neurotoxin group, and there was significant difference (P＜0.05); content of MDA was remarkably decreased after 3-NP repetitively preconditionings as compared with that in neurotoxin group, and there was greatly significant difference (P＜0.01); meanwhile, there was also significant difference between 3-NP repetitively preconditionings group and 3-NP single preconditioning group (P＜0.05). ③As compared with that in blank control group, content GSH in 3-NP single administration group was not changed; content of GSH in 3-NP repetitively administrations group was increased (P＜0.05); content of GSH in neurotoxin group was decreased as compared with that in blank control group (P＜0.01); content of GSH in 3-NP single preconditioning group was not changed as compared with that in neurotoxin group (P＞0.05); content of GSH was increased after 3-NP repetitively preconditionings, and there was significant difference (P＜0.05); meanwhile, there was significant difference between 3-NP repetitively preconditionings group and 3-NP single preconditioning group (P＜0.05).CONCLUSION: 3-NP repetitively preconditionings can activate synthesis of GSH, protect dopamine neurons through decreasing production of MDA.

BACKGROUND: Brain-derived neurotrophic factor(BDNF) is a potent dopaminergic neurotrophin. The major pathological change in Parkinson disease(PD) is the degeneration and death of dopaminergic neurons in the substantia nigra pars compacta. There is a possibility that the onset of PD is associated with BDNF genetic polymorphisms.OBJECTIVE: To investigate the relationship between BDNF genetic polymorphisms and sporadic Parkinson disease(SPD) in Chinese population with the expectation of offering some genetic data for the primary rehabilitation and prevention of the disease.DESIGN: Explorative study based on DNA samples of SPD patients as study group and DNA samples of healthy population as control group.SETTING: Neurological Department of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, and Human Genome Center of Huazhong University of Science and Technology.PARTICIPANTS: Subjects included DNA samples of 85 SPD patients(study group, Han population, living in Huazhong area for a long term) offered by Department of Neurology of Wuhan Union Hospital and DNA samples of health persons(control group, Han population, living in Huazhong area for a long term) offered by Human Genome Center of Huazhong University of Science and Technology.METHODS: The genotype of healthy controls and SPD patients was analyzed with the polymerase chain reaction-restriction fragment length polymorphism technique (PCR-RFLP).MAIN OUTCOME MEASURES: Genotypes and alleles of the two polymorphisms: G196A and C270T of the two groups.RESULTS: G/A genotype was dominant in both SPD patients and control group with frequencies of 50.6% and 52.0% respectively. The C/C genotype occurred with the frequency of 100% in both groups. There were no significant differences in genotype and allele frequencies of G196A and C270T between SPD and control group( P ＞ 0. 05).CONCLUSION: No association existed between BDNF genetic polymorphisms and the onset of SPD in Chinese Han population of Huazhong area.

Mutations in the parkin gene have recently been identified in familial and isolated patients with early-onset Parkinson disease (PD) and that subregions between exon 2 and 4 of the parkin gene are hot spots of deletive mutations. To study the distribution of deletions in the parkin gene among variant subset patients with PD in China, and to explore the role of parkin gene in the pathogenesis of PD, 63 patients were divided into early onset and later onset groups. Exons 1-12 were amplified by PCR, templated by the genomic DNA of patients, and then the deletion distribution detected by agarose electrophoresis. Four patients were found to be carrier of exon deletions in 63 patients with PD. The location of the deletion was on exon 2 (1 case), exon 3 (2 cases) and exon 4 (1 case). All patients were belong to the group of early onset PD. The results showed that parkin gene deletion on exon 2, exon 3 and exon 4 found in Chinese population contributes partly to early onset PD.
Exons/*genetics ; *Gene Deletion ; Parkinson Disease/*genetics ; Point Mutation ; Ubiquitin-Protein Ligases/*genetics

To investigate the distribution of possible novel mutations from parkin gene in variant subset of patients with Parkinson's disease (PD) in China and explore whether parkin gene plays an important role in the pathogenesis of PD, 70 patients were divided into early-onset group and late-onset group; 70 healthy subjects were included as controls. Genomic DNA from 70 normal controls and from those of PD patients were extracted from peripheral blood leukocytes by using standard procedures. Mutations of parkin gene (exon 1-12) in all the subjects were screened by PCR-single strand conformation polymorphism (SSCP), and further sequencing was performed in the samples with abnormal SSCP results, in order to confirm the mutation and its location. A new missense mutation Gly284Arg in a patient and 3 abnormal bands in SSCP electrophoresis from samples of another 3 patients were found. All the DNA variants were sourced from the samples of the patients with early-onset PD. It was concluded that Parkin point mutation also partially contributes to the development of early-onset Parkinson's disease in Chinese.
DNA Mutational Analysis ; Exons ; Genotype ; Parkinson Disease/*genetics ; *Point Mutation ; Polymorphism, Single-Stranded Conformational ; Ubiquitin-Protein Ligases/biosynthesis ; Ubiquitin-Protein Ligases/*genetics

Mutations in the parkin gene have recently been identified in familial and isolated patients with early-onset Parkinson disease (PD) and that subregions between exon 2 and 4 of the parkin gene are hot spots of deletive mutations. To study the distribution of deletions in the parkin gene among variant subset patients with PD in China, and to explore the role of parkin gene in the pathogenesis of PD, 63 patients were divided into early onset and later onset groups. Exons 1-12 were amplified by PCR, templated by the genomic DNA of patients, and then the deletion distribution detected by agarose electrophoresis. Four patients were found to be carrier of exon deletions in 63 patients with PD. The location of the deletion was on exon 2 (1 case), exon 3 (2 cases) and exon 4 (1 case). All patients were belong to the group of early onset PD. The results showed that parkin gene deletion on exon 2, exon 3 and exon 4 found in Chinese population contributes partly to early onset PD.
Adult ; Aged ; Exons ; genetics ; Female ; Gene Deletion ; Humans ; Male ; Middle Aged ; Parkinson Disease ; genetics ; Point Mutation ; Ubiquitin-Protein Ligases ; genetics

The objective of this study was to assess the clinical evidence for or against mood stabilizers as a treatment for Alzheimer's disease (AD). We searched 5 databases from their inception to January 2010. Five randomized clinical trials of mood stabilizers to treat human patients suffering from AD were included. These trials assessed the effectiveness of mood stabilizers as an adjunct treatment to conventional anti-dementia drugs on behavioral and psychological symptoms, especially on agitation. Methodological quality was assessed using the Jadad score. The results suggested a significant effect in favor of placebo on the Mini-Mental Status Examination [n=270, weight mean difference (WMD), -0.89; 95% confidence intervals (Cis) -1.69 to -0.09, P=0.03] and on the Neuropsychiatric Inventory total (NPI total) (n=51, WMD, 3.71; 95% Cis 0.15 to 7.26, P=0.04). There were no significant differences in change scores on total Brief Psychiatric Rating Scale (BPRS total),NPI/BPRS agitation, Cohen-Mansfield Agitation Inventory total and Physical Self Maintenance Scale between mood stabilizers and placebo. Only one of these studies was free of methodological limitations (Jadad score=5). In conclusion, based on the existing evidence, mood stabilizers are ineffective or even harmful as a treatment for AD.