RESUMEN

BACKGROUND: The pathogenesis of Parkinson's disease (PD) is complex; it includes mitochondrial dysfunction, oxidative stress, and neuroinflammation. Notably, Toll-like receptors (TLRs) may activate inflammatory or anti-inflammatory responses in Parkinson's disease. Vinpocetine has been tested as an anti-inflammatory in both animal and in vitro research. Thus, it is important to test whether the anti-inflammatory properties of vinpocetine may have a protective effect in PD patients. METHODS: Eighty-nine Parkinson's disease patients and 42 healthy controls were recruited for this study. All patients were randomly assigned to either the traditional therapy group (T PD group, n = 46) or the vinpocetine group (V PD group, n = 43), in a blinded manner. Both treatments were administered for 14 days. RESULTS: Administration of vinpocetine reduced mRNA levels of TLR2/4, as well as protein levels of the downstream signalling molecules, MyD88 and NF-κB; moreover, it lowered the expression levels of serum inflammatory cytokines, TNF-α and MCP-1. Notably, vinpocetine increased TLR3 mRNA levels, as well as protein levels of the downstream signalling molecules TRIF-ß and IRF-3, and serum levels of the anti-inflammatory cytokines IL-10 and IL-8. Furthermore, vinpocetine produced a robust increase in the Mini Mental State Examination score, compared to that achieved by using levodopa therapy. CONCLUSION: Vinpocetine treatment may exhibit anti-inflammatory activity and alleviate cognitive impairment.

Asunto(s)

Fármacos Neuroprotectores/uso terapéutico , Enfermedad de Parkinson/sangre , Enfermedad de Parkinson/tratamiento farmacológico , Receptores Toll-Like/sangre , Alcaloides de la Vinca/uso terapéutico , Anciano , Biomarcadores/sangre , Estudios de Casos y Controles , Estudios de Cohortes , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fármacos Neuroprotectores/farmacología , Distribución Aleatoria , Receptores Toll-Like/antagonistas & inhibidores , Alcaloides de la Vinca/farmacología

RESUMEN

BACKGROUND: Development of Parkinson's disease (PD) is attributed to both genetic and environmental factors. Furthermore,GAPDH may play a key role in the development of neurodegenerative disease. Examination of genetic polymorphism in patients with sporadic PD will help uncover the mechanisms of PD pathogenesis and provide new insights into the treatment of PD. METHODS AND RESULTS: The SNaPshot method was applied to determine the gene sequences in 265 patients with idiopathic PD and 269 control cases (sex- and age-matched). The rs1136666 polymorphism of GAPDH was determined to be closely associated with PD. Subsequently, the CC genotype of the rs1136666 fragment was transfected into SH-SY5Y cells via a plasmid. The genetic expression of rs1136666 CC could induce SH-SY5Y cell injury and apoptosis via regulation of the oxidant-antioxidant and apoptosis-antiapoptosis balance. rs1136666 CC of the GAPDH had a pro-apoptotic effect similar to that of rotenone, and combination of the rs1136666 CC genetic variation and the rotenone neurotoxic effect could aggravate oxidative stress, cell injury, and apoptosis better than either single treatment alone. CONCLUSION: This study confirmed that the rs1136666 CC allele of theGAPDH increased the risk of PD, particularly in older male patients.

Asunto(s)

Apoptosis/efectos de los fármacos , Gliceraldehído-3-Fosfato Deshidrogenasa (Fosforilante)/metabolismo , Estrés Oxidativo/efectos de los fármacos , Enfermedad de Parkinson/genética , Antioxidantes/farmacología , Estudios de Casos y Controles , Supervivencia Celular/efectos de los fármacos , Femenino , Humanos , Masculino , Enfermedad de Parkinson/tratamiento farmacológico , Riesgo , Rotenona/toxicidad , Factores Sexuales

RESUMEN

Objective To evaluate the diagnostic value of current perception threshold (CPT) for diabetic peripheral neuropathy by comparing with nerve conduction velocity (NCV). Methods Sixty patients with type 2 diabetes were enrolled. The CPT and SNCV were examined respectively. Results The abnormal rates of the CPT and SNCV were 68.33％and 36.67％in all patients, respectively. The abnormal rates of the CPT and SNCV were 88.46％and 53.85％in symptomatic group. The abnormal rates of the CPT and SNCV were 47.06％ 17.65％ in asymptomatic group. In patients with disease less than five years, the abnormal rates of the CPT and SNCV were 55.17％ and 24.14％. In patients with disease greater than five years, the abnormal rates of the CPT and SNCV were 77.42％ and 48.39％. The abnormal rate was statistically significant difference (P<0.05) between two examination. Conclusion CPT and NCV were consistency in the diagnosis of diabetic peripheral neuropathy. For early asymptomatic patients, CPT have more advantages to inspect the sub-clinical patients.

RESUMEN

Objective To evaluate the detection of culture filtrate protein 10 (CFP10) and 6000 early secretory antigenic target (ESAT-6) in cerebrospinal fluid to be used in diagnosing tuberculous meningitis. Methods Dot enzyme linked immunosorbent assay ( Dot ELISA) method that was improved by applying concentrated cerebrospinal fluid was used to detect CFP10 and ESAT-6 in cerebrospinal fluid to analyze small protein antigen secreted by M. tuberculosis. Cerebrospinal fluid of 111 subjects were collected,in which 58 specimens were clinically diagnosed as tuberculous meningitis and 53 as non-tuberculous.CFP10 and ESAT-6 were detected in cerebrospinal fluid using Dot ELISA method and the results were analyzed. Results The sensitivities of detecting CFP10 and ESAT-6 antigen were 93.1% and 91.4% respectively, and the specificities were 92. 5% and 94. 3% respectively. The sensitivities and specificities are generally higher compared with the other methods of detecting M. tuberculosis or materials of M. tuberculosis by acid-fast staining or mycobacterium tuberculosis culture and polymerase chain reaction.Conclusions Using Dot ELISA method to detect CFP10 and ESAT-6 in cerebrospinal fluid to diagnose tuberculous meningitis has a high sensitivity and specificity. Our study provided the evidence of detecting the specific antigen of M. tuberculosis to be used in diagnosing tuberculosis.