RESUMO
Matrix metalloproteinases (MMPs) are substantial regulators of learning and memory and might be involved in neurodegeneration. It is known that MMPs are involved in pathogenesis of Alzheimer's disease (AD) and are particularly involved in the amyloid-ß processing pathway. However, information on circulating levels of these proteins and their tissue inhibitors (TIMPs) in AD and other neurodegenerative dementia (ND) diseases such as dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD) is not clear. Therefore, this study was directed toward finding out how plasma levels of MMP-2, MMP-9, TIMP-1, and TIMP-2 vary in AD, DLB, and FTD; and investigating the correlation of the levels of MMPs and their inhibitors with clinical parameters of the patients. MMP-2, MMP-9, TIMP-1, and TIMP-2 levels were measured by enzyme linked immunosorbent assay (ELISA). Plasma MMP-2 levels were significantly lower in all the patient groups than in the age-matched healthy controls (HCs) (pâ<â0.05). MMP-9 levels were significantly lower in the FTD patients than in the HCs (pâ<â0.05). Also, TIMP-1 levels were lower in the AD and FTD patients than in the HCs (pâ<â0.05). TIMP-2 levels were similar in all the groups. These findings highlight the importance of circulating MMPs in ND and suggest that MMPs and their inhibitors might play a role in impaired amyloid-ß peptide metabolism which is responsible for the genesis and progression of ND. Furthermore, measurement of MMP-2 and MMP-9 and their inhibitors may be of great importance for large scale basic research and clinical studies of ND.
Assuntos
Doença de Alzheimer/sangue , Demência Frontotemporal/sangue , Doença por Corpos de Lewy/sangue , Metaloproteinase 2 da Matriz/sangue , Metaloproteinase 9 da Matriz/sangue , Inibidor Tecidual de Metaloproteinase-1/sangue , Inibidor Tecidual de Metaloproteinase-2/sangue , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVES/HYPOTHESIS: To investigate the blood levels of TNF-α, IL-10, and IL-12 in the idiopathic sudden sensorineural hearing loss patients, and the change of these cytokine levels after treatment. STUDY DESIGN: Prospective clinical trial. METHODS: Twenty-three patients with idiopathic sudden sensorineural hearing loss and 20 healthy people were selected as study and control groups. Blood samples for TNF-α, IL-10, and IL-12 were taken before treatment and 6 weeks after treatment. The study group was given combined treatment including dexamethasone, heparin, pentoxifyline, vitamin B1, and B6 for 10 days, and was divided into two groups: treatment responders and treatment nonresponders. The treatment responders group was also divided into three groups according to most accepted criteria for improvement in the literature. Audiograms were taken before treatment and 6 weeks after treatment to determine the response to the treatment. RESULTS: There was no significant difference between pre- and posttreatment values of IL-10 and IL-12 in all study groups (P > 0.05). There was also no significant difference between pre- and posttreatment values of TNF-α in treatment responders (P > 0.05). Treatment nonresponders had more elevated posttreatment values of TNF-α than pretreatment values (P < 0.05). CONCLUSION: IL-10 and IL-12 may not play a critical role in idiopathic sudden sensorineural hearing loss. But our data supports the role of TNF-α in the pathophysiology of idiopathic sudden sensorineural hearing loss, and TNF-α receptor blockers may have benefits in these patients.