PURPOSE: It has been suggested that the pineal hormone melatonin(MEL) protects neurons in vitro from excitotoxicity mediated by kainate-sensitive glutamate receptors and from oxidative stress-induced DNA damage and apoptosis. The present study evaluated the antioxidatives and anti-inflammatory effect of melatonin on kainic acid(KA)-induced neuronal injury in the hippocampus in vivo. METHODS: 30 adult male Sprague-Dawley rats were divided into two equal groups. Control group was treated with KA only and test group was treated with KA and MEL. We injected 10 mg/kg KA intraperitoneal into rats. This results in selective neuronal injury accompanied by intense microglial activation and triggers DNA damage in the hippocampus. We tested the in vivo efficacy of MEL in preventing KA-induced neuronal injury and neuroinflammation in the hippocampus. MEL(2.5 mg/kg) was injected i.p. four times : 20 min before KA, immidiately after, and 1 and 2 h after the KA. Rats were sacrificed 72 h later and their hippocampi were examined for evidence of DNA damage (in situ dUTP-end-labeling, i.e. TUNEL staining), cell viability(H&E staining), microglial (isolectin-B4 histochemistry), astroglial responses(glial fibrillary acidic protein, GFAP immunohistochemistry), and lipid peroxidation(4-hydroxynonenal immunohistochemistry). RESULTS: The cumulative dose of 10 mg/kg MEL attenuates KA-induced neuronal death as well as microglial activation and lessens DNA breaks. CONCLUSION: A possible mechanism of MEL-provided neuroprotection lies in its antioxidant and anti-inflammatory action. Present data suggest that MEL holds potential for the treatment of acute brain pathologies such as epilepsy-associated brain damage, stroke, and brain trauma.
Adult ; Animals ; Apoptosis ; Brain ; Brain Injuries ; DNA Breaks ; DNA Damage ; Epilepsy ; Hippocampus ; Humans ; In Situ Nick-End Labeling ; Kainic Acid ; Male ; Melatonin* ; Neurons* ; Pathology ; Rats ; Rats, Sprague-Dawley ; Receptors, Glutamate ; Stroke

PURPOSE: Angiotensin converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) are associated with a decreased incidence of new-onset diabetes mellitus (NODM). The aim of this study was to compare the protective effect of ACEI versus ARBs on NODM in an Asian population. MATERIALS AND METHODS: We investigated a total of 2817 patients who did not have diabetes mellitus from January 2004 to September 2009. To adjust for potential confounders, a propensity score matched (PSM) analysis was performed using a logistic regression model. The primary end-point was the cumulative incidence of NODM, which was defined as having a fasting blood glucose > or =126 mg/dL or HbA1c > or =6.5%. Multivariable cox-regression analysis was performed to determine the impact of ACEI versus ARB on the incidence of NODM. RESULTS: Mean follow-up duration was 1839+/-1019 days in all groups before baseline adjustment and 1864+/-1034 days in the PSM group. After PSM (C-statistics=0.731), a total 1024 patients (ACEI group, n=512 and ARB group, n=512) were enrolled for analysis and baseline characteristics were well balanced. After PSM, the cumulative incidence of NODM at 3 years was lower in the ACEI group than the ARB group (2.1% vs. 5.0%, p=0.012). In multivariate analysis, ACEI vs. ARB was an independent predictor of the lower incidence for NODM (odd ratio 0.37, confidence interval 0.17-0.79, p=0.010). CONCLUSION: In the present study, compared with ARB, chronic ACEI administration appeared to be associated with a lower incidence of NODM in a series of Asian cardiovascular patients.
Adult ; Aged ; Angiotensin Receptor Antagonists/*therapeutic use ; Angiotensin-Converting Enzyme Inhibitors/*therapeutic use ; Asian Continental Ancestry Group/*statistics & numerical data ; Blood Glucose/analysis ; Diabetes Mellitus/*diagnosis/*epidemiology ; Dose-Response Relationship, Drug ; Drug Monitoring/methods ; Female ; Follow-Up Studies ; Humans ; Hypertension/*drug therapy ; Incidence ; Kaplan-Meier Estimate ; Logistic Models ; Male ; Middle Aged ; Multivariate Analysis ; Propensity Score ; Republic of Korea/epidemiology ; Risk Factors