Melatonin Protects Against Titanium Oxide-Induced Neurotoxicity: Neurochemical, Neurobehavioral, and Histopathological Evidences.

titania (titanium dioxide, TiO2) is known to induce neurotoxicity and CNS dysfunctions. Numerous studies have explored the neuroprotective effects of melatonin against neurotoxicity. This study evaluates the potential of melatonin to protect against titania-induced neurotoxicity and the role of the Keap1/Nrf2/ARE signaling pathway. One group of animals were treated with Titania (0.045 and 0.075 g/rat) alone while the other with added melatonin (1 mg/kg and 3 mg/kg) and behavioral alterations were assessed using OFT (open field test). Neurochemical and histopathological changes were also studied in the hippocampus by analyzing kelch ECH associating protein 1 (Keap1), nuclear factor erythroid 2-related factor 2 (Nrf2), and antioxidant response element (ARE). It was seen that the animals with added Melatonin had improved behavioral scores in the OFT, like anxiety and motor dysfunction triggered by TiO2. Melatonin also reduced lipid peroxidation, ROS, GSSG, IL1ß, TNFα, Bax, and Keap1 levels, but boosted GSH, GPx, GR, SOD,IL10,IL4, Bcl2, Nrf2, and ARE levels and improved quadruple mitochondrial enzyme complex activity in titania-treated animals. Histopathological examination showed melatonin induced cytoprotection against vacuolization and necrosis in granular cells of DG and pyramidal cells of CA1 area of the hippocampus. In our study, pretreatment with melatonin reduced titania-induced neurotoxicity in the hippocampus through a mechanism potentially mediated by the Keap-1/Nrf2/ARE pathway.

Frequency of autoimmune thyroid disease in chronic urticaria.

OBJECTIVE: To determine the frequency of autoimmune thyroid disease in diagnosed cases of chronic urticaria (CU) and the association between hypothyroidism and chronic urticaria if any. STUDY DESIGN: Non-interventional, descriptive study. PLACE AND DURATION OF STUDY: Department of Physiology, Dow University of Health Sciences, Karachi, from December 2004 to January 2006. METHODOLOGY: The patients were selected from Department of Dermatology and Medical Units of Civil Hospital, Jinnah Postgraduate Medical Centre, the Aga Khan Hospital and community clinics. A total number of 60 patients were enrolled in this study. In all patients, serum antithyroid autoantibodies (antithyroglobulin and antimicrosomal/thyroperoxidase), thyroid profile (serum TSH, T3 and FT4), complete blood count, erythrocyte sedimentation rate and IgE levels were carried out. The proportions were compared using chi-square test with significance at p < 0.05. RESULTS: Forty seven (78%) patients were found to have chronic urticaria (history and laboratory reports). Out of 47 patients with diagnosis of CU, elevated titres of antithyroglobulin (TGA) and antimicrosomal antibodies (TMA) were found to be present in 20 (42.6%) and 27 (57.4%) patients respectively. Serum TSH level (thyroid stimulating hormone) was increased and T3, FT4 were decreased in 20 (42.6%) patients (p < 0.001). A total number of 20 (42.5%) patients were found to be hypothyroid with chronic urticaria of greater than 6 weeks duration. CONCLUSION: This study shows a statistically significant association between hypothyroidism and chronic urticaria. Full thyroid profile (serum thyroid autoantibodies, serum TSH, T3 and FT4) is highly recommended in patients with diagnosis of chronic urticaria.

Serum antithyroid antibodies in female patients with chronic urticaria.

OBJECTIVE: To determine the frequencies of serum antithyroglobulin and antimicrosomal autoantibodies in female patients with chronic urticaria, and the association between thyroid autoantibodies and chronic urticaria, if any. STUDY DESIGN: Non-interventional, case-control analytic study. PLACE AND DURATION OF STUDY: This study was carried out by the Department of Physiology, Dow University of Health Sciences, Karachi, from December 2004 to January 2006 on patients selected from Department of Dermatology and Medical Units of Civil Hospital, Jinnah Postgraduate Medical Centre and The Aga Khan University Hospital, Karachi and from the Community Clinics in Karachi. METHODOLOGY: A total number of 90 subjects were enrolled and divided in three groups consisting of 30 patients each. Group 1 comprised of patients with diagnosis of chronic urticaria, Group 2 of diagnosed cases of hypothyroidism with/without urticaria, and Group 3 of normal age and gender-matched healthy volunteers. In all patients, serum antithyroid autoantibodies (antithyroglobulin and antimicrosomal) and thyroid profile (serum T3, T4 and TSH levels) was carried out. Chi-square test was used to determine significance of proportion of variables at p < 0.05. RESULTS: Elevated titres of antithyroglobulin antibodies were found to be present in 9 (30%) patients in Group 1 (chronic urticaria), 24 (80%) patients in Group 2 (known cases of hypothyroidism) compared to control. Elevated titres of antimicrosomal antibodies were found to be present in 13 (43.3%) patients in Group 1, 27 (90%) patients in Group 2 (known cases of hypothyroidism) compared to control. The association between hypothyroidism and chronic urticaria with regard to autoantibodies titres was highly significance (p <0.001). CONCLUSION: A highly statistically significant association was found between chronic urticaria and hypothyroidism with special regard to antithyroglobulin and antimicrosomal autoantibodies. Therefore, assays of these two autoantibodies are justified for the early diagnosis of autoimmune thyroiditis in combination with chronic urticaria for better treatment options.