Objective: Mild cognitive impairment (MCI) is a cognitive syndrome in the elderly individuals. MCI drug treatment is still under debate. On the other hand, MCI progress is higher in people with diabetes mellitus type 2. This study was designed to determine the effect of Memantine on oxidant and antioxidant indexes among the elderly with prediabetes and MCI. Method: The present study is a double-blind randomized clinical trial which was conducted on 50 elderly patients over 60 years of age who had been diagnosed with prediabetes and MCI. Subjects were divided into intervention and control groups. The intervention group was treated with Memantine and Metformin and the control group received Metformin only. The data were collected before and after the study by blood tests and clinical examination and analyzed by using correlation test, independent and paired sample t-test in SPSS v.23 software. Results: The subjects included 22 men and 28 women. The mean age subject was 72.87 ± 3.95. Regarding the control group, the oxidative indexes including Advanced Glycation End Products (AGEs) and Advanced oxidation protein products (AOPP) decreased significantly (p value<0.001, df: 48). Regarding the intervention group, the oxidant indexes including AGEs and AOPP significantly decreased. In addition, antioxidant indexes such as LAP and Lecithin-cholesterol acyltransferase (LCAT) indexes increased considerably (p value<0.001, df: 48). Conclusion: Based on the results, the combination therapy with Memantine and Metformin for elderly patients with Prediabetic State and MCI may decrease oxidant indexes and increase the effect on antioxidant indices.
Colorectal cancer (CRC) as one the most common cancer type is associated with oxidative stress. Surgery is the only curative modality for early-stage CRC. The aim of this study was to evaluate the oxidative damage biomarkers as well as enzymatic and nonenzymatic antioxidants in patients with CRC before and after tumor resection and in healthy controls. 60 patients with stage I/II colorectal adenocarcinoma and 43 healthy controls were recruited in this study. We measured plasma levels of oxidative damage biomarkers, including advanced oxidation protein products (AOPP), advanced glycation end products (AGEs), malondialdehyde (MDA), and oxidized low-density lipoprotein (ox-LDL) at baseline and after tumor removal. We also evaluated the plasma activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) as enzymatic antioxidants and the ferric reducing antioxidant power (FRAP) assay for nonenzymatic antioxidant capacity. Patients with CRC had significantly higher AGE, AOPP, MDA, and ox-LDL and also FRAP levels and higher SOD and GPx and lower CAT activity levels compared to healthy controls ( p < 0.05 ). We did not observe any statistically significant correlation between redox biomarkers and the size and stage of the tumor. AGEs ( 72.49 ± 4.7 vs. 67.93 ± 8.8 , p < 0.001 ), AOPP ( 137.64 ± 21.9 vs. 119.08 ± 33.1 , p < 0.001 ), MDA ( 3.56 ± 0.30 vs. 3.05 ± 0.33 , p < 0.001 ), and ox-LDL ( 19.78 ± 0.97 vs. 16.94 ± 1.02 , p < 0.001 ) concentrations reduced significantly after tumor removal. The largest effect sizes were found in ox-LDL ( d = − 2.853 , 95% CI 2.50-3.19) and MDA ( d = − 1.617 , 95% CI 0.43-0.57). Serum FRAP levels ( 1097.5 ± 156.7 vs. 1239.3 ± 290 , p < 0.001 ) and CAT ( 2.34 ± 0.34 vs. 2.63 ± 0.38 , p < 0.001 ), GPx ( 102.37 ± 6.58 vs. 108.03 ± 6.95 , p < 0.001 ), and SOD ( 5.13 ± 0.39 vs. 5.53 ± 0.31 , p < 0.001 ) activity levels increased significantly after surgery. The largest effect sizes among antioxidants were seen in SOD ( d = 1.135 , 95% CI 0.46-0.34) and GPx ( d = 0.836 , 95% CI 0.35-0.23). This study indicated that patients with colorectal cancer had higher levels of oxidative stress and antioxidant activity compared to healthy controls. After surgical resection of tumor, we observed a substantial improvement in redox homeostasis.
Despite few studies on intracellular heat shock protein70, the clinical association between insulin resistance and extracellular heat shock protein70 (eHSP70) is not well studied. In the current study, we examined the association between homeostatic model assessment-insulin resistance (HOMA-IR) and eHSP70 in patients with type 2 diabetes (T2DM) and healthy controls. A total of 145 patients with T2DM and 41 matched healthy controls were selected. Patients and controls were divided based on waist circumference (WC) to two groups, and eHSP70 was compared between them. The association between HOMA-IR and eHSP70 was examined using regression models adjusted for age, high-sensitive C-reactive protein (hs-CRP), and central obesity as confounding factors. While eHSP70 and hs-CRP were significantly correlated with HOMA-IR in patients with T2DM (p = 0.032, 0.025, respectively), there was no correlation between eHSP70 and HOMA-IR in the control group. Extracellular HSP70 and hs-CRP were not correlated in healthy controls. But a significant association appeared between eHSP70 and hs-CRP in patients with T2DM (p = 0.05). Both BMI and WC were not correlated with eHSP70 in both groups. Extracellular HSP70 was positively associated with HOMA-IR in patients with T2DM, independent from hs-CRP and obesity. We also showed eHSP70 levels remained unchanged through increase in BMI or WC in patients with T2D and in healthy controls. Our findings suggest that eHSP70 may contribute to the pathogenesis of T2DM by increasing insulin resistance.
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