Therapeutic effects of resveratrol and Omega-3 in mice atherosclerosis: focus on histopathological changes.

BACKGROUND: Resveratrol and omega-3 have been shown to prevent atherosclerosis. However, histopathological changes and their comparison have not been studied well. This study investigated the therapeutic effects of resveratrol and omega-3 in experimental atherosclerosis of mice. METHODS: We divided sixty 6-week-old male C57BL/6 mice into six groups and followed for 10 weeks: (1) standard diet, (2) atherogenic diet, (3) atherogenic diet along with resveratrol from the start of the sixth week, (4) atherogenic diet along with omega-3 from the start of the sixth week, (5) standard diet along with resveratrol from the start of the sixth week, (6) standard diet along with omega-3 from the start of the sixth week. RESULTS: The mice fed on an atherogenic diet had a larger fat area and a thicker aortic wall thickness than mice fed on a standard diet. The use of omega-3 and resveratrol in the mice with an atherogenic diet resulted in a significantly reduced fat area (p-value = 0.003), and resveratrol had a significantly higher effect. Omega-3 or resveratrol induced a significant reduction in aortic wall thickness in mice on an atherogenic diet, and there was no significant difference between them. Among the mice with a standard diet, this study did not observe any significant changes in the fat area or the aortic wall thickness with the consumption of omega-3 or resveratrol. CONCLUSIONS: Resveratrol and omega-3 had a regressive and therapeutic role in atherosclerosis, with a more significant effect in favor of resveratrol.

Improvement in Redox Homeostasis after Cytoreductive Surgery in Colorectal Adenocarcinoma.

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.

Comparison of primary versus secondary prevention of cardiovascular disease in patients with type2 diabetes: Focus on achievement of ABC goals.

BACKGROUND: Primary and secondary prevention of cardiovascular disease is of utmost importance in the management of patients with diabetes. OBJECTIVES: We studied a group of Iranian patients with type2 diabetes to provide an overview of the current status of secondary prevention of cardiovascular disease in the Middle East. METHODS: This is a cross-sectional study of 2029 Patients with type2 diabetes including 323 patients with coronary artery disease (CAD) were recruited. Achievement of goals in HbA1c (A), blood pressure (B) and LDL-cholesterol(C) was assessed. RESULTS: The study showed 25.3% of CAD positive patients achieved HbA1c <7% compared to 30% in CAD negative patients. The achievement of blood pressure ≤140/90 mmHg was 53.2% and 52.8% in CAD positive and CAD negative patients respectively. There was no difference in the achievement of all three ABC goals between the two groups (p = 0.733). After logistic regression analysis, history of hypertension had the highest odds ratio for CAD. CONCLUSION: Although ABC control has an important impact on the prevention of cardiovascular outcomes, the ideal goal needs further efforts to be achieved.

Inflammatory, oxidative stress and anti-oxidative markers in patients with endometrial carcinoma and diabetes.

BACKGROUND: The role of chronic inflammation and oxidative stress in the development of diabetes and cancer has been established. In this study, we aimed to investigate inflammatory and oxidative stress markers in patients with diabetes (DM) and endometrial carcinoma (EC) separately and in combination. METHODS: In a case-control study design, a total of 88 participants were enrolled including: 37 patients with EC (19 with DM and 18 without DM), 29 with type2 diabetes and 22 healthy controls. Cancer patients were sampled before treatment. Serum oxidative stress markers including: oxidized low density lipoprotein (ox-LDL,) nitric oxide (NO), advanced glycation end-products (AGEs) and advanced oxidation protein products (AOPP), malondialdehyde (MDA); ferric reducing ability of plasma (FRAP), as an antioxidant marker, and inflammatory markers including: Interleukin 6 (IL6), C reactive protein (CRP) and tumor necrosis factor alpha (TNFα) were measured. RESULTS: Ox-LDL, NO, MDA, AOPP and AGE were increased in all patients either with endometrial carcinoma and/or diabetes compared to healthy controls (p < 0.05). Patients with both EC and DM had higher oxidative markers including: OX-LDL (17.47 ±â€¯0.84 vs. 12.36 ±â€¯0.91), NO (82.27 ±â€¯5.75 vs. 76.34 ±â€¯5.36), MDA (3.3 ±â€¯0.1 vs. 2.75 ±â€¯0.48) and AGE (73.89 ±â€¯5.71 vs. 69.02 ±â€¯3.14) compared to those with EC alone (ρ < 0.05). Levels of FRAP was lower in patients with both diabetes and cancer, cancer alone and diabetes alone compared to healthy controls (p < 0.05). Inflammatory markers, TNFα, IL6 and hs-CRP, were also significantly increased in patients with EC with and without DM compared to controls (ρ < 0.05). However, there were no significant differences between two groups of EC regarding to inflammatory markers (ρ > 0.05). Patients with DM had significantly higher levels of inflammatory markers compared to control group (all ρ < 0.05). In addition, significant subadditive interaction effect between EC and DM regarding levels of oxLDL, NO, AGE, AOPP and FRAP) was observed (p < 0.05). CONCLUSION: Increased levels of chronic inflammatory and oxidative stress markers were observed in both endometrial carcinoma and diabetes. Additional effect of diabetes in patients with cancer was mediated more significantly via increase in oxidative stress rather than inflammatory markers.

Loss of Inverse Association between Framingham Risk Score and Estimated Glomerular Filtration Rate in Moderate to Severe Diabetic Kidney Disease.

BACKGROUND: We investigated the association of estimated glomerular filtration rate (eGFR) with Framingham risk score (FRS), and actual cardiovascular disease (CVD) in patients with type 2 diabetes (T2DM). We also assessed improvement in FRS for prediction of CVD after inclusion of eGFR and albuminuria. METHODS: A total of 571 patients with T2DM and mean age 55 were divided into 2 groups based on the presence of CVD. Participants without CVD were then divided into three groups according to FRS. CVD is defined as an episode of CCU admission, Myocardial infarction, history of coronary artery bypass graft surgery or percutaneous intervention. FRS is calculated using the Wilson 1998 Circulation equation, which includes age, sex, high blood pressure, smoking, high-density lipoprotein (HDL), total cholesterol and diabetes as components to assess CVD risk in 10 years. RESULTS: An inverse adjusted association between eGFR and prevalent CVD was confirmed by multiple logistic regression analysis (OR = 0.84, 95% CI: 0.74, 0.94, P = 0.03). We observed every 10 mL/min/1.73 m2 decrease in eGFR is related to 3% increase in FRS in patients without chronic kidney disease (CKD) (coefficient = -0.03, P < 0.001). The association between FRS and GFR and also CVD and eGFR were not significant in patients with CKD (P = 0.12; P = 0.17, respectively). Predictive values for FRS components with and without considering eGFR and albuminuria were calculated (0.74 and 0.75, respectively). CONCLUSION: Inclusion of eGFR and albuminuria in the FRS formula did not improve the predictive value of the model. We showed an inverse association between eGFR and FRS in early stages of diabetic kidney disease, which was lost in patients with CKD.

Association of extracellular heat shock protein 70 and insulin resistance in type 2 diabetes; independent of obesity and C-reactive protein.

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.

Pulse pressure and diabetes treatments: Blood pressure and pulse pressure difference among glucose lowering modality groups in type 2 diabetes.

Type 2 diabetes is associated with higher pulse pressure. In this study, we assessed and compared effects of classic diabetes treatments on pulse pressure (PP), systolic blood pressure (SBP), and diastolic blood pressure (DBP) in patients with type 2 diabetes.In a retrospective cohort study, 718 non-hypertensive patients with type 2 diabetes were selected and divided into 4 groups including metformin, insulin, glibenclamide+metformin, and metformin+insulin. They were followed for 4 consecutive visits lasting about 45.5 months. Effects of drug regimens on pulse and blood pressure over time were assessed separately and compared in regression models with generalized estimating equation method and were adjusted for age, duration of diabetes, sex, smoking, and body mass index (BMI).Studied groups had no significant change in PP, SBP, and DBP over time. No significant difference in PP and DBP among studied groups was observed (PP:P = 0.090; DBP:P = 0.063). Pairwise comparisons of PP, SBP, and DBP showed no statistically significant contrast between any 2 studied groups. Interactions of time and treatment were not different among groups.Our results demonstrate patients using metformin got higher PP and SBP over time. Averagely, pulse and blood pressure among groups were not different. Trends of variation in pulse and blood pressure were not different among studied diabetes treatments.