Translational research : the journal of laboratory and clinical medicine
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Lipoprotein(a) [Lp(a)] is a cardiovascular disease (CVD) risk factor, where inflammation impacts levels differentially across ethnicity. We investigated the effect of systemic [serum amyloid A (SAA)] and vascular [pentraxin-3 (PTX-3)] inflammation on Lp(a) levels across different apolipoprotein(a) [apo(a)] sizes in a biethnic population. Lp(a) and allele-specific apo(a) levels, apo(a) sizes, SAA, and PTX-3 levels were determined in 336 Caucasians and 224 African Americans. ⋯ We did not find any significant associations between allele-specific apo(a) and SAA or PTX-3 levels among Caucasians with smaller (<26 K4) apo(a) sizes. In conclusion, increased levels of SAA, but not PTX-3, were associated significantly with higher Lp(a) levels for smaller (<26 K4) apo(a) sizes in African Americans. Our results implicate that a proinflammatory stimulus may result in an increased cardiovascular risk through a selective increase in Lp(a) levels among African Americans who carry a smaller apo(a) size.
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The role of the vascular endothelial growth factor (VEGF) gene polymorphism in proliferative diabetic retinopathy (PDR) is controversial. VEGF seems to play a central role in mediating microvascular pathology in proliferative diabetic retinopathy (PDR). Recently, a +405 G/C VEGF polymorphism was shown to be associated with PDR. ⋯ In a multivariate logistic regression analysis (using sex and body mass index as clinically significant variables and HbA1c and genotype as statistically significant variables) was then used to determine independent associations and adjusted odds ratios (ORs), the GG genotype (compared with the CC genotype) was an independent predictor of PDR [OR = 1.87, 95% confidence interval (CI) = 1.034-3.383 P = 0.039]. The HbA1c was more common in the PDR group (P = 0.004); in a multivariate regression, the association remained significant (OR = 1.194, 95% CI = 1.056-1.350, P = 0.005). These findings suggest that the VEGF +405 GG polymorphism might be associated with the risk of proliferative diabetic retinopathy in an Iranian population.
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High levels of lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) are associated with inflammation, atherosclerosis, and coronary heart disease events. In addition, Lp-PLA(2) has been linked to classical markers of endothelial activation, including soluble vascular cell adhesion molecule-1 (sVCAM-1). Although treatment with fenofibrate reduces Lp-PLA(2) mass, it is unclear whether fenofibrate reduces sVCAM-1 levels or whether an association exists between any changes observed in Lp-PLA(2) and sVCAM-1. ⋯ No associations were observed between Lp-PLA(2) and sVCAM-1 at baseline or post-treatment. In conclusion, fenofibrate treatment in hypertriglyceridemic subjects reduced the levels of Lp-PLA(2) mass and sVCAM-1, but only in those with elevated baseline levels of these biomarkers. The greatest reductions in Lp-PLA(2) levels were observed in individuals with Lp-PLA(2) concentrations indicative of increased cardiovascular disease risk (>200 ng/mL).
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Oxidative stress has been implicated broadly as a cause of cell death and neural degeneration in multiple disease conditions; however, the evidence for successful intervention with dietary antioxidant manipulations has been mixed. In this study, we investigated the potential for protection of cells in the inner ear using a dietary supplement with multiple antioxidant components, which were selected for their potential interactive effectiveness. ⋯ Taken together, our data suggest that prenoise oral treatment with the high-nutrient diet can protect cells in the inner ear and reduce PTS in mice. The demonstration of functional and morphologic preservation of cells in the inner ear with oral administration of this antioxidant supplemented diet supports the possibility of translation to human patients and suggests an opportunity to evaluate antioxidant protection in mouse models of oxidative stress-related disease and pathology.
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Sirtuin 1 (SIRT1) is a longevity gene that protects cells against oxidative and genotoxic stress. This study aimed to investigate the associations of SIRT1 gene single nucleotide polymorphisms (SNPs), rs7895833, rs7069102, and rs2273773, with various laboratory data in 1279 Japanese health checkup examinees. The genotyping was performed using a polymerase chain reaction (PCR) with confronting 2-pair primers (CTPP) assay. ⋯ The T allele of rs2273773 in men carried a high risk for hyperglycemia. In conclusion, these SIRT1 gene polymorphisms are associated with high body fat and blood pressure in Japanese, especially in men. The allele frequencies of rs7895833 and rs7069102, which are different from Caucasians, might explain why Japanese show less marked obesity compared with Caucasians.