Elisabeth Fragopoulou

Platelet activating factor (PAF) and activity of its biosynthetic and catabolic enzymes in blood and leukocytes of male patients with newly diagnosed heart failure

OBJECTIVES To evaluate platelet activating factor (PAF) levels, its metabolic enzymes activity and its associations with other inflammatory markers in heart failure (HF) patients. DESIGN AND METHODS PAF, and two of its key biosynthetic enzymes [lyso-PAF acetyltransferase (lyso-PAF-AT) and DTT-insensitive CDP-choline:1-alkyl-2-acetyl-sn-glycerol cholinephosphotransferase (PAF-CPT)] along with its catabolic enzymes [PAF-acetylhydrolase (PAF-AH) and lipoprotein-associated phospholipase-A(2) (Lp-PLA(2))] were measured in serum and leukocytes of twelve newly diagnosed male HF patients. Serum CRP, TNF-alpha, IL-6, sCD14 and CD40L were also determined. RESULTS PAF ranged from 0.03 to 5.6 pmol/mL. Median lyso-PAF-AT, PAF-CPT, PAF-AH and Lp-PLA(2) activities were 4.1, 68.42, 644.44 pmol/min/mg protein and 51.42 pmol/min/microL correspondingly. Lyso-PAF-AT and PAF-CPT activities positively correlated with CRP, IL-6 and with each other, whereas PAF-CPT activity correlated with sCD14 and CD40L (P<0.05). CONCLUSIONS PAFs biosynthetic enzyme activities correlated with inflammatory and immunologic molecules, which are activated in HF. Our study indicates a potential role of PAF in HF patients.

Cognitive Function and Oxidative Stress After Carotid Endarterectomy: Comparison of Propofol to Sevoflurane Anesthesia

OBJECTIVE To examine the antioxidant role of propofol in ischemia-reperfusion during carotid endarterectomy (CEA) and its influence on cognitive dysfunction after CEA. DESIGN A randomized prospective study. SETTING Single-center study in a university hospital. PARTICIPANTS Forty-four patients. INTERVENTIONS Patients underwent elective CEA under general anesthesia with either sevoflurane (group S, n = 21) or propofol (group P, n = 23). MEASUREMENTS AND MAIN RESULTS Cognitive function was assessed with the Mini-Mental State Examination (MMSE) before CEA, 1 hour after CEA, and 24 hours after CEA. Blood samples from the radial artery and the internal jugular vein were drawn before carotid clamping and 5 minutes following unclamping, and peripheral blood was obtained 24 hours postoperatively. Samples were analyzed for lactate, S100B, and P-selectin concentrations and for the antioxidative markers malondialdehyde/low-density lipoprotein ratio and nitrate + nitrite concentrations. Compared with group S, patients in group P exhibited a greater increase in their MMSE values 24 hours postoperatively. Patients who had their MMSE performance reduced at 24 hours also were significantly fewer in group P (13% v 43% in group S, p<0.05). Significantly lower levels of lactate and S100B were observed in arterial and jugular vein samples in group P. In addition, the jugular vein-arterial differences of malondialdehyde-to-low-density lipoprotein ratio and nitrates + nitrites concentrations were lower during propofol anesthesia. CONCLUSIONS Propofol seemed to improve cognitive performance after CEA. This improvement was associated with decreased indices of ischemic cerebral damage and seemed to be due to antioxidative effect in the ischemic cerebral circulation.

Blood redox status is associated with the likelihood of nonalcoholic fatty liver disease irrespectively of diet's total antioxidant capacity

It is well established that oxidative stress is implicated in nonalcoholic fatty liver disease pathogenesis, whereas the dietary intake of antioxidants has been reported to be low in patients with the disease. We hypothesized that blood redox status measurements would be associated with nonalcoholic fatty liver disease presence and severity, and that diets total antioxidant capacity could moderate the aforementioned association. The study sample consisted of 73 patients with nonalcoholic fatty liver disease, of which 58 were matched by age, sex, and body mass index with 58 controls. Diets total antioxidant capacity was estimated through the ferric-reducing antioxidant power, the total radical-trapping antioxidant parameter, and the Trolox equivalent antioxidant capacity scores, whereas blood redox status was assessed by measuring thiobarbituric acid reactive substances levels, the enzymatic activity of glutathione peroxidase, and serum resistance to oxidation. Diets total antioxidant capacity scores and glutathione peroxidase activity were not significantly associated with the disease presence or severity. Both thiobarbituric acid reactive substances and serum resistance to oxidation were significantly associated with the likelihood of nonalcoholic fatty liver disease (odds ratios [ORs], 7.769 [P= .007] and 0.936 [P= .033], respectively), independently of abdominal fat level, degree of insulin resistance, blood lipid levels, markers of subclinical inflammation, and diets total antioxidant capacity, but not with the disease histologic severity or stage. Our results support the association between blood redox status and the likelihood of nonalcoholic fatty liver disease regardless of diets total antioxidant capacity.

Synthesis of New Nebularine Analogues and Their Inhibitory Activity against Adenosine Deaminase

A number of new 2,6-disubstituted-1-deazanebularine analogues as well as two structurally related pyrazole-fused tricyclic nucleosides were prepared. Their synthesis was carried out by the conversion of 6-amino-2-picoline to a suitable 1-deazapurine, followed by a Vorbrüggen type glycosylation and subsequent elaboration of the condensed pyrazole ring. The synthesized nebularine analogues proved to be weak adenosine deaminase inhibitors.

Biomarkers and Gene Polymorphisms in Members of Long- and Short-lived Families: A Longevity Study

Background: The influence of biomarkers in human lifespan has been investigated but with no clear results yet. Materials and methods: Lipids, Uric Acid (UA), Adiponectin (ADIPOQ), Insulin-like Growth Factor (IGF-1), cholesteryl ester transfer protein (CETP) and angiotensin-converting enzyme (ACE) proteins, as well as CETP, ADIPOQ, insulin-like growth factor binding protein-3 (IGFBP3) and ACE-gene polymorphisms were evaluated in 149 Greek individuals. The Long-Lived Families (LON) (n=84) comprised of 3 generations: long-lived aged ≥90 years (P), offspring (FL1) and their grandchildren (FL2), while the Short-Lived Families (EAD) (n=65) where both parents died <75 years, comprised of 2 generations: middle-aged (FD1) and children (FD2). Results: Serum CETP and IGF-1 levels were lower, whereas AdipoQ concentrations were higher in P compared with FL1 and FL2 members (CETP: p = 0.03 for both comparisons; IGF-1 p < 0.001 for both comparisons and ADIPOQ: p = 0.001 and p = 0.004, respectively). Furthermore, serum triglycerides, UA and glucose concentrations were higher in FD1 compared with FD2 subjects (p=0.001, 0.02 and ≤0.001, respectively). In FD2 and FL2, CETP levels were lower in individuals with B2B2 compared with B1B1 genotype (p=0.007). Additionally, ACE concentrations were higher in individuals with DD compared with II genotype in both Families (p=0.001). After adjustment for age and gender, CETP levels were lower in P and FL2 individuals with B2B2 compared with the B1B1 genotype (p=0.004 and 0.007, respectively). Conclusion: Increase serum TGs, UA and GL concentrations were higher in the middle-aged individuals compared with their children in families independently of their lifespan. The serum adiponectin concentration was the highest in the oldest old individuals implying beneficial influence on lifespan. Independently of family’s lifespan history, the youngest individuals with CETPB2B2 genotype, compared with individuals with CETPB1B1 genotypes, had lower serum CETP concentrations. The knowledge of the unfavourable gene(s)influencing human lifespan may be helpful in encouraging individuals to follow healthier lifestyle habits and better control their high-risk biomarkers.

Influence of Genes on the Lifespan of Long- and Short-Lived Families

lease cite this article in press as: Kol f Cardiology (2017), http://dx.doi.o tp://dx.doi.org/10.1016/j.hjc.2017 09-9666/a 2017 Hellenic Cardiologi ense (http://creativecommons.org/ There is enormous personal concern regarding lifespan. Investigation of the biological basis of human lifespan, is warranted due to the long lifespan of humans. Genetic studies have identified a limited number of loci associated with human longevity by examining the phenotype of age at death or survival to advanced age. Long-lived people are defined as those who live at least 90 years. Long-lived people overcome or avoid some of the most deadly diseases, such as cancer and atherosclerosis, or develop stabilized disease. Many genes are related to the risk of progression of such deadly diseases, such as cholesteryl ester transfer protein (CETP), apolipoprotein E (ApoE ), angiotensin converting enzyme (ACE ), and adiponectin (ADIPOQ). Genes possibly involved in cancer pathology include insulin-like growth factor (IGF ), p53, and Fork-head box O3A. This study focused on 5 variants of each of the following genes: CETP, AIPOQ, IGFBP3, and ACE. CETP polymorphisms, such as TaqIB (rs708272) and I405 V (rs5882), were found to be associated with atherosclerosis, left main coronary disease and longevity. The ACE gene, particularly the rs1799752 polymorphism, has been evaluated in the pathogenesis of hypertension, coronary artery disease (CAD), heart failure, and, more recently, longevity. ADIPOQ is a determinant of insulin sensitivity that exerts anti-inflammatory and anti-atherogenic effects. A common variant of the ADIPOQ gene (þ45T>G, rs2241766) is associated with the risk of CAD. The IGF-1 gene appears to be