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Thessaloníki, Greece

Mande P.V.,National Health Research Institute | Parikh F.R.,Research Center Clinic | Hinduja I.,INKUS IVF Clinic | Zaveri K.,INKUS IVF Clinic | And 3 more authors.
Reproductive BioMedicine Online

Antibodies to multiple ovarian antigens have been proposed as markers of ovarian autoimmunity. The role of ovarian autoantibodies has been widely discussed in the pathophysiology of premature ovarian failure and unexplained infertility, but the autoantigens are yet to be identified. Three immunodominant ovarian autoantigens, α-actinin 4 (αACTN4), heat shock 70 protein 5 (HSPA5) and β-actin (ACTB), have been identified using anti-ovarian antibody-positive sera from women with idiopathic premature ovarian failure (n = 50) and women undergoing IVF (n = 695), using mass spectrometry. These autoantigens were subsequently validated using Western blot, immunohistochemistry and enzyme-linked immunosorbent assay. These autoantigens are localized to different components of the ovary such as the ooplasm of the oocyte, theca, granulosa, corpus luteum and zona pellucida. All the above antigens were found to be expressed in the ooplasm throughout follicular development. All the autoantigens are expressed specifically in the oocyte except αACTN4. The three autoantigens could contribute to the array of biomarkers to be used for developing specific and sensitive tests for diagnosis of women at risk of premature ovarian failure and IVF failure due to ovarian autoimmunity and could give an insight into the molecular mechanisms involved in the pathophysiology of these conditions. Anti-ovarian antibodies (AOA) have been reported in women with premature ovarian failure and unexplained infertility. Among women with infertility, those with evidence of ovarian autoimmunity appear to have poorer IVF-embryo transfer outcomes. Diagnosis of an autoimmune mechanism in these pathologies has relied for a long time on the detection of AOA. Little is known about the precise ovarian antigenic targets in terms of its molecular and cellular identities that are recognized by the antibodies and immune cells in autoimmune diseases of the ovary. In the present study, we observed that 31% of the total women recruited under an IVF-embryo transfer programme (group I) and 46% of women with premature ovarian failure (group II) tested positive for AOA. Three immunodominant ovarian autoantigens, namely non-muscle α-actinin 4, heat shock 70 protein 5 and cytoplasmic β-actin, were identified using mass spectrometry and validated and characterized using AOA-positive sera from women from both groups. Further investigation of the identified targets could give us an insight into the molecular mechanism involved in the pathophysiology of human ovarian autoimmunity. © 2011, Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved. Source

Athyros V.G.,Aristotle University of Thessaloniki | Katsiki N.,Aristotle University of Thessaloniki | Tziomalos K.,Aristotle University of Thessaloniki | Gossios T.D.,Aristotle University of Thessaloniki | And 6 more authors.
Archives of Medical Science

Introduction: The effect of cardiovascular disease (CVD) prevention measures aimed at elderly patients requires further evidence. We investigated the effect of statin treatment (targeted to achieve guideline goals) on CVD outcomes in different age groups to determine whether statins are more beneficial in the elderly. Material and methods: The primary endpoint of this post hoc analysis of the GREek Atorvastatin and Coronary-heart-disease Evaluation (GREACE) study (n = 1,600 patients with established coronary heart disease (CHD), mean follow-up 3 years) was the absolute and relative CVD event (a composite of death, myocardial infarction, revascularization, unstable angina, heart failure and stroke) risk reduction in age quartiles (each n = 200). Patients on "structured care" with atorvastatin (n = 800) followed up by the university clinic and treated to lipid goal were compared with the corresponding quartiles on "usual care" (n = 800) followed up by specialists or general practitioners of the patient's choice outside the hospital. Results: In the elderly (mean age 69 ±4 and 70 ±3 years in the "structured" and "usual care", respectively) the absolute CVD event reduction between "structured" and "usual care" was 16.5% ( p < 0.0001), while in the younger patients (mean age 51 ±3 years and 52 ±3 years in the "structured" and "usual care", respectively) this was 8.5% (p = 0.016); relative risk reduction (RRR) 60% (p < 0.0001) vs. 42% respectively (p = 0.001). The elderly had higher rates of chronic kidney disease and higher uric acid levels, plus an increased prevalence of diabetes, metabolic syndrome and non-alcoholic fatty liver disease. These factors might contribute to the increased CVD risk in older patients. Conclusions: All age groups benefited from statin treatment, but the elderly on "structured care" had a greater absolute and relative CVD risk reduction than the younger patients when compared with the corresponding patients assigned to "usual care". These findings suggest that we should not deprive older patients of CVD prevention treatment and lipid target achievement. Copyright © 2013 Termedia & Banach. Source

Athyros V.G.,Aristotle University of Thessaloniki | Tziomalos K.,University College London | Karagiannis A.,Aristotle University of Thessaloniki | Anagnostis P.,Endocrinology Clinic | Mikhailidis D.P.,University College London
Current Drug Targets

White adipose tissue (WAT) is an important endocrine organ that secretes approximately 30 biologically active peptides and proteins, collectively termed "adipokines". These are either produced exclusively by WAT (mainly adiponectin, leptin and resistin) or also by other tissues [e.g. tumour necrosis factor (TNF)-alpha, interleukin (IL)-6, plasminogen activator inhibitor (PAI)-1, angiotensinogen]. Adipokines play a central role in body homeostasis including the regulation of food intake and energy balance, insulin action, lipid and glucose metabolism, angiogenesis and vascular remodelling, regulation of blood pressure and coagulation. Excess WAT, especially visceral obesity, is linked to obesity-related health problems through insulin resistance (IR) [leading to type 2 diabetes mellitus (T2DM)] and systemic lowgrade inflammation [leading to cardiovascular disease (CVD)]. The adipokines are important mediators of these adverse effects. This review describes the role of proinflammatory adipokines in the pathogenesis of IR and of the chronic inflammatory state associated with visceral obesity. Moreover, it summarises treatment options for the normalisation of adipokine levels, which might confer an additional clinical benefit in the effort to prevent or treat obesity-related T2DM and CVD. © 2010 Bentham Science Publishers Ltd. Source

Athyros V.G.,Aristotle University of Thessaloniki | Tziomalos K.,Aristotle University of Thessaloniki | Gossios T.D.,Aristotle University of Thessaloniki | Griva T.,Aristotle University of Thessaloniki | And 6 more authors.
The Lancet

Long-term statin treatment reduces the frequency of cardiovascular events, but safety and efficacy in patients with abnormal liver tests is unclear. We assessed whether statin therapy is safe and effective for these patients through post-hoc analysis of the Greek Atorvastatin and Coronary Heart Disease Evaluation (GREACE) study population. GREACE was a prospective, intention-to-treat study that randomly assigned by a computer-generated randomisation list 1600 patients with coronary heart disease (aged <75 years, with serum concentrations of LDL cholesterol >2·6 mmol/L and triglycerides <4·5 mmol/L) at the Hippokration University Hospital, Thessaloniki, Greece to receive statin or usual care, which could include statins. The primary outcome of our post-hoc analysis was risk reduction for first recurrent cardiovascular event in patients treated with a statin who had moderately abnormal liver tests (defined as serum alanine aminotransferase or aspartate aminotransferase concentrations of less than three times the upper limit of normal) compared with patients with abnormal liver tests who did not receive a statin. This risk reduction was compared with that for patients treated (or not) with statin and normal liver tests. Of 437 patients with moderately abnormal liver tests at baseline, which were possibly associated with non-alcoholic fatty liver disease, 227 who were treated with a statin (mainly atorvastatin 24 mg per day) had substantial improvement in liver tests (p<0·0001) whereas 210 not treated with a statin had further increases of liver enzyme concentrations. Cardiovascular events occurred in 22 (10) of 227 patients with abnormal liver tests who received statin (3·2 events per 100 patient-years) and 63 (30) of 210 patients with abnormal liver tests who did not receive statin (10·0 events per 100 patient-years; 68 relative risk reduction, p<0·0001). This cardiovascular disease benefit was greater (p=0·0074) than it was in patients with normal liver tests (90 [14] events in 653 patients receiving a statin [4·6 per 100 patient-years] vs 117 [23] in 510 patients not receiving a statin [7·6 per 100 patient-years]; 39 relative risk reduction, p<0·0001). Seven (<1) of 880 participants who received a statin discontinued statin treatment because of liver-related adverse effects (transaminase concentrations more than three-times the upper limit of normal). Statin treatment is safe and can improve liver tests and reduce cardiovascular morbidity in patients with mild-to-moderately abnormal liver tests that are potentially attributable to non-alcoholic fatty liver disease. None. © 2010 Elsevier Ltd. Source

Athyros V.G.,Aristotelian University | Ganotakis E.S.,University of Crete | Tziomalos K.,Aristotelian University | Papageorgiou A.A.,Aristotelian University | And 6 more authors.
Current Medical Research and Opinion

There is a need to evaluate the prevalence of metabolic syndrome (MetS) diagnosed by the new Joint Interim Societies (JIS) MetS definition. The JIS definition was compared with three previous definitions to assess their ability to predict cardiovascular disease (CVD) risk. A cross-sectional analysis of a representative sample of Greek adults (n Combining double low line9669) was performed to estimate the prevalence of MetS and CVD using the JIS vs. the three older definitions of MetS: the National Cholesterol Education Program-Adult Treatment Panel-III (NCEP-ATP-III), the International Diabetes Federation (IDF) and the American Heart Association/National Heart Lung and Blood Institute (AHA/NHLBI) definitions. The age-adjusted MetS prevalence was 45.7, 43.4, 24.5 and 26.3 (ANOVA p <0.001) with the JIS, IDF, NCEP and AHA/NHLBI definitions. The prevalence of CVD was 11.4 in the whole study population and 17.6, 18.3, 23.3, 22.6 and in subjects with MetS according to the JIS, IDF, NCEP and AHA/NHLBI definitions (ANOVA p <0.001). The prevalence of CVD was only 10.4 (i.e., lower than in the whole study population) in subjects with MetS according to the JIS but not according to the NCEP-ATP-III and AHA/NHLBI definitions (p <0.001 vs. subjects with MetS as defined by NCEP-ATP-III or AHA/NHLBI). When diagnosed according to the new JIS definition, the prevalence of MetS was high in a Greek Mediterranean cohort (nearly half of the adult population). The NCEP-ATP-III and AHA/NHLBI definitions were more predictive of CVD risk than the new JIS definition. These findings, though limited by the cross sectional analysis, may have implications regarding the choice of the definition to diagnose MetS. © 2010 Informa UK Ltd. Source

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