Ioannis Papassotiriou - Academia.edu (original) (raw)
Papers by Ioannis Papassotiriou
Children
Although YKL-40 is a promising diagnostic biomarker of sepsis in adults, its value in neonatal se... more Although YKL-40 is a promising diagnostic biomarker of sepsis in adults, its value in neonatal sepsis is not known. The study objectives included assessing the levels and diagnostic value of serum YKL-40 in term neonates with sepsis and comparing YKL-40 with other commonly used inflammatory biomarkers. In this pilot case–control study, 45 term neonates (30 septic and 15 non-septic, as controls), 4 to 28 days old, were prospectively studied. The International Pediatric Sepsis Consensus Conference criteria were applied to diagnose sepsis. During the acute phase (admission) and remission of sepsis, blood samples were collected from cases (while from controls they were only collected once) for routine laboratory tests, cultures, and the measurement of serum YKL-40 levels via Elisa. In the acute phase of sepsis, YKL-40 levels were significantly elevated in comparison with remission (p = 0.004) and controls (p = 0.003). YKL-40 levels did not differ significantly between patients in remiss...
Critical Reviews in Clinical Laboratory Sciences, 2019
Growth differentiation factor-15 (GDF-15), also known as macrophage inhibitory cytokine-1 (MIC-1)... more Growth differentiation factor-15 (GDF-15), also known as macrophage inhibitory cytokine-1 (MIC-1) or non-steroidal anti-inflammatory drug-activated gene (NAG-1) has been identified as a biomarker of response to treatment and prognosis in cardiovascular diseases. GDF-15 is a member of the transforming growth factor-b superfamily and is involved in several pathological conditions such as inflammation, cancer, cardiovascular, pulmonary and renal diseases. Cardiac myocytes produce and secrete GDF-15 in response to oxidative stress, stimulation with angiotensin II or proinflammatory cytokines, ischemia, and mechanical stretch. Other cellular sources of GDF-15 production are macrophages, vascular smooth muscle cells, endothelial cells, and adipocytes, which secrete GDF-15 in response to oxidative or metabolic stress or stimulation of proinflammatory cytokines. GDF-15 is induced in hypertrophic and dilated cardiomyopathy after volume overload, ischemia, and heart failure. GDF-15 can be used as a marker of prognosis in patients with cardiovascular disorders, in combination with conventional prognostic factors, such as Nterminal pro B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hs-TnT).
Clinical Chemistry and Laboratory Medicine (CCLM), 2018
Brain, behavior, and immunity, 2018
To gain a comprehensive understanding of the multidimensional complex systems structure of the st... more To gain a comprehensive understanding of the multidimensional complex systems structure of the stress response and related health outcomes, we utilized network analysis in a sample of 328 healthy participants in two steps. In a first step, we focused on associations between measures of basal hypothalamic-pituitary-adrenal axis functioning and subjective stress perceptions. In a second step, we linked these diverse stress-related measures to biomarkers and self-reports of health and sleep. Overall, measures clustered depending on their method of assessment, with high correlations between different saliva-based indices of diurnal cortisol regulation, between cortisol and cortisone levels in hair, between different biological health indicators (systemic inflammatory activity and body mass index), between state (experience sampling) and trait (questionnaire-based) self-reports of stress and wellbeing, and between different self-reports of sleep. Bridges between clusters suggested that i...
Clinical chemistry and laboratory medicine, Jan 2, 2018
European journal of haematology, 2018
Levels of the angiogenic cytokines placental growth factor (PlGF) and soluble Fms-like tyrosine k... more Levels of the angiogenic cytokines placental growth factor (PlGF) and soluble Fms-like tyrosine kinase-1 (sFlt-1) and the angiogenic balance, expressed by sFlt-1/PlGF ratio, are perturbed in sickle-cell disease and iron overload, but they have not been evaluated in non-transfusion-dependent thalassemia (NTDT). We measured levels of PlGF, sFlt-1 and vWF:antigen in patients with NTDT of beta-thalassemia genotype, and correlated them with erythrocytic indices and markers of iron overload, inflammation, and tissue hypoxia. Thirty-four NTDT patients with mean hemoglobin level of 8.4 g/dL were included in the study along with 20 apparently healthy individuals who served as controls. Ferritin, LDH, and hs-CRP were higher in patients as compared to controls. We found significant differences between patients and controls in regard to levels of PlGF (52.2 vs 17.2 pg/mL, P < .001), sFlt-1/PlGF (2 vs 4.7, P < .001), and vWF:antigen (88 vs 77.1 IU/dL, P < .01). There was a strong correl...
Clinical biochemistry, Jan 27, 2017
The pathophysiology of atherosclerosis in type 2 diabetes mellitus (T2DM) is multifactorial. The ... more The pathophysiology of atherosclerosis in type 2 diabetes mellitus (T2DM) is multifactorial. The association of vascular indices with circulating biomarkers of inflammation and insulin resistance and their role in the long-term cardiovascular prognosis in T2DM patients were currently investigated. Patients with T2DM and poor glycemic control without known cardiovascular diseases (n=119) at baseline were enrolled and followed for about 9years. The end-point was the occurrence of any cardiovascular event (coronary heart disease, stroke, peripheral artery disease or cardiovascular death). Aortic pulse wave velocity (PWV), augmentation index (AIx), brachial flow-mediated dilation (FMD), hsCRP, Chitinase-3-like protein 1 (YKL-40), Neutrophil Gelatinase-Associated Lipocalin (NGAL), Fatty Acid Binding Protein (FABP-4) were assessed. Higher YKL-40 and NGAL were associated with higher PWV, while higher YKL-40 and FABP-4 were related to higher AIx (p<0.05 for all). In univariate Cox regres...
The Endocrine Society's 93rd Annual Meeting & Expo, June 4–7, 2011 - Boston, 2011
Handbook of Anthropometry, 2012
Adipose tissue is no longer considered an inert tissue simply devoted to energy storage, but it h... more Adipose tissue is no longer considered an inert tissue simply devoted to energy storage, but it has emerged as an active organ in regulating a variety of physiological processes. Adipokines, such as leptin, adiponectin, resistin, adipsin, and visfatin, are proteins secreted by the adipocytes and released into the circulation, participating in the regulation of insulin sensitivity, food intake, inflammation, immunity, and vascular sclerosis. The prevalence of obesity is dramatically increasing worldwide in both children and adults and, along with the increase of obesity, is a parallel increase in the prevalence of comorbid disorders such as hyperlipidemia, arterial hypertension, insulin resistance, and diabetes type 2. In obesity, adipocytes enlarge and macrophages infiltrate adipose tissue, resulting in the large-scale release of several adipokines and in an imbalance between molecules and peptides secreted by the adipose tissue. The proinflammatory cytokines contribute to the “low-grade inflammatory state” of obese individuals, especially those with the Metabolic Syndrome (MetS), a clustering of metabolic abnormalities related to obesity, in both adults and children. Leptin and adiponectin are the two most studied adipokines in neonates, children, and adults and the majority of studies in obese individuals have shown hyperleptinemia and hypoadiponectinemia compared to normal-weight individuals. Furthermore, levels of circulating leptin are negatively associated with insulin sensitivity and conversely, adiponectin improves insulin sensitivity by stimulating glucose uptake and fatty acid oxidation in skeletal muscle. However, anthropometric changes during growth and puberty as well as changes in endocrine and metabolic parameters may contribute to the varied effects of adipokines on insulin sensitivity and the metabolic profile.
Experimental hematology, 1998
Patients with the nondeletion genotype of hemoglobinopathy H (HbH or beta4) disease have higher p... more Patients with the nondeletion genotype of hemoglobinopathy H (HbH or beta4) disease have higher proportions of HbH and more severe tissue hypoxia than patients with the deletion genotype. Because these patients' red blood cells (RBCs) contain mainly two Hb species, HbH and HbA, the high proportion of HbA can be exploited by lowering its oxygen affinity; this would probably increase oxygen delivery to the RBCs and improve the patients' clinical phenotype. Allosteric effectors that induce a low-affinity Hb may be useful in this regard. We investigated the effect of a bezafibrate derivative, RSR-4, on the oxygen affinity of RBCs and purified hemolysates containing HbA and HbH. This allosteric effector crosses RBC membranes and binds reversibly to the alpha-chains of deoxy-Hb, decreasing hemoglobin oxygen affinity. The blood used was obtained from a patient with HbH disease (alphaTSaudi homozygote) whose HbH level was 33.5% as measured by high-performance liquid chromatography. ...
Metabolism, 2007
Central adiposity plays an important role in the insulin resistance of the polycystic ovary syndr... more Central adiposity plays an important role in the insulin resistance of the polycystic ovary syndrome (PCOS) through the dysregulated production of various adipokines. Polycystic ovary syndrome has also been described as a low-grade inflammation state characterized by elevated levels of C-reactive protein (CRP). Furthermore, CRP is a strong independent predictor of the metabolic syndrome and cardiovascular disease. Recently, the adiponectin-to-leptin (A/L) ratio has been proposed as a potential atherogenic index in obese type 2 diabetic patients. The aim of this study was to evaluate the potential role of the A/L ratio in the metabolic and proinflammatory phenotype of PCOS. We studied 74 Greek women with PCOS
Metabolism, 2009
Females with a history of premature adrenarche are at high risk of developing polycystic ovary sy... more Females with a history of premature adrenarche are at high risk of developing polycystic ovary syndrome (PCOS) and features of the metabolic syndrome later in life. Coagulation disorders, subclinical inflammation, and oxidative stress have been reported in patients with PCOS and metabolic syndrome. These factors were studied in a group of adolescents with a history of premature adrenarche. This is a cross-sectional study that determined the biochemical-hormonal profile and indices of inflammation, coagulation, and oxidative stress in 45 adolescent girls with a history of premature adrenarche and 19 age- and body mass index-matched controls. Girls with premature adrenarche had hyperandrogenism and higher indices of insulin resistance than controls. They also had significantly higher C-reactive protein (0.76 +/- 0.65 vs 0.41 +/- 0.31 mg/L, P = .0001) and plasminogen activator inhibitor 1 (37.6 +/- 24.7 vs 24.47 +/- 4.6 ng/mL, P = .034), and lower tissue plasminogen activator values in comparison with controls (3.5 +/- 1.5 vs 5.2 +/- 2.12 ng/mL, P = .0019). Both C-reactive protein(r = 0.545, P = .0001) and plasminogen activator inhibitor 1 (r = 0.36, P = .04) were positively correlated with oxidative stress, whereas tissue plasminogen activator was positively correlated (r = 0.37, P = .02) with total antioxidant status. None of these factors was correlated with androgens or indices of insulin resistance. Adolescent girls with a history of premature adrenarche display metabolic deviations usually encountered in subjects with PCOS and metabolic syndrome, such as subclinical inflammation and fibrinolytic abnormalities.
Metabolism, 2011
The adipokine visfatin has been proposed to exert insulin-mimicking effects and to play a role in... more The adipokine visfatin has been proposed to exert insulin-mimicking effects and to play a role in the development of metabolic syndrome. Preterm infants are at risk for the later development of insulin resistance and, possibly, for other components of metabolic syndrome. Dietary long-chain polyunsaturated fatty acids (LCPUFAs) during the perinatal period may reduce the risk of metabolic syndrome. The authors&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; objective was to study the circulating concentrations of visfatin in preterm infants and to examine associations of visfatin with anthropometric measurements, metabolic indices, and dietary LCPUFAs. Serum visfatin concentrations were determined by enzyme-linked immunosorbent assay at mean (SD) 33.8 (11.7) days of life in 60 healthy preterm infants (gestational age, 32.7 [1.9] weeks) randomly assigned to be fed since birth either a formula containing LCPUFA (arachidonic and docosahexaenoic acid) (+LCPUFA group) or the same formula without LCPUFA (-LCPUFA group). Associations of visfatin with anthropometric parameters, serum glucose, insulin, homeostasis model assessment index of insulin resistance, blood lipids, and adiponectin levels were examined. Serum visfatin levels were significantly higher in the +LCPUFA than in the -LCPUFA group (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .001) and correlated positively with body weight z score (β = 0.31, P = .02), total cholesterol (β = 0.34, P = .01), high-density lipoprotein cholesterol (HDL-C) (β = 0.47, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .001), and adiponectin levels (β = 0.29, P = .03), but not with indices of insulin sensitivity. In multiple regression analysis, HDL-C and dietary LCPUFAs correlated independently with serum visfatin levels. Circulating visfatin levels in preterm infants are independently associated with HDL-C levels and dietary LCPUFAs. Whether the higher visfatin levels in the +LCPUFA preterm infant group are beneficial for the later health of these infants remains to be determined.
Metabolism, 2013
Childhood obesity is associated with an increased risk for atherosclerosis mediated by the pathog... more Childhood obesity is associated with an increased risk for atherosclerosis mediated by the pathogenetic mechanisms that lead to the development of the Metabolic Syndrome (MetS). High-Sensitivity Troponin T (hs-TnT) is a specific marker of ischemic myocardial damage, whereas a minimal elevation of this biomarker has been found in adults with a high-risk for cardiovascular disease. We hypothesized that hs-TnT might be altered in obese children with and/or without the Mets. Fifty-seven (34 males) obese and 25 non-obese (6 males) children were assessed at the Childhood Obesity Clinic of our department. Obesity was defined using the IOTF criteria. Metabolic syndrome was defined with the IDF criteria. Hs-TnT was measured using an electrochemiluminescence-based assay. The entire group of obese children had significantly higher hs-TnT concentrations [4.1 ± 3.4 ng/L] (p=0.029) than the non-obese ones [3.0 ± 0.2 ng/L), however, in both groups the levels of the cardiac biomarker were within the normal range. Comparison of the obese children with or without the MetS and the non-obese, revealed that those with the MetS had significantly higher hs-TnT (6.7±7.1 ng/L) than the obese without MetS (3.7 ± 2.1 ng/L) [p=0.044], and the non-obese [p=0.014]. Hs-TnT did not differ between the obese without MetS and the non-obese. Circulating concentrations of hs-TnT in obese children with the MetS are higher than those of the obese without the MetS and the non-obese, suggesting that it is obesity-related metabolic changes rather than obesity per se linked to increased hs-TnT in children.
Journal of Proteomics, 2014
The Spartathlon race (brisk walking a distance of 246 km in less than 36 h) was employed as a mod... more The Spartathlon race (brisk walking a distance of 246 km in less than 36 h) was employed as a model of severe physical stress to investigate proteomic alterations in the plasma of athletes at the start (Athens) and finish (Sparta) of the race, as well as 48 h after the race (Post). The athletes' plasma was analyzed by 2D gel electrophoresis (2-DE) and the differentially expressed proteins were identified by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry (MS). The ProteoSeek™ Albumin/IgG removal kit and the ProteoMiner™ enrichment kit were utilized to detect medium-and low-abundance proteins, whose expression may be masked due to high-abundance proteins. Our results were confirmed by Western blot and biochemical analyses. Overall fifty-two proteins were differentially expressed between the starting point, the finishing line and two days after the end of the race. Of these, thirty proteins were involved in inflammation, while the rest concerned anti-oxidation, anti-coagulation and iron and vitamin D transport. These results indicate that prolonged physical stress affects circulating stress-related proteins, which might be employed as biomarkers of stress-related diseases. Biological significance The current study employed the Spartathlon, as a model of prolonged endurance exercise, to identify and isolate putative biomarkers of inflammation under extreme physical stress conditions. These protein quantitative variations may pave the way to exploration and
Hormone Research in Paediatrics, 2009
Context: The very high carrier frequency of 21-hydroxylase deficiency worldwide has been postulat... more Context: The very high carrier frequency of 21-hydroxylase deficiency worldwide has been postulated as indicating a survival advantage. The ‘mediators’ of such an effect remain speculative. Objective: To look for possible differences in the metabolic and atherogenic risk profile of carriers and noncarriers of CYP21A2 gene mutations at puberty in order to identify possible mediators of the presumed survival advantage for the carriers. It is anticipated that by studying atherogenic risk factors at such an early developmental stage, age-related alterations in these factors may be minimized. Methods: The study group included 45 adolescent girls diagnosed in our center with premature pubarche, 29 of whom were noncarriers and 16 carriers of CYP21A2 mutations. The two groups did not differ in chronological age, age at pubarche or menarche, pubertal stage, body mass index and waist-to-hip ratio. Biochemical and hormonal profile markers as well as markers of endothelial dysfunction were dete...
Hemoglobin, 2004
... (Oxon) 1 , Joanne Traeger‐Synodinos, D.Phil. (Oxon) 1 , Christina Vrettou, D.Phil. ... Identi... more ... (Oxon) 1 , Joanne Traeger‐Synodinos, D.Phil. (Oxon) 1 , Christina Vrettou, D.Phil. ... Identification of two new α‐thalassemia mutations in exon 2 of the α1‐globin gene. Hemoglobin 2001; 25(4)391–396 Abstract. Cooper DN, Krawczak M, Antonarakis SE. ...
Hemoglobin, 2010
Hb Agrinio [α29(B10)Leu→Pro] is a highly unstable variant, classified as a nondeletional α-thalas... more Hb Agrinio [α29(B10)Leu→Pro] is a highly unstable variant, classified as a nondeletional α-thalassemia (α-thal) mutation. To date it has only been described in individuals of Greek and Cypriot origin. Evaluation of the phenotypic presentation of 12 Hb Agrinio homozygotes or compound heterozygotes, diagnosed in a single center in Greece during a 15-year period, found a wide clinical expression, ranging from thalassemia intermedia (with or without transfusion requirement) to Hb H hydrops fetalis, with some phenotype-to-genotype correlation. The often severe clinical presentation of Hb Agrinio homozygotes or Hb Agrinio compound heterozygotes, coinheriting severe α-thal determinants, indicates that molecular identification of carriers of the Hb Agrinio mutation should be considered within the context of screening programs involving individuals of Greek and Cypriot origin. Selective molecular investigation of candidate carriers is facilitated by the observation that all heterozygotes for the Hb Agrinio mutation present with at least one hematological parameter implicating an α-thal carrier state.
Children
Although YKL-40 is a promising diagnostic biomarker of sepsis in adults, its value in neonatal se... more Although YKL-40 is a promising diagnostic biomarker of sepsis in adults, its value in neonatal sepsis is not known. The study objectives included assessing the levels and diagnostic value of serum YKL-40 in term neonates with sepsis and comparing YKL-40 with other commonly used inflammatory biomarkers. In this pilot case–control study, 45 term neonates (30 septic and 15 non-septic, as controls), 4 to 28 days old, were prospectively studied. The International Pediatric Sepsis Consensus Conference criteria were applied to diagnose sepsis. During the acute phase (admission) and remission of sepsis, blood samples were collected from cases (while from controls they were only collected once) for routine laboratory tests, cultures, and the measurement of serum YKL-40 levels via Elisa. In the acute phase of sepsis, YKL-40 levels were significantly elevated in comparison with remission (p = 0.004) and controls (p = 0.003). YKL-40 levels did not differ significantly between patients in remiss...
Critical Reviews in Clinical Laboratory Sciences, 2019
Growth differentiation factor-15 (GDF-15), also known as macrophage inhibitory cytokine-1 (MIC-1)... more Growth differentiation factor-15 (GDF-15), also known as macrophage inhibitory cytokine-1 (MIC-1) or non-steroidal anti-inflammatory drug-activated gene (NAG-1) has been identified as a biomarker of response to treatment and prognosis in cardiovascular diseases. GDF-15 is a member of the transforming growth factor-b superfamily and is involved in several pathological conditions such as inflammation, cancer, cardiovascular, pulmonary and renal diseases. Cardiac myocytes produce and secrete GDF-15 in response to oxidative stress, stimulation with angiotensin II or proinflammatory cytokines, ischemia, and mechanical stretch. Other cellular sources of GDF-15 production are macrophages, vascular smooth muscle cells, endothelial cells, and adipocytes, which secrete GDF-15 in response to oxidative or metabolic stress or stimulation of proinflammatory cytokines. GDF-15 is induced in hypertrophic and dilated cardiomyopathy after volume overload, ischemia, and heart failure. GDF-15 can be used as a marker of prognosis in patients with cardiovascular disorders, in combination with conventional prognostic factors, such as Nterminal pro B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hs-TnT).
Clinical Chemistry and Laboratory Medicine (CCLM), 2018
Brain, behavior, and immunity, 2018
To gain a comprehensive understanding of the multidimensional complex systems structure of the st... more To gain a comprehensive understanding of the multidimensional complex systems structure of the stress response and related health outcomes, we utilized network analysis in a sample of 328 healthy participants in two steps. In a first step, we focused on associations between measures of basal hypothalamic-pituitary-adrenal axis functioning and subjective stress perceptions. In a second step, we linked these diverse stress-related measures to biomarkers and self-reports of health and sleep. Overall, measures clustered depending on their method of assessment, with high correlations between different saliva-based indices of diurnal cortisol regulation, between cortisol and cortisone levels in hair, between different biological health indicators (systemic inflammatory activity and body mass index), between state (experience sampling) and trait (questionnaire-based) self-reports of stress and wellbeing, and between different self-reports of sleep. Bridges between clusters suggested that i...
Clinical chemistry and laboratory medicine, Jan 2, 2018
European journal of haematology, 2018
Levels of the angiogenic cytokines placental growth factor (PlGF) and soluble Fms-like tyrosine k... more Levels of the angiogenic cytokines placental growth factor (PlGF) and soluble Fms-like tyrosine kinase-1 (sFlt-1) and the angiogenic balance, expressed by sFlt-1/PlGF ratio, are perturbed in sickle-cell disease and iron overload, but they have not been evaluated in non-transfusion-dependent thalassemia (NTDT). We measured levels of PlGF, sFlt-1 and vWF:antigen in patients with NTDT of beta-thalassemia genotype, and correlated them with erythrocytic indices and markers of iron overload, inflammation, and tissue hypoxia. Thirty-four NTDT patients with mean hemoglobin level of 8.4 g/dL were included in the study along with 20 apparently healthy individuals who served as controls. Ferritin, LDH, and hs-CRP were higher in patients as compared to controls. We found significant differences between patients and controls in regard to levels of PlGF (52.2 vs 17.2 pg/mL, P < .001), sFlt-1/PlGF (2 vs 4.7, P < .001), and vWF:antigen (88 vs 77.1 IU/dL, P < .01). There was a strong correl...
Clinical biochemistry, Jan 27, 2017
The pathophysiology of atherosclerosis in type 2 diabetes mellitus (T2DM) is multifactorial. The ... more The pathophysiology of atherosclerosis in type 2 diabetes mellitus (T2DM) is multifactorial. The association of vascular indices with circulating biomarkers of inflammation and insulin resistance and their role in the long-term cardiovascular prognosis in T2DM patients were currently investigated. Patients with T2DM and poor glycemic control without known cardiovascular diseases (n=119) at baseline were enrolled and followed for about 9years. The end-point was the occurrence of any cardiovascular event (coronary heart disease, stroke, peripheral artery disease or cardiovascular death). Aortic pulse wave velocity (PWV), augmentation index (AIx), brachial flow-mediated dilation (FMD), hsCRP, Chitinase-3-like protein 1 (YKL-40), Neutrophil Gelatinase-Associated Lipocalin (NGAL), Fatty Acid Binding Protein (FABP-4) were assessed. Higher YKL-40 and NGAL were associated with higher PWV, while higher YKL-40 and FABP-4 were related to higher AIx (p<0.05 for all). In univariate Cox regres...
The Endocrine Society's 93rd Annual Meeting & Expo, June 4–7, 2011 - Boston, 2011
Handbook of Anthropometry, 2012
Adipose tissue is no longer considered an inert tissue simply devoted to energy storage, but it h... more Adipose tissue is no longer considered an inert tissue simply devoted to energy storage, but it has emerged as an active organ in regulating a variety of physiological processes. Adipokines, such as leptin, adiponectin, resistin, adipsin, and visfatin, are proteins secreted by the adipocytes and released into the circulation, participating in the regulation of insulin sensitivity, food intake, inflammation, immunity, and vascular sclerosis. The prevalence of obesity is dramatically increasing worldwide in both children and adults and, along with the increase of obesity, is a parallel increase in the prevalence of comorbid disorders such as hyperlipidemia, arterial hypertension, insulin resistance, and diabetes type 2. In obesity, adipocytes enlarge and macrophages infiltrate adipose tissue, resulting in the large-scale release of several adipokines and in an imbalance between molecules and peptides secreted by the adipose tissue. The proinflammatory cytokines contribute to the “low-grade inflammatory state” of obese individuals, especially those with the Metabolic Syndrome (MetS), a clustering of metabolic abnormalities related to obesity, in both adults and children. Leptin and adiponectin are the two most studied adipokines in neonates, children, and adults and the majority of studies in obese individuals have shown hyperleptinemia and hypoadiponectinemia compared to normal-weight individuals. Furthermore, levels of circulating leptin are negatively associated with insulin sensitivity and conversely, adiponectin improves insulin sensitivity by stimulating glucose uptake and fatty acid oxidation in skeletal muscle. However, anthropometric changes during growth and puberty as well as changes in endocrine and metabolic parameters may contribute to the varied effects of adipokines on insulin sensitivity and the metabolic profile.
Experimental hematology, 1998
Patients with the nondeletion genotype of hemoglobinopathy H (HbH or beta4) disease have higher p... more Patients with the nondeletion genotype of hemoglobinopathy H (HbH or beta4) disease have higher proportions of HbH and more severe tissue hypoxia than patients with the deletion genotype. Because these patients' red blood cells (RBCs) contain mainly two Hb species, HbH and HbA, the high proportion of HbA can be exploited by lowering its oxygen affinity; this would probably increase oxygen delivery to the RBCs and improve the patients' clinical phenotype. Allosteric effectors that induce a low-affinity Hb may be useful in this regard. We investigated the effect of a bezafibrate derivative, RSR-4, on the oxygen affinity of RBCs and purified hemolysates containing HbA and HbH. This allosteric effector crosses RBC membranes and binds reversibly to the alpha-chains of deoxy-Hb, decreasing hemoglobin oxygen affinity. The blood used was obtained from a patient with HbH disease (alphaTSaudi homozygote) whose HbH level was 33.5% as measured by high-performance liquid chromatography. ...
Metabolism, 2007
Central adiposity plays an important role in the insulin resistance of the polycystic ovary syndr... more Central adiposity plays an important role in the insulin resistance of the polycystic ovary syndrome (PCOS) through the dysregulated production of various adipokines. Polycystic ovary syndrome has also been described as a low-grade inflammation state characterized by elevated levels of C-reactive protein (CRP). Furthermore, CRP is a strong independent predictor of the metabolic syndrome and cardiovascular disease. Recently, the adiponectin-to-leptin (A/L) ratio has been proposed as a potential atherogenic index in obese type 2 diabetic patients. The aim of this study was to evaluate the potential role of the A/L ratio in the metabolic and proinflammatory phenotype of PCOS. We studied 74 Greek women with PCOS
Metabolism, 2009
Females with a history of premature adrenarche are at high risk of developing polycystic ovary sy... more Females with a history of premature adrenarche are at high risk of developing polycystic ovary syndrome (PCOS) and features of the metabolic syndrome later in life. Coagulation disorders, subclinical inflammation, and oxidative stress have been reported in patients with PCOS and metabolic syndrome. These factors were studied in a group of adolescents with a history of premature adrenarche. This is a cross-sectional study that determined the biochemical-hormonal profile and indices of inflammation, coagulation, and oxidative stress in 45 adolescent girls with a history of premature adrenarche and 19 age- and body mass index-matched controls. Girls with premature adrenarche had hyperandrogenism and higher indices of insulin resistance than controls. They also had significantly higher C-reactive protein (0.76 +/- 0.65 vs 0.41 +/- 0.31 mg/L, P = .0001) and plasminogen activator inhibitor 1 (37.6 +/- 24.7 vs 24.47 +/- 4.6 ng/mL, P = .034), and lower tissue plasminogen activator values in comparison with controls (3.5 +/- 1.5 vs 5.2 +/- 2.12 ng/mL, P = .0019). Both C-reactive protein(r = 0.545, P = .0001) and plasminogen activator inhibitor 1 (r = 0.36, P = .04) were positively correlated with oxidative stress, whereas tissue plasminogen activator was positively correlated (r = 0.37, P = .02) with total antioxidant status. None of these factors was correlated with androgens or indices of insulin resistance. Adolescent girls with a history of premature adrenarche display metabolic deviations usually encountered in subjects with PCOS and metabolic syndrome, such as subclinical inflammation and fibrinolytic abnormalities.
Metabolism, 2011
The adipokine visfatin has been proposed to exert insulin-mimicking effects and to play a role in... more The adipokine visfatin has been proposed to exert insulin-mimicking effects and to play a role in the development of metabolic syndrome. Preterm infants are at risk for the later development of insulin resistance and, possibly, for other components of metabolic syndrome. Dietary long-chain polyunsaturated fatty acids (LCPUFAs) during the perinatal period may reduce the risk of metabolic syndrome. The authors&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; objective was to study the circulating concentrations of visfatin in preterm infants and to examine associations of visfatin with anthropometric measurements, metabolic indices, and dietary LCPUFAs. Serum visfatin concentrations were determined by enzyme-linked immunosorbent assay at mean (SD) 33.8 (11.7) days of life in 60 healthy preterm infants (gestational age, 32.7 [1.9] weeks) randomly assigned to be fed since birth either a formula containing LCPUFA (arachidonic and docosahexaenoic acid) (+LCPUFA group) or the same formula without LCPUFA (-LCPUFA group). Associations of visfatin with anthropometric parameters, serum glucose, insulin, homeostasis model assessment index of insulin resistance, blood lipids, and adiponectin levels were examined. Serum visfatin levels were significantly higher in the +LCPUFA than in the -LCPUFA group (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .001) and correlated positively with body weight z score (β = 0.31, P = .02), total cholesterol (β = 0.34, P = .01), high-density lipoprotein cholesterol (HDL-C) (β = 0.47, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .001), and adiponectin levels (β = 0.29, P = .03), but not with indices of insulin sensitivity. In multiple regression analysis, HDL-C and dietary LCPUFAs correlated independently with serum visfatin levels. Circulating visfatin levels in preterm infants are independently associated with HDL-C levels and dietary LCPUFAs. Whether the higher visfatin levels in the +LCPUFA preterm infant group are beneficial for the later health of these infants remains to be determined.
Metabolism, 2013
Childhood obesity is associated with an increased risk for atherosclerosis mediated by the pathog... more Childhood obesity is associated with an increased risk for atherosclerosis mediated by the pathogenetic mechanisms that lead to the development of the Metabolic Syndrome (MetS). High-Sensitivity Troponin T (hs-TnT) is a specific marker of ischemic myocardial damage, whereas a minimal elevation of this biomarker has been found in adults with a high-risk for cardiovascular disease. We hypothesized that hs-TnT might be altered in obese children with and/or without the Mets. Fifty-seven (34 males) obese and 25 non-obese (6 males) children were assessed at the Childhood Obesity Clinic of our department. Obesity was defined using the IOTF criteria. Metabolic syndrome was defined with the IDF criteria. Hs-TnT was measured using an electrochemiluminescence-based assay. The entire group of obese children had significantly higher hs-TnT concentrations [4.1 ± 3.4 ng/L] (p=0.029) than the non-obese ones [3.0 ± 0.2 ng/L), however, in both groups the levels of the cardiac biomarker were within the normal range. Comparison of the obese children with or without the MetS and the non-obese, revealed that those with the MetS had significantly higher hs-TnT (6.7±7.1 ng/L) than the obese without MetS (3.7 ± 2.1 ng/L) [p=0.044], and the non-obese [p=0.014]. Hs-TnT did not differ between the obese without MetS and the non-obese. Circulating concentrations of hs-TnT in obese children with the MetS are higher than those of the obese without the MetS and the non-obese, suggesting that it is obesity-related metabolic changes rather than obesity per se linked to increased hs-TnT in children.
Journal of Proteomics, 2014
The Spartathlon race (brisk walking a distance of 246 km in less than 36 h) was employed as a mod... more The Spartathlon race (brisk walking a distance of 246 km in less than 36 h) was employed as a model of severe physical stress to investigate proteomic alterations in the plasma of athletes at the start (Athens) and finish (Sparta) of the race, as well as 48 h after the race (Post). The athletes' plasma was analyzed by 2D gel electrophoresis (2-DE) and the differentially expressed proteins were identified by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry (MS). The ProteoSeek™ Albumin/IgG removal kit and the ProteoMiner™ enrichment kit were utilized to detect medium-and low-abundance proteins, whose expression may be masked due to high-abundance proteins. Our results were confirmed by Western blot and biochemical analyses. Overall fifty-two proteins were differentially expressed between the starting point, the finishing line and two days after the end of the race. Of these, thirty proteins were involved in inflammation, while the rest concerned anti-oxidation, anti-coagulation and iron and vitamin D transport. These results indicate that prolonged physical stress affects circulating stress-related proteins, which might be employed as biomarkers of stress-related diseases. Biological significance The current study employed the Spartathlon, as a model of prolonged endurance exercise, to identify and isolate putative biomarkers of inflammation under extreme physical stress conditions. These protein quantitative variations may pave the way to exploration and
Hormone Research in Paediatrics, 2009
Context: The very high carrier frequency of 21-hydroxylase deficiency worldwide has been postulat... more Context: The very high carrier frequency of 21-hydroxylase deficiency worldwide has been postulated as indicating a survival advantage. The ‘mediators’ of such an effect remain speculative. Objective: To look for possible differences in the metabolic and atherogenic risk profile of carriers and noncarriers of CYP21A2 gene mutations at puberty in order to identify possible mediators of the presumed survival advantage for the carriers. It is anticipated that by studying atherogenic risk factors at such an early developmental stage, age-related alterations in these factors may be minimized. Methods: The study group included 45 adolescent girls diagnosed in our center with premature pubarche, 29 of whom were noncarriers and 16 carriers of CYP21A2 mutations. The two groups did not differ in chronological age, age at pubarche or menarche, pubertal stage, body mass index and waist-to-hip ratio. Biochemical and hormonal profile markers as well as markers of endothelial dysfunction were dete...
Hemoglobin, 2004
... (Oxon) 1 , Joanne Traeger‐Synodinos, D.Phil. (Oxon) 1 , Christina Vrettou, D.Phil. ... Identi... more ... (Oxon) 1 , Joanne Traeger‐Synodinos, D.Phil. (Oxon) 1 , Christina Vrettou, D.Phil. ... Identification of two new α‐thalassemia mutations in exon 2 of the α1‐globin gene. Hemoglobin 2001; 25(4)391–396 Abstract. Cooper DN, Krawczak M, Antonarakis SE. ...
Hemoglobin, 2010
Hb Agrinio [α29(B10)Leu→Pro] is a highly unstable variant, classified as a nondeletional α-thalas... more Hb Agrinio [α29(B10)Leu→Pro] is a highly unstable variant, classified as a nondeletional α-thalassemia (α-thal) mutation. To date it has only been described in individuals of Greek and Cypriot origin. Evaluation of the phenotypic presentation of 12 Hb Agrinio homozygotes or compound heterozygotes, diagnosed in a single center in Greece during a 15-year period, found a wide clinical expression, ranging from thalassemia intermedia (with or without transfusion requirement) to Hb H hydrops fetalis, with some phenotype-to-genotype correlation. The often severe clinical presentation of Hb Agrinio homozygotes or Hb Agrinio compound heterozygotes, coinheriting severe α-thal determinants, indicates that molecular identification of carriers of the Hb Agrinio mutation should be considered within the context of screening programs involving individuals of Greek and Cypriot origin. Selective molecular investigation of candidate carriers is facilitated by the observation that all heterozygotes for the Hb Agrinio mutation present with at least one hematological parameter implicating an α-thal carrier state.