Filia Apostolakou

5 ES P E Poster presented at: i) Both groups demonstrated the typical circadian cortisol rhythm with highest levels in the morning and lowest in the evening. Significantly lower cortisol concentrations were observed in children with ADHD across the day compared to controls (P<0.05). Moreover, children with ADHD had significantly lower CAR and cortisol AUC (P<0.001). In both groups, the secretion pattern of αamylase showed lowest levels in the morning and highest in the afternoon. Altered Stress System Activity in Children with ADHD

REFERENCES 1. Orazi A, O'Malley D, Jiang J, et al. Acute panmyelosis with myelofibrosis: an entity distinct from acute megakaryoblastic leukemia. Mod Pathol. 2005;18:603-614. doi:10.1038/modpathol. 3800348 2. Bae E, Park C-J, Cho Y-U, et al. Differential diagnosis of myelofibrosis based on WHO 2008 criteria: acute panmyelosis with myelofibrosis, acute megakaryoblastic leukemia with myelofibrosis, primary myelofibrosis and myelodysplastic syndrome with myelofibrosis. Int J Lab Hematol. 2013;35:629-636. doi:10.1111/ijlh.12101 3. Thiele J, Kvasnicka HM, Zerhusen G, et al. Acute panmyelosis with myelofibrosis: a clinicopathological study on 46 patients including histochemistry of bone marrow biopsies and follow-up. Ann Hematol. 2004;83:513-521. doi:10.1007/s00277-004-0881-8 4. National Cancer Database National Cancer Database (NCDB) Participant Use Data File (2004–2016 PUF). Accessed October 12, 2020. 5. Surveillance, Epidemiology, and End Results (SEER) Program (www. seer.cancer.gov) SEER*Stat Database: Incidence SEER 18 Regs Research Data + Hurricane Katrina Impacted Louisiana Cases, Nov 2018 Sub (2000–2016) and (1975–2016 varying) <Katrina/Rita Population Adjustment> Linked To County Attributes Total U.S., 1969–2017 Counties, National Cancer Institute, DCCPS, Surveillance Research Program, released April 2019, based on the November 2018 submission. 6. Suvajdzic N, Marisavljevic D, Kraguljac N, et al. Acute panmyelosis with myelofibrosis: clinical, immunophenotypic and cytogenetic study of twelve cases. Leuk Lymphoma. 2004;45(9):1873-1879. doi: 10.1080/10428190410001683688 7. Konuma T, Kondo T, Kawata T, et al. Adult acute myeloid leukemia working Group of the Japan Society for hematopoietic cell transplantation. Hematopoietic cell transplantation for acute Panmyelosis with myelofibrosis: a retrospective study in Japan. Biol Blood Marrow Transplant. 2019;25(1):e23–e27. doi:10.1016/j. bbmt.2018.08.006

Iron-induced cardiotoxicity remains the leading cause of morbidity and mortality in patients with transfusion-dependent β-thalassemia major. Heart failure in these patients, which may be reversible but has a poor prognosis, is characterized by myocardial iron deposition-related early diastolic dysfunction. Amino-terminal pro-brain natriuretic peptide (NT-proBNP) is a sensitive biomarker for the detection of asymptomatic left ventricular dysfunction. In this study, we prospectively evaluated plasma NT-proBNP levels in 187 adult patients aged 19-54 years with β-TM. Possible correlations with the proposed recently cardiac iron concentration based on an equation derived from heart T2* assessment by MRI: [Fe] = 45.0 × [T2*](-1.22) with [Fe] in milligrams per gram dry weight and T2* in milliseconds were explored. We found that: 143 patients had no cardiac hemosiderosis, defined as [Fe] < 1.1 mg/g dry weight, corresponding to T2* > 20 ms and 44 patients had cardiac hemosiderosis, defined as [Fe] > 1.2mg/g dry weight. The main results of the study showed that: a) NT-proBNP levels were markedly increased in thalassemic patients (152.2 ± 190.1 pg/mL, ranged from 6.0 to 1336.0 pg/mL compared to normal control levels 40.1 ± 19.7 pg/mL, p < 0.001, b) NT-proBNP levels were significantly higher in patients with cardiac hemosiderosis compared to patients without cardiac hemosiderosis (185.1 ± 78.0 vs 128.9 ± 20.2 pg/mL, p < 0.05), c) NT-proBNP levels correlated with [Fe] values (r = 0.387, p < 0.001). This correlation was significant in patients with cardiac hemosiderosis (r = 0.520, p < 0.001), but not in patients without cardiac hemosiderosis (p > 0.1), and d) no significant correlation was found between NT-proBNP levels and left ventricular ejection fraction values, (p > 0.3). Our study demonstrated for first time the significant association of NT-proBNP levels and cardiac iron concentration in patients with β-thalassemia major linking blood chemistry and imaging techniques. Multicenter studies of these parameters during iron chelation therapies are needed to validate their association and further exploit its clinical use.

The association between circulating adipocyte fatty acid-binding protein (A-FABP) levels and coronary artery disease (CAD) is reported. In this case-control study, we investigated the relationship between plasma levels of A-FABP and severity of coronary artery disease (CAD) in Turkish subjects. We also assessed its relationship to alternative biomarkers. Two hundred and eighty patients undergoing coronary angiography were enrolled in the study. By means of coronary angiography, the study population was divided into subjects without any angiographically detectable CAD (no vessel disease; n: 88) and individuals with single vessel disease (n:65), double or triple vessel disease (n: 127). Lipid concentrations were measured by an autoanalyzer and A-FABP, lipoprotein associated phospholipase A2 (Lp-PLA2), Oxidized-LDL (Ox-LDL) and high-sensitivity C-reactive protein (hsCRP) levels by a commercial enzyme-linked immunosorbent assay (ELISA) kit. In our study population, total cholesterol and LDL cholesterol levels did not differ significantly between the groups. Levels of HDL cholesterol, A-FABP, Lp-PLA2, ox-LDL and hsCRP were significantly different among groups. The higher levels of A-FABP, Lp-PLA2, ox-LDL and hsCRP levels were shown in patients with double/triple vessel disease. There was not a significant correlation between A-FABP and other biomarkers in CAD patients. Initially, plasma levels of A-FABP were significantly elevated in CAD patients with double/triple vessel disease. Our results demonstrated alterations in A-FABP levels with severity of CAD and, therefore, indirectly support the hypothesis of an active role for A-FABP in the pathogenesis of CAD.

The aim of this study was to explore the relation between mothers’ parenting stress and the functioning of the hypothalamic–pituitary–adrenal axis (HPAA), as expressed by daily salivary cortisol concentrations, in their children diagnosed with attention deficit hyperactivity disorder (ADHD). Seventy-five children aged 6–11 years diagnosed with ADHD predominant hyperactive-impulsive/combined (ADHD–HI/C, N = 49) and inattentive symptoms (ADHD–I, N = 26) and 45 healthy peers and their mothers participated in the study. Μothers completed measures assessing their children’s ADHD status, perceived parenting stress (Parenting Stress Index – Short Form, PSI–SF), mothers’ symptoms of psychopathology, social support and socioeconomic status. Children’s salivary cortisol samples were collected at six different time points on a single day. Mothers of children with ADHD–HI/C reported higher levels of parenting stress than mothers of children with ADHD–I and controls. All PSI–SF subscales showed ...

High mobility group box 1 protein (HMGB1) has been suggested to be involved in the immune dysfunction and inflammation reported in autism spectrum disorder (ASD). We aimed to assess HMGB1 serum concentrations (SCs) in high-functioning ASD children compared to typically developing (TD) controls and to explore their associations with the autism spectrum quotient (AQ), the empathy quotient (EQ), and the systemizing quotient (SQ). The study involved 42 ASD children and 38 TD children, all-male, aged between 6.1 and 13.3 years old. HMGB1 SCs were measured by enzyme-linked immunosorbent assay (ELISA). Groups were comparable regarding age, general IQ, birth weight, and maternal age at birth. ASD children showed significantly higher HMGB1 SCs compared to TD children (1.25 ± 0.84 ng/mL versus 1.13 ± 0.79 ng/mL, respectively, p = 0.039). The Spearman’s rho revealed that HMGB1 SCs were positively correlated with the AQ attention to detail subscale (rs = 0.46, p = 0.045) and with the SQ total s...

Background Coronavirus SARS-CoV-2, the causative agent of COVID-19, has caused a still evolving global pandemic. Given the worldwide vaccination campaign, the understanding of the vaccine-induced versus COVID-19-induced immunity will contribute to adjusting vaccine dosing strategies and speeding-up vaccination efforts. Methods Anti-spike-RBD IgGs and neutralizing antibodies (NAbs) titers were measured in BNT162b2 mRNA vaccinated participants (n = 250); we also investigated humoral and cellular immune responses in vaccinated individuals (n = 21) of this cohort 5 months post-vaccination and assayed NAbs levels in COVID-19 hospitalized patients (n = 60) with moderate or severe disease, as well as in COVID-19 recovered patients (n = 34). Results We found that one (boosting) dose of the BNT162b2 vaccine triggers robust immune (i.e., anti-spike-RBD IgGs and NAbs) responses in COVID-19 convalescent healthy recipients, while naïve recipients require both priming and boosting shots to acquir...

The aim of this study was to investigate the kinetics of neutralizing antibodies (NAbs) and anti-SARS-CoV-2 anti-S-RBD IgGs up to three months after the second vaccination dose with the BNT162b2 mRNA vaccine. NAbs and anti-S-RBD levels were measured on days 1 (before the first vaccine shot), 8, 22 (before the second shot), 36, 50, and three months after the second vaccination (D111) (NCT04743388). 283 health workers were included in this study. NAbs showed a rapid increase from D8 to D36 at a constant rate of about 3% per day and reached a median (SD) of 97.2% (4.7) at D36. From D36 to D50, a slight decrease in NAbs values was detected and it became more prominent between D50 and D111 when the rate of decline was determined at −0.11 per day. The median (SD) NAbs value at D111 was 92.7% (11.8). A similar pattern was also observed for anti-S-RBD antibodies. Anti-S-RBDs showed a steeper increase during D22–D36 and a lower decline rate during D36–D111. Prior COVID-19 infection and young...

Growing evidence suggests that chronic low-grade inflammation can be reduced through mindfulness-based mental training interventions. However, these results are inconsistent and based on patient populations with heterogeneous conditions. Similar research in healthy adults is lacking. Moreover, common intervention protocols involve varying combinations of different contemplative practices, such that it remains unclear which types of training most effectively influence biomarkers of inflammation. The present study investigated the effect of three distinct 3-month training modules cultivating a) interoception and present-moment focus (Presence), b) socio-affective skills (Affect), or c) socio-cognitive skills (Perspective) on the inflammatory biomarkers interleukin-6 (IL-6) and high sensitive C-reactive protein (hs-CRP) in 298 healthy adults. We observed no group-level effect of training on either biomarker, but trend-level interactions of training type and participant sex. In addition...

Growth differentiation factor-15 (GDF-15) is a member of the TGF-beta family, which is involved in several pathological conditions, including inflammation, cancer, cardiovascular, pulmonary and renal diseases. GDF-15 has prognostic value in patients with cardiovascular disorders and adds prognostic information to conventional prognostic factors, such as NT-proBNP and high-sensitivity troponin (hs-TnT). Cardiac involvement is the most important determinant of prognosis in patients with AL amyloidosis and cardiac biomarkers have major prognostic importance in AL. The aim of the study was to explore the value of GDF-15 in patients with AL amyloidosis. We measured the circulating levels of GDF-15, NT-proBNP and hs-TnT in 77 patients with newly diagnosed AL amyloidosis, before and 3 months post frontline treatment. GDF-15 was measured by a novel pre-commercial immunoassay (Roche Diagnostics). Patients' median age was 68 years; most patients had cardiac (61%) or renal involvement (74%...

Neutrophil gelatinase-associated lipocalin (NGAL) is a 25 kDa protein, which is produced by the injured tubule epithelium. In contrast to serum creatinine (sCr), NGAL is specifically induced in the damaged nephron and then released into blood and urine; thus it is considered as an early marker of renal tubular injury. Our group has recently shown that urinary and serum NGAL were elevated in the vast majority (90% and 70%, respectively) of newly diagnosed patients with multiple myeloma (MM), while serum cystatin-C (CysC), an accurate marker of GFR, was elevated in 70% of them. However, there is no information for the value of these markers in patients with MGUS, asymptomatic MM (AMM), as well as in symptomatic MM post treatment. Thus, we measured urinary and serum NGAL and serum CysC in 40 patients with MGUS (23M/17F, median age 72 years), 36 with AMM (16M/20F, 60 years) and 120 healthy controls. Furthermore, we measured serum NGAL and CysC in 39 newly diagnosed symptomatic MM patien...

5082 Vascular Endothelial Growth Factor Receptor-1 (VEGF-R1) is a receptor tyrosine kinase specific for the angiogenic factors VEGF-A, VEGF-B and placenta growth factor (PlGF), which is also a member of the VEGF family. In contrast to VEGF, the role of PlGF and VEGFR-1 in neovascularization is less clear. Angiogenesis is increased in patients with multiple myeloma (MM) and correlated with inferior outcome in several studies. The role of PlGF and VEGFR-1 has not been evaluated in MM. Therefore, we measured the circulating levels of PlGF and VEGFR-1: i) in 64 patients with newly diagnosed myeloma: 16 with asymptomatic disease (7M/9F; median age 59 years, range 37–82 years) and 48 with symptomatic myeloma (30M/18F; median age 70 years, range 45–89 years; ii) in 8 patients with MGUS (4M/4F; median age 72 years, range 39–84 years); and iii) in 20 healthy, gender and age-matched controls. PlGF and sVEGFR-1 were measured in serum samples using an electrochemiluminescence immunoassays (ECLI...

1084 Background: Angiogenic growth factors, such as the vascular endothelial growth factor (VEGF) family of proteins, govern numerous aspects of vessel homeostasis. Placental growth factor (PlGF) is a member of the VEGF family of angiogenic proteins and is expressed in placental, cardiac, and lung tissue. Placental growth factor (PlGF) and its receptor the fms-like tyrosine kinase receptor 1 (Flt-1 or VEGF-R1) are novel therapeutic targets for angiogenic disorders. These growth factors exert pleiotropic effects, potentially beneficial, such as the promotion of angiogenesis, and/or potentially harmful pro-inflammatory effects, such as the promotion of endothelial dysfunction and pulmonary hypertension. von Willebrand factor (vWF) has been proposed as a biomarker of endothelial damage/dysfunction because increased plasma levels have been found in inflammatory and atherosclerotic vascular diseases and is defined as a novel link between hemostasis and angiogenesis. Patients and Methods:...

Sickle cell disease (SCD) is an inherited hemoglobinopathy characterized by pathological polymerization of hemoglobin, increased red cell rigidity, poor microvascular blood flow, with consequent tissue ischemia and infarction. Thus, hemolytic anemia, vaso-occlusion and vasculopathy are the hallmarks of its clinical presentation. Several other factors contribute to the clinical variability, which is present in SCD, including leukocyte dysfunction, platelet interactions with endothelial cells, pro-inflammatory cytokines, oxidative stress, reduced nitric oxide (NO) availability and hemostatic activation. Placental growth factor (PlGF) is a member of the vascular endothelial growth factor superfamily, which plays an important role in both inflammation and neoangiogenesis. Recently it has been reported that markers of iron overload are associated with high plasma level of PlGF and early mortality [Wang et al, Blood 2014]. Furthermore, in SCD patients, hemolysis can lead to a prothromboti...

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...

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...

Growth differentiation factor-15 (GDF-15) improves prognostication in patients with cardiovascular disorders in addition to conventional cardiac markers (NT-proBNP, troponins) and has shown prognostic value in patients with renal diseases. In patients with AL amyloidosis cardiac involvement is the major determinant of prognosis and cardiac markers define prognosis, while biomarkers of renal involvement stratify renal risk. We explored the prognostic importance of serum levels of GDF-15 in patients with AL amyloidosis, in two independent cohorts. The prognostic value of GDF-15 levels was initially evaluated in a cohort of 107 consecutive patients with previously untreated patients with AL amyloidosis from Athens, Greece and was then validated in a second cohort of 202 consecutive previously untreated patients from Pavia, Italy. High GDF-15 levels were associated with a higher risk of early death and poor overall survival independently of NT-proBNP and hsTnT or hsTnI levels. At 6 mont...

There is growing evidence for dysregulation of the stress system in individuals with Attention Deficit Hyperactivity Disorder (ADHD). The stress system includes neuroanatomical and functional components that function in concert to maintain homeostasis and its main effectors are the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic/adrenomedullary nervous system (SNS). As stress system activity demonstrates a distinct circadian variation, we aimed to describe simultaneously, diurnal rhythms of both the HPA axis and the SNS in children with ADHD and a comparison group. Moreover, we attempted to investigate stress responses to a physical stressor, venipuncture, in both groups. Sixty-two prepubertal children with ADHD combined (ADHD-C) or inattentive (ADHD-I) type and 40 typically developing children provided saliva samples at six specific time points during a day, as well as before and 10 min after a scheduled morning venipuncture. Salivary cortisol and α- amylase were sele...

Cortisol, a key mediator of the stress response, has been associated with obesity and metabolic syndrome manifestations as early as in childhood. Scalp hair cortisol has been proposed as a reliable index of long-term circulating cortisol. We aimed to investigate whether obese prepubertal girls have higher scalp hair cortisol than normal-weight controls and whether hair cortisol levels are correlated with salivary cortisol concentrations in these groups. In this cross-sectional study, 25 obese girls and 25 normal-weighted, age-matched girls were enrolled. Anthropometric evaluation, blood chemistry and salivary cortisol measurements were performed, and body mass index (BMI) and areas under the curve with respect to ground (AUCg) were calculated. Hair cortisol determination was performed with liquid chromatography-tandem mass spectrometry. Both hair cortisol concentrations and salivary cortisol AUCs were higher in the obese than the normal-weight girls (p < .001 and p = .002, respec...

Disturbances of oxidative stress and antioxidant status have been reported in patients with Β-ThM and in a limited number of patients with ThI. To I) study relevant biomarkers of iron metabolism, oxidative stress and antioxidant status, in untransfused patients with ThI and II) evaluate the relation of changes in biomarkers to the clinicalhematological phenotype and genotype. Biomarkers of iron metabolism (ferritin, NTBI, sTfR), of oxidant activity (MDA, GSSG, GSSC/GSHT, NO) and of antioxidant enzymes (GR, GPx, SOD) and Vitamins (E, C, A) were estimated and analyzed in 20 controls and 33 patients with ThI, sub-classified into mild (17) and severe (16) types. All but five were untransfused. Clinical phenotypes of mild and severe ThI were related to distinct genotypes, 11 for mild and 14 for severe. The three iron biomarkers were significantly increased in both ThI types compared to controls and in severe compared to mild types. The ferritin levels (total iron load) had a highly signi...

Hepcidin production is homeostatically regulated by iron stores, anemia and hypoxia. We evaluated the effect of iron overload and of ineffective erythropoeisis on hepcidin expression in patients with thalassemia major. Liver hepcidin mRNA levels correlated with hemoglobin concentration and inversely correlated with serum transferrin receptor, erythropoietin and non-transferrin-bound iron. They did not correlate with indices of iron load. Urinary hepcidin levels were disproportionably suppressed in regards to iron burden. We conclude that hepcidin expression is regulated mainly by increased erythropoietic activity rather than by iron load and that hepcidin plays a central regulatory role in iron circulation and iron toxicity in patients with thalassemia.

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.

To assess and compare the individual effect of different chelation agents on urinary iron excretion (UIE), we asked every patient, receiving combined chelation treatment with deferiprone (DFP) and deferoxamine (DFO), to provide four 24-hours urine samples; 2 samples were collected during days when patient was receiving only DFP, whereas the other 2 were collected when both chelation agents were administrated. Thirty young patients (15 males and 15 females) with beta-thalassemia major and a mean age of 18.54+/-4.62 years participated in the study. Mean serum ferritin concentrations were calculated 1 year prior and 1 year after the urine collection. A significant reduction in ferritin (P=0.001) was shown in the whole patients' series. Combined administration of DFO and DFP resulted in a statistically significant higher UIE than DFP alone (P=0.0007). On an individual basis, DFO and DFP resulted in a median 2.3-fold increase in UIE compared to monotherapy with DFP, ranging from 0.28 to 7.34-fold. Despite this wide variability, combined chelation treatment with DFO and DFP seems to act additively in the majority of the patients, whereas in some patients the huge increase in UIE with DFO and DFP can only be attributed to a synergistic effect.

Epidemiologic studies have indicated a relationship between serum lipids and cancer, and it is possible that lipid abnormalities are involved in the mechanism of oncogenesis. This study was performed to investigate serum lipid alterations in patients with acute lymphoblastic leukemia (ALL) at diagnosis and during remission of the disease. Plasma lipids and lipoproteins were measured at diagnosis, prior to the administration of induction treatment, and every 2 months for the first 12 months of the maintenance phase of chemotherapy in 64 patients with ALL. Nearly all patients demonstrated a predictable pattern of serum lipid alterations that consisted of extremely low levels of high-density lipoprotein cholesterol, elevated triglycerides, and elevated low-density lipoprotein cholesterol. Patients studied again during remission demonstrated a return to normal values, and the difference was statistically significant. The results suggest that at diagnosis of ALL an abnormality in lipid metabolism is present, which is reversed during remission.

Continuous reactive oxygen species (ROS) production in individuals with sickle cell disease (SCD) may alter their overall redox status and cause tissue damage. The aim of this study was to evaluate oxidative stress in patients with SCD using two new assays, FORT (free oxygen radical test) and FORD (free oxygen radical defense) along with assessment of glutathione system including superoxide dismutase (SOD), glutathione reductase (GR) and glutathione peroxidase (GPx) activities, vitamins A, C and E, malondialdehyde (MDA), non-transferrin bound iron (NTBI) and nitric oxide (NO) concentrations. A total of 40 patients with SCD and 25 apparently healthy volunteers (control group) were enrolled in the study. Components of glutathione system, vitamins A, C, and E, and malondialdehyde were determined with reverse-phase HPLC, non-transferrin bound iron (NTBI) was assessed with atomic absorption spectroscopy using graphite furnace, superoxide dismutase (SOD), glutathione reductase (GR) and glutathione peroxidase (GPx) activities were determined spectrophotometrically in red cell lysates, nitric oxide (NO) was detected colorimetrically, while FORT and FORD using colorimetric assays, as two point-of-care tests. The findings revealed significant impairment of the glutathione system indicated by reduced GSH(total) (p<0.00001), GSH(reduced) (p<0.00001) and GSSG (p>0.056) values of SCD patients compared to the control group. ROS expressed as FORT were significantly increased (p<0.00001), while antioxidant defense expressed as FORD was significantly reduced (p<0.02) in SCD group compared to the control group. Age and genotype of the patients as well as therapy of their disease appeared to play no role in their oxidative status.

Adipocyte fatty acid-binding protein (A-FABP) abundantly expressed in mature adipocytes and activated macrophages has dramatic effects on atherosclerosis in mice. Whether this pathophysiological role of A-FABP may also apply to atherosclerotic disease in humans is still unknown. This study investigated associations among serum A-FABP levels, cardiovascular risk factors, and long-term secondary cardiovascular disease (CVD) outcome in patients with coronary heart disease. Serum A-FABP levels were measured in 1069 patients with prevalent coronary heart disease and a 10-year prospective follow-up was conducted (median, 119.5 [interquartile range, 74.1-120.6] months). During this period 204 patients (incidence, 24.0/1000 patient-years) experienced a secondary cardiovascular disease event (defined as cardiovascular death, nonfatal myocardial infarction, or nonfatal cerebrovascular stroke). At baseline, circulating A-FABP was positively associated with a cluster of metabolic and inflammatory risk factors and independently predicted the presence of the metabolic syndrome (odds ratio per unit increase of natural log-transformed A-FABP, 2.95; 95% CI, 2.22-3.92, P<0.001). On long-term follow-up, subjects with high baseline A-FABP showed an increased risk for secondary cardiovascular disease events (hazard ratio per unit increase, 1.52; 95% CI, 1.18-1.95; P=0.001), which was attenuated after multivariable adjustment (hazard ratio 1.30; 95% CI, 0.98-1.73). In contrast, A-FABP remained significantly associated with cardiovascular death even after multivariable adjustment (hazard ratio, 1.75; 95% CI, 1.17-2.62, P=0.007). Circulating A-FABP levels are associated with long-term prognosis in patients with coronary heart disease and may represent an important pathophysiological mediator of atherosclerosis, which may point to a new target of treatment options.