Soluble endothelial adhesion molecules and inflammation markers in patients with beta-thalassemia intermedia

The term thalassemia intermedia, indicates a clinical condition of intermediate severity between thalassaemia minor, the asymptomatic carrier, and thalassaemia major, the transfusion-dependent, severe form. Thromboembolic events frequently complicate the outcome of thalassemia intermedia patients, reflecting a hypercoagulable state to which endothelial activation is believed to play an important role. The aim of this study was to evaluate the levels of soluble endothelial adhesion molecules that reflect endothelial activation and dysfunction and levels of chronic inflammation markers in the serum of beta-thalassemia intermedia patients. Thirty-five Greek patients with beta-thalassemia intermedia that have received different types of treatment (Hydroxyurea, splenectomy, untreated), aged 8-63 years, were included in the study. Twenty apparently healthy individuals matched forage and sex, formed the control group. Measurements of sVCAM-1, sICAM-1, sTM, P-selectin, E-selectin and CRP levels were performed using immunoassays. We found that all endothelial adhesion molecules and CRP were significantly increased in patients (p<0.001) and not influenced by treatment. A negative correlation was observed between levels of sICAM-1 and sTM and this finding agrees with the results of studies, which propose this correlation as a predictive marker of increased risk for vascular damage. No correlation was observed between endothelial adhesion molecules and inflammation markers. These findings support the hypothesis that a serious degree of endothelial activation and damage along with a state of chronic inflammation underlie the pathophysiology of beta-thalassemia intermedia. Furthermore, these findings are of particular importance in patients who can otherwise be characterized by a subtle clinical phenotype and may have an important role in their clinical care. (C) 2009 Elsevier Inc. All rights reserved

Adhesion molecules and high-sensitivity C-reactive protein levels in patients with sickle cell beta-thalassaemia

Background and aim The primary symptoms of sickle cell disease (SCD) arise from vaso-occlusive crises. The pathogenesis of these crises is complex phenomenon where endothelial activation and damage has a major role. Chronic inflammation also plays an important role in the pathophysiology of SCD. We aimed to investigate endothelial activation in Caucasian Greek patients with SCD by means of measuring adhesion molecules and markers of inflammation. Subjects and methods Twenty-eight patients with SCD aged 563 years were included in the study. Most of the patients (23/28) were double heterozygotes for sickle cell/beta-thalassaemia, while five patients (5/28) were sickle cell homozygotes. Patients were treated with one/or more of hydroxyurea, therapeutic phlebotomies, blood transfusion or splenectomy. Twenty apparently healthy individuals matched for age and sex formed the control group. Measurements of soluble intercellular adhesion molecule-1, (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), P-selectin, E-selectin, soluble thrombomodulin (sTM) and high-sensitivity C-reactive protein (hs-CRP) levels were performed using immunoassays in both patients and healthy individuals. Results We found that all endothelial adhesion molecules and hs-CRP were significantly increased (P < 0 center dot 001) in patients with SCD compared with controls, while sTM levels did not differ significantly (P > 0 center dot 05) and this increase was not influenced by the treatment. Conclusion Our findings demonstrate the high degree of endothelial activation and damage seen in sickle cell patients even in steady-state condition, as well as the important chronic inflammation underlying the pathophysiology of this widespread disease

Assessment of oxidative stress in patients with sickle cell disease: The glutathione system and the oxidant-antioxidant status

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. (C) 2011 Elsevier Inc. All rights reserved

Data on eNOS T786 and G894T polymorphisms and peripheral blood eNOS mRNA levels in Sickle Cell Disease

In this article, we present data on endothelial Nitric Oxide Synthase (eNOS) gene T786C and G894T polymorphisms in Greek steady-state Sickle Cell Disease patients in comparison to healthy controls. Moreover, eNOS mRNA levels were determined in peripheral blood samples from 18 patients and 9 controls. This article complements our recently published article named “Prognostic value of eNOS T786C and G894T polymorphisms in Sickle Cell Disease” (I. Armenis, V. Kalotychou, R. Tzanetea, Z. Kontogeorgiou, D. Anastasopoulou, M. Mantzourani, M. Samarkos, K. Pantos, K. Konstantopoulos, I. Rombos, 2016) [1]