Analysis of the correlations between oxidative stress, gelatinases and their tissue inhibitors in the human subjects with obstructive sleep apnea syndrome

Obstructive sleep apnea syndrome (OSAS) is commonly associated with endothelial dysfunction, atherosclerosis and cardiovascular disorders. On the basis of this observation, our aim was to examine the oxidative status and the matrix metalloproteases (MMP) profile in a group of subjects with OSAS. We enrolled 48 subjects with OSAS defined after a 1-night cardiorespiratory sleep study, who were subsequently subdivided in two subgroups according to the severity of OSAS (low grade = L-OSAS; high grade= H-OSAS). We measured the parameters of oxidative stress, such as lipid peroxidation, protein oxidation, total antioxidant status (TAS), nitric oxide metabolites (NOx), and the plasma concentrations of the gelatinases (MMP-2 and MMP-9) and their tissue inhibitors (TIMP-1 and TIMP-2). We found a significant impairment of oxidative status in H-OSAS compared to L-OSAS and higher plasma levels of MMP-9 and TIMP-1 in H-OSAS compared to L-OSAS. In this study we observed a positive correlation between TBARS and MMP-9, a positive correlation between PC and MMP-9, and a negative correlation between NOx and MMP-9, especially in the whole group of OSAS subjects. These data underline how strong interrelationships among some parameters of the oxidative stress, in particular those reflecting lipid peroxidation, protein oxidation and NOx, and MMP-9 are evident in OSAS subjects. All these information may be useful in the clinical practice keeping in mind the cardiovascular complications generally accompanying the obstructive sleep apnea syndrome

PO-0940: Feasibility of planning CT to MVCT deformable registration for ìdose of the dayî calculation in helical Tomotherapy

Núm. a Art públic: 1135Digitalitzat per Tecnodo

Erythrocyte deformability, plasma lipid peroxidation and plasma protein oxidation in a group of OSAS subjects

Considering that obstructive sleep apnea syndrome (OSAS) is usually associated with endothelial dysfunction, atherosclerosis and cardiovascular disorders, our aim was to examine the erythrocyte deformability and the oxidative status in a group of OSAS subjects. We consecutively enrolled 48 subjects with OSAS defined after a 1-night cardiorespiratory sleep study, subsequently subdivided according to the apnea/hypopnea index (AHI) value in two subgroups: Low (L = 21 subjects with AHI30). We evaluated the erythrocyte deformability, expressed as elongation index (EI) and the parameters of the oxidative status, such as lipid peroxidation (expressed as thiobarbituric acid-reactive substances TBARS) and protein oxidation (measured as carbonyl groups PC). In the entire group and in the two subgroups of OSAS subjects we found a decreased erytrocyte deformability at all shear stresses, not correlated with the plasmatic oxidative stress nor with the polysomnographic parameters. Lipid peroxidation was increased in the whole group and in the H subgroup of OSAS while protein oxidation showed a different trend. As in OSAS the osmotic fragility and the metabolism of the red cells seem to be not impaired, the oxidative damage to the red cell membrane proteins might be responsible for the reduced erythrocyte deformability. This rheological alteration, in addition to the increase in whole blood and plasma viscosity and to the erythrocyte hyperaggregation, could influence the microcircolatory profile in OSAS subjects

Lipid peroxidation and protein oxidation are related to the severity of OSAS

OBJECTIVE: Obstructive sleep apnea syndrome (OSAS) is associated with elevated cardiovascular morbidity and mortality. Considering that oxidative stress is involved in endothelial dysfunction and atherosclerosis development, our aim was to examine lipid peroxidation and protein oxidation, two parameters of oxidative status, in a group of subjects with OSAS. PATIENTS AND METHODS: We consecutively enrolled 48 patients (36 men and 12 women; mean age 49.7\ub114.6 yrs) with OSAS, subsequently subdivided according to the apnea/hy-popnea index (AHI) value in two subgroups: Low (L= 21 subjects with AHI30). We examined lipid peroxidation, expressed as TBARS, and protein oxidation, measured as carbonyl groups in plasma samples from fasting venous blood. RESULTS: We observed that TBARS and car-bonyl groups were significantly higher in subjects with AHI > 30 in comparison with the L subgroup and the whole group of OSAS subjects. In addition, we found that these parameters were positively correlated with neck and waist circumference, with the AHI value and with the oxygen desaturation index, and negatively correlated with the mean oxygen saturation. CONCLUSIONS: Lipid peroxidation and protein oxidation in OSAS patients are significantly correlated with the severity of the disease

Gelatinases and their tissue inhibitors in a group of subjects with obstructive sleep apnea syndrome

Obstructive sleep apnea syndrome (OSAS) is associated with an elevated risk of cardiovascular events and stroke. Matrix metalloproteinases (MMPs) are endopeptidases involved in extracellular matrix degradation and then in the development and progression of cardiovascular diseases. Our aim was to evaluate plasma levels of gelatinases (MMP-2 and MMP-9) and their tissue inhibitors (TIMP-1 and TIMP-2) in a group of subjects with OSAS. We enrolled 48 subjects (36 men and 12 women; mean age 49.7 \ub1 14.68 yrs) with OSAS diagnosed with a 1-night cardiorespiratory study and then we subdivided these subjects into two subgroups according to the apnea/hypopnea index (AHI): Low (L = 21 subjects with AHI <30) and High (H = 27 subjects with AHI >30). We measured plasma concentration of the gelatinases and their inhibitors using ELISA kits. We observed a significant increase in plasma concentration of MMP-9, MMP-2, TIMP-1 and TIMP-2 in the entire group of OSAS subjects and in the two subgroups, with higher levels in the H in comparison with the L subgroup. In the whole group of OSAS subjects we also noted a significant decrease in MMP-9/TIMP-1 ratio in comparison with normal controls. Only MMP-9 was significantly correlated with the severity of the disease, expressed as AHI, with the oxygen desaturation index and also with the mean oxygen saturation. MMPs pattern is altered in OSAS and significantly influenced by the severity of the disease; it probably contributes to the vascular remodeling that leads to the atherosclerotic disease and cardiovascular complications

Validation of an elastic registration technique to estimate anatomical lung modification in Non-Small-Cell Lung Cancer Tomotherapy

<p>Abstract</p> <p>Background</p> <p>The study of lung parenchyma anatomical modification is useful to estimate dose discrepancies during the radiation treatment of Non-Small-Cell Lung Cancer (NSCLC) patients. We propose and validate a method, based on free-form deformation and mutual information, to elastically register planning kVCT with daily MVCT images, to estimate lung parenchyma modification during Tomotherapy.</p> <p>Methods</p> <p>We analyzed 15 registrations between the planning kVCT and 3 MVCT images for each of the 5 NSCLC patients. Image registration accuracy was evaluated by visual inspection and, quantitatively, by Correlation Coefficients (CC) and Target Registration Errors (TRE). Finally, a lung volume correspondence analysis was performed to specifically evaluate registration accuracy in lungs.</p> <p>Results</p> <p>Results showed that elastic registration was always satisfactory, both qualitatively and quantitatively: TRE after elastic registration (average value of 3.6 mm) remained comparable and often smaller than voxel resolution. Lung volume variations were well estimated by elastic registration (average volume and centroid errors of 1.78% and 0.87 mm, respectively).</p> <p>Conclusions</p> <p>Our results demonstrate that this method is able to estimate lung deformations in thorax MVCT, with an accuracy within 3.6 mm comparable or smaller than the voxel dimension of the kVCT and MVCT images. It could be used to estimate lung parenchyma dose variations in thoracic Tomotherapy.</p

Nitric oxide metabolites (nitrite and nitrate) in several clinical condition

We determined the concentration of nitric oxide metabolites (NO2-+ NO3-), expressed as NOx, in several clinical conditions. Regarding this, we have examined 25 subjects with arterial hypertension, 41 subjects with chronic kidney disease in conservative treatment, 106 subjects with metabolic syndrome subdivided according to the presence (n=43) or not (n=63) of diabetes mellitus, 48 subjects with obstructive sleep apnea syndrome (OSAS),14 women with systemic sclerosis complicated with Raynaud's phenomenon, 42 dialyzed subjects and 105 young subjects with acute myocardial infarction (AMI). In subjects with arterial hypertension, chronic kidney disease, metabolic syndrome, systemic sclerosis, as well as, in dialyzed and AMI subjects, we found at baseline a NOx increase. In dyalized subjects after a standard dialysis session, we observed a decrease in NOx. The increase in NOx in juvenile AMI was significantly influenced by cigarette smoking and less by cardiovascular risk factors and the extent of coronary lesions; at 3 and 12 months later than the initial event, we observed a decrease of NOx that remains significantly higher than the control group. In subjects with OSAS no difference in NOx was noted in comparison with normal controls, although their subdivision according to the apnea/hypopnea index operates a clear distinction regarding NOx concentration

EP-1349: Long term results of a phase I-II study of moderate hypofractionated IGRT in prostate cancer

Pregnant women diagnosed with gestational diabetes mellitus subjected to diet (GDMd) that do not reach normal glycaemia are passed to insulin therapy (GDMi). GDMd associates with increased human cationic amino acid transporter 1 (hCAT-1)-mediated transport of L-arginine and nitric oxide synthase (NOS) activity in foetoplacental vasculature, a phenomenon reversed by exogenous insulin. Whether insulin therapy results in reversal of the GDMd effect on the foetoplacental vasculature is unknown. We assayed whether insulin therapy normalizes GDMd-associated foetoplacental endothelial dysfunction. Primary cultures of human umbilical vein endothelial cells (HUVECs) from GDMi pregnancies were used to assay L-arginine transport kinetics, NOS activity, p44/42mapk and protein kinase B/Akt activation, and umbilical vein rings reactivity. HUVECs from GDMi or GDMd show increased hCAT-1 expression and maximal transport capacity, NOS activity, and eNOS, and p44/42mapk, but not Akt activator phosphorylation. Dilation in response to insulin or calcitonin-gene related peptide was impaired in umbilical vein rings from GDMi and GDMd pregnancies. Incubation of HUVECs in vitro with insulin (1 nmol/L) restored hCAT-1 and eNOS expression and activity, and eNOS and p44/42mapk activator phosphorylation. Thus, maternal insulin therapy does not seem to reverse GDMd-associated alterations in human foetoplacental vasculature.Fondo Nacional de Desarrollo Científico y Tecnológico Chileno 1150377 , 1150344 , 11150083Servicio de Salud de Medicina Oriente de Chile 1938–2016Marie Curie International Research 295185 - EULAMDIM