Sanja Stankovic

Parameters of antioxidative defense in type 2 diabetic patients with cardiovascular complications

OBJECTIVE. Diabetes‐associated oxidative stress is a consequence of both increased production of free radicals and reduced capacity of antioxidative defense. Prolonged hyperglycemia is the major factor in the pathogenesis of atherosclerosis in diabetes which can lead to cardiovascular complications. The aim of this study was to test the parameters of antioxidative defense in type 2 diabetic patients. METHODS. A total of 117 type 2 diabetics with and without cardiovascular complications were examined in order to find out the influence of hyperglycemia, type and duration of complications and duration of diabetes on the extent of disorder of antioxidative parameter values: superoxide dismutase (SOD), glutathione peroxidase (GSH‐Px), glutathione reductase (GR) and total antioxidant status (TAS). RESULTS. Compared to healthy control subjects, type 2 diabetic patients with cardiovascular complications (CVC) had significantly lower SOD (P<0.0001), GSH‐Px (P<0.0001), GR ( P = 0.0002) and TAS values (P<0.0001). In type 2 diabetic subjects with CVC, males had significantly lower SOD (778.7±103.2 U/gHb, P<0.01) and GR activities (52.2±8.9 U/L, P<0.001) compared to females (839.3±94.9 U/gHb; 58.5±9.1 U/L). Significant and positive correlation was found between glucose levels and SOD (r = 0.375 for P<0.05) and GSH‐Px (r = 0.384, P<0.05 ) activity in the group of complications‐free diabetics, while significant negative correlation between glucose and GSH‐Px values (r = −0.382, P<0.05) was found in the group of type 2 diabetics with coronary artery disease (CAD) and hypertension (HTA) and with CAD and acute myocardial infarction (AMI) (r = −0.860 P<0.05), and highly negative correlation between glucose and SOD levels (r = −0.590, P<0.05) in the group of diabetic subjects with CAD, AMI and HTA. Likewise, there was highly significant negative correlation of SOD (r = −0.949, P<0.05) and TAS (r = −0.393 for P = 0.038) with duration of diabetes in the group of diabetics with CAD and HTA. CONCLUSION. Our results confirm the hypothesis that there is reduced antioxidative defense in type 2 diabetics with prominent cardiovascular complications, which negatively correlates with glucose concentrations and duration of diabetes and cardiovascular complications.

Immediate Versus Delayed Invasive Intervention for Non-STEMI Patients : The RIDDLE-NSTEMI Study

OBJECTIVES This study aimed to assess the clinical impact of immediate versus delayed invasive intervention in patients with non-ST-segment myocardial infarction (NSTEMI). BACKGROUND Previous studies found conflicting results on the effects of earlier invasive intervention in a heterogeneous population of acute coronary syndromes without ST-segment elevation. METHODS We randomized 323 NSTEMI patients to an immediate-intervention group (<2 h after randomization, n = 162) and a delayed-intervention group (2 to 72 h, n = 161).The primary endpoint was the occurrence of death or new myocardial infarction (MI) at 30-day follow-up. RESULTS Median time from randomization to angiography was 1.4 h and 61.0 h in the immediate-intervention group and the delayed-intervention group, respectively (p < 0.001). At 30 days, the primary endpoint was achieved less frequently in patients undergoing immediate intervention (4.3% vs. 13%, hazard ratio: 0.32, 95% confidence interval: 0.13 to 0.74; p = 0.008). At 1 year, this difference persisted (6.8% in the immediate-intervention group vs. 18.8% in delayed-intervention group; hazard ratio: 0.34, 95% confidence interval: 0.17 to 0.67; p = 0.002). The observed results were mainly attributable to the occurrence of new MI in the pre-catheterization period (0 deaths + 0 MIs in the immediate-intervention group vs. 1 death + 10 MIs in the delayed-intervention group). The rate of deaths, new MI, or recurrent ischemia was lower in the immediate-intervention group at both 30 days (6.8% vs. 26.7%; p < 0.001) and 1 year (15.4% vs. 33.1%; p < 0.001). CONCLUSIONS Immediate invasive strategy in NSTEMI patients is associated with lower rates of death or new MI compared with the delayed invasive strategy at early and midterm follow-up, mainly due to a decrease in the risk of new MI in the pre-catheterization period. (Immediate Versus Delayed Invasive Intervention for Non-STEMI Patients [RIDDLE-NSTEMI]; NCT02419833).

Genetic aspects of ischemic stroke: coagulation, homocysteine, and lipoprotein metabolism as potential risk factors

Stroke is one of the most common causes of death and long term disability throughout the world. It may be the outcome of a number of monogenic disorders or, more commonly, a polygenic multifactorial disease. Numerous studies have investigated the role of genetics in the pathogenesis of ischemic stroke, with varied and often contradictory results. The candidate ‘stroke risk’ genes affecting haemostasis (F5, F2, FGA/FGB, F7, F13A1, vWF, F12, SERPINE1, ITGB3/ITGA2B, ITGA2, GP1BA, TPA, TAFI, THBD, PZ, ANX5), homocysteine metabolism (MTHFR, CBS, MTR), and lipid metabolism (apo E, LPL, CETP, ABCA1, apo AI, apo CIII, apo AIV, apo AV, apo B, apo H, apo(a), PON1/2/3, LDLR/LOX-1) are evaluated in this review. By examining meta-analyses and case-control studies, we made a classification of gene/gene polymorphisms according to the degree of association with ischemic stroke risk. The data assembled could be very useful for further meta-analysis and for future clinical applications.

New insights into the pathogenesis of perinatal hypoxic-ischemic brain injury.

Background:  Pathogenesis of perinatal hypoxic‐ischemic brain injury (HIE) is complex. In this study, we examined the role of neuroinflammation, oxidative stress and growth factors in perinatal hypoxic‐ischemic brain damage.

The association of lipoprotein parameters and C-reactive protein in patients with age-related macular degeneration.

Background: Age-related macular degeneration (AMD) is the most common cause of visual impairment in individuals over 50 years of age, with the prevalence of 0.05% before the age of 50 rising to 30% after 74 years of age. An elevated concentration of plasma lipoproteins is considered to be one of the risk factors of AMD development. The aim of our study was to analyze the concentration of serum lipoproteins – total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), non-LDL cholesterol and triglycerides – as well as apolipoproteins – apoA1, apoB and Lp(a) – along with C-reactive protein (CRP) in patients with AMD in order to explore the possible association of lipid and inflammatory parameters with the pathogenesis of AMD. Material and Methods: In the cross-sectional study in the University clinical setting, 79 patients with AMD, aged 71.47 ± 7.02 years, and 84 aged-matched control subjects were included. The patients underwent complete ophthalmological examination including visual acuity assessment, color fundus photography and fluorescein angiography. Results: Statistical processing data revealed significantly higher total (p = 0.0002), LDL (p = 0.023), non-HDL cholesterol (p = 0.0014) and CRP (p = 0.049) values in AMD patients compared to control subjects. Conclusions: Based on the obtained results, it may be concluded that lipid status disorder and inflammation could play an important role in the development of AMD in elderly people.

B-type natriuretic peptide predicts new-onset atrial fibrillation in patients with ST-segment elevation myocardial infarction treated by primary percutaneous coronary intervention.

The predictive value of B-type natriuretic peptide (BNP) with respect to the occurrence of new-onset atrial fibrillation (AF) in patients with ST-segment elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention (PCI) is unknown. The aim of this study was to evaluate whether BNP has a predictive value for the occurrence of new-onset AF in patients with STEMI treated by primary PCI. In 180 patients with STEMI treated by primary PCI, BNP concentrations were measured 24h after chest pain onset. The Receiver Operating Characteristic analysis was performed to identify the most useful BNP cut-off level for the prediction of AF. The patients were divided into the two groups according to calculated cut-off level: high BNP group (BNP≥720 pg/mL, n=33) and low BNP group (BNP<720 pg/mL, n=147). The incidence of AF was 5.0%, and occurred more frequently in high BNP group (7/33, 21.2%) than in low BNP group (2/147, 1.4%), (p<0.001). Patients with high BNP were older (p=0.017), had more often anterior wall infarction (p=0.015), higher Killip class on admission (p=0.038), higher peak troponin I (p=0.002), lower left ventricular ejection fraction (p=0.029) than patients with low BNP. After multivariate adjustment, BNP was an independent predictor of AF (OR 3.70, 95% CI 1.40-9.77, p=0.008). BNP independently predicts the occurrence of new-onset AF in STEMI patients treated by primary PCI.

Age-dependent modulation of central ghrelin effects on food intake and lipid metabolism in rats

Ghrelin is an endogenous peptide potentially useful in therapy of anorexia and other age-related metabolic disturbances. We evaluated the influence of age on the orexigenic and lipid metabolism-altering effects of ghrelin. Peripubertal, young, adult and middle-aged rats (1, 2, 7 and 12 months old, respectively) were treated with 5 daily intracerebroventricular injections of ghrelin (0.15 nmol) or saline (control). The food intake was measured daily before treatment, while white adipose tissue and serum/plasma samples for detection of lipid metabolites/hormones were collected at the end of the experiment. The values of cumulative food intake and body weight gain declined, while the white adipose tissue deposits and blood concentrations of triglycerides, cholesterol and free fatty acids all increased with age. Ghrelin significantly increased all parameters, but the stimulatory effects on body weight gain and food intake were more pronounced in peripubertal/young rats, while the increase in white adipose mass, triglyceride and low-density lipoprotein cholesterol levels was more noticeable in adult/middle-aged animals. The decrease in sensitivity to ghrelin-mediated stimulation of food intake in older animals could not be explained by alterations in ghrelins ability to reduce anorexigenic hormones insulin and leptin. However, the higher responsiveness of aged rats to ghrelin-mediated increase in lipid metabolites was accompanied by an increase in adrenocorticotropic hormone and corticosterone levels. These results indicate that aging, while reducing sensitivity to ghrelin-mediated increase in body weight gain and food intake, might enhance the responsiveness to the stimulatory effects of ghrelin on lipid metabolites and hypothalamic-pituitary-adrenal axis activity.

Combined effects of cadmium and decabrominated diphenyl ether on thyroid hormones in rats.

The aim of this study was to see how a mixture of cadmium (Cd) and decabrominated diphenyl ether (BDE209) affect thyroid function, namely thyroid-stimulating hormone (TSH), thyroxin (T4), free thyroxin (FT4), triiodothyronin (T3), and free triiodothyronin (FT3) in Wistar rats (eight per group) receiving either a single substance or their combination by gavage for 28 days. Three groups were receiving Cd alone in the doses of 2.5 mg kg-1, 7.5 mg kg-1, or 15 mg kg-1 b. w. a day, three groups were receiving BDE209 in the doses of 1000 mg kg-1, 2000 mg kg-1, or 4000 mg kg-1 b. w. a day, while nine groups were receiving different mixtures of Cd and BDE209 in these doses (3x3 design). The results have indicated that the Cd+BDE209 mixtures more potently disrupt thyroid hormone homeostasis than would be expected from these chemicals alone.

The effect of a gender difference in the apolipoprotein E gene DNA polymorphism on serum lipid levels in a Serbian healthy population.

Abstract To date, no data have been available on relationship between apolipoprotein E polymorphism and lipid levels in Serbian populations. Blood samples were obtained from 591 healthy normal individuals (193 women and 398 men). A 244 bp sequence of the apolipoprotein E gene including the two polymorphic sites was amplified by polymerase chain reaction. After digestion with Hhal, DNA fragments were visualized by microplate array diagonal gel electrophoresis. In men, levels of both total and low-density lipoprotein cholesterol among the three apolipoprotein E genotype groups differed significantly (p <0.05). The ε2 allele was associated with lower concentrations of both total and low-density lipoprotein cholesterol, where the ε4 allele had the opposite effects. No significant effects of apolipoprotein E polymorphism on serum lipid levels were observed in women. The presented data could be taken into consideration in any future disease risk evaluation in this population.

Myeloperoxidase: New Roles for an Old Molecule

Myeloperoxidase: New Roles for an Old Molecule Myeloperoxidase (MPO) is a member of the heme peroxidase-cyclooxygenase superfamily. It is abundantly expressed in neutrophils and monocytes. During inflammation MPO is released from leukocytes and catalyzes the formation of several reactive species and tissue damage. In this article we present state of the art knowledge on the general properties, biosynthesis and processing and trafficking of MPO. The basic functions of MPO in inflammation and oxidative stress are discussed in detail. This article also summarizes the studies that investigated the relationship between MPO and cardiovascular disease. An overview of the assays for determination of MPO, the sample type and preanalytical procedures is given. Future studies are needed before this marker is introduced into routine clinical practice. Mijeloperoksidaza: Nove Uloge Starog Molekula Mijeloperoksidaza (MPO) član je superfamilije hem peroksidaza-ciklooksigenaza. Većinom je eksprimirana u neutrofilima i monocitima. Tokom zapaljenja MPO se oslobađa iz leukocita i katalizuje formiranje nekoliko reaktivnih vrsta i oštećenje tkiva. U ovom radu prikazane su osnovne karakteristike MPO, biosinteza, obrada i transport MPO. Osnovne funkcije MPO u zapaljenju i oksidativnom stresu su detaljno opisane. Ovaj rad sumira rezultate epidemiološ kih studija koje su ispitivale povezanost MPO i kardiovaskularnih bolesti. Takođe su prikazane metode određivanja MPO, vrste biološkog materijala u kojima se može određivati, kao i preanalitički postupci. Dodatne studije su neophodne pre nego što se otpočne sa rutinskom primenom ovog markera u praksi.