Adam Szczepanik

Impairment of the oxygen-dependent microbicidal mechanisms of polymorphonuclear neutrophils in patients with type 2 diabetes is not associated with increased susceptibility to infection

Phagocytosis, bactericidal capacity and some selected parameters of oxygen-dependent bactericidal mechanisms were evaluated in 20 patients with type 2 diabetes being in similar (intermediate) state of metabolic control and in 15 healthy individuals. Polymorphonuclear neutrophils (PMNs) from diabetics showed normal ability to phagocytose staphylococci, a decreased Intracellular bacteria killing, the impaired stimulated superoxide anion (O2-) and hydrogen peroxide (H2O2) production and the low intracellular myeloperoxidase activity. The obtained data seem to indicate that the decreased bacterial killing by PMNs isolated from diabetics are partly at least related to an impairment of the oxygen-dependent bactericidal mechanisms. Since none of the diabetic patients suffered from recurrent infection the clinical significance of our finding is still uncertain.

The plasma concentration of advanced oxidation protein products and arterial stiffness in apparently healthy adults

Background: Oxidative stress plays an important role in the pathogenesis of atherosclerosis. Advanced oxidation protein products (AOPP) are markers of oxidative stress and mediators of inflammation. Increased arterial stiffness is associated with increased risk of cardiovascular mortality and morbidity. The aim of this study was to evaluate the relationship between an indirect marker of arterial stiffness and the AOPP level in apparently healthy individuals. Methods and results: Arterial stiffness was estimated with the use of the stiffness index (SIDVP) which significantly correlated with age, mean blood pressure, body fat content and AOPP. The SIDVP was associated with AOPP concentration in both single (R = 0.22, p = 0.03) and multiple regression models adjusted for age, sex, mean blood pressure and body fat content (R2 = 42%, p < 0.0001). Conclusions: The AOPP concentration is elevated in healthy people with increased values of stiffness index. This finding supports the concept that oxidative stress may contribute to arterial stiffening in humans.

Polymorphonuclear Neutrophils Function in Untreated Patients with Chronic Myeloid Leukemia

Morphologically mature polymorphonuclear neutrophils (PMN) isolated from the peripheral blood of 30 patients were examined. These cells manifested the diminution of phagocytosis, random migration, chemotaxis, thermotaxis and bactericidal capacity. The surface charge of circulating PMN and the percent representation of cells with receptor for Fc IgG were significantly decreased. Stimulated as well as unstimulated oxygen consumption, production of O2- and H2O2 were significantly decreased, whereas the hexose monophosphate shunt activity was similar to that noticed in controls. The aggregation of leukemic PMN was practically normal, however their adherence was significantly higher. The possible mechanisms responsible for the observed PMN defects are discussed.

Prospective evaluation of hydroperoxide plasma levels and stable nitric oxide end products in patients subjected to angioplasty for coronary artery disease

BACKGROUND Oxidative stress appears to be involved in several processes that contribute to atherogenesis and restenosis following vascular intervention. METHODS The aim of our study was to evaluate prospectively the plasma concentrations of a hydroperoxide (ROOH) and nitric oxide end product (NO(x)) in patients subjected to coronary angioplasty (PTCA) and routine control angiography 6 months after the initial procedure. We prospectively studied 48 consecutive patients (39 men, nine women, mean age 52 years) with stable angina who underwent successful elective angioplasty. A vascular segment was considered successfully treated when the residual luminal narrowing in the dilated segment immediately after angioplasty was <50%. Angiographic follow-up was obtained in all of the patients. Plasma samples were drawn at baseline (before angioplasty) and serially after angioplasty (1, 3 and 6 months afterwards). Hydroperoxides were determined by the FOX II assay (ferrous oxidation in xylenol orange, Pierce Rockford, IL). Nitrate was converted in the presence of NO3 reductase. The Griess reagent was used for the measurement of NO2. RESULTS The overall angiographic restenosis rate was 35%. There were no significant differences in clinical variables between the patients with or without restenosis. The baseline levels (0.8+/-0.09 vs. 0.6+/-0.2 micromol/l) as well as the concentrations of authentic lipid hydroperoxide in plasma after 1 month (0.7+/-0.09 vs. 1.0+/-0.2 micromol/l) and 6 months (0.8+/-0.1 vs. 1.0+/-0.2 micromol/l) were similar in both groups. Three months after the angioplasty a significant increase in the ROOH level was noticed in the patients with restenosis (0.9+/-0.1 vs. 1.4+/-0.2, P=0.04). Plasma levels of NO(x) were similar in both groups at baseline (23.6+/-2.1 vs. 22.7+/-2.6 micromol/l) and 1 month after procedure (24.4+/-2.2 vs. 23.4+/-3.3 micromol/l). However, in patients with restenosis significant decreases in stable NO end products were observed 3 and 6 months after PTCA (18.1+/-1.5 vs. 13.3+/-1.7, P=0.04; 14.2+/-1.0 vs. 8.7+/-1.3, P=0.02, respectively). CONCLUSIONS In patients with angiographic restenosis a significant increase in lipid peroxidation accompanied by a reduction in the stable end products of nitric oxide in plasma is observed several months after PTCA.

Fibrinolytic Therapy and n-Acetylocysteine in the Treatment of Patients with Acute Myocardial Infarction: Its Influence on Authentic Plasma Hydroperoxide Levels and Polymorphonuclear Neutrophil Oxygen Metabolism

Recently it has been demonstrated that the administration of n-acetylocysteine (NAC), in combination with streptokinase, significantly diminished oxidative stress in patients with myocardial infarction. The aim of our study was to assess the influence of NAC treatment, as adjunct therapy in an evolving myocardial infarction, on the polymorphonuclear count, superoxide anion and hydrogen peroxide levels and nitric oxide production by PMNs and authentic plasma hydroperoxide (ROOH). Treatment of patients with NAC in addition to reperfusion therapy was accompanied by a significant decrease in the number of circulating polymorphonuclear neutrophils. However, the oxygen metabolism of PMNs was not affected by NAC administration. The concentration of authentic plasma hydroperoxide was significantly reduced by the administration of NAC which suggests diminished oxidative stress during acute myocardial infarction.

Effect of Selected Antiarrhythmic Drugs on the Superoxide Anion Production by Polymorphonuclear Neutrophils in vitro

The oxygen radicals produced by polymorphonuclear neutrophils (PMN) during ischemia and reperfusion play an important role in the development of arrhythmias. We investigated the influence of selected antiarrhythmic drugs on PMN superoxide anion production. Amiodarone, verapamil and propranolol significantly decreased the stimulated superoxide anion production, which may be an additional mechanism of their antiarrhythmic activity. The fast sodium channel inhibitors lidocaine, procainamide and mexiletine affected neither spontaneous nor stimulated superoxide anion production.

Effects of magnetic resonance imaging on polymorphonuclear neutrophil functions.

RATIONALE AND OBJECTIVES Limited research has been performed on the effects of magnetic resonance (MR) imaging on the immune system. To our knowledge, there are no reported studies of MR imaging effects on the polymorphonuclear neutrophil (PMN) system. Therefore, we evaluated the influence of MR imaging exposure on PMNs. METHODS In vivo and in vitro studies were performed on 36 patients undergoing MR imaging. The following were estimated in blood samples: leukocyte and PMN count, PMN phagocytosis and bactericidal capacity, percentage of cells with expression of surface receptor for the Fc fragment of immunoglobulin G (IgG), PMN superoxide, hydrogen peroxide production, and plasma lysozyme activity. Another sample of patients was used to eliminate temperature as an influence on changes in PMN functions. RESULTS Both in vitro and in vivo MR imaging led to a decrease in PMNs and an increase in PMN phagocytosis, bactericidal capacity, hydrogen peroxide production, and percentage of cells with expression of surface receptor for Fc IgG. Superoxide anion production did not change significantly. Elevated temperature, stress, and anxiety were excluded as influences on our results. CONCLUSION The PMN system is affected seriously by MR imaging.

Prognosis after acute coronary syndrome in relation with ventricular-arterial coupling and left ventricular strain.

BACKGROUND The value of modern non-invasive indices of the left ventricle (LV) and arterial system function, and their interaction for determining prognosis in contemporarily treated patients with acute coronary syndrome (ACS) is not well established. The study aimed to determine the association of ventricular-arterial (VA) coupling, LV global longitudinal peak systolic strain (GLPSS), global strain rate (GSR) and end-diastolic volume at end-diastolic pressure 30mmHg (V30) with long-term clinical outcomes in patients with ACS. METHODS Echocardiography was applied in 569 ACS patients followed up for >12months after hospitalization. Univariate Cox proportional hazard regression models adjusted to various clinical factors, including reduced LV ejection fraction <40%, were used to compare patients between the first and third tertiles of various indices of LV and arterial systems function and their interaction for the prediction of a combined end-point (defined as either stroke, myocardial infarction or death). Results are presented as hazard ratio (HR) with 95% confidence interval (CI). RESULTS There were 57 clinical outcomes during a median follow-up of 625days. Increased VA coupling >1.68 (HR 2.4; 95% CI: 1.04-5.6); V30>107mL (HR 4.5; 95% CI: 1.9-10.6), GLPSS > -12.8% (HR 2.4; 95% CI: 1.02-5.7), GSR > -0.96 1/s (HR 3.8; 95% CI: 1.6-9.1) were robustly associated with increased hazard. CONCLUSIONS With a sample of contemporarily treated ACS patients, abnormal values of non-invasive indices of LV function and their interaction with arterial system, predict adverse clinical outcomes, independently of LV ejection fraction.

The influence of treatment of hypercholesterolemic patients with simvastatin on plasma chemotactic activity and adherence of neutrophils

BACKGROUND there is some evidence to indicate that statins may affect the function of immune and inflammatory cells. This study investigates the influence of short term treatment with simvastatin on plasma chemotactic activity and adherence of polymorphonuclear neutrophils in hypercholesterolemic patients. METHODS AND RESULTS 20 hypercholesterolemic patients (250-400 mg/dl) were given simvastatin (20 mg daily for 12 weeks). Peripheral blood samples were taken before and after 4 and 12 weeks of the therapy. The percentage of neutrophils adhering to plastic surface coated with albumin was significantly higher when cells were incubated with plasma obtained after 12 weeks of treatment with simvastatin in comparison with plasma collected before the therapy (unstimulated neutrophils: 5.945+/-0.475% vs. 8.155+/-0.96%, P=0.0477, stimulated neutrophils: 39.09+/-4.540% vs. 29.18+/-3.702%, P=0.032). There was a significant negative correlation between adherence of stimulated neutrophils and total cholesterol levels ((r)=-0.2796, 95% CI -0. 4999 to -0.02526, r(2)=0.07817, P=0.032). Migration of neutrophils towards plasma obtained after 12 weeks of treatment with simvastatin was significantly higher than towards plasma collected before the therapy (7.038+/-1.127 vs. 4.505+/-0 618 P=0.0475). CONCLUSION treatment of hypercholesterolemic patients with simvastatin increases the chemotactic activity of plasma and augments the adherence of human neutrophils.

A new micromethod for the evaluation of Fc receptor expression on polymorphonuclear neutrophils.

A simple method for the evaluation of rosetting polymorphonuclear neutrophils is described. It uses small (200 microliter) quantities of heparinized whole blood and is simpler than the micromethod proposed by Buescher and Gallin. The high concentration of neutrophils and paucity of lymphocytes considerably simplify the evaluation of specimens and make the technique particularly useful in granulopenic states. There was a close correlation between results obtained using this technique and those from a standard method requiring the isolation of polymorphonuclear neutrophils.