Increased level of advanced oxidation products (AOPP) as a marker of oxidative stress in patients with acute coronary syndrome.

Oxidative stress impairs endothelial function and may play an important role in the pathogenesis of acute cardiovascular diseases. Advanced oxidation protein products (AOPP) were proposed as one of the possible markers of oxidative injury, which originates under oxidative and carbonyl stress and increase global inflammatory activity. The present study was undertaken to compare AOPP concentrations in a control group of healthy individuals without ICHS (I), patients with stable angina pectoris (II), patients with acute coronary syndrome over 48 hours without ST elevations (III), and patients with ST elevation myocardial infarction (IV). Coronaronary angiography, risk factors and anamnestic data were analyzed. We examined 73 probands with signs of myocardial ischemia, mean age of 61.5 years (64% males) subjected to coronarography and 21 healthy individuals. No significant difference was found between venous blood and coronary samples, or between infarction and non-infarction arteries in the group IV. AOPP concentrations in healthy individuals in the group I (82.9 +/- 29.3 mmol/l) did not differ significantly from patients in group II (89.6 +/- 26.7 mmol/l) and group III (112.3 +/- 54.6 mmol/l). A significant difference in AOPP values was found between the groups I and IV, and between the groups II and IV (82.9 +/- 29.3 mmol/l vs. 125.8 +/- 101 mmol/l, p = 0.02, and 89.6 +/- 26.7 mmol/l vs. 125.8 +/- 101 mmol/l, p = 0.02). No correlations were found between AOPP and body mass index (BMI), nicotinism, left ventricular ejection fraction, parameters of glucose and lipid metabolism. ROC analysis revealed that AOPP concentrations of 89 mmol/l had 64% sensitivity and 71% specificity for revealing an acute coronary syndrome (AUC 0.65, 95% CI 0.55-0.80). AOPP are significantly increased in patients with acute coronary syndromes with ST segment elevation, but also tend to increase in patients with non-ST elevation myocardial infarction. Our observations suggest that AOPP may be used as a marker of oxidative stress and as a prognostic factor for severe forms of cardiovascular disease. A cut-off value of 89 mmol/l can be used with 64% sensitivity and 71% specificity for revealing acute coronary syndrome.

The antioxidant acetylcysteine reduces oxidative stress by decreasing level of AOPPs.

Oxidative stress and especially its connection with many diseases has been discussed much recently. Among markers of oxidative stress there appear new and quite specific ones called advanced oxidation protein products (AOPPs). We tried to influence the level of AOPPs by an antioxidant therapy with N-acetylcysteine. Fourteen individuals with many cardiovascular risk factors were examined. All these patients were administered acetylcysteine (NAC) 600 mg/day orally during 20 days. Before starting the therapy we determined AOPP, albumin cobalt binding (ACB), glucose, creatinine, urea, ALT, AST, cholesterol, LDL, HDL and triglycerides values in peripheral venous blood in all individuals. After finishing our intervention we determined AOPP, ACB and glucose level again. Our results show a statistically significant decrease in AOPP levels after 20-day N-acetylcysteine therapy (medians, initially 82.2, at study end 74.3 umol/l, p = 0.039). We demonstrate a significant decrease in AOPP levels after 20-day N-acetylcysteine therapy in dose 600 mg/day.

Resistin - concentrations in persons with type 2 diabetes mellitus and in individuals with acute inflammatory disease.

UNLABELLED: Resistin is a recently discovered signal molecule, which could help elucidation of the pathophysiology of the insulin resistance and its correlation with obesity. As little information was available about resistin determination in venous blood at the time of our study, we focused on the question whether any correlation exists between persons with type 2 diabetes mellitus, with systemic inflammation, healthy persons and resistin concentrations and laboratory markers of inflammation, peptone, BMI. Differences of resistin values in these types of volunteers were studied as well. METHODS: Persons under study were divided into 3 groups: group A - with clinical signs of inflammatory disease of respiratory tract, leukocytosis > 10000/ul and CRP concentration > 50 mg/l (n = 35); group B - with well controlled type 2 DM treated by oral antidiabetic drugs, without clinical signs of inflammation and negative case history of acute disease (n = 12); group C - without clinical signs of inflammation and negative case history of acute disease (n = 77). For all volunteers we determined BMI index and examined resistin, leptin, interleukin 6, TNF-alpha, Na, K, Cl, insulin, cholesterol, HDL-cholesterol, LDL-cholesterol, triacylglycerols, creatinine, uric acid, ALT, AST, GMT, P, Mg and albumin in serum. RESULTS: Persons with clinical signs of severe inflammation had higher concentrations of Il6, CRP, resistin and a markedly lower BMI, decreased values of glucose, sodium, triacylglycerols, cholesterol, LDL-cholesterol and HDL-cholesterol compared to diabetics of type 2 (p < 0.05). Persons with clinical signs of severe inflammation showed significantly higher concentrations of TNF-alpha, Il6, CRP, resistin, glucose, leptin and considerably lower values of albumin, sodium and HDL-cholesterol than healthy individuals (p < 0.05). Persons with type 2 DM had markedly higher values of BMI, CRP, glucose, triacylglycerols, LDL-cholesterol, GMT and leptin, compared to healthy volunteers (p < 0.05). None of the three groups differed markedly in age or sex. Healthy volunteers show a significant correlation between leptin and resistin (correlation coefficient 0.82); this correlation was not found in patients with inflammation and type 2 DM. The group of volunteers with inflammations was found to have a significant positive correlation between resistin and inflammatory markers (correlation coefficient 0.3-0.5), negative correlation between resistin and cholesterol. We also found positive correlations between leptin and BMI as well as negative correlations between leptin and CRP. No significant correlations between resistin and other studied parameters were found in persons with type 2 DM. CONCLUSION: In healthy population a correlation was found between leptin and resistin concentrations in serum. In patients with severe inflammatory disease a correlation between resistin concentration and laboratory markers of inflammation was shown, however, no correlation was found between leptin and resistin. Resistin concentration in the serum of these patients is significantly higher ( p < 0.01) compared to healthy subjects and well controlled persons with type 2 DM with signs of insulin resistance. This may be due to a direct effect of inflammatory cytokines on resistin production. In persons with type 2 DM no significant correlations were found between resistin and other individual parameters ( insulin sensitivity markers, BMI or leptin). Resistin concentrations in persons with type 2 DM do not differ from concentrations of common population.

Adiponectin concentrations as a criterion of metabolic control in persons with type 2 diabetes mellitus?

UNLABELLED: Adiponectin (ADP) is an adipocytokin with many antiatherogenic properties; its decreased level is associated with numerous atherogenic diseases and syndromes (e.g. diabetes mellitus (DM), dyslipidemia, endothelial dysfunction, hypertension, and obesity). Decreased ADP values in blood may be an independent risk factor of atherosclerotic (ATS) complications. AIM OF THE STUDY: 1) Do persons with type 2 diabetes have lower ADP values than individuals without DM but with a high risk of ATS complications? 2) Do ADP values differ between persons with well controlled and persons with uncontrolled type 2 diabetes? We examined 109 patients of the Metabolic Center of Hospital Sternberk. Out of them, 58 had type 2 diabetes, others were individuals with variously expressed risk factors of early atherosclerosis (obesity, hypertension, age, family history, smoking, dyslipidemia, etc.). In all persons under this study the following parameters were determined in peripheral venous blood: adiponectin, resistin, leptin, ObRe, cholesterol, HDL-cholesterol, triacylglycerols, glucose, HbA1c, creatinine, urea, ALT, AST, CRP, homocysteine, thrombocyte aggregation after CPG induction. The whole group was divided according to the presence of type 2DM into two subgroups; persons with diabetes were divided into the well controlled and uncontrolled subgroups. All data obtained were processed statistically using the software SPSS for Windows and Medcalc. The adiponectin/BMI index correlated negatively with HbA1c value (correlation coefficient -0.37, p = 0.00053), triacylglycerols (-0.4, p = 0.000001), P-glucose (-0.3, p = 0.0017), uricemia (-0.35, p = 0.0007) and positively with HDL-cholesterol value (0.6, p=0.00001). Women had higher adiponectin values than men. Persons with hypertension and with diabetes mellitus, individuals with atherogenic lipotype or persons with inflammation signs had lower values than individuals without these diseases and syndromes. Persons with wellcontrolled diabetes mellitus had higher values than persons with uncontrolled diabetes (medians of the adiponectin/BMI index 9.7 vs. 6.7, p < 0.01). Persons with type 2 diabetes mellitus have lower ADP values than persons with a high ATS risk without diabetes mellitus. Persons with wellcontrolled diabetes mellitus (DM) and with satisfactory compensation have significantly higher ADP levels (independently of other metabolic parameters of DM control). ADP may be a new marker of metabolic control in persons with a high risk of atherosclerotic complications.

Preliminary experience with resistin assessment in common population.

Resistin is a signal peptide produced by adipose tissue. Mice models have confirmed that resistin may play an important role in insulin resistance. Its function in the human organism has not been elucidated yet. Since in common population the resistin concentrations are not known (no validated commercial set is available), we performed resistin assessment using the ELISA method (with satisfying analytical characteristics) in a population of 123 non-obese probands without signs of insulin resistance and/or inflammation. Mean resistin values amounted to 14.3 ng/ml (reference limit of 7.3-21.3 ng/ml).