Prognostic Value of Redox Status Biomarkers in Patients Presenting with STEMI or Non-STEMI: A Prospective Case-Control Clinical Study.

(1) Background: The aim of our study was to determine the role of oxidative stress (OS) during early evaluation of acute ST-elevated myocardial infarction (STEMI) and non-ST-elevated myocardial infarction (NSTEMI) patients in order to define the role of redox balance in profiling the development of myocardial infarction (MI). (2) Methods: This prospective observational case-control study included 40 consecutive STEMI and 39 NSTEMI patients hospitalized in the coronary care unit of the cardiology clinic at the Kragujevac Clinical Center, Serbia, between 1 January 2016 and 1 January 2017. Blood samples were collected from all patients for measuring cardio-specific enzymes at admission and 12 h after admission to evaluate systemic oxidative stress biomarkers and the activity of antioxidant enzymes. (3) Results: In this study, participants were predominately female (52%), with a mean age of 56.17 ± 1.22 years old in the STEMI group and 69.17 ± 3.65 in the non-STEMI group. According to the Killip classification, the majority of patients (>50%) were at the second and third level. We confirmed the elevation of superoxide anion radicals in the non-STEMI group 6 h after admission in comparison with the STEMI and CTRL groups, but levels had decreased 12 h after admission. Levels of hydrogen peroxide were statistically significantly increased in the NSTEMI group. A positive correlation of superoxide anion radicals and levels of troponin I at admission was observed (r = 0.955; p = 0.045), as well as an inverse correlation between reduced glutathione and levels of NT-pBNP measured 6 h after admission (r = -0.973; p = 0.027). (4) Conclusions: We confirmed that superoxide anion radicals and reduced glutathione observed together with hs-troponin I at admission and NT-pBNP during hospital treatment could be predictors of ST evolution.

Anthropometric Measurements and Admission Parameters as Predictors of Acute Respiratory Distress Syndrome in Hospitalized COVID-19 Patients.

Aim: We aimed to single out admission predictors of acute respiratory distress syndrome (ARDS) in hospitalized COVID-19 patients and investigate the role of bioelectrical impedance (BIA) measurements in ARDS development. Method: An observational, prospective cohort study was conducted on 407 consecutive COVID-19 patients hospitalized at the University Clinical Center Kragujevac between September 2021 and March 2022. Patients were followed during the hospitalization, and ARDS was observed as a primary endpoint. Body composition was assessed using the BMI, body fat percentage (BF%), and visceral fat (VF) via BIA. Within 24 h of admission, patients were sampled for blood gas and laboratory analysis. Results: Patients with BMI above 30 kg/m2, very high BF%, and/or very high VF levels were at a significantly higher risk of developing ARDS compared to nonobese patients (OR: 4.568, 8.892, and 2.448, respectively). In addition, after performing multiple regression analysis, six admission predictors of ARDS were singled out: (1) very high BF (aOR 8.059), (2) SaO2 < 87.5 (aOR 5.120), (3) IL-6 > 59.75 (aOR 4.089), (4) low lymphocyte count (aOR 2.880), (5) female sex (aOR 2.290), and (6) age < 68.5 (aOR 1.976). Conclusion: Obesity is an important risk factor for the clinical deterioration of hospitalized COVID-19 patients. BF%, assessed through BIA measuring, was the strongest independent predictor of ARDS in hospitalized COVID-19 patients.

Genome instability in peripheral blood lymphocytes of patients with heart failure and reduced ejection fraction.

Heart failure (HF) is a complex clinical condition characterized by functional and structural defects of the myocardium, but genetic and environmental factors are considered to play an important role in the development of the disease. In the present study, we investigated the genome instability (DNA and chromosomal damage) in patients with heart failure with reduced ejection fraction (HFrEF) ≤40% and its association with risk factors. The studied population included 48 individuals, of which 29 HFrEF patients (mean age 57.41 ± 5.74 years) and 19 healthy controls (mean age 57.63 ± 6.09 years). The genetic damage index in peripheral blood lymphocytes was analyzed using the comet assay, while micronuclei frequency and nuclear division index were analyzed using the cytokinesis-block micronucleus assay. Our results showed that HFrEF patients had a significantly higher genetic damage index compared with the healthy controls (P < .001). Cytokinesis-block micronucleus assay showed that the average micronucleus frequency in peripheral blood lymphocytes of patients was significantly higher, while the nuclear division index values were significantly lower than in controls (P < .01). Using multiple linear regression analysis, pathological state, ejection fraction, creatinine, glucose, associated disease, residence, proBNP, troponin, urea, ACE-inhibitors, and length of the drug therapy were identified as predictors of DNA and/or chromosomal damage in HF patients. We can conclude that DNA and chromosomal damage was increased in patients with HF, which may be a consequence of disease and/or drug therapy.

DNA and chromosomal damage in peripheral blood lymphocytes in patients with acute coronary syndrome undergoing a coronary angiography.

OBJECTIVE: The aim of the study was to evaluate the DNA and chromosomal damage in peripheral blood lymphocytes (PBLs) of patients with acute coronary syndrome (ACS) and to explore the effect of coronary angiographies in these patients. METHODS: The study included ACS patients who underwent a coronary angiography (CAG) and healthy controls. The ACS sample was divided into two groups: patients with unstable angina pectoris (UAP) and acute myocardial infarction (AMI). The frequency of DNA damage [expressed as genetic damage index (GDI)] was analyzed using the comet assay pre- and post-CAG. Chromosomal aberrations were measured as micronuclei (MNs) frequency using the cytokinesis-block MN (CBMN) assay. Additionally, detailed anamnestic data were taken from the each patient. RESULTS: Increased levels of DNA and chromosomal damage have been revealed in ACS patients compared to the healthy controls. GDI values were also significantly higher in AMI patients than in UAP patients. A highly significant increase of DNA damage was also observed in all patients post-CAG. There was significantly higher MN frequency and significantly lower nuclear division index (NDI) in AMI patients than in UAP patients' pre-CAG. After CAG, there was no significant difference in MN frequencies and NDI values between UAP and AMI patients. CONCLUSION: Correlated with disease severity, our results showed that AMI patients have higher levels of both DNA and chromosomal damage in PBLs compared to UAP patients. The increased level of genome instability was especially evident post-CAG compared to the observed damage pre-CAG.

Influence of Different ß-Blockers on Platelet Aggregation in Patients With Coronary Artery Disease on Dual Antiplatelet Therapy.

INTRODUCTION: The use of ß-blockers in the treatment of patients with coronary heart disease is associated with a decrease in the frequency of angina pectoris and mortality of patients. Due to the severity of the disease and previous cardiovascular interventions, many patients with coronary artery disease (CAD) use dual antiplatelet therapy to achieve greater inhibition of platelet aggregation. The influence of ß-blockers on platelet aggregation in patients using antiplatelet therapy is not well understood. OBJECTIVE: To examine the effect of different ß-blockers on platelet aggregation in patients on dual antiplatelet therapy. METHODOLOGY: The study included 331 patients who were treated at the Department of Cardiology, Clinical Center Kragujevac during 2011. Patients were divided into 4 groups depending on the type of ß-blockers that were used (bisoprolol, nebivolol, metoprolol, and carvedilol). Platelet aggregation was measured using the multiplate analyzer and expressed through the value of adenosine diphosphate (ADP) test (to assess the effect of clopidogrel), ASPI test (to assess the effect of acetyl salicylic acid), TRAP test (to assess baseline platelet aggregation), and the ratio of ADP/TRAP and ASPI/TRAP ASPI/TRAP (ASPI - aranchidonic acid induced aggregation, TRAP - thrombin receptor activating peptide) representing the degree of inhibition of platelet aggregation compared to the basal value. In consideration were taken the representation of demographic, clinical characteristics, laboratory parameters, and cardiovascular medications between the groups. RESULTS: Patients who used nebivolol had a significantly lower value of the ratio of ADP/TRAP (0.39 ± 0.30) compared to patients who used bisoprolol (0.48 ± 0.26; P = .038), and trend toward the lower values of ADP test (328.0 ± 197.3 vs 403.7 ± 213.2; P = .059), while there was no statistically significant difference in values of other laboratory parameters of platelet function between other groups. CONCLUSION: Patients with CAD on dual antiplatelet therapy who used nebivolol had significantly lower levels of residual ADP-induced platelet aggregation compared to baseline than patients who used bisoprolol.

NT-proBNP for prognostic and diagnostic evaluation in patients with acute coronary syndromes.

BACKGROUND AND AIM: N terminal-proB-type natriuretic peptide (NT-proBNP) is synthesised and secreted from the ventricular myocardium. This marker is known to be elevated in patients with acute coronary syndromes (ACS). We evaluated NT-proBNP asa significant diagnostic marker and an important independent predictor of short-term mortality (one month) in patients with ACS. METHODS: NT-proBNP and cardiac troponin I (cTI) were assessed in 134 consecutive patients (median age 66 years, 73% male)hospitalised for ACS in a cardiological university department. The patients were classified into ST-elevation ACS (STE-ACS, n = 74) and non-ST-elevation ACS (NSTE-ACS, n = 60) groups based on the ECG findings on admission. Patients with Killip class ≥ II were excluded. RESULTS: The serum level of NT-proBNP on admission was significantly higher (p < 0.0005), while there was no difference in cTI serum level in the NSTE-ACS patients compared to STE-ACS patients. There was a significant positive correlation between NT-proBNP and cTI in the NSTE-ACS (r = 0.338, p = 0.008) and STE-ACS (r = 0.441, p < 0.0005) patients. There was a significant difference in NT-proBNP (p < 0.0005) and cTI (p < 0.0005) serum level between ACS patients who died within 30 days or who survived after one month. The increased NT-proBNP level is the strongest predictor of mortality in ACS patients, also NT-proBNP cut-point level of 1,490 pg/mL is a significant independent predictor of mortality. CONCLUSIONS: We demonstrated the differences and the correlation in the secretion of NT-proBNP and cTI in patients with STE-ACS vs. NSTE-ACS. Our results provide evidence that NT-proBNP is a significant diagnostic marker and an important independent predictor of short-term mortality in patients with ACS.

The influence of bisoprolol dose on ADP-induced platelet aggregability in patients on dual antiplatelet therapy.

PURPOSE: Dual antiplatelet therapy is recommended after acute coronary syndrome or after percutaneous coronary intervention with coronary stent implantation. Many of the patients on dual antiplatelet therapy receive ß-blockers; some of them could have antiaggregatory effect. Bisoprolol is a highly selective adrenoceptor-blocker, which is often used in the settings of percutaneous coronary intervention or acute coronary syndrome in patients on dual antiplatelet therapy. Its antiaggregative effect has not been extensively studied. Therefore, the aim of this study is to investigate the effect of bisoprolol on ADP-induced platelet aggregation in patients on dual antiplatelet therapy. METHODS: Platelet aggregability has been measured in 100 patients on dual antiplatelet therapy with multiplate analyzer using ADP test in blood samples anticoagulated with heparin. ADP test values have been expressed by arbitrary units/minute. In univariate and multivariate regression analyses, we have investigated the influence of bisoprolol and its dose and also different factors, such as risk factors, concomitant drugs and their dosage, laboratory findings, on ADP test values. RESULTS: Univariate regression analysis showed significant correlation between the bisoprolol dose and the ADP test value (P=0.046, B=52.55, 95% confidence interval 0.87-104.23), which was also shown in the multivariate regression analysis (P=0.018; B=57.011; 95% confidence interval 10.455-103.567). CONCLUSION: We have identified a positive correlation between bisoprolol dose and ADP-induced platelet aggregability in patients on dual antiplatelet therapy.

[The acute and subchronic effect of 3, 4-methylenedioxymethamphetamine on body temperature in rats].

INTRODUCTION: The consumption of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) is known to cause severe hyperthermia in humans. This is of extreme importance since ecstasy is often consumed at "rave" parties, where dancing takes place in a warm environment, which may exacerbate the effect of MDMA on thermoregulation. The present study was performed in order to evaluate the effects of single and repeated administration of MDMA on body temperature in Wistar rats. MATERIAL AND METHODS: The study included 72 male Wistar rats, housed in groups of four in cages at a room temperature of 222 degrees C. They were divided in two groups. The rats in the first group were treated with oral solution of MDMA (5 mg/kg, 10 mg/kg, 20 mg/kg, 40 mg/kg) and their temperature was measured hourly until 8th hour. The rats in the second group were treated with oral solution of MDMA (5 mg/kg, 10 mg/kg, 20 mg/kg) every day during 15 days and their temperature was measured daily at 0th, 1st, 3rd, 5th and 8th hour. Temperature was measured by inserting a thermocouple probe 2.5 cm into the rectum. RESULTS: Both groups showed dose dependent increase of body temperature, determined by rectal temperature measurements. The magnitude of hyperthemic response caused by subchronic administration of MDMA was markedly diminished during the experiment. CONCLUSION: The hyperthermic effect of MDMA was dose-dependent. The magnitude of the hyperthermic response was markedly diminished in subchronic administration.

[The acute effects of 3,4-methylenedioxymethamphetamine on oxidative stress in rat brain].

INTRODUCTION: Oxidative stress and oxygen free radicals are thought to play an important role in acute effects of a number of neurotoxic processes. 3,4-Methylenedioxymethamphetamine (MDMA, ecstasy), a ring substituted amphetamine derivate, has attracted a great deal of media attention in recent years due to its widespread abuse as recreational drug by the young generation. The aim of the present study was to evaluate the acute effects of 3,4-methylenedioxymethamphetamine on oxidative stress parameters (index of lipid peroxidation--ILP, superoxide radicals O2-, superoxide dismutase--SOD and glutathione--GSH) in frontal cortex, striatum and hippocampus in Wistar rats. MATERIALS AND METHODS: The study included 40 male Wistar rats (200-250 g), housed 4 per cage having free access to food and water. MDMA was dissolved in distillated water and administered peroraly at 5, 10, 20 or 40 mg/kg. 8 hours following MDMA, the rats were killed by decapitation, their brains were rapidly removed and the brain structures were dissected out on ice and analyzed biochemically. RESULTS: Acute peroral administration of a single dose (5, 10, 20 and 40 mg/kg) resulted in increase of ILP, O2-, SOD and decrease of GSH. CONCLUSION: The results obtained in the present study suggest that oxidative stress plays a crucial role in MDMA-induced neurotoxicity and that the mechanism of MDMA neurotoxicity may vary between brain regions.

N-methyl-3,4-methylenedioxyamphetamine-induced hepatotoxicity in rats: oxidative stress after acute and chronic administration.

BACKGROUND: The underlying mechanisms of N-methyl-3,4-methylenedioxyamphetamine--MDMA--induced hepatotoxicity are still unknown. The aim of this study was to evaluate hepatic oxido-reductive status in the rats liver after the single and repeated administration of MDMA. METHODS: MDMA was dissolved in distilled water and administered in the doses of 5 mg, 10 mg, 20 mg, and 40 mg/kg. The animals from the acute experiment were treated per os with the single dose of the appropriate solution, through the orogastric tube. The animals from the chronic experiment were treated per os, with the doses of 5, 10, or 20 mg/kg of MDMA every day during 14 days. The control groups were treated with water only. Eight hours after the last dose, the animals were sacrificed, dissected, their livers were rapidly removed, frozen and stored at -70 degrees C until the moment of analysis. The parameters of oxidative stress in the crude mitochondrial fractions of the livers were analyzed. RESULTS: Superoxide dismutase (SOD) activity increased in the livers of the animals that were treated with single doses of MDMA. Chronically treated animals showed the increased SOD activity only after the highest dose (20 mg/kg). The content of reduced glutathione decreased in both groups, but the depletion was much more expressed after the single administration. Lipid peroxidation index increased in dose-dependent manner in both groups, being much higher after the single administration. CONCLUSION: The increased index of lipid peroxidation and the decreased reduced glutathione levels suggested that MDMA application induced the state of oxidative stress in the liver. These changes were much more expressed after the single administration of MDMA.