Browsing by Author "Skrbic, Ranko (6506440995)"

Type 2 diabetes mellitus (T2DM) increases the risk of cardiovascular disease, especially myocardial injury. Due to their hy[1]poglycemic effects, glucagon-like peptide-1 receptor agonists (GLP-1RAs) are efficiently used for T2DM management. GLP[1]1RAs also have anti-inflammatory and antioxidative effects and can improve cardiac function. The aim of this study was to investigate the cardioprotective effects of liraglutide, a GLP-1RA, on isoprenaline-induced myocardial injury in rats. The study included four groups of animals. They were pretreated with saline for 10 days + saline on days 9 and 10 (control), saline for 10 days + isoprenaline on days 9 and 10 (isoprenaline group), liraglutide for 10 days + saline on days 9 and 10 (liraglutide group), and liraglutide for 10 days, and on days 9 and 10 isoprenaline was administered. This study evaluated ECG, myocar[1]dial injury markers, oxidative stress markers, and pathohistological changes. The results showed that liraglutide mitigated the isoprenaline-induced cardiac dysfunction recorded by ECG. Liraglutide reduced serum markers of myocardial injury such as high-sensitive troponin I, aspartate aminotransferase, alanine aminotransferase, reduced thiobarbituric acid reactive sub[1]stances, increased catalase and superoxide dismutase activity, increased reduced glutathione level, and improved lipid profile. Liraglutide induced antioxidative protection and alleviated isoprenaline-induced myocardial injury. © 2023, Canadian Science Publishing. All rights reserved.

Type 2 diabetes mellitus (T2DM) increases the risk of cardiovascular disease, especially myocardial injury. Due to their hy[1]poglycemic effects, glucagon-like peptide-1 receptor agonists (GLP-1RAs) are efficiently used for T2DM management. GLP[1]1RAs also have anti-inflammatory and antioxidative effects and can improve cardiac function. The aim of this study was to investigate the cardioprotective effects of liraglutide, a GLP-1RA, on isoprenaline-induced myocardial injury in rats. The study included four groups of animals. They were pretreated with saline for 10 days + saline on days 9 and 10 (control), saline for 10 days + isoprenaline on days 9 and 10 (isoprenaline group), liraglutide for 10 days + saline on days 9 and 10 (liraglutide group), and liraglutide for 10 days, and on days 9 and 10 isoprenaline was administered. This study evaluated ECG, myocar[1]dial injury markers, oxidative stress markers, and pathohistological changes. The results showed that liraglutide mitigated the isoprenaline-induced cardiac dysfunction recorded by ECG. Liraglutide reduced serum markers of myocardial injury such as high-sensitive troponin I, aspartate aminotransferase, alanine aminotransferase, reduced thiobarbituric acid reactive sub[1]stances, increased catalase and superoxide dismutase activity, increased reduced glutathione level, and improved lipid profile. Liraglutide induced antioxidative protection and alleviated isoprenaline-induced myocardial injury. © 2023, Canadian Science Publishing. All rights reserved.

BACKGROUND: Critically ill COVID-19 patients are usually subjected to clinical, laboratory, and radiological diagnostic procedures resulting in numerous findings. Utilizing these findings as indicators for disease progression or outcome prediction is particularly intriguing. OBJECTIVES: Exploring the significance of dynamic changes in haematological and biochemical parameters in predicting the mortality of critically ill COVID-19 patients. METHODS: The present study was a prospective and observational study involving mechanically ventilated 75 critically ill adult COVID-19 patients with hypoxemic respiratory failure. The collected data included baseline patient characteristics, treatment options, outcome, and laboratory findings at admission and 7 days after. The dynamics of the obtained findings were compared between survivors and non-survivors. RESULTS: The 28-day survival rate was 61.3%. In the group of non-survivors significant dynamic changes were found for C-reactive protein (p= 0.001), interleukin-6 (p< 0.001), lymphocyte (p= 0.003), neutrophil-lymphocyte ratio (p= 0.003), platelets (p< 0.001), haemoglobin (p< 0.001), iron (p= 0.012), and total iron-binding capacity (p< 0.001). Statistically significant changes over time were found for ferritin (p= 0.010), D-dimer (p< 0.001), hs-troponin T (p< 0.002), lactate dehydrogenase (p= 0.001), glucose (p= 0.023), unsaturated iron-binding capacity (p= 0.008), and vitamin D (p< 0.001). CONCLUSION: The dynamic changes in inflammatory, haematological and biochemical parameters can predict disease severity, and outcome. © 2025 - IOS Press. All rights reserved.

BACKGROUND: Critically ill COVID-19 patients are usually subjected to clinical, laboratory, and radiological diagnostic procedures resulting in numerous findings. Utilizing these findings as indicators for disease progression or outcome prediction is particularly intriguing. OBJECTIVES: Exploring the significance of dynamic changes in haematological and biochemical parameters in predicting the mortality of critically ill COVID-19 patients. METHODS: The present study was a prospective and observational study involving mechanically ventilated 75 critically ill adult COVID-19 patients with hypoxemic respiratory failure. The collected data included baseline patient characteristics, treatment options, outcome, and laboratory findings at admission and 7 days after. The dynamics of the obtained findings were compared between survivors and non-survivors. RESULTS: The 28-day survival rate was 61.3%. In the group of non-survivors significant dynamic changes were found for C-reactive protein (p= 0.001), interleukin-6 (p< 0.001), lymphocyte (p= 0.003), neutrophil-lymphocyte ratio (p= 0.003), platelets (p< 0.001), haemoglobin (p< 0.001), iron (p= 0.012), and total iron-binding capacity (p< 0.001). Statistically significant changes over time were found for ferritin (p= 0.010), D-dimer (p< 0.001), hs-troponin T (p< 0.002), lactate dehydrogenase (p= 0.001), glucose (p= 0.023), unsaturated iron-binding capacity (p= 0.008), and vitamin D (p< 0.001). CONCLUSION: The dynamic changes in inflammatory, haematological and biochemical parameters can predict disease severity, and outcome. © 2025 - IOS Press. All rights reserved.

INTRODUCTION: This study was created to analyze dynamic alterations in coagulation, hematological and biochemical parameters and their association with mortality of COVID-19 patients. To identify the most sensitive biomarkers as predictors of mortality more research is required. METHODS: The present study was a prospective, one-year-long observational study conducted on all critically ill, COVID-19 patients with respiratory failure. The following data were collected: demographic and clinical characteristics of the study population, comorbidities, coagulation, biochemical and hematological parameters. The primary outcome was the proportion of patients who died. RESULTS: 91 patients with median age 60 (50-67), 76.9% male, met the acute respiratory distress syndrome criteria. It was tested whether dynamic change (delta-Δ) of parameters that were found to be predictors of mortality is independently associated with poor outcome. Adjusted (multivariate) analysis was used, where tested parameters were corrected for basic and clinical patients characteristics. The only inflammatory parameter which dynamic change had statistically significant odds ratio was ΔCRP (p < 0.005), while among coagulation parameters statistically significant OR was found for Δ fibrinogen (p < 0.005) in predicting mortality. CONCLUSION: Monitoring of coagulation, hematological and biochemical parameters abnormalities and their dynamical changes can potentially improve management and predict mortality in critically ill COVID -19 patients. © 2023 - IOS Press. All rights reserved.

INTRODUCTION: This study was created to analyze dynamic alterations in coagulation, hematological and biochemical parameters and their association with mortality of COVID-19 patients. To identify the most sensitive biomarkers as predictors of mortality more research is required. METHODS: The present study was a prospective, one-year-long observational study conducted on all critically ill, COVID-19 patients with respiratory failure. The following data were collected: demographic and clinical characteristics of the study population, comorbidities, coagulation, biochemical and hematological parameters. The primary outcome was the proportion of patients who died. RESULTS: 91 patients with median age 60 (50-67), 76.9% male, met the acute respiratory distress syndrome criteria. It was tested whether dynamic change (delta-Δ) of parameters that were found to be predictors of mortality is independently associated with poor outcome. Adjusted (multivariate) analysis was used, where tested parameters were corrected for basic and clinical patients characteristics. The only inflammatory parameter which dynamic change had statistically significant odds ratio was ΔCRP (p < 0.005), while among coagulation parameters statistically significant OR was found for Δ fibrinogen (p < 0.005) in predicting mortality. CONCLUSION: Monitoring of coagulation, hematological and biochemical parameters abnormalities and their dynamical changes can potentially improve management and predict mortality in critically ill COVID -19 patients. © 2023 - IOS Press. All rights reserved.

Background: Isoprenaline (ISO), a synthetic catecholamine and a β-adrenoceptor agonist, is widely used to develop an experimental model of myocardial injury (MI) in rats. The leading hypothesis for ISO-induced MI in rats is that it results from catecholamine overstimulation, oxidative stress, inflammatory responses, and development of cardiomyopathy during ISO administration. Folic acid (FA) reduces oxidative stress, improves endothelial function and prevents apoptosis, thereby contributing to cardiovascular protection. This study aimed to investigate the potentially protective effect of FA pretreatment on ISO-induced MI in rats. Methods: For 7 days, adult male Wistar albino rats were pretreated with 5 mg/kg/day of FA. On the sixth and seventh days, MI in rats was induced by administering 85 mg/kg/day of ISO. Prooxidant markers in plasma samples, antioxidant capacity in erythrocyte lysates, cardiac damage markers, lipid profile, electrocardiography (ECG) and histopathological analysis were evaluated. Results: FA pretreatment significantly alleviated changes induced by ISO; it decreased the homocysteine and high-sensitivity troponin I level. FA moderately decreased the reactive oxygen species (ROS) levels (superoxide anion radical, hydrogen peroxide and thiobarbituric acid reactive substances) and improved the antioxidant activities of catalase, superoxide dismutase and reduced glutathione. ISO reduced the nitrite level and FA significantly alleviated this change. Conclusion: It can be concluded that FA, as a mild antioxidant, could be an appropriate cardioprotective substance in the rat model of ISO-induced MI. © 2023 Akadémiai Kiadó, Budapest.

Current data suggest that aristolochic acid (AA) exposure is a putative cause of Balkan endemic nephropathy (BEN), a chronic kidney disease strongly associated with upper tract urothelial carcinoma. The cellular metabolism of AA is associated with the production of reactive oxygen species, resulting in oxidative distress. Purpose: Therefore, the aim of this study was to analyze individual, combined and cumulative effect of antioxidant gene polymorphisms (Nrf2 rs6721961, KEAP1 rs1048290, GSTP1AB rs1695, GSTP1CD rs1138272, GPX3 rs8177412 and MDR1 rs1045642), as well as GSTP1ABCD haplotypes with the risk for BEN development and associated urothelial cell carcinoma in 209 BEN patients and 140 controls from endemic areas. Experimental method: Genotyping was performed using polymerase chain reaction (PCR) and PCR with confronting two-pair primers (PCR-CTTP) methods. Results: We found that female patients carrying both variant GPX3 rs8177412 and MDR1 rs1045642 genotypes in combination exhibited significant risk towards BEN (OR 1 = 3.34, 95% CI = 1.16–9.60, p = 0.025; OR 2 = 3.79, 95% CI = 1.27–11.24, p = 0.016). Moreover, significant association was determined between GPX3rs8174412 polymorphism and risk for urothelial carcinoma. Carriers of variant GPX3*TC + CC genotype were at eight-fold increased risk of BEN-associated urothelial tumors development. There was no individual or combined impact on BEN development and BEN-associated tumors among all examined polymorphisms. The haplotype consisting of variant alleles for both polymorphisms G and T was associated with 1.6-fold increased risk although statistically insignificant (OR = 1.64; 95% CI = 0.75–3.58; p = 0.21). Conclusions: Regarding GPX3 rs8177412 polymorphism, the gene variant that confers lower expression is associated with significant increase in upper urothelial carcinoma risk. Therefore, BEN patients carrying variant GPX3 genotype should be more frequently monitored for possible upper tract urothelial carcinoma development. © 2023 by the authors.

Takotsubo syndrome (TTS) is a stress-induced cardiomyopathy, characterized by an increased concentration of catecholamines, free radicals, and inflammatory cytokines, endothelial dysfunction, and increased apoptotic activity. High doses of isoprenaline are used in animal models to induce Takotsubo (TT)-like myocardial injury. The aim of the study was to investigate the antiapoptotic effects of liraglutide in experimental TTS and its role in the NF-κB pathway. Wistar rats were pretreated with liraglutide for 10 days, and on days 9 and 10, TT-like myocardial injury was induced with isoprenaline. After the sacrifice on day 11, hearts were isolated for histopathological and immunohistochemical analysis. Liraglutide reduced isoprenaline-induced cardiomyocyte apoptosis by decreasing cleaved caspase-3 (CC3), BCL-2-associated X protein (BAX), and NF-κB and increasing B-cell lymphoma/leukemia-2 (BCL-2). An increase in NF-κB in isoprenaline-treated rats was in positive correlation with proapoptotic markers (BAX and CC3) and in negative correlation with antiapoptotic marker BCL-2. Liraglutide increased BCL-2 and decreased NF-κB, BAX, and CC3, preserving the same correlations of NF-κB to apoptotic markers. It is concluded that liraglutide protects cardiomyocytes against isoprenaline-induced apoptosis in experimental TT-like myocardial injury through downregulation of the NF-κB pathway. © 2024 by the authors.

Takotsubo syndrome (TTS) is a stress-induced cardiomyopathy, characterized by an increased concentration of catecholamines, free radicals, and inflammatory cytokines, endothelial dysfunction, and increased apoptotic activity. High doses of isoprenaline are used in animal models to induce Takotsubo (TT)-like myocardial injury. The aim of the study was to investigate the antiapoptotic effects of liraglutide in experimental TTS and its role in the NF-κB pathway. Wistar rats were pretreated with liraglutide for 10 days, and on days 9 and 10, TT-like myocardial injury was induced with isoprenaline. After the sacrifice on day 11, hearts were isolated for histopathological and immunohistochemical analysis. Liraglutide reduced isoprenaline-induced cardiomyocyte apoptosis by decreasing cleaved caspase-3 (CC3), BCL-2-associated X protein (BAX), and NF-κB and increasing B-cell lymphoma/leukemia-2 (BCL-2). An increase in NF-κB in isoprenaline-treated rats was in positive correlation with proapoptotic markers (BAX and CC3) and in negative correlation with antiapoptotic marker BCL-2. Liraglutide increased BCL-2 and decreased NF-κB, BAX, and CC3, preserving the same correlations of NF-κB to apoptotic markers. It is concluded that liraglutide protects cardiomyocytes against isoprenaline-induced apoptosis in experimental TT-like myocardial injury through downregulation of the NF-κB pathway. © 2024 by the authors.