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Background : The pathophysiological mechanism underlying pregnancy complications is not entirely known. Although it is currently impossible to predict the occurrence of redox imbalance, it is possible to identify women with a high or medium risk of developing this disease prior to a negative outcome by non-invasive diagnostic methods. The Aim : This study aimed to examine the possible role of the parameter of oxidative stress (OS) measured in early pregnancy in the screening/treatment of obesity and its complications during pregnancy. Methods : This research was designed as a prospective observational cross-sectional clinical study which included 40 non-obese and 31 obese pregnant women between 11 and 13 g.w. who were managed in the Department of Obstetrics, University Clinical Center Kragujevac in Serbia. We collected anthropometric and clinical indicators, maternal and pregnancy factors, and measured prooxidative parameters from blood samples. Results : We observed significantly increased levels of the superoxide anion radical, hydrogen peroxide and the index of lipid peroxidation in the Obese group in comparison with the Non-Obese group and significantly decreased bioavailability of nitrites in the Obese group in comparison with the Non-Obese group. Conclusions : The determination of systemic parameters of OS in early pregnancy could be a good methodological approach in the screening/treatment of obesity during pregnancy and this approach should be followed for the screening of endothelial dysfunction in pregnancy which needs further monitoring and/or treatment.

Objective: To evaluate the possible effects of apical periodontitis (AP) on cardiac function, structure, and oxidative stress (OS) in rats with diabetes mellitus type 2 (T2DM)., Design: Forty-eight (Wistar albino, male) rats were randomized into four groups: control healthy (CTRL), normoglycemic with AP (AP), T2DM, and T2DM with AP (T2DM+AP). T2DM was induced by streptozotocin and a high-fat diet. AP was induced by pulp exposure to the oral environment for 4 weeks and analyzed radiographically. In the blood samples insulin and glucose were established. In vivo, cardiac function was evaluated by echocardiography. Ex vivo cardiac function was assessed by the Langendorff technique. Heart tissue was analyzed pathophysiologically. OS was determined in cardiac tissue homogenate and coronary venous effluent, spectrophotometrically., Results: Impaired glycoregulation was observed in the T2DM+AP group compared to the T2DM, AP, and CTRL groups. The T2DM+AP group was associated with disturbed echocardiography and cardiodynamic parameters. The levels of superoxide anion radical, nitrite, and index of lipid peroxidation were significantly increased, while the superoxide dismutase and catalase were significantly decreased in the T2DM+AP group compared to T2DM, AP, and CTRL groups. The radiographic AP area was significantly larger in the T2DM+AP compared to the AP group., Conclusion: AP was associated with increased glucose levels, impaired cardiac function, structure, and OS in diabetic rats. Diabetes was related to an increased radiographic AP area. The study may be a starting point for further research to clarify the effects of AP on cardiac function in various models of systemic diseases., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Obesity was included in the International Classification of Diseases in 1990 as a chronic disease characterized by the excessive accumulation of body fat and a body mass index (BMI) greater than 30 kg/m 2 ., Aim: This systematic review was aimed to examine the role of marital status in determining body mass index and the risk of obesity., Methods: We performed a systematic literature search using three databases (PubMed (Medline), Embase, and Google Scholar) with the search query., Results: Of the 105 studies included in the systematic review, 76 studies (72%) reported a greater risk of obesity in married individuals compared to unmarried individuals. A meta-analysis of 24 studies included a total population of 369,499 participants: 257,257 married individuals (40,896 of whom had obesity) and 112,242 comparison subjects (single, divorced, or widowed individuals, 15,084 of whom had obesity). Odds ratios for obesity found a significant pooled odds ratio for obesity in married individuals compared with controls (OR 1.70; 95% CI 1.38-2.10). The socioeconomic environment was not the same throughout the period of studies analyzed. The odds of obesity in married individuals during economic crises was greater than during the period between crises: OR 2.56 (95% CI 2.09-3.13) during crises vs. OR 1.55 (95% CI 1.24-1.95) between crises., Conclusion: The results of this review confirm the importance of considering marital status in determining the risk of obesity., Competing Interests: The authors declare no conflicts of interest.

Introduction: Leiomyosarcoma (LMS), together with smooth muscle tumors of uncertain malignant potential (STUMP) and benign leiomyomas, belongs to a heterogeneous group of uterine neoplasms. According to the World Health Organization, tumors originating from uterine smooth muscle fibers are the second most frequent tumors. It is challenging to distinguish between STUMP and LMS because of an overlap of symptoms, lack of a precise definition, and unequivocal information obtained using imaging diagnostic methods. Following myomectomy or hysterectomy with laparoscopic or laparotomy surgery and a definitive histological diagnosis of STUMP, the course of treatment is determined by the need to preserve fertility. In 2014, the U.S. Food and Drug Administration published an alert that unprotected laparoscopic morcellation is correlated with a 3-fold higher likelihood of dissemination of malignant cells and disease progression. Unprotected morcellation was independently associated with a higher risk of disease recurrence after demolition or conservative surgery, with a relative risk of 2.94., Conclusion: Hematoperitoneum resulting from the spontaneous rupture of a uterine tumor is a rare gynecological emergency, with very few cases reported in the last decade., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Bicanin-Ilic, Ilic, Dimitrijevic, Mujkovic, Jovic, Rakic, Arsenijevic, Nikolic-Turnic, Balovic, Peric, Mitrovic and Nikolov.)

(1) Background and Objective : Excessive gestational weight gain is associated with serious complications such as pre-eclampsia, fetal macrosomia and a more frequent need for cesarean section. The aim of this study is to develop a simple screening model that includes maternal age, BMI and nutritive habits in the second trimester in order to predict the risk of GDM in the population of pregnant women in the territory of the Republic of Serbia. (2) Materials and Methods : This single-center, prospective and case-control study was performed in the University Clinical Center "Dr. Dragisa Misovic Dedinje", Belgrade, Serbia and included 54 women with singleton pregnancies during the second trimester from July 2023 to November 2023. We used basic demographic and socio-epidemiological data, as well as data of the present comorbidities and previous pregnancies/births. The Serbian version of the Nutritive Status Questionnaire (NSQ) was used to estimate the nutritive habits in GDM ( n = 22) and non-GDM groups ( n = 32). (3) Results : We observed less frequent vegetable and fruit consumption in the GDM group in comparison with the non-GDM group; meat and chicken intake was 2-3 times per week in both groups; meat products were consumed 2-3 times per week in the GDM group and 2-3 times per month in the non-GDM group; milk products were consumed once a day in 31.8% of GDM patients and twice per day in 24.1% of non-GDM patients. Sweets (cakes, ice creams, biscuits) were consumed very often (2-3 times per week) in the GDM group (36.4%), while in the non-GDM group this habit was less frequent (26.7%). Cronbach alpha and internal consistency for this instrument were very good (Cronbach alpha = 0.87). (4) Conclusions : We have found that a non-adequate intake of fruits/vegetables, dairy and whole grain, as well as an excessive intake of sugar/artificially sweetened beverages and dairy, was associated with a higher risk of gestational diabetes mellitus (OR = 0.04; 95% CI).

(1) Background: The prevalence of workplace violence within the health sector varies between 50 and 88%. Depending on the health care environment, the percentages mentioned can be much higher. (2) The aim of this study was to determine the prevalence, characteristics, factors, and consequences of violence against healthcare workers (physicians, nurses, and technicians) in psychiatric institutions in the Republic of Serbia. Additionally, this study should validate the Serbian version of the aggression questionnaire, which could be a significant tool in recognizing and assessing any type of violence against health care workers in psychiatric institutions. (3) Methods: This study was designed as an observational questionnaire study that included 191 health workers (physicians, medical technicians, workers in kitchens or maintenance, and others) from three psychiatric institutions. As an instrument, this study validated and used the Serbian version of the aggression standardized questionnaire. We observed the primary and secondary outcomes of potential violence in psychiatric institutions against healthcare workers using different parameters. (4) Results: The internal consistency of each item as well as the instrument was very good (the mean Cronbach alfa = 0.91). A total of 104 of the participants never experienced physical violence, while more than five times that had 20 health workers (10.5%). We observed the statistical significance of gender, age, working status (permanent/limited) and professional status (physician/medical technician/worker etc.) on physical attack incidence. (5) Conclusions: The incidence of violence against healthcare workers is very high, especially in terms of physical assault and threats in the workplace. The majority of the victims were women who work as medical technicians, attacked by male patients with unknown motivation. A number of changes in the structure and organizational culture of the hospital are required. All hospital employees, employers, patients, and their families share responsibility for the creation of a safe workplace.

This study evaluated the effect of sacubtril/valsartan on cardiac remodeling, molecular and cellular adaptations in experimental (rat) model of hypertension-induced hypertrophic cardiomyopathy. Thirty Wistar Kyoto rats, 10 healthy (control) and 20 rats with confirmed hypertension-induced hypertrophic cardiomyopathy (HpCM), were used for this study. The HpCM group was further subdivided into untreated and sacubitril/valsartan-treated groups. Myocardial structure and function were assessed using echocardiography, Langendorff's isolated heart experiment, blood sampling and qualitative polymerase chain reaction. Echocardiographic examinations revealed protective effects of sacubitril/valsartan by improving left ventricular internal diameter in systole and diastole and fractional shortening. Additionally, sacubitril/valsartan treatment decreased systolic and diastolic blood pressures in comparison with untreated hypertensive rats. Moreover, sacubitril/valsartan treatment reduced oxidative stress and apoptosis (reduced expression of Bax and Cas9 genes) compared to untreated rats. There was a regular histomorphology of cardiomyocytes, interstitium, and blood vessels in treated rats compared to untreated HpCM rats which expressed hypertrophic cardiomyocytes, with polymorphic nuclei, prominent nucleoli and moderately dilated interstitium. In experimental model of hypertension-induced hypertrophic cardiomyopathy, sacubitril/valsartan treatment led to improved cardiac structure, haemodynamic performance, and reduced oxidative stress and apoptosis. Sacubitril/valsartan thus presents as a potential therapeutic strategy resulted in hypertension-induced hypertrophic cardiomyopathy., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Objectives : This study was conducted to examine the influence of different swimming and running protocols as forms of physiological preconditioning on an isolated rat heart's ischemia/reperfusion injury. Materials and Methods : This study was conducted on 60 male Wistar albino rats (6 weeks old, bw: 200 ± 20 g), divided into: CTRL group-a sedentary control group; sAeT-a group that underwent aerobic swimming conditioning using a swimming protocol for 8 weeks; sAnT-a group that underwent anaerobic swimming conditioning; rAeT-a group that underwent aerobic running conditioning; and rAnT-a group that underwent anaerobic running conditioning. After the preconditioning protocols, ex vivo estimating of myocardial function according to the Langendorff technique was performed. Results : The anaerobic running training decreased heart rate and the anaerobic swimming training reduced coronary flow, demonstrating the difference in the physiological heart response of aerobic/anaerobic physical training ( p < 0.05). Heart rate was significantly reduced in both training swimming groups after a period of ischemia ( p < 0.05). On the other hand, the anaerobic running protocol induced a significantly decreased heart rate in comparison with the aerobic running group and the sedentary group ( p < 0.05). Conclusions : The data from this experimental study support many protective training effects, i.e., improved contractility, improved resting heart rate, and increased physical work capacity and exercise tolerance. Physical training in the form of anaerobic running induces greater heart preconditioning for reperfusion injury in comparison with anaerobic swimming training.

Objective: The aim of this meta-analysis is to explore all the available literature to obtain updated data about the potential use of antioxidants in the treatment of rheumatoid arthritis (RA) and its ability to reduce disease progression and cardiovascular risk., Methods: This systematic review and meta-analysis was performed strictly in accordance with the PRISMA guidelines. English and Chinese databases were searched with a retrieval time up to March 2023. These databases included the PubMed, Embase, Medline Complete, Web of Sciences and Cochrane Collaboration, Wanfang, China National Knowledge Infrastructure, and VIP databases. This literature search was formulated by the two researchers independently. The search strategy consists of reading, collecting the literature, and conducting the preliminary screening. After that, they provide the final selection of the literature according to the inclusion criteria and data extraction. Also, for all studies, the risk bias was assessed to evaluate the quality of the included references. The content of the risk assessment of bias included the following criteria: random allocation method, allocation plan hiding, blind method, completeness of result data, and selectivity of reporting of results, as well as other biases. The main outcomes were clinical efficiency of antioxidant therapy (C-reactive protein, DAS28 score, HAQ, Number of tender joints, etc.) and oxidative stress indicators (catalase, superoxide dismutase, or total antioxidant capacity)., Results: We observed, in most of the studies, the small or moderate effects of antioxidant treatment. The mean effect size is 0.525, and that means that moderate effects were observed in 30 selected RCTs. Also, this effect is confirmed in the 1652 patients with RA with the mean confidence interval of 0.276 (lower limit) and 0.983 (upper limit). Cohen coefficient was calculated at 0.05., Conclusion: The existing evidence is that antioxidants can reduce systemic and local oxidative stress and can reduce damage as the main agent involved in autoimmune diseases such as rheumatoid arthritis.

The aim of this study was to evaluate the efficacy of endoscopic polypectomy as a therapeutic treatment for malignant alteration of colorectal polyps. In a 5-year research, 89 patients were included, who were tested and treated at the University Clinical Center Kragujevac, Kragujevac, Serbia, with the confirmed presence of malignant alteration polyps of the colon by colonoscopy, which were removed using the method of endoscopic polypectomy and confirmed by the histopathological examination of the entire polyp. After that, the same group of patients was monitored endoscopically within a certain period, controlling polypectomy locations and the occurrence of a possible remnant of the polyp, in the period of up to 2 years of polypectomy. We observed that, with an increasing size of polyps, there is also an increase in the percentage of the complexity of endoscopic resection and the appearance of remnant with histological characteristics of the invasive cancer. The highest percentage of incomplete endoscopic resection and the appearance of remnant with histological characteristics of the invasive cancer were shown at malignant altered polyps in the field of tubulovillous adenoma. Eighteen patients in total underwent the surgical intervention. In conclusion, our data support the high efficacy of endoscopic polypectomy for the removal of the altered malignant polyp., Competing Interests: Conflict of interest: The authors declare that there is no conflict of interest regarding the publication of this article., (© 2023 the author(s), published by De Gruyter.)

Background: This study explored the effects of hyperbaric oxygen therapy (HBOT) on the cardiovascular system and oxidative stress in streptozotocin-induced diabetic rats. Wistar albino rats were divided into four groups: DM group (diabetic rats), DM+HBOT group (diabetic rats exposed to HBOT for 1 h daily, five days a week, at 2.8 atmosphere absolute (ATA) with 100% oxygen for two weeks), DM+INS group (diabetic rats treated with neutral protamine hagedorn (NPH) insulin at a dosage of 3-5 U/day), and DM+HBOT+INS group (diabetic rats treated with both NPH insulin and HBOT for two weeks)., Methods: Evaluations included glycemic control, oxidative stress parameters, and cardiac function measurements., Results: NPH insulin treatment reduced blood glucose levels, although normoglycemia was not achieved. The DM+HBOT+INS group demonstrated the lowest pro-oxidative marker levels. NPH insulin treatment improved cardiac function, and combination therapy effectively restored cardiac function in diabetic animals., Conclusions: NPH insulin treatment reduced hyperglycemia and improved cardiac function in diabetic rats. The combined approach of NPH insulin and HBOT resulted in decreased pro-oxidative markers. These findings provide valuable insights for managing cardiovascular complications and oxidative stress in diabetes.

The study's objective was to ascertain the results of sub-chronic therapy of various diuretics on the ischemia/reperfusion dysfunction of the heart in hypertensive rats by a global ischemia in an isolated rat heart model. The research included 40 spontaneously hypertensive male rats (Wistar Kyoto strain, body mass 250 ± 30 g, 8 weeks old) grouped into four groups. The animals were treated for 4 weeks with 10 mg/kg of hydrochlorothiazide, indapamide, or spironolactone per os. After a period of sub-chronic treatment, we analyzed hemodynamic measurements, echocardiography, and myocardial function according to the Langendorff retrograde perfusion method. The hearts were subjected to 20 min of global ischemia and then reperfused for 30 min (I20:R30). Cardiovascular parameters that depict the left ventricle functions were continuously monitored, while flowmetry was used to determine coronary flow values. Markers of oxidative stress were estimated from coronary venous effluent using spectrophotometry. All three examined diuretics (hydrochlorothiazide, spironolactone, indapamide) lowered the production of the majority of the detected prooxidants, reducing myocardial oxidative damage. The cardiological examination of heart function in vivo demonstrated that treatment with indapamide and spironolactone mitigates left ventricular hypertrophy but without significant lowering of blood pressure or increment in ejection fraction. Additionally, monitoring of cardiac function ex vivo indicated the cardiodepressant effect of spironolactone in spontaneously hypertensive rats., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

(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.

Background: Three selective and most used inhibitors of PDE-5-sildenafil, vardenafil and tadalafil- have been successfully used for the treatment of erectile dysfunction. Erectile dysfunction and cardiovascular diseases might be considered as two dissimilar clinical signs of the identical systemic disease. PDE-5 inhibitors can through different models and mechanisms induce vasodilation, decrease apoptosis and cell proliferation, and they are widely present in various tissues that make them promising targets in a range of cardiovascular diseases., Methods: PubMed was explored to identify papers published from 1990-2019, presenting data for the most used PDE-5 inhibitors (sildenafil, tadalafil or vardenafil) in treatment of cardiovascular diseases., Results: This article analyses the therapeutic potentials of PDE-5 inhibitors in cardiovascular diseases and discusses mechanisms, possible risks and limitations. Comparable to earlier studies, newer studies suggest cardioprotective effects of PDE-5 inhibitors, which include different models and mechanisms and do not indicate an increased rate of significant cardiovascular adverse reactions. Dissimilarity in the pharmacokinetics and pharmacodynamics of PDE-5 inhibitors are significant to their risk- benefit profile and clinical use. Some of the studies suggesting infarct size reduction after PDE-5 inhibition described the especially close dose-effect relation, other studies dosage adaptation in drug- drug interactions., Conclusion: PDE-5 inhibitors indicate the encouraging useful effects by ischemia/reperfusion injury, myocar-dial infarction, cardiac hypertrophy, cardiomyopathy and systolic and diastolic congestive heart failure. Therefore, this and similar reviews can help for additional clinical targeting in the therapy of cardiovascular diseases., Competing Interests: Conflict of interest The authors declare that there is no conflict of interest., (Copyright © 2023 Corbic et al. Published by Tehran University of Medical Sciences.)

Background and objectives : Taking into consideration the confirmed role of oxidative stress in ischemia/reperfusion injury and the insufficiency in knowledge regarding the phosphodiesterase 5 (PDE5)-mediated effects on the cardiovascular system, the aim of our study was to investigate the influence of two PDE5 inhibitors, tadalafil and vardenafil, with or without the addition of N(G)-nitro-L-arginine methyl ester (L-NAME), on oxidative stress markers, coronary flow and left ventricular function, both ex vivo and in vivo. Methods : This study included 74 male Wistar albino rats divided into two groups. In the first, 24 male Wistar rats were orally treated with tadalafil or vardenafil for four weeks in order to perform in vivo experiments. In the second, the hearts of 50 male Wistar albino were excised and perfused according to the Langendorff technique in order to perform ex vivo experiments. The hearts were perfused with tadalafil (10, 20, 50 and 200 nM), vardenafil (10, 20, 50 and 200 nM) and a combination of tadalafil/vardenafil and L-NAME (30 μM). The CF and oxidative stress markers, including nitrite bioaviability (NO 2 - ), superoxide anion radical (O 2 - ), and the index of lipid peroxidation, were measured in coronary effluent. Results : The L-arginin/NO system acts as the mediator in the tadalafil-induced effects on the cardiovascular system, while it seems that the vardenafil-induced increase in CF was not primarily induced by the NO system. Although tadalafil induced an increase in O 2 - in the two lowest doses, the general effects of both of the applied PDE5 inhibitors on oxidative stress were not significant. The ejection function was above 50% in both groups. Conclusions : Our results showed that both tadalafil and vardenafil improved the coronary perfusion of the myocardium and LV function by increasing the EF.

The main goal of this study was to investigate the cardioprotective properties in terms of effects on cardiodynamics of perfluorocarbon emulsion (PFE) in ex vivo-induced ischemia-reperfusion injury of an isolated rat heart. The first part of the study aimed to determine the dose of 10% perfluoroemulsion (PFE) that would show the best cardioprotective effect in rats on ex vivo-induced ischemia-reperfusion injury of an isolated rat heart. Depending on whether the animals received saline or PFE, the animals were divided into a control or experimental group. They were also grouped depending on the applied dose (8, 12, 16 ml/kg body weight) of saline or PFE. We observed the huge changes in almost all parameters in the PFE groups in comparison with IR group without any pre-treatment. Calculated in percent, dp/dt max was the most changed parameter in group treated with 8 mg/kg, while the dp/dt min, SLVP, DLVP, HR, and CF were the most changed in group treated with 16 mg/kg 10 h before ischemia. The effects of 10% PFE are more pronounced if there is a longer period of time from application to ischemia, i.e., immediate application of PFE before ischemia (1 h) gave the weakest effects on the change of cardiodynamics of isolated rat heart. Therefore, the future of PFE use is in new indications and application methods, and PFE can also be referred to as antihypoxic and antiischemic blood substitute with mild membranotropic effects., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The main objective of this study was to evaluate the evolution of physical and daily routine, dietary habits, and mental and social health in individuals with recent COVID-19 infection., Methods: A qualitative prospective cross-sectional study was conducted from 01 October 2021 to 01 March 2022, which included 80 working-age adults from the territory of Central Serbia who had PCR-confirmed SARS-CoV-2 infection in the previous six months. Two structured pre-coded closed-ended questionnaires were submitted to the participants: a questionnaire about post-COVID-19 status (pCOVq) and a shortened version of the World Health Organization's Quality of Life Scale (WHOQOL-BREF)., Results: The presence of the COVID-19 disease in the previous period of 6 months among the working-age participants significantly affected the duration of aerobic, anaerobic, and high-intensity physical activities, but also the possibility of performing certain activities such as walking, which represents basic aerobic activity and a measure of general health among middle-aged participants. In the majority of cases (78%), in the post-COVID-19 period, participants indicated a decline in educational and productive activities., Conclusion: Post-COVID status in working-aged participants consists of reduced physical activity, lower quality of life, and similar nutritional habits. Health policies should be more focused on these findings.

d- chiro -Inositol (DCI), an isomer of inositol, possesses antioxidative and endothelial protective properties. Possibly due to a deficiency of insulin mediators, polycystic ovary syndrome (PCOS) is often associated with insulin resistance (IR) and hyperinsulinemia, likely responsible for an elevated production of reactive oxygen species. We investigated oxidative-related alterations of inositol in the blood of women with PCOS before and after treatment with DCI. A total of 38 normal-weight PCOS women were investigated before and after DCI administration (500 mg/day for 12 weeks; n  = 38) by evaluating serum testosterone, serum androstenedione, fasting serum insulin, fasting serum glucose, and parameters of IR. From the blood, we determined biomarkers of oxidative stress: superoxide anion radicals, hydrogen peroxide, nitric oxide, and the index of lipid peroxidation. The activity of catalase and superoxide dismutase and the reduced glutathione (GSH) content in the hemolysate were also assessed. Data showed that PCOS patients' plasma underwent oxidative stress, as indicated by the higher level of prooxidants and reduced cytosolic GSH content. DCI treatment significantly improved the metabolic parameters. Also, serum values of testosterone were reduced. In conclusion, PCOS patients suffer from a systemic oxidative stress that induces endothelial dysfunction. Treatment with DCI is effective in reducing hormonal, metabolic, and oxidative abnormalities in PCOS patients by improving IR.

Background: The purpose of this study was to compare home and office BP in the adjustment of antihypertensive treatment. Methods: This study was an open, prospective, noninterventional, multicenter clinical trial that occurred between July 2019 and February 2020, in 34 cities in the territory of the Republic of Serbia, which monitored 1581 participants for 6 months. Depending on the used blood pressure monitoring method used, all patients were divided into control (office BP monitoring) and experimental (home BP telemonitoring) groups. We collected anamnestic data and data about systolic blood pressure (SP), in mmHg, diastolic blood pressure (DP), in mmHg, and heart rate (HR), in beats/minute, from all patients. Results: SP values were significantly different at baseline, and at the second, third, and fourth visits between the two tested groups. Home and office BP decreased significantly (p < 0.000) during the 6-month follow-up. We observed a statistically significant influence of the presence of diabetes mellitus and dyslipidemia on the dynamics of differences between SP monitoring values. Conclusions: Our study suggests that novel technologies in BP monitoring can be excellent alternatives for BP assessment in hypertensive patients with other cardiovascular risk factors such as diabetes and dyslipidemia.

This study was aimed to examine the influence of acclimatization on the change of concentration of stress hormones in men's serum exposed to heat stress during physical training. The study included a total of 40 men, aged 19-21 years, divided randomly into four groups: CTRL group: control, exposed to the Exercise Tolerance Testing in comfortable conditions; O group: exposed to Exercise Tolerance Testing in a warm environment; P group: exposed to passive acclimation to heat for 10 days, followed by Exercise Tolerance Testing in a warm environment; A group: exposed to active acclimation to heat for 10 days, followed by Exercise Tolerance Testing in a warm environment. All participants were tested for thermoregulation and acclimatization, skin and tympanic temperature, heart rate (HR), hormonal status and sweating. The mean skin temperature was the lowest in the control group of subjects exposed to physical exertion under comfortable conditions, and at each point of measurement it was statistically significantly different from that of the other study groups (p < 0.001). Sweating intensity was statistically significantly the lowest in the CTRL group (0.32 ± 0.04 l/m 2 /h; p < 0.001), compared to all other groups. Cortisol was significantly altered in O group (632.2 ± 92.3; 467.2 ± 89.7), testosterone levels were significantly altered in P (19.2 ± 9.3; 16.4 ± 7.3) and in A groups (22.1 ± 12.4; 14.9 ± 9.9), while prolactin was changed in O (392.1 ± 51.3; 181.4 ± 42.3), P (595.1 ± 191.1; 191.2 ± 52.5), and A group (407.4 ± 189.3; 173.4 ± 43.9) after the experimental period. The impact of acclimatization on hormonal indicators emphasizes its importance in the response of the endocrine system of soldiers to perform military activities in warm climates., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This research was a prospective, cross-sectional observational study of 128 health workers in the central part of the Republic of Serbia. The study surveyed health workers (physicians, pharmacists and nurses) who worked during peaks of the COVID-19 pandemic in the Republic of Serbia in June and November 2020. The Maslach Burnout Survey for Medical Personnel addresses three scales: (a) emotional exhaustion (EE) measures feelings of being emotionally overextended and exhausted by one's work; (b) depersonalization (DP) measures an unfeeling and impersonal response toward recipients of one's service, care treatment, or instruction; and (c) personal accomplishment (PA) measures feelings of competence and successful achievement in one's work. Linear regression and the chi-square test were used to test a relationship between the input variables (x) and the single output variable (y). We can conclude that most health workers had a high degree of emotional exhaustion, but also a low degree of depersonalization and a high degree of sense of personal achievement. Nurses and physicians had similar answers on the pandemic during their work, but pharmacists had different answers.

This review aimed to provide a summary on the traditional uses, phytochemistry, and pharmacological activities in the cardiovascular system and cardiotoxicity of Melissa officinalis (MO), with the special emphasis on the protective mechanisms in different cardiovascular pathologies. MO is a perennial aromatic herb commonly known as lemon balm, honey balm, or bee balm, which belongs to Lamiaceae family. Active components are mainly located in the leaves or essential oil and include volatile compounds, terpenoid (monoterpenes, sesquiterpenes, triterpenes), and polyphenolic compounds [rosmarinic acid (RA), caffeic acid, protocatechuic acid, quercitrin, rhamnocitrin, luteolin]. For centuries, MO has been traditionally used as a remedy for memory, cognition, anxiety, depression, and heart palpitations. Up until now, several beneficial cardiovascular effects of MO, in the form of extracts (aqueous, alcoholic, and hydroalcoholic), essential oil, and isolated compounds, have been confirmed in preclinical animal studies, such as antiarrhythmogenic, negative chronotropic and dromotropic, hypotensive, vasorelaxant, and infarct size-reducing effects. Nonetheless, MO effects on heart palpitations are the only ones confirmed in human subjects. The main mechanisms proposed for the cardiovascular effects of this plant are antioxidant free radical-scavenging properties of MO polyphenols, amelioration of oxidative stress, anti-inflammatory effects, activation of M2 and antagonism of β1 receptors in the heart, blockage of voltage-dependent Ca 2+ channels, stimulation of endothelial nitric oxide synthesis, prevention of fibrotic changes, etc. Additionally, the main active ingredient of MO-RA, per se , has shown substantial cardiovascular effects. Because of the vastness of encouraging data from animal studies, this plant, as well as the main ingredient RA, should be considered and investigated further as a tool for cardioprotection and adjuvant therapy in patients suffering from cardiovascular diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Draginic, Jakovljevic, Andjic, Jeremic, Srejovic, Rankovic, Tomovic, Nikolic Turnic, Svistunov, Bolevich and Milosavljevic.)

The aim of our study was to investigate the influence of 12 weeks of consumption of chokeberry extract on redox status, body composition, lipid profile, and biochemical parameters in active handball players. The study included 16 handball players aged 16-24 years (20.26 ± 2.86 years). Every morning before training, players received 30 mL of liquid chokeberry extract for 12 weeks during the regular competition season. The research consisted of morphofunctional and biochemical testing, which was performed at three points (at the beginning of the study and at 6 and 12 weeks after extract consumption). After the chokeberry extract treatment, we observed significant changes in three main aspects. The 12 week supplementation with chokeberry extract decreased the levels of prooxidants (TBARS and nitrites) and increased catalase activity. Analyzing the dynamic of body composition showed a decrease in body fat (9.4 ± 0.5 vs. 7.3 ± 0.6 kg) as well as its percent in a body (11.4 ± 0.4% vs. 8.8 ± 0.4%). On the other hand, the analysis showed an increase of high-density lipoprotein (1.3 ± 0.3 vs. 1.6 ± 0.2 mmol/L) and hemoglobin (144.4 ± 11.7 vs. 151.7 ± 9.9 g/L) after 6 weeks of treatment. At the same time, a decrease in leukocytes (7.2 × 10 9  ± 2.8 vs. 6.5 ± 1.2 × 10 9 /L) and an increase in red blood cells count (4.9 ± 0.4 × 10 9 vs. 5.5 ± 0.5 × 10 9 /L) were observed. Overall, these results emphatically show that the use of chokeberry extract dietary supplement induced a wide range of beneficial effects in the examined group of athletes.

The present study aimed to estimate the effects of high-protein diet (PD)-isolated whey protein and omega-3 fatty acids-docosahexaenoic and eicosapentaenoic acid on oxidative parameters of rats treated with Olanzapine (OLZ). Experiments were carried out on 8-week-old Wistar albino male rats (n = 64) weighing 200 ± 20 g. By dietary and pharmacological treatment, all animals were divided into 8 groups: 1. CTRL group; 2. CTRL + OLZ group; 3. CTRL + FA group; 4. CTRL + OLZ + FA group; 5. PD group; 6. PD + OLZ group; 7. PD + FA group; 8. PD + OLZ + FA group. After 6 weeks of pharmacological/diet treatment, all animals were sacrificed to collect blood samples and determine the biomarkers of oxidative stress. The following oxidative stress markers were measured spectrophotometrically: superoxide anion radical (O 2 - ), hydrogen peroxide (H 2 O 2 ), nitric oxide (NO - ), index of lipid peroxidation measured as TBARS, reduced glutathione, catalase and superoxide dismutase. The study has shown that Olanzapine treatment was associated with increased release of pro-oxidants and diminished activity of anti-oxidant markers. Additional supplementation with PD and FA succeeded in abolishing the negative influence in most of the measured parameters. However, these beneficial impacts were stronger in the case of their separate application, which could be the practical and clinical importance of these results.

Previous studies have suggested that thiamine has antioxidant activity and could decrease the production of ROS in various disorders. Our study focused on the effect of thiamine hydrochloride in the reversal of DOX-induced cardiotoxicity and compared it with the reversal in the absence of thiamine pre-treatment. Rats were divided into groups as follows: (a) thiamine + doxorubicin (TIA + DOX), (b) doxorubicin (DOX) and c) healthy (CTRL) groups. For 7 days, thiamine hydrochloride was administered at a dose of 25 mg/kg per day intraperitoneally, while a single dose of 15 mg/kg doxorubicin was injected into all groups except the CTRL group. We measured the following parameters: maximum rate of left ventricular development (dp/dt max), minimum rate of left ventricular development (dp/dt min), systolic left ventricular development (SLVP), diastolic left ventricular development (DLVP), heart rate (HR) and coronary flow (CF), pro-oxidative and antioxidative markers, cardiac activity, and histopathological evaluation. In our study, cardiac contractility was significantly altered after DOX treatment and diminished by thiamine pre-treatment. Additionally, pro-oxidant parameters were significantly increased in the DOX group. The levels of O 2 - , H 2 and TBARS were significantly increased in the DOX group and decreased in the DOX + T group compared to those in the DOX group. Morphometric analyses showed moderately expressed interstitial fibrosis and degenerately modified cardiac muscle fibres, with signs of interfibrillary congestion, vacuolar degeneration and myocytolysis in the DOX group as visualized by H&E and Masson's Trichrome staining. Pre-treatment of thiamine hydrochloride before doxorubicin administration could decrease oxidative stress production, increase myocardial contractility and enhance the antioxidant defence system.2 and TBARS were significantly increased in the DOX group and decreased in the DOX + T group compared to those in the DOX group. Morphometric analyses showed moderately expressed interstitial fibrosis and degenerately modified cardiac muscle fibres, with signs of interfibrillary congestion, vacuolar degeneration and myocytolysis in the DOX group as visualized by H&E and Masson's Trichrome staining. Pre-treatment of thiamine hydrochloride before doxorubicin administration could decrease oxidative stress production, increase myocardial contractility and enhance the antioxidant defence system.

This study investigated different dietary strategies, high-fat (HFd), or standard diet (Sd) alone or in combination with standardized Aronia melanocarpa extract (SAE), as a polyphenol-rich diet, and their effects on lipids and fatty acids (FA) in rats with metabolic syndrome (MetS). Wistar albino rats were randomly divided into two groups: healthy and rats with MetS, and then depending on dietary patterns on six groups: healthy rats fed with Sd, healthy rats fed with Sd and SAE, rats with MetS fed with HFd, rats with MetS fed with HFd and SAE, rats with MetS fed with Sd, and rats with MetS fed with Sd and SAE. 4 weeks later, after an overnight fast (12-14 h), blood for determination of total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), index of lipid peroxidation (measured as TBARS), and FA was collected. Increased FA and lipid concentration found in MetS rats were reduced when changing dietary habits from HFd to Sd with or without SAE consumption. Consumption of SAE slightly affects the FA profiles, mostly palmitoleic acid in healthy rats and PUFA in MetS + HFd rats. Nevertheless, in a high-fat diet, SAE supplementation significantly decreases n-6/n-3 ratio, thereby decreasing systemic inflammation. Further researches are warranted to confirm these effects in humans.

This study aimed to assess the impact of high-intensity interval training (HIIT) vs. moderate-intensity continuous training (MIT) on cardiodynamic parameters in isolated rat heart. Wistar albino rats were randomly assigned to groups according to running protocol: sedentary control, MIT, and HIIT; spontaneous hypertensive rat (SHR) sedentary control, SHR + MIT, and SHR + HIIT. HIIT groups performed the running in 5 sprints × 45-55 m/min for 30-90 s, with 2 min of rest after each sprint, while MIT groups performed the running of 10-15 m/min for 1 h with 3 min of rest every 100 m; both protocols were implemented 5 days/week over 4 weeks with 1 week of adaptation before protocols started. Isolated rat hearts were perfused according to Langendorff technique at gradually increased coronary perfusion pressures (40-120 cmH 2 O). Using a sensor placed in the left ventricle, we registered maximum and minimum rate of pressure development in the left ventricle, systolic and diastolic left ventricular pressure, and heart rate. Coronary flow was measured flowmetrically. MIT was connected with cardiac depression in normotensive conditions, while HIIT leads to cardiac depression in hypertensive rats. HIIT induced more significant increase of contractile and relaxation parameters of the isolated rat heart, especially in hypertensive animals.

This study was aimed to assess the impact of aerobic and anaerobic type of exercise on blood pressure and redox status in normotensive and hypertensive rats. After 1 week of preconditioning feeding and 1 week of preconditioning running regimen, Wistar albino rats (n = 72; bw: 270 ± 50 g) were randomly assigned to three groups according to running protocol (high-intensity interval training (HIIT) or moderate-intensity training (MIT)): sedentary control, MIT, HIIT; spontaneous hypertensive sedentary control (SHR), SHR + MIT and SHR + HIIT. Blood pressure (BP) measurement was performed by a tail-cuff noninvasive method BP system. After 48 h of rest following the final training, the rats were fasted for 24 h and sacrificed under ketamine/xylazine anesthesia and blood samples were collected. The level of the next prooxidants were measured: superoxide anion radical (O 2 - ); hydrogen peroxide (H 2 O 2 ); nitrite level (NO 2 - ) and index of lipid peroxidation (thiobarbituric acid reactive substances), and the activity of antioxidative enzymes: reduced glutathione (GSH) superoxide dismutase (SOD) and catalase (CAT) activity. After the last week of running, HIIT strongly affected SP, DP, and HR in SHR rats compared to other hypertensive rats, as well as after MIT in normotensive conditions. We have found that HIIT training protocol induced a higher increase of O 2 - and H 2 O 2 as compared to MIT. Findings of the present study pointed out that contrary to normotensive conditions, in hypertensive conditions both training regimes reduced the BP levels, which was more prominent in case of HIIT. In addition, MIT seems to be connected with milder disturbance of pro-oxidant production and better antioxidant response.

The aim of this study was to examine and compare the effects of the acute administration of verapamil or amlodipine as representatives of the calcium channel blockers or nicorandil as a representative of the mitochondrial ATP-dependent potassium (K ATP ) channel opener to cardiac contractility, coronary flow, and oxidative stress markers on ischemia/reperfusion injury in the isolated rat heart. The hearts of adult male Wistar albino rats (n = 60 total, 12 per group) were divided into five groups, two controls (preconditioning with Krebs-Henseleit solution) and three experimental depending on acute administrated pharmacological agents (0,63 µmol/L of verapamil, 0,1 µmol/L of amlodipine, and 200 µmol/L of nicorandil). After stabilization and 5 min of preconditioning in experimental groups, hearts from I/R control and all experimental groups underwent global ischemia (20 min) and reperfusion (30 min). Hearts from sham group were continuously followed for 50 min, after stabilization period. Cardiodynamic parameters and coronary flow were recorded at the end of stabilization (S), at the last minute of pharmacological preconditioning (P) and at intervals of 5 min after global ischemia, during reperfusion, or in case of sham group during 20-50 min after stabilization. At the same intervals, we collected coronary venous effluent from which we spectrophotometrically measured the parameters of oxidative stress: the index of lipid peroxidation, superoxide anion radical, hydrogen peroxide, and nitrite. In summary, our findings clearly indicate that the blocking of the calcium channel or the activation of K ATP may mediate the protective effect of myocardial preconditioning. The ex vivo results showed that all examined drugs after ischemia and reperfusion have beneficial cardioprotective properties associated with lower values of major pro-oxidative molecules. Obtained effects seem to be the most convincible in case of nicorandil.

The aim of our study was to examine the effects of different dietary strategies, high-fat (HFd) or standard diet (Sd) alone or in combination with standardized oral supplementation (0.45 mL/kg/day) of Aronia melanocarpa extract (SAE) in rats with metabolic syndrome (MetS). SAE is an official product of pharmaceutical company Pharmanova (Belgrade, Serbia); however, the procedure for extraction was done by EU-Chem company (Belgrade, Serbia). Rats were divided randomly into six groups: control with Sd, control with Sd and SAE, MetS with HFd, MetS with HFd and SAE, MetS with Sd and MetS with Sd and SAE during 4 weeks. At the end of the 4-week protocol, cardiac function and liver morphology were assessed, while in the blood samples glucose, insulin, iron levels and systemic redox state were determined. Our results demonstrated that SAE had the ability to lower blood pressure and exert benefits on in vivo and ex vivo heart function. Moreover, SAE improved glucose tolerance, attenuated pathological liver alterations and oxidative stress present in MetS. Obtained beneficial effects of SAE were more prominent in combination with changing dietary habits. Promising potential of SAE supplementation alone or in combination with different dietary protocols in triggering cardioprotection should be further examined in future.

This research is designed to test the hypothesis that elevated homocysteine (Hcy) levels in vivo, caused by a deficit in vitamin B complex, promote changes in cardiac function and redox status that lead to heart failure. In order to conduct the study, we used adult male Wistar albino rats (n = 30; 4 weeks old; 100 ± 15 g body weight). Hyperhomocysteinaemia (HHcy) in these animals was achieved by dietary manipulation. For 4 weeks, the animals were fed with a standard rodent chow (control, CF), a diet enriched in methionine with no deficiency in B vitamins (i.e., folic acid, B6 and B12) (HMNV) or a diet enriched in methionine and deficient in B vitamins (HMLV). After 28 days of dietary manipulation, all animals were killed. The rat hearts were isolated and retrogradely perfused according to the Langendorff technique at a gradually increasing perfusion pressure. We found a negative correlation between elevated serum Hcy and total body and heart weight. The maximum rate of left ventricular pressure development was significantly increased in the HMNV group compared with in the other groups. Systolic left ventricular pressure was significantly changed in all groups. HHcy induces remodelling of the cardiac tissues, as moderate HHcy is associated with more prominent interstitial and perivascular fibrosis. Our results suggest that a high methionine diet without vitamin B complex causes profound negative effects associated with HHcy., (© 2018 John Wiley & Sons Australia, Ltd.)