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Abstract: Cardiometabolic diseases, such as type 2 diabetes mellitus (DM) and cardiovascular disease (CVD), are a great health concern. The strategies aimed to increase awareness and prevention, in conjunction with timely diagnosis and optimal management of these conditions, represent the main lines of action to improve life expectancy and quality. In recent years, the introduction of innovative therapies for the treatment of DM and CVD has provided new hope for high-risk patients. Yet, the implementation of preventive measures in achieving cardiometabolic health is far from successful and requires further improvement. The development of cardiometabolic disorders is a complex, multifactorial process involving several metabolic pathways as well as genetic and environmental factors. Decreasing cumulative exposure during the entire life course and timely recognition and targeting of potential risk-enhancing factors could pave the way toward more successful prevention of cardiometabolic disorders. Nowadays, in the era of “omics” technologies, it is possible to identify novel biomarkers and therapeutic targets, which offers the possibility to apply an individualized approach for each patient. This review will discuss potential applications of genomic, transcriptomic, epigenetic and metabolomic biomarkers for the personalized prevention of cardiometabolic diseases.

Background: The pandemic of severe acute respiratory syndrome by coronavirus 2 (SARS-CoV-2) is a multi-system disease caused by a diffuse systemic process involving a complex interaction of the inflammatory, immunological and coagulative cascades. This study aims to identify the most effective biomarkers to predict a poor outcome in the intensive care unit patients with severe COVID-19 disease. Methods: A single-centre retrospective observational study enrolled 69 deceased and 20 recovered patients treated in the Intensive Care Unit of the General Hospital Gradiska in the period from March 1, 2021. until April 1, 2022. We evaluated the leukocytes, lymphocytes, neutrophils, platelets, hemoglobin, neutrophil lymphocyte ratio (NPR), platelet lymphocyte ratio (PLR), systemic immune-inflammation index (SII). In addition, we evaluated the IL-6, ferritin, CRP, D-dimer, magnesium, bilirubin and lactate dehydrogenase. Results: Between deceased and recovered patients on admission to the ICU, there was a significant difference between the following parameters: leukocytes x109/L 11.5 (8.86-14.75) vs 9.4 (5.9-11.9), p =0.026; neutrophils x109/L 10.15 (7.81-12.74) vs 8.60 (4.8-10.3) p=0.022; NLR 15.01 (10.60-24.33) vs 9.45 (5.10-14.90) p=0.02; SII 3712 (2240-6543) vs 1949 (993-3720) p=0.003. The magnesium level increased significantly over time in the group of patients who died, while the hemoglobin level and platelet count decreased. ROC analysis showed the following AUC values: leukocytes 0.774; neutrophils 0.781; NLR 0.786; SII 0.776; D-dimer 0.741and bilrubine 0.713. Conclusions: In this retrospective study leukocytes, neutrophils, NLR, SII, D-dimer, bilirubin determined at hospital admission had a high value in predicting death among patients with severe COVID-19.

The purpose of this study was to examine demographic and baseline characteristics of patients with vascular injuriesof extremities and to define the most relevant factors which influenced an early outcome, as well as limb salvage after the management of vascular trauma.This study used the database that included 395 patients with peripheral arterial injuries, who were treated in the tertiary vascular university center in the period between 2005-2020. Exclusion criteria were isolated thoracic, abdominal and neck injuries as well as iatrogenic injuries and injuries of intravenous addicts. Univariate binary logistic regression analysis and multiple logistic regression were used to determine risk factors for lomb loss (after vascular reconstruction) or mortality. Decision to perform primary amputation (without vascular reconstruction) was based on surgeons' preference and experience.Out of 395 vascular injuries treated in the period 2005-2020, 210 (53.2%) presented with non-iatrogenic vascular injuries of upper and lower extremities were analyzed. According to the univariate regression analysis, hemorrhage as the main clinical manifestation on admission (p=0.035) and early reintervention (p=0.048) increased, while an early patency of repaired artery (0.010) significantly decreased a 30-day amputation rate. Multivariate logistic regression analysis of these three variables showed that only early patency of repaired artery significantly decreased the early amputation rate (p=0.009).Based on presented experience, the patency of vascular reconstruction plays a crucial role in limb salvage in patients with non-iatrogenic peripheral vascular injuries. All factors that might influence the patency should be in focus of improvement.

Translations of instruments for measuring quality of life developed in certain, mostly more developed, parts of the world usually do not cover regionally specific aspects of health-related quality of life, even after transcultural validation. The aim of this study was to develop and validate a reliable questionnaire in Serbian, Croatian, Bosnian, and Montenegrin languages suitable for measuring health-related quality of life in adults.The study was of a cross-sectional type, assessing the reliability and validity of a newly developed questionnaire for measuring health-related quality of life (HRQoL) in adults residing in western Balkan states (WB-HRQoL). It was conducted on a sample of 489 adults from Serbia, Croatia, BosniaHerzegovina, and Montenegro, with a mean age of 52.2±14.4 years and a male/female ratio of 195/294 (39.9%/60.1%).The definitive version of the WB-HRQoL scale with 19 items showed very good reliability, with Cronbach's alpha 0.905. The scale was temporally stable, and satisfactory results were obtained for divergent and convergent validity tests. Exploratory factorial analysis brought to the surface four domains of health-related quality of life, namely the physical, psychical, social, and environmental.The WB-HRQoL scale is a reliable and valid generic instrument for measuring HRQoL that takes into account the cultural specifics of the western Balkan region.Prenos instrumentov za merjenje kakovosti življenja, razvitih v nekaterih, večinoma razvitejših delih sveta, zahteva transkulturno validacijo. Kljub temu tovrstni instrumenti običajno ne zajemajo regionalno specifičnih vidikov kakovosti življenja, povezanih z zdravjem. Namen študije je bil razviti in potrditi zanesljiv vprašalnik v srbskem, hrvaškem, bosansko-hrvaško-srbskem in črnogorskem jeziku, primeren za merjenje kakovosti življenja, povezanega z zdravjem odraslih.V presečni študiji smo ocenili zanesljivost in veljavnost novo razvitega vprašalnika za merjenje kakovosti življenja, povezanega z zdravjem (HRQoL) pri odraslih, ki prebivajo v državah zahodnega Balkana (WB-HRQoL). V študijo smo vključili 489 odraslih iz Srbije, Hrvaške, Bosne in Hercegovine ter Črne gore s povprečno starostjo 52,2 ± 14,4 let in razmerjem med moškimi in ženskami 195 : 294 (39,9 : 60,1 %).Dokončna različica lestvice WB-HRQoL z 19 elementi je pokazala zelo dobro zanesljivost (koeficient Cronbach alfa 0,905). Lestvica je bila stabilna, tako za divergentne kot konvergentne teste veljavnosti smo pridobili zadovoljive rezultate. Raziskovalna faktorska analiza je pokazala štiri področja zdravstvene kakovosti, povezane z zdravjem: fizično, psihično, socialno in okoljsko.Lestvica WB-HRQoL je zanesljiv in veljaven generični instrument za merjenje HRQoL, ki upošteva kulturne posebnosti regije zahodnega Balkana.

Objective. Recent studies have shown that the red cell distribution width- (RDW-) to-platelet (PLT) count ratio (i.e., RPR) and the mean platelet volume (MPV)/PLT ratio (i.e. MPR) are more sensitive markers of atherosclerosis-connected risk than RDW and PLT alone. The present study is aimed at investigating the oxidative stress status and these two new markers of platelet activation in two different heart surgery modalities: cardiopulmonary bypass (CPB) and off-pump coronary artery bypass (OPCAB). We also aimed to test the possible relationship between RPR and MPR, respectively, and the severity and complexity of atherosclerotic plaque, measured as Syntax Score. Patients and Methods. A total of 107 patients encompassed this prospective study (i.e., 60 patients in CPB group and 47 patients in OPCAB). Blood samples were drawn at several time intervals: before skin incision (t1), immediately after intervention (t2), 6 h (t3), 24 h (t4), 48 h (t5), and 96 h after cessation of the operation (t6). Results. The values of RPR and MPR were similar in CPB and OPCAB before surgery and started to rise in t2 (i.e., immediately after the intervention). This increase lasted to t5 (i.e., 48 hours after the intervention), when it became the highest. After that, both markers started to regress about the 96th hour after the beginning of surgery. Nominal values of both indices were higher in CPB than in OPCAB in all study points after the surgery. Furthermore, a significantly higher level of antioxidative parameters (i.e., total sulfhydryl groups and paraoxonase 1) in the OPCAB group compared to the CPB group was noted at t5 study point (i.e., 48 hours after the surgery), whereas no significant difference was noted in prooxidant levels (i.e., lipid hydroperoxides and advanced oxidation protein products) between these groups at this study point. MPR and RPR correlated positively with Syntax Score at several study points after the surgery completion. Syntax Score, MPR, and RPR showed good clinical accuracy in surgery-related complication prediction (( AUC = 0.736 ), 95th CI (0.616-0.856), P = 0.003 )). Conclusion. When combined, MPV, RDW, and platelet count, such as MPR and RPR, could be good predictors of coronary artery disease status, regarding the aspect of joint inflammation, oxidative stress, and thrombosis.

IntroductionTelomeres are protective chromosomal ends. Short telomeres are a proven biomarker of biological aging. We aimed to find an association of telomere length and telomerase activity in circulating leukocytes and thromboaspirates of patients with acute myocardial infarction. Furthermore, association of the telomere-telomerase system with oxidative stress markers (as common risk factors for coronary artery disease (CAD)) was tested.Material and methodsPatients were selected from the patients admitted to the intensive care unit with acute myocardial infarction with ST-segment elevation (STEMI), with the following inclusion criteria – STEMI patients between 18 and 80 years old of both genders and candidates for primary percutaneous coronary intervention, with infarction pain present for a maximum of 12 h. In all the patients leukocyte telomere length, telomerase activity and scores related to oxidative-stress status (Protective, Damage and OXY) were evaluated.ResultsPatients were divided into different groups: with stable angina pectoris (AP) (n = 22), acute myocardial infarction with: STEMI (n = 93), non-obstructive coronary arteries (MINOCA) (n = 7), blood vessel rupture (n = 6) at three time points, and compared to the group of 84 healthy subjects. Telomerase activity was significantly higher in all CAD sub-groups compared to the control group (AP = 0.373 (0.355–0.386), STEMI = 0.375 (0.349–0.395), MINOCA = 0.391 (0.366–0.401), blood vessel rupture = 0.360 (0.352–0.385) vs. CG = 0.069 (0.061–0.081), p < 0.001), while telomeres were significantly shorter in STEMI, MINOCA and blood vessel rupture groups compared to the control group (STEMI = 1.179 (0.931–1.376), MINOCA = 1.026 (0.951–1.070), blood vessel rupture = 1.089 (0.842–1.173) vs. CG = 1.329 (1.096–1.624), p = 0.030]. Values of OXY score were significantly higher in STEMI and MINOCA patients compared to the control group and AP patients (5.83 (4.55–7.54) and 10.28 (9.19–10.72) vs. 4.94 (3.29–6.18) and 4.18 (2.58–4.86), p < 0.001). Longer telomeres and higher telomerase activity were found in thromboaspirates, compared to the peripheral blood leukocytes in the same patients (1.25 (1.01–1.84) vs. 1.18 (0.909–1.516), p = 0.036; and 0.366 (0.367–0.379) vs. 0.366 (0.367–0.379), p < 0.001, respectively). In addition, telomere length and telomerase activity had good diagnostic ability to separate STEMI patients from healthy persons.ConclusionsLeukocyte telomere length and telomerase activity can differentiate CAD patients from healthy persons, and relate CAD to oxidative stress.

Introduction: Obtaining, understanding, interpreting, and acting on health information enables people with diabetes to engage and make health decisions in various contexts. Hence, inadequate health literacy (HL) could pose a problem in making self-care decisions and in self-management for diabetes. By applying multidimensional instruments to assess HL, it is possible to differentiate domains of functional, communicative, and critical HL. Objectives: Primarily, this study aimed to measure the prevalence of inadequate HL among type 2 diabetes mellitus patients and to analyze the predictors influencing health literacy levels. Secondly, we analyzed if different self-reported measures, unidimensional instruments (Brief Health Literacy instruments (BRIEF-4 and abbreviated version BRIEF-3), and multidimensional instruments (Functional, Communicative and Critical health literacy instrument (FCCHL)) have the same findings. Methods: The cross-sectional study was conducted within one primary care institution in Serbia between March and September 2021. Data were collected through Serbian versions of BRIEF-4, BRIEF-3, and FCCHL-SR12. A chi-square test, Fisher’s exact test, and simple logistic regression were used to measure the association between the associated factors and health literacy level. Multivariate analyses were performed with significant predictors from univariate analyses. Results: Overall, 350 patients participated in the study. They were primarily males (55.4%) and had a mean age of 61.5 years (SD = 10.5), ranging from 31 to 82 years. The prevalence of inadequate HL was estimated to be 42.2% (FCCHL-SR12), 36.9% (BRIEF-3) and 33.8% (BRIEF-4). There are variations in the assessment of marginal and adequate HL by different instruments. The highest association was shown between BRIEF-3 and total FCCHL-SR12 score (0.204, p < 0.01). The total FCCHL-SR12 score correlates better with the abbreviated BRIEF instrument (BRIEF-3) than with BRIEF-4 (0.190, p < 0.01). All instruments indicated the highest levels for the communicative HL domain and the lowest for the functional HL domain with significant difference in functional HL between the functional HL of FCCHL-SR12 and both BRIEF-3 and BRIEF-4 (p = 0.006 and 0.008, respectively). Depending on applied instruments, we identified several variables (sociodemographic, access to health-related information, empowerment-related indicators, type of therapy, and frequency of drug administration) that could significantly predict inadequate HL. Probability of inadequate HL increased with older age, fewer children, lower education level, and higher consumption of alcohol. Only high education was associated with a lower probability of inadequate HL for all three instruments. Conclusions: The results we obtained indicate that patients in our study may have been more functionally illiterate, but differences between functional level could be observed if assessed by unidimensional and multidimensional instruments. The proportion of patients with inadequate HL is approximately similar as assessed by all three instruments. According to the association between HL and educational level in DMT2 patients we should investigate methods of further improvement.

BackgroundOxidative stress is implicated in both, the onset and the progression of type 1 diabetes mellitus (T1DM). There is accumulated evidence of increased biomarkers of oxidative stress in newly diagnosed, T1DM patients without complications, and in those with advanced disease. In this cross-sectional study, we investigated factors affecting oxidative stress status in pediatric patients with T1DM.MethodsAdvanced oxidation protein products (AOPP), prooxidant-antioxidant balance (PAB), total sulfhydryl (SH) groups, and superoxide dismutase (SOD) activity were determined in 170 children and adolescents with T1DM. Principal component analysis was used to investigate clustering of clinical and laboratory variables associated with elevated oxidative stress and reduced antioxidative defense biomarkers.ResultsFactor analysis extracted five factors, interpreted as (1) “weight status factor” including age, BMI, waist and hip circumferences; (2) “proatherogenic factor” that included LDL-cholesterol, non-HDL-cholesterol, and triglycerides; (3) “metabolic control factor” including glucose and HbA1c; (4) “renal marker factor” with positive loading of urinary albumin excretion rate and negative loading of GFR; and (5) “antiatherogenic factor” that included HDL-cholesterol. High AOPP levels were independently predicted by “proatherogenic” (OR: 2.32; 95% CI: 1.44–3.71; p ConclusionsCardiometabolic risk factors and renal function are associated with oxidative stress in pediatric T1DM patients.

We investigated circulating levels of inflammatory biomarkers pentraxin-3 (PTX3), cyclophilin A (CypA), and heparin-binding epidermal growth factor-like growth factor (HB-EGF); oxidative stress; and antioxidant status markers in the patients with ST-segment elevation acute myocardial infarction (STEMI) to better understand a relationship between inflammation and oxidative stress. We examined the impact of oxidative stress on high values of inflammatory parameters. The study included 87 patients with STEMI and 193 controls. We observed a positive correlation between PTX3 and HB-EGF (ρ = 0.24, P = .027), CyPA, and sulfhydryl (SH) groups (ρ = 0.25, P = .026), and a negative correlation between PTX3 and SH groups (ρ = −0.35, P = .001) in patients with STEMI. To better understand the effect of the examined parameters on the occurrence of high concentrations of inflammatory parameters, we grouped them using principal component analysis. This analysis identified the 4 most contributing factors. Optimal cutoff values for discrimination of patients with STEMI from controls were calculated for PTX3 and HB-EGF. An independent predictor for PTX3 above the cutoff value was a “metabolic-oxidative stress factor” comprised of glucose and oxidative stress marker prooxidant-antioxidant balance (odds ratio = 4.449, P = .030). The results show that higher PTX3 values will occur in patients having STEMI with greater metabolic and oxidative stress status values.

Background:Propolis and N-acetylcysteine have positiveimpact on respiratory tract health. Also, it has been sug-gested that they have beneficial effects on serum lipid andoxidative stress status, but the available data are limitedand mostly gained from animal models. In this study weevaluated the effects of propolis and N-acetylcysteine sup-plementation (PropoMucil®) on lipid status, lipoproteinsubclasses distribution and paraoxonase 1 activity in sub-jects with acute respiratory infection.Methods:Twenty subjects with acute respiratory infectionwere included. PropoMucil®granules for oral solution (80mg of dry propolis extract and 200 mg of N-acetylcysteine)were administered tree times per day for ten days. Serumlipid profile, paraoxonase 1 activity and low-density andhigh-density lipoprotein size and subclasses distributionwere assessed at baseline and after supplementation.Results:Following ten days of supplementation lipid statusremained unchanged, but a significant increase of low-density lipoprotein particle size and proportion of high-den-sity lipoprotein 3a particles were found (P

Background. Metabolic alterations, particularly disorders of lipoprotein metabolism in COVID-19, may affect the course and outcome of the disease. This study aims at evaluating the lipoprotein profile and redox status in SARS-CoV-2 infected patients with different pneumonia severity and their association with lethal outcomes. Methods. The prospective cohort study was performed on 98 COVID-19 patients with mild, moderate, and severe pneumonia. Lipid and inflammatory parameters, lipoprotein subclasses, and redox status biomarkers were determined at the study entry and after one week. Results. Compared to patients with mild and moderate pneumonia, severely ill patients had higher oxidised low-density lipoprotein (oxLDL) and malondialdehyde levels and lower high-density lipoprotein cholesterol (HDL-C) concentrations and paraoxonase 1 activity. Reduction in the proportion of large HDL 2a subclasses with a concomitant increase in the proportion of smallest HDL 3c and small dense LDL (sdLDL) particles was observed in patients with severe disease during the time. However, these changes were reversed in the mild and moderate groups. The results showed a positive association between changes in oxLDL and total antioxidative status. However, prooxidants and antioxidants in plasma were lower in patients with lethal outcomes. Conclusions. Increased levels of oxLDL and sdLDL particles may contribute to the severity of COVID-19. The role of oxidative stress should be clarified in further studies, mainly its association with lethal outcomes.

Inflammatory biomarkers - pentraxin-3 (PTX3), cyclophilin A (CypA) and heparin-binding epidermal growth factor-like growth factor (HB-EGF) were examined in patients with ST-segment elevation myocardial infarction (STEMI) undergoing revascularization with primary percutaneous coronary intervention (pPCI) and stent implanting. Investigated parameters were compared between patients with and without obstructive coronary artery disease (CAD). In addition, their changes were tested in circulation before and immediately after pPCI. The study group consisted of 81 STEMI patients. Patients were classified in the STEMI-CAD group if they had significant obstructive CAD or in MINOCA group if they had no significant stenosis. In STEMI-CAD patients inflammatory parameters were determined prior to and after pPCI intervention. Immediately after pPCI, in STEMI-CAD patients levels of PTX3 were significantly lower (1.52 vs. 2.17 μg/L

Background: Patients with chronic diseases, like diabetes need to continuously perform tasks associated with self-management especially with medications they use. It is shown that the patients with diabetes with limited HL and PTHL cannot read medication labels correctly, may misuse their medications, spend much more on therapy and generally have difficulties in understanding printed care instructions and perceiving health advice and warnings. There has been an increasing demand for valid and reliable instruments for HL and PTHL assessment in this population. This review aims to search and critically discuss instruments used to assess HL and PTHL in people with type 2 diabetes and propose their use in different settings.Methods: Authors conducted a comprehensive, electronic search of original studies using a structured approach of the Scopus and PubMed databases, during November and the first 2 weeks of December 2020 to find relevant papers. The review was conducted in accordance with the Cochrane guidelines and the reporting was based on the PRISMA-ScR. The comparison of instruments was made by utilizing a comparison model related to their structure, measurement scope, range, psychometric properties, validation, strengths, and limitations.Results: The final number of included studies was 24, extracting the following identified instruments: Korean Functional Test HL, NVS, FCCHL, HLS-EU-47, TOFLHA, S-TOFHLA, REALM-R, 3-brief SQ, REALM, HLQ and DNT-15. In all, FCCHL and 3-brief SQ are shown with the broadest measurement scopes. They are quick, easy, and inexpensive for administration. FCCHL can be considered the most useful and comprehensive instrument to screen for inadequate HL. The limitation is that the English version is not validated. Three-brief SQ has many advantages in comparison to other instruments, including that it is less likely to cause anxiety and shame. These instruments can be considered the best for measuring functional HL in patients with diabetes mellitus type 2 and other chronic diseases. PTHL instruments (REALM and DNT-15) did not find the best application in this population.Conclusions: The future research should be directed in validation of the FCCHL in English and establishing of the structural validity of this questionnaire. Developing a specific PTHL questionnaire for this population will be of great help in management of their disease.

Objective. Coronary artery bypass grafting (CABG) represents the significant source of increased oxidative stress (OS). We aimed to follow the OS status parameters (i.e., ischemia-modified albumin (IMA), malondialdehyde (MDA), superoxide anion, prooxidant-antioxidant balance (PAB), total oxidant status (TOS), total antioxidant status (TAS), and superoxide-dismutase (SOD)) change through the predefined study times in two different surgical procedures, i.e., cardiopulmonary bypass (CPB) and off-pump coronary artery bypass grafting (OPCAB). Additionally, we aimed to investigate those OS status parameters in specific study times according to SYNTAX score (SS), an established angiographic score for evaluating the extensity and severity of coronary artery disease. Patients and Methods. A total of 107 patients that were planned to undergo CABG were included (i.e., 47 patients in OPCAB and 60 patients in CPB group). Blood samples were taken at 6 time intervals: before surgery (t1), immediately after intervention (t2), 6 h (t3), 24 h (t4), 48 h (t5), and 96 h after termination of the operation (t6). Results. IMA levels were higher in CPB than that in OPCAB baseline and rose in CPB group in t2 point. TOS decreased in both study groups, compared to baseline values, but without statistical significance. Superoxide anion and PAB significantly increased in t3-t6 study times, in both groups. MDA significantly increased only in CPB group in t5 and t6 interval. MDA was significantly higher in CPB group compared to OPCAB in t6 study point. CPB patients had significantly lower TAS compared to OPCAB patients at the beginning and in t2 and t3 study points. They also had significantly lower SOD activities compared to OPCAB, baseline, and in several study points. Moreover, TAS, SOD, and TAS/TOS ratio were significantly lower, whereas PAB and TOS/TAS were significantly higher in patients with high SS compared to corresponding groups. SOD activity, IMA, and TAS level were the best predictors of high SS. Conclusion. CPB patients were in more severe ischemia baseline than OPCAB group and IMA rose in CPB patients immediately after the surgery end, but not later. Also, the antioxidant status was significantly lower, whereas the prooxidant status was significantly higher in patients with high SS compared to corresponding groups. SOD activity, IMA, and TAS level were the best predictors of CAD (as determined with SS), showing that SOD and IMA had very good discriminatory capability towards higher SS status.

Coronary artery disease (CAD) is one of the most important causes of mortality and morbidity in wide world population. Dyslipidemia, inflammation and oxidative stress may contribute to disruption of endothelium structure and function, atherosclerosis and CAD. Our study was aimed to determine whether Cu/Zn superoxide dismutase (Cu/Zn SOD) and Mn superoxide dismutase (Mn SOD) gene expression could be modulated by oxidative stress in CAD patients.This study included 77 CAD patients and 31 apparently healthy persons. Serum lipid levels, high sensitivity C-reactive protein (hsCRP), total antioxidant status (TAS) and thiobarbituric acid-reacting substances (TBARS) were measured. SOD isoenzymes gene expression was determined in peripheral blood mononuclear cells using quantitative polymerase chain reaction.Mn SOD messenger ribonucleic acid (mRNA) levels were significantly lower in CAD patients than in controls (p=0.011), while Cu/Zn SOD mRNA levels did not change significantly between tested groups (p=0.091). We found significantly lower high-density lipoprotein-cholesterol (HDL-c) (p0.001) and TAS (p0.001) levels and significantly higher hsCRP (p=0.002) and TBARS (p0.001) in CAD patients than in controls. There were significant positive correlations between TAS and Mn SOD mRNA (ρ=0.243, p=0.020) and TAS and Cu/Zn SOD mRNA (r=0.359, p0.001). TBARS negatively correlated only with Cu/Zn SOD mRNA (ρ=-0.215, p=0.040). TAS levels remained independent predictor for Mn SOD mRNA levels (OR=2.995, p=0.034).Results of this study showed that Mn SOD gene expression were decreased in CAD patients compared to controls and can be modulated by non-enzymatic antioxidant status in blood.Koronarna arterijska bolest (KAB) je jedan od najvažnijih uzročnika mortaliteta i morbiditeta u širokoj svetskoj populaciji. Dislipidemija, inflamacija i oksidativni stres mogu doprineti poremecaju strukture i funkcije endotela, nastanku ateroskleroze i KAB. Naša studija je imala za cilj da utvrdi da li ekspresije gena Cu/Zn supsoksid dismutaze (Cu/Zn SOD) i Mn superoksid dismutaze (Mn SOD) mogu da budu promenjene pod uticajem oksidativnog stresa kod pacijenata sa KAB.Ova studija je obuhvatila 77 pacijenata sa KAB i 31 naizgled zdravih osoba kod kojih su određeni nivoi serumskih lipida, visoko osetljivi C-reaktivni protein (hsCRP), ukupni antioksidativni status (TAS) i tiobarbituratna kiselina-reagujuće supstance (TBKRS). Ekspresija gena izoenzima SOD određena je u mononuklearnim ćelijama periferne krvi pomoću metode kvantitativne lančane reakcije polimeraze.Nivoi informacione ribonukleinske kiseline (iRNK) Mn SOD su značajno bili niži kod pacijenata sa KAB nego kod kontrole (p=0,011), dok se nivoi Cu/Zn SOD iRNK nisu značajno razlikovali između ispitanih grupa (p=0,091). Kod pacijenata sa KAB utvrđeni su znatno nižinivoi holesterola u lipoproteinima visoke gustine (HDL-h) (p0,001) i TAS (p0,001) i znatno veće koncentracije hsCRP (p=0,002) i TBKRS (p0,001). Postojale su značajne pozitivne korelacije između TAS i iRNK Mn SOD (ρ=0,243, p=0,020) i TAS i iRNK Cu/Zn SOD (ρ= 0,359, p0,001). TBKRS su bile u negativnoj korelaciji samo sa iRNK Cu/Zn SOD (ρ =-0,215, p= 0,040). TAS je bio nezavisni prediktor za nivoe iRNK Mn SOD (OR=2,995, p=0,034).Rezultati ove studije pokazali su da je ekspresija Mn SOD gena smanjena kod pacijenata sa KAB u poređenju sa kontrolnom grupom i da može biti modulirana neenzimskim antioksidativnim statusom u krvi.

Cathepsin S (CTSS) is a cysteine protease involved in atherogenesis. We compared the plasma CTSS as well as other biomarkers of atherosclerosis in patients with abdominal aortic aneurysms (AAA) and aortoiliac occlusive disease (AOD), aiming to identify the underlying pathogenic mechanisms of the disease development. Also, we hypothesised that the level of plasma CTSS simultaneously increases with a decrease of plasma high-density lipoprotein cholesterol (HDL-C) values.33 patients with AAA and 34 patients with AOD were included in this study.There was no difference in the level of plasma CTSS between the two analysed groups (p=0.833). In the patients with AAA, the plasma CTSS was correlated with HDL-C (r = -0.377, p = 0.034) and total bilirubin (r =0.500, p = 0.003) while, unexpectedly, it was not correlated with cystatin C (Cys C) (r =0.083, p = 0.652). In the patients with AOD, the plasma CTSS correlated with triglycerides (r = 0.597, p0.001), only. When the patients were divided according to HDL-C (with HDL-C ≤0.90 and HDL-C0.90 mmol/L), the plasma CTSS values differed among these groups (31.27These results provide the first evidence that CTSS negatively correlated with HDL-C and bilirubin in patients with AAA. It is possible that differences in the association of the CTSS and other markers of atherosclerosis can determine whether atherosclerotic aorta will develop dilatation or stenosis.Katepsin S (CTSS) je cisteinska proteaza uključena u aterogenezu. Uporedili smo plazmatski CTSS kao i druge biomarkere ateroskleroze kod pacijenata sa aneurizmom abdominalne aorte (AAA) i aorto ilijačnom okluzivnom bolešću (AOD) sa ciljem da se identifikuju osnovni patogeni mehanizmi razvoja bolesti. Takođe, pretpostavili smo da se nivo plazmatskog CTSS istovremeno povećava sa smanjenjem vrednosti holesterola plazmatskih lipoproteina visoke gustine (HDL-C).Ova studija je obuhvatila 33 pacijenta sa AAA i 34 pacijenta sa AOD.Nije bilo razlike u nivou plazmatskog CTSS izme|u dve analizirane grupe (p = 0,833). Kod pacijenata sa AAA, plazmatski CTSS je bio u korelaciji sa HDL-C (r = -0,377, p = 0,034) i ukupnim bilirubinom (r = - 0,500, p = 0,003), dok, neočekivano, nije bio u korelaciji sa cistatinom C (Cys C) (r = 0,083, p = 0,652). Kod pacijenata sa AOD, plazmatski CTSS je bio u korelaciji sa trigliceridima (r = 0,597,p0.001). Kada su pacijenti podeljeni prema HDL-C (sa HDL-C ≤ 0,90 i HDL-C0,90 mmol/L), vrednosti plazmatskog CTSS su se razlikovale među grupama (31,27 naspram 25,61 μg/L, respektivno, p0,001).Ovi rezultati pružaju prvi dokaz da je CTSS negativno povezan sa HDL-C i bilirubinom kod pacijenata sa AAA. Pretpostavka je da se na osnovu razlike u asocijaciji CTSS-a i drugih markera ateroskleroze može utvrditi da li će ateroskleroza aorte dovesti do dilatacije ili stenoze.

Background/Aim. Valid and reliable instruments were emphasized in the studies of pharmacotherapy literacy which is the capacity to obtain, evaluate, calculate, and comprehend basic information about pharmacotherapy and actions necessary to make appropriate medication-related decisions. The aims of this study were: to develop an instrument for assessment of pharmacotherapy health literacy among parents of pre-school children in Serbia (PTHL-SR) and to evaluate psychometric properties. Methods. This study was a four-stage methodological one, conducted from November 2015 to October 2016. The instrument content was established through qualitative and quantitative expert reviews in the first and second phase. Experts had to answer about the clarity and relevance of questions. The Content Validity Ratio (CVR) and index (CVI) were calculated based on the necessity and relevance of questions. Third phase was pre-testing of initial instrument to assess comprehensibility of questions. In the fourth phase, 300 parents completed questionnaire at several kindergartens in Belgrade, to determine questionnaire’s reliability through internal consistency, using the Cronbach’s alpha coefficient and correlation between classes. Results. The 14-items questionnaire was developed (initial PTHL-SR) and pre-tested on a pilot sample. It had 4 groups of questions about knowledge, understanding, numerical skills and access to medicines-related information. The Content Validity Ratio (CVR = 0.875) was significant and adequate (Lawshe CVR8 = 0.780). Conclusion. PTHL-SR is a reliable instrument for assessment of pharmacotherapy literacy among parents of pre-school children in Serbia and can be used for the evaluation of understanding, calculating and accessing medicines-related information. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. 41004]

IntroductionDyslipidemia, inflammation and immunological processes play a key role in the development of atherosclerosis. This study investigates the relationship of different phenotypes of low-density lipoprotein (LDL) and high-density lipoprotein (HDL), human antibodies G classes against oxLDL (IgG anti-oxLDL antibodies) and inflammatory marker pentraxin-3 (PTX3) in patients with ST-segment elevation acute myocardial infarction (STEMI). Among STEMI patients with different Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery (SYNTAX) score, we analyzed predictive abilities of these biomarkers to assess disease outcome.Material and methodsIn 69 STEMI, 21 patients with stable angina pectoris (AP) and 67 healthy controls, IgG anti-oxLDL antibodies and PTX3 were determined by ELISA. Gradient gel electrophoresis was used for lipoprotein subclasses separation.ResultsWe found significantly lower HDL and LDL diameters (pConclusionsSmaller LDL and HDL particles are associated with elevated IgG anti-oxLDL antibodies in healthy subjects, but with increased PTX3 level in STEMI patients. In addition, we found that smaller LDL size was independent predictor of higher SYNTAX score. Further studies are needed to expand our preliminary observations.

The objective of this study was to formulate extended-release mucoadhesive buccal tablets of propranolol hydrochloride in order to provide a prolonged absorption of propranolol hydrochloride from the buccal mucosa and to reduce presystemic metabolism and thus provide a better therapeutic effect. Besides, the aim was to perform comparative in vivo pharmacokinetic and hemodynamic studies of the developed extended-release (ER) propranolol hydrochloride 10 mg mucoadhesive buccal tablets and commercial immediate-release (IR) propranolol hydrochloride 10 mg tablets in spontaneously hypertensive rats. Formulation with 15% polyethylene oxide showed the highest degree of propranolol hydrochloride permeation, satisfactory mucoadhesiveness, and extended-release of propranolol hydrochloride, thus it was selected for further in vivo study. The pharmacokinetic study in rats showed the superiority of ER mucoadhesive buccal tablets over IR tablets in terms of propranolol hydrochloride absorption extent (AUC values: 70.32 ± 19.56 versus 31.69 ± 6.97 µg·h/mL), although lower maximum plasma propranolol hydrochloride concentration (Cmax) was achieved. However, no statistically significant difference was observed in Cmax between these treatments. The hemodynamic study showed that ER mucoadhesive buccal tablets provide a more pronounced decrease primarily in heart rate, but also in systolic and diastolic arterial pressure, as well as a longer heart rate reduction compared to IR tablets.

Heparin-binding EGF-like growth factor (HB-EGF) is involved in atherosclerosis progression. We investigated association between plasma HB-EGF levels and lipid, oxidative stress and inflammatory biomarkers in pediatric patients with type 1 diabetes mellitus (T1DM). Levels of HB-EGF, high-sensitive C-reactive protein (hsCRP), prooxidant-antioxidant balance (PAB), total antioxidant status (TAS), oxidized low-density lipoproteins (oxLDL), metabolic control and serum lipid parameters and paraoxonase 1 (PON1) activity were determined in 74 patients and 40 controls. In comparison to controls, patients had significantly higher levels (

The application assessment of different programs was performed with equivalence tests for method transfer pro second-order derivative spectrophotometry. The digital second-order derivative spectra were calculated on different instruments; GBC Scientific Equipment Cintra 20 (Cintral v.2.6 and Spectral v.1.70 software programs) and Thermo Scientific Evolution 300 (VISIONPro software) were analyzed using the amplitude A/B ratio (A = 2D265,263; B = 2D263,261). Amplitude A/B ratio is the resolution parameter for derivative spectrophotometry prescribed in European Pharmacopoeia. The obtained values for A/B ratio were either very similar or significantly different among programs: 0.669 (Cintral v.2.6), 0.549 (Spectral v.1.70), 0.556 (medium indirect VISIONPro), 0.557 (one-step Savitzky–Golay 7 VISIONPro), 0.689 (two-step Savitzky–Golay 7 VISIONPro). Method transfer was possible between Spectral v.1.70 and VISIONPro (medium indirect and one-step Savitzky–Golay 7), but the values obtained in Cintral v.2.6 were not comparable to the other programs. The absorbance data exported from both instruments were additionally calculated in OriginPro8 which provided almost the same mean A/B values (0.627 Cintral v.2.6; 0.624 VISIONPro), confirming that the two instruments recorded the same zero-order spectra. The calculation of resolution parameter could be used for verification of program comparison, which would enable transfer between sender and receiver laboratory. The accordance between program algorithms was confirmed when acceptable differences for values of resolution parameter (A/B ratios) were achieved.

The background of this study was transfer assessment for H3BO3 assays according to different pharmacopoeias’ monographs and verification of the crucial parameters—the polyols’ excess (mannitol, glycerine, sorbitol), the initial H3BO3 concentrations and the indicator’s concentrations. The purpose of the work was the comparative study according to different pharmacopoeias: the European (EP 9), the American (USP 35-NF 30), the Japanese (JP XVII), important for quality control of H3BO3, as an active component or an excipient. pH analyses were set up to establish the effects of selected polyols and the initial H3BO3 concentrations. For evaluation of assay results and methods’ equivalence, standard t test and two one-sided t test (TOST) were applied. Pharmacopoeias’ procedures propose volumetric analyses by 1 M NaOH standard solution with visual end-point detection (phenolphthalein) using sufficiently high H3BO3 concentrations and less excess of polyols, as the good alternative to potentiometric method. The influence of phenolphthalein’s concentration (0.1%, 1%), evidenced as relevant factor, caused the difference shown by standard t test: 99.82% (EP 9) and 99.66% (JP XVII). Equivalences between three methods were confirmed by TOST procedures with defined acceptance criterion ± 2% derived from the mean value (99.83%). The comparative study results pointed out that the initial phenolphthalein’s concentration was the crucial influencing factor on harmonization of assay mean values, which was confirmed by TOST application for the methods’ equivalency in method transfer evaluation. The best possible correlation between the lowest excess of polyol-sorbitol and the highest initial boric acid concentration was proved by JP XVII, which was indicated by pH-metric analyses. Graphic abstract: [Figure not available: see fulltext.]

The aim of this study was to determine the reference values for thyrotropin (TSH), thyroid hormones (total and free thyroxine, T4 and fT4; total and free triiodothyronine, T3 and fT3), thyroglobulin (Tg) and thyroid antibodies (thyroid peroxidase, TPOAb and thyroglobulin antibody, TgAb) in the population of the Republic of Srpska.A total of 250 euthyroid subjects were enrolled in this study. A direct method for choosing reference subjects was used to establish reference intervals. The hormones and thyroid antibodies were measured by an electrochemiluminescence immunoassay method (ECLIA, Roche Diagnostics, Mannheim, Germany). We calculated the reference intervals by MedCalc, version 12.1.4.0 (MedCalc software, Belgium) as recommended by the IFCC (CLSI C28-A3).Using guidelines recommended by the National Academy of Clinical Biochemistry (NACB) and based on standard statistical approaches, the reference intervals derived for TSH, fT4, T4, fT3, T3 were 0.75-5.32 mIU/L, 12.29-20.03 pmol/L, 73.49-126,30 nmol/L, 4.11-6.32 pmol/L, 1.15-2.32 nmol/L and for Tg, TPOAb, TgAb were 3.63-26.00 μg/L,18.02 mIU/L,98.00 mIU/L, respectively. We found a significant difference (p0.05) in TSH and fT3 values between different age groups as well as in T4, fT4 and fT3 values between ge nder groups.The established reference values for the population of the Republic of Srpska were significantly different from the values recommended by the manufacturer of reagents (Roche Diagnostics). Our results showed that a laboratory needs to establish its own reference values in order to set up a proper diagnosis, as well as to treat patients successfully.Cilj ovog rada bio je da se utvrde referentne vrednosti tireotropnog hormona (TSH), tireoidnih hormona (ukupni tiroksin, T4 i slobodni tiroksin, fT4; ukupni trijodtironin, T3 i slobodni trijodtironin, fT3), tireoglobulina (Tg) i anti tela štitne žlezde (antitela na tireoperoksidazu, TPO-At i tireoglobulinska antitela, Tg-At) kod stanovništva Republike Srpske.Ukupno 250 eutireoidnih ispitanika bilo je uključeno u ovo istraživanje. Korišćen je direktan način izbora referentnih osoba za utvrđivanje referentnog intervala. Hormoni i antitela štitne žlezde određivani su u serumu elektrohemiluminiscentnom metodom (ECLIA, Roche Diagnostics, Mannheim, Germany). Referentne granice su određene korištenjem programa MedCalc, verzija 12.1.4.0 (MedCalc software, Belgium) po preporuci IFCC (CLSI C28-A3).Koristeći smernice Nacionalne akademije za kliničku biohemiju (NACB) i na temelju standardnih statistiČkih pristupa utvrđeni referentni intervali za TSH, fT4, T4, fT3, T3 bili su 0,75–5,32 mIU/L, 12,29–20,03 pmol/L, 73,49– 126,30 nmol/L, 4.11–6.32 pmol/L, 1,15–2,32 nmol/L kao i za Tg, TPOAt, TgAt 3, 63–26,00 μg/L,18,02 mIU/L,98,00 mIU/L. Takođe, postojala je i značajna razlika između različitih starosnih grupa za TSH i fT3 vrednosti, kao i razlika za T4, fT4 i fT3 vrednosti između žena i muškaraca.Dobijene referentne vrednosti za populaciju Republike Srpske znatno su se razlikovale od vrednosti preporučenih od strane proizvođača reagensa (Roche Diagnostics). Rezultati su ukazali da laboratorije moraju da izrade sopstvene referentne vrednosti sa ciljem postavljanja prave dijagnoze, kao i uspešnog lečenja pacijenata.

Background and objectives: Pharmacotherapy literacy (PHTL) is an individual&rsquo, s capacity to obtain, evaluate, calculate, and comprehend basic information about pharmacotherapy and pharmacy-related services necessary to make appropriate medication-related decisions, regardless of the mode of content delivery (e.g., written, oral, visual images and symbols). It is already proven that low PHTL of parents can cause serious problems in the treatment of a pediatric population. We aimed to identify the differences in parental PHTL levels, socio-demographic and health-related characteristics (chronic disease of a child, breastfeeding of a child, annual visits to a pediatrician, parental-self-estimation of health status) between rural and urban areas and to investigate the influence of living in rural areas on a low PHTL level. Materials and methods: Our study was cross-sectional with a validated 14-item instrument (&ldquo, Parental pharmacotherapy literacy questionnaire&mdash, Serbian&rdquo, ), which assessed overall PHTL and its three domains of knowledge, understanding and numerical skills necessary for the safe use of medicines. We analyzed 250 parents of pre-school children (1&ndash, 7 years old) in rural areas and 182 parents from urban areas in Serbia. Results: Every tenth parent from rural and every fourth parent from urban areas had the highest PHTL level or more than 85% correct answers. However, 51% and 28% of parents in rural and urban areas, respectively, had a low PHTL level (less than 65% correct answers), [Х2(1, n = 432) = 33.2, p &lt, 0.001]. Parents from different areas statistically differed in age, education level, employment, breastfeeding and annual visits to pediatrician rate. Those from rural areas had almost twice the probability of low PHTL levels (ORa = 2.033, p = 0.003) than their urban counterparts, independently of other examined parental characteristics. Conclusions: Parents from rural areas have more difficulties to obtain, evaluate, calculate and comprehend basic information related to pharmacotherapy than parents from urban areas.

Background and objectives: Pharmaceutical literacy skills of parents are crucial for appropriate and safe medication use in pre-school children (ages 1&ndash, 7 years). A recent study on pharmacotherapy literacy from Serbia showed that one in five parents have difficulty understanding common information about the use of medicines. Because antipyretics are considered to be the most frequently used group of over-the-counter (OTC) medications during the pre-school period, we aimed to: (i) examine parental practice and expectations in antipyretic medication use, and (ii) analyze associations of parental practice and expectations related to socio-economic status and pharmacotherapy literacy. Materials and methods: A cross-sectional survey using a self- report validated specific instrument was conducted with the parents of pre-school children in kindergartens in Belgrade, Serbia. Pharmacotherapy literacy refers to the knowledge and personal skills needed to meet the complex demands of medicine use in both healthcare and non-healthcare settings. A comprehensive literature review, expert-focus group consultation, and pre-testing were employed in 4-item multiple-choice test development to explore practice and expectations related to the use of OTC pediatric antipyretic medicines. Results: The final analytical cohort was comprised of 813 participants, the majority (63.3%) chose a medicine based on a physician&rsquo, s suggestion and only 15.4% of parents reported they would follow the advice of a pharmacist. More than a half of parents (54.1%) would need advice about antipyretic medicine from a pharmacist, firstly in a simpler language. Parents satisfied with the information given by a pharmacist had higher pharmacotherapy literacy, compared to parents with lower levels (OR&ndash, 0.718, 95%CI (0.597&ndash, 0.865), p &lt, 0.001). Men had a higher expectation of pharmacists to explain medicine use in a simpler language (OR&ndash, 1.630, 95%CI (1.063&ndash, 2.501), p = 0.025), as well as parents with three or more children (OR&ndash, 2.527, 95%CI (1.43&ndash, 4.459), p = 0.001). Parents with higher knowledge about medicine use were less likely to ask for simpler information (OR&ndash, 0,707, 95%CI (0,583&ndash, 0,856), p &lt, 0,001). Conclusions: Our main finding is that practice in antipyretic OTC medicine use was associated with levels of parental pharmacotherapy literacy. The expectations of pharmacists were higher among parents with lower levels of pharmacotherapy literacy, who expected more information in a simpler and more precise language. This study highlighted the need for pharmacists to identify risks in parental practice and to provide information about medicines to parents of pre-school children in a simpler and more appropriate way.

Carnitine is essential for energy metabolism and spermatozoa maturation. Combining L-carnitine and L-acetylcarnitine with micronutrients has been investigated as a treatment for infertility in men. We evaluated the effects of a therapeutic formulation, Proxeed Plus, on sperm parameters in oligoasthenozoospermic men. This prospective, randomised, double-blind, placebo-controlled clinical trial involved 175 males (19-44 years) with idiopathic oligoasthenozoospermia who failed to impregnate their partners (12 months). Males received Proxeed Plus or placebo for 3 and 6 months. Sperm volume, progressive motility and vitality significantly (p lt 0.001) improved after 6 months compared to baseline. Sperm DNA fragmentation index significantly decreased compared to baseline (p lt 0.001) and the 3-month therapy (p = 0.014) in treated men. Increased seminal carnitine and alpha-glucosidase concentration also positively correlated with improved progressive motility. Decreased DNA fragmentation index was the good predictor of progressive sperm motility >10%, and simultaneous measurement of changes in sperm vitality and DNA fragmentation index gave the highest probability of sperm motility 10% (AUC = 0.924; 95% CI = 0.852-0.996; p lt 0.001). Logistic regression analyses revealed DNA fragmentation index decrease as the only independent predictor of sperm motility 10% (OR = 1.106; p = 0.034). We have demonstrated the beneficial effects of carnitine derivatives on progressive motility, vitality and sperm DNA fragmentation. Combining metabolic and micronutritive factors is beneficial for male infertility.

Telomerase is RNA directed polymerase which acts as reverse transcriptase based on its own RNA component. It is considered to be involved in the pathology of many diseases and is recognized as a potential biomarker. The aims were to determine the sample storage conditions and the time frame for samples analysis, then to prove reliability of enzyme activity measurement with real-time telomeric repeat amplification protocol (TRAP) and to evaluate the suitable standard samples for telomerase activity measurements. Samples used for stability and freeze-thaw study were peripheral blood leukocytes, obtained from apparently healthy persons, patients with diagnosed cancer and cell lines. Telomerase activity was measured using TRAP method, while standard evaluation was done using nuclear magnetic resonance (NMR) technique. Storage at -20 degrees C preserved telomerase activity in samples from cancer patients for at least 14 days (21.46 +/- 0.135 versus 21.84 +/- 0.357, p = .756), while samples obtained from healthy persons should be stored at -80 degrees C. We observed significant decrease of telomerase activity at freeze thaw cycle 5 in cancer patients' samples (21.46 +/- 0.135 versus 23.09 +/- 0.316, p lt .05), and in healthy persons' ones already at cycle 3 (22.74 +/- 0.107 versus 24.85 +/- 0.151, p lt .05). Telomerase activity from cell lines samples showed overall greater stability regarding the storage period and freeze-thaw cycles and it was considered for standard sample, which was confirmed by NMR analysis. Telomerase enzyme had adequate stability while efficacy, linearity, and reproducibility of TRAP method were acceptable for bio-analytical methods. All this indicated that telomerase could be a reliable biomarker.

This study aimed to evaluate the oxidative stress status and two markers of platelet activation and reactivity in off-pump versus on-pump coronary artery bypass surgery. Study groups of 65 patients with double coronary artery bypass grafting were divided into cardiopulmonary bypass (CPB) and off-pump coronary artery bypass groups. In serial blood samples, lipid hydroperoxides (LOOH), serum paraoxonase (PON1), advanced oxidation protein products (AOPP), total sulfhydryl groups (tSHG) and red blood cell distribution width (RDW) to platelet (Plt) ratio (RPR) and mean platelet volume (MPV) to platelet (Plt) ratio (MPR) index were determined to compare the extent of oxidative stress and platelet activation. The MPR and RPR rose significantly in the post-operative period (P lt 0.001) in both groups. The increase was higher in the CPB group, but this difference reached borderline significance at 48 h post-operatively. The AOPP/tSHG index increased 6 h after surgery, preceded by a significant fall of the PON1/LOOH ratio, more evident in the CPB group. Multiple linear regression analysis showed explicit connection between these markers and surgery-related clinical conditions. Receiver operating characteristic analysis enabled estimation of the clinical accuracy of oxidative plus platelet-related indices in prediction of surgery caused complications (area under the curve for the model consisted of oxidative stress parameters and platelet activation indices was above 0.9, P lt 0.001). Results showed higher oxidative stress and undesirable platelet activation in the CPB group. Oxidative status markers and platelet activity indices showed good clinical accuracy to predict the development of possible surgical complications.

Atherosclerosis is a chronic inflammatory disease which starts early in life and depends on many factors, an important one being dyslipoproteinemia. According to several studies, atherosclerotic plaques or their precursors could be seen in children younger than 10 years. During later life, interaction with a sedentary way of life, as well as unhealthy nutrition, smoking, alcohol consumption, obesity and family history of cardiovascular disease cause the burden of atherosclerotic disease.Study included 624 children (316 boys, 308 girls), aged from 7-13 years. We analysed socio-demographic data (BMI, blood pressure, cardiovascular family history, smoking status), as well as lipid status with lipoprotein little a-Lp(a), and apolipoproteins: Apo AI, Apo B-100 for all children. This enabled us to calculate new atherogenic indices Tg/HDL-c, lipid tetrad index (LTI) and lipid pentad index (LPI). Cardiovascular risk for later life was estimated by using modified Risk Score for Young Individuals (RS), which divided the subjects according to the score level: low, medium and higher risk.The older children (13 y) had better lipid status than the younger children, i.e. significantly lower total cholesterol, LDL-C, triglycerides and non-HDL-C concentration and significantly higher HDL-C concentration than the younger children and this was in accordance with the RS level. Children with a positive family history of CV disease had significantly higher Lp(a) concentration and blood pressure. LPI was significantly higher in children with a higher RS.The results of our work could be used for cardiovascular risk assessment in apparently healthy children to provide preventive measures which could control the changeable risk factors.Ateroskleroza je hronična inflamatorna bolest koja počinje rano u detinjstvu i zavisi od mnogo faktora; jedan od najvažnijih je dislipoproteinemija. Razvoj aterosklerotskog plaka počinje pre desete godine života. Interakcija sa sedentarnim načinom života, nezdravom ishranom, pušenjem, unošenjem alkohola, gojaznošću i pozitivnom porodičnom anamnezom za kardiovaskularne bolesti uzrokuje razvoj aterosklerotske bolesti u kasnijem dobu. Cilj ove studije je bio da se kod zdrave dece izmere i procene pomenuti faktori rizika i kvantifikuje rizik za razvoj ateroskleroze kasnije u životu.U studiju je uključeno 624 deteta (316 dečaka i 308 devojčica), uzrasta 7–13 godina. Analizirali smo indeks telesne mase – ITM, krvni pritisak, porodičnu anamnezu, status pušenja, osnovni lipidni status sa dodatnim parametrima: koncentracija lipoproteina a–Lp(a) i apolipoproteina: Apo AI, Apo B-100. Računali smo nove aterogene indekse: odnos koncentracija Tg i HDL-c, lipid tetrad (LTI) i lipid pentad indeks (LPI). Rizik za razvoj kardiovaskularnih bolesti u kasnijem životu je procenjivan upotrebom Skora rizika za mlade osobe (SR) na osnovu koga su ispitanici podeljeni na one sa niskim, srednjim i višim rizikom.Starija deca (13 g.) imaju bolji lipidni status od mlađe dece, tj. niže koncentracije LDL-h, triglicerida i non-HDL-h i više koncentracije HDL-h, što je bilo u skladu sa nivoom SR. Deca sa pozitivnom porodičnom anamnezom imala su više koncentracije Lp(a) i viši krvni pritisak. LPI je bio značajno viši kod dece sa višim SR.Rezultati ove studije bi se mogli koristiti za procenu kardiovaskularnog rizika kod zdrave dece, da bi se sprečio nastanak nekih od faktora rizika.

Preclinical Research Major depressive disorder (MDD) is a major psychiatric illness and it is predicted to be the second leading cause of disability by 2020 with a lifetime prevalence of about 13%. Selective serotonin reuptake inhibitors (SSRIs) are the most commonly used therapeutic class for MDD. However, response to SSRI treatment varies considerably between patients. Biomarkers of treatment response may enable clinicians to target the appropriate drug for each patient. Biomarkers need to have accuracy in real life, sensitivity, specificity, and relevance to depression. Introduction of MDD biomarkers into the health care system can increase the overall cost of clinical diagnosis of patients. Because of that, decisions to allocate health research funding must be based on drug effectiveness and cost-effectiveness. The assessment of MDD biomarkers should include reliable evidence of associated drug effectiveness, adverse events and consequences (reduced productivity and quality of life, disability) and effectiveness of alternative approaches, other drug classes or behavioral or alternative therapies. In addition, all the variables included in an economic model (probabilities, outcomes, and costs) should be based on reliable evidence gained from the literature-ideally meta-analyses-and the evidence should also be determined by informed and specific expert opinion. Early assessment can guide decisions about whether or not to continue test development, and ideally to optimize the process. Drug Dev Res 77 : 374-378, 2016. © 2016 Wiley Periodicals, Inc.

Since the rise in plasma adiponectin levels in chronic kidney disease (CKD) patients has not yet been elucidated, we sought to investigate if patients on hemodialysis (HD) have altered expression of adiponectin receptors in peripheral blood mononuclear cells (PBMCs) compared to healthy subjects.This study included 31 patients with chronic kidney disease on HD and 33 healthy subjects (CG). Circulating adiponectin levels were measured by ELISA while AdipoR1 and AdipoR2 mRNA levels in PBMCs were determined by real-time PCR.Plasma adiponectin levels were significantly higher in patients compared to control group (P=0.036). After adjustment for age, BMI and creatinine, this difference became even more significant (P=0.004). In both groups adiponectin correlated with creatinine (CG: r=-0.472, P=0.006; HD: r=-0.375, P=0.038), triglycerides (CG: r=- 0.490, P=0.004; HD: r=-0.488, P=0.005), insulin (CG: r=-0.386, P=0.038; HD: r=-0.506, P=0.012) and high density lipoprotein cholesterol (HDL-C) (CG: r=-0.672, P0.001; HD: r=-0.584, P=0.001). Significantly lower expression of PBMCs AdipoR1 mRNA was found in patients compared to CG (P=0.034), while AdipoR2 mRNA levels were similarly expressed in PBMCs in both groups.Complex pathological processes in CKD cause downregulation of AdipoR1 which could ultimately influence AdipoR1 protein levels leading to a state of ≫adiponectin resistance≪.S obzirom na to da razlozi povišenih vrednosti adiponektina u hroničnoj bubrežnoj insuficijenciji (HBI)još uvek nisu razja šnjeni, cilj ovog istraživanja bio je da se ispita da li pacijenti na hemodijalizi (HD) imaju promenjen nivo genske ekspresije adiponektinskih receptora u mononuklearnim ćelijama periferne krvi u odnosu na zdrave ispitanike.Ova studija je obuhvatila 31 pacijenta sa hroničnom bubrežnom insuficijencijom na hemodijalizi (HD) i33 zdrava ispitanika (KG). Koncentracija cirkulišućeg adiponektina određena je ELISA metodom, a nivoi iRNK adiponektinskih receptora AdipoR1 i AdipoR2 u mononuklearnim ćelijama periferne krvi odreleni su metodomKoncentracija adiponektina u plazmi pacijenata bila je značajno viša u odnosu na zdrave ispitanike (P= 0,036). Nakon korekcije ža godine, BMI i koncentraciju kreatinina, ova razlika je postala još značajnija (P=0,004). U obe grupe ispitanika koncentracija adiponektina je korelisala sa koncentracijom kreatinina (KG: r=-0,472, P=0,006; HD: r=-0,375, P=0,038), koncentracijom trij glicerida (KG: r=-0,490, P = 0,004; HD: r=-0,488, P=0,005), koncentracijom insulina (KG: r=-0,386, P=0,038; HD: r=-0,506, P=0,012) i koncentracijom holesterola u lipoproteinima velike gustine (KG: r=-0,672, P0,001; HD: r=-0,584, P=0,001). Pacijenti su imali značajno niži nivo iRNK AdipoR1 u mononuklearnim ćelijama periferne krvi u porelenju sa zdravim ispitanicima (P=0,034), dok se nivo iRNK AdipoR2 nije značajno razlikovao među posmatranim grupama.Kompleksni patološki procesi u HBI izazivaju nishodnu regulaciju AdipoR1 gena, što bi moglo uticati na nivo AdipoR1 proteina, vodeći u stanje ≫adiponektinske rezistencije≪.

Background Chronic renal failure, particularly end-stage renal disease, is a serious health problem associated with a high mortality rate. Uremic syndrome leads to increased oxidative stress, inflammation, and dyslipidemia. Aims To examine superoxide dismutase isoenzyme gene expression in peripheral blood mononuclear cells of patients on hemodialysis and to determine the associations between superoxide dismutase isoenzyme gene expression, oxidative stress, and non-enzymatic antioxidative protection. Study Design Case control study. Methods This study included 33 patients on hemodialysis (age, 55.33±15.31 years old) and 33 apparently healthy controls (age, 45.37±8.92 years old). Superoxide dismutase isoenzyme messenger ribonucleic acid levels were determined by real-time polymerase chain reaction. General biochemical parameters, high sensitivity C-reactive protein, total antioxidant status, thiobarbituric acid-reactive substances, and the superoxide anion radical were also determined. Results Normalized Cu/Zn superoxide dismutase and Mn superoxide dismutase messenger ribonucleic acid levels were significantly higher in patients than controls (p

Some cardiovascular complications in patients with chronic kidney disease and end-stage renal disease may be caused by structurally and functionally modified lipoproteins. Redox status (advanced oxidation protein products [AOPPs]), prooxidant–antioxidant balance, total protein sulfhydryl (SH-groups), and paraoxonase 1 (PON1) activity were assessed in 77 renal patients and 20 controls. Lipoproteins were isolated using ultracentrifugation. PON1, PON3, and pentraxin-3 concentration were determined by enzyme-linked immunosorbent assay (ELISA). Dyslipidemia-Oxy-Inflammation (DOI) score was calculated as a sum of dyslipidemia, oxidative stress, and inflammation scores. The dyslipidemia score ( P < .001), oxy score ( P < .01), inflammation score (P < .001), and the DOI score ( P < .001) were higher in patient groups compared with controls. The very-low-density lipoprotein (VLDL) fraction contained the highest amount of AOPP ( P < .001) compared with other lipoprotein fractions in all groups. The low-density lipoprotein (LDL) fraction contained elevated AOPP in all groups compared with the high-density lipoprotein (HDL) fraction ( P < .001). Significant positive correlation was observed between AOPP in LDL fraction and DOI score (ρ = 0.510, P < .01). Dyslipidemia, oxidative stress, and inflammation play an interactive role in renal disease and are mutually associated with redox status in VLDL, LDL, and HDL lipoproteins in plasma of renal patients.

Cardiovascular complications, as the main cause of mortality in renal patients, are followed with altered lipoproteins composition. Considering that paraoxonase-1 (PON1) is an anti-oxidative enzyme located mainly on HDL particles, the current study has aim to investigate whether failure of kidney function leads to changes in the distribution of PON1 activity between different HDL subclasses.In 77 renal patients (21 chronic kidney disease (CKD) and 56 end stage renal disease (ESRD) patients on dialysis) and 20 healthy subjects PON1 activity on HDLSerum paraoxonase (p0.01) and arylesterase activity (p0.001) of PON1 as well as its concentration (p0.01) were significantly lower in CKD and ESRD patients compared to controls. Relative proportion of HDLThis study showed that altered HDL subclasses distribution, changed PON1 activities on different HDL subclasses as well as diminished anti-oxidative protection could be important factors in atherosclerosis development in CKD and ESRD patients.

Parental health literacy plays an important role in children’s health. Experiences from pharmacy practice show that is necessary to check if parents understand instructions about use of medicines for children. This study aimed to assess pharmacotherapy literacy of parents of pre-school children and to examine association of parental pharmacotherapy literacy level with parent’s socio-demographic characteristics. The study was cross-sectional, conducted among parents of pre-school children (1–7 years of age), in kindergartens in several municipalities of Belgrade, Serbia, during regular parents meetings, from May to October 2016. Functional health literacy was measured by the Serbian version of the Short Test of Functional Health Literacy in Adults (S-TOFHLA). Parental pharmacotherapy literacy was assessed with newly constructed PTHL-SR questionnaire with good psychometric characteristics (Parental pharmacotherapy literacy questionnaire—Serbian). Overall, 813 parents participated in the study, mostly females (81.30%), between 30 to 40 years of age (70.85%) with two children (56.70%). Almost all of our study participants (99%) had adequate health literacy as assessed by S-TOFHLA. Mean score on PTHL-SR was 72.83% (standard deviation was 13.37), with better results among females than males (72% of women were in the group of highest PTHL-SR results). Our study showed that many parents (76.5%) knew the appropriate usage of non-prescription medicine for children, 57.2% parents were able to correctly calculate the dose of oral syrup for a child, and only 43.3% were able to interpret non-prescription dosage information written on the package. The majority of parents (61.3%) would make a dosage to child based on age and not on their weight. Every fifth parent with adequate functional health literacy measured by S-TOFHLA test, achieved the lowest results measured by PTHL-SR. Higher performance of the PTHL-SR was significantly correlated with education (p < 0.001), female sex (p < 0.001), married parents and those living in common-law (p < 0.001), older parents (p < 0.05) and parents who have more children (p < 0.05), and are non-smokers (p < 0.05). These results provide evidence that limitations in understanding common information about use of medicines are widespread among parents of pre-school children and encourage efforts for further investigation. PTHL-SR questionnaire may be a useful tool for identification of parents who need more instructions and assistance from healthcare providers, above all in providing better communication, written or spoken at community pharmacy settings.

Introduction: Cardiovascular complications, as the main cause of mortality in renal patients, are followed with altered lipoproteins composition. Considering that paraoxonase-1 (PON1) is an anti-oxidative enzyme located mainly on HDL particles, the current study has aim to investigate whether failure of kidney function leads to changes in the distribution of PON1 activity between different HDL subclasses. Materials and methods: In 77 renal patients (21 chronic kidney disease (CKD) and 56 end stage renal disease (ESRD) patients on dialysis) and 20 healthy subjects PON1 activity on HDL2 and HDL3 subclasses was determined by zymogram method that combines gradient gel electrophoresis separation of HDL subclasses and measurement of PON1 activity in the same gel. Results: Serum paraoxonase (p lt 0.01) and arylesterase activity (p lt 0.001) of PON1 as well as its concentration (p lt 0.01) were significantly lower in CKD and ESRD patients compared to controls. Relative proportion of HDL3 subclasses was higher in ESRD patients than in healthy participants, while HDL2 subclasses was significantly decreased in CKD (p lt 0.05) and ESRD (p lt 0.001) patients, as compared to controls. Furthermore, control subjects had higher PON1 activity on HDL2 (CKD and ESRD patients p lt 0.001) and HDL3 (CKD p lt 0.05; ESRD patients p lt 0.001) subclasses in comparison with the both patients groups. Also, significant negative correlation was found between paraoxonase activity of PON1 in serum and creatinine concentration (rho = -0.373, p lt 0.01). Conclusions: This study showed that altered HDL subclasses distribution, changed PON1 activities on different HDL subclasses as well as diminished anti-oxidative protection could be important factors in atherosclerosis development in CKD and ESRD patients.

Context: Polyphenols and flavonoids in artichoke leaf tincture (ALT) protect cells against oxidative damage. Objectives: We examined ALT effects on deoxyribonucleic acid (DNA) damage and lipid profiles in rat plasma and gene expression in rat aorta [haemeoxygenase-1 (HO1), haemeoxygenase-2 (HO2), NADPH oxidase 4 (NOX-4), monocyte chemoattractant protein-1 (MCP-1) and nuclear factor (erythroid-derived 2)-like 2 (Nrf2)]. Materials and methods: Eighteen male Wistar albino rats were divided into three groups (n = 6/group): The control group (CG) was fed with standard pellet chow for 11 weeks; the AD group was fed for a similar period of time with pellet chow supplemented with 2% cholesterol, 3% sunflower oil and 1% sodium cholate. The ADA group was fed with pellet chow (for 1 week), the atherogenic diet (see above) for the following 4 weeks and then with ALT (0.1 mL/kg body weight) and atherogenic diet for 6 weeks. According to HPLC analysis, the isolated main compounds in ALT were chlorogenic acid, caffeic acid, isoquercitrin and rutin. Results: Normalized HO-1 [0.11 (0.04–0.24)] and MCP-1 [0.29 (0.21–0.47)] mRNA levels and DNA scores [12.50 (4.50–36.50)] were significantly lower in the ADA group than in the AD group [0.84 (0.35–2.51)], p = 0.021 for HO-1 [0.85 (0.61–3.45)], p = 0.047 for MCP-1 and [176.5 (66.50–221.25)], p = 0.020 for DNA scores. HO-1 mRNA was lower in the ADA group than in the CG group [0.30 (0.21–0.71), p = 0.049]. Conclusions: Supplementation with ALT limited the effects of the atherogenic diet through reduced MCP-1 expression, thereby preventing oxidative damage.

Introduction: Dyslipidaemia contributes to the occurrence of colorectal cancer (CRC). We hypothesized that qualitative changes of lipoproteins are associated with the risk for CRC development. This study analyses low-density lipoprotein (LDL) and high-density lipoprotein (HDL) diameters, as well as distribution of LDL and HDL subclasses in patients with CRC, with an aim to determine whether advanced lipid testing might be useful in predicting the risk for the onset of this malignancy. Materials and methods: This case-control study included 84 patients with newly diagnosed CRC and 92 controls. Gradient gel electrophoresis was applied for separation of lipoprotein subclasses and for LDL and HDL diameters determination. Lipid parameters were measured using routine enzymatic methods. Results: Total cholesterol, HDL and LDL-cholesterol were significantly lower in CRC patients compared to controls (4.47 mmol/L vs. 5.63 mmol/L; 0.99 mmol/L vs. 1.27 mmol/L; 2.90 mmol/L vs. 3.66 mmol/L; P lt 0.001, respectively). Patients had significantly smaller LDL (25.14 nm vs. 26.92 nm; P lt 0.001) and HDL diameters (8.76 nm vs. 10.17 nm; P lt 0.001) and greater proportion of small, dense LDL particles (54.0% vs. 52.9%; P = 0.044) than controls. Decreased LDL and HDL diameters were independent predictors of CRC (OR = 0.5, P = 0.001 and OR = 0.5, P = 0.008, respectively), and alongside with age and HDL-cholesterol concentrations formed the optimal cost-effective model, providing adequate discriminative abilities for CRC (AUC = 0.89) and correct patients classification (81%). Conclusions: Patients with CRC have decreased LDL and HDL diameters and increased proportion of smaller particles. LDL and HDL diameters determination could be useful in assessing the risk for CRC development.

We compared factors of inflammation - high sensitivity C-reactive protein (hsCRP) and pentraxin-3 (PTX3), and we explored their relationship with coronary artery disease (CAD). Also, we tested the usefulness of hsCRP and PTX3 in the risk assessment of coronary stenosis development and the diagnostic ability of these biomarkers to detect disease severity.The study group consisted of 93 CAD patients undergoing coronary angiography. Patients were divided into CAD(0), representing subclinical stenosis, and CAD (1-3), representing significant stenosis in one, two or three vessels.We determined the concentration of lipid status parameters, hsCRP and PTX3. We found significantly lower PTX3 and hsCRP concentrations in CAD(0) than in CAD(1-3) group. Concentration of PTX3 showed an increasing trend with the increasing number of vessels affected. The area under ROC curve (AUC) for the combinations of hsCRP and PTX3 with lipid parameters had useful accuracy for detecting CAD(1-3) patients (AUC=0.770,PTX3 is a promising independent diagnostic marker for identifying patients with CAD, and a useful indicator of disease progression. In all the analyses PTX3 showed better performance than hsCRP. A combination of PTX3, hsCRP with the lipid status parameters provides risk stratification of the development of coronary stenosis and better classification than their individual application.Visokoosetljivi C-reaktivni protein (hsCRP), kao marker hronične inflamacije, može biti korišćen u proceni rizika od kardiovaskularnih bolesti. Cilj rada je bio da se uporede markeri inflamacije hsCRP i pentraksin-3 (PTX3) i da se ispita njihova veza sa koronarnom arterijskom bolešću (KAB). Takođe, analiziran je značaj hsCRP i PTX3 u proceni rizika za koronarnu stenozu i dijagnostička sposobnost ovih biomarkera da utvrde težinu bolesti.Istraživanjem je obuhvaćeno 93 pacijenta koji su podvrgnuti koronarnoj angiografiji. Pacijenti sa subkliničkom stenozom na koronarnim krvnim sudovima svrstani su u KAB(0) grupu, dok su pacijenti sa značajnom stenozom na jednom, dva ili tri krvna suda svrstani u KAB(1–3) grupu. Određivane su koncentracije parametara lipidnog statusa, hsCRP i PTX3.Prosečne koncentracije PTX3 i hsCRP kod pacijenata u KAB(0) grupi bile su značajno niže u poređenju sa koncentracijama istih parametara u KAB(1–3) grupi. Koncentracija PTX3 pokazala je značajnu pozitivnu korelaciju sa porastom broja krvnih sudova zahvaćenih stenozom. Površina ispodOdređivanje PTX3 pomaže u identifikaciji osoba sa KAB i može biti korisno u proceni progresije bolesti. U svim analizama PTX3 je, kao biomarker, pokazao bolje dijagnostičke karakteristike u poređenju sa hsCRP. Kombinacija PTX3, hsCRP i parametara lipidnog statusa, u poređenju sa njihovom pojedinačnom upotrebom, obezbeđuje bolju klasifikaciju pacijenata u zavisnosti od težine KAB.

Objective: The connection of oxidative stress with dyslipidemia creates a newly-emerging atherosclerosis risk factor involved in acute ischemic stroke development. This study analyzed the influence of oxidative stress on structural changes of high-density lipoprotein (HDL) particles connected with modification in protective paraoxonase 1 (PON1) activity. Methods: This study used 185 patients with acute ischemic stroke and 185 apparently healthy controls. Oxidative stress status, PON1 status, lipids and high-sensitivity C-reactive protein (hsCRP) were determined. In isolated HDL lipoprotein fraction we determined selected markers of oxidative stress (malondialdehyde, MDA) and the content of total sulfhydryl (SH) groups. The capability of oxidative and PON1 status parameters to discriminate patients according to survival status was evaluated. Results: Stroke patients had lower HDL-cholesterol than controls and a remarkable fall in PON1 activity (control group-227 U/L, survivors-42 U/L, lethal outcome group-61 U/L, p lt 0.001), along with more prominent inflammation. Pronounced oxidative stress and impaired antioxidative protection was present among patients. HDL fraction analysis revealed a significant decrease of SH groups content (control group vs. patients, p lt 0.05) and increased in MDA content in patients (lethal outcome vs. control group, p lt 0.05). According to logistic regression analysis, the best predictor of disease outcome was oxidative stress marker - prooxidative-antioxidative balance (PAB). Conclusions: Pronounced oxidative stress in this group of acute ischemic stroke patients probably led to HDL structural changes, which could further cause an alteration or decrease of PON1 activity. Evidence of increased prooxidant level associated with decreased protective, antioxidative factors suggests their mutual involvement in this complex pathology.