The multidimensional value of natriuretic peptides in heart failure, integrating laboratory and clinical aspects.

Natriuretic peptides (NP) play an essential role in heart failure (HF) regulation, and their measurement has improved diagnostic and prognostic accuracy. Clinical symptoms and objective measurements, such as NP levels, should be included in the HF definition to render it more reliable and consistent among observers, hospitals, and healthcare systems. BNP and NT-proBNP are reasonable surrogates for cardiac disease, and their measurement is critical to early diagnosis and risk stratification of HF patients. NPs should be measured in all patients presenting with dyspnea or other symptoms suggestive of HF to facilitate early diagnosis and risk stratification. Both BNP and NT-proBNP are currently used for guided HF management and display comparable diagnostic and prognostic accuracy. Standardized cutoffs for each NP assay are essential for data comparison. The value of NP testing is recognized at various levels, including patient empowerment and education, analytical and operational issues, clinical HF management, and cost-effectiveness.

Effects of four-week lasting aerobic treadmill training on hepatic injury biomarkers, oxidative stress parameters, metabolic enzymes activities and histological characteristics in liver tissue of hyperhomocysteinemic rats.

Disruptions in homocysteine (Hcy) metabolism may increase the liver's susceptibility to developing conditions such as alcoholic liver disease, viral hepatitis, hepatocellular carcinoma (HCC), and cirrhosis. The aim of this study was to examine effects of aerobic treadmill training on hepatic injury biomarkers in sera, oxidative stress parameters, the activity of metabolic enzymes, and histological characteristics in the liver tissue of rats with experimentally induced hyperhomocysteinemia. Male Wistar albino rats were divided into four groups (N = 10, per group): C-saline 0.2 mL/day sc. 2×/day for 14 days + saline 0.5 mL ip.1×/day for 28 days; H-homocysteine 0.45 µmol/g b.w. 2×/day for 14 days + saline 0.5 mL ip.1×/day for 28 days; CPA-saline 0.2 mL/day sc. 2×/day for 14 days + aerobic treadmill training for 28 days; and HPA-homocysteine 0.45 µmol/g b.w. 2×/day for 14 days + aerobic treadmill training for 28 days. The serum albumin concentration was decreased in both physically active (PA) groups compared to sedentary groups. Concentration of malondialdehyde in liver tissue homogenates was lower in both PA groups compared to the H group. The total lactate dehydrogenase and malate dehydrogenase activities were significantly elevated in the HPA group compared to the C and H groups. Activities of aminotransferases in sera samples, and activities of catalase and superoxide dismutase in liver tissue did not significantly differ between groups. No significant histological changes were found in liver tissue in groups. This study demonstrated that aerobic treadmill training can reduce lipid peroxidation in liver tissue under hyperhomocysteinemic conditions, providing a protective effect. However, hyperhomocysteinemia can alter energy metabolism during aerobic exercise, shifting it toward anaerobic pathways and leading to elevated lactate dehydrogenase activity in the liver. Given that conditions like hyperhomocysteinemia are associated with an increased risk of cardiovascular diseases and liver damage, understanding how exercise influences these dynamics could guide therapeutic approaches.

Validation and verification framework and data integration of biosensors and in vitro diagnostic devices: a position statement of the IFCC Committee on Mobile Health and Bioengineering in Laboratory Medicine (C-MBHLM) and the IFCC Scientific Division.

Advances in technology have transformed healthcare and laboratory medicine. Biosensors have emerged as a promising technology in healthcare, providing a way to monitor human physiological parameters in a continuous, real-time, and non-intrusive manner and offering value and benefits in a wide range of applications. This position statement aims to present the current situation around biosensors, their perspectives and importantly the need to set the framework for their validation and safe use. The development of a qualification framework for biosensors should be conceptually adopted and extended to cover digitally measured biomarkers from biosensors for advancing healthcare and achieving more individualized patient management and better patient outcome.

Factors contributing to variability in metformin concentration in polycystic ovary syndrome.

AIM: To investigate the factors affecting metformin concentrations after chronic administration in patients with polycystic ovary syndrome (PCOS), focusing on the pharmacokinetic variability and its implications for personalized therapy. METHODS: This study enrolled 53 PCOS patients undergoing long-term metformin treatment at the Clinic for Gynecology and Obstetrics in Nis, Serbia, from February to December 2019. Pharmacokinetic parameters were measured from blood samples, and metformin concentrations were determined with validated analytical techniques. RESULTS: There was a significant variability in metformin concentrations among PCOS patients, with body mass index (BMI) identified as a major influencing factor. Higher BMI was associated with lower plasma metformin levels, a finding suggesting an altered pharmacokinetic profile in obese patients. CONCLUSIONS: This study highlights the critical role of BMI in influencing metformin pharmacokinetics in PCOS patients and underscores the need for personalized treatment strategies in patients with PCOS.

Expression Pattern and Prognostic Significance of the Long Non-Coding RNA Metastasis-Associated Lung Adenocarcinoma Transcript 1 in Chronic Lymphocytic Leukemia.

Dysregulated expression of the long non-coding RNA MALAT1 has been implicated in the pathogenesis and progression of a variety of cancers, including hematological malignancies, but it has been poorly investigated in chronic lymphocytic leukemia (CLL). In this study, the expression of MALAT1 was measured using a quantitative reverse-transcriptase polymerase chain reaction in the peripheral blood mononuclear cells of 114 unselected, newly diagnosed CLL patients in order to analyze its association with clinical, laboratory, and molecular patients' characteristics at diagnosis, as well as its prognostic relevance. MALAT1 was found to be upregulated in CLL patients in comparison to healthy controls, and expression levels were not related to age, leukocyte, lymphocyte and platelet count, serum ß2-microglobulin, and IGHV somatic hypermutational status. On the other hand, high MALAT1 expression was associated with several favorable prognostic markers (high hemoglobin, low serum lactate dehydrogenase, earlier clinical stages, CD38-negative status), but also with unfavorable cytogenetics. Furthermore, an association between high MALAT1 levels and longer time to first treatment and overall survival in IGHV-unmutated CLL subtype was observed. In summary, our results imply that high MALAT1 expression at diagnosis may be a predictor of better prognosis and point to MALAT1 expression profiling as a candidate biomarker potentially useful in clinical practice.

Effects of four weeks lasting aerobic physical activity on cardiovascular biomarkers, oxidative stress and histomorphometric changes of heart and aorta in rats with experimentally induced hyperhomocysteinemia.

The aim of this study was to examine the effects of hyperhomocysteinemia and aerobic physical activity on changes of cardiovascular biomarkers in sera, oxidative stress in cardiac tissue, and histomorphometric parameters of heart and aorta in rats. Experiments were conducted on male Wistar albino rats organized into four groups (n = 10, per group): C (control group): 0.9% NaCl 0.2 mL/day; H (homocysteine group): homocysteine 0.45 µmol/g b.w./day; CPA (control + physical activity group): 0.9% NaCl 0.2 mL/day and a program of physical activity on a treadmill; and HPA (homocysteine + physical activity group) homocysteine 0.45 µmol/g b.w./day and a program of physical activity on a treadmill. Substances were applied subcutaneously twice a day. Lipid peroxidation and relative activity of Mn-superoxide dismutase isoform were significantly higher in active hyperhomocysteinemic rats in comparison to sedentary animals. Atherosclerotic plaques were detected in aorta samples of active hyperhomocysteinemic rats and also, they had increased left ventricle wall and interventricular septum, and transverse diameter of cardiomyocytes compared to sedentary groups. Aerobic physical activity in the condition of hyperhomocysteinemia can lead to increased oxidative stress in cardiac tissue and changes in histomorphometric parameters of the heart and aorta, as well increased lipid parameters and cardiac damage biomarkers in sera of rats.

The Value of Troponin Measurement in Carotid Revascularization: A Scoping Review.

PURPOSE: Patients undergoing carotid endarterectomy (CEA) or carotid artery stenting (CAS) are at substantially increased risk of short-term and long-term cardiac complications. Still, the role of perioperative troponin in predicting cardiac events remains unclear. The objective was to systematically summarize the existing evidence on the topic and provide directions for further research. MATERIALS AND METHODS: Studies that examined perioperative troponin values and its association with myocardial injury, and/or myocardial infarction (MI), and/or major adverse cardiac events (MACE) and postoperative mortality in exclusively CEA/CAS patients, published in English until March 15, 2022, were retrieved through a systematic search of MEDLINE and Web of Science. The study selection process was independently performed by 2 authors, while the third researcher resolved disagreements. RESULTS: Four studies with 885 participants met the inclusion criteria. Age, chronic kidney disease, presentation of carotid disease, type of closure (primary closure/venous patch/Dacron/polytetrafluoroethylene patch), coronary artery disease, chronic heart failure, and the long-term use of calcium channel blockers represent risk factors for troponin elevation, which occurred in 11% to 15.3%. Myocardial infarction and MACE occurred in 23.5% to 40%, that is, 26.5% of patients with troponin elevation, respectively, during the first 30 postoperative days. Elevated postoperative troponin levels were significantly associated with adverse cardiac events during the long-term surveillance period. The rates of cardiac-related and all-cause mortality were higher in patients with postoperative troponin elevation. CONCLUSION: Troponin measurement could be helpful in the prediction of adverse cardiac events. The predictive role of preoperative troponin, the patient population in whom routine troponin sampling should be used, and a comparison of different treatment methods/anesthesia techniques in carotid patients should be further examined. CLINICAL IMPACT: The present scoping review critically appraises the extent and nature of the existing literature data on the predictive value of troponin on the occurrence of cardiac complications in patients undergoing CEA and CAS. In particular, it provides clinicians with essential insights by systematically summarizing the core evidence and identifying knowledge gaps that may direct future research. This, in turn, may significantly alter the current clinical practice and perhaps even reduce the incidence of cardiac complications in patients undergoing CEA/CAS.

Sudden cardiac death in long-term follow-up in patients treated with primary percutaneous coronary intervention.

Objective. Most studies analyzing predictors of sudden cardiac death (SCD) after acute myocardial infarction included only high-risk patients or index reperfusion had not been performed in all patients. The aim of our study was to analyze the incidence of SCD and determine the predictors of SCD occurrence during 6-year follow-up of unselected patients with ST-elevation myocardial infarction (STEMI), treated with primary percutaneous coronary intervention (pPCI). Method. we analysed 3114 STEMI patients included included in the University Clinical Center of Serbia STEMI Register. Patients presenting with cardiogenic schock were excluded. Echocardiographic examination was performed before hospital discharge. Results. During 6-year follow-up, lethal outcome was registered in 297 (9.5%) patients, of whom 95 (31.9%) had SCD. The highest incidence of SCD was recorded in the first year of follow-up, when SCD was registered in 25 patients, which is 26.3% of the total number of patients who had had SCD, i.e. 0.8% of the patients analyzed. The independent predictors for the occurrence of SCD during 6-year follow-up were EF < 45% (HR 3.07, 95% 1.87-5.02), post-procedural TIMI flow <3 (HR 2.59, 95%CI 1.37-5.14), reduced baseline kidney function (HR 1.87, 95%CI 1.12-2.93) and Killip class >1 at admission (HR 1.69, 95%CI 1.23-2.97). Conclusion. There is a low incidence of SCD in unselected STEMI patients treated with primary PCI. Predictors of SCD occurence during long-term follow-up in analyzed patients are clinical variables that are easily recorded during index hospitalization and include: EF ≤45%, post-procedural flow TIMI < 3, Killip class >1, and reduced baseline kidney function.

Serum High-Mobility Group Box 1 and Heme Oxygenase-1 as Biomarkers in COVID-19 Patients at Hospital Admission.

The careful monitoring of patients with mild/moderate COVID-19 is of particular importance because of the rapid progression of complications associated with COVID-19. For prognostic reasons and for the economic management of health care resources, additional biomarkers need to be identified, and their monitoring can conceivably be performed in the early stages of the disease. In this retrospective cross-sectional study, we found that serum concentrations of high-mobility group box 1 (HMGB1) and heme oxygenase-1 (HO-1), at the time of hospital admission, could be useful biomarkers for COVID-19 management. The study included 160 randomly selected recovered patients with mild to moderate COVID-19 on admission. Compared with healthy controls, serum HMGB1 and HO-1 levels increased by 487.6 pg/mL versus 43.1 pg/mL and 1497.7 pg/mL versus 756.1 pg/mL, respectively. Serum HO-1 correlated significantly with serum HMGB1, oxidative stress parameters (malondialdehyde (MDA), the phosphatidylcholine/lysophosphatidylcholine ratio (PC/LPC), the ratio of reduced and oxidative glutathione (GSH/GSSG)), and anti-inflammatory acute phase proteins (ferritin, haptoglobin). Increased heme catabolism/hemolysis were not detected. We hypothesize that the increase in HO-1 in the early phase of COVID-19 disease is likely to have a survival benefit by providing protection against oxidative stress and inflammation, whereas the level of HMGB1 increase reflects the activity of the innate immune system and represents levels within which the disease can be kept under control.

The Impact of Kidney Function on the Slow-Flow/No-Reflow Phenomenon in Patients Treated with Primary Percutaneous Coronary Intervention: Registry Analysis.

Objective: The objective of this study is to analyze the impact of declining kidney function on the occurrence of the slow-flow/no-reflow phenomenon in patients with ST-elevation myocardial infarction (STEMI) treated with primary PCI (pPCI), as well as the analysis of the prognostic impact of the slow-flow/no-reflow phenomenon on short- and long-term mortality in these patients. Methods: We analyzed 3,115 consecutive patients. A value of the glomerular filtration rate (eGFR) at the time of admission of eGFR <90 ml/min/m2 was considered a low baseline eGFR. The follow-up period was 8 years. Results: The slow-flow/no-reflow phenomenon through the IRA was registered in 146 (4.7%) patients. Estimated GFR of <90 ml/min/m2 was an independent predictor for the occurrence of the slow-flow/no-reflow phenomenon (OR 2.91, 95% CI 1.25-3.95, p < 0.001), and the risk for the occurrence of the slow-flow/no-reflow phenomenon increased with the decline of the kidney function: eGFR 60-89 ml/min/m2: OR 1.94 (95% CI 1.22-3.07, p = 0.005), eGFR 45-59 ml/min/m2: OR 2.55 (95% CI 1.55-4.94, p < 0.001), eGFR 30-44 ml/min/m2: OR 2.77 (95% CI 1.43-5.25, p < 0.001), eGFR 15-29 ml/min/m2: OR 5.84 (95% CI 2.84-8.01, p < 0.001). The slow-flow/no-reflow phenomenon was a strong independent predictor of short- and long-term all-cause mortality: 30-day mortality (HR 2.62, 95% CI 1.78-3.57, p < 0.001) and 8-year mortality (HR 2.09, 95% CI 1.49-2.09, p < 0.001). Conclusion: Reduced baseline kidney function was an independent predictor for the occurrence of the slow-flow/no-reflow phenomenon, and its prognostic impact started with the mildest decrease in eGFR (below 90 ml/min/m2) and increased with its further decline. The slow-flow/no-reflow phenomenon was a strong independent predictor of mortality in the short- and long-term follow-up of the analyzed patients.

Use of the WISN method to assess the health workforce requirements for the high-volume clinical biochemical laboratories.

BACKGROUND: The clinical laboratory services, as an essential part of health care, require appropriate staff capacity to assure satisfaction and improve outcomes for both patients and clinical staff. This study aimed to apply the Workload Indicators of Staffing Need (WISN) method for estimating required laboratory staff requirements for the high-volume clinical biochemical laboratories. METHODS: In 2019, we applied the WISN method in all 13 laboratories within the Center for Medical Biochemistry of the University Clinical Centre of Serbia (CMB UCCS). A review of annual routinely collected statistics, laboratory processes observations, and structured interviews with lab staff helped identify their health service and additional activities and duration of these activities. The study outcomes were WISN-based staff requirements, WISN ratio and difference, and a recommendation on the new staffing standards for two priority laboratory workers (medical biochemists and medical laboratory technicians). RESULTS: Medical biochemists' and laboratory technicians' annual available working time in 2019 was 1508 and 1347 working hours, respectively, for the workload of 1,848,889 samples. In general, the staff has four health service, eight support, and 15 additional individual activities. Health service activities per sample can take from 1.2 to 12.6 min. Medical biochemists and medical laboratory technicians spend almost 70% and more than 80% of their available working time, undertaking health service activities. The WISN method revealed laboratory workforce shortages in the CMB (i.e. current 40 medical biochemists and 180 medical laboratory technicians as opposed to required 48 medical biochemists and 206 medical laboratory technicians). Workforce maldistribution regarding the laboratory workload contributes to a moderate-high workload pressure of medical biochemists in five and medical laboratory technicians in nine organizational units. CONCLUSIONS: The WISN method showed mainly a laboratory workforce shortages and workload pressure in the CMB UCCS. WISN is a simple, easy-to-use method that can help decision-makers and policymakers prioritize the recruitment and equitable allocation of laboratory workers, optimize their utilization, and develop normative guidelines in the field of clinical laboratory diagnostics. WISN estimates require periodic reviews.

Target association rule mining to explore novel paediatric illness patterns in emergency settings.

BACKGROUND AND AIMS: To assess the hospitalized sick children admitted to the pediatric emergency department (ED) and to find new patterns of clinical and laboratory attributes using association rule mining (ARM). METHODS: In this observational study, 158 children with median (IQR) age 11 months and a PRISM III score of 5 (2-9) were enrolled. Hotspot data mining method was applied to assess clinical attributes, lab investigations and pre-defined outcome parameters of children and their association in sick hospitalized children aged 1 month to 12 years. RESULTS: We obtained 30 rules with value for outcome as discharge is given attributes as follows: duration of hospitalization > 4 days, lactate > 1.2 mmol/L, platelet = 3.67/µL, dur_ventil = 0 h, serum K = 5.2 mmol/L, SBP = 120 mmHg, pCO2 = 41.9 mmHg, PaO2 = 163 mmHg, age = 92 months, heart rate > 114-159 per minute, temperature > 98 °F, GCS (Glasgow Coma Scale) > 7-14, gas K = 4.14 mmol/L, gas Na = 138.1 mmol/L, BUN (Blood Urea Nitrogen) = 18.69 mg/dL, Diagnosis > 1-718, Creatinine = 1.2 mg/dL, serum Na = 148 mmol/L, shock = 2, Glucose = 144 mg/dL, Mg(i) > 0.23 meq/L, BUN > 6.54 mg/dL. CONCLUSION: ARM is an effective data analysis technique to find meaningful patterns using clinical features with actual numbers in pediatric critical illness. It can prove to be important while analysing the association of clinical attributes with disease pattern, its features, and therapeutic or intervention success patterns.

The Effects of a Meldonium Pre-Treatment on the Course of the LPS-Induced Sepsis in Rats.

A dysregulated and overwhelming response to an infection accompanied by the exaggerated pro-inflammatory state and metabolism disturbance leads to the fatal outcome in sepsis. Previously we showed that meldonium, an anti-ischemic drug clinically used to treat myocardial and cerebral ischemia, strongly increases mortality in faecal-induced peritonitis (FIP) in rats. We postulated that the same mechanism that is responsible for the otherwise strong anti-inflammatory effects of meldonium could be the culprit of the increased mortality. In the present study, we applied the LPS-induced model of sepsis to explore the presence of any differences from and/or similarities to the FIP model. When it comes to energy production, despite some shared similarities, it is evident that LPS and FIP models of sepsis differ greatly. A different profile of sympathoadrenal activation may account for this observation, as it was lacking in the FIP model, whereas in the LPS model it was strong enough to overcome the effects of meldonium. Therefore, choosing the appropriate model of sepsis induction is of great importance, especially if energy homeostasis is the main focus of the study. Even when differences in the experimental design of the two models are acknowledged, the role of different patterns of energy production cannot be excluded. On that account, our results draw attention to the importance of uninterrupted energy production in sepsis but also call for much-needed revisions of the current recommendations for its treatment.

How Well Do Laboratories Adhere to Recommended Guidelines for Cardiac Biomarkers Management in Europe? The CArdiac MARker Guideline Uptake in Europe (CAMARGUE) Study of the European Federation of Laboratory Medicine Task Group on Cardiac Markers.

BACKGROUND: The CARdiac MARker Guideline Uptake in Europe (CAMARGUE) program is a multi-country audit of the use of cardiac biomarkers in routine clinical practice. METHODS: An email link to a web-based questionnaire of 30 multiple-choice questions was distributed via the professional societies in Europe. RESULTS: 374 questionnaires were returned from 39 countries, the majority of which were in northern Europe with a response rate of 8.2%-42.0%. The majority of the respondents were from hospitals with proportionately more responses from central hospitals than district hospitals. Cardiac troponin was the preferred cardiac biomarker, evenly split between cardiac troponin T (cTnT) and cardiac troponin I (cTnI). Aspartate transaminase and lactate dehydrogenase are no longer offered as cardiac biomarkers. Creatine kinase, creatine kinase MB isoenzyme, and myoglobin continue to be offered as part of the cardiac biomarker profile in approximately on 50% of respondents. There is widespread utilization of high sensitivity (hs) troponin assays. The majority of cTnT users measure hs-cTnT. 29.5% of laboratories measure cTnI by a non-hs method but there has been substantial conversion to hs-cTnI. The majority of respondents used ng/L and use the 99th percentile as the upper reference limit (71.9% of respondents). A range of diagnostic protocols are in use. CONCLUSIONS: There is widespread utilization of hs troponin methods. A significant minority do not use the 99th percentile as recommended and there is, as yet, little uptake of very rapid diagnostic strategies. Education of laboratory professionals and clinicians remains a priority.

Effects of Iron Oxide Nanoparticles on Structural Organization of Hepatocyte Chromatin: Gray Level Co-occurrence Matrix Analysis.

Gray level co-occurrence matrix (GLCM) analysis is a contemporary and innovative computer-based algorithm that can be used for the quantification of subtle changes in a cellular structure. In this work, we use this method for the detection of discrete alterations in hepatocyte chromatin distribution after in vivo exposure to iron oxide nanoparticles (IONPs). The study was performed on 40 male, healthy C57BL/6 mice divided into four groups: three experimental groups that received different doses of IONPs and 1 control group. We describe the dose-dependent reduction of chromatin textural uniformity measured as GLCM angular second moment. Similar changes were detected for chromatin textural uniformity expressed as the value of inverse difference moment. To the best of our knowledge, this is the first study to investigate the impact of iron-based nanomaterials on hepatocyte GLCM parameters. Also, this is the first study to apply discrete wavelet transform analysis, as a supplementary method to GLCM, for the assessment of hepatocyte chromatin structure in these conditions. The results may present the useful basis for future research on the application of GLCM and DWT methods in pathology and other medical research areas.

Insulin resistance surrogates and left ventricular hypertrophy in normotensive obese children.

BACKGROUND: The relationship between different surrogates of insulin resistance and left ventricular geometry in obese children is still unclear. OBJECTIVE: We sought to explore the relationship between commonly used measures of insulin sensitivity/resistance (homeostatic model assessment index, serum uric acid, and triglycerides to high-density lipoprotein cholesterol ratio) and left ventricular geometry in normotensive obese children. METHODS: In this cross-sectional study, 32 normotensive obese children were examined. Transthoracic echocardiography was used to measure left ventricular mass index and relative wall thickness. Homeostasis model assessment index, serum uric acid level, and a ratio of triglycerides to high-density lipoprotein cholesterol were used as markers of the insulin resistance. Simple and partial correlation analyses (to control for the effects of body mass index) were conducted to explore relationship between studied variables and left ventricular mass index or relative wall thickness as outcome variables. RESULTS: We found positive correlations between homeostasis model assessment index and relative wall thickness (r = 0.47, p = 0.03) which remained significant after controlling for the effect of body mass index, z-score (r = 0.48, p = 0.03). The cutoff level of homeostasis model assessment index with the optimum sensitivity (Sn) and specificity (Sp) derived from the receiver operating characteristic (ROC) curves for predicting concentric remodelling was ≥5.51 with Sn = 83.33 and Sp = 68.75. CONCLUSION: There is a positive relationship between homeostasis model assessment index and relative wall thickness of obese normotensive children which may help to distinguish at risk obese normotensive children for the development of concentric left ventricular remodelling.

Four Weeks of Aerobic Training Affects Cardiac Tissue Matrix Metalloproteinase, Lactate Dehydrogenase and Malate Dehydrogenase Enzymes Activities, and Hepatorenal Biomarkers in Experimental Hyperhomocysteinemia in Rats.

The aim of this study was to investigate the effect of the application of homocysteine as well as its effect under the condition of aerobic physical activity on the activities of matrix metalloproteinases (MMP), lactate dehydrogenase (LDH) and malate dehydrogenase (MDH) in cardiac tissue and on hepato-renal biochemical parameters in sera of rats. Male Wistar albino rats were divided into four groups (n = 10, per group): C: 0.9% NaCl 0.2 mL/day subcutaneous injection (s.c.); H: homocysteine 0.45 µmol/g b.w./day s.c.; CPA saline (0.9% NaCl 0.2 mL/day s.c.) and a program of physical activity on a treadmill; and HPA homocysteine (0.45 µmol/g b.w./day s.c.) and a program of physical activity on a treadmill. Subcutaneous injection of substances was applied 2 times a day at intervals of 8 h during the first two weeks of experimental protocol. Hcy level in serum was significantly higher in the HPA group compared to the CPA group (p < 0.05). Levels of glucose, proteins, albumin, and hepatorenal biomarkers were higher in active groups compared with the sedentary group. It was demonstrated that the increased activities of LDH (mainly caused by higher activity of isoform LDH2) and mMDH were found under the condition of homocysteine-treated rats plus aerobic physical activity. Independent application of homocysteine did not lead to these changes. Physical activity leads to activation of MMP-2 isoform and to increased activity of MMP-9 isoform in both homocysteine-treated and control rats.

Translocator Protein Modulation by 4'-Chlorodiazepam and NO Synthase Inhibition Affect Cardiac Oxidative Stress, Cardiometabolic and Inflammatory Markers in Isoprenaline-Induced Rat Myocardial Infarction.

The possible cardioprotective effects of translocator protein (TSPO) modulation with its ligand 4'-Chlorodiazepam (4'-ClDzp) in isoprenaline (ISO)-induced rat myocardial infarction (MI) were evaluated, alone or in the presence of L-NAME. Wistar albino male rats (b.w. 200-250 g, age 6-8 weeks) were divided into 4 groups (10 per group, total number N = 40), and certain substances were applied: 1. ISO 85 mg/kg b.w. (twice), 2. ISO 85 mg/kg b.w. (twice) + L-NAME 50 mg/kg b.w., 3. ISO 85 mg/kg b.w. (twice) + 4'-ClDzp 0.5 mg/kg b.w., 4. ISO 85 mg/kg b.w. (twice) + 4'-ClDzp 0.5 mg/kg b.w. + L-NAME 50 mg/kg b.w. Blood and cardiac tissue were sampled for myocardial injury and other biochemical markers, cardiac oxidative stress, and for histopathological evaluation. The reduction of serum levels of high-sensitive cardiac troponin T hs cTnT and tumor necrosis factor alpha (TNF-α), then significantly decreased levels of serum homocysteine Hcy, urea, and creatinine, and decreased levels of myocardial injury enzymes activities superoxide dismutase (SOD) and glutathione peroxidase (GPx) as well as lower grades of cardiac ischemic changes were demonstrated in ISO-induced MI treated with 4'-ClDzp. It has been detected that co-treatment with 4'-ClDzp + L-NAME changed the number of registered parameters in comparison to 4'-ClDzp group, indicating that NO (nitric oxide) should be important in the effects of 4'-ClDzp.

The Effects of a Meldonium Pre-Treatment on the Course of the Faecal-Induced Sepsis in Rats.

Sepsis is a life-threatening condition caused by the dysregulated and overwhelming response to infection, accompanied by an exaggerated pro-inflammatory state and lipid metabolism disturbance leading to sequential organ failure. Meldonium is an anti-ischemic and anti-inflammatory agent which negatively interferes with lipid metabolism by shifting energy production from fatty acid oxidation to glycolysis, as a less oxygen-demanding pathway. Thus, we investigated the effects of a four-week meldonium pre-treatment on faecal-induced sepsis in Sprague-Dawley male rats. Surprisingly, under septic conditions, meldonium increased animal mortality rate compared with the meldonium non-treated group. However, analysis of the tissue oxidative status did not provide support for the detrimental effects of meldonium, nor did the analysis of the tissue inflammatory status showing anti-inflammatory, anti-apoptotic, and anti-necrotic effects of meldonium. After performing tissue lipidomic analysis, we concluded that the potential cause of the meldonium harmful effect is to be found in the overall decreased lipid metabolism. The present study underlines the importance of uninterrupted energy production in sepsis, closely drawing attention to the possible harmful effects of lipid-mobilization impairment caused by certain therapeutics. This could lead to the much-needed revision of the existing guidelines in the clinical treatment of sepsis while paving the way for discovering new therapeutic approaches.

Quantifying atherogenic lipoproteins for lipid-lowering strategies: consensus-based recommendations from EAS and EFLM.

The joint consensus panel of the European Atherosclerosis Society (EAS) and the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) recently addressed present and future challenges in the laboratory diagnostics of atherogenic lipoproteins. Total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDLC), LDL cholesterol (LDLC), and calculated non-HDLC (=total - HDLC) constitute the primary lipid panel for estimating risk of atherosclerotic cardiovascular disease (ASCVD) and can be measured in the nonfasting state. LDLC is the primary target of lipid-lowering therapies. For on-treatment follow-up, LDLC shall be measured or calculated by the same method to attenuate errors in treatment decisions due to marked between-method variations. Lipoprotein(a) [Lp(a)]-cholesterol is part of measured or calculated LDLC and should be estimated at least once in all patients at risk of ASCVD, especially in those whose LDLC declines poorly upon statin treatment. Residual risk of ASCVD even under optimal LDL-lowering treatment should be also assessed by non-HDLC or apolipoprotein B (apoB), especially in patients with mild-to-moderate hypertriglyceridemia (2-10 mmol/L). Non-HDLC includes the assessment of remnant lipoprotein cholesterol and shall be reported in all standard lipid panels. Additional apoB measurement can detect elevated LDL particle (LDLP) numbers often unidentified on the basis of LDLC alone. Reference intervals of lipids, lipoproteins, and apolipoproteins are reported for European men and women aged 20-100 years. However, laboratories shall flag abnormal lipid values with reference to therapeutic decision thresholds.