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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.

Objective: Polycystic ovary syndrome (PCOS) is associated with altered lipid profile and increased small, dense LDL particles (sdLDL). Considering that paraoxonase 1 (PON1) is an anti-oxidative enzyme located on high-density lipoprotein (HDL) particles, the aim of this study was to investigate the connection between oxidative stress (OS) and PON1 activity with lipoprotein subclasses in PCOS depending on obesity. Methods: In 115 PCOS patients lipoprotein subclasses distributions were determined by gradient gel electrophoresis. OS status was assessed by total oxidative status (TOS), advanced oxidation protein products (AOPP), malondialdehyde (MDA), prooxidant-Antioxidant balance (PAB), total antioxidant status (TAS) and superoxide dismutase (SOD) and PON1 activity. Results: Overweight/obese PCOS patients (n=55) had increased OS compared to normal weight patients (n=60). In addition, overweight/obese group had lower HDL size and higher proportion of HDL 3a subclasses (P

OBJECTIVE: The aim of the study was to assess the potential role of oxidative stress and lipid status in the onset of preeclampsia.METHODS: 138 high-risk pregnant women were prospectively followed....

The aim of this multicentric study was to assess the impacts of oxidative stress, inflammation, and the presence of small, dense, low-density lipoproteins (sdLDL) on the antioxidative function of high-density lipoprotein (HDL) subclasses and the distribution of paraoxonase-1 (PON1) activity within HDL in patients with ST-segment elevation acute myocardial infarction (STEMI). In 69 STEMI patients and 67 healthy control subjects, the lipoproteins’ subclasses were separated using polyacrylamide gradient (3–31%) gel electrophoresis. The relative proportion of sdLDL and each HDL subclass was evaluated by measuring the areas under the peaks of densitometric scans. The distribution of the relative proportion of PON1 activity within the HDL subclasses (pPON1 within HDL) was estimated using the zymogram method. The STEMI patients had significantly lower proportions of HDL2a and HDL3a subclasses (p = 0.001 and p < 0.001, respectively) and lower pPON1 within HDL3b (p = 0.006), as well as higher proportions of HDL3b and HDL3c subclasses (p = 0.013 and p < 0.001, respectively) and higher pPON1 within HDL2 than the controls. Independent positive associations between sdLDL and pPON1 within HDL3a and between malondialdehyde (MDA) and pPON1 within HDL2b were shown in the STEMI group. The increased oxidative stress and increased proportion of sdLDL in STEMI are closely related to the compromised antioxidative function of small HDL3 particles and the altered pPON1 within HDL.

Introduction: Indirect estimation of reference intervals (RIs) is straightforward and inexpensive procedure for determination of intra-laboratory RIs. We applied the indirect approach to assess RIs for haematological parameters in capillary blood of pre-school children, using results stored in our laboratory database. Materials and methods: We extracted data from laboratory information system, for the results obtained by automatic haematology analyser in capillary blood of 154 boys and 146 girls during pre-school medical examination. Data distribution was tested, and logarithmic transformation was applied if needed. Reference intervals were calculated by the nonparametric percentile method. Results: Reference intervals were calculated for: RBC count (4.2-5.4 x1012/L), haemoglobin (114-146 g/L), MCH (25.0-29.4 pg), MCHC (321-368 g/L), RDW-SD (36.1-43.5 fL), WBC count (4.5-12.3 x109/L), neutrophils count (1.7-6.9 x109/L) and percentage (29.0-69.0%), lymphocytes count (1.6-4.4 x109/L) and percentage (21.9-60.7%), PLT (165-459 x109/L), MPV (8.1-11.4 fL) and PDW (9.2-14.4%). Gender specific RIs were calculated for monocytes count (male (M): 0.2-1.6 x109/L; female (F): 0.1-1.4 x109/L) and percentage (M: 2.5-18.3%; F: 1.8-16.7%), haematocrit (M: 0.34-0.42 L/L; F: 0.34-0.43 L/L), MCV (M: 73.4-84.6 fL; F: 75.5-84.2 fL) and RDW (M: 12.1-14.3%; F: 11.7-13.9%), due to observed gender differences in these parameters (P = 0.031, 0.028, 0.020, 0.012 and 0.001; respectively). Estimated RIs markedly varied from the literature based RIs that are used in the laboratory. Conclusions: Indirect method employed in this study enables straightforward assessment of RIs in pre-school children. Herein derived RIs differed from the literature-based ones, indicating the need for intra-laboratory determination of RIs for specific populations and sample types.

Aim: Despite many efforts, reliable biomarkers for the prediction and diagnosis of colorectal cancer (CRC) are still missing. Insulin-like growth factor 1 (IGF-1) and E-cadherin are recognized as potential biomarkers, but their diagnostic capacity is largely unexplored in CRC. The aim of this work is to investigate IGF-1 and E-cadherin levels with respect to various characteristics of CRC and to estimate their diagnostic potential. Method: Seventy CRC patients and 75 healthy individuals were enrolled. IGF-1 and E-cadherin were determined using enzyme-linked immunosorbent assay. The predictive and diagnostic capacities of IGF-1 and E-cadherin were estimated by logistic regression analysis and by determination of the area under the receiver operating characteristic (ROC) curve (AUC). Results: Concentrations of IGF-1 were lower (P = 0.019) while levels of E-cadherin were higher (P < 0.001) in CRC patients than in controls. IGF-1 concentration decreased in parallel with age and progression of CRC (P = 0.023). Also, IGF-1 was higher in men with CRC than in women (P = 0.003). E-cadherin levels were unaffected by variations in either anthropometric characteristics of CRC patients, or localization, grade and stage of the tumour. Both IGF-1 and E-cadherin were independently associated with CRC (P = 0.040; P < 0.001, respectively). The diagnostic accuracy of IGF-1 was estimated as acceptable (AUC = 0.757; P < 0.001), while the diagnostic accuracy of E-cadherin was outstanding (AUC = 0.954; P < 0.001). Conclusions: Decreased IGF-1 and increased E-cadherin levels were found in CRC patients. IGF-1, but not E-cadherin, concentrations differed according to age, gender and stage of CRC. Both markers were independently associated with the presence of the disease, while E-cadherin demonstrated high diagnostic accuracy.

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.

Background:Vitamin D deficiency is repeatedly reported in colorectal cancer (CRC). Since cholesterol and vitamin D share common precursor 7-dehydrocholesterol (7-DHC), it would be important to explore the associations of key vitamin D metabolites and serum lipid parameters in patients with high and low grade CRC. The aim of this study was toanalyze relationships between serum 25(OH)D3,24,25(OH)2D3 and 7-DHC levels and serum lipids inpatients with CRC, and to evaluate their potential for prediction of risk for development of high grade CRC. Methods:We recruited 82 patients CRC and 77 controls.7-DHC, 25(OH)D3 and 24,25(OH)2D3 were quantified by LC-MS/MS methods.Results:7-DHC, 25(OH)D3 and vitamin D metabolic ratio(VDMR) were significantly lower in CRC patients than in control group (P

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.

The presence of residual cardiovascular disease (CVD) risk is a current dilemma in clinical practice; indeed, despite optimal management and treatment, a considerable proportion of patients still undergo major CV events. Novel lipoprotein biomarkers are suggested as possible targets for improving the outcomes of patients at higher risk for CVD, and their impact on major CV events and mortality have previously been investigated. Innovative antidiabetic therapies have recently shown a significant reduction in atherogenic lipoproteins, beyond their effects on glucose parameters; it has also been suggested that such anti-atherogenic effect may represent a valuable mechanistic explanation for the cardiovascular benefit of, at least, some of the novel antidiabetic agents, such as glucagon-like peptide-1 receptor agonists. This emphasizes the need for further research in the field in order to clearly assess the effects of innovative treatments on different novel biomarkers, including atherogenic lipoproteins, such as small dense low-density lipoprotein (LDL), lipoprotein(a) (Lp(a)) and dysfunctional high-density lipoprotein (HDL). The current article discusses the clinical importance of novel lipid biomarkers for better management of patients in order to overcome residual cardiovascular risk.

Introduction The link between preeclampsia and dyslipidemia has been established. Even though lipid profile parameters have been intensively investigated in the pathology of preeclampsia, their accurate molecular mechanisms of action have not been fully decoded. Objectives We aimed to identify the specifics of cholesterol metabolism in women affected by late‑onset preeclampsia and single out potential biomarkers associated with late‑onset syndrome. Patient s and methods A total of 90 pregnant women with a priori risk for preeclampsia were monitored at 4 time points during gestation and, based on the outcome of pregnancy, they were classified into the high‑risk group (70 women) and the preeclampsia group (20 women). Cholesterol metabolic profiling was done using liquid chromatography‑tandem mass spectrometry. Result s The only significant change in the preeclampsia group was an increase in the lathosterol level (P = 0.001). The first‑trimester lathosterol level was higher in the preeclampsia group compared with the high‑risk group (P = 0.02). Further, in the preeclampsia group, positive correlations were found between desmosterol and β‑sitosterol (ρ = 0.474; P = 0.03) in the third trimester, desmosterol and campesterol changes between the second and the first (ρ = 0.546; P = 0.02), and the third and first trimesters (ρ = 0.754; P

Epidemiological data have demonstrated a significant association between the presence of type 2 diabetes mellitus (T2DM) and the development of colorectal cancer (CRC). Chronic hyperglycemia, insulin resistance, oxidative stress, and inflammation, the processes inherent to T2DM, also play active roles in the onset and progression of CRC. Recently, small dense low-density lipoprotein (LDL) particles, a typical characteristic of diabetic dyslipidemia, emerged as another possible underlying link between T2DM and CRC. Growing evidence suggests that antidiabetic medications may have beneficial effects in CRC prevention. According to findings from a limited number of preclinical and clinical studies, glucagon-like peptide-1 receptor agonists (GLP-1RAs) could be a promising strategy in reducing the incidence of CRC in patients with diabetes. However, available findings are inconclusive, and further studies are required. In this review, novel evidence on molecular mechanisms linking T2DM with CRC development, progression, and survival will be discussed. In addition, the potential role of GLP-1RAs therapies in CRC prevention will also be evaluated.

Background and aims: Dyslipidemia in type 1 diabetes mellitus (T1DM) is characterised by altered distributions of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subclasses. Recent studies suggested that proprotein convertase subtilisin/kexin 9 (PCSK9) may contribute to the development of dyslipidemia in T1DM. In this cross-sectional study, we investigated the association between PCSK9 and lipoprotein subclasses in young T1DM patients, with respect to glycemic control. Methods: Plasma PCSK9 and lipoprotein subclasses were determined in 207 patients with T1DM (106 boys and 101 girls), aged 13.9 +/- 3.0 years and treated by intensive insulin therapy. Results: Plasma PCSK9 levels significantly increased with worsening of glycemic control (p lt 0.001). T1DM patients with poor glucoregulation had the highest proportion of small, dense LDL (sdLDL) and smaller HDL particles, as well. PCSK9 was positively associated with markers of glucose homeostasis and serum lipid parameters only in patients with suboptimal/poor glucoregulation. In well-controlled T1DM, plasma PCSK9 level was inversely associated with a relative proportion of sdLDL particles (p lt 0.01) and this association remained significant in multivariate analysis. In T1DM patients with suboptimal/poor glycemic control, PCSK9 was positively associated with the proportion of the smallest HDL3c particles (p lt 0.001), but negatively with HDL size (p lt 0.05). Conclusions: The extent of achieved metabolic control modifies the association between PCSK9 and lipoprotein subclasses in T1DM. Further investigations are needed to reveal whether the observed effects of glycemic control on PCSK9 and sdLDL levels have causal consequences on CVD risk in young patients with T1DM.

Resistin might be involved with general inflammation and endothelial dysfunction observed in preeclampsia. We aimed to investigate longitudinal changes in resistin concentrations during high-risk pregnancies and evaluate their significance in preeclampsia development. Ninety-one patients were recruited at 11-14 weeks of gestation. They were followed towards the end of each trimester and before their deliveries. Of the 91 pregnant women, 21 developed preeclampsia, while 70 women did not develop preeclampsia despite being at risk. Compared to the 1

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.

Colorectal cancer (CRC) is a highly prevalent malignancy with multifactorial etiology, which includes metabolic alterations as contributors to disease development. Studies have shown that lipid status disorders are involved in colorectal carcinogenesis. In line with this, previous studies have also suggested that the serum high-density lipoprotein cholesterol (HDL-C) level decreases in patients with CRC, but more recently, the focus of investigations has shifted toward the exploration of qualitative properties of HDL in this malignancy. Herein, a comprehensive overview of available evidences regarding the putative role of HDL in CRC will be presented. We will analyze existing findings regarding alterations of HDL-C levels but also HDL particle structure and distribution in CRC. In addition, changes in HDL functionality in this malignancy will be discussed. Moreover, we will focus on the genetic regulation of HDL metabolism, as well as the involvement of HDL in disturbances of cholesterol trafficking in CRC. Finally, possible therapeutic implications related to HDL will be presented. Given the available evidence, future studies are needed to resolve all raised issues concerning the suggested protective role of HDL in CRC, its presumed function as a biomarker, and eventual therapeutic approaches based on HDL.

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 (

Recent findings implied the significance of reactive oxygen species (ROS) as a part of tyrosine kinase inhibitors (TKIs) pharmacological activity. Evidences also suggested that toxic effects of TKIs were related to ROS production. The results regarding benefits of vitamin E usage alongside with prescribed TKIs therapy are ambiguous. We aimed to examine oxidative stress and antioxidative defense in human serum treated with four different TKIs and their possible interactions with hydrosoluble vitamin E analog (Trolox). An in-vitro experiment with serum pool as a substitute model was performed. Different parameters of oxidative stress and antioxidative defense were measured in serum pool with and without addition of TKIs (axitinib, crizotinib, nilotinib, and imatinib), before and after addition of Trolox. Z score statistic was used for calculation of Prooxidative and Antioxidative scores. The highest oxidative potential was recorded for samples incubated with imatinib and nilotinib, while the lowest damaging scores were observed for crizotinib and axitinib (nilotinib vs. imatinib, P

Asymptomatic outdoor dogs can be carriers of Babesia canis, but data describing the development of an acute phase response (APR) are not available. We hypothesised that these dogs have a moderate APR that could be detected by hematological and biochemical changes. Two groups of Babesia-exposed dogs were represented by nine B. canis PCR-positive and twenty B. canis PCR-negative, seroreactive dogs. The control group consisted of ten Babesia-naïve dogs. Serum amyloid A (SAA), paraoxonase-1 (PON-1), complete blood count, and biochemistry parameters were analysed by standard methodologies. Protein and lipoprotein fractions were separated using agarose gel electrophoresis (GE), and the dominant diameters of lipoproteins were assessed on gradient GE. Results were evaluated using non-parametric tests and the Receiver Operating Characteristic curve. SAA (median 39.0 μg/mL, range 2.2–48.8 μg/mL), total protein (median 74.7 g/L, range 57.1–98.3 g/L) and the dominant diameter of α-lipoproteins (median 13.31 nm, range 12.09–14.17 nm) in B. canis PCR-positive dogs were higher relative to dogs in the control group or dogs that were PCR-negative but seroreactive (p

Background:Non-cholesterol sterols (NCS) are promising biomarkers for estimation of cholesterol homeostasis properties. In addition, determination of NCS in high-density lipoprotein (HDL) fraction (HDL-NCS) could provide information on cholesterol efflux. However, matrix effects interfere in liquid chromatography–mass spectrometry (LC-MS)analysis of NCS, thereby impairing the method sensitivity.The aims of this study were development, optimization and validation of LC-MS method for quantification of NCS in serum and HDL-NCS. Additionally, matrix effect interfer-ences and methods application in individual serum samples were examined.Methods:HDL precipitating reagent was used for HDL isolation. Matrix effect was examined by comparing different surrogates by simple regression analysis. Validation was conducted according to the FDA-ICH guideline. 20 healthy volunteers were recruited for testing of method application.Results:The observed matrix effect was 30%, and matrix comparison showed that cholesterol was the dominant contributor to the matrix effect. Cholesterol concentration was adjusted by construction of the calibration curve for serum and HDL fraction (5 mmol/L and 2.5 mmol/L,respectively). The intra- and inter- run variabilities for NCSs were 4.7–10.3% for serum NCS and 3.6–13.6% for HDL-NCS and 4.6–9.5% for serum NCSs and 2.5–9.8% for HDL-NCS, respectively. Recovery studies showed satisfactory results for NCSs: 89.8–113.1% for serum NCS and85.3–95.8% for HDL-NCS. Conclusions:The method was successfully developed and optimized. The matrix interference was solved by customising calibration curves for each method and sample type.The measurement of NCS in HDL fraction was proposed for the first time as potentially useful procedure in biomedical researches. Uvod: Neholesterolski steroli (NHS) predstavljaju potencijalne biomarkere homeostaze holesterola. Pored toga, određivanje NHS u HDL frakciji (HDL-NHS) moglo bi da pruži dodatne informacije o efluksu holesterola. Međutim, određivanje NHS metodom tečne hromatografije - masene spektrometrije (LC-MS) je podložno uticaju matriksa usled čega dolazi do sniženja osetljivost metode. Studija je prvenstveno imala za cilj razvoj, optimizaciju i validaciju LC-MS metode za kvantifikaciju NHS u serumu i HDL-NHS. Pored toga, detaljno je ispitan efekat matriksa i metoda primenjena za analizu uzoraka seruma zdravih dobrovoljaca. Metode: Izolacija HDL frakcije je izvršena upotrebom precipitirajućeg reagensa. Efekat matriksa je ispitan poređenjem različitih surogat matriksa regresionom analizom. Validacija je sprovedena u skladu sa FDA-ICH vodičem za validaciju bioanalitičkih metoda. Korišćeni su serumi 20 zdravih dobrovoljaca u cilju kliničke evaluacije metode. Rezultati: Efekat matriksa je iznosio 30% i dalja analiza je pokazala da je holesterol bio glavni uzročnik efekta matriksa. U cilju rešavanja ove interferencije, kalibracione krive za su pripremljene u metanolnom rastvoru holesterola koncentracije 5 mmol/L, a za kvantifikaciju HDL-NHS u metanolnom rastvoru holesterola koncentracije 2,5 mmol/L. Varijacije unutar serije su bile 4,7-10,3% za NHS i 3,6-13,6% za HDL-NHS, a između serija 4,6-9,5% za NHS i 2,5-9,8% za HDL-NHS. Studije prinosa analita su pokazale zadovoljavajuće rezultate: 89,8-113,1% za NHS i 85,3-95,8% za HDL-NHS. Zaključak: Metoda je uspešno optimizovana i validirana. Interferencija usled prisustva holesterola je korigovana upotrebom odgovarajućih kalibracionih krivih za svaku vrstu uzorka. Određivanje HDL-NHS je po prvi put predloženo kao potencijalno korisna procedura u biomedicinskim istraživanjima.

BackgroundWe evaluated the qualitative characteristics of high-density lipoprotein (HDL) particles in metabolically healthy and unhealthy overweight and obese subjects.MethodsThe study involved 115 subject individuals classified as metabolically healthy and unhealthy, as in overweight and obese groups. Commercial enzyme-linked immunosorbent assay (ELISA) kits were used to measure oxidized HDL (OxHDL) and serum amyloid A (SAA) concentrations. Lipoprotein subfractions were separated using nondenaturing gradient gel electrophoresis.ResultsAn independent association was shown between increased OxHDL/HDL-cholesterol ratio and the occurrence of metabolically unhealthy phenotype in the overweight and obese groups. The OxHDL/HDL-cholesterol ratio showed excellent and acceptable diagnostic accuracy in determination of metabolic health phenotypes (overweight group, AUC = 0.881; obese group, AUC = 0.765). Accumulation of smaller HDL particles in metabolically unhealthy subjects was verified by lipoprotein subfraction analysis. SAA concentrations did not differ significantly between phenotypes.ConclusionsIncreased OxHDL/HDL-cholesterol ratio may be a potential indicator of disturbed metabolic health in overweight and obese individuals.

Colorectal cancer (CRC) is a highly prevalent malignancy. Previous studies suggested that cholesterol might play a signficant role in malignant transformation and proliferation. Non-cholesterol sterols (NCS), which are transported by serum lipoproteins alongside cholesterol, are regarded as cholesterol synthesis and absorption markers. Quantification of NCS in serum and HDL fraction (NCSHDL), could provide a better insight into the cholesterol metabolism. The aim of this study was to examine the status of cholesterol synthesis and cholesterol absorption markers in serum and HDL fraction and explore their interrelation in CRC patients. Current study was designed as observational, case-control study. The study included 73 CRC patients and 95 healthy subjects. NCS and NCSHDL concentrations were determined by HPLC-MS/MS. Based on NCS and NCSHDL concentrations, different cholesterol homeostasis indices were calculated. Patients had significantly lower NCS (P

Systemic sclerosis (SSc) is an autoimmune connective tissue disease which affects various tissues and organs, including skin, lungs, kidneys, gastrointestinal tract and cardiovascular system. Cardiac involvement is the most commonly recognized problem and a significant cause of morbidity. The brain natriuretic peptide (BNP) is a previously known marker of elevated cardiovascular risk in SSc, but the levels of BNP in various forms of SSc have not been investigated so far.The aim of our study was to evaluate the influence of SSc on the function of the right ventricle and the right atrium using the echocardiographic parameters. Moreover, we examined the levels of BNP in different forms of SSc as well as the association of disease severity with the plasma concentrations of BNP.We included 42 patients with newly diagnosed SSc and patients whose disease had been diagnosed earlier. SSc patients and non-SSc control patients were examined by using echocardiography and the concentrations of BNP were determined.We analyzed differences in the parameters of right ventricle (RV) function and right atrium (RA) function between SSc patients and healthy controls. The two groups had similar distribution of gender, but SSc patients were significantly older than controls. RV wall thickness was increased in SSc patients (p0.001), while right ventricular end-systolic area (RVGiven the obtained results, the laboratory determination of BNP could be useful in differentiating different forms of systemic sclerosis as well as in predicting the severity of the disease and future cardiovascular complications.Sistemska skleroza (SSc) jeste autoimuna bolest vezivnog tkiva koja utiče na različita tkiva i organe, uključujući kožu, pluća, bubrege, gastrointestinalni trakt i kardiovaskularni sistem. Komplikacije na srcu su najčešće prepoznat problem i značajan uzrok morbiditeta. Moždani natriuretski peptid (BNP) odranije je poznat marker povišenog kardiovaskularnog rizika u SSc, ali nivoi BNP-a u različitim formama SSc do sada nisu ispitivani.Cilj naše studije bio je proveriti uticaj SSc na funkciju desne komore i desne pretkomore praćenjem ehokardiografskih parametara. Takođe, ispitivali smo koncentracije BNP-a u različitim formama SSc.U studiju je uključeno 42 bolesnika sa novootkrivenom SSc, kao i bolesnici kod kojih je bolest ranije dijagnostikovana. Bolesnicima sa SSc i kontrolnoj grupi obavljen je ultrazvučni pregled srca i određena koncentracija BNP-a.Analizirali smo razlike u parametrima funkcija desne komore i desne pretkomore između bolesnika sa SSc i zdravih osoba. Zadebljanje zida desne komore je veće kod bolesnika sa SSc (p0,001), dok se površine desne komore u sistoli (RVS obzirom na dobijene rezultate, laboratorijsko određivanje BNP-a moglo bi biti korisno u diferencijaciji različitih oblika sistemske skleroze, kao i u predviđanju težine bolesti i budućih kardiovaskularnih komplikacija.

The aim of this study was to explore oxidative stress status, especially the enzyme myeloperoxidase in children with end-stage renal disease. Also, we investigated possible associations between the atherogenic index of plasma and these parameters.Lipid status parameters, oxidative stress status parameters, and myeloperoxidase concentration were measured in the sera of 20 children in the last stage of chronic renal disease (ESRD) and 35 healthy children of matching age and sex. The Atherogenic Index of Plasma (AIP) was calculated according to the appropriate equation.We did not find any significant differences in myeloperoxidase concentrations between the investigated groups (p=0.394). Oxidative stress parameters were, however, significantly higher in the patient group (p0.001), as well as the atherogenic index of plasma (p0.001). Myeloperoxidase concentration and advanced oxidation protein product (AOPP) concentration were independently associated with increased AIP in the patient group (p0.05).Changes in AIP in children with ERSD are associated with the oxidative stress status and myeloper-oxidase concentration.Cilj ove studije bio je da se ispita status oksidativnog stresa, naročito enzima mijeloperoksidaze kod dece u terminalnoj fazi bubrežne insuficijencije. Takođe smo istraživali potencijalnu povezanost između aterogenog indeksa plazme i ovih parametara.Parametri lipidnog statusa, parametri statusa oksidativnog stresa i koncentracija mijeloperoksidaze mereni su u serumu 20 dece u finalnoj fazi hronične bubrežne insuficijencije (HBI) i 35 zdrave dece odgovarajućeg uzrasta i pola. Aterogeni indeks plazme (AIP) izračunat je pomoću odgovarajuće jednačine.Između ispitivanih grupa nisu otkrivene značajne razlike u koncentracijama mijeloperoksidaze (p=0,394). Međutim, parametri oksidativnog stresa bili su značajno viši u grupi obolelih (p0,001) kao i aterogeni indeks plazme (p0,001). Koncentracija mijeloperoksidaze i koncentracija proizvoda uznapredovale proteinske oksida cije (eng. AOPP) bili su nezavisno povezani sa povišenim AIP-om u grupi obolelih (p0,05).Promene u AIP-u kod dece sa HBI povezane su sa statusom oksidativnog stresa i koncentracijom mijeloperoksidaze.

Osteoporosis is characterised by reduced bone mineral density (BMD), increased bone fragility and risk of fractures. We investigated clinical significance of bone turnover biomarkers determination for the prediction of fracture risk and response to therapy. We performed three months follow-up study in 48 women with osteoporosis. During the follow-up period 32 patients were on antiresorptive and 16 patients received anabolic therapy. Serum alkaline phosphatase (ALP), osteocalcin, C-terminal telopeptide of collagen type I and vitamin D were measured before and 3 months after initiation of the therapy. Higher osteocalcin and ALP levels were significantly associated with increased risk of BMD loss. Following antiresorptive therapy levels of C-terminal telopeptide (P lt 0.001) and osteocalcin (P lt 0.001) significantly decreased. Anabolic therapy significantly increased osteocalcin (P lt 0.01). At the study entry 25.5% of the patients had optimal levels of 25(OH)D and 17% had severe vitamin D deficiency. Vitamin D supplementation during three months improved vitamin D status of the patients (P lt 0.001). In conclusion, our data indicate that osteocalcin and C-terminal telopeptide determination may be useful for BMD loss prediction and monitoring of osteoporosis therapy. This study confirmed importance of vitamin D testing in osteoporosis in order to detect the patients with deficiency and determine the need for supplementation. Osteoporoza se karakteriše smanjenom mineralnom gustinom kostiju, što povećava fragilnost kostiju i rizik za nastanak fraktura. U ovoj studiji pratili smo 48 pacijentkinja sa osteoporozom tokom tri meseca sa ciljem da utvrdimo značaj određivanja koštanih biomarkera u proceni rizika od fraktura i praćenju terapije osteoporoze. Tokom trajanja studije 32 pacijentkinje su bile na antiresorptivnoj, a 16 na anaboličkoj terapiji. Svim pacijentkinjama odredili smo aktivnost alkalne fosfataze (ALP) i koncentracije osteokalcina, C-terminalnog telopeptida kolagena tip I i vitamina D u serumu pre i tri meseca nakon uvođenja terapije. Sa povećanjem nivoa osteokalcina i ALP rastao je rizik za smanjenje mineralne gustine kostiju (BMD). Antiresorptivna terapija dovela je do značajnog smanjenja koncentracija C-terminalnog telopeptida (P lt 0,001) i osteokalcina (P lt 0,001). Tokom anaboličke terapije nivo osteokalcina je značajno porastao (P lt 0,01). Na početku studije 25,5% pacijentkinja je imalo optimalne koncentracije 25(OH)D u serumu, a tešku deficijenciju 17% žena. Nakon 3 meseca suplementacije većina je poboljšala status vitamina D (P lt 0,001). Naši rezultati ukazuju da određivanje osteokalcina i C-terminalnog telopeptida može biti korisno za predviđanje rizika za smanjenje BMD i praćenje efekata terapije osteoporoze. Takođe, potvrđena je važnost određivanja koncentracije 25(OH)D za procenu statusa vitamina D u osteoporozi, u cilju otkrivanja pacijenata sa insuficijencijom i utvrđivanja potrebe za suplementacijom.

Unfavorable lipid profile presents one of most important risk factor for cardiovascular disease in renal pathology. Myeloperoxidase (MPO) as enzyme which oxidizes lipoproteins and paraoxonase1 (PON1) as anti-oxidative enzyme have been involved in pathogenesis of cardiovascular disease. In the present study we sought to assess oxidative stress status, lipoprotein subclasses distribution as well as functionality of high density lipoprotein (HDL) trough MPO/PON1 ratio in children with chronic kidney disease (CKD) and children after renal transplantation.PON1 activity and oxidative stress parameters were measured spectrophotometrically, while MPO concentration was determined using immunoassay. Separation of lipoprotein subclasses was performed by vertical gradient gel electrophoresis in 19 children with different stage of CKD and 19 post-transplantation patients (PT).CKD patients had increased MPO/PON1 ratio and higher prevalence of smaller HDL subclasses when compared to PT subjects. Also, there was a significant positive correlation between MPO level and MPO/PON1 ratio with relative proportion of smaller HDL subclasses.Children with CKD have impaired HDL distribution that is improved after kidney transplantation. Since that measurement of HDL distribution and functionality are not routinely available, MPO/PON1 ratio may be useful marker that could provide necessary information.Displipidemija predstavlja jedan od osnovnih faktora rizika za razvoj kardiovaskularnih bolesti kod pacijenata sa hroničnim bubrežnim bolestima (CKD). Mijeloperoksidaza (MPO) je enzim koji dovodi do oksidativne modifikacije lipoproteinskih čestica, dok sa druge strane, paraoksonaza 1 (PON 1) predstavlja antioksidativni enzim koji sprečava ove procese. Cilj ove studije bio je ispitivanje oksidativnostresnog statusa i raspodele lipoproteinskih čestica kod dece sa različitim stadijumima CKD i nakon transplantacije bubrega. Takođe, u ovoj studiji je ispitivan odnos MPO/PON1 i njegova veza sa promenama distribucije HDL.U studiji je učestvovalo 19 dece u različitim stadijumima CKD i 19 dece nakon transplantacije bubrega (PT). Parametri oksidativno-stresnog statusa i aktivnost enzima PON 1 određeni su spektrofotometrijskim metodama, dok je koncentracija MPO određena imunoesejem. Razdvajanje lipoproteinskih subfrakcija vršeno je metodom vertikalne gradijent gel elektoforeze.U CKD grupi su dobijene statistički značajno više vrednosti odnosa MPO/PON1, kao i veći procenat malih HDL čestica u poređenju sa PT grupom. Takođe, uočena je statistički značajna pozitivna korelacija između MPO/PON1 odnosa i relativnog udela malih, HDL čestica kod ovih pacijenata.Rezultati ove studije pokazuju da transplantacija kod dece sa hroničnim bolestima bubrega dovodi do pomeranja raspodele HDL subfrakcija ka česticama sa bolje očuvanim funkcionalnim svojstvima. Odnos MPO/PON1 može biti koristan marker funkcionalnosti HDL.

Background: Elevated concentrations of resistin have been reported in colorectal cancer (CRC), but its interactions with adenylate cyclase-associated protein 1 (CAP-1) are largely unexplored. We investigated resistin plasma concentration, peripheral blood mononuclear cells (PBMCs) resistin messenger ribonucleic acid (mRNA), and CAP-1 mRNA levels in CRC patients, as well as the impact of resistin gene polymorphism rs1862513 on the examined markers. We also explored associations of resistin with high-density lipoprotein cholesterol (HDL-C) and predictive potential of our parameters for CRC. Methods: Eighty-six patients with CRC and 75 healthy adults were included. Commercial ELISA kit was used for obtaining resistin’s concentrations, while polymerase chain reaction (PCR) method was applied for evaluation of resistin and CAP-1 mRNA levels and rs1862513 polymorphism. Results: Plasma resistin and CAP-1 mRNA levels were higher in CRC patients (p < 0.001 and p < 0.05, respectively), while resistin mRNA levels were lower (p < 0.001). Negative association existed among plasma resistin and HDL-C concentrations (ρ = − 0.280; p < 0.05). A model including age, body-mass index, HDL-C, low-density lipoprotein cholesterol (LDL-C), and plasma resistin concentrations as independent predictors of CRC showed very good diagnostic accuracy (AUC = 0.898). We found no associations of rs1862513 with the examined markers. Conclusions: Our study demonstrated increased plasma resistin and CAP-1 mRNA levels, implying their possible interaction in CRC. The association among plasma resistin and HDL-C might indicate that HDL-C is involved in alterations of resistin’s secretion process. As a hallmark of personalized medicine, multi-marker approach in determination of resistin-related parameters might be useful for prediction and prevention of CRC development.

BackgroundNon-alcoholic fatty liver disease is a frequent ailment with known complications, including those within the cardiovascular system. Associations between several indicators of high-density lipoprotein metabolism and function with clinical and laboratory parameters for the assessment of fatty liver index, a surrogate marker of non-alcoholic fatty liver disease, were evaluated.MethodsThe study comprised 130 patients classified according to fatty liver index values: fatty liver index ResultsIncreased lecithin–cholesterol acyltransferase activity correlated with increased fatty liver index ( P ConclusionsHigher lecithin–cholesterol acyltransferase activity is associated with elevated fatty liver index values. Significant independent association between triglycerides and lecithin–cholesterol acyltransferase activity might indicate a role of hypertriglyceridaemia in alterations of lecithin–cholesterol acyltransferase activity in individuals with elevated fatty liver index.

A direct and an indirect relationship between paraoxonase 1 (PON1) and atherosclerosis exists. Given PON1's physical location within high-density lipoprotein (HDL) particles and its recognized enzyme activity, it is certainly reasonable to suggest that PON1 facilitates the antiatherogenic nature of HDL particles. PON1 also plays a role in regulating reverse cholesterol transport, antioxidative, anti-inflammatory, antiapoptotic, vasodilative, and antithrombotic activities and several endothelial cell functions. HDL dysfunctionality is a more recent issue and seems to be centered on pathological conditions affecting HDL structure and size profiles. This review is focused on the role of PON1 status in different atherosclerosis-related diseases that we have studied over the last twenty years (coronary heart disease, acute ischemic stroke, diabetes mellitus type 2, end-stage renal disease, chronic obstructive pulmonary disease, and sarcoidosis) with the aim to determine the true value of PON1 as a biomarker. The role of PON1 in cancer is also covered, as risk factors and mechanisms underlying both atherosclerosis and cancer share common features. © 2019 International Union of Biochemistry and Molecular Biology

Background Babesia canis infection induces a marked acute phase response (APR) that might be associated with alteration in lipid and lipoprotein metabolism and disease prognosis. Hypothesis Dogs with B. canis-induced APR develop dyslipidemia with altered lipoprotein concentration and morphology. Animals Twenty-nine client-owned dogs with acute B. canis infection and 10 clinically healthy control dogs. Methods Observational cross-sectional study. Serum amyloid A (SAA) was measured using ELISA. Cholesterol, phospholipids, and triglycerides were determined biochemically. Lipoproteins were separated using agarose gel electrophoresis. Lipoprotein diameter was assessed by polyacrylamide gradient gel electrophoresis; correlation with ApoA-1 (radioimmunoassay) and SAA was determined. Results Dogs with B. canis infection had a marked APR (median SAA, 168.3 mu g/mL; range, 98.1-716.2 mu g/mL) compared with controls (3.2 mu g/mL, 2.0-4.2 mu g/mL) (P < .001). Dogs with B. canis infection had significantly lower median cholesterol (4.79 mmol/L, 1.89-7.64 mmol/L versus 6.15 mmol/L, 4.2-7.4 mmol/L) (P = .02), phospholipid (4.64 mmol/L, 2.6-6.6 mmol/L versus 5.72 mmol/L, 4.68-7.0 mmol/L) (P = .02), and alpha-lipoproteins (77.5%, 27.7%-93.5% versus 89.2%, 75.1%-93.5%) (P = .04), and higher ApoA-1 (1.36 U, 0.8-2.56 U versus 0.95 U, 0.73-1.54 U) concentrations (P = .02). Serum amyloid A correlated with high-density lipoproteins (HDLs) diameter (rho = .43; P = .03) and ApoA-1 (rho = .63, P < .001). Conclusions and Clinical Importance Major changes associated with B. canis-induced APR in dogs are related to concentration, composition, and morphology of HDL particles pointing to an altered reverse cholesterol transport. Parallel ApoA-1 and SAA concentration increase is a unique still unexplained pathophysiological finding.

Type 2 diabetes mellitus is a chronic high-prevalence metabolic disease, which is characterized by hyperglycaemia, but also with lipid and protein metabolism disorders. Patients with type 2 diabetes have a high risk for cardiovascular disease (CVD) development and dyslipidemia is considered as a key marker of this increased risk. Hypertriglyceridemia, reduced high density lipoprotein cholesterol (HDL-c) concentrations, and a shift in low-density lipoprotein particles (LDL) distribution toward the small, triglycerides-rich particles, are the most important changes in the lipid profile in diabetes.Type 2 diabetes is a metabolic disorder associated with low grade inflammation and oxidative stress, so in this condition high density lipoprotein particles (HDL) also undergo structural and functional changes and, as a consequence, lose their atheroprotective role. Dyslipidemia treatment in type 2 diabetes patients younger than 40 and without any other risk factor for CVD development starts with changes in a lifestyle, but in patients older than 40 years, first line medications are statins.Glycemic and lipid control in type 2 diabetes patients significantly reduces CVD risk. Dijabetes melitus tip 2 je hronično oboljenje sa visokom prevalencom, koje se karakteriše hiperglikemijom, ali i poremećajima u metabolizmu lipida i proteina. Pacijenti sa tipom 2 dijabetesa imaju visok rizik za razvoj kardiovaskularnih bolesti (KVB) i upravo se dislipidemija smatra ključnim uzročnikom ovog povećanog rizika. Hipertrigliceridemija, snižena koncentracija holesterola u lipoproteinskim česticama visoke gustine (HDL-h) i promena u raspodeli lipoproteinskih čestica niske gustine (LDL) u smeru većeg udela malih čestica, bogatih trigliceridima, predstavljaju najvažnije promene lipidnog profila koje se odnose na dislipidemiju u dijabetesu. Kako je dijabetes stanje kontinuirane blage inflamacije niskog stepena i stalne produkcije slobodnih radikala, HDL lipoproteinske čestice takođe podležu strukturnim i funkcionalnim promenama, usled čega gube svoje ateroprotektivne osobine. Terapija dislipidemije kod pacijenata mlađih od 40 godina bez prisutnih drugih faktora rizika za razvoj KVB počinje promenom životnog stila, a kod pacijenata starijih od 40 godina lekovi izbora u terapiji su statini. Glikemijska i lipidna kontrola kod pacijenata sa tipom 2 dijabetesa značajno umanjuje rizik od nastanka KVB.

Background: Previous studies revealed decreased level of high-density lipoprotein cholesterol (HDL-C) as important factor for development of colorectal cancer (CRC). Quantity and structure of HDL particles depend on activities of lipid transfer proteins lecithin:cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP), but this topic is largely unexplored in CRC. The main objective of this study was to investigate activities of LCAT and CETP in patients with CRC. Additionally, we analyzed activity of paraoxonase-1 (PON-1), as a main carrier of HDL-antioxidant function. Materials and methods: Ninety-nine CRC patients and 101 healthy individuals were included. LCAT and CETP activities were assessed by measuring rates of formation and transfer of cholesteryl esters. PON-1 paraoxonase and arylesterase activities were measured. Results: Lower levels of HDL-C (p lt .001) were observed in cohort of patients, alongside with decreased LCAT (p lt .050) and increased CETP activity (p lt .050). Both PON-1 activities were diminished in CRC (p lt .050 and p lt .001 respectively). Univariate logistic regression singled out HDL-C level (OR = 0.218, p lt .001), CETP activity (OR = 1.010, p lt .01) and mass (OR = 0.994, p lt .001) as possible markers of elevated CRC risk. CETP mass maintained its predictive significance when adjusted for traditional risk factors and level of oxidative stress (OR = 0.993, p lt .001; OR = 0.982, p lt .050, respectively). Conclusion: Our results demonstrated increased CETP and decreased LCAT and PON-1 activities in CRC patients. In preliminary analysis CETP mass was identified as potential significant predictor of CRC development, suggesting that alterations in HDL-C levels, alongside with changes in HDL structure might have a role in carcinogenesis.

Glikohemoglobin (HbA1c) je važan parametar za praćenje dugoročne metaboličke kontrole i procenu rizika za razvoj hroničnih komplikacija kod pacijenata sa dijabetes melitusom (DM). U ovoj studiji ispitivali smo povezanost postignute metaboličke kontrole u tipu 2 DM sa rizikom za razvoj i primenjenim modalitetom lečenja sindroma dijabetesnog stopala (SDS). U istraživanju je učestvovalo 111 pacijenata (80 muškaraca i 31 žena) sa tipom 2 DM, starosti 65,5 ± 9,8 godina. Kod 41 pacijenta SDS je lečen neoperativnim (konzervativnim) pristupom, hirurška intervencija manjeg obima (amputacija u predelu stopala) je izvršena kod 41, a opsežna hirurška intervencija (amputacija u predelu potkolenice) kod 29 pacijenata. Koncentracije biohemijskih parametara i HbA1c su određene standardnim laboratorijskim metodama. U ispitivanoj grupi najučestaliji faktor rizika za nastanak SDS (82% pacijenata) bila je neadekvatna glikoregulacija (HbA1c>8%). Utvrdili smo da su pacijenti koji su lečeni hirurškim putem imali statistički značajno više vrednosti HbA1c u poređenju sa pacijentima koji su lečeni neoperativnim pristupom (P8%). The level of HbA1c was significantly higher in surgically treated patients than in the conservatively treated group (P

Background: Obesity-related childhood hypertension is associated with disturbances of serum lipids, but less is known about distribution of lipoprotein subclasses and activities of proteins involved in reverse cholesterol transport in hypertensive obese children. Our objective was to determine low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subclasses distribution and activities of lecithin:cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) in hypertensive and non-hypertensive obese children.Methods: A total of 40 hypertensive and 25 non-hypertensive obese children were enrolled. Lipoprotein subclasses were assessed by polyacrylamide gradient gel electrophoresis. LCAT and CETP activities were determined as a rate of formation and a rate of transfer of cholesteryl esters.Results: Despite of comparable values of serum lipid parameters, a shift toward smaller LDL and HDL subclasses was observed in hypertensive compared to normotensive obese children. Activities of LCAT were similar, but proatherogenic CETP activities were significantly higher in the hypertensive group (p= 0.036). LCAT/net CETP ratio inversely correlated with relative proportion of small, dense LDL particles ( =-0.423; p= 0.025) in the group with hypertension.Conclusions: The results of our study demonstrated a tendency toward altered distribution of lipoprotein subclasses in favor of more proatherogenic particles in childhood hypertension. Also, hypertensive obese children had increased proatherogenic CETP activity.

Specifically altered lipid profile and physiological hyperlipidemia during pregnancy are considered essential for the normal course of pregnancy and fetal development. This specific alteration of the lipid profile raises the questions about potential proaterogenic effect of these altered lipid parameters during pregnancy and its influence on the development of cardiovascular disease in women later in life. Research topic was also the association of altered lipid profile during pregnancy with the development of complications in pregnancy, especially gestational diabetes, hypertension and preeclampsia. Through the mediation of cholesterol ester transfer protein (CETP), the activity of which grows in mid-gestation, there are exchanges of the triglycerides between VLDL and LDL or HDL particle, which leads to increased accumulation of triglycerides in these particles, causes them to become smaller and denser with much greater atherogenic potential. These changes in lipid profile point out that a large number of pregnancies increase risk of development of cardiovascular diseases later in life. In order to optimize the predictive capacity of the lipid profile during pregnancy, it is recommended to determine the indexes of lipid.

Obesity, a pandemic of the modern world, is intimately associated with dyslipidemia, which is mainly driven by the effects of insulin resistance and pro-inflammatory adipokines. However, recent evidence suggests that obesity-induced dyslipidemia is not a unique pathophysiological entity, but rather has distinct characteristics depending on many individual factors. In line with that, in a subgroup of metabolically healthy obese (MHO) individuals, dyslipidemia is less prominent or even absent. In this review, we will address the main characteristics of dyslipidemia and mechanisms that induce its development in obesity. The fields, which should be further investigated to expand our knowledge on obesity-related dyslipidemia and potentially yield new strategies for prevention and management of cardiometabolic risk, will be highlighted. Also, we will discuss recent findings on novel lipid biomarkers in obesity, in particular proprotein convertase subtilisin/kexin type 9 (PCSK9), as the key molecule that regulates metabolism of low-density lipoproteins (LDL), and sphingosine-1-phosphate (S1P), as one of the most important mediators of high-density lipoprotein (HDL) particles function. Special attention will be given to microRNAs and their potential use as biomarkers of obesity-associated dyslipidemia.

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.

Background: Sarcoidosis is an inflammatory disease with pulmonary and extrapulmonary manifestations. In such pathologic conditions, increased oxidative stress and rearrangement of high-density lipoprotein (HDL) and low-density lipoprotein (LDL) may occur. Objective: This study evaluated association of oxidative stress and lipoprotein subclasses in severe forms of pulmonary and pulmonary plus extrapulmonary sarcoidosis. Methods: Lipid parameters, LDL and HDL subclass distributions, high-sensitivity C-reactive protein (hsCRP), serum amyloid A (SAA), paraoxonase 1 (PON1), malondialdehyde (MDA), total-oxidant status (TOS), sulfhydryl (SH) groups, pro-oxidant anti-oxidant balance (PAB) were determined in 77 patients (53 isolated pulmonary and 24 pulmonary plus extrapulmonary) and 139 controls. Results: Both pulmonary and extrapulmonary sarcoidosis patients had significantly higher levels of triglycerides and TOS (P

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.

Objective: Paediatric patients with type 1 diabetes mellitus (T1DM) frequently develop other autoimmune disorders; most commonly autoimmune thyroiditis (ATD) and celiac disease (CD). In this study we evaluated whether co-existing autoimmune diseases had significant impact on lipid and lipoprotein subclasses, as known cardiovascular risk factors in T1DM. Design and methods: Study included 201 subjects with T1DM (14.1 +/- 2.9 years) and 141 age-and gender-matched controls. ATD was presented in 30 and CD in 15 T1DM patients. Serum lipid parameters were determined by routine laboratory methods and plasma low-density (LDL) and high-density lipoprotein (HDL) subclasses by gradient-gel electrophoresis method. Results: Both groups of T1DM patients with concomitant autoimmune disease had significantly lower HDL-C levels (P lt 0.05) than the patients with T1DM only, but comparable to control group (P = 0.436). T1DM patients had significantly higher (P lt 0.001) proportion of small HDL subclasses than controls. Mean value of atherosclerosis index in patients with T1DM + CD was the highest (1.75 +/- 0.86) and it was significantly higher than the index in patients with T1DM only (1.33 +/- 0.51; P lt 0.05). LDL size did not differ between the groups of T1DM patients and control group (P= 0.619). The size of HDL particles was significantly reduced (P lt 0.05) in the groups with associated autoimmune diseases. The patients with co-existing autoimmune diseases had higher risk of low HDL-C level (OR: 2.96; P lt 0.05). Conclusions: The results have shown significant impact of co-existing autoimmune diseases on lipid profile in patients with T1DM. The most prominent changes were found in HDL lipoprotein characteristics in T1DM + CD group.