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Background: An accurate measurement of serum thyroid stimulating hormone (TSH) is crucial for a thyroid disorder diagnosis and management. We compared the values of TSH between three automated immunoassays with aims to provide insights into variations in TSH levels that are important for a clinical decision: 2.50 mIU/L, 4.00 mIU/L and 10.00 mIU/L.Methods: We measured TSH with three different fully automated immunoassays: Abbott (Architect ci8200), Siemens (ADVIA Centaur XP) and Roche (Cobas e411). Serum was collected from 110 patients between August 2018 and January 2019. The results were compared using the Passing-Bablok regression method. Additionally, linear regression coefficients were calculated after logarithmic transformation of data.Results: Although all three regression coefficients were high (r2 > 0.98), the slopes from Passing-Bablok plots for the correlation of Abbott with either Roche or Siemens were merely 0.66 and 0.73, respectively. The slope for the correlation of Roche and Siemens was 1.11. Consecutively, the results obtained by the Roche and Siemens methods were proportionally higher than those obtained by the Abbott method (38% and 52%, respectively) at all measured ranges.Conclusions: Although immunoassays correlated among themselves, they cannot achieve the same values for clinical decisions for hypothyroidism (clinical requirements). Clinicians should be conscious of these limitations. A harmonisation of the methods is needed to meet clinical requirements and to enable appropriate clinical decisions in cases of hypothyroidism.Likewise, we suggest the introduction of borderline and high risk values of TSH for hypothyroidism depending on immunoassays to avoid misdiagnosis.

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

Background/Aim. Glycosylated haemoglobin (HbA1c) is currently the gold standard for glucose monitoring in the patients with diabetes. The aim of the present study was to examine the level of success in implementing international guideline targets with regard to glycaemic control in the patients with type 2 diabetes in the Republic of Srpska. This study also aimed to determine the association of albuminuria with the glycaemic control and lipid levels in this patient population. Methods. The participating diabetic patients were those registered in the project titled ??Estimation of the quality of glycoregulation and presence of vascular complications in the persons with diabetes in the Republic of Srpska.? The study was conducted as a cross-sectional study including 1037 patients. HbA1c was determined by a turbidimetric inhibition immunoassay used Roche Diagnostics. Total cholesterol, triglycerides, LDL-C, and HDL-C were determined by reagents from Roche Diagnostics (Roche Diagnostics, Mannheim, Germany) as well as albumin and creatinine in the urine. Results. Mean value for HbA1c was 7.35 ? 1.61% (57 ? 18 mmol/moL). The 49.46% of all participants achieved target values of HbA1c (< 7% or 53 mmol/moL) and 40.30% had albumin to creatinine ratio (ACR) < 30 mg/g. When the patients were divided according to HbA1c (with HbA1c < 7%, 519 patients, and HbA1c ? 7.0%, 510 patients) the ACR values were different between these groups (39.00 vs. 79.50, p < 0.001). We found no significant difference with respect to lipid status between the groups. Conclusion. The patients with type 2 diabetes in the Republic of Srpska, in a large percentage, did not meet targets for glycaemic control. Improvements are necessary in the treatment and maintenance of this disease process to ensure achievement of goals in management of diabetes, which in turn would decrease longstanding complications of type 2 diabetes.

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

Pomegranate peel contains high levels of various phytochemicals. We evaluated the effects of pomegranate peel extract (PoPEx) consumption on plasma lipid profile, fatty acids (FA) level and blood pressure (BP) in patients with diabetes mellitus type 2 (DMT2). Thirty-seven subjects were recruited in this double blind, placebo controlled randomized trial. The study group (n = 19) received over 8 week’s capsules containing PoPEx twice a daily, while the placebo group received placebo. Treatment with PoPEx induced a significant lowering of both systolic and diastolic BP. The plasma levels of triglycerides, low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio (LDL-C/HDL-C), and HbA1c were significantly decreased, while the level of HDL-C was significantly increased, compared with placebo intake. Moreover, the PoPEX treatment significantly improved the plasma lipids fatty acids content. It is concluded that consumption of PoPEx in DMT2 subject had favourable effects on some metabolic parameters, BP, lipid profile and plasma lipid FA composition.

SummaryBackground: High-density lipoproteins (HDL) have atheroprotective biological properties: antioxidative, anti-apoptotic, anti-inflammatory, and they have the efflux capacity of cellular cholesterol. Plasma mRNA analysis can be used to investigate statin pleiotropy in vivo as a new analytical tool for non-invasive assessment of gene expression in vascular beds. The aim of this study was to assess the pleiotropic effects of atorvastatin in stable angina patients with highrisk values (group A) as compared with patients who had borderline and desirable HDL-cholesterol (HDL-C) values (group B).Methods: The atorvastatin therapy (20 mg/day) was given to forty-three patients with stable angina for 10 weeks. We investigated three statin pleiotropy-targeted genes: intercellular adhesion molecule-1, chemokine (C-C motif) ligand 2 and cathepsin S and assessed by gel electrophoresis gradient the effects of atorvastatin on HDL size and subclasses.Results: In group A, after therapy, HDL-C concentration was significantly increased but not in group B. Atorvastatin lowered plasma chemokine (C-C motif) ligand 2 and intercellular adhesion molecule-1 mRNA levels in both groups, but did not change the plasma cathepsin S mRNA levels. In group A only, baseline total bilirubin showed negative cor relations with the genes of cathepsin S (r=-0.506; p=0.023) and significantly increased after therapy.Conclusion: HDL-C and bilirubin can be promising therapeutic targets in the treatment of cardiovascular diseases. Analysis of cell-free mRNA in plasma might become a useful tool for estimating statin pleiotropy

85th Congress of the European-Atherosclerosis-Society (EAS), 2017.

Introduction The aim of this study was to estimate the correlation between C-reactive protein levels and leading risk factors for cardiovascular disease in men. Material and methods The study included 183 working capable men chosen randomly from the regular systematical check-up in Health Centre Banja Luka in 2006. Standard laboratory methods were used to establish the following: total cholesterol, triglyceride and HDL-cholesterol level and LDL-cholesterol level was calculated. . High sensitive C-reactive protein level was measured by immunuturbidimetric method CRP (Latex) HS Roche Diagnostic. Results Average values of high sensitive C-reactive protein for the whole group was 1.69 mg/L, total cholesterol 5.73 mmol/L, HDL-cholesterol 1.38 mmol/L, LDL-cholesterol 3.40 mmol/L. The average value for the systolic blood pressure was 132.9 mmHg, dyastolic blood pressure 85.4 mmHg, and body mass index 28.47 kg/m2. Out of the overall number of examinees, 74 were smokers (40.4%) and 109 (59.6%) nonsmokers. The statistical analysis showed that there was a statistically significant difference between C-reactive protein level in the group with dyastolic blood pressure below 90 mmHg and above (p

The aim of our research is to determine whether the time of blood sampling and fasting of patients have an impact on TSH values.A total of 198 participants were enrolled in this study and classified into five groups: A--the first sample collection for TSH measurement was taken between 7:00 and 8:00 a.m. at fasting and the second after 140 min without food intake; B--between 7:00 and 8:00 a.m. at fasting and the second after 140 min with food intake; C--between 7:00 and 8:00 a.m. at fasting the previous day and the second one between 7:00 and 8:00 a.m. at fasting the following day; D--between 9:00 and 10:00 a.m. at fasting the previous day and the second one between 9:00 and 10:00 a.m. at fasting the following day, and E--between 9:00 and 10:00 a.m. at fasting the previous day and the second one between 7:00 and 8:00 a.m. on the following day. Serum TSH concentration was measured by electrochemiluminescence immunoassay (ECLIA, Roche Diagnostics, Mannheim, Germany).TSH values (mIU/L) were in group A: 2.50 (2.20-2.81) first samples, 1.74 (1.52-1.96) second samples, p0.001; B: 2.11 (1.52-2.72) first samples, 1.56 (1.13-1.81) second samples, p0.001; C: 2.60 (2.28-2.91) first samples, 2.23 (1.92-2.53) second samples, p0.001; D: 1.80 (1.48-2.11) first samples, 1.77 (1.44-2.09) second samples, p0.597; and E: 1.32 (1.11-2.16) first samples, 1.67 (1.48-2.93) second samples, p0.001.The time of sample collection must be standardised for the purpose of standardisation and harmonisation of TSH measurements.

In vitro and animal studies indicate that statins increase heme oxygenase-1 gene (HMOX1) expression, which then, presumably, increases plasma bilirubin concentration. However, clinical confirmation that statins concomitantly increase HMOX1 expression and plasma bilirubin concentration is lacking. We hypothesized that in patients with stable angina atorvastatin therapy (20 mg/day for 10 weeks) concomitantly increases total bilirubin concentration and HMOX1 expression, as assessed non-invasively by plasma analysis.In 44 patients with stable angina plasma concentrations of total bilirubin, HMOX1 mRNA and HMOX1 protein were measured before and after the statin treatment, as well as plasma concentrations of oxidized low-density lipoprotein (OxLDL), malondialdehyde (MDA), monocyte chemoattractant protein (MCP-1) and C-reactive protein (CRP).Atorvastatin treatment increased total bilirubin concentration (median 6.95 μmol/L vs. 8.55, + 23.02%; p0.001), but did not change plasma HMOX1 mRNA and HMOX1 protein concentrations. Plasma concentrations of OxLDL (- 31.85%, p0.001), MCP-1 (- 16.20%, p = 0.020) and CRP (- 7.32%, p = 0.010) were decreased but MDA was not decreased (15.32%, p = 0.107). Within subjects, increment of plasma bilirubin concentration did not correlate with the changes in HMOX1 mRNA and protein concentrations, but correlated with low-density lipoprotein cholesterol decrement (r = - 0.374, p = 0.012). Bilirubin increment did not correlate with the changes in oxidative and inflammatory markers.Our prospective observational trial finally confirms that atorvastatin (20 mg/day for 10 weeks) increases plasma total bilirubin concentration. However, it seems that this effect is HMOX1-independent.

Introduction. The aim of this study was to estimate if negative lifestyle habits such as alcohol consumption, smoking and physical inactivity affect the lipid profile values. Material and methods. The study included 250 workers on regular examination in the Gradiska Health Center in the period from 2001 to 2002. There were 113 (45.2%) men and 137 (54.8%) women. The examinees were divided into three groups according age (25-39, 40-49 and 50-60 respectively). Standard laboratory methods were used to establish the following: total cholesterol, triglyceride and HDL-cholesterol level, LDL cholesterol, atherosclerosis index (AI) and total cholesterol/HDL cholesterol. Results Using a questionnaire, we have found out that out of 250 examinees 48.80% consume alcohol regularly, 50.80% are smokers and 36% are physically. The mean total cholesterol was high in all groups and it was 6.41 mmol/l. The mean triglyceride level was 1.88 mmol/l and mean HDL cholesterol was 1.48 mmol/l, I A was 2.99 and total cholesterol/HDL cholesterol ratio was 4.69. Statistical analysis showed that there was a statistically significant relationship between triglyceride values and alcohol consumption, smoking and physical activity (p

Aim: We hypothesized that, in stable angina patients, atorvastatin therapy lowers the cathepsin S (CTSS) concentrations, as assessed non-invasively according to a plasma analysis. In addition, the low-density lipoprotein (LDL) and high-density lipoprotein (HDL) size and subclasses in the plasma were analysed to establish the association between CTSS and lipoprotein metabolism and determine whether this association is atorvastatin-sensitive. Methods: A total of 43 patients with stable angina received atorvastatin therapy (20 mg/day, 10 weeks). The plasma CTSS mRNA levels, CTSS protein concentrations and CTSS activity, as well as LDL and HDL size and subclasses, were analysed before and after treatment. Results: Atorvastatin treatment did not change the plasma CTSS mRNA levels, although it lowered the plasma CTSS concentrations and activity. An increased plasma CTSS concentration and activity were found to be associated with a more atherogenic LDL subclass profile (a decreased dominant LDL size and increased percentage of small, dense LDL particles). The atorvastatin-induced CTSS-lowering effect was concomitant with an improvement in the LDL subclass profile, and the changes were found to be interrelated. Concomitant, interrelated changes in the CTSS levels and LDL subclass profiles were found in the LDL phenotype B patients only (a dominant LDL diameter of lt = 25.5 nm at the start of the study). In this subgroup, lowering of the plasma CTSS mRNA level also correlated with lowering of the proportion of small, dense LDL particles. Conclusions: Atorvastatin-induced CTSS-lowering and LDL subclass profile improvements in the plasma of LDL phenotype B patients with stable angina are concomitant and interrelated.