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Open access

Gulbuz Sezgin, Guler Ozturk, Rana Turkal and Burcu Caykara

Summary

Background: Vitamin D regulates calcium and phosphorus metabolism, and it is essential for bone formation. Several factors can affect vitamin D levels in plasma. In present study we compare vitamin D levels of outpatients, who admit to Maltepe University Hospital between 2011 and 2013 and had vitamin D measurements regarding gender, age, and season.

Methods: Hospital records were evaluated to identify the outpatients with vitamin D levels and their gender, age, and vitamin D levels and the seasons of measurements were recorded.

Results: Data of 4860 subjects (74% female) were analyzed and 69.2% were between 18–64 years old. Vitamin D levels were as follows: 43.1% ≤ 10 ng/mL, 31.9% between 10 ng/mL and 20 ng/mL, 16.1% between 20 ng/mL and 30 ng/mL, and only 8.9% ≥ 30 ng/mL. The number of females with vitamin D levels < 10 ng/mL was significantly higher than that of males, while the number of males with vitamin D levels between 10 ng/mL and 20 ng/mL was significantly higher than that of females (P = 0.001) for each of the individuals, 6.2% and 11.1% had sufficient levels in winter and summer, respectively. Overall, it was observed that 6.6% of individuals between 18–44 years old, 8.2% of individuals between 45–64 years old and 10.3% of individuals over 65 years old had vitamin D levels > 30 ng/mL.

Conclusions: The prevalence of vitamin D deficiency in outpatients of Maltepe University Hospital in Marmara region was 75% (< 20 ng/mL).

Open access

Samar Damiati

Summary

Background: Although vitamin D in not a traditional marker for cardiovascular and renal diseases, several studies have proposed a correlation between vitamin D deficiency and these diseases due to the effect of vitamin D on endothelial function. Asymmetric and symmetric dimethyl arginine (ADMA and SDMA, respectively) are endogenous markers of endothelial dysfunction, and are considered as future markers for the assessment of cardiovascular and renal diseases. The present study investigated the association of kidney function tests (urea and creatinine) and dimethylarginine toxins (ADMA and SDMA) in women with vitamin D insufficiency or deficiency. Indeed, sex hormones (estrogen and testosterone) were analyzed in the participants.

Methods: Women were divided into two groups: premenopausal women (younger than 50 years) and postmenopausal women (older than 50 years). Urea, creatinine, estrogen, testosterone, ADMA, and SDMA levels were analyzed when vitamin D level was deficient or insufficient in the participants.

Results: The premenopausal women group showed no significant correlations between dimethylarginine toxins and renal failure tests or sex hormones. In the elderly (postmenstrual) women group, only SDMA was significantly correlated with urea and creatinine, while both ADMA and SDMA were not correlated with sex hormones.

Conclusions: Although ADMA and SDMA are promising candidates of endothelial dysfunction and are increased in menopause and aging, no direct link between ADMA and further progression of renal failure was observed in women with low vitamin D levels. In contrast, a possible direct correlation between SDMA and renal dysfunction was noticed, but only in an age-dependent manner.

Open access

Dragana Popovic, Katarina Lalic, Aleksandra Jotic, Tanja Milicic, Jelena Bogdanovic, Maja Đorđevic, Sanja Stankovic, Veljko Jeremic and Nebojsa M. Lalic

Summary

Background: We analyzed cardiovascular inflammatory (C-reactive protein (CRP), interleukin 6 (IL-6)), haemostatic (homocysteine) risk markers in lean and obese patients at admission and acute hyperglicemic crisis (AHC) resolving, involving diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS).

Methods: In that context, we included group A: N=20 obese, B: N=20 lean patients with DKA; C: N=10 obese, D: N=10 lean patients with HHS; E: N=15 obese, F: N=15 lean controls. CRP, IL-6, homocysteine were determined by ELISA.

Results: Our results showed that CRP, IL-6, and homocysteine levels decreased in all groups: (A: p<0.001; B: p<0.001, C: p<0.05; D: p<0.001 mg/L), (A: p<0.001 B: p<0.001, C: p<0.001, D: p<0.01 pg/mL), (A: p<0.001, B: p <0.001; C: p<0.05, D: p=0.001 μmol/L), respectively, at resolving AHC. However, CRP persisted higher (p<0.001, p<0.01), IL-6 lower (p<0.05, p<0.001), while homo cysteine levels turned out to be similar to controls.

Conclusions: AHC is associated with increased inflammatory and hemostatic cardiovascular risk markers. Also, insulin therapy in AHC has had more pronounced favorable effect on IL-6 and homocystein than on CRP.

Open access

Muhammed Emin Keles, Afshin Samadi, Selen Yilmaz Isikhan, Yusuf Ziya Sener, Ali Sezgin, Emine Keles, Incilay Lay and Uğur Canpolat

Summary

Background: Oxysterols have been shown to play a role in plaque formation while ischemia modified albumin (IMA) is widely accepted as an acute marker for ischemia. The effort test is one of the methods used to identify the presence of coronary artery disease. Thus, there may be a relationship between effort test result and the levels of IMA, 7-ketocholesterol (7-KC) and cholestane-3β,5α,6β,-triol (C-triol).

Methods: Thirty patients who underwent effort test and 30 healthy subjects were included in the study. IMA levels were determined with the albumin-cobalt binding test, 7-KC and C-triol levels were determined with LC-MS/MS. Among the patients, two subgroups were identified according to the results of the effort test, group 1 consisted of patients with a positive effort test (n = 12), and group 2 consisted of patients who had a negative effort test (n = 18).

Results: 7-KC levels of patients were significantly higher compared to healthy subjects (39.87 ± 2.13 ng/mL, 20.26 ± 1.35 ng/mL; p=0.001). In patients, post-test 7- KC levels were significantly lower than pre-test levels (posttest vs. pre-test: 37.73 ± 2.44 ng/mL vs. 41.07 ± 2.18 ng/mL; p<0.001). There was a significant difference in post-test 7-KC levels among all study groups (negative, positive and healthy: 37.73 ± 2.44 ng/mL, 39.87 ± 2.13 ng/mL, 20.26 ± 1.35 ng/mL, respectively). There was no significant difference in IMA levels.

Conclusions: Patients with positive effort test had significantly higher levels of 7-KC. Additionally, after the effort test, the 7-KC value was reduced. 7-KC is a biomarker of oxidative damage and its value or changes before and after the effort test may be used as a biomarker in the diagnosis and follow-up of coronary artery disease.

Open access

Marko Baralić, Voin Brković, Vesna Stojanov, Sanja Stanković, Nataša Lalić, Petar Đurić, Ljubica Đukanović, Milorad Kašiković, Milan Petrović, Marko Petrović, Milan Stošović and Višnja Ležaić

Summary

Background: Vascular calcification (VC) is highly prevalent in dialysis (HD) patients, and its mechanism is multifactorial. Most likely that systemic or local inhibitory factor is overwhelmed by promoters of VC in these patients. VC increased arterial stiffness, and left ventricular hypertrophy. Thus, the present study aimed to investigate the association of VC and myocardial remodeling and to analyze their relationship with VC promoters (fibroblast growth factor 23-FGF23, Klotho, intact parathormon-iPTH, vitamin D) in 56 prevalent HD patients (median values: age 54 yrs, HD vintage 82 months).

Methods: Besides routine laboratory analyzes, serum levels of FGF 23, soluble Klotho, iPTH, 1,25-dihydroxyvitamin D3; pulse wave velocity (PWV); left ventricular (LV) mass by ultrasound; and VCs score by Adragao method were measured.

Results: VC was found in 60% and LV concentric or eccentric hypertrophy in 50% patients. Dialysis vintage (OR 1.025, 95%CI 1.007–1.044, p=0.006) FGF23 (OR 1.006, 95% CI 0.992–1.012, p=0.029) and serum magnesium (OR 0.000, 95%CI 0.000–0.214, p=0.04) were associated with VC. Changes in myocardial geometry was associated with male sex (beta=-0.273, 95% CI -23.967 1.513, p=0.027), iPTH (beta 0.029, 95%CI -0.059–0.001, p=0.027) and vitamin D treatment (beta 25.49, 95%CI 11.325–39.667, p=0.001). Also, patients with the more widespread VC had the highest LV remodeling categories. PWV was associated patient’s age, cholesterol, diastolic blood pressure, LV mass (positively) and serum calcium (negatively), indicating potential link with atherosclerotic risk.

Conclusions: Despite to different risk factors for VC and myocardial remodeling, obtained results could indicate that risk factors intertwine in long-term treatment of HD patients and therefore careful and continuous correction of mineral metabolism disorders is undoubtedly of the utmost importance.

Open access

Wei Zhang, Junlei Chen, Xinxia Li, Yuwen Wang and Jiutong Li

Summary

Background: To establish a fast and simple quantitative method for detection of heart-type fatty acid-binding protein (H-FABP) in serum based on a background fluorescence quenching immunochromatographic assay.

Methods: A detection card based on the double-antibody sandwich double-antibody method with background fluorescence quenching was developed for quantitative measurement of H-FABP in serum. The optimal concentrations of control for coating the test and control lines were determined as well as the concentrations of gold-labeled antibodies used in preparing the detection system. The detection method for H-FABP in serum was established and validated using real-world clinical samples.

Results: The optimal concentrations of labeling antibody and coating antibody were 5.0 μg/mL and 1.0 mg/mL, respectively. The test card had a sensitivity of 1.15 ng/mL over a linear concentration range of 0–100 ng/mL. Based on three batches prepared for testing the card, the relative standard deviation (RSD) within batches was less than 15% without a significant difference (P=0.942). The detection method was tested against common interfering substances in serum, such as bilirubin, triglyceride and serum anticoagulants ethylenediamine tetraacetic acid (EDTA), heparin, detected. The test method was further validated with 50 clinical serum samples, and the test results were comparable with standard reference detection methods with good correlation (R=0.95).

Conclusion: Our study presents a new method with strong specificity and sensitivity for the detection of H-FABP in serum, which could promote H-FABP detection in a broad range of applications.

Open access

Goran Milosevic, Nikola Kotur, Nada Krstovski, Jelena Lazic, Branka Zukic, Biljana Stankovic, Dragana Janic, Theodora Katsila, George P. Patrinos, Sonja Pavlovic and Lidija Dokmanovic

Summary

Acute lymphoblastic leukemia is the most common childhood malignancy. Optimal use of anti leukemic drugs has led to less toxicity and adverse reactions, and a higher survival rate. Thiopurine drugs, including 6-mercaptopurine, are mostly used as antileukemic medications in the maintenance phase of treatment for children with acute lymphoblastic leukemia. For those patients, TPMT genotype- tailored 6-mercaptopurine therapy is already implemented in the treatment protocols. We investigated the role of TPMT, ITPA, ABCC4 and ABCB1 genetic variants as predictors of outcome and 6-mercaptopurine induced toxicity during the maintenance phase of treatment in pediatric acute lymphoblastic leukemia. Sixty-eight children with acute lymphoblastic leukemia were enrolled in this study. Patients have been treated according to ALL IC-BFM 2002 or ALL IC-BFM 2009 protocols. Toxicity and adverse events have been monitored via surrogate markers (off-therapy weeks, episodes of leu - ko penia and average 6-mercaptopurine dose) and a prob- abilistic model was employed to predict overall 6-mercaptopurine related toxicity. We confirmed that patients with acute lymphoblastic leukemia that carry inactive TPMT allele(s) require 6- mercaptopurine dose reduction. ITPA and ABCC4 genetic variants failed to show an association with 6-mercapto - purine induced toxicity during the maintenance phase. Carriers of ABCB1 variant allele experienced greater hepatotoxicity. The probabilistic model Neural net which considered all the analysed genetic variants was assessed to be the best prediction model. It was able to discriminate ALL patients with good and poor 6-mercaptopurin tolerance in 71% of cases (AUC=0.71). This study contributes to the design of a panel of pharmacogenetic markers for predicting thiopurineinduced toxicity in pediatric ALL.

Open access

Andrijana Milošević Georgiev, Dušanka Krajnović, Jelena Kotur-Stevuljević, Svetlana Ignjatović and Valentina Marinković

Summary

A number of risk behaviours, such as smoking, overweight, excessive alcohol intake, insufficient physical activity, excessive and frequent intake of salt, reduced fruit and vegetable intake, increased fat intake, which constitute living habits of an individual can influence the occurrence of hypertension and hyperglycaemia. The changing of these lifestyles can reduce the risk of developing prehypertension and prediabetes. The survey was conducted at student’s campuses. The respondents were subjected to the height, weight, blood glucose and blood pressure. Respondents filled in previously created questionnaire that was approved by the Ethics Committee for Biomedical Research Faculty of Pharmacy, University of Belgrade. The percentage of respondents with a glucose value above the reference value was 14.6% (n=19), 2.4% (n=3) had values greater than 7 mmol/L without being diagnosed with diabetes, and accordingly, 2.4% (n=3) had elevated HbA1c values (above 42 mmol/mol or 6.0%). The percentage of respondents with elevated systolic and diastolic blood pressure was 14.9% and 7.4% respectively. Regarding calculated risk scores, they showed parallel increase with increas-ing of BMI (HPS), systolic and diastolic pressure (OHS), and glucose concentration (OPS). When analysing all the factors that could cause the later development of diabetes, which is associated with hypertension as well, it is observed that the student population is very much exposed to those factors. The results of this study cannot be representative for the general population of students, but they can provide recommendations for further research.

Open access

Neda Milinković, Svetlana Ignjatović, Zorica Šumarac and Nada Majkić-Singh

Summary

An adequate assessment of the measurement uncertainty in a laboratory medicine is one of the most important factors for a reliable interpretation of the results. A large number of standards and guidelines indicate the need for a proper assessment of the uncertainty of measurement results in routine laboratory practice. The available documents generally recommend participation in the proficiency schemes/ external quality control, as well as the internal quality control, in order to primarily verify the quality performance of the method. Although all documents meet the requirements of the International Standard, ISO 15189, the standard itself does not clearly define the method by which the measurement results need to be assessed and there is no harmonization in practice regarding to this. Also, the uncertainty of measurement results is the data relating to the measured result itself, but all factors that influence the interpretation of the measured value, which is ultimately used for diagnosis and monitoring of the patient's treatment, should be taken into account. So in laboratory medicine, an appropriate assessment of the uncertainty of the measurement results should have the ultimate goal of reducing diagnostic uncertainty. However, good professional laboratory practice and understanding analytical aspects of the test for each individual laboratory is necessary to adequately define the uncertainty of measurement results for specific laboratory tests, which helps to implement good clinical practice. Also, setting diagnoses in medicine is a decision with a certain degree of uncertainty, rather than statistically and mathematically calculated conclusion.

Open access

Gianni Turcato, Gianfranco Cervellin, Antonio Bonora, Danieli Prati, Elisabetta Zorzi, Giorgio Ricci, Gian Luca Salvagno, Antonio Maccagnani and Giuseppe Lippi

Summary

The usual history of chronic heart failure (HF) is characterized by frequent episodes of acute decompensation (ADHF), needing urgent management in the emergency department (ED). Since the diagnostic accuracy of routine laboratory tests remains quite limited for predicting short-term mortality in ADHF, this retrospective study investigated the potential significance of combining red blood cell distribution width (RDW) with other conventional tests for prognosticating ADHF upon ED admission. We conducted a retrospective study including visits for episodes of ADHF recorded in the ED of the Uni versity Hospital of Verona throughout a 4-year period. Demo - graphic and clinical features were recorded upon patient presentation. All patients were subjected to standard Chest X-ray, electrocardiogram (ECG) and laboratory testing in - cluding creatinine, blood urea nitrogen, B-type natriuretic peptide (BNP), complete blood cell count (CBC), sodium, chloride, potassium and RDW. The 30-day overall mortality after ED presentation was defined as primary endpoint. Results: The values of sodium, creatinine, BNP and RDW were higher in patients who died than in those who survived, whilst hypochloremia was more frequent in patients who died than in those who survived. The multivariate model, incorporating these parameters, displayed a modest efficiency for predicting 30-day mortality after ED admission (AUC, 0.701; 95% CI, 0.662-0.738; p=0.001). Notably, the inclusion of RDW in the model significantly enhanced prediction efficiency, with an AUC of 0.723 (95% CI, 0.693-0.763; p<0.001). These results were confirmed with net reclassification improvement (NRI) analysis, showing that combination of RDW with conventional laboratory tests resulted in a much better prediction performance (net reclassification index, 0.222; p=0.001). The results of our study show that prognostic assessment of ADHF patients in the ED can be significantly improved by combining RDW with other conventional laboratory tests.