Fatma Ucar

APRI, the FIB-4 score, and Forn's index have noninvasive diagnostic value for liver fibrosis in patients with chronic hepatitis B.

Objectives The aim of this study was to evaluate the potential use of serum transforming growth factor-&bgr;1 (TGF-&bgr;1), tissue inhibitor of metalloproteinase-1 (TIMP-1), fetuin-A, and fibroblast growth factor 21 (FGF21) in the detection of liver fibrosis in patients with chronic hepatitis B (CHB). The value of the noninvasive fibrosis models – that is, the aspartate aminotransferase to platelet ratio index (APRI), the fibrosis index based on the four factors (FIB-4) score, and Forn’s index – was also examined. Materials and methods CHB patients who underwent liver biopsy for the evaluation of fibrosis were included in the study. A total of 73 patients were divided into two groups according to their METAVIR scores (F0–1, no/minimal fibrosis; F2–4, significant fibrosis). Serum levels of TGF-&bgr;1, TIMP-1, fetuin-A, and FGF21 were measured besides APRI, FIB-4, and Forn’s scores. The area under the receiver operating characteristic curve was measured for each parameter, followed by calculation of sensitivity, specificity, and positive and negative predictive values. Results APRI, FIB-4, and Forn’s index scores were significantly higher in patients with significant fibrosis (P<0.05). There was no difference between no/minimal fibrosis and significant fibrosis groups in terms of serum levels of TGF&bgr;-1, TIMP-1, fetuin-A, and FGF21 (P>0.05). The areas under the receiver operating characteristic curve for TGF-&bgr;1, TIMP-1, fetuin-A, FGF21, APRI, FIB-4, and Forn’s index were 0.445, 0.483, 0.436, 0.585, 0.662, 0.687, and 0.680, respectively. Conclusion Our results suggest that serum TGF-&bgr;1, TIMP-1, fetuin-A, and FGF21 are not useful for the assessment of the extent of liver fibrosis in CHB in this patient group. However, APRI, FIB-4, and Forn’s index have a better diagnostic value in patients with significant fibrosis than in those with no/minimal fibrosis.

ADAMTS1, ADAMTS5, ADAMTS9 and aggrecanase-generated proteoglycan fragments are induced following spinal cord injury in mouse

ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) proteinases are involved in a variety of biological processes such as angiogenesis, cancer and arthritis. ADAMTSs appears to be responsible for the cleavage of proteoglycans in several tissues including brain and cartilage. Chondroitin sulfate proteoglycans (CSPGs) maintains the integrity of the brain extracellular matrix and major inhibitory contributors for glial scar and neural plasticity. The activity of aggrecanases in the central nervous system (CNS) has been reported. ADAMTSs are an enzyme degrading CSPGs in the brain. However, there is a little knowledge regarding ADAMTSs in the CNS. We investigated the expression levels of ADAMTSs mRNAs by RT-PCR after spinal cord injury in mouse. Transcripts encoding 4 of the 19 known ADAMTSs were evaluated in the mouse spinal cord following injury. ADAMTS1, -5 and -9 expression levels were found to be upregulated. No change was observed in ADAMTS4 expression. By means of immunohistochemistry, ADAMTSs were detected in the astrocytes implying its cellular source in SCI. Western blot analyses indicated that aggrecanase-generated proteoglycan fragments are produced after SCI.

The relationship between oxidative stress and nonalcoholic fatty liver disease: Its effects on the development of nonalcoholic steatohepatitis.

Abstract Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are the most common underlying causes of chronic liver injury. They are associated with a wide spectrum of hepatic disorders including basic steatosis, steatohepatitis, and cirrhosis. The molecular and cellular mechanisms underlying hepatic injury in NAFLD and NASH are still unknown. This review describes the roles of oxidative stress and inflammatory responses in the pathogenesis of NAFLD and its progression to NASH.

Plasma homocysteine concentrations and serum lipid profile as atherosclerotic risk factors in subclinical hypothyroidism.

BACKGROUND AND OBJECTIVES Because subclinical thyroid dysfunction may be a risk factor for cardiovascular disease, we evaluated the atherosclerosis tendency in subclinical hypothyroid (SCH) patients. PATIENTS AND METHODS Fifty-three subclinical hypothyroid patients (serum thyrotropin [TSH] concentrations >4.12 mU/L) were compared with a control group of 50 euthyroid subjects whose age, sex and body mass indices were similar to the patient group. We tested whether serum TSH concentrations were correlated with plasma total homocysteine concentration (tHcy), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC) and triglycerides (TG). RESULTS There was a significant statistical difference between the patient and control groups for normal free T4 (1.02±0.17 vs. 0.86±0.13, P<.001), TSH (1.64±1.02 vs. 6.62±2.61, P<.001), TC (185±39 vs. 206±42, P=.01), TG (103±54 vs. 132±85, P=.04), LDL-C (114±33 vs. 127±36, P=.04), and TC/HDL-C (3.81±106 vs. 4.19±1.02, P=.04), respectively. No statistically significant difference was found between the two groups for HDL-C, VLDL-C, LDL-C/HDL-C, and tHcy. Serum TSH was significantly correlated with plasma tHcy (r=0.55; P=.001), TC (r=0.52; P=.001), LDL-C (r=0.49; P=.001), TC/HDL-C (r=0.38; P=.002) and LDL-C/HDL-C (r=0.36; P=.004) across all participants. CONCLUSION Our study suggests that the atherogenicity of SCH is not mediated by hyperhomocysteinemia. Associated hyperlipidemia may explain the observed increased risk of coronary artery disease in patients with SCH.

The role of reactive oxygen species and oxidative stress in carbon monoxide toxicity: An in-depth analysis

Abstract The underlying mechanism of the central nervous system (CNS) injury after acute carbon monoxide (CO) poisoning is interlaced with multiple factors including apoptosis, abnormal inflammatory responses, hypoxia, and ischemia/reperfusion-like problems. One of the current hypotheses with regard to the molecular mechanism of CO poisoning is the oxidative injury induced by reactive oxygen species, free radicals, and neuronal nitric oxide. Up to now, the relevant mechanism of this injury remains poorly understood. The weakening of antioxidant systems and the increase of lipid peroxidation in the CNS have been implicated, however. Accordingly, in this review, we will highlight the relationship between oxidative stress and CO poisoning from the perspective of forensic toxicology and molecular toxicology.

Estimation of biological variation and reference change value of glycated hemoglobin (HbA1c) when two analytical methods are used

OBJECTIVES Available data on biological variation of HbA1c revealed marked heterogeneity. We therefore investigated and estimated the components of biological variation for HbA1c in a group of healthy individuals by applying a recommended and strictly designed study protocol using two different assay methods. DESIGN AND METHODS Each month, samples were derived on the same day, for three months. Four EDTA whole blood samples were collected from each individual (20 women, 9 men; 20-45 years of age) and stored at -80°C until analysis. HbA1c values were measured by both high performance liquid chromatography (HPLC) (Shimadzu, Prominence, Japan) and boronate affinity chromatography methods (Trinity Biotech, Premier Hb9210, Ireland). All samples were assayed in duplicate in a single batch for each assay method. Estimations were calculated according to the formulas described by Fraser and Harris. RESULTS The within subject (CV(I))-between subject (CV(G)) biological variations were 1.17% and 5.58%, respectively for HPLC. The calculated CV(I) and CV(G) were 2.15% and 4.03%, respectively for boronate affinity chromatography. Reference change value (RCV) for HPLC and boronate affinity chromatography was 5.4% and 10.4% respectively and individuality index of HbA(1c) was 0.35 and 0.93 respectively. CONCLUSIONS This study for the first time described the components of biological variation for HbA1c in healthy individuals by two different assay methods. Obtained findings showed that the difference between CV(A) values of the methods might considerably affect RCV. These data regarding biological variation of HbA(1c) could be useful for a better evaluation of HbA(1c) test results in clinical interpretation.

Greater Efficiency Observed 12 Months Post-Implementation of an Automatic Tube Sorting and Registration System in a Core Laboratory/ Veća Efikasnost Uočena 12 Meseci Posle Implementacije Sistema za Automatsko Sortiranje i Registrovanje Uzoraka u Centralnoj Laboratoriji

Summary Bachground: Sample classification and registration have been recognized as important and time-consuming processes in laboratories. There is increasing pressure on laboratories to automate processes due to intense workload and reduce manual procedures and errors. The aim of the present study was to evaluate the positive effects of an automatic tube registration and sorting system on specimen processing. Methods: An automatic tube registration and sorting system (HCTS2000 MK2, m-u-t AG, Wedel, Germany) was evaluated. Turnaround time (TAT), rate of sample rejection and unrealized tests were examined 12 months pre- and post-implementation of the automatic tube sorting and registration system. Results: The mean TAT of routine chemistry immunoassay, complete blood cell count (CBC) and coagulation samples were significantly improved (P<0.001). The number of rejected samples and unrealized tests was insignificantly decreased post-implementation of the system (0.4% to 0.2% and 4.5% to 1.4%, respectively) (P>0.05). Conclusions: By reducing delays and errors in the preanalytical processing and sorting of samples, significant improvements in specimen processing were observed after implementation of the system. These results suggest that an automatic tube registration and sorting system may also be used to improve specimen processing in a higher-volume core laboratory. Kratak sadržaj Uvod: Klasifikacija i registracija uzoraka u laboratorijama prepoznate su kao važni i dugotrajni procesi. Laboratorije su pod sve većim pritiskom da automatizuju postupke zbog velikog obima posla i smanje manuelne procedure i greške. Cilj ove studije bio je da se procene pozitivni efekti jednog sistema za automatsko registrovanje i sortiranje uzoraka na njihovu obradu. Metode: Ocenjivali smo sistem za automatsko registrovanje i sortiranje uzoraka (HCTS2000 MK2, m-u-t AG, Wedel, Nemačka). Ukupno vreme za obradu uzorka (turnaround time), stopa odbacivanja uzorka i nerealizovani testovi obradeni su 12 meseci pre i posle implementacije sistema za automatsko sortiranje i registrovanje uzoraka. Rezultati: Srednje ukupno vreme obrade uzoraka za rutinske hemijske imunoeseje, kompletnu krvnu sliku i koagulaciju bilo je značajno bolje (P<0,001). Broj odbačenih uzoraka i nerealizovanih testova bio je smanjen, iako ne značajno, posle implementacije sistema (sa 0,4% na 0,2%, odnosno sa 4,5% na 1,4%) (P>0,05). Zaključak: Zahvaljujući ređim slučajevima kašnjenja i redim greškama prilikom preanalitičke obrade i sortiranja uzoraka, uočena su značajna poboljšanja u obradi uzoraka posle implementacije ovog sistema. Naši rezultati pokazuju da se sistemi za automatsko registrovanje i sortiranje mogu koristiti radi poboljšane obrade uzoraka i u centralnim laboratorijama sa velikim obimom posla.

Evaluation of the analytical performance of Unicel DXI 800 for the Total 25 (OH) Vitamin D measurements.

OBJECTIVES We assessed the analytical performance of newly developed Access 25(OH) Vitamin D Total assay with Beckman Coulter Unicel DXI 800 and evaluated the agreement between a reference method liquid chromatography/tandem mass spectrometry (LC-MS/MS) and a chemiluminescence method (LIAISON, DiaSorin). DESIGN AND METHODS 160 serum samples were included. Deming Regression analysis and Bland-Altman plots were used. The concordance correlation coefficient (CCC) was used to assess the degree of agreement between assays and the reference method. RESULTS The CV% values of Unicel DXI 800 for within-run, between-run and between-day were lower than 6%. When compared to LC-MS/MS, the Access 25(OH) Vitamin D Total assay demonstrated an R value of 0.9444 (intercept -0.089, slope 0.951), with an average bias of -2.9%, and the LIAISON 25(OH) Vitamin D Total assay an R value of 0.9405 (intercept -0605, slope 0.924), with an average bias of -13.6%. In comparison with the LIAISON 25(OH) Vitamin D Total assay, the Access 25(OH) Vitamin D Total assay demonstrated an R value of 0.9498 (intercept 0.528, slope 1.029), with an average bias of 1.2%. The agreement with the LC-MS/MS method, based on values of the CCC, was moderate for the Unicel DXI 800 and LIAISON method (0.95, 0.94 respectively). CONCLUSIONS The new, automated Access 25(OH) Vitamin D Total assay showed an acceptable correlation with LC-MS/MS and LIAISON. Both methods moderately achieved to classify the patients according to their vitamin D status. However, we need further standardization of vitamin D assays to enhance the accuracy and comparability.

First data on the biological variation and quality specifications for plasma ammonia concentrations in healthy subjects.

Abstract Background: Most of the factors causing preanalytical and analytical variation in ammonia measurement have been identified. Biological variation data for ammonia is still lacking. We therefore estimated the components of biological variation (within-subject=CVI and between-subject=CVG), reference change value (RCV) and quality specifications for ammonia in a group of healthy individuals using fresh and frozen plasma samples. Methods: Blood samples from 20 healthy subjects were collected in K2EDTA tubes daily over a period of 4 consecutive days from each subject. Each plasma sample was split into two aliquots; one was immediately analyzed as the samples were collected and the other was stored –80 °C until testing at the end of the collection period and analyzed at once in one analytical run. All samples were analyzed in duplicate. Estimations were calculated according to Fraser and Harris methods. Results: CVI value for fresh samples (13.78%) was significantly lower than that in frozen samples (18.91%) (p<0.001). However, there was no statistically significant difference in CVG values between fresh (16.91%) and frozen (18.43%) samples (p=0.570). The index of individuality did not exceed 1.4 for fresh and frozen samples. The estimated RCVs were high for both fresh and frozen samples (43.37% and 56.85%, respectively). Quality specifications were established. Conclusions: The present study for the first time described the components of biological variation for ammonia in healthy individuals. These data regarding biological variation of ammonia could be useful for a better evaluation of ammonia test results in clinical interpretation and for determining quality specifications based on biological variation.

Serum vaspin and adiponectin levels in patients with prolactinoma

Abstract Background: Studies investigating serum vaspin and adiponectin levels in patients with prolactinoma are inconclusive. The aim of this study was to evaluate serum vaspin and adiponectin levels in patients with prolactinoma and healthy controls. Methods: A total of 42 prolactinoma patients (Group 1, 21 patients; Group 2, 21 patients) and 30 healthy controls were enrolled in the study. Group 1 consisted of newly diagnosed patients who were never treated or had not received a dopamine agonist (DA) within 6 months prior to screening. Group 2 consisted of prolactinoma patients who were on DA treatment for at least 6 months at the time of screening. The control group (group 3) consisted of healthy controls. Results. Patients with prolactinoma had higher homeostasis model assessment of insulin resistance and lower quantitative insulin sensitivity check index values in comparison to healthy controls (p < 0.001 for both). Serum levels of adiponectin and vaspin were also significantly lower in prolactinoma patients when compared to the control group (p < 0.01 and p < 0.001, respectively). Following adjustment for confounding factors, the respective odds ratios for prolactinoma in patients in the lower subgroup compared with those in the higher subgroup for adiponectin and vaspin were 2.733 (0.621–12.035; p > 0.05) and 5.041 (1.191–21.339; p < 0.05). Conclusion: This is the first study to demonstrate the presence of low vaspin levels in patients with prolactinomas. Further studies are needed to help establish the roles of vaspin and adiponectin in prolactinoma patients.