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Jovicic S.,Center for Medical Biochemistry | Ignjatovic S.,University of Belgrade | Majkic-Singh N.,University of Belgrade
Journal of Medical Biochemistry | Year: 2012

Vitamin D is not technically a vitamin, since it is not an essential dietary factor. It is rather a prohormone produced photochemically in the skin from 7-dehydrocholesterol. Vitamin D and its metabolites may be categorized as either cholecalciferols or ergocalciferols. Cholecalciferol (vi - tamin D3) is the parent compound of the naturally occurring family and is produced in the skin from 7-dehydrocholesterol on exposure to the ultraviolet B portion of sunlight. Vitamin D2 (ergocalciferol), the parent compound of the other family, is manufactured by irradiation of ergosterol produced by yeasts and its potency is less than one-third of vitamin D3's potency. The steps in the vitamin D endocrine system include the following: 1) the photoconversion of 7- dehydrocholesterol to vitamin D3 in the skin or dietary intake of vitamin D3; 2) metabolism of vitamin D3 by the liver to 25-hydroxyvitamin-D3 [25(OH)D3 ], the major form of vitamin D circulating in the blood compartment; 3) conversion of 25(OH)D3 by the kidney (functioning as an endocrine gland) to the hormone 1,25-dihydroxyvitamin D3 [1,25(OH)2D3 ]; 4) systemic transport of the dihydroxylated metabolite 1,25(OH)2D3 to distal target organs; and 5) binding of 1,25(OH)2D3 to a nuclear receptor (VDR) at target organs, followed by generation of appropriate biological responses. The activation of vitamin D to its hormonal form is mediated by cytochrome P450 enzymes. Six cytochrome P450 (CYP) isoforms have been shown to hydroxylate vitamin D. Four of these, CYP27A1, CYP2R1, CYP3A4 and CYP2J3, are candidates for the enzyme vitamin D 25-hy - droxylase that is involved in the first step of activation. The highly regulated, renal enzyme 25-hydroxyvitamin D-1a-hy - dro xylase contains the component CYP27B1, which completes the activation pathway to the hormonal form 1,25(OH)2D3. A five-step inactivation pathway from 1,25(OH)2D3 to calcitroic acid is attributed to a single multifunctional CYP, CYP24A1, which is transcriptionally in du - ced in vitamin D target cells by the action of 1,25(OH)2D3. An additional key component in the operation of the vitamin D endocrine system is the plasma vitamin D binding protein (DBP), which carries vitamin D3 and its metabolites to their metabolism and target organs. DBP is a specific, high-affinity transport protein. It is synthesized by the liver and circulates in great excess, with fewer than 5% of the binding sites normally occupied. 1,25(OH)2D3, acts as a ligand for a nuclear transcription factor, vitamin D receptor - VDR, which like all other nuclear receptors, regulates gene transcription and cell function. The widespread presence of VDR, and the key activating (1a-hydroxylase, CYP27B1) and inactivating (24-hydroxylase, CYP24A1) en - zy mes in most mammalian cells means that the cells in these tissues have the potential to produce biological res pon ses, depending on the availability of appropriate amounts of vi - tamin D3. Thanks to this widespread presence of elements of vitamin D endocrine system, its biological features are being recognized outside bone tissue, i.e. calcium and pho - sphate metabolism. Source


Mladenovic D.,University of Belgrade | Hrncic D.,University of Belgrade | Petronijevic N.,University of Belgrade | Jevtic G.,University of Belgrade | And 5 more authors.
American Journal of Physiology - Gastrointestinal and Liver Physiology | Year: 2014

Neurosteroids are involved in the pathogenesis of hepatic encephalopathy (HE). This study evaluated the effects of finasteride, inhibitor of neurosteroid synthesis, on motor, EEG, and cellular changes in rat brain in thioacetamide-induced HE. Male Wistar rats were divided into the following groups: 1) control; 2) thioacetamide-treated group, TAA (300 mg·kg−1·day−1); 3) finasteride-treated group, FIN (50 mg·kg−1·day−1); and 4) group treated with FIN and TAA (FIN + TAA). Daily doses of TAA and FIN were administered in three subsequent days intraperitoneally, and in the FIN + TAA group FIN was administered 2 h before every dose of TAA. Motor and reflex activity was determined at 0, 2, 4, 6, and 24 h, whereas EEG activity was registered about 24 h after treatment. The expressions of neuronal (NeuN), astrocytic [glial fibrilary acidic protein (GFAP)], microglial (Iba1), and oligodendrocyte (myelin oligodendrocyte glycoprotein) marker were determined 24 h after treatment. While TAA decreased all tests, FIN pretreatment (FIN + TAA) significantly improved equilibrium, placement test, auditory startle, head shake reflex, motor activity, and exploratory behavior vs. the TAA group. Vital reflexes (withdrawal, grasping, righting and corneal reflex) together with mean EEG voltage were significantly higher (P < 0.01) in the FIN + TAA vs. the TAA group. Hippocampal NeuN expression was significantly lower in TAA vs. control (P < 0.05). Cortical Iba1 expression was significantly higher in experimental groups vs. control (P < 0.05), whereas hippocampal GFAP expression was increased in TAA and decreased in the FIN + TAA group vs. control (P < 0.05). Finasteride improves motor and EEG changes in TAA-induced HE and completely prevents the development of hepatic coma. © 2014 the American Physiological Society. Source


Vasiljevic-Pokrajcic Z.,University of Belgrade | Marinkovic J.,Institute for Medical Statistics and Informatics | Vukcevic V.,University of Belgrade | Stefanovic B.,University of Belgrade | And 3 more authors.
JACC: Cardiovascular Interventions | Year: 2016

Objectives This study aimed to assess the clinical impact of immediate versus delayed invasive intervention in patients with non-ST-segment myocardial infarction (NSTEMI). Background Previous studies found conflicting results on the effects of earlier invasive intervention in a heterogeneous population of acute coronary syndromes without ST-segment elevation. Methods We randomized 323 NSTEMI patients to an immediate-intervention group (<2 h after randomization, n = 162) and a delayed-intervention group (2 to 72 h, n = 161).The primary endpoint was the occurrence of death or new myocardial infarction (MI) at 30-day follow-up. Results Median time from randomization to angiography was 1.4 h and 61.0 h in the immediate-intervention group and the delayed-intervention group, respectively (p < 0.001). At 30 days, the primary endpoint was achieved less frequently in patients undergoing immediate intervention (4.3% vs. 13%, hazard ratio: 0.32, 95% confidence interval: 0.13 to 0.74; p = 0.008). At 1 year, this difference persisted (6.8% in the immediate-intervention group vs. 18.8% in delayed-intervention group; hazard ratio: 0.34, 95% confidence interval: 0.17 to 0.67; p = 0.002). The observed results were mainly attributable to the occurrence of new MI in the pre-catheterization period (0 deaths + 0 MIs in the immediate-intervention group vs. 1 death + 10 MIs in the delayed-intervention group). The rate of deaths, new MI, or recurrent ischemia was lower in the immediate-intervention group at both 30 days (6.8% vs. 26.7%; p < 0.001) and 1 year (15.4% vs. 33.1%; p < 0.001). Conclusions Immediate invasive strategy in NSTEMI patients is associated with lower rates of death or new MI compared with the delayed invasive strategy at early and midterm follow-up, mainly due to a decrease in the risk of new MI in the pre-catheterization period. (Immediate Versus Delayed Invasive Intervention for Non-STEMI Patients [RIDDLE-NSTEMI]; NCT02419833) © 2016 by the American College of Cardiology Foundation. Source


Plebani M.,University of Padua | Barth J.H.,Leeds Teaching Hospitals NHS Trust | Chen W.,National Center for Clinical Laboratories | De Oliveira Galoro C.A.,University of Campinas | And 8 more authors.
Clinical Chemistry and Laboratory Medicine | Year: 2014

Quality indicators (QIs) are fundamental tools for enabling users to quantify the quality of all operational processes by comparing it against a defined criterion. QIs data should be collected over time to identify, correct, and continuously monitor defects and improve performance and patient safety by identifying and implementing effective interventions. According to the international standard for medical laboratories accreditation, the laboratory shall establish and periodically review QIs to monitor and evaluate performance throughout critical aspects of pre-, intra-, and post-analytical processes. However, while some interesting programs on indicators in the total testing process have been developed in some countries, there is no consensus for the production of joint recommendations focusing on the adoption of universal QIs and common terminology in the total testing process. A preliminary agreement has been achieved in a Consensus Conference organized in Padua in 2013, after revising the model of quality indicators (MQI) developed by the Working Group on "Laboratory Errors and Patient Safety" of the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC). The consensually accepted list of QIs, which takes into consideration both their importance and applicability, should be tested by all potentially interested clinical laboratories to identify further steps in the harmonization project. Source


Topic E.,University of Zagreb | Beletic A.,Center for Medical Biochemistry | Beletic A.,FLM Working Group Congresses and Postgraduate Education | Zima T.,Charles University
Biochemia Medica | Year: 2013

Introduction: Continuing professional development (CPD) with corresponding crediting system is recognized as essential for the laboratory medicine specialists to provide optimal service for the patients. Article presents results of the survey evaluating current CPD crediting practice among members of European Federation of Clinical Chemistry and Laboratory Medicine (EFLM). Materials and methods: A questionnaire had been forwarded to presidents/national representatives of all EFLM members, with invitation to provide information about CPD programmes and crediting policies, as well as feedback on individual CPD categories, through scoring their relevance. Results: Complete or partial answers were received from 28 of 38 members. In 23 countries, CPD programmes exist and earn credits, with 19 of them offering access to non-medical scientists. CPD activities are evaluated in all participating countries, regardless to the existence of an official CPD programme. Among participating members with mandatory specialists' licensing (22/28), CPD is a prerequisite for relicensing in 13 countries. Main categories recognized as CPD are: continuing education (24 countries), article/book (17/14 countries) authorship and distance learning (14 countries). The highest median score of relevance (20) is allocated to professional training, editor/authorship and official activities in professional organizations, with the first category showing the least variation among scores. Conclusions: Majority of EFLM members have developed CPD programmes, regularly evaluated and accompanied by crediting systems. Programmes differ in accessibility for non-medical scientists and impact on relicensing eligibility. Continuing education, authorship and e-learning are mainly recognized as CPD activities, although the professional training is appreciated as the most important individual CPD category. © Croatian Society of Medical Biochemistry and Laboratory Medicine. Source

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