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3. Is there a difference in the phthalate exposure between adults with metabolic disorders and healthy ones?

Author

Stepanović Kristina, Vuković Bojan, Milanović Maja, Milošević Nataša, Bosić-Živanović Dragana, Stojadinović Aleksandra, Tomić-Naglić Dragana, Lepić Sanja, Milić Nataša, and Medić-Stojanoska Milica

Subjects
endocrine system diseases, phthalic acid, monoethyl phthalate, risk assessment, serbia, Medicine (General), R5-920
Abstract

Background/Aim. Phthalates are recognized as endocrine-disrupting compounds and are extensively present in a variety of everyday products. Chronic exposure to phthalates is suspected to be associated with a range of health disorders. The aim of the study was to examine the abundance of phthalate metabolites in the urine samples among adults in the Autonomous Province of Vojvodina, Serbia, and to determine the prevalence of phthalate metabolites in healthy individuals and those with metabolic disorders such as obesity and newly diagnosed type 2 diabetes mellitus (T2DM). Methods. For the study purpose, the first morning urine sample of 308 participants was screened for the presence of 10 phthalate metabolites: mono-ethyl phthalate (MEP), mono-(2-ethylhexyl) phthalate (MEHP), mono-n-butyl phthalate (MBP), mono-iso-allyl phthalate (MiAP), mono-n-allyl phthalate (MnAP), mono-cyclohexyl phthalate (MCHP), mono-benzyl phthalate (MBzP), mono-n-octyl phthalate (MOP), mono-n-propyl phthalate (MPP) and mono-methyl phthalate (MMP). Results. At least one phthalate metabolite was detected in the first morning urine sample in 50.32% of the examined population. The most frequently detected phthalate metabolites were MEP and MEHP. Out of all phthalate-positive participants, 38.3% of them had one, 10.7% had two, while 1.3% of participants had three phthalate metabolites in the first morning urine sample. A significant difference (p < 0.05) between groups was observed on MEP and MMP frequency, while border-line significant difference (p < 0.1) between groups was observed on MEHP and MCHP frequency. Conclusion. In the Vojvodina region, both healthy adults and those with metabolic disorders such as obesity and newly diagnosed T2DM are predominantly exposed to di-ethyl phthalate and di-(2-ethylhexyl)phthalate since MEP and MEHP were the most frequently detected phthalate metabolites. Further re-search is required in order to provide more details of the phthalates influence on the adverse health effects.

Published
2022
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4. Neurometabolic Profile in Obese Patients: A Cerebral Multi-Voxel Magnetic Resonance Spectroscopy Study.

Author

Vuković, Miloš, Nosek, Igor, Slotboom, Johannes, Medić Stojanoska, Milica, and Kozić, Duško

Subjects
NUCLEAR magnetic resonance spectroscopy, CEREBRAL hemispheres, CINGULATE cortex, WHITE matter (Nerve tissue), BRAIN metabolism, COMPULSIVE eating
Abstract

Background and Objectives: Obesity-related chronic inflammation may lead to neuroinflammation and neurodegeneration. This study aimed to evaluate the neurometabolic profile of obese patients using cerebral multivoxel magnetic resonance spectroscopy (mvMRS) and assess correlations between brain metabolites and obesity markers, including body mass index (BMI), waist circumference, waist-hip ratio, body fat percentage, and indicators of metabolic syndrome (e.g., triglycerides, HDL cholesterol, fasting blood glucose, insulin, and insulin resistance index (HOMA-IR)). Materials and Methods: This prospective study involved 100 participants, stratified into two groups: 50 obese individuals (BMI ≥ 30 kg/m2) and 50 controls (18.5 ≤ BMI < 25 kg/m2). Anthropometric measurements, body fat percentage, and biochemical markers were evaluated. All subjects underwent long- and short-echo mvMRS analysis of the frontal and parietal supracallosal subcortical and deep white matter, as well as the cingulate gyrus, analyzing NAA/Cr, Cho/Cr, and mI/Cr ratios, along with absolute concentrations of NAA and Cho. Results: Obese participants exhibited significantly decreased NAA/Cr and Cho/Cr ratios in the deep white matter of the right cerebral hemisphere (p < 0.001), while absolute concentrations of NAA and Cho did not differ significantly between groups (p > 0.05). NAA levels showed negative correlations with more reliable obesity parameters (waist circumference and waist-to-hip ratio) but not with BMI, particularly in the deep frontal white matter and dorsal anterior cingulate gyrus of the left cerebral hemisphere. Notably, insulin demonstrated a significant negative impact on NAA (ρ = −0.409 and ρ = −0.410; p < 0.01) and Cho levels (ρ = −0.403 and ρ = −0.392; p < 0.01) at these locations in obese individuals. Conclusions: Central obesity and hyperinsulinemia negatively affect specific brain regions associated with cognitive and emotional processing, while BMI is not a reliable parameter for assessing brain metabolism. [ABSTRACT FROM AUTHOR]

Published
2024
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6. Mediastinal ectopic thyroid tissue as diferential diagnostic problem: A case report

Author

Stojanoski Stefan, Bjelović Milorad, Ilinčić Branislava, Vučković Dejan, Kozić Duško, and Medić Stojanoska Milica

Subjects
congenital abnormalities, diagnosis, differential, histological techniques, mediastinal neoplasms, thyroid gland, Medicine (General), R5-920
Abstract

Introduction. Mediastinal ectopic thyroid tissue (ETT) rep-resents a rare entity. Clinically, it can manifest with thyroid gland dysfunction or with symptoms and signs caused by a compressive effect on the surrounding structures, but in most cases it is an asymptomatic condition and incidental finding. All pathologic processes, including malignancy that can occur in the orthotopic thyroid gland can also develop in the ETT. Case report. We presented a case of a 17-year-old female with incidentally found mediastinal ETT. Besides ETT, the patient had an orthotopic thyroid gland and was euthyroid. During follow-up, mild compressive symptoms developed. Magnetic resonance imaging examination showed a non-significant increase of the mediastinal mass volume, but due to its morphological changes, a suspicion of another etiology was raised. A discrepancy between the positive technetium-99m pertechnetate and negative 131 iodine radionuclide imaging of the mediastinal mass was highly suspicious for malignancy. Surgery was performed and the pathologist confirmed that it was a colloid goiter in the mediastinal ETT. Conclusion. Mediastinal ectopic thyroid tissue should be taken into account in the differential diagnosis of the mediastinal tumor mass. An increase in the size of the mediastinal ETT, development of compressive symptoms or suspected malignant alteration require surgical treatment.

Published
2021
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10. Osteoporosis reversibility in a patient with celiac disease and primary autoimmune hypothyroidism on gluten free diet: A case report

Author

Kovačev-Zavišić Branka, Ičin Tijana, Novaković-Paro Jovanka, Medić-Stojanoska Milica, and Bajkin Ivana

Subjects
celiac disease, hypothyroidism, diet+ gluten-free, treatment outcome, Medicine (General), R5-920
Abstract

Introduction. Secondary osteoporosis occurs in many diseases. Celiac disease-induced osteoporosis is the consequence of secondary hyperparathyroidism. Biochemical bone markers show predominance of bone resorption, thus making the bisphosphonates the first line therapy option. Intestinal mucosal changes are reversible on gluten-free diet. Osteoporosis reversibility is also possible, provided postmenopausal osteoporosis risk factors independent from celiac disease are not present. Case report. We presented a postmenopausal woman with at least a 10-year history of celiac disease prior to diagnosis, which had overt secondary hyperparathyroidism with insufficient status of vitamin D and a significant bone mass reduction. At the time of diagnosis of celiac disease the patient was receiving 250 􀆬g of levothyroxine daily without achieving optimal substitution. Three years after the initiation of gluten-free diet the patient was without any signs and symptoms of the disease. All laboratory findings were within normal range. It was decided to treat the underlying disease and to supplement calcium and vitamin D without the initiation of bisphosponate therapy. Conclusion. Osteoporosis regression justified this therapeutic approach. The presence of primary autoimmune hypothyroidism makes this case specific, since the inability for optimal substitution therapy with a high daily dose of levothyroxine provoked the suspicion of celiac disease.

Published
2015
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11. The influence of hyperprolactinemia on coagulation parameters in females with prolactinomas

Author

Medić-Stojanoska Milica, Mitić Gorana, Mitić Igor, Spasić Dragan T., Ćurić Nikola, Pekić Sandra, Kovačev-Zavišić Branka, and Popović Vera

Subjects
hypeprolactinemia, hemostatic system, coagulation, Medicine
Abstract

Introduction. Currently there is little information on the effects of prolactin (PRL) on the coagulation and fibrinolytic systems. Objective. The aim of this study was to evaluate the effects of hypeprolactinemia on the parameters of the hemostatic system and activation of the coagulation system. Methods. We studied PRL levels, body mass index (BMI), values of activated partial thromboplastin time (aPTT), prothrombin time (PT), thrombin time (TT), D-dimer level, von Willebrand factor antigen (vWFAg) and fibrinogen in 15 young female patients with microprolactinomas before and after therapy and in 15 healthy female controls. Results. As expected, pretreatment PRL levels were significantly higher in patients than in controls (140.90±42.87 vs. 12.53±4.05 ng/ml; p

Published
2014
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12. The quality of life in patients with diabetes mellitus type 2

Author

Bosić-Živanović Dragana, Medić-Stojanoska Milica, and Kovačev-Zavišić Branka

Subjects
diabetes mellitus type 2, quality of life, questionaires, comorbidity, Medicine (General), R5-920
Abstract

Background/Aim. Through its various activities, World Health Organization (WHO) contributed to increasing the understanding of the concept of quality of life. People with diabetes have a lower quality of life than people without chronic illnesses. The aim of this study was to examine the differences in the quality of life, related to health, in patients with diabetes mellitus (DM) type 2 by age, gender and type of therapy. Methods. We performed a cross-sectional study at the outpatient department of the Clinical Center in Novi Sad and the Health Center Ruma - General Practice. The group consisted of 90 patients with DM type 2, 41 men and 49 women. The age of respondents was from 40 to 80 years and they were classifed into four groups according to the ten-year age intervals. We applied WHO Quality of life questinnaire - BREF 100 composed of four domains: physical health, psychological health, social relationships and environment. The general questionnaire asks questions about socio-demographic data, duration of diabetes, the last value of blood glucose and glycosylated hemoglobin, training for self-control and its implementation, informing patients about their disease, therapy and its impact on daily activities and the presence of comorbidity. In statistical analysis the following tests were used: Student’s t-test, Ftest, ANOVA (one way). Results. The average duration of DM type 2 was 11.2 ± 9.2 years. Most of the patients (76%) were trained to self-control and 91% received enough information about their disease. Oral hypoglycemic preparations were used by 49%, insulin by 21%, and oral drugs and insulin by 29% patients while 1% were on a special regime of a diet therapy. Daily activities were performed without difficulties by over 29%, with some difficulties by 41% and 30% of patients who could not perform daily activities. The patients with DM type 2 had significantly lower scors in all 4 domains of quality of life (physical health, psychological health, social relations, environment). The biggest influence was on physical domains (51.31). Education level had an impact on physical and psychological domains. Comorbidity was found in 83% of the respondents. The most common were: arterial hypertension (63%), chronic cardiovascular disease (46%), neuropathy (23%), impaired vision 24%, elevated blood lipids (39%) and amputation of toes or feet (2.2%). The average value HbA1C in the group with comorbidity was 8.47% and in the group without comorbidity 6.46%. The subjects with comorbidity had low quality of life assessment in relation to the group without comorbidity: the domain of physical health (45.64 vs 79.66), psychological health (50.3 vs 76.86), social relations (52.97 vs 75.46) and environment (52.7 vs 75.06). Conclusion. Diabetes mellitus type 2 has negative influence on the quality of life. It contributes to the presence of comorbidity. The occurrence of comorbidity was associated with higher glucosylated HbA1C values. There was no difference in the assessment of quality of life regarding gender, age, or the type of therapy used. The quality of life was assessed as low in patients with comorbidity. However, certain personality characteristics play a decisive role in self-evaluation.

Published
2012
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14. Mastiha has efficacy in immune-mediated inflammatory diseases through a microRNA-155 Th17 dependent action

Author

Amerikanou, Charalampia, primary, Papada, Efstathia, additional, Gioxari, Aristea, additional, Smyrnioudis, Ilias, additional, Kleftaki, Stamatia-Angeliki, additional, Valsamidou, Evdokia, additional, Bruns, Victoria, additional, Banerjee, Rajarshi, additional, Trivella, Maria Giovanna, additional, Milic, Natasa, additional, Medić-Stojanoska, Milica, additional, Gastaldelli, Amalia, additional, Kannt, Aimo, additional, Dedoussis, George V., additional, and Kaliora, Andriana C., additional

Published
2021
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15. Curcumin Efficacy in a Serum/glucose Deprivation-induced Neuronal PC12 Injury Model

Author

Kanoni, Stavroula, Kumar, Satish, Amerikanou, Charalampia, Kurth, Mary Jo, Stathopoulou, Maria, Bourgeois, Stephane, Masson, Christine, Kannt, Aimo, Cesarini, Lucia, Kontoe, Maria-Spyridoula, Milanović, Maja, Roig, Francisco, Beribaka, Mirjana, Campolo, Jonica, Jiménez-Hernández, Nuria, Milošević, Nataša, Llorens, Carlos, Smyrnioudis, Ilias, Francino, M. Pilar, Milić, Nataša, Kaliora, Andriana, Trivella, Maria Giovanna, Ruddock, Mark, Medić-Stojanoska, Milica, Gastaldelli, Amalia, Lamont, John, Deloukas, Panos, Dedoussis, George, Visvikis-Siest, Sophie, Interactions Gène-Environnement en Physiopathologie Cardio-Vasculaire (IGE-PCV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Birjand University of Medical Sciences [Birjand, Iran] (BUMS), Sabanci University [Istanbul], Mashhad University of Medical Sciences, and Albert Einstein College of Medicine [New York]

Subjects
0301 basic medicine, congenital, hereditary, and neonatal diseases and abnormalities, Curcumin, Antioxidant, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Apoptosis, Inflammation, Pharmacology, medicine.disease_cause, PC12 Cells, Article, Lipid peroxidation, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, medicine, Animals, Humans, Viability assay, chemistry.chemical_classification, Reactive oxygen species, nutritional and metabolic diseases, General Medicine, Rats, 3. Good health, Oxidative Stress, Glucose, 030104 developmental biology, chemistry, medicine.symptom, 030217 neurology & neurosurgery, Oxidative stress
Abstract

Background: Glucose/serum deprivation (GSD), has been used for understanding molecular mechanisms of neuronal damage during ischemia. It has been suggested that curcumin may improve neurodegenerative diseases. Aim: In this study, the protective effects of curcumin and its underlying mechanisms were investigated in PC12 cells upon GSD-induced stress. Methods: PC12 cells were cultured in DMEM overnight and then incubated in GSD condition for either 6 or 12h. GSD-treated cells were pretreated with various concentrations of curcumin (10, 20, and 40 μM) for 5h. The cell viability, apoptosis, reactive oxygen species (ROS) level, oxidative stress, expression of apoptosis-related genes, and IL-6 were determined. Results: Curcumin increased cell viability and caused an anti-apoptotic effect in PC12 cells exposed for 12h to GSD . Curcumin also increased antioxidant enzyme expression, suppressed lipid peroxidation, and decreased interleukin-6 secretion in PC12 cells subjected to GSD. In addition, pretreatment with curcumin down-regulated pro-apoptotic (Bax), and up-regulated antiapoptotic (Bcl2) mediators. Conclusion: Curcumin mitigates many of the adverse effects of ischemia, and therefore, should be considered as an adjunct therapy in ischemic patients.

Published
2021
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16. Nutrigenetic Interactions Might Modulate the Antioxidant and Anti-Inflammatory Status in Mastiha-Supplemented Patients With NAFLD

Author

Kanoni, Stavroula, primary, Kumar, Satish, additional, Amerikanou, Charalampia, additional, Kurth, Mary Jo, additional, Stathopoulou, Maria G., additional, Bourgeois, Stephane, additional, Masson, Christine, additional, Kannt, Aimo, additional, Cesarini, Lucia, additional, Kontoe, Maria-Spyridoula, additional, Milanović, Maja, additional, Roig, Francisco J., additional, Beribaka, Mirjana, additional, Campolo, Jonica, additional, Jiménez-Hernández, Nuria, additional, Milošević, Nataša, additional, Llorens, Carlos, additional, Smyrnioudis, Ilias, additional, Francino, M. Pilar, additional, Milić, Nataša, additional, Kaliora, Andriana C., additional, Trivella, Maria Giovanna, additional, Ruddock, Mark W., additional, Medić-Stojanoska, Milica, additional, Gastaldelli, Amalia, additional, Lamont, John, additional, Deloukas, Panos, additional, Dedoussis, George V., additional, and Visvikis-Siest, Sophie, additional

Published
2021
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18. Ispitivanje uloge AIP gena u patogenezi adenoma hipofize na životinjskom i ljudskom modelu

Author

Popović-Brkić, Vera, Korbonits, Márta, Petakov, Milan, Medić-Stojanoska, Milica, Miljić, Dragana, Stojanović, Marko L., Popović-Brkić, Vera, Korbonits, Márta, Petakov, Milan, Medić-Stojanoska, Milica, Miljić, Dragana, and Stojanović, Marko L.

Abstract

Naučno interesovanje za aryl hydrocarbon receptor-interacting protein (AIP) gen poteklo je od saznanja da su pacijenti sa inaktivirajućim AIP mutacijama predisponirani za razvoj velikih, invazivnih tumora hipofize, somatotropinoma ili prolaktinoma, koji se javljaju u mlađem dobu i otporni su na lečenje. Zebrice (Danio rerio) - (ZF) kao eksperimetalni životinjski model pružaju anatomske i fukcionalne sličnosti sa ljudskim neuroendokrinim sistemom. AIP gen je evoluciono visoko konzerviran i široko eksprimiran u organizmu. Fiziološka uloga AIP proteina u zdravoj hipofizi nije poznata. Zapažena je kolokalizacija AIP proteina sa hormonom rasta (HR) u sekretornim vezikulama somatotrofa. Prisustvo proteina AIP u serumu pokazano je proteomičkom analizom. Ciljevi: Na životinjskom modelu ZF ispitivan je uticaj inaktivacije AIP gena na tumorigenezu na nivou hipofize. Na ljudskom modelu ispitivana je fiziološka uloga AIP proteina na nivou hipofize. Pretpostavljena kosekrecija AIP i HR je ispitivana analizom serumskog nivoa AIP i HR bazno i u toku testova stimulacije ili supresije sekrecije HR kod ispitanika sa očuvanom sekrecijom HR, pacijenata sa deficitom HR (GHD) i pacijenata sa akromegalijom – nekontrolisanom hipersekrecijom HR. Studija na životinjskom modelu – Materijal i metode: Inaktivacija AIP gena - knock down (AIP KD) na embrionima ZF ostvarena je primenom antisens morfolino oligonukleotida u jednoćelijskom stadijumu razvoja. Kontrolni embrioni su tretirani neaktivnim oligonukleotidima sa 5 promenjenih baznih parova (KMo). Neinjektirani embrioni iz istog legla - wild type (WT) analizirani su kao netretirana kontrola. Svi embrioni (N=307) su inkubirani pod istim uslovima po 5 dana tokom kojih je morfometrijski analiziran njihov razvoj. Whole mount in situ hibridizacija za AIP korišćena je za ispitivanje ekspresije AIP gena kod normalnih zebrica (WT) i za potvrdu inaktivacije kod AIP KD. 120h nakon oplodnje, sprovedeno je whole mount imunobojenje ispitivanih i kontrolni, Scientific interest for aryl hydrocarbon receptor-interacting protein (AIP) gene originates from the fact that patients with inactivating AIP mutations are predisposed to large, invasive, GH- or PRL-secreting pituitary tumours, occurring at a younger age and poorly responsive to treatment. The zebrafish (ZF) model provides anatomical and functional similarities to human neuroendocrine system. AIP is evolutionarily well conserved and widely distributed throughout organism. The role of AIP in normal pituitary function is largely unknown. AIP is co-localized with growth hormone (GH) in somatotroph secretory vesicles. Serum AIP protein was proteomically identified. We aimed at investigating the role of AIP inactivation on pituitary tumorigenesis in ZF model and investigating the physiological role of AIP at pituitary level in human model. We investigated whether AIP and GH are co-secreted by measuring serum AIP and GH levels at baseline and after GH stimulation and suppression tests using in vivo human models of normal GH secretion, patients with GH deficiency (GHD) and patients with GH hypersecretion - acromegaly. Animal model study - Material and Methods: AIP knock down (KD) ZF embryos were generated using antisense morpholino oligonucleotides injected at one-cell stage. Control embryos were injected with 5-base mispaired oligonucleotide as control morpholinos (CM). Wild type (WT) embryos from the same batch served as uninjected controls. All embryos (N=307) were incubated in the same conditions for 5 days, and assessed during development. Whole mount in situ hybridization for AIP was used to confirm the inactivation in AIP KD and to asses AIP expression in WT. At 120 hours post fertilization (hpf) whole mount immunostaining of all embryos was performed with anti-PRL antibodies (rabbit anti-salmon polyclonal 1:2000). A total of 15 embryos (5 from each group) were randomly selected for digital microscopy. Pituitary staining was assessed by image analysis software (NIH

Published
2019

20. Kliničke i epidemiološke karakteristike sindroma multiple endokrine neoplazije tip 1 i mehanizmi inaktivacije MEN1 gena u tumorskim tkivima endokrinog i van endokrinog sistema

Author

Damjanović, Svetozar, Petakov, Milan, Novaković, Ivana, Medić Stojanoska, Milica, Isailović, Tatjana V., Damjanović, Svetozar, Petakov, Milan, Novaković, Ivana, Medić Stojanoska, Milica, and Isailović, Tatjana V.

Abstract

Multipla endokrina neoplazija tip 1 (MEN1) je nasledni tumorski sindrom koji se u svom klasičnom obliku karakteriše pojavom primarnog hiperparatiroidizma (PHPT), neuroendokrinih tumora pankreasa (pNET) i pituitarnih adenoma (PA). Gen odgovoran za nastanak sindroma jeste MEN1 gen koji kodira protein menin, ubikvitarno eksprimirani protein koji učestvuje u brojnim ćelijskim procesima. Germinativna mutacija u MEN1 genu i gubitak heterozigotnosti (GH) govore u prilog tumor-supresorske uloge menina u ovim tumorima. Uprskos ubikvitarnoj ekspresiji menina, za MEN1 je karakteristična predilekcija za endokrine organe. Ipak, ni svi endokrini organi nemaju istu predispoziciju za nastanak tumora. Iako je GH očekivani mehanizam inaktivacije, izvesni stepen heterogenosti među tumorima postoji i u pogledu inaktivacije gena. Razlozi ovakve tkivne specifičnosti nisu razjašnjeni. Cilj studije: Cilj ove doktorske disertacije jeste da se ispitaju kliničke, patohistološke i genetske karakteristike pacijenata sa MEN1 sindromom, kao i analiza inaktivacije MEN1 gena u endokrinim i neendokrinim tumorima ovih pacijenata. Materijal i metode: retrospektivno su analizirane genetičke, kliničke i patohistološke karekteristike 102 uzastopna pacijenta sa MEN1 sindromom (prosečna starost 41,1  18,7 godina, od 3 do 72 godine, žene 68,6%, muškarci 31,4%). Direktno sekvenciranje i MLPA MEN1 gena sprovedeno je kod svih pacijenata. Gubitak genskog materijala 11q13 ispitivan je na 30 različitih uzoraka MEN1 tumora od 10 ispitanika. Rezultati: Analizirano je 75 indeksnih pacijenata i njihovih 27 srodnika koji su pripadali 31 različitoj porodici. PHPT je nađen kod 70/88, (79,5%), PA kod 59/88 (67%) a pNET kod 27/88 (30.7 %) pacijenata. Četrnaest (20,9%) pacijenata je bilo asimptomatsko. Mutacija u MEN1 genu je nađena kod 53,3% (40/75) indeksnih slučajeva, odnosno 65,7% u ukupnom broju ispitanika. Većina pacijenata su bile žene, ali je ovo naročito bilo izraženo među MEN1-negativnim pacijentima (86% odn. 59, Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant heritable cancer syndrome characterized by the occurrence of primary hyperparathyroidism (PHPT), pancreatic neuroendocrine tumor (pNET) and pituitary adenoma (PA). The gene responsible for MEN1 is MEN1 tumor suppressor gene which encodes menin, ubiquitously expressed scaffold protein, influencing various cellular processes. The coexistence of heterozygous germline mutation in MEN1 gene, and loss of heterozygosity (LOH) in tumor tissues, demonstrates tumor suppressor role of menin in these tumors. Despite ubiquitous expression of menin, there is strong tissue specificity for endocrine tissue, but some endocrine organs are more frequently affected than other. Although LOH is an expected mechanism of gene inactivation in tumor-suppressor genes, there is heterogeneity in types of gene inactivation among tumors. The aim of the study: The aim of this doctoral thesis is to examine clinical, pathohistological and genetic characteristics of patients with MEN1 syndrome, and to analyze mechanisms of inactivation of MEN1 gene in endocrine and non-endocrine MEN1 tumors in these patients. Materials and methods: Genetic, clinical and histopathological features were analyzed in a retrospective study of 102 consecutive patients with MEN1 (mean age 41,1  18,7 years, range 3 – 72, females 68,6%, males 31,4%). Direct sequencing and MLPA of MEN1 gene were performed in all patients. The presence of 11q13 loss was examined in 30 different MEN1 tumors belonging to 10 patients. Results: We have analyzed 75 index cases and 27 family members, belonging to 31 different families. PHPT was found in 70/88, (79,5%), PA in 59/88 (67%) and pNET in 27/88 (30.7 %) patients. Fourteen (20,9%) patients were asymptomatic...

Published
2018

21. Značaj određivanja vitamina D u pacijenata sa dijabetes melitusom tipa 2

Author

Popović Brkić, Vera, Lalić, Nebojša, Pekić Đurđević, Sandra, Medić Stojanoska, Milica, Kavarić, Sreten J., Popović Brkić, Vera, Lalić, Nebojša, Pekić Đurđević, Sandra, Medić Stojanoska, Milica, and Kavarić, Sreten J.

Abstract

Uvod: Nedostatak vitamina D je dobro poznat faktor rizika za oboljenja kostiju, ali je sve više podataka da izmjenjena homeostaza vitamin D ima ulogu u razvoju šećerne bolesti tipa 2 (T2DM), dislipidemije, hipertenzije i drugih kardiovaskularnih oboljenja (KVO). Cilj: Utvrditi učestalost nedostatka vitamina D kod pacijenata sa šećernom bolešću tipa 2, bez i sa KVO, korelirati nivo vitamina D sa antropometrijskim i metaboličkim parametrima i odrediti prediktore nedostatka vitamina D. Pacijenti i metodologija: U studiju je bilo uključeno 88 pacijenata sa T2DM (49 muškaraca/39 žena, uzrasta 61.0 ± 0.9 godina, indeksa tjelesne mase (ITM) 29.9 ± 0.4 kg/m2) i 67 pacijenata (44 muškaraca/23 žena, uzrasta 63.6 ± 1.0 godina, ITM 29.2 +/- 0.5 kg/m2) sa T2DM i KVO (infarkt miokarda kod 57 pacijenata i angina pektoris kod 10 pacijenata). Ovi pacijenti su upoređeni sa 87 zdravih ispitanika (35 muškaraca/52 žena, uzrasta 52.8 ± 1.4 godina, ITM 27.2 ± 0.5 kg/m2). Kod svih ispitanika mjereni su: tjelesna težina, tjelesna visina, obim struka i računat je ITM, mjeren je arterijski pritisak i bilježena je primjena antihipertenzivnih lekova. Takođe, mjeren je nivo ukupnog holesterola, triglicerida, hemoglobina A1c (HbA1c) i 25-hidroksi-vitamina D [25(OH)D] u serumu. Prema koncentraciji 25(OH)D u serumu, svi ispitanici su podjeljeni u tri grupe: težak nedostatak vitamina D (≤ 15 ng/mL), nedovoljnost vitamina D (15-20 ng/mL) i dovoljan nivo vitamina D (> 20 ng/mL). Korelirali smo nivo vitamina D sa antropometrijskim podacima i metaboličkim parametrima i odredili smo prediktore nedostatka vitamina D. Rezultati: Težak nedostatak vitamina D nađen je kod 16.1% zdravih ispitanika, kod 21.6% pacijenata sa T2DM i kod 26.9% pacijenata sa T2DM i KVO. Pacijenti sa T2DM koji su imali nedostatak vitamina D imali su i povećanu tjelesnu težinu, obim struka, koncentraciju holesterola i triglicerida, u poređenju sa pacijentima sa T2DM koji su imali normalan nivo vitamina D. Koncentracija 25(OH)D u serum, Vitamin D deficiency is a well-established risk factor for bone disease, but emerging data suggest that altered vitamin D homeostasis may play a role in the development of type 2 diabetes mellitus (T2DM), dyslipidemia, hypertension, and other cardiovascular diseases (CVD). The aim of this study was to investigate the prevalence of vitamin D deficiency in patients with T2DM with/without CVD, to correlate it with anthropometric and metabolic parameters and to determine the predictors of vitamin D deficiency. Patients and methods: A total of 88 patients with T2DM (49 male/39 female, aged 61.0 ± 0.9 yrs, body mass index (BMI) 29.9 ± 0.4 kg/m2) and 67 patients (44 male/23 female, aged 63.6 ± 1.0 yrs, BMI 29.2 ± 0.5 kg/m2) with T2DM and CVD (myocardial infarction in 57 patients and angina pectoris in 10 patients) were included in this study. These patients were compared with 87 healthy subjects (35 male/52 female, aged 52.8 ± 1.4 yrs, BMI 27.2 ± 0.5 kg/m2). Weight, height, waist circumference, BMI, blood pressure and history of antihypertensive drugs were recorded in all patients. Also, total cholesterol, triglycerides, hemoglobin A1c (HbA1c) and 25-hydroxy-vitamin D [25(OH)D] levels were measured in all. According to 25(OH)D level, all subjects were divided into three categories: severe vitamin D deficiency (≤ 15 ng/mL), vitamin D insufficiency (15-20 ng/mL) and vitamin D sufficiency (> 20 ng/mL). We correlated vitamin D levels with anthropometric and metabolic status and determined the predictors of vitamin D deficiency. Results: Severe vitamin D deficiency was registered in 16.1% healthy subjects, in 21.6% patients with T2DM and in 26.9% patients with T2DM and CVD. Patients with T2DM who were vitamin D deficient had increased weight, waist circumference, cholesterol and triglyceride levels when compared with patients with T2DM who had sufficient vitamin D level. 25(OH)D levels correlated with BMI and waist circumference in all subjects, but did not correlate with metab

Published
2018

22. SAT-290-Association of liver inflammation and fibrosis score with noninvasive biomarkers in non-alcoholic fatty liver disease: Preliminary results from the MAST4HEALTH study

Author

Apostolou-Karampelis, Konstantinos, Amerikanou, Charalampia, Barone, Angela, Medic-Stojanoska, Milica, Milic, Natasa, Bjelan, Mladen, Stojanoski, Stefan, MilanoviC, Maja, Milosevic, Natasa, Kaliora, Andriana, Varlamis, Iraklis, Smirnioudis, Ilias, Cesarini, Lucia, Belli, Luca S., Vanzulli, Angelo, Campolo, Jonica, Vezou, Chara, Trivella, Maria Giovanna, Gastaldelli, Amalia, Banerjee, Rajarshi, and Dedoussis, George

Published
2019
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23. Uticaj estara ftalne kiseline na tiroidnu funkciju

Author

Medić-Stojanoska, Milica, Milić, Nataša, Kovačev-Zavišić, Branka, Mitrović, Milena, Žarković, Miloš, Suđi, Jan, Ćurić, Nikola, Bajkin, Ivana, Medić-Stojanoska, Milica, Milić, Nataša, Kovačev-Zavišić, Branka, Mitrović, Milena, Žarković, Miloš, Suđi, Jan, Ćurić, Nikola, and Bajkin, Ivana

Abstract

Uvod: Poslednjih godina u fokusu istraživača je efekat sintetskih jednjenja na endokrini sistem. Estri ftalne kiseline se koriste u procesu plastifikacije, kao industrijski rastvarači, lubrikanti, aditivi u tekstilnoj industriji, u pesticidima, kozmetičkim proizvodima. Raste broj dokaza da je tiroidna žlezda podložna dejstvu endokrinih disruptora. Tiroidni hormoni imaju važnu ulogu u regulaciji rasta, tkivne diferencijacije, energetskog metabolizma, reprodukcije i formiranja centralnog nervnog sistema. Brojna istraživanja ukazala su da ftalati deluju kao EDs. Ciljevi istraživanja: 1. Procena izloženosti populacije mono-etilheksil-ftalatu (MEHP) i mono-etil-ftalatu (MEP). 2. Evaluacija razlika u nivou pokazatelja tirodine funkcije između ftalat pozitivnih i ftalat negativnih ispitanika i između gojaznih i normalno uhranjenih ftalat pozitivnih ispitanika. 3.Utvrđivanje razlika u serumskom nivou leptina gojaznih ispitanika sa i bez pozitivnih ftalatnih metabolita i procena povezanosti leptina sa MEP i MEHP i pokazateljima tiroidne funkcije. Izbor ispitanika i metod rada: Istraživanje je sprovedeno kao studija preseka, obuhvatilo je 201 ispitanika. Ispitanici su podeljeni u grupu MEP/MEHP pozitivnih i negativnih i na podgupe normalno uhranjenih i gojaznih. Od antropometrijskih mera određena je telesna visina, telesna masa, obim struka i indeks telesne mase. Laboratorijske analize: jutarnji uzorak urina za određivanje MEP i MEHP; našte uzet uzorka venske krvi za FT4, FT3, TSH i leptin. Statististička analiza sprovedena je na softverskom paketu SPSS. Rezultati: Polovina stanovništva je izložena ftalatima. MEP dovodi do povišenja FT4 samo u subpopulaciji gojaznih. Nije utvrđen statistički značajan uticaj MEP na FT3. Kod gojaznih MEP pozitivnih osoba ženskog pola povišen je TSH. MEHP uzrokuje sniženje FT4 kod normalno uhranjenih ispitanika, a kod normalno uhranjenih muškaraca snižava FT3. Nije utvrđen uticaj MEHP na tirotropin. U gojaznih nije ustanovljen uticaj DEHP i DEP, Introduction: Effects of synthesized chemicals on endocrine system has been in the focus in the last years. Phthalates are used in plasticization, as industrial solvents, lubricants, textile industry additives, in pesticides and cosmetic products. Evidence for thyroid disruption is growing. Thyroid hormones (TH) have an important role in regulation of growth, tissue differentiation, energy metabolism, reproduction and central nervous system formation. Studies show phthalates can cause endocrine disruption. Aims: 1. Estimation of burden of mono-ethyl phthalate (MEP) and di-2-ethylheksyl phthalate(MEHP) in the population. 2. Evaluation of differences in TH and TSH in MEP/MEHP positive and negative participants, as in obese and lean MEP/MEHP positive participants. 3. Evaluation of differences in leptin in obese MEP/MEHP positive and negative subjects and evaluation of the connection between leptin, MEP, MEHP and thyroid indicators. Patients and methods: This was a cross-sectional study that comprised 201 subjects divided into MEP/MEHP positive and negative group, further subdivided in obese and lean. Anthropometric parameters done: body height, body weight, waist and body mass index. Laboratory tests done: morning urine sample analysis for MEP/MEHP and venous sample analysis for free thyroxine (FT4), free tri-iodothyronine (FT3), thyroid stimulating hormone (TSH) and leptin. Statistical analysis was done in SPSS. Results: Half of subjects were exposed to phthalates. MEP induced an increase in FT4 in obese participants and had no influence on FT3. TSH was increased in obese MEP positive female subjects. MEHP induced a decrease in FT4 in lean participants and a decrease of FT3 in lean males. There was no correlation between MEHP and TSH. Influence of MEP/MEHP on leptin secretion. A tendency for negative correlation between leptin and FT4 was seen. There was no influence of leptin on FT3 and TSH. Conclusion: Our population is greatly exposed to phthalates. MEP and MEHP in

Published
2016

28. Uticaj ftalata iz spoljašnje sredine na neke metaboličke poremećaje

Author

Medić-Stojanoska, Milica, Kovačev Zavišić, Branka, Popović Brkić, Vera, Milić, Nataša, Ćurić, Nikola, Stokić, Edita, Bosić-Živanović, Dragana, Medić-Stojanoska, Milica, Kovačev Zavišić, Branka, Popović Brkić, Vera, Milić, Nataša, Ćurić, Nikola, Stokić, Edita, and Bosić-Živanović, Dragana

Abstract

Uvod. Ftalati su endokrini disruptori, široko se koriste kao plastifikatori, rastvarači i aditivi u mnogim potrošačkim proizvodima. Eksperimentalni podaci i humane studije sugerišu na povezanost ftalata sa gojaznošću i dijabetesom. Cilj. Utvrditi da li su i koji urinami metaboliti ftalata prisutni i da li postoje razlike u njihovim nivoima između bolesnika s tipom 2 šećeme bolesti, gojaznih i kontrolne grupe zdravih osoba; da li postoji povezanost između metabolita ftalata i gojaznosti, lipida i lipoproteina seruma, glikemije, insulinemije i insulinske rezistencije. Metode. Istraživanje je obuhvatilo 305 ispitanika, podeljenih u 3 grupe: gojazni (n=104), dijabetesni bolesnici tip 2 (n=101) i zdrave osobe (n=100), oba pola. U svih ispitanika su izvršena antropometrijska merenja (BMI i obim struka), određivanje serumskih lipida (ukupni holesterol, trigliceidi, HDL i LDL holesterol), te glikemija, insulinemija i izračunat indeks insulinske rezistencije (HOMA IRI). U jutarnjem uzorku urina meren je nivo 10 ftalatnih metabolita: mono-metil ftalat (MMP), mono-etil ftalat (MEP), mono-n-butil ftalat (MnBP), mono- benzil ftalat (MBzP), mono-cikloheksil ftalat (MCHP), mono-n-propil ftalat (MPP), mono-n-amil ftalat (MnAP), mono-izo-amil ftalat (MiAP), mono- n-oktil ftalat (MOP), mono-2-etilheksil ftalat (MEHP). U odnosu na prisustvo ftalata u urinu svaka grupa je podeljena u podgrupe na one sa prisutnim ftalatima i one bez ftalata u urinu, odnosno na podgrupe MEP pozitivne, MEP negativne, MEHP pozitivne i MEHP negativne. Rezultati. Kod polovine ispitanika registrovali smo prisustvo u urinu pojedinih metabolita ftalata. Najčešći su bili MEHP i MEP. Najveća sličnost u nivou MEP-a i MEHP-a je bila između gojaznih i dijabetesnih ispitanika. U odnosu na antropometrij ske parametre uočena je pozitivna korelacija MEP-a sa BMI i obimom struka, a negativna korelacija MEHP-a sa BMI i obimom struka, ali su bile nesignifikantne. Samo kod MEHP pozitivnih kontrolne grupe uočena je statistič, Introduction. Phthalates are endocrine disruptors, widely used as plasticizers, solvents and additives in a wide range of consumer products. Experimental data and human studies suggest that phthalate exposure is linked with obesity and diabetes. Aim. To determine whether urinary phthalate metabolites are present, which ones are present, whether there are differences between their levels among the patients with type 2 diabetes, obesity patients and a control group of healthy individuals; whether there is a link between phthalate metabolites and obesity, lipids, serum lipoproteins, glycemia, insulinemia and insulin resistance. Methods. The research included 305 participants divided into three groups: obesity patients (n=104), type 2 diabetes patients (n=101) and healthy individuals (n=100) in both sexes. Anthropometric measurements were taken from all participants (BMI and waist circumference), as well as measurement of serum lipids (total cholesterol, triglycerides, HDL and LDL cholesterol), glycemia, insulinemia and a calculation of insulin resistance index (HOMA IRI). The levels of ten phthalate metabolites were measured in a morning sample of urine: Mono-methyl phthalate (MMP), Mono-ethyl phthalate (MEP), Mono-n-butyl phthalate (MnBP), Mono-benzyl phthalate (MBzP), Mono- cyclohexyl phthalate (MCHP), Mono-n-propyl phthalate (MPP), Mono-n-amyl phthalate (MnAP), Mono-iso-amyl phthalate (MiAP), Mono-n-octyl phthalate (MOP), Mono-2- ethylhexyl phthalate (MEHP). Regarding the presence of phthalates in urine, each group was divided into subgroups, containing phthalates and or not containing phthalates, i.e. subgroups MEP positive and MEP negative, MEHP positive and MEHP negative. Results. In a half of participants, we have registered the presence of certain phthalate metabolites in urine, most often MEHP and MEP. The highest similarity in the levels of MEHP and MEP was between obesity and diabetes participants. Regarding anthropometric measurements, positive correlation

Published
2015

29. Praćenje vrednosti insulinu sličnog faktora rasta tip 1 u serumu i brzine rasta tokom terapije hormonom rasta kod dece

Author

Vlaški, Jovan, Katanić, Dragan, Sajić, Silvija, Stojadinović, Aleksandra, Medić-Stojanoska, Milica, Velisavljev-Filipović, Gordana, Vorgučin, Ivana, Vlaški, Jovan, Katanić, Dragan, Sajić, Silvija, Stojadinović, Aleksandra, Medić-Stojanoska, Milica, Velisavljev-Filipović, Gordana, and Vorgučin, Ivana

Abstract

Hormon rasta ima ključnu ulogu u mnogim fiziološkim procesima, anabolički efekti, stimulisanje rasta dugih kostiju, regulacija transkripcije gena u ciljnim ćelijama su uglavnom posredovani preko mitogenog polipeptida, insulinu sličan faktor rasta tip 1 (insulin like growth factor 1-IGF-1). Hormon rasta indukuje proizvodnju IGF-1 u jetri, koji reaguje sa receptorima ciljnih organa indukujući rast, odnosno IGF-1 posreduje svim stimulativnim dejstvima hormona rasta na kost, hrskavicu, rast mišić a i na metabolizam masti i ugljenih hidrata. U proceni redovnosti, bezbednosti i efikasnosti terapije hormonom rasta koristi se merenje koncentracije IGF-1 u serumu. Istraživanje je urađeno kao retrospektivno-prospektivna studija, a obuhvatilo je 80 pacijenata na terapiji hormonom rasta koja se kontrolišu i leče na Odeljenju za endokrinologiju, dijabetes i bolesti metabolizma Instituta za zdravstvenu zaštitu dece i omladine Vojvodine u Novom Sadu. Istraživani uzorak je obuhvatio 80 pacijenata, od kojih 35 dece sa nedostatkom hormona rasta, 24 dece rođene male za gestacionu dob i 21 devojčicu sa Tarnerovim sindromom. Svi ispitanici su praćeni od početka primene hormona rasta i tokom prve dve godine terapije hormonom rasta. U ovom istraživanju su praćeni auksološki i laboratorijski parametri u cilju ispitivanja odgovora na terapiju hormonom rasta. Praćene su bazalne vrednosti IGF-1 i promene nivoa IGF-1 u serumu tokom terapije hormonom rasta i korišćene da bi se ispitao odgovor na terapiju hormonom rasta, praćenjem brzine rasta, promena skora standardnih devijacija - SSD za telesnu visinu i koštanog sazrevanja. Ciljevi istraživanja su bili da se utvrdi povezanost vrednosti insulinu sličnog faktora rasta tip 1, brzine rasta i koštanog sazrevanja tokom terapije hormonom rasta. Takođe je poređena brzina rasta dece sa deficitom hormona rasta, devojčica sa T arnerovim sindromom i dece rođene male za gestaciono doba na terapiji hormonom rasta. U istraživanom uzorku, dvogodišnjim praćen, Growth hormone plays a key role in many physiological processes. The anabolic effects, the stimulation of growth of the long bones and the regulation of gene transcription in the target cells are mediated mainly via mitogenic polypeptide and insulin-like growth factor type 1 (insulin like growth factor 1-IGF-1). Growth hormone induces the production of IGF-1 in the liver, which interacts with receptors of the target organs inducing growth, that is, IGF-1 mediates all the stimulating effects of growth hormone on bone, cartilage, muscle growth and the metabolism of fats and carbohydrates. In assessing the regularity, safety and efficacy of growth hormone therapy, measuring the concentration of IGF-1 in serum is used. The survey was conducted as a retrospective-prospective study and involved 80 patients treated with growth hormone, monitored and treated at the Department of Endocrinology, Diabetes and Metabolic Diseases, at the Institute for Health Protection of Children and Youth of Vojvodina in Novi Sad. Investigated sample included 80 patients, of whom 35 children have growth hormone deficiency, 24 children were born small for gestational age and 21 girls with Turner syndrome. All the patients were monitored from the beginning of the administration of growth hormone and during the first two years of growth hormone therapy. In this study, auxological and laboratory parameters were monitored for the purpose of examining the response to treatment of growth hormone. The basal values of IGF-1 and changes in IGF-1 levels in serum, along with monitoring the rate of growth velocity and recent changes in standard deviation - SSD for body height and bone maturation, were monitored during growth hormone therapy and used for the evaluation of the response to growth hormone therapy. The objectives of the study were to determine the correlation of insulin-like growth factor type 1 values, the growth velocity and maturation of bone during growth hormone therapy. Also, the growth v

Published
2015

30. Procena rizika za koštane prelome kod žena sa postmenopauznom osteoporozom

Author

Kovačev-Zavišić, Branka, Medić-Stojanoska, Milica, Mitrović, Milena, Stefanović, Dušan, Rankov, Olivera, Kovačev-Zavišić, Branka, Medić-Stojanoska, Milica, Mitrović, Milena, Stefanović, Dušan, and Rankov, Olivera

Abstract

Osteoporosis is a systemic skeletal disease characterized by low bone mass and changes in bone tissue microarchitecture with consequent suspectability in bone fracture. In medical literature, many risk factors for fractures are descibed. WHO after many multicentric studies integrated most important risk factors for fracture in FRAX Questionnaire, which has not been tested so far in women's population in Serbia. Finding the most important singular risk factor for fracture in our population of postmenopausal women, and cummulative contribution of few most important risk factors for fractures, will contribute to adequate choice of curable postmenopausal osteoporosis and prevention from bone fractures. The aim of this study is to determine conection between risk factors for fracfures and fractures in postmenopausal women's population; to determine which of those factors are the most important for osteoporotic fractures in examined postmenopausal women's population. Section study of 529 postmenopausal women diagnosed with osteoporosis or osteopenia was performed. Following fracfure risk factors were examined: age, time of menarha and menopause, antropometric parameters (body height, body weight, BMI), reduction of body height, value of T score measured at the predilection sites, lactation period, smoking, using corticosteroids, early diseases and early fractures, family history of fractures and parity. Results show that age, early disease including using corticosteroids, T score and smoking are leading risk factors for fracfures at postmenopausal women. Two of examined risk factors can highly contribute to developing fractures in examined postmenopausal women's population. It this research it is showed that cut off T score from < -2,5 SD, which is used for diagnosing osteopeorosis is not adequate to estimate risk factor for fracture; we suggest testing T score value of < -2,8 SD in future. Mathematical processing of T score at tree sites at the same time (L1-4, femur nec

Published
2014

31. Uticaj statusa vitamina D na metaboličku aktivnost kosti i koštanu masu kod bolesnika sa alkoholnom cirozom jetre

Author

Damjanov, Dragomir, Ćurić, Nikola, Medić-Stojanoska, Milica, Nagorni, Aleksandar, Hadnađev, Ljiljana, Kovačev Zavišić, Branka, Jovanović, Dušan, Savić, Željka, Damjanov, Dragomir, Ćurić, Nikola, Medić-Stojanoska, Milica, Nagorni, Aleksandar, Hadnađev, Ljiljana, Kovačev Zavišić, Branka, Jovanović, Dušan, and Savić, Željka

Abstract

Uvod: Hepatička osteodistrofija je termin koji obuhvata metaboličke bolesti kosti udružene sa hroničnim bolestima jetre. U alkoholnoj cirozi (AC) jetre postoji visoka zastupljenost deficijencije vitamina D proporcionalna stepenu disfunkcije jetre, ali njena uloga u patogenezi hepatičke osteodistrofije nije dovoljno objašnjena. Nivo 25(OH)D odražava status vitamina D. Kod AC jetre izmenjena je metabolička aktivnost kosti i suprimirano je formiranje kosti što dovodi do smanjenja koštane mase. U centru interesovanja je postizanje optimalnog statusa vitamina D. Stavovi o suplementaciji vitaminom D kod AC jetre nisu jasno definisani. Cilj rada: Utvrditi nivo vitamina D, ispitati metaboličku aktivnost kosti i mineralnu gustinu kosti kod bolesnika sa AC jetre. Utvrditi efekte suplementacije sa 1000 IU vitamina D3 na dan tokom godinu dana u odnosu na metaboličku aktivnost kosti i mineralnu gustinu kosti kod ispitivanih bolesnika. Bolesnici i metode: Istraživanje je sprovedeno na Klinici za gastroenterologiju i hepatologiju Kliničkog centra Vojvodine u Novom Sadu kao prospektivna intervencijska studija sa primenom suplementacije sa 1000 IU vitamina D3 na dan kod bolesnika sa AC jetre. Grupu bolesnika koja je uključena u istraživanje (1) činilo je 70 bolesnika muškog pola sa dijagnozom AC jetre. Bolesnici su imali četiri pregleda (P), odnosno tačke studije: P1-uključivanje bolesnika i započinjanje suplementacije vitaminom D; P2, P3 i P4 posle tri, šest i dvanaest meseci suplementacije vitaminom D, redom. Prilikom svakog pregleda rađene su analize funkcije jetre, metabolizma kosti i statusa vitamina D. Na početku (P1) i na kraju istraživanja (P4) vršeno je merenje mineralne gustine kosti (BMD) DXA metodom. Gubitak bolesnika od P1 do P4 bio je dvadeset, na različitim tačkama studije. Prvi deo istraživanja odnosi se na Grupu bolesnika koja je uključena u istraživanje (1) i završila prvi pregled (P1). Pedeset bolesnika je završilo kompletno istraživanje po predviđenom protokolu i, Introduction: The term Hepatic osteodystrophy defines a group of metabolic bone diseases associated with underlying chronic liver disease. Alcoholic liver cirrhosis (ALC) is characterized by high incidence of vitamin D deficiency that is proportional to the level of liver failure; however, its role in the pathogenesis of hepatic osteodystrophy has not yet been fully elucidated. The level of 25(OH)D best reflects the vitamin D status. ALC is characterized by changed bone metabolic activity and suppressed bone formation, resulting in the decrease in bone mass. The key topic of interest is the achievement of optimal vitamin D status. The attitude of health professionals towards vitamin D supplementation in alcoholic liver cirrhosis has not yet been clearly defined. The aim of the research: Determining of vitamin D levels, investigating the metabolic activity of the bone and bone mass in patients with alcoholic liver cirrhosis (ALC); Determining the effects of vitamin D3 supplementation at the dose 1000 IU/day during a one-year period in relation to metabolic activity of the bone and bone mineral density (BMD) in the investigated patient population. Patients and methods: The research was conducted at the Clinic for Gastroenterology and Hepatology of the Clinical Centre of Vojvodina in Novi Sad. The research was designed as a prospective interventional study implicating vitamin D3 supplementation at the dose 1000 IU/day to patients with ALC. The investigated patient population (1) encompassed 70 male patients diagnosed with ALC. The patients underwent four examinations (P), that is, research phases: P1 – inclusion of the patient into the study and introduction of vitamin D supplementation; P2, P3 and P4 after 3, 6 and 12 months of vitamin D supplementation treatment, respectively. Each examination included the analysis of liver function, bone metabolism and vitamin D status. At the beginning (P1) and at the end (P4) of the investigation period, bone mineral density (BMD)

Published
2014

34. Possible influence of the environmental pollutant bisphenol A on the cardiometabolic risk factors.

Author

Milošević, Nataša, Jakšić, Vladimir, Sudji, Jan, Vuković, Bojan, Ičin, Tijana, Milić, Nataša, and Medić Stojanoska, Milica

Subjects
CARDIOVASCULAR diseases risk factors, OBESITY, PHENOLS, ENVIRONMENTAL exposure, BODY mass index, WAIST circumference
Abstract

Bisphenol A (BPA) is a ubiquitous environmental pollutant which is often associated with various health issues. In this study 103 healthy female volunteers in reproductive age from Serbian north province Vojvodina were enrolled and examined for the BPA exposure in the urine samples after 12 h of fasting. BPA was found in 35.92 % (37/103) of subjects. Statistically significant increment in waist circumference (p = 0.045) and waist-to-height ratio (p = 0.037) was observed among the BPA positive women in comparison with the women who had the same energetic balance and had not been exposed to BPA. Linear correlation was obtained between the BPA concentration in urine samples and body mass index (r2 = 0.35,p = 0.003) waist circumference (r2 = 0.21,p = 0.02) and waist-to-height ratio (r2 = 0.25,p = 0.01) among the obese. High energetic intake and reduced physical activity additionally pronounced BPA positive association with obesity. No statistically significant difference was observed in triglycerides, HDL and LDL cholesterol levels between the BPA exposed and BPA non-exposed female volunteers. [ABSTRACT FROM PUBLISHER]

Published
2017
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36. LEKOVI, TIREOSTIMULIŠUĆI HORMON I CENTRALNI HIPOTIREOIDIZAM.

Author

Medić-Stojanoska, Milica

Subjects
*DRUG side effects, *THYROTROPIN, *GLYCOPROTEIN hormones, *PITUITARY hormones, *HYPOTHYROIDISM
Abstract

A great number of drugs affect thyroid function by different mechanisms. A wide range of mechanisms include modifications to the hypopthlamo-pituitary axis, synthesis and secretion of thyroid homone by thyroid and change in thyroid hormone metabolism as well as their acitivities in tissue. A small subset of drugs including glucocorticoids, dopamine and dopamine agonists, somatostatine analogs and rexinoids cause suppression of TSH and central hypothyreoidism.This central hypothyroidism usually is not cllinically evident and its medical treatment is not necessery. Non-thyroidal illness syndrome (NTIS) also causes TSH suppression and central hypothyreoidism by complex mechanisms. It becomes clinically apparent if the treatment of NTIS is associated with using glucocorticoids and dopamine and then possibilities possibilities of treatment this hypothreoidism should be considered. Different mechanisams by which these drugs cause central hypothyreoidism and their clinial relevance were analysed in this review. [ABSTRACT FROM AUTHOR]

Published
2013

37. Potential influence of the phthalates on normal liver function and cardiometabolic risk in males.

Author

Milošević, Nataša, Milić, Nataša, Živanović Bosić, Dragana, Bajkin, Ivana, Perčić, Ivanka, Abenavoli, Ludovico, and Medić Stojanoska, Milica

Subjects
PHTHALATE esters, HEART metabolism disorders, MALES, BLOOD serum analysis, AMINOTRANSFERASES
Abstract

Phthalates are ubiquitous environmental contaminants, massively used in industry as plasticizers and additives in cosmetics, which may impair the human endocrine system inducing fertility problems, respiratory diseases, obesity, and neuropsychological disorders. The aim of this study was to examine the influence of the monoethyl phthalate (MEP) and mono-(2-ethylhexyl) phthalate (MEHP) on the liver function and cardiometabolic risk factors in males. In this research, 102 male participants (51 normal weight and 51 overweight/obese) were enrolled and examined for phthalate metabolites exposure in urine samples after 12 h of fasting. MEP was found in 28.43% (29/102) volunteers, while MEHP was detected among 20.59% (21/102) participants. Statistically significant increment in transaminase serum levels was observed in MEP-positive normal weight subgroup. Linear correlation was obtained between MEP concentration in urine samples and triglyceride (TG) serum levels (r2 = 0.33; p < 0.01), visceral adiposity index (VAI) (r2 = 0.41; p < 0.01), lipid accumulation product (LAP) (r2 = 0.32; p < 0.01), and TG to high-density lipoprotein (HDL) ratio (r2 = 0.40, p < 0.01) among the obese. The MEHP-positive normal weight volunteers had statistically significant increment of body mass index (p = 0.03) compared to MEHP-negative participants. Urine MEHP concentrations were negatively correlated with HDL serum levels (r2 = 0.31; p < 0.05) in the normal weight subgroup. The phthalates exposure may be related to statistically significant ALT and AST serum levels increment as well as with increased BMI, while the phthalate levels in the urine may be correlated with increased TG and decreased HDL cholesterol serum levels and associated with indicators of cardiometabolic risk and insulin resistance as LAP and VAI. [ABSTRACT FROM AUTHOR]

Published
2018
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38. SUPKLINIČKA TIREOTOKSIKOZA.

Author

Medić-Stojanoska, Milica

Abstract

Supklinička tireotoksikoza (ST) se definiše kao stanje praćeno sniženim ili suprimovanim vrednostima tireostimulišućeg hormona (TSH), uz normalne vrednosti tireoidnih hormona (ukupnih i slobodnih), bez simptoma hipertireoidizma. Češći je u žena i incidenca se povećava sa starenjem. Prema podacima raznih epidemioloških studija, prevalenca se kreće od 0,7% do 12,4% i na nju utiču brojni faktori. Uzroci mogu biti endogeni i egzogeni. ST ne predstavlja samo biohemijski nalaz jer je praćena kliničkim posledicama. Brojne studije preseka, longitudinalne studije i intervencijske studije su pokazale da postoji jasna povezanost između ST i rizika od atrijalne fibrilacije i fraktura. Povezanost između atrijalne fibrilacije i smanjenja koštanog denziteta sa ST je dozno zavisna i postoji objašnjenje biološkog mehanizma nastanka. Podaci o povezanosti ST i koronarne bolesti, te ukupnog i kardiovaskularnog mortaliteta, kao i sa psihičkim poremećajima (poremećajima raspoloženja, kognitivnim poremećajima, poremećajem kvaliteta života) manje su konzistentni i ne potvrđuju je. U odnosu na lečenje ST ne postoji jasno definisan stav. Preporuka je da se ST leči kada postoji tireoidna bolest i TSH < 0,1 mU/L ili manji. Kada su vrednosti TSH >0,1 - < 0,4 mU/L u ST, a prisutna je i tireoidna bolest, uvođenje terapije treba razmotriti zavisno od prisustva i drugih faktora rizika (starost >65 godina, postmenopauza, osteoporoza, kardiološka oboljenja). Lečenje se sprovodi primenom radioaktivnog joda ili tireosupresivne terapije. Zaključak: U okviru ovog predavanja, pored epidemioloških podataka, etiologije i preporuka za postavljanje dijagnoze ST, ukazaće se na njen klinički značaj i daće se terapijski algoritam kada i kako sprovesti lečenje ST. [ABSTRACT FROM AUTHOR]

Published
2012

39. HYPOTHYROIDISM AFTER FINE NEEDLE ASPIRATION BIOPSY OF THYROID NODULES - A CASE REPORT.

Author

PRODANOVIĆ SIMEUNOVIĆ, Jovana, IČIN, Tijana, POPOVIĆ, Đorđe, BENC, Damir, STEPANOVIĆ, Kristina, and MEDIĆ STOJANOSKA, Milica

Subjects
*NEEDLE biopsy, *THYROIDITIS, *THYROID hormones, *THYROID gland, *HYPOTHYROIDISM, *AUTOIMMUNE thyroiditis
Abstract

Introduction. Fine needle aspiration biopsy is a non-surgical invasive diagnostic method for the cytological evaluation of the thyroid gland. Complications of fine needle aspiration biopsy are rare. Case Report. A female patient, 64 years of age, underwent left-sided nodulectomy in 2006, due to a follicular adenoma of the thyroid gland. In September of 2016, ultrasonography of the thyroid gland confirmed a node in the right lobe, approximately 10 mm in the longest diameter. The thyroid-stimulating hormone level was within the reference range (1,8 mIU/L), as well as calcitonin and carcinoembryonic antigen levels, but with elevated anti-thyroid peroxidase antibodies and anti-thyroglobulin antibodies, so fine needle aspiration was indicated. The cytological finding indicated a suspected follicular lesion and total thyroidectomy with an ex tempore biopsy was proposed in November of 2016. Prior to the surgery, hormone levels were measured and high thyroid-stimulating hormone levels were recorded (79 mIU/L). Further investigation showed low levels of free thyroid hormone concentrations, and levothyroxine was initiated at a dose of 75 mcg per day and the surgical treatment was delayed. The indicated dose of levothyroxine resulted in satisfactory values of the thyroid gland free hormones, and in February 2017, right-sided lobectomy was performed, whereas the histopathological findings indicated lymphocytic thyroiditis. Levothyroxine replacement therapy showed satisfactory results in the postoperative period. Further outpatient ultrasonographic monitoring showed a residual thyroid tissue, with slightly non-homogeneous echostructure in the left thyroid bed, 12 x 11 x 32 mm in size. Regular follow-up was suggested. Conclusion. Hypothyroidism has not been reported as a fine needle aspiration complication in the available literature. [ABSTRACT FROM AUTHOR]

Published
2019
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40. EFFECTS OF PHTHALIC ACID ESTERS ON FETAL HEALTH.

Author

BAJKIN, Ivana, BJELICA, Artur, IČIN, Tijana, DOBRIĆ, Vesna, KOVAČEV ZAVIŠIĆ, Branka, and MEDIĆ STOJANOSKA, Milica

Subjects
*PHTHALATE esters, *FETUS, *ENDOCRINE disruptors, *FETAL development, *PUBERTY, *HYDROLYSIS, *HYPOSPADIAS, *HEALTH
Abstract

Introduction. Phthalates are synthetic industrial compounds capable of disrupting endocrine system. Effects of phthalates depend on dosage, duration of action and stage of development of the individual, thus making the fetus, newborn, and children at puberty the most vulnerable groups. Metabolism of Phthalates: Metabolism of these compounds consists of at least two steps: hydrolysis and conjugation. They are mainly excreted in urine, with a low percent being excreted through feces. Exposure to Phthalates. Exposure to the effects of phthalates begins at the intrauterine stage since the phthalates pass through the placental barrier. Phthalates may be found in plastic products, toys, medical equipment, industrial materials, food, and clothes. Determination of Phthalate Levels in Humans. Urine is the best sample for evaluating phthalate levels in humans because of rapid phthalate metabolism and high concentrations of metabolites in the urine. Fetal Testicular Dysgenesis Syndrome: Fetal testicular dysgenesis syndrome involves disorders of male genital tract such as shortened anogenital distance, hypospadia, cryptorchidism, malformations of seminal vesicles, prostate, epididymis and it results from the harmful effects of phthalates. Other Effects of Phthalates on Health. Negative effects of phthalates on female health are mostly reflected in anovulation, premature puberty, changes in duration of pregnancy. There is a possible effect on neurocognitive development, occurrence of allergies, asthma, testicular carcinoma, hepatic and renal damages, insulin resistance and obesity, thyroid dysfunction. Conclusion. Further studies are needed to establish the safe phthalate concentration in certain products and to determine more negative consequences of exposure to phthalate. [ABSTRACT FROM AUTHOR]

Published
2014
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41. Association between phthalic acid esters and polycystic ovarian syndrome

Author

Milankov, Andrijana, Bjelica, Artur, Medić-Stojanoska, Milica, Mitrović, Milena, Ćurić, Nikola, Milošević, Nataša, Milić, Nataša, and Macut, Đuro

Subjects
endokrini disruptori, ftalne kiseline, zagađivači životne sredine, faktori rizika, sindrom policističnih jajnika, metabolički sindrom, kardiovaskularne bolesti, metaboličke bolesti, Endocrine Disruptors, Phthalic Acids, Environmental Pollutants, Risk Factors, Polycystic Ovary Syndrome, Metabolic Syndrome, Cardiovascular Diseases, Metabolic Diseases
Abstract

Uvod: Ftalati su vrsta endokrinih disruptora koji se široko koriste kao plastifikatori i rastvarači ali i kao aditivi brojim proizvodima koji se svakodnevno koriste. Prema dosadašnjim studijama na eksperimentalnim životinjama, ali i u humanoj populaciji, diestri ftalne kiseline utiču na reproduktivni sistem, učestvuju u nastanku insulinske rezistencije i gojaznosti. Sindrom policističnih ovarijuma (PCOS) je najčešći endokrinološki poremećaj reproduktivnog sistema žena u generativnom periodu. Insulinska rezistencija i centralna gojaznost, kao faktori kardiometaboličkog sindroma imaju značajnu ulogu u etiologiji PCOS. Ciljevi: Utvrditi prisustvo metabolita ftalne kiseline kod žena u reproduktivnom periodu u našoj sredini, kao i da li postoji povezanost ovih endokrinih disruptora sa antropometrijskim parametrima, parametrima glikoregulacije, lipidima i lipoproteinima seruma, gonadotropinima, polnim hormonima, leptinom i indeksima kardiometaboličkog rizika kod žena sa sindromom policističnih jajnika. Metode: Istraživanje je obuhvatalo 61 ženu sa sindromom policističnih jajnika koje su podeljene u dve podgrupe: 31 ispitanica sa PCOS i prisutnim ftalatnim metabolitima u urinu i 30 ispitanica sa PCOS bez ftalatnih metabolita u urinu. Kontrolnu grupu je činilo 30 zdravih žena. Kod svih ispitanica vršena su antropometrijska merenja (TV, TM, OS) i određivane vrednosti parametara glikoregulacije (glikemija i insulinemija, izačunat je HOMA index), lipidi i lipoproteini seruma (ukupan holesterol, trigliceridi, LDL i HDL holesterol), gonadotropini (LH i FSH), polni hormoni (estradiol i testosteron) i leptin. U proceni kardiometaboličkog rizika korišćena su dva indeksa LAP i VAI. Iz jutarnjeg uzorka urina određivano je prisustvo i koncentracija 10 ftalatnih metabolita: Mono-metil ftalat- MMP, Mono-etil ftalat - MEP, Mono-n-butil ftalat - MBP, Mono-n-propil ftalat- MPP, Mono-izo-amil ftalat - MiAP, Mono-n-amil ftalat - MnAP, Mono-cikloheksil ftalat - MCHP, Monobenzil ftalat- MBzP, Mono-(2-etilheksil) ftalat- MHEP, Mono-n-octil ftalat-MOP. Za statističku obradu podataka korišćeni su odgovarajući parametarski i neparametarski testovi. Rezultati: Kod 51 % ispitanica sa PCOS potvrđeno je prisustvo ftalatnih metabolita u urinu. Najzastupljeniji ftalatni metabolit je bio MEHP, zatim MEP, ali je potvrđeno i prisustvo MMP, MPP i MOP. Kod ispitanica sa PCOS su potvrđene statistički značajne korelacije između ukupnih ftalatnih metabolita i BMI, obima struka, glikemije, insulinemije, HOMA indeksa, ukupnog holesterola, triglicerida, LDL holesterola, leptina i testosterona. Analizom pojedinačnih ftalatnih metabolita utvrđene su pozitivne korelacije između MMP i obima struka, parametara glukoznog metabolizma, ukupnog holesterola, LDL holesterola, triglicerida, LAP i VAI indeksa. Zaključak: Kod žena sa PCOS u reproduktivnom periodu u našoj sredini je potvrđeno prisustvo ftalanih metabolita. Najviše koncentracije su verifikovane za MEHP i MEP, ukazujući na visoku ekspoziciju di-etilheksil ftalatu (DEHP) i di-etil ftalatu (DEP). Ukupni ftalati značajno povećavaju vrednosti parametara koje učestvuju u razvoju metaboličkog sindroma kod PCOS, ali i povećavaju kardiovaskularni rizik ovih bolesnica. Direktna, značajna veza je potvrđena između MMP i testosterona, parametara i indeksa kardiometaboličkog sindroma., Introduction: Phthalates are a type of endocrine disruptor widely used as plasticizers and solvents but also as additives to many products that are used daily. According to previous studies in experimental animals, but also in the human population, phthalic diesters affect the reproductive system, participate in the onset of insulin resistance and obesity. Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder of the reproductive system of women in the generative period. Insulin resistance and central obesity, as factors of cardiometabolic syndrome, have a significant role in the etiology of PCOS. Objectives: To determine the presence of phthalic acid metabolites in women in the reproductive period in our environment, and whether there is a connection between these endocrine disruptors with anthropometric parameters, glycoregulation parameters, lipids and serum lipoproteins, gonadotrophins, sex hormones, leptin and indexes of cardiometabolic risk in women with polycystic ovarian syndrome. Methods: The study included 61 women with polycystic ovarian syndrome divided into two subgroups: 31 subjects with PCOS and present phthalate metabolites in urine and 30 subjects with PCOS without phthalate metabolites in urine. The control group consisted of 30 healthy women. In all subjects, anthropometric measurements were carried out (TV, TM, WC) and the values of glycoregulation parameters (glycemia and insulinemia, HOMA index), lipids and serum lipoproteins (total cholesterol, triglycerides, LDL I HDL cholesterol), gonadotropins FSH), sex hormones (estradiol and testosterone) and leptin. In the assessment of cardiometabolic risk LAP and VAI indexes were determined. From the morning urine sample, the presence and concentration of 10 phthalate metabolites were determined: Mono-methyl phthalate-MMP, Mono-ethyl phthalate-MEP, Mono-n-butyl phthalate-MBF, Mono-n- propyl phthalate- MPP, Mono-iso-amyl phthalate – MiAP, Mono-n-amyl phthalate – MnAP, Mono-cyclohexyl phthalate-MCHP, Monobenzyl phthalate-MBzP, Mono- (2-ethylhexyl) phthalate-MHEP, Mono-n-octyl phthalate-MOP. For statistical data processing, appropriate parametric and non-parametric tests were used. Results: 51% of subjects with PCOS confirmed the presence of phthalate metabolites in urine. The most common phthalate metabolite was MEHP, then MEP, but the presence of MMP, MPP and MOP also was confirmed. In subjects with PCOS, a statistically significant correlations between total phthalate metabolites and BMI, waist circumference, glycemia, insulinemia, HOMA index, total cholesterol, triglyceride, LDL cholesterol, leptin and testosterone were confirmed. By analyzing individual phthalate metabolites, a positive correlations between MMP and waist circumference, glycoregulation parameters, total cholesterol, LDL cholesterol, triglyceride, testosterone and LAP and VAI index were determined. Conclusion: In women with PCOS in the reproductive period, the presence of phthalic metabolites in our environment was confirmed. The highest concentrations were verified for MEHP and MEP, indicating a high exposure of DEHP and DEP. Total phthalates significantly increase the values of parameters involved in the development of metabolic syndrome in PCOS, but also increase the cardiovascular risk of these patients. A direct, significant association was confirmed between MMP and testosterone, parameters and index of cardiometabolic syndrome.

Published
2019

42. Kliničke i epidemiološke karakteristike sindroma multiple endokrine neoplazije tip 1 i mehanizmi inaktivacije MEN1 gena u tumorskim tkivima endokrinog i van endokrinog sistema

Author

Isailović, Tatjana V., Damjanović, Svetozar, Petakov, Milan, Novaković, Ivana, and Medić Stojanoska, Milica

Subjects
MEN1 gene, MEN1 gen, MEN1 sindrom, MEN1 syndrome, loss of heterozigosity, endocrine and nonendocrine tumors, gubitak heterozigotnosti, MEN1 fenokopija, novootkrivene mutacije, endokrini i neendokrini tumori, MEN1 phenocopy, novel mutations
Abstract

Multipla endokrina neoplazija tip 1 (MEN1) je nasledni tumorski sindrom koji se u svom klasičnom obliku karakteriše pojavom primarnog hiperparatiroidizma (PHPT), neuroendokrinih tumora pankreasa (pNET) i pituitarnih adenoma (PA). Gen odgovoran za nastanak sindroma jeste MEN1 gen koji kodira protein menin, ubikvitarno eksprimirani protein koji učestvuje u brojnim ćelijskim procesima. Germinativna mutacija u MEN1 genu i gubitak heterozigotnosti (GH) govore u prilog tumor-supresorske uloge menina u ovim tumorima. Uprskos ubikvitarnoj ekspresiji menina, za MEN1 je karakteristična predilekcija za endokrine organe. Ipak, ni svi endokrini organi nemaju istu predispoziciju za nastanak tumora. Iako je GH očekivani mehanizam inaktivacije, izvesni stepen heterogenosti među tumorima postoji i u pogledu inaktivacije gena. Razlozi ovakve tkivne specifičnosti nisu razjašnjeni. Cilj studije: Cilj ove doktorske disertacije jeste da se ispitaju kliničke, patohistološke i genetske karakteristike pacijenata sa MEN1 sindromom, kao i analiza inaktivacije MEN1 gena u endokrinim i neendokrinim tumorima ovih pacijenata. Materijal i metode: retrospektivno su analizirane genetičke, kliničke i patohistološke karekteristike 102 uzastopna pacijenta sa MEN1 sindromom (prosečna starost 41,1  18,7 godina, od 3 do 72 godine, žene 68,6%, muškarci 31,4%). Direktno sekvenciranje i MLPA MEN1 gena sprovedeno je kod svih pacijenata. Gubitak genskog materijala 11q13 ispitivan je na 30 različitih uzoraka MEN1 tumora od 10 ispitanika. Rezultati: Analizirano je 75 indeksnih pacijenata i njihovih 27 srodnika koji su pripadali 31 različitoj porodici. PHPT je nađen kod 70/88, (79,5%), PA kod 59/88 (67%) a pNET kod 27/88 (30.7 %) pacijenata. Četrnaest (20,9%) pacijenata je bilo asimptomatsko. Mutacija u MEN1 genu je nađena kod 53,3% (40/75) indeksnih slučajeva, odnosno 65,7% u ukupnom broju ispitanika. Većina pacijenata su bile žene, ali je ovo naročito bilo izraženo među MEN1-negativnim pacijentima (86% odn. 59% kod nosilaca, p

Published
2018

43. Značaj određivanja vitamina D u pacijenata sa dijabetes melitusom tipa 2

Author

Kavarić, Sreten J., Popović Brkić, Vera, Lalić, Nebojša, Pekić Đurđević, Sandra, and Medić Stojanoska, Milica

Subjects
kardiovaskularno oboljenje, diabetes mellitus type 2, arterial hypertension, cardiovascular, Vitamin D, dijabetes melitus tip 2, arterijska hipertenzija
Abstract

Uvod: Nedostatak vitamina D je dobro poznat faktor rizika za oboljenja kostiju, ali je sve više podataka da izmjenjena homeostaza vitamin D ima ulogu u razvoju šećerne bolesti tipa 2 (T2DM), dislipidemije, hipertenzije i drugih kardiovaskularnih oboljenja (KVO). Cilj: Utvrditi učestalost nedostatka vitamina D kod pacijenata sa šećernom bolešću tipa 2, bez i sa KVO, korelirati nivo vitamina D sa antropometrijskim i metaboličkim parametrima i odrediti prediktore nedostatka vitamina D. Pacijenti i metodologija: U studiju je bilo uključeno 88 pacijenata sa T2DM (49 muškaraca/39 žena, uzrasta 61.0 ± 0.9 godina, indeksa tjelesne mase (ITM) 29.9 ± 0.4 kg/m2) i 67 pacijenata (44 muškaraca/23 žena, uzrasta 63.6 ± 1.0 godina, ITM 29.2 +/- 0.5 kg/m2) sa T2DM i KVO (infarkt miokarda kod 57 pacijenata i angina pektoris kod 10 pacijenata). Ovi pacijenti su upoređeni sa 87 zdravih ispitanika (35 muškaraca/52 žena, uzrasta 52.8 ± 1.4 godina, ITM 27.2 ± 0.5 kg/m2). Kod svih ispitanika mjereni su: tjelesna težina, tjelesna visina, obim struka i računat je ITM, mjeren je arterijski pritisak i bilježena je primjena antihipertenzivnih lekova. Takođe, mjeren je nivo ukupnog holesterola, triglicerida, hemoglobina A1c (HbA1c) i 25-hidroksi-vitamina D [25(OH)D] u serumu. Prema koncentraciji 25(OH)D u serumu, svi ispitanici su podjeljeni u tri grupe: težak nedostatak vitamina D (≤ 15 ng/mL), nedovoljnost vitamina D (15-20 ng/mL) i dovoljan nivo vitamina D (> 20 ng/mL). Korelirali smo nivo vitamina D sa antropometrijskim podacima i metaboličkim parametrima i odredili smo prediktore nedostatka vitamina D. Rezultati: Težak nedostatak vitamina D nađen je kod 16.1% zdravih ispitanika, kod 21.6% pacijenata sa T2DM i kod 26.9% pacijenata sa T2DM i KVO. Pacijenti sa T2DM koji su imali nedostatak vitamina D imali su i povećanu tjelesnu težinu, obim struka, koncentraciju holesterola i triglicerida, u poređenju sa pacijentima sa T2DM koji su imali normalan nivo vitamina D. Koncentracija 25(OH)D u serumu korelirala je sa ITM i obimom struka kod svih ispitanika, ali nije korelirala sa metaboličkim parametrima (lipidi, HbA1c). Takođe, pacijenti sa T2DM i KVO koji su imali i arterijsku hipertenziju, imali su niže koncentracije vitamina D u poređenju sa zdravim ispitanicima. Nije bilo značajne razlike u koncentraciji vitamina D 7 između normotenzivnih i hipertenzivnih pacijenata sa T2DM. Najbolji prediktori koncentracije vitamina D kod svih ispitanika bilu su tjelesna težina, obim struka i ITM. Zaključak: Kod pacijenata sa T2DM, a posebno kod onih sa udruženim i KVO postoji velika učestalost nedostatka vitamina D. Nadoknada vitamina D mogla bi da ima pozitivne efekte, ali još uvijek nema dovoljno dokaza da se preporuči rutinska primjena vitamina D. Vitamin D deficiency is a well-established risk factor for bone disease, but emerging data suggest that altered vitamin D homeostasis may play a role in the development of type 2 diabetes mellitus (T2DM), dyslipidemia, hypertension, and other cardiovascular diseases (CVD). The aim of this study was to investigate the prevalence of vitamin D deficiency in patients with T2DM with/without CVD, to correlate it with anthropometric and metabolic parameters and to determine the predictors of vitamin D deficiency. Patients and methods: A total of 88 patients with T2DM (49 male/39 female, aged 61.0 ± 0.9 yrs, body mass index (BMI) 29.9 ± 0.4 kg/m2) and 67 patients (44 male/23 female, aged 63.6 ± 1.0 yrs, BMI 29.2 ± 0.5 kg/m2) with T2DM and CVD (myocardial infarction in 57 patients and angina pectoris in 10 patients) were included in this study. These patients were compared with 87 healthy subjects (35 male/52 female, aged 52.8 ± 1.4 yrs, BMI 27.2 ± 0.5 kg/m2). Weight, height, waist circumference, BMI, blood pressure and history of antihypertensive drugs were recorded in all patients. Also, total cholesterol, triglycerides, hemoglobin A1c (HbA1c) and 25-hydroxy-vitamin D [25(OH)D] levels were measured in all. According to 25(OH)D level, all subjects were divided into three categories: severe vitamin D deficiency (≤ 15 ng/mL), vitamin D insufficiency (15-20 ng/mL) and vitamin D sufficiency (> 20 ng/mL). We correlated vitamin D levels with anthropometric and metabolic status and determined the predictors of vitamin D deficiency. Results: Severe vitamin D deficiency was registered in 16.1% healthy subjects, in 21.6% patients with T2DM and in 26.9% patients with T2DM and CVD. Patients with T2DM who were vitamin D deficient had increased weight, waist circumference, cholesterol and triglyceride levels when compared with patients with T2DM who had sufficient vitamin D level. 25(OH)D levels correlated with BMI and waist circumference in all subjects, but did not correlate with metabolic parameters (lipids, HbA1c). Hypertensive patients with T2DM with CVD were vitamin D insufficient in comparison with healthy subjects. This cross-sectional study showed that there were no differences in vitamin D levels between 9 normotensive and hypertensive patients with T2DM. The best predictors of vitamin D level in all subjects were weight, waist circumference and BMI. Conclusion: The high prevalence of vitamin D deficiency in patients with T2DM and particularly in patients with T2DM and CVD suggests that supplementation with vitamin D may be beneficial although there is still not sufficient evidence for recommending prescribing vitamin D.

Published
2018

44. Uticaj estara ftalne kiseline na tiroidnu funkciju

Author

Bajkin, Ivana, Medić-Stojanoska, Milica, Milić, Nataša, Kovačev, Zavišić Branka, Mitrović, Milena, Žarković, Miloš, Suđi, Jan, Ćurić, Nikola, and Kovačev-Zavišić, Branka

Subjects
faktori vezani za pol, ftalne kiseline, dibutil ftalat, tirotropin, Phthalic Acids, Thyroid Gland, dietilheksil ftalat, Thyrotropin, Environmental Exposure, Endocrine Disruptors, Thyroid Function Tests, Dibutyl Phthalate, Diethylhexyl Phthalate, Obesity, Sex Factors, Thyroxine, testovi tiroidne funkcije, endokrini disruptori, tiroidna žlezda, gojaznost, izloženost spoljašnjim faktorima, tiroksin
Abstract

Uvod: Poslednjih godina u fokusu istraživača je efekat sintetskih jednjenja na endokrini sistem. Estri ftalne kiseline se koriste u procesu plastifikacije, kao industrijski rastvarači, lubrikanti, aditivi u tekstilnoj industriji, u pesticidima, kozmetičkim proizvodima. Raste broj dokaza da je tiroidna žlezda podložna dejstvu endokrinih disruptora. Tiroidni hormoni imaju važnu ulogu u regulaciji rasta, tkivne diferencijacije, energetskog metabolizma, reprodukcije i formiranja centralnog nervnog sistema. Brojna istraživanja ukazala su da ftalati deluju kao EDs. Ciljevi istraživanja: 1. Procena izloženosti populacije mono-etilheksil-ftalatu (MEHP) i mono-etil-ftalatu (MEP). 2. Evaluacija razlika u nivou pokazatelja tirodine funkcije između ftalat pozitivnih i ftalat negativnih ispitanika i između gojaznih i normalno uhranjenih ftalat pozitivnih ispitanika. 3.Utvrđivanje razlika u serumskom nivou leptina gojaznih ispitanika sa i bez pozitivnih ftalatnih metabolita i procena povezanosti leptina sa MEP i MEHP i pokazateljima tiroidne funkcije. Izbor ispitanika i metod rada: Istraživanje je sprovedeno kao studija preseka, obuhvatilo je 201 ispitanika. Ispitanici su podeljeni u grupu MEP/MEHP pozitivnih i negativnih i na podgupe normalno uhranjenih i gojaznih. Od antropometrijskih mera određena je telesna visina, telesna masa, obim struka i indeks telesne mase. Laboratorijske analize: jutarnji uzorak urina za određivanje MEP i MEHP; našte uzet uzorka venske krvi za FT4, FT3, TSH i leptin. Statististička analiza sprovedena je na softverskom paketu SPSS. Rezultati: Polovina stanovništva je izložena ftalatima. MEP dovodi do povišenja FT4 samo u subpopulaciji gojaznih. Nije utvrđen statistički značajan uticaj MEP na FT3. Kod gojaznih MEP pozitivnih osoba ženskog pola povišen je TSH. MEHP uzrokuje sniženje FT4 kod normalno uhranjenih ispitanika, a kod normalno uhranjenih muškaraca snižava FT3. Nije utvrđen uticaj MEHP na tirotropin. U gojaznih nije ustanovljen uticaj DEHP i DEP na leptinsku sekreciju.Uočena je tendencija negativne korelacije leptina i FT4 kod gojaznih, dok uticaja na FT3 i TSH nema. Zaključak: Naša populacija je u velikoj meri izložena ftalatima. Potvrđeno je da MEP i MEHP imaju uticaj na pojedine indikatore tiroidne funkcije. Ftalati u našem istraživanju ne uzrokuju poremećaj leptinske skrecije, a leptin ima blag uticaj jedino na FT4., Introduction: Effects of synthesized chemicals on endocrine system has been in the focus in the last years. Phthalates are used in plasticization, as industrial solvents, lubricants, textile industry additives, in pesticides and cosmetic products. Evidence for thyroid disruption is growing. Thyroid hormones (TH) have an important role in regulation of growth, tissue differentiation, energy metabolism, reproduction and central nervous system formation. Studies show phthalates can cause endocrine disruption. Aims: 1. Estimation of burden of mono-ethyl phthalate (MEP) and di-2-ethylheksyl phthalate(MEHP) in the population. 2. Evaluation of differences in TH and TSH in MEP/MEHP positive and negative participants, as in obese and lean MEP/MEHP positive participants. 3. Evaluation of differences in leptin in obese MEP/MEHP positive and negative subjects and evaluation of the connection between leptin, MEP, MEHP and thyroid indicators. Patients and methods: This was a cross-sectional study that comprised 201 subjects divided into MEP/MEHP positive and negative group, further subdivided in obese and lean. Anthropometric parameters done: body height, body weight, waist and body mass index. Laboratory tests done: morning urine sample analysis for MEP/MEHP and venous sample analysis for free thyroxine (FT4), free tri-iodothyronine (FT3), thyroid stimulating hormone (TSH) and leptin. Statistical analysis was done in SPSS. Results: Half of subjects were exposed to phthalates. MEP induced an increase in FT4 in obese participants and had no influence on FT3. TSH was increased in obese MEP positive female subjects. MEHP induced a decrease in FT4 in lean participants and a decrease of FT3 in lean males. There was no correlation between MEHP and TSH. Influence of MEP/MEHP on leptin secretion. A tendency for negative correlation between leptin and FT4 was seen. There was no influence of leptin on FT3 and TSH. Conclusion: Our population is greatly exposed to phthalates. MEP and MEHP influence certain thyroid indicators i.e. cause thyroid disruption. Phthalates do not influence leptin secretion in our study. There is a mild effect of leptin on FT4.

Published
2016

45. Praćenje vrednosti insulinu sličnog faktora rasta tip 1 u serumu i brzine rasta tokom terapije hormonom rasta kod dece

Author

Vorgučin, Ivana, Vlaški, Jovan, Katanić, Dragan, Sajić, Silvija, Stojadinović, Aleksandra, Medić-Stojanoska, Milica, and Velisavljev-Filipović, Gordana

Subjects
Poremećaji rasta, Rast, Bone Development, Insulin-Like Growth Factor I, Growth Hormone, Growth, Turner Syndrome, Growth Disorders, Child, Infant, Small for Gestational Age, Razvoj kostiju, Infant, Insulinu sličan faktor rasta tip 1, Hormon rasta, Tarnerov sindrom, Deca, Novorođenče rođeno malo za gestacionu dob, Small for Gestational Age
Abstract

Hormon rasta ima ključnu ulogu u mnogim fiziološkim procesima, anabolički efekti, stimulisanje rasta dugih kostiju, regulacija transkripcije gena u ciljnim ćelijama su uglavnom posredovani preko mitogenog polipeptida, insulinu sličan faktor rasta tip 1 (insulin like growth factor 1-IGF-1). Hormon rasta indukuje proizvodnju IGF-1 u jetri, koji reaguje sa receptorima ciljnih organa indukujući rast, odnosno IGF-1 posreduje svim stimulativnim dejstvima hormona rasta na kost, hrskavicu, rast mišić a i na metabolizam masti i ugljenih hidrata. U proceni redovnosti, bezbednosti i efikasnosti terapije hormonom rasta koristi se merenje koncentracije IGF-1 u serumu. Istraživanje je urađeno kao retrospektivno-prospektivna studija, a obuhvatilo je 80 pacijenata na terapiji hormonom rasta koja se kontrolišu i leče na Odeljenju za endokrinologiju, dijabetes i bolesti metabolizma Instituta za zdravstvenu zaštitu dece i omladine Vojvodine u Novom Sadu. Istraživani uzorak je obuhvatio 80 pacijenata, od kojih 35 dece sa nedostatkom hormona rasta, 24 dece rođene male za gestacionu dob i 21 devojčicu sa Tarnerovim sindromom. Svi ispitanici su praćeni od početka primene hormona rasta i tokom prve dve godine terapije hormonom rasta. U ovom istraživanju su praćeni auksološki i laboratorijski parametri u cilju ispitivanja odgovora na terapiju hormonom rasta. Praćene su bazalne vrednosti IGF-1 i promene nivoa IGF-1 u serumu tokom terapije hormonom rasta i korišćene da bi se ispitao odgovor na terapiju hormonom rasta, praćenjem brzine rasta, promena skora standardnih devijacija - SSD za telesnu visinu i koštanog sazrevanja. Ciljevi istraživanja su bili da se utvrdi povezanost vrednosti insulinu sličnog faktora rasta tip 1, brzine rasta i koštanog sazrevanja tokom terapije hormonom rasta. Takođe je poređena brzina rasta dece sa deficitom hormona rasta, devojčica sa T arnerovim sindromom i dece rođene male za gestaciono doba na terapiji hormonom rasta. U istraživanom uzorku, dvogodišnjim praćenjem terapije hormonom rasta je postignut dobar odgovor na terapiju, među decom sa nedostatkom hormona rasta je 71,5% postiglo normalnu telesnu visinu (±2 SSDTV) posle dve godine terapije hormonom rasta, 79,2% dece rođene male za gestacionu dob i 42,9% devojčica sa Tarnerovim sindromom. Značajna zastupljenost dece prepubertetskog uzrasta na početku terapije hormonom rasta, među decom sa nedostatkom hormona rasta 77,2%, među decom rođenom malom za gestacionu dob 79,1% i među devojčicama sa Tarnerovim sindromom 90,5% što je značajno uticalo na uspešnost terapije. Tokom terapije hormonom rasta je utvrđeno povećanje brzine rasta i SSD TV kod sve tri grupe ispitanika. U sve tri grupe ispitanika je tokom terapije hormonom rasta utvrđen porast nivoa IGF-1 seruma i SSDIGF-1 i ubrzanje koštanog sazrevanja tokom terapije hormonom rasta. Za prvih šest meseci terapije nema statistički značajnih razlika među grupama u brzini rasta (p>0,05), dok je za period prve i druge godine terapije hormonom rasta utvrđeno da postoji statistički značajna razlika među grupama (p0,5). U ovom istraživanju je praćenjem auskoloških i laboratrijskih parametara tokom dvogodišnje primene hormona rasta, konstruisano više matematičkih modela za predviđanje odgovora na terapiju hormona rasta koji su statistički veoma značajani sa visokim koeficijentom višestruke linearne korelacije. U ovom istraživanju nije dobijena statistički značajna korelacija izmedju nivoa promene IGF-1 i brzine rasta za ceo uzorak, kao ni za decu sa nedostatkom hormona rasta, decu rođenu malu za gestacionu dob i devojčice za Tarnerovim sindromom. Nije dobijena statistički značajna korelacija izmedju nivoa promene IGF-1 i ubrzanja koštanog sazrevanja za ceo uzorak i za tri grupe pacijenata., Growth hormone plays a key role in many physiological processes. The anabolic effects, the stimulation of growth of the long bones and the regulation of gene transcription in the target cells are mediated mainly via mitogenic polypeptide and insulin-like growth factor type 1 (insulin like growth factor 1-IGF-1). Growth hormone induces the production of IGF-1 in the liver, which interacts with receptors of the target organs inducing growth, that is, IGF-1 mediates all the stimulating effects of growth hormone on bone, cartilage, muscle growth and the metabolism of fats and carbohydrates. In assessing the regularity, safety and efficacy of growth hormone therapy, measuring the concentration of IGF-1 in serum is used. The survey was conducted as a retrospective-prospective study and involved 80 patients treated with growth hormone, monitored and treated at the Department of Endocrinology, Diabetes and Metabolic Diseases, at the Institute for Health Protection of Children and Youth of Vojvodina in Novi Sad. Investigated sample included 80 patients, of whom 35 children have growth hormone deficiency, 24 children were born small for gestational age and 21 girls with Turner syndrome. All the patients were monitored from the beginning of the administration of growth hormone and during the first two years of growth hormone therapy. In this study, auxological and laboratory parameters were monitored for the purpose of examining the response to treatment of growth hormone. The basal values of IGF-1 and changes in IGF-1 levels in serum, along with monitoring the rate of growth velocity and recent changes in standard deviation - SSD for body height and bone maturation, were monitored during growth hormone therapy and used for the evaluation of the response to growth hormone therapy. The objectives of the study were to determine the correlation of insulin-like growth factor type 1 values, the growth velocity and maturation of bone during growth hormone therapy. Also, the growth velocity in children with growth hormone deficiency was compared with the growth velocity in girls with Turner syndrome and in children born small for gestational age while treated with growth hormone. Two-year monitoring of growth hormone therapy in the study sample has show n good response to therapy. 71.5% of children with growth hormone deficiency, 79.2% of children born small for gestational age, and 42.9% of girls with Turner syndrome achieved normal body height (± 2 SSDTV) after two years of growth hormone therapy. There was a significant share of children at prepubertal age at the beginning of growth hormone therapy: 77.2% of children with growth hormone deficiency, 79.1% of children born small for gestational age and 90.5% of girls with Turner syndrome, which significantly influenced the success of the therapy. During the growth hormone therapy there was an increase of growth velocity and SSD TV in all three groups of children. An increase in levels of IGF-1 serum and SSDIGF-1 and acceleration of bone maturation were determined in all three groups of patients during growth hormone therapy. For the first six months of therapy there was no statistically significant difference between groups in growth velocity (p> 0.05), while the period of the first and second year of growth hormone therapy showed a statistically significant difference between groups (p 0.5). By monitoring auxological and laboratory parameters during the two years of application of growth hormone, several highly statistically significant mathematical models for predicting the response to treatment of growth hormone were constructed in this study with a high coefficient of multiple linear correlation. In this study, there was no statistically significant correlation between the level of change in IGF-1 and growth velocity for the entire sample, as well as for children with growth hormone deficiency, children born small for gestational age and girls for Turner syndrome. There was no statistically significant correlation between the level of change in IGF-1 and acceleration of bone maturation for the entire sample and for the three groups of patients.

Published
2015

46. Uticaj ftalata iz spoljašnje sredine na neke metaboličke poremećaje

Author

Bosić-Živanović, Dragana, Medić-Stojanoska, Milica, Kovačev, Zavišić Branka, Popović, Brkić Vera, Milić, Nataša, Ćurić, Nikola, Stokić, Edita, Kovačev Zavišić, Branka, and Popović Brkić, Vera

Subjects
Endokrini disruptori, Gojaznost, Dietilheksil ftalat, Phthalic Acids, Dijabetes melitus tip 2, Endocrine Disruptors, Diabetes Mellitus Type 2, Zagađivači okoline, Ftalne kiseline, Obesity, Diethylhexyl Phthalate, Environmental Pollutants
Abstract

Uvod. Ftalati su endokrini disruptori, široko se koriste kao plastifikatori, rastvarači i aditivi u mnogim potrošačkim proizvodima. Eksperimentalni podaci i humane studije sugerišu na povezanost ftalata sa gojaznošću i dijabetesom. Cilj. Utvrditi da li su i koji urinami metaboliti ftalata prisutni i da li postoje razlike u njihovim nivoima između bolesnika s tipom 2 šećeme bolesti, gojaznih i kontrolne grupe zdravih osoba; da li postoji povezanost između metabolita ftalata i gojaznosti, lipida i lipoproteina seruma, glikemije, insulinemije i insulinske rezistencije.Metode. Istraživanje je obuhvatilo 305 ispitanika, podeljenih u 3 grupe: gojazni (n=104), dijabetesni bolesnici tip 2 (n=101) i zdrave osobe (n=100), oba pola. U svih ispitanika su izvršena antropometrijska merenja (BMI i obim struka), određivanje serumskih lipida (ukupni holesterol, trigliceidi, HDL i LDL holesterol), te glikemija, insulinemija i izračunat indeks insulinske rezistencije (HOMA IRI). U jutarnjem uzorku urina meren je nivo 10 ftalatnih metabolita: mono-metil ftalat (MMP), mono-etil ftalat (MEP), mono-n-butil ftalat (MnBP), mono- benzil ftalat (MBzP), mono-cikloheksil ftalat (MCHP), mono-n-propil ftalat (MPP), mono-n-amil ftalat (MnAP), mono-izo-amil ftalat (MiAP), mono- n-oktil ftalat (MOP), mono-2-etilheksil ftalat (MEHP). U odnosu na prisustvo ftalata u urinu svaka grupa je podeljena u podgrupe na one sa prisutnim ftalatima i one bez ftalata u urinu, odnosno na podgrupe MEP pozitivne, MEP negativne, MEHP pozitivne i MEHP negativne. Rezultati. Kod polovine ispitanika registrovali smo prisustvo u urinu pojedinih metabolita ftalata. Najčešći su bili MEHP i MEP. Najveća sličnost u nivou MEP-a i MEHP-a je bila između gojaznih i dijabetesnih ispitanika. U odnosu na antropometrij ske parametre uočena je pozitivna korelacija MEP-a sa BMI i obimom struka, a negativna korelacija MEHP-a sa BMI i obimom struka, ali su bile nesignifikantne. Samo kod MEHP pozitivnih kontrolne grupe uočena je statistički značajna pozitivna korelacija MEHP-a i obima struka. Utvrđena je statistički značajna negativna korelaciju MEP-a i HDL holesterola, a pozitivna korelacija MEP-a i triglicerida samo kod gojaznih. Samo u kontrolnoj grupi MEHP pozitivnih postojala je statistički značajna negativna korelacija sa HDL holesterolom. Postojala je pozitivna korelacija MEP-a i HOMA-IRI, a pozitivna korelacija MEHP-a sa glikemijom samo kod MEHP pozitivnih DM tip 2. Zaključak. Potvrđeno je da je kontaminacija ftalatima prisutna u našoj populaciji, a najčešće su prisutni MEHP i MEP, ukazujući na ekspoziciju DEHP i DEP. Indirektno smo stekli uvid da povećana izloženost DEP i DEHP može doprineti nastanku izvesnih poremećaja lipida i lipoproteina, insulinskoj rezistenciji kao i razvoju gojaznosti., Introduction. Phthalates are endocrine disruptors, widely used as plasticizers, solvents and additives in a wide range of consumer products. Experimental data and human studies suggest that phthalate exposure is linked with obesity and diabetes. Aim. To determine whether urinary phthalate metabolites are present, which ones are present, whether there are differences between their levels among the patients with type 2 diabetes, obesity patients and a control group of healthy individuals; whether there is a link between phthalate metabolites and obesity, lipids, serum lipoproteins, glycemia, insulinemia and insulin resistance. Methods. The research included 305 participants divided into three groups: obesity patients (n=104), type 2 diabetes patients (n=101) and healthy individuals (n=100) in both sexes. Anthropometric measurements were taken from all participants (BMI and waist circumference), as well as measurement of serum lipids (total cholesterol, triglycerides, HDL and LDL cholesterol), glycemia, insulinemia and a calculation of insulin resistance index (HOMA IRI). The levels of ten phthalate metabolites weremeasured in a morning sample of urine: Mono-methyl phthalate (MMP), Mono-ethyl phthalate (MEP), Mono-n-butyl phthalate (MnBP), Mono-benzyl phthalate (MBzP), Mono- cyclohexyl phthalate (MCHP), Mono-n-propyl phthalate (MPP), Mono-n-amyl phthalate (MnAP), Mono-iso-amyl phthalate (MiAP), Mono-n-octyl phthalate (MOP), Mono-2- ethylhexyl phthalate (MEHP). Regarding the presence of phthalates in urine, each group was divided into subgroups, containing phthalates and or not containing phthalates, i.e. subgroups MEP positive and MEP negative, MEHP positive and MEHP negative. Results. In a half of participants, we have registered the presence of certain phthalate metabolites in urine, most often MEHP and MEP. The highest similarity in the levels of MEHP and MEP was between obesity and diabetes participants. Regarding anthropometric measurements, positive correlation has been registered between MEP and BMI and waist circumference, while negative correlation has been registered between MEHP and BMI and waist circumference, but it was insignificant. Only in MEHP positive control group, statistically significant positive correlation between MEHP and waist circumference has been registered. Statistically significant negative correlation between MEP and HDL cholesterol has been registered, while positive correlation between MEP and triglycerides has been registered only in obesity patients group. Only in MEHP positive control group statistically significant negative correlation with HDL cholesterol has been registered. There has been a positive correlation between MEP and HOMA-IRI, while positive correlation between MEHP and glycemia has been registered only in MEHP positive DM type 2. Conclusion. It has been confirmed that our population is contaminated with phthalates, most commonly MEHP and MEP, indicating exposure to DEHP and DEP. Indirectly, we have realized that an increased exposure to DEHP and DEP can contribute to the development of certain lipid and lipoprotein disorders, insulin resistance, as well as the development of obesity.

Published
2015

47. Uticaj statusa vitamina D na metaboličku aktivnost kosti i koštanu masu kod bolesnika sa alkoholnom cirozom jetre

Author

Savić, Željka, Damjanov, Dragomir, Ćurić, Nikola, Medić-Stojanoska, Milica, Nagorni, Aleksandar, Hadnađev, Ljiljana, Kovačev, Zavišić Branka, Jovanović, Dušan, and Kovačev Zavišić, Branka

Subjects
Liver Cirrhosis, Kosti + metabolizam, Alkoholna ciroza jetre, Vitamin D + terapijska primena, Deficijencija vitamina D, Gustina kostiju, Funkcionalni testovi jetre, Dijetetski suplementi, Bone and Bones + metabolism, Alcoholic, Vitamin D Deficiency, Liver Function Tests, Bone Density, Dietary Supplements, Liver Cirrhosis, Alcoholic, Vitamin D + therapeutic use
Abstract

Uvod: Hepatička osteodistrofija je termin koji obuhvata metaboličke bolesti kosti udružene sa hroničnim bolestima jetre. U alkoholnoj cirozi (AC) jetre postoji visoka zastupljenost deficijencije vitamina D proporcionalna stepenu disfunkcije jetre, ali njena uloga u patogenezi hepatičke osteodistrofije nije dovoljno objašnjena. Nivo 25(OH)D odražava status vitamina D. Kod AC jetre izmenjena je metabolička aktivnost kosti i suprimirano je formiranje kosti što dovodi do smanjenja koštane mase. U centru interesovanja je postizanje optimalnog statusa vitamina D. Stavovi o suplementaciji vitaminom D kod AC jetre nisu jasno definisani. Cilj rada: Utvrditi nivo vitamina D, ispitati metaboličku aktivnost kosti i mineralnu gustinu kosti kod bolesnika sa AC jetre. Utvrditi efekte suplementacije sa 1000 IU vitamina D3 na dan tokom godinu dana u odnosu na metaboličku aktivnost kosti i mineralnu gustinu kosti kod ispitivanih bolesnika. Bolesnici i metode: Istraživanje je sprovedeno na Klinici za gastroenterologiju i hepatologiju Kliničkog centra Vojvodine u Novom Sadu kao prospektivna intervencijska studija sa primenom suplementacije sa 1000 IU vitamina D3 na dan kod bolesnika sa AC jetre. Grupu bolesnika koja je uključena u istraživanje (1) činilo je 70 bolesnika muškog pola sa dijagnozom AC jetre. Bolesnici su imali četiri pregleda (P), odnosno tačke studije: P1-uključivanje bolesnika i započinjanje suplementacije vitaminom D; P2, P3 i P4 posle tri, šest i dvanaest meseci suplementacije vitaminom D, redom. Prilikom svakog pregleda rađene su analize funkcije jetre, metabolizma kosti i statusa vitamina D. Na početku (P1) i na kraju istraživanja (P4) vršeno je merenje mineralne gustine kosti (BMD) DXA metodom. Gubitak bolesnika od P1 do P4 bio je dvadeset, na različitim tačkama studije. Prvi deo istraživanja odnosi se na Grupu bolesnika koja je uključena u istraživanje (1) i završila prvi pregled (P1). Pedeset bolesnika je završilo kompletno istraživanje po predviđenom protokolu i oni se zbog realizacije svih pregleda i ponovljenih merenja posmatraju kao: Grupa bolesnika koja je završila istraživanje (2). Rezultati: (1): Kod bolesnika sa AC jetre utvrđena je deficijencija vitamina D, snižen nivo osteokalcina, normalni nivoi CrossLapsa, PTH, ukupnog i jonizovanog kalcijuma, fosfora i magnezijuma. Osteopeniju je imalo 42,65% a osteoporozu 14,71% ispitanika. Kod svih ispitanika najniži BMD izmeren je na vratu femura. (2): Suplementacija vitaminom D dovela je do značajnog porasta 25(OH)D. U odnosu na osteokalcin konstatovana je pozitivna razlika vrednosti P1/P4, iako je nivo ostao ispod donje granice normale. Kod nivoa CrossLapsa i PTH razlika P1/P4 je negativna, ali su nivoi u sva četiri merenja u okviru referentnih vrednosti. Na lumbalnoj kičmi došlo je do poboljšanja BMD za 0.87%, a pogoršanja su na vratu femura -1.87 % i kuku -1.65%. Konstatovano je i poboljšanje funkcije jetre. Zaključci: Kod bolesnika sa AC jetre poboljšanje statusa vitamina D dovodi do povećanja formiranja kosti i poboljšanja koštane mase na lumbalnoj kičmi. Neophodno je određivanje statusa vitamina D kod svih bolesnika sa AC jetre i uvođenje suplementacije vitaminom D kod bolesnika koji imaju nivo 25(OH)D < 80 nmol/l, uz tromesečne kontrole efekta. Kod postavljanja dijagnoze AC jetre potrebno je inicijalno određivanje BMD. Kod suplementacije vitaminom D nakon inicijalnog DXA pregleda sledeći se preporučuje nakon jedne do dve godine., Introduction: The term Hepatic osteodystrophy defines a group of metabolic bone diseases associated with underlying chronic liver disease. Alcoholic liver cirrhosis (ALC) is characterized by high incidence of vitamin D deficiency that is proportional to the level of liver failure; however, its role in the pathogenesis of hepatic osteodystrophy has not yet been fully elucidated. The level of 25(OH)D best reflects the vitamin D status. ALC is characterized by changed bone metabolic activity and suppressed bone formation, resulting in the decrease in bone mass. The key topic of interest is the achievement of optimal vitamin D status. The attitude of health professionals towards vitamin D supplementation in alcoholic liver cirrhosis has not yet been clearly defined. The aim of the research: Determining of vitamin D levels, investigating the metabolic activity of the bone and bone mass in patients with alcoholic liver cirrhosis (ALC); Determining the effects of vitamin D3 supplementation at the dose 1000 IU/day during a one-year period in relation to metabolic activity of the bone and bone mineral density (BMD) in the investigated patient population. Patients and methods: The research was conducted at the Clinic for Gastroenterology and Hepatology of the Clinical Centre of Vojvodina in Novi Sad. The research was designed as a prospective interventional study implicating vitamin D3 supplementation at the dose 1000 IU/day to patients with ALC. The investigated patient population (1) encompassed 70 male patients diagnosed with ALC. The patients underwent four examinations (P), that is, research phases: P1 – inclusion of the patient into the study and introduction of vitamin D supplementation; P2, P3 and P4 after 3, 6 and 12 months of vitamin D supplementation treatment, respectively. Each examination included the analysis of liver function, bone metabolism and vitamin D status. At the beginning (P1) and at the end (P4) of the investigation period, bone mineral density (BMD) was measured by means of dual-energy x-ray absorptiometry (DXA) method. Twenty patients dropped out from the research at different stages throughout the investigation period (P1 to P4). The first part of the investigation pertains to the Group of patients who were included into the study (1) and completed the first examination (P1). Fifty patients have completed the entire research according to the foreseen protocol encompassing all examinations and repeated measurements. These patients are considered a Group of patients who completed the research (2) Results: (1): In ALC patients, vitamin D deficiency and decreased osteocalcin levels were established, as well as normal levels of CrossLaps, PTH, total and ionized calcium, phosphorus and magnesium. Osteopenia and osteoporosis were established in 42.65% and 14.71% of patients, respectively. The lowest BMD was measured in the femoral neck in all patients. (2): Vitamin D supplementation resulted in significant increase in 25(OH)D. Analysis of osteocalcin level revealed positive P1/P4 difference, even though the level remained below the lower normal limit. The levels of CrossLaps and PTH revealed negative P1/P4 difference; however, the levels determined at all four measurements were within the reference values. An improvement of BMD for 0.87% was established in lumbar spine, whereas a decrease was noticed in femoral neck (1.87%) and hip (1.65%). Furthermore, an improvement of liver function was established. Conclusions: Improvement of vitamin D status in ALC patients results in an increase of bone formation and improvement of body mass in lumbar spine. Determining the vitamin D status in all patients with ALC is of outmost importance, as well as the vitamin D supplementation of patients with levels of 25(OH)D < 80 nmol/l along with the monitoring of treatment outcome at three-month intervals. Establishment of the diagnosis of alcoholic liver cirrhosis should encompass initial measurement of BMD. In case of vitamin D supplementation treatment, the initial DXA examination should be repeated after the period of one to two years.

Published
2014

48. Assessment of risk for bone fractures in women with postmenopausal osteoporosis

Author

Rankov, Olivera, Kovačev, Zavišić Branka, Medić-Stojanoska, Milica, Mitrović, Milena, and Stefanović, Dušan

Subjects
Osteoporosis, postmenopausal, Risk factors, Bone density, Bone disease, metabolic, Osteoporotis fractures
Abstract

Osteoporosis is a systemic skeletal disease characterized by low bone mass and changes in bone tissue microarchitecture with consequent suspectability in bone fracture. In medical literature, many risk factors for fractures are descibed. WHO after many multicentric studies integrated most important risk factors for fracture in FRAX Questionnaire, which has not been tested so far in women's population in Serbia. Finding the most important singular risk factor for fracture in our population of postmenopausal women, and cummulative contribution of few most important risk factors for fractures, will contribute to adequate choice of curable postmenopausal osteoporosis and prevention from bone fractures. The aim of this study is to determine conection between risk factors for fracfures and fractures in postmenopausal women's population; to determine which of those factors are the most important for osteoporotic fractures in examined postmenopausal women's population. Section study of 529 postmenopausal women diagnosed with osteoporosis or osteopenia was performed. Following fracfure risk factors were examined: age, time of menarha and menopause, antropometric parameters (body height, body weight, BMI), reduction of body height, value of T score measured at the predilection sites, lactation period, smoking, using corticosteroids, early diseases and early fractures, family history of fractures and parity. Results show that age, early disease including using corticosteroids, T score and smoking are leading risk factors for fracfures at postmenopausal women. Two of examined risk factors can highly contribute to developing fractures in examined postmenopausal women's population. It this research it is showed that cut off T score from < -2,5 SD, which is used for diagnosing osteopeorosis is not adequate to estimate risk factor for fracture; we suggest testing T score value of < -2,8 SD in future. Mathematical processing of T score at tree sites at the same time (L1-4, femur neck and femur-total) in order to estimate fracture risk factor, we find new formula that we called NS index, which can predict new fracture in postmenopausal women's population with probability of 61,24 percents, which is more percent probability than measuring T score at one site.

Published
2014

50. [Disturbances of lipid and lipoprotein metabolism in hypeprolactinemia and acromegaly].

Author

Medić-Stojanoska M and Pletikosić I

Subjects
Female, Human Growth Hormone physiology, Humans, Prolactin physiology, Acromegaly metabolism, Hyperprolactinemia metabolism, Lipid Metabolism, Lipoproteins metabolism
Abstract

The synthesis and metabolism of lipids and lipoproteins are regulated by a number of hormones, among which are prolactine and growth hormone. The levels of triglycerides, total cholesterol and LDL, although within normal range, were higher in hypeprolactinemia than after the therapy with dopamine agonists in hypeprolactinemic females. This is confirmed by the results of our research and other studies. The changes of total, LDL and non HDL-cholesterol were significant. No significant differences in the level of HDL-cholesterol was confirmed. The mechanisms of the onset of this disturbance has not yet been explained. Recent studies suggest that prolactin has not only the indirect, but also the direct impact on metabolism of lipids and lipoproteins. Acromegaly is also associated with a higher prevalence of a disbalanced metabolism of lipids and lipoproteins. The hypersecretion of GH is often associated with hypertriglyceridaemia. The levels of total cholesterol and HDL cholesterol were normal, higher or lower in these studies. The LDL cholesterol showed higher levels. The level of lipoprotein (a), apoprotein (A, E) were higher in 30% of the patients with acromegaly. The hypersecretion of GH and PRL can increase cardiovascular risk due to their association with disturbances of lipid metabolism.

Published
2009

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