Browsing by Author "Micić, Jelena (7005054108)"

[No abstract available]

Introduction: Drug-induced liver injury (DILI) is one of the most common causes of liver damage. A large number of drugs, dietary supplements, and herbal medications can cause hepatotoxicity. In some situations, it is difficult to distinguish between DILI and autoimmune hepatitis, especially when the mechanism is immune-mediated. Albendazole is a drug that has been used for decades for the treatment of parasitic infections in humans. One of the side effects is liver enzyme elevation, but rarely requires the discontinuation of therapy. Previous experience has shown that hypersensitivity is the most common mechanism of albendazole hepatotoxicity. Case report: Here we presented a paediatric patient in whom albendazole induced severe liver injury. In laboratory analyses, in addition to markedly elevated transaminases and parameters of cholestasis, there was also a significant increase in IgG, so autoimmune hepatitis was considered. Even though the liver histology indicated toxic liver disease, prednisolone was started. Corticosteroid therapy resulted in the complete normalization of liver function, as well as IgG. With the cessation of corticosteroid therapy, transaminases, bilirubin and gamma-glutamyl transferase (GGT) remained within normal levels, but an increase in anti-smooth muscle antibodies (SMA) was noted in immunological analyses after one year of follow-up. Conclusions: Immune-mediated hepatotoxicity from albendazole is one possible mechanism of liver injury. The use of albendazole in the treatment of parasitic infections, especially in children, requires close monitoring. The question remains as to whether albendazole is a drug that can induce autoimmune hepatitis in the paediatric population. Copyright © 2022 Dragutinović et al. This is an open-access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Introduction: Drug-induced liver injury (DILI) is one of the most common causes of liver damage. A large number of drugs, dietary supplements, and herbal medications can cause hepatotoxicity. In some situations, it is difficult to distinguish between DILI and autoimmune hepatitis, especially when the mechanism is immune-mediated. Albendazole is a drug that has been used for decades for the treatment of parasitic infections in humans. One of the side effects is liver enzyme elevation, but rarely requires the discontinuation of therapy. Previous experience has shown that hypersensitivity is the most common mechanism of albendazole hepatotoxicity. Case report: Here we presented a paediatric patient in whom albendazole induced severe liver injury. In laboratory analyses, in addition to markedly elevated transaminases and parameters of cholestasis, there was also a significant increase in IgG, so autoimmune hepatitis was considered. Even though the liver histology indicated toxic liver disease, prednisolone was started. Corticosteroid therapy resulted in the complete normalization of liver function, as well as IgG. With the cessation of corticosteroid therapy, transaminases, bilirubin and gamma-glutamyl transferase (GGT) remained within normal levels, but an increase in anti-smooth muscle antibodies (SMA) was noted in immunological analyses after one year of follow-up. Conclusions: Immune-mediated hepatotoxicity from albendazole is one possible mechanism of liver injury. The use of albendazole in the treatment of parasitic infections, especially in children, requires close monitoring. The question remains as to whether albendazole is a drug that can induce autoimmune hepatitis in the paediatric population. Copyright © 2022 Dragutinović et al. This is an open-access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Introduction Premature ovarian failure (POF) is characterized by amenorrhea, hypergonadotropism and hypoestrogenism in women bellow 40 years. Osteoporosis is one of the late complications of POF. Objective To correlate collagen type I alpha1 (COLIA1) gene polymorphism with bone mineral density (BMD) in women with POF. Methods We determined the COLIA1 genotypes SS, Ss, ss in 66 women with POF. Single nucleotide polymorphism (G to T substitution) within the Sp 1-binding site in the first intron of the COLIA1 gene was assessed by polymerase chain reaction (PCR) followed by single-stranded conformation polymorphism (SSCP) analysis. Bone mineral density (BMD) was measured at the lumbar spine region by dual X-ray absorptiometry. Statistics: Kruskal-Wallis ANOVA, Chi-square test, Spearman correlation test. Results The relative distribution of COLIA1 genotype alleles was SS - 54.4%, Ss - 41.0% and ss - 4.5%. No significant differences were found between genotype groups in body mass index, age, duration of amenorrhea or BMD. A significant positive correlation was observed between BMI and parity. Conclusion The COLIA1 gene is just one of many genes influencing bone characteristics. It may act as a marker for differences in bone quantity and quality, bone fragility and accelerated bone loss in older women. However, in young women with POF, COLIA1 cannot identify those at higher risk for osteoporosis.

Uterine fibroids (leiomyomas and myomas) are the most common benign gynecological condition in patients presenting with abnormal uterine bleeding, pelvic masses causing pressure or pain, infertility and obstetric complications. Almost a third of women with fibroids need treatment due to symptoms. Objectives: In this review we present all currently available treatment modalities for uterine fibroids. Methods: An extensive search for the available data regarding surgical, medical and other treatment options for uterine fibroids was conducted. Review: Nowadays, treatment for fibroids is intended to control symptoms while preserving future fertility. The choice of treatment depends on the patient’s age and fertility and the number, size and location of the fibroids. Current management strategies mainly involve surgical interventions (hysterectomy and myomectomy hysteroscopy, laparoscopy or laparotomy). Other surgical and non-surgical minimally invasive techniques include interventions performed under radiologic or ultrasound guidance (uterine artery embolization and occlusion, myolysis, magnetic resonance-guided focused ultrasound surgery, radiofrequency ablation of fibroids and endometrial ablation). Medical treatment options for fibroids are still restricted and available medications (progestogens, combined oral contraceptives andgonadotropin-releasing hormone agonists and antagonists) are generally used for short-term treatment of fibroid-induced bleeding. Recently, it was shown that SPRMs could be administered intermittently long-term with good results on bleeding and fibroid size reduction. Novel medical treatments are still under investigation but with promising results. Conclusions: Treatment of fibroids must be individualized based on the presence and severity of symptoms and the patient’s desire for definitive treatment or fertility preservation. © 2024 by the authors.

INTRODUCTION Each frac ture of long or pelvic bones as well as large con tusions of subcutaneous fattis sue cause releasing of fat globules that rapidly penetrate into cir culation through the ruptured veins of the injured tissue, and reach the lung cir culation [1, 2]. During the first phase, fat emboli block the func tional lung cir culation by their mechanical effect in cap illaries pro ducing so called isolated post-traumatic lung fat embolism [3]. The sur face layer of a fat embolus, which is prac tically in liquid state, behaves as a membrane of very high density, i.e., as it is under high pres sure which obstruct the blood stream [4] that is finally stopped at the level of lung blood ves sels with diameter of approximately 20 μ [5]. This pathophysiological mechanism pro duces cor pulmonale acutum, with poor patho logical find ings [8]. Nowadays, the post-mortem diagnosis of lung fat embolism is based on micro scop i cal exam i na tion of tis sue spec i mens, usu ally pre pared with special histological staining (Sudan III) [9]. The grad ing of fat embolism accord ing to Sevitt’s criteria is gen erally accepted [10]. Tak - ing of slices from apicoventral areas of the lungs has been recommended [11]. With lon ger outliving period, the total number of fat emboli in the lung cir culation grad ually decreases, due to their disintegration and resorption. It has been stated that fat glob ules completely disappear about 4-6 weeks after injury, and that they should not be searched for microscopically in this post-traumatic phase [11]. OBJECTIVES The aim of our work was to determine whether the age of injured, their gender, total severity of trauma, out living period, and hypo volemic shock that develops after injuring, may induce development of more severe forms of post-traumatic lung fat embolism. MATERIAL AND METHODS A prospective histological study was per formed on the autopsy material of the Institute of Forensic Medicine in Belgrade. The analyzed sam - plecon sisted of individuals with injuries that might be a source of fat emboli (fractures of long bones, large contusions of subcutaneous fat tissue). The lung slices were systematically taken and stained with special fat staining (Sudan III). In each par ticular case, the grade of lung fat embolism was counted on the basis of microscopical appear ance, according to Sevitt’s cri teria. The total severity of trauma was estimated by cal culation of the Injury Severity Score (ISS) [13, 14]. In no cases from the analyzed sample, the fat embolism was mentioned as either singular or plural cause of death. The obtained results were ana lyzed by means of appropriates statistical methods (ANOVA, LSD-test, χ2 test, Man-Whitney test, Fischer’s test of correctprob ability). RESULTS AND DISCUSSION The ana lyzed sample included 58 fatally injured individuals, 39 males and 19 females. The aver age age was 54.10 years (SD16.56), the average value of ISS was 34.69 (SD5.88), and the average outliving period was 3.74 days (SD5.88). However, all these data look differently when the analyzed sample has been stratified and analyzed according to the estimated grade of lung fat embolism. It was not showed that severity of lung fat embolism depends on sex of the injured (χ2=0.842; p>0.05). The groups with the slightest and the most severe grade of lung fat embolism are statistically significantly differentin relation to age of individuals (ANOVA, p=0.017). By means of LSD test, it has been showed that the group with the most severe grade of lung fat embolism (grade III) is statistically significantly different com paring to other two groups (with grade I and II) in relation to the age of injured (the values are p0.16 and p0.19 respectively, and the both groups are less than p0.05). In the group with the most severe grade of lung fat embo lism, the older indi vid u als are sta tis ti cally significantly represented comparing to other two groups. CONCLUSION The anal ysis of our sample showed that the most severe grade of post-traumatic lung fat embolism (microscopical grade III accord ing to Sevitt’s criteria) was determined in older indi viduals, more severely injured, and with shorter out living period. The sever ity of fat embolism depends neither on sex of the injured, nor on development of post-traumatic hypovolemic shock. The obtained results related to the influence of hypovolemic shock on severity of fat embolism should be accepted with a caution. Namely, some times there is an intention to sim plify a procedure of creating of autopsy conclusion about the cause of death, so that loss of blood is not mentioned at all, in spite of fact that it could have been a con current cause of death, while in other cases exsanguination is designated as a sole cause of death, for getting the pos sibility that fat embolism could have really been the immediate cause of death. © 2014, Serbia Medical Society. All rights reserved.

It has been an entire century since the introduction of insulin into clinical practice, which, among other, led to improvements of fertility and pregnancy outcomes of women suffering from gestational diabetes. The prevalence of diabetes worldwide and in Serbia is high and tends to increase as a consequence of modern lifestyle. Nevertheless, modern diagnostic and therapeutic approaches enable people with diabetes to achieve and complete pregnancies without adverse outcomes. Gestational diabetes can be considered as non-communicable disease and efforts should be made to determine its effects on offspring. In the context of COVID-19 pandemic, diabetes mellitus was identified as an important risk factor for severe forms of the disease. © 2023, Serbia Medical Society. All rights reserved.

Introduction: Trichomoniasis is the most common non-viral sexually transmitted infection that increases the risk of cervical cancer. Trichomonas vaginalis (T. vaginalis) can regulate the pro-inflammatory cytokine production in the host cells. Toll-like receptors (TLRs) are a family of the pattern recognition receptors (PRRs) of mammalian cells, expressed in various host cells and have an important role in recognizing pathogens, and pro-inflammatory responses. The aim of the present study is to investigate the role of TLR5 in cervical cancer cells (HeLa) and human vaginal epithelial cells (HVECs) exposed to T. vaginalis. Methodology: First, the cells and parasites were cultured in RPMI and trypticase yeast extract maltose (TYM), respectively. After adaption of parasite and epithelial cells by RPMI-TYM medium co-culture (9:1 vol/vol), HVECs and HeLa cells were stimulated with T. vaginalis trophozoites (24-hour incubation at 37 °C, 5% CO2). Following RNA extraction and cDNA synthesis, the gene expression levels of TLR5, IRAK1, and NF-κB were assessed using real-time PCR. Besides, the protein levels were measured using western blotting. All tests and controls were normalized using β-actin as a housekeeping control. Results: Real-time PCR results showed an increased gene expression of TLR5, IRAK1, and NF-κB in T. vaginalis exposed HVECs and HeLa cells compared to the control group (p < 0.05). Additionally, western blot analysis showed a statistically significant increase in TLR5, and NF-κB proteins in both groups after exposure to the parasite (p < 0.05). Conclusions: These findings provide insight into the host-parasite interaction, and the results indicated that T. vaginalis could stimulate TLR5 and activate related pathways. Copyright © 2023 Mohammadi Esfanjani et al. This is an open-access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Introduction: Trichomoniasis is the most common non-viral sexually transmitted infection that increases the risk of cervical cancer. Trichomonas vaginalis (T. vaginalis) can regulate the pro-inflammatory cytokine production in the host cells. Toll-like receptors (TLRs) are a family of the pattern recognition receptors (PRRs) of mammalian cells, expressed in various host cells and have an important role in recognizing pathogens, and pro-inflammatory responses. The aim of the present study is to investigate the role of TLR5 in cervical cancer cells (HeLa) and human vaginal epithelial cells (HVECs) exposed to T. vaginalis. Methodology: First, the cells and parasites were cultured in RPMI and trypticase yeast extract maltose (TYM), respectively. After adaption of parasite and epithelial cells by RPMI-TYM medium co-culture (9:1 vol/vol), HVECs and HeLa cells were stimulated with T. vaginalis trophozoites (24-hour incubation at 37 °C, 5% CO2). Following RNA extraction and cDNA synthesis, the gene expression levels of TLR5, IRAK1, and NF-κB were assessed using real-time PCR. Besides, the protein levels were measured using western blotting. All tests and controls were normalized using β-actin as a housekeeping control. Results: Real-time PCR results showed an increased gene expression of TLR5, IRAK1, and NF-κB in T. vaginalis exposed HVECs and HeLa cells compared to the control group (p < 0.05). Additionally, western blot analysis showed a statistically significant increase in TLR5, and NF-κB proteins in both groups after exposure to the parasite (p < 0.05). Conclusions: These findings provide insight into the host-parasite interaction, and the results indicated that T. vaginalis could stimulate TLR5 and activate related pathways. Copyright © 2023 Mohammadi Esfanjani et al. This is an open-access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Lyme endocarditis is extremely rare manifestation of Lyme disease. The clinical manifestations of Lyme endocarditis are non-specific and can be very challenging diagnosis to make when it is the only manifestation of the disease. Until now, only a few cases where reported. Physicians should keep in mind the possibility of borrelial etiology of endocarditis in endemic areas. Appropriate valve tissue sample should be sent for histopathology, culture, and PCR especially in case of endocarditis of unknown origin PCR on heart valve samples is recommended. With more frequent PCR, Borrelia spp. may be increasingly found as a cause of infective endocarditis. Prompt diagnosis and treatment of Lyme carditis may prevent surgical treatment and pacemaker implantations. Due to climate change and global warming Lyme disease is a growing problem. Rising number of Lyme disease cases we can expect and rising number of Lyme endocarditis. © Copyright © 2020 Nikolić, Boljević, Bojić, Veljković, Vuković, Paglietti, Micić and Rubino.

Lyme endocarditis is extremely rare manifestation of Lyme disease. The clinical manifestations of Lyme endocarditis are non-specific and can be very challenging diagnosis to make when it is the only manifestation of the disease. Until now, only a few cases where reported. Physicians should keep in mind the possibility of borrelial etiology of endocarditis in endemic areas. Appropriate valve tissue sample should be sent for histopathology, culture, and PCR especially in case of endocarditis of unknown origin PCR on heart valve samples is recommended. With more frequent PCR, Borrelia spp. may be increasingly found as a cause of infective endocarditis. Prompt diagnosis and treatment of Lyme carditis may prevent surgical treatment and pacemaker implantations. Due to climate change and global warming Lyme disease is a growing problem. Rising number of Lyme disease cases we can expect and rising number of Lyme endocarditis. © Copyright © 2020 Nikolić, Boljević, Bojić, Veljković, Vuković, Paglietti, Micić and Rubino.

Background: The major clinical dilemma managing acute rhinosinusitis (ARS) in pediatric population is distinguishing uncomplicated rhinosinusitis from a complicated bacterial ARS and orbital complications, the latter requiring antimicrobials and surgical intervention. However, factors associated with severe orbital complications and the optimum management strategy remains controversial. The objectives of this study were to characterize the clinical outcomes of children with orbital complications of ARS and to identify risk factors associated with disease severity. Methods: This retrospective cohort analysis evaluated the clinical outcomes of 61 children admitted for orbital complications between January 1, 2002 and December 31, 2017. Descriptive statistics were performed to examine the demographics and clinical findings. We compared groups using Mann-Whitney U test for continuous variables and χ2 for categorical variables. Results: Although two-thirds of children had received prehospital antibiotics, half of the cohort presented with post-septal orbital complications. While 83% of isolates obtained from the same patients were susceptible to the prehospital antibiotics given, the majority of those who received prehospital antibiotics nevertheless required surgical intervention. We observed significant association between the age of presentation and disease severity. Children >5 years of age presented with more severe orbital complications despite prehospital antibiotics and were more likely to require surgical intervention (P < 0.001). Conclusions: In this study, stage II/III orbital complications at presentation and older age were the most important determinants of medical treatment failure. Early referral to eye, nose and throat (ENT) should be considered for children >5 years with ARS due to worse orbital complications despite prehospital antibiotics. © 2019 Pediatric Infectious Disease Journal. All rights reserved.

When coronary artery, which is located subepicardially, submerges into myocardium and then, after a short intramural course, again appears subepicardially, it is called embedded coronary, while a part of myocardium above - a myocardial bridge. Muscular bridges are usually small and have no clinical significance. In the proximal part of coronary artery, preceding a myocardial bridge, there occurs a disturbance of blood course and myocardial perfusion, turbulence, collecting of lipids and mucopolysaccharides, lesion of elastica, which all leads to atheromatous lesions of intima of the arterial proximal part and to the resultant complications of atheroma. Degenerative changes of myocardium and its blood vessels, and in connection with it myocardial vulnerability, could be a consequence of this congenital arterial variation. We report a case of a 40-year-old male, without medical data about previous diseases, who died suddenly and unexpectedly in his apartment. The autopsy and microscopical examination revealed an acute ischemic lesion, myocardial bridge in the middle part of the left coronary artery descending branch and the complicated atherosclerotic plaque proximally of this bridge. © 2003, Serbia Medical Society. All rights reserved.

Premature ovarian failure (POF) is the occurrence of hypergonadotropic hypoestrogenic amenorrhea in women under the age of forty years. It is idiopathic in 74-90% patients. Known cases can be divided into primary and secondary POF. In primary POF genetic aberrations can involve the X chromosome (monosomy, trisomy, translocations, deletions) or autosomes. Genetic mechanisms include reduced gene dosage and non-specific chromosome effects impairing meiosis, decreasing the pool of primordial follicles and increasing atresia due to apoptosis or failure of follicle maturation. Autoimmune ovarian damage is caused by alteration of T-cell subsets and T-cell mediated injury, increase of autoantibody producing B-cells, a low number of effector/cytotoxic lymphocyte, which decreases the number and activity of natural killer cells. Bilateral oophorectomy, chemotherapy, radiotherapy and infections cause the secondary POF. Symptoms of POF include irritability, nervousness, loss of libido, depression, lack of concentration, hot flushes, weight gaining, dry skin, vaginal dryness, frequent infections etc.The diagnosis is confirmed by the level of FSH of over 40IU/L and estradiol below 50 pmol/L in women aged below 40 years. Biochemical and other hormonal analysis (free thyroxin,TSH, prolactin, testosterone), karyotype (>30 years of age), ultrasound of the breasts and pelvis are advisable. Optimal therapy is combined estrogen progestagen therapy given in a sequential rhythm, after excluding absolute contraindications.Testosterone can be added to adnexectomized women and those with a low libido. Sequential estrogen progestagen replacement therapy is the first line therapy for ovulation induction in those looking for pregnancy and after that oocyte donation will be advised. Appropriate estro-progestagen therapy improves the quality of life and prevents complications such as cardiovascular diseases, osteoporosis, stroke etc.

Introduction: In addition to known systemic manifestations, coronavirus disease (COVID-19) can cause serious neurological manifestations as a result of damage to the central and peripheral nervous system. Case report: A 62-year-old male with medical history of arterial hypertension and type 2 diabetes mellitus was admitted to the hospital, complaining of high fever, fatigue, cough, and disturbed mental state. He was diagnosed with COVID-19, had fever of up to 38 °C 7 days before admission, dry cough, and became disoriented and psychotic after 5 days. The chest X-ray and computed tomography (CT) of the head were normal. Following a lumbar puncture, the patient was diagnosed with encephalitis based on clinical and laboratory findings (pleocytosis and hyperproteinorachia in cerebrospinal fluid (CSF)). CSF was checked with the polymerase chain reaction meningitis-encephalitis panel which excludes the more common viral or bacterial causes of encephalitis. Anti-edematous, anti-inflammatory, anticoagulant, gastroprotective, and other symptomatic medications were administered. Ataxic gait was the only focal neurological abnormality identified during neurological assessment. The chest CT did not reveal COVID-19 pneumonia and brain magnetic resonance imaging revealed only cortical reductive brain alterations. The COVID-19 swab test after 10 days was negative. The patient was recovered and released from hospital treatment with normal physical findings and without neurological abnormalities. Conclusions: The diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) encephalitis can be challenging, and it is usually based on the exclusion of other etiological agents of brain infections. Copyright © 2025 Poluga et al.

Introduction: Toxoplasma gondii is an obligate intracellular parasite affecting a broad range of warm-blooded animals, including humans. Infection acquired during pregnancy can be transmitted to the fetus and leading to serious problems such as spontaneous abortion, stillbirth, or severe mental and/or physical handicaps in the child. The purpose of this study was to investigate the seroprevalence of Toxoplasma infection and related risk factors in pregnant woman. Methodology: The study enrolled 1200 serum samples of pregnant women from February-November 2017. Then the samples were tested for the presence of anti-T. gondii antibodies (Ab) using enzyme-linked immunosorbent assay. Results: Out of the 1200 samples, 381 (31.7%) and 41 (3.4%) subjects were positive for IgG and IgM Ab, respectively. Among the evaluated risk factors, the seroprevalence of Toxoplasma infection was not related to the occupation in a significant way. However significant relationship was observed with factors such as; contact with soil, cats, consumption of raw washed vegetables, and washed hands before meals. Conclusions: According to the results, more than two-thirds of pregnant women are susceptible to Toxoplasma infection, hence training health care programs should be provided to prevent infection. © 2024 Barzgar et al.

Introduction: Toxoplasma gondii is an obligate intracellular parasite affecting a broad range of warm-blooded animals, including humans. Infection acquired during pregnancy can be transmitted to the fetus and leading to serious problems such as spontaneous abortion, stillbirth, or severe mental and/or physical handicaps in the child. The purpose of this study was to investigate the seroprevalence of Toxoplasma infection and related risk factors in pregnant woman. Methodology: The study enrolled 1200 serum samples of pregnant women from February-November 2017. Then the samples were tested for the presence of anti-T. gondii antibodies (Ab) using enzyme-linked immunosorbent assay. Results: Out of the 1200 samples, 381 (31.7%) and 41 (3.4%) subjects were positive for IgG and IgM Ab, respectively. Among the evaluated risk factors, the seroprevalence of Toxoplasma infection was not related to the occupation in a significant way. However significant relationship was observed with factors such as; contact with soil, cats, consumption of raw washed vegetables, and washed hands before meals. Conclusions: According to the results, more than two-thirds of pregnant women are susceptible to Toxoplasma infection, hence training health care programs should be provided to prevent infection. © 2024 Barzgar et al.

Background and Objectives: Mutations in succinate dehydrogenase (SDH) and fumarate hydratase (FH) give rise to various familial cancer syndromes, with these alterations being characteristic of certain types of histomorphologically specific leiomyomas that hold significant predictive value. Materials and Methods: This study presents two cases of uterine leiomyomas exhibiting rare histomorphological and genetic characteristics, which are crucial for prognosis and further treatment. Results: Distinct histopathological features such as marked nuclear atypia, intracellular eosinophilic globules, and abnormal intratumoral vessels raise suspicion for specific leiomyoma subtypes, which carry predictive significance for additional hereditary cancer syndromes. Immunohistochemical analysis confirmed FH/SDH deficiency in both patients, who underwent careful follow-up. Conclusions: This study describes two cases involving unusual leiomyomas, the histopathological characteristics of which may easily go unrecognized. These features hold predictive significance because their specific mutations point to additional hereditary cancer syndromes, highlighting the need for further examinations. © 2024 by the authors.