Browsing by Author "Janković, Radmila (36875127400)"

Introduction Chronic intestinal pseudo-obstruction represents a group of rare disorders characterized by impaired gastrointestinal motility in the absence of mechanical bowel obstruction. These disorders can be primary or secondary, with autoimmune intestinal leiomyositis falling into the latter category. This condition is observed in adolescence and adulthood but is very rarely seen in children, especially in infancy. Case outline A nine-month-old male infant was hospitalized due to persistent vomiting, abdominal bloating, and distension. After diagnostic evaluations and failure of conservative treatment measures, surgical formation of an ileostomy was performed. During the procedure, intestinal samples were obtained, revealing T lymphocyte infiltration of the intestine. Immunological blood analyses showed elevated serum immunoglobulins and smooth muscle autoantibodies. Combined with histological findings and elevated inflammatory markers, a diagnosis of autoimmune intestinal leiomyositis was established. Immunosuppressive therapy was initiated, leading to normalization of inflammatory markers and resolution of clinical symptoms. After four years of immunomodulatory therapy, the ileostomy was closed, and intestinal biopsies showed no inflammatory infiltrates. Five years later, the boy remains free of gastrointestinal symptoms, with normal growth and development. Conclusion Although a rare condition, autoimmune intestinal leiomyositis is an important differential diagnostic entity in chronic intestinal pseudo-obstruction. Early disease recognition with intestinal biopsies, coupled with prompt and aggressive immunosuppressive therapy, enables favorable therapeutic outcomes. © 2025, Serbia Medical Society. All rights reserved.

Recent findings have demonstrated that serotonin is an important participant in the development and progression of peripheral artery diseases. Taking this into consideration, the goals of this study were to investigate the effects of serotonin on isolated Wistar rat femoral arteries in both healthy and diabetic animals, with and without artery occlusion, with a particular focus on determining the role of calcium in this process. Contraction experiments with serotonin on intact and denuded femoral artery rings, in the presence or absence of nifedipine and ouabain (both separately, or in combination), as well as Ca2+-free Krebs-Ringer bicarbonate solution were performed. The serotonin-induced results were concentration dependent, but only in healthy animals. The endothelium-dependent contraction of the femoral artery was assessed. In healthy animals, the endothelium-reliant part of contraction was dependent on the extracellular calcium, while the smooth muscle-related part was instead dependent on the intracellular calcium. In diabetic animals, both nifedipine and ouabain influenced serotonin-induced vascular effects by blocking intracellular calcium pathways. However, this was diminished after the simultaneous administration of both blockers. © 2017 John Wiley & Sons Australia, Ltd

Recent findings have demonstrated that serotonin is an important participant in the development and progression of peripheral artery diseases. Taking this into consideration, the goals of this study were to investigate the effects of serotonin on isolated Wistar rat femoral arteries in both healthy and diabetic animals, with and without artery occlusion, with a particular focus on determining the role of calcium in this process. Contraction experiments with serotonin on intact and denuded femoral artery rings, in the presence or absence of nifedipine and ouabain (both separately, or in combination), as well as Ca2+-free Krebs-Ringer bicarbonate solution were performed. The serotonin-induced results were concentration dependent, but only in healthy animals. The endothelium-dependent contraction of the femoral artery was assessed. In healthy animals, the endothelium-reliant part of contraction was dependent on the extracellular calcium, while the smooth muscle-related part was instead dependent on the intracellular calcium. In diabetic animals, both nifedipine and ouabain influenced serotonin-induced vascular effects by blocking intracellular calcium pathways. However, this was diminished after the simultaneous administration of both blockers. © 2017 John Wiley & Sons Australia, Ltd

Background/Aim. Autopsy studies rarely investigate the causes of natural death in psychiatric population. The aim of this study was to examine the causes of death among the subjects with various psychiatric disorders in whom a clinical (pathoanatomical) autopsy was requested. Methods. The study group included 118 patients (65% men, 35% women, mean age 58.2 ± 13.6 years) with a psychiatric diagnosis, in whom a clinical autopsy was performed. We compared the distribution of causes of natural death among psychiatric patients and other patients, representatives of the general population who died of natural causes. We also analyzed the difference between clinical diagnoses of cause of death and the autopsy findings in psychiatric patients. Results. Psychiatric patients died earlier than the control group (58 vs. 69 years), usually due to the respiratory (46%) and cardiovascular diseases (37%). The most common diagnoses in psychiatric patients were organic psychoses and dementias (F00-F09) and schizophrenia and schizoaffective disorders (F20-F29). Majority of the patients (55%) died in general hospitals vs. specialized psychiatric hospitals (45%) due to somatic diseases. There was a significant difference in the distribution of causes of death compared to the control group in which the cardiovascular diseases dominated. Even in 64% of psychiatric patients there was a discrepancy between the clinical diagnosis of the cause of death and definite autopsy findings. Conclusion. The assessment of somatic diseases in psychiatric patients is insufficient, especially in specialized psychiatric hospitals. That leads to a significant discrepancy between clinical diagnosis of the cause of death and autopsy findings. Therefore, it is necessary to pay additional attention in diagnostics and treatment of somatic diseases in these patients to improve their health care. © 2019, Inst. Sci. inf., Univ. Defence in Belgrade. All rights reserved.

Background/Aim. Organophosphate pesticides (OPs) are used extensively worldwide in agriculture and forestry, and their application represents a major health problem for humans and animals. The aim of this study was to investigate the possibility of the adaptation of an organism to the prolonged administration of a low dose of diazinon. Methods. The study was conducted on a total of 60 male Wistar rats. The first 30 rats were divided into four equal diazinon groups (n = 6) and the control one (corn oil). Diazinon was orally administered once at doses: 200, 400, 600, 800 mg/kg (one dose – one group). The concentration of glucose, the activity of α-amylase and the relative activity of LDH1-LDH5 isoenzymes in the blood were measured 24 hours after the application. The remaining 30 rats were divided into two equal diazinon groups (n = 10) and the control one (corn oil). The first group was treated during 7 days, and the second during 14 days with 55 mg/kg of diazinon (1/10 of previously determined LD50 value). The histopathology of the pancreas and the liver, as well as the relative activities of LDH isoenzymes in the blood, were determined after the completion of both time periods. Results. Single administration of increasing doses of diazinon resulted in a significant increase in the concentrations of glucose, activity of α-amylase and LDH isoenzymes. Subacute application of a low diazinon dose induced histopathological changes in the pancreas manifested by acinar cell necrosis, and in the liver in the form of portal hepatitis and multifocal necrosis. The cumulative doses resulted in statistically significantly lower activities of LDH isoenzymes compared with the single administration of these doses, indicating a lower degree of the cells damage after the subacute diazinon administration. Conclusion. Subacute administration of a low dose of diazinon leads to a different adaptation degree of organs and organ systems to toxic effects caused by this organophosphate. © 2021 Inst. Sci. inf., Univ. Defence in Belgrade. All rights reserved.

Aging is closely related to the main aspects of multiple sclerosis (MS). The average age of the MS population is increasing and the number of elderly MS patients is expected to increase. In addition to neurons, N-methyl-D-aspartate receptors (NMDARs) are also expressed on non-neuronal cells, such as immune cells. The aim of this study was to investigate the role of NMDARs in experimental autoimmune encephalomyelitis (EAE) in young and aged rats. Memantine, a non-competitive NMDAR antagonist, was administered to young and aged Dark Agouti rats from day 7 after immunization. Antagonizing NMDARs had a more favourable effect on clinical disease, reactivation, and apoptosis of CD4+ T cells in the target organ of aged EAE rats. The expression of the fractalkine receptor CX3CR1 was increased in memantine-treated rats, but to a greater extent in aged rats. Additionally, memantine increased Nrf2 and Nrf2-regulated enzymes’ mRNA expression in brain tissue. The concentrations of superoxide anion radicals, malondialdehyde, and advanced oxidation protein products in brain tissue were consistent with previous results. Overall, our results suggest that NMDARs play a more important role in the pathogenesis of EAE in aged than in young rats. © 2024 by the authors.

Aging is closely related to the main aspects of multiple sclerosis (MS). The average age of the MS population is increasing and the number of elderly MS patients is expected to increase. In addition to neurons, N-methyl-D-aspartate receptors (NMDARs) are also expressed on non-neuronal cells, such as immune cells. The aim of this study was to investigate the role of NMDARs in experimental autoimmune encephalomyelitis (EAE) in young and aged rats. Memantine, a non-competitive NMDAR antagonist, was administered to young and aged Dark Agouti rats from day 7 after immunization. Antagonizing NMDARs had a more favourable effect on clinical disease, reactivation, and apoptosis of CD4+ T cells in the target organ of aged EAE rats. The expression of the fractalkine receptor CX3CR1 was increased in memantine-treated rats, but to a greater extent in aged rats. Additionally, memantine increased Nrf2 and Nrf2-regulated enzymes’ mRNA expression in brain tissue. The concentrations of superoxide anion radicals, malondialdehyde, and advanced oxidation protein products in brain tissue were consistent with previous results. Overall, our results suggest that NMDARs play a more important role in the pathogenesis of EAE in aged than in young rats. © 2024 by the authors.

Background and Objectives: Ovarian cancer is the leading cause of death among gynecological tumors. PD-1/PD-L1 immunoregulatory mechanism is activated in ovarian cancers. Lymphocyte infiltration is a significant factor that affects its expression. We analyzed the correlation between localization of lymphocytic infiltrate and PD-L1 expression in epithelial ovarian tumors. Materials and Methods: PD-L1 expression was analyzed in 328 subjects, 122 with epithelial ovarian carcinoma, 42 with atypical proliferative tumor, and 164 with benign epithelial ovarian tumor. Expression in central and invasive tumor parts in epithelial ovarian carcinoma was combined with the most pronounced lymphocyte reaction. Immunohistochemical analysis was performed using the tissue microarray and correlated with a set of histopathology parameters. Results: PD-L1 expression was most prominent in epithelial ovarian carcinoma with different levels of expression observed between invasive and central tumor segments. A high level of PD-L1 expression on tumor cells was more frequently present in the invasive than in the central tumor parts (p < 0.001) only in high-grade serous ovarian carcinoma (HGSC). There was no significant correlation between peritumoral lymphocytic infiltrate and PD-L1 expression regardless of tumor segment. In the central tumor parts of HGSC, there was a correlation of intratumoral lymphocytic infiltrate with a higher level of PD-L1 expression (p = 0.003). Conclusions: The most prominent PD-L1 expression was observed in the invasive tumor parts of HGSC. Only the central parts of the HGSC exhibited significant PD-L1 expression in association with considerable intratumoral lymphocytic infiltrate. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Purpose: Programmed death-ligand 1 (PD-L1) was expressed in various gynecology tumors. High-grade ovarian cancers could be a potential target for immune anti-PD-L1 modulate therapy. Antibodies targeting PD-L1 molecules are emerging cancer therapeutics. This study was designed to evaluate the expression of PD-L1 marker in the high-grade ovarian cancer types and evaluate its prognostic potential. Methods: The study included 18 patients with ovarian high-grade serous cancer (HGSC) and 11 patients with clear cell cancer (CCC) histology type, both in the International Federation of Gynecology and Obstetrics (FIGO) stage I. The expression of the PD-L1 marker was measured by tissue microarray-based immunohistochemistry. Expression levels of PD-L1 were correlated with the presence of tumor-infiltrating lymphocyte (TIL) and other histopathology parameters. Results: HGSC ovarian cancers predominantly had low PD-L1 expression, while CCC ovarian cancers had high PD-L1 expression (p < 0.001). PD-L1 expression did not show significant differences considering analyzed parameters other than histology type (localization, size, FIGO stage, lymphovascular invasion, tumor necrosis, and presence of TIL) among all ovarian cancers. There was no statistically significant difference in any of the tumor characteristics within histologic types of ovarian cancers. Conclusion: PD-L1 expression was significantly higher in clear cell histology type than in high-grade serous ovarian cancers in FIGO I stage. © 2022, The Author(s) under exclusive licence to Association of Gynecologic Oncologists of India.

Background. Actinomycosis (ACM) is a rare infectious granulomatous disease caused by Actinomyces, a Gram-positive, filamentous, saprophytic bacteria. There are several types of pediatric ACM, such as orocervicofacial (55%) and other less common forms: abdominopelvic and thoracic. We report a case of a 16-year-old who presented with abdominal ACM in the setting of acute appendicitis. After the case report, we provide a short literature review of pediatric appendicular ACM cases published. Case. A 16-year-old boy presented with nausea, vomiting, pain in the upper part of the abdomen and fever (37.5°C) lasting for 24 hours. On physical examination, the patient’s epigastrium and lower right abdominal quadrant were tender. White cell count and C-reactive protein (CRP) were elevated at 16,300/µL and 48.6mg/L respectively. Ultrasonography (US) showed appendicolith and edema of the appendiceal wall, focally with stratification as well as periappendiceal inflammation. The patient underwent a classic appendectomy, and the postoperative course was without complications. Histopathological analysis showed diffuse transmural neutrophilic infiltration of the appendix, focally with areas of necrosis and abscesses. There were numerous brightly eosinophilic colonies made of filamentous bacteria, located predominantly in submucosa. Special stains Grocott-Gomori’s Methenamine Silver and Gram were positive and a diagnosis of ACM was made. Conclusions. Although appendicitis is very common in the general population, appendicitis associated with ACM is very rare, accounting for 0.02%-0.06%, especially in the pediatric population. Diagnosis can be very challenging because they usually present with non-specific symptoms, and can form masses that mimic malignancies. Although rare, clinicians and pathologists should be aware of this entity. Satisfactory results and complete cure are achieved with adequate antibiotic therapy and surgery. In most cases, if there are no associated diseases, early and accurate diagnosis ensure an excellent prognosis. © 2023, Turkish National Pediatric Society. All rights reserved.

[No abstract available]

Aim To analyze the expression of autophagy markers p62, LC3, and Beclin1 in ovarian cancer tissue and evaluate the prognostic potential of these markers. Methods The study enrolled 328 patients: 122 with epithelial ovarian carcinoma, 42 with atypical proliferative tumor, and 164 with benign epithelial ovarian tumor. The expression of p62, LC3, and Beclin1 was analyzed in central and invasive tumor segments with immunohistochemistry combined with tissue microarray. The expression levels of the analyzed markers were correlated with relevant histopathology parameters. Results The expression of all analyzed markers was most remarkable in epithelial ovarian carcinoma. There was a strong positive correlation between the expressions of p62 and LC3, while these two markers negatively correlated with Beclin1. High-grade serous carcinoma had higher p62 and LC3 levels, and lower Beclin1 levels than other tumor types. This expression profile was also observed in more advanced tumor stages. Conclusion Prominent p62 and LC3 expression in combination with weak Beclin1 expression in high-grade serous carcinoma indicates potential for the application of autophagy inhibitors in patients with this tumor subtype. © 2022 Medicinska Naklada Zagreb. All rights reserved.

BACKGROUND: Myoepitheliomas are tumors composed predominantly or exclusively of myoepithelial cells, usually arising in salivary glands. Cutaneous/soft tissue localization is very rare, especially for the malignant myoepitheliomas. CASE REPORT: We presented a case of myoepithelial carcinoma involving subcutaneous adipose tissue of the left forearm in a woman aged 62 years. The tumor was composed of epithelioid and hyaline cell types, arranged in diffuse sheets, nests and loose clusters within hyalinized and myxoid matrix. The neoplasm displayed high-grade cytologic atypia with some cells having pleomorphic, hyperchromatic nuclei, and others showing vesicular nuclei, large nucleoli with scattered bizarre giant cells. High mean mitotic count of 7 mitoses/10 high power filds and extensive necrosis favoured the diagnosis of malignancy. Immunohistochemical staining was positive for cytokeratin (AE1/AE3), epithelial membrane antigen, S-100 protein, glial fibrillary acidic protein, and vimentin. CONCLUSION: Considering the subcutaneous localization, myoepithelial immunophenotype and high-grade cytologic atypia the neoplasm was classified as a soft-tissue myoepithelial carcinoma.

Crohn’s disease (CD) is a chronic inflammatory bowel condition with increasing global incidence. Diagnosing CD is challenging and requires close collaboration between clinicians and pathologists due to the lack of specific diagnostic criteria. Histologically, CD is characterized by transmural inflammation, crypt distortion, metaplasia, and granulomas, although granulomas are not always present. Schaumann bodies (SB), initially described in sarcoidosis, are rare in CD but have been reported in about 10% of cases. This case report presents a 4-year-old female with chronic hemorrhagic diarrhea, severe anemia, and elevated inflammatory markers. Endoscopic and histological evaluations suggested CD, with the presence of SB in the gastric mucosa. Further investigations ruled out sarcoidosis, confirming a diagnosis of multi-segmental, very early onset CD with atypical histological features. SB are inclusions composed of calcium carbonate crystals and conchoid bodies, typically found within giant cells. The presence of SB in the mucosa is rare, limiting their diagnostic significance in endoscopic biopsies. Differential diagnosis should exclude other granulomatous diseases such as intestinal tuberculosis and sarcoidosis. This case highlights the importance of considering SB in the diagnosis of CD, particularly in pediatric patients. © 2024 by the authors.

The concept of diversity, equity, inclusion and belonging is essential for research and academic programs and institutions worldwide, but although women do not lag behind men at entry and graduation from Serbian universities, equitable leadership does and it further hinders outcomes in every way: from translational science via healthcare up to legislative efforts to protect children, women and elderly. Although all these may seem as l’art-pour-l’art issues when compared to mere survival in war zones on two continents and all issues women face under circumstances of displacement and bans on rights to education, healthcare and sounds of their own voices in public, still it is the ongoing fight for rights lost in silence and where one least expects it that has to push every human being to fight for the oppressed and underprivileged. © 2024, Serbia Medical Society. All rights reserved.