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Volume 53, Issue 4, 2025

Online ISSN: 2560-3310

ISSN: 0350-8773

Volume 53 , Issue 4, (2025)

Published: 30.06.2025.

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01.12.2020.

Professional paper

Respiratory epithelium: Place of entry and / or defense against SARS-CoV-2 virus

Coronavirus Disease (COVID-19) is caused by the RNA virus SARS-CoV-2. The primary receptor for the virus is most likely Angiotensin-converting enzyme 2 (ACE2), and the virus enters the body by infecting epithelial cells of the respiratory tract. Through the activation of Toll Like Receptors (TLRs), epithelial cells begin to synthesize various biologically active molecules. The pathophysiology of the COVID 19 is primarily attributed to the hyperactivation of host's immune system due to direct damage to the cells, with consequent release of proinflammatory substances, but also due to the activation of the innate immune response through the activation of alveolar macrophages and dendrite cells (DC). A strong proinflammatory reaction causes damage to alveolar epithelial cells and vascular endothelium. Respiratory epithelial cells, alveolar macrophages and DC are likely to be the most important cells involved in the innate immune response to the virus, since prolonged and excessive SARS-CoV-2-induced activation of these cells leads to the secretion of cytokines and chemokines that massively attract leukocytes and monocytes to the lungs and cause lung damage.

Snežana Leštarević, Slađana Savić, Leonida Vitković, Predrag Mandić, Milica Mijović, Mirjana Dejanović, Dragan Marjanović, Ivan Rančić, Milan Filipović

01.12.2017.

Professional paper

The effect of morphine on development of ulcer lesions of the rats exposed to indomethacin induced stress

Oxidative stress plays an important role in development of ulcer lessions of the rats exposed to indomethacin induced stress. It has been suggested that endogenous opioids releassed during the stress may attenuate gastric ulcer lesions. The aim of this study was to investigate effects of morpine on development of ulcer lessions, pathohistological alterations and antioxidative status in stomach of the rats exposed to indomethacin induced stress. Research was performed on adult, male Wistar rats weighting 200-230 g. Indomethacin stress was induced by intragastric administration of indomethacin at a dose of 20 mg/kg b.w. 6 hours before sacrificing. Morphine was applied intraperitoneally, in the doses of 10 mg/kg b.w. 15 minutes before indomethacin induced stress. The size of lesions in the form of petechiae and erosion, is expressed as the total surface of changes (mm2), i.e. ulcer index (UI). The pathohistological samples were analyzed by Leica DML S2 light microscope, and specific changes were photodocumented with Canon Power Shot S70 digital camera. In the homogenate of the stomach, the activity of catalase (CAT), glutathione peroxidase (GSHPx), glutathione reductase (GR) and xanthine oxidase (XOD) were measured, as well as the reduced glutathione content (GSH) and the lipid peroxidation intensity (Lpx). Morphine significantly reduced the ulcer index (UI) in animals exposed to indomethacin stress and the presence of large amounts of mucus in the stomach mucosal was established histopathologically. The use of morphine in the pretreatmant of indomethacin induced stress statistically significantly reduced the activity of all enzymes in the stomach compared to the control group, and this activity of catalase (CAT), glutathione peroxidase (GSHPx) and glutathione reductase (GR ), xanthine oxidase (XOD),as well as the lipid peroxidation intensity (Lpx), while the reduced glutathione content remained unchanged. Gastroprotective morphine activity in animals exposed to indomethacin induced stress is most likely a consequence of the strengthening of cytoprotective mechanisms rather than antioxidant action.

Julijana Rašić, Snežana Hudomal-Janićijević, Zorica Stanojević-Ristić, Bojana Kisić, Snežana Stević, Leonida Vitković, Milica Mijović

01.12.2017.

Professional paper

Concentrations of sodium 3α, 7α--dihydroxy-12-oxo 5β cholanate in biological material after its intravenous and intranasal application

Newly synthetized derivative of bile acid, sodium salt of 3α, 7α-dihydroxy-12-oxo 5β cholanic acid (monoketocholanate) expressed a good characteristic as intranasal transport enhancer of xenobiotics.The aim of our sudy was to explore if it has an influence on bile metabolism and to measure its concentration in blood and bile after intravenous and intranasal administration. The experiment was performed in vivo on adult male Wistar rats. The determination of monoketocholanate (MKCh) in rats blood and bile, was carried out by high-performance liquid chromatography (HPLC), on an HP ODS2 column, using methanol/acetonitrile/acetate buffer as mobile phase. Absorbances were measured at 210 nm.Blood samples were taken from the prepared right axillary artery in 0, 1, 5, 10, 20, 30, 60, 90, 120 and 180 minutes from the beginning of the experiment. Bile was collected in a half an hour intervals,during the three hour period. The results showed that MKCh changed the amount of excreted bile depending on the way of application. Intranasal application increased the bile volume and the MKCh concentration, both in blood and bile compared to the intravenous application (p<0.05). Distributionm of MKCh through animal organism depends on the way of application of the substance, which probably determines its caracterisation as the transport promotor of applied xenobiotics. HPLC has proved as aa relatively simple, fast and effective method for the determination of synthetic bile acid,MKCh in these biological materials.

Snežana Stević, Momir Mikov, Zorica Stanojević-Ristić, Julijana Rašić, Leonida Vitković

01.01.2017.

Professional paper

Specificity and sensitivity of preoperative total serum prostate specific antigen in diagnosis most common histopathological change of prostate

Determination of preoperative prostate-specific antigen (PSA) value is primary procedure in diagnosis of different pathological prostate changes (prostate cancer-PC, prostatic intraepithelial neoplasia-PIN and benign prostatic hyperplasia-BPH), followed by digital rectal examination and prostate biopsy as gold standard. Disadvantage of high sensitivity and low specificity of PSA testing in diagnosis of PC is a problem in clinical practice. Aim was to determine the diagnostic performance of PSA in diagnosis of PC, PIN and BPH. The study included 100 patients divided into three groups: 70 with PC, 20 with a PIN and 10 with BPH. Patients with PIN and BPH were control group. Preoperative PSA values were determined by Tandem-R, The patients were divided into subgroups by baseline PSA level as follows: 4-10, 11-20, 21-30, 31-40 and> 40. The definitive histopathological diagnosis was made on routine hematoxylineosin slides. The area under the receiver operating characteristic curve (ROC), sensitivity-SE and specificity-SP of each PSA level were evaluated for PC. Preoperative serum PSA levels in patients with PC (median-35.82 ng/ml, min-6 ng/ml, max-960.40 ng/ml) were significantly higher than with PIN (median-9.15 ng/ml, min-3.16 ng/ml, max-27.61 ng/ml) and BPH (median-8.68 ng/ml, min0.80 ng/ml, max-31.20 ng/ml). The best diagnostic characteristics of the PSA are on limit value 10 ng/ml (AUC=0.781, SE=92.9%; SP=63.3%; p<0,0001). PSA is of great help in diagnosis of advanced and initial form of PC. The chance of PC diagnosis was greater than that for other pathological changes when PSA level was higher than 10 ng/ml.

Milica Mijovic, Danica Vukicevic, Branislav Djerkovic, Sladjana Savic, Leonida Vitkovic, V. Nedeljkovic

01.06.2016.

Professional paper

Correlation of number of tumor buds and tumor stage in large bowel carcinomas

Standardized staging of tumors takes into account the depth of invasion of the intestinal wall and the presence of local or distant metastases, specifically focusing to precisely estimate length of patient survival. This assessment system does not fully reflect the biological behaviour of cancer individually, ie. tumor aggressiveness and ability of recurrence tumor after medical treatment. Futuremore, cancer at some patients have more aggressive growth than other carcinomas in the same clinical stage, because there are other parameters that determine the biological behaviors of colon cancer, which are not included in the standard classification of determining tumor stage. One of the recent arguments which are due in the spotlight is "tumor budding", which represents one cell or group of up to five non-differentiated tumor cells, which are found in the stroma out of the invasive front line of cancer. There are 92 colon cancer and upper rectum processed, which are collected at General Hospital in Trebinje and Medical Center in Kosovska Mitrovica. The aim is to determine whether there is a correlation between the number of tumor budding and stage of tumors in colorectal cancer. The tumor stage is determined by Astler Coller classification. Investigation, based on χ2-test, leads to the conclusion that there is not a statistical significance in tumor budding distribution in relation to tumor stage according to the Astler Coller classification (p = 0.383; p> 0.05).

Branislav Djerkovic, Milica Mijovic, Danica Vukicevic, Mihajlo Vukmirovic, Leonida Vitkovic, Vladica Nedeljkovic

01.12.2015.

Professional paper

Distribution of high-risk types of human papillomavirus compared to histopathological findings in cervical biopsies in women

Introduction: In over of 99% cases of cervical cancer its appearing is preceded by persistent cervical epithelium infection caused by high-risk oncogenic types of human papillomavirus (HPV). The aim of the study was to examine the distribution of high-risk oncogenic HPV types compared to patohistological diagnoses of cervical diseases in women. Materials and methods: The study included 56 women with suspected premalignant and malignant cervical lesions, due to suspected colposcopic and cytological findings (Papanicolaou test). The HPV typing by "in situ" hybridization method on high-risk HPV types 16, 18, 31 and 33 was performed in all patients from cervical smear as well as cervical biopsy. Histological findings of cervical biopsy was a "gold standard" in the analysis of materials. Results: Histologically detected premalignant or malignant changes of the cervix were found at 34 (60.7%) of all 56 examined women: 17 of them had LSIL, 13 of them had HSIL, while 4 had squamous cell carcinoma. A positive HPV test had a 47 (84%) of them with a prove of the presence of one or more types of HPV. The most common type of virus was HPV 16 and it was detected in 27 (48.2%) women, followed by HPV 31 that was detected in 26 (46.4%) women, HPV 18 in 18 (32.1%) of women and HPV 33 in 4 (7.1%) women. The infection caused by oncogenic type HPV16 was significantly more frequent in patients with HSIL and cervical cancer (p<0,001), while the infection caused by oncogenic type HPV 31 was significantly more frequent in patients with LSIL and cervicitis (p=0,003). The distribution of HPV 18 and HPV 33 types was not statistically significantly different in patients with different histological findings (HPV 18, p = 0.41; HPV 33, p = 1.0). Conclusion: Based on our results we can conclude that there is a good correlation of HPV infection with pre-malignant cervical lesions and cervical cancer. The incidence of HPV type 16 infection increased with severity of cervical lesions and it is usually detected high-risk oncogenic type virus in women with severe cervical lesions type like HSIL and cancer are. HPV 31 is the most common high-risk type of HPV of mild type lesions, like LSIL and cervicitis are. We believe that women infected by high-risk oncogenic HPV types, although without histologically diagnose of cervical lesion, should be more frequent controle by colposcopy and cytology (Papanicolaou) test, because of possible disease progression to a more advanced level.

Leonida Vitković, Ž. Perišić, G. Trajković, M. Mijović, S. Savić, S. Leštarević, B. Đerković

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