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Organophosphorus compounds induce irreversible inhibition of acetylcholinesterase, which then produces clinically manifested muscarinic, nicotinic and central effects. The aim of the study was to analyse the clinical signs of acute paraoxon poisoning in rats and to determine the relationship between the intensity of signs of poisoning and the dose of paraoxon and/or the outcome of poisoning in rats. Animals were treated with either saline or atropine (10 mg/kg intramuscularly). The median subcutaneous lethal dose (LD50) of paraoxon was 0.33 mg/kg and protective ratio of atropine was 2.73. The presence and intensity of signs of poisoning in rats (dyspnoea, lacrimation, exophthalmos, fasciculations, tremor, ataxia, seizures, piloerection, stereotypic movements) were observed and recorded for 4 h after the injection of paraoxon. Intensity of these toxic phenomena was evaluated as: 0 - absent, 1 - mild/moderate, 2 - severe. Fasciculations, seizures and tremor were more intense at higher doses of paraoxon and in non-survivors. In unprotected rats piloerection occurred more often and was more intense at higher doses of paraoxon as well as in non-survivors. In atropine-protected rats, piloerection did not correlate with paraoxon dose or outcome of poisoning. The intensity of fasciculations and seizures were very strong prognostic parameters of the poisoning severity.

Tamara Maksimovic, A. Mandić, S. Maksimovic, Ivan Kuhajda, Milorad Bijelović, N. Stevanovic

Introduction. Ovarian cancer is the most lethal gynecological cancer. The most common manifestation of thoracic metastasis is pleural effusion. Pleural effusion with positive cytology is regarded as stage IVa of the International Federation of Gynecology and Obstetrics classification, and the overall five-year survival in these patients is less than 20%. We analyzed the data of patients with ovarian cancer who were treated at the Oncology Institue of Vojvodina, in order to establish the incidence of malignant pleural effusions, laterality of pleural effusions, and clinical manifestations. Material and Methods. The study included 731 patients with ovarian cancer who were treated at the Oncology Institue of Vojvodina from January 2012 to May 2020. The obtained data were compared with data found in the literature in the same period. Results. The incidence of malignant pleural effusion in our study was 5.75%; right-sided pleural effusion was found in 57.15% of patients, 33.33% of patients had effusion on the left side, and 9.52% had bilateral effusions. Thus, unilateral effusion was found in 90.48% of cases, and bilateral in only 9.52%. The most common symptom was dyspnea, reported in 33 patients (78.6%). Conclusion. The incidence of malignant pleural effusion in our study was most similar to data found by Zamboni et al. published in 2015; the right side was the dominant side of pleural effusions. The most common symptoms were dyspnea, shortnes of breath and chest pain.

J. Berendika, S. Jungić, B. Tubić, I. Rakita, M. Vještica, D. Đokanović, Z. Gojković, Nikolina Mirčeta et al.

Background / Aim: Up until ten years ago stage four melanoma was considered a disease with extremely poor prognosis. Standard therapy during this period of time was dacarbazine chemotherapy. Patients with better performance status were treated with immunotherapy cytokine IL-2. In the last ten years eight medications have been approved by the FDA for the therapy of melanoma. The goal of this study was to determine objective response rate (ORR), median overall survival (OS), median progression free survival (PFS) and safety in patients with advanced and metastatic cutaneous melanoma treated with targeted therapy and immunotherapy at the University Clinical Centre of the Republic of Srpska (Centre). Methods: A non-randomised observational retrospective/prospective trial was conducted to investigate first experiences with the use of targeted therapy and immunotherapy at the Centre and compare the results with the literature data. A total of 23 patients received BRAF targeted therapy for the treatment of metastatic cutaneous melanoma in the first line of treatment. Nine patients received vemurafenib, fourteen patients received a combination of BRAF/MEK inhibitor. Nine patients were treated with pembrolizumab immunotherapy. The trial was performed in a period from May 2017 until December 2020. Results: In patients receiving vemurafenib ORR was 44.4 %, median PFS was 5 months (95 % CI, 1 to 11) and the median OS was 9 months (95 % CI, 2 to 17). In the vemurafenib/cobimetinib group ORR was 71.4 %. Median PFS was 9 months and median OS was 12 months. ORR in patients receiving pembrolizumab was 22.9 %, median PFS was 3 months (95 % CI, 1 to 11) and the median OS was 4.5 months (95 % CI, 2 to 12). Results in all three groups were inferior compared to the results from the literature except for ORR in patients receiving vemurafenib and vemurafenib/cobimetinib. Adverse events were tolerable and manageable and were similar to those described in the literature. Conclusion: Based on the experience with the targeted and immunotherapy in the Centre, which was presented in this study, it was concluded that in conditions when there is limited access to drugs, the greatest benefit have the patients who meet the inclusion criteria in clinical trials.

Background/Aim: With the adoption of legislation over the Austro-Hungarian rule (1878-1918) apothecary in Bosnia and Herzegovina (B&H) became a regulated profession, which enabled the arrival of graduated pharmacists. The aim of the paper was to present in which towns on the B&H territory public pharmacies were opened over this period and their owners. Methods: A retrospective and descriptive research was conducted at the Archives of the Republic of Srpska, the Museum of the Republic of Srpska and the Archives of Bosnia and Herzegovina. The method of the qualitative secondary data analysis was applied. Results: With the arrival of Masters of Pharmacy from all parts of the Austro-Hungary, an increasing number of public pharmacies began to open. Concessions for the opening pharmacies were initially granted to foreigners and among the settlers, pharmacists there were mostly Czechs, Croats, Poles, Hungarians, Slovaks, who completed pharmacy studies at universities in Vienna, Zagreb, Prague, Lviv, Graz, Innsbruck, Krakow. In the beginning, there were no locally educated pharmacists and the first appeared at the end of the 19th and the beginning of the 20th century. During this period at least one pharmacy was opened in many towns, two worked in Banja Luka, Mostar, Tuzla and Bijeljina and seven in Sarajevo. In the first years, each pharmacy was staffed by only one pharmacist and over time there were more pharmacy staff in the pharmacies. Twenty years after the occupation, public pharmacies owned by Masters of Pharmacy were opened in thirty three towns around B&H and in 1918 there were forty eight public pharmacies in thirty eight towns. Conclusion: The number of public pharmacies and qualified pharmacy staff in B&H increased over the Austro-Hungarian rule from 1878 to 1918, which contributed to the improvement of the profession, health and social conditions in the country during this period.

Naim Salki, Emira vraka, Namik Trtak, Lara Krnjojelac

Technical problems have accrued and we were not able to place abstract here in it's full length. Abstract can we found in the pdf version of the paper attached down below.

D. Laketić, Marko Šimić, J. Boljanović, D. Jović, C. Alexopoulos, B. Vitošević, A. Zelenović, L. Dinić et al.

Introduction/Objective. The aim of this study was to examine the immunohistochemical features of the vascularization of the anterior cruciate ligament (ACL), as well as the quantification of capillaries within the three segments of the ACL; proximal, middle and distal. The quantification and metric characteristics of mast cells of the ACL are the second goal of this research. Methods. Thirty human ACL of 30 persons, obtained during routine autopsy, were examined under the microscope, following immunohistochemical reactions against CD34 of blood vessels and MastTrip of mast cells. Results The middle genicular artery (MGA) close to the ACL gave off branches for the supply of ligament itself. Each field of mm2 contained an average number of 1113.84 (959-1240), microvessels in ACL proximal third, an average number of 1145.43 (924-1310) microvessels in ACL middle third, and an average number of 1134.55 (889 to 1451) microvessels in ACL distal third. An average number of mast cells of the ACL was 3.8 per mm2. In the peripheral synovial zone of the ACL we counted 12.6 mast cells per mm2. An average area value of the mast cells was 124.7 ?m2, and an average value of shorter and longer axis of the mast cells was 11.2 x 15.0 ?m. Conclusion. There was no statistically significant differences between the average numbers of intraligamentous microvessels of the ACL thirds (p>0.05), confirming and supporting our hypothesis of uniform distribution of blood supply within the ACL.

Vildana Jahić, Jagoda Balaban, Đuka Ninković-Baroš, D. Lukić, D. Jović, Andrea Stanojević, B. Pavlovska

Leser-Trélat (LT) sign (syndrome) is a rare, distinctive clinical phenomenon that is manifested by a sudden, eruptive, appearance of multiple itchy seborrheic keratoses (SK) that sometimes coincide with occult malignancy. A 73-year-old patient came for examination of numerous, large seborrheic keratoses (SK) on the skin. According to the patient's statement, SK did not occur suddenly and "eruptively". Nevertheless, ultrasound and endoscopic evaluation were suggested to the patient to exclude the Leser-Trélat phenomenon. The patient was then diagnosed with an occult, asymptomatic rectal neoplasm. The occurrence of numerous seborrheic keratoses (especially if they are "eruptive", large and bizarre in shape), should raise suspicion of LT phenomenon, or internal malignancy in the patient, and result in relevant diagnostic procedures to detect possible latent malignancy. It would be wise for the doctors of all disciplines to be acquainted with the existence of the LT sign (syndrome) and possible clinical implications of it.

Duška Jović, Snežana Petrović-Tepić, D. Knezevic, Daniela Dobrovoljski, Nataša Egeljić-Mihailović, Aleksandar Tepić, M. Burgic-Radmanovic

Introduction: Unintentional falls are the leading cause of traumatic injuries, without fatal consequences, with significant morbidity in the population of children and adolescents. Goal: The main goal of this research was to analyze the manner of falling in relation to age and gender, and to assess the type of injury and the anatomical region of the body affected by the injury sustained during a fall in patients ≤19 years of age treated in the emergency medical services in the Republic of Srpska. Material and methods: A cross-section study with retrospective analysis of the national e-database WebMedic from 11 emergency medical services between January 2018 and December 2020 was conducted. Research included patients with diagnosis of unintentional injury caused by a fall, aged ≤19 years. Descriptive statistics and the Chi-square test were used for comparisons between groups. Results: During the observed period, 857 cases of unintentional falls were identified, where 87.5% were referred for hospitalization. The group of children aged 0 to 9 years (55.7%) was more often treated for falls (p<0.001), and boys were affected 6.7 times more often than girls (p<0.001). Falls from the same level caused different types of injuries depending on the age and gender of the children (p<0.001). According to the type of injury, superficial injuries (36.8%) and open wounds (29.4%) were most often identified, and the most frequently affected body region was the head (52.0%). Conclusion: The group of children up to the age of nine and males were more often affected by superficial injuries and open wounds, with head injuries being predominant in all age groups. These results could indicate the necessity of creating programs with targeted prevention.

Dragana Đurić, Filip Milošević, D. Todorović, V. Živković, I. Srejovic, V. Jakovljevic, M. Stojiljković, R. Škrbić et al.

Background/Aim: Optimal intake of magnesium minerals is essential in maintaining the coordinated physiological functions of cells, tissues and organs. The importance of this element is reflected in the fact that it is the fourth most abundant cation in the human body, participating as a cofactor in more than three hundred enzymatic reactions. Its presence is necessary for the proper functioning of a number of vital functions, such as glycaemic control, the work of the heart and the vascular system and it can potentially play a role in the regulation of body weight. Aim of this study was to investigate the effects of subchronic intake of magnesium hydrocarbonate-rich water on changes in body weight, organ weight and cardiovascular variables in rats with streptozotocin-induced diabetes. Methods: Wistar rats (n = 28) were divided into 4 groups: two control groups, on tap water (TW-C, n = 7) and magnesium hydrocarbonate-rich water (MW-C, n = 7); and two experimental groups with streptozotocin-induced diabetes, on tap water (TW-DM, n = 7) and magnesium hydrocarbonate-rich water (MW-DM, n = 7). The values of body weight, organ weight and cardiovascular parameters were compared after 6 weeks between control groups of rats on subchronic treatment with tap water (TW-C) and magnesium hydrocarbonate-rich water (MW-C) and between groups with streptozotocin-induced diabetes on tap water (TW-DM) and with magnesium hydrocarbonate-rich water (MW-DM). Results: By comparing the values of cardiovascular parameters between groups, significant (p < 0.05) positive effects of magnesium hydrocarbonate-rich water were registered on the values of systolic and pulse blood pressure in diabetic rats fed with magnesium hydrocarbonate-rich water (MW-DM) compared to those fed with tap water (TW-DM). In contrast, no significant effect of magnesium hydrocarbonate on changes in body weight and organ weight was observed. Conclusion: Based on the results, the beneficial effects of magnesium hydrocarbonate-rich water in the regulation of blood pressure can be clearly observed. Potential effects on other cardiovascular variables and body weight and organ weight should be further investigated.

Tatjana Erceg-Rukavina, Dragana Dragicevic-Cvjetkovic, Dragana Đurić, M. Stojiljković, R. Škrbić

Background/Aim: Type 2 diabetes is a common comorbidity in patients with knee osteoarthritis. Bearing in mind that obesity and insulin resistance are risk factors for the development of knee osteoarthritis, physical therapy and balneotherapy containing hydrogen sulphide (H2S) has a positive effect on the functional and metabolic status of these patients. This work was aimed to investigate the effect of sulphate-sulphide-rich mineral baths containing H2S on the level of serum glucose in patients with knee osteoarthritis. Methods: An open prospective randomised clinical trial included patients suffering from stage I and II of the knee osteoarthritis. Patients were divided into two groups of 40 subjects each: control group and experimental group. All subjects underwent inpatient physical treatment consisting of kinesitherapy and transcutaneous electrical nerve stimulation (TENS) 6 days a week. Patients from experimental group, in addition to all the mentioned treatments, also took sulphate-sulphide mineral water baths once a day for 30 minutes for 7 days, unlike the patients from control group who took tap water baths, according to the same schedule. The level of serum glucose was monitored in all patients on admission, after discharge and 6 months after the treatment. The Student t-test was used for statistical data processing and p < 0.05 was considered as statistically significant. Results: Study included 80 patients of both sexes, with an average age of 67.00 ± 5.75 years. All patients had elevated serum glucose values on admission. The initial levels of glycaemia in the control and experimental groups were not significantly different (6.99 ± 1.95 and 7.88 ± 1.90 mmol/L, respectively). At discharge, patients who performed balneotherapy had a statistically significant decrease in serum glucose values compared to patients from the control group (by 1.84 vs 0.26 mmol/L, p < 0.001). This effect did not persist six months after the end of the treatment (p > 0.05). Conclusion: The application of balneotherapy with sulphate-sulphide mineral baths containing H2S as a potent gas transmitter significantly reduces serum glucose levels in patients with knee osteoarthritis.

Dragana Đurić, Nina Gatarić, D. Todorović, S. Stanković, Dragana Dragicevic-Cvjetkovic, M. Stojiljković, R. Škrbić, S. Vučković

Background/Aim: Hypomagnesaemia is one of the most detected electrolyte abnormalities in diabetics. Modulation of numerous cardiovascular pathophysiological processes is a potential goal for anti-diabetic therapy. Magnesium supplementation prevents subclinical tissue magnesium deficiency, thus delaying the onset of metabolic imbalance in diabetes, but long-term effects of magnesium supplementation in chronic diabetes and numerous pathophysiological processes remain unknown. Aim of this study was to determine the effects of subchronic intake of magnesium hydrocarbonate-rich mineral water on cardiometabolic markers and electrolytes in rats with streptozotocin-induced diabetes. Methods: A total of 28 Wistar, male rats, body weight 160 g at start, were divided into four groups of 7 each: two controls, group that drank tap water and received a single ip injection of saline (0.9 % NaCl) (TW-C), group that drank mineral water rich in magnesium hydrocarbonate and received a single ip injection of saline (0.9 % NaCl) (MW-C); and two experimental groups with streptozotocin-induced diabetes, group that drank tap water and received a single ip injection of streptozotocin (100 mg/kg) in saline (0.9 % NaCl, 1 mL) (TW-DM), group that drank mineral water rich in magnesium hydrocarbonate and received a single ip injection of streptozotocin (100 mg/kg) in saline (0.9 % NaCl, 1 mL) (MW-DM). Results: Regarding the biochemical parameters, a decrease was observed in the MW-C group for vitamin B12 and proteins, while triglycerides were higher compared to the TW-C group. By comparing the haemostatic biomarkers between TW-C and MW-C groups, a statistically significant decrease was found for fibrinogen, while the electrolyte analysis showed an increase in phosphates for the MW-C group. Biochemical value comparison between TW-DM and MWDM groups showed that magnesium hydrocarbonate usage in diabetic rats did not significantly reduce glycaemia although the average glycaemic values were lower in the group treated with magnesium hydrocarbonate. Regarding the electrolyte values, a statistically significant decrease was observed for sodium, potassium and phosphate in the MW-DM group. The MW-DM group also showed a significant increase in iron value compared to TW-DM group. Conclusion: Subchronic intake of magnesium hydrocarbonate-rich mineral water, as a form of magnesium supplementation, did not cause a significant improvement in glycaemia or normalisation of diabetes-induced dyslipidaemia. This study showed the reduction of fibrinogen value, thus indicating the possibility of usage of this form of magnesium supplementation in different pro-thrombogenic conditions.

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