Takotsubo syndrome (TTS) is an acute heart failure syndrome characterised by catecholamine-induced oxidative tissue damage. Punica granatum, a fruit-bearing tree, is known to have high polyphenolic content and has been proven to be a potent antioxidant. This study aimed to investigate the effects of pomegranate peel extract (PoPEx) pre-treatment on isoprenaline-induced takotsubo-like myocardial injury in rats. Male Wistar rats were randomised into four groups. Animals in the PoPEx(P) and PoPEx + isoprenaline group (P + I) were pre-treated for 7 days with 100 mg/kg/day of PoPEx. On the sixth and the seventh day, TTS-like syndrome was induced in rats from the isoprenaline(I) and P + I groups by administering 85 mg/kg/day of isoprenaline. PoPEx pre-treatment led to the elevation of superoxide dismutase and catalase (p < 0.05), reduced glutathione (p < 0.001) levels, decreased the thiobarbituric acid reactive substances (p < 0.001), H2O2, O2− (p < 0.05), and NO2− (p < 0.001), in the P + I group, when compared to the I group. In addition, a significant reduction in the levels of cardiac damage markers, as well as a reduction in the extent of cardiac damage, was found. In conclusion, PoPEx pre-treatment significantly attenuated the isoprenaline-induced myocardial damage, primarily via the preservation of endogenous antioxidant capacity in the rat model of takotsubo-like cardiomyopathy.

Background/Aim: Clinical research nursing is a well-known concept in Europe and other countries. The purpose of this study was to investigate the nurses' knowledge and attitudes towards clinical research and their opinions and self-evaluation about clinical research nursing and factors affecting them. Methods: A cross sectional study was conducted at the University Clinical Centre of the Republic of Srpska (UCCRS). A questionnaire included 50 questions/ statements was created in order to address the aims of the research and afterwards distributed to 120 nurses from 6 departments. Results: Response rate was 91.6 %. Most of the respondents showed a low level of knowledge, but positive attitude related to clinical research. Nurses who participated in clinical research were confident in their competencies according to their self-evaluation. Conclusion: Systematic approach to the additional nurses education could have a significant impact on a success of clinical research.

Background and Objectives: Benzodiazepines (BZDs) are among the most prescribed psychotropic drugs and significant number of patients use these drugs for longer periods than recommended. The objective of this study was to determine the factors associated with prescribing of BZDs at the primary healthcare level. Materials and Methods: A retrospective analysis of family physicians’ prescriptions from the databases of family medicine teams of the Republic of Srpska was performed. The number of BZDs users, as well as the total number of prescriptions, were determined. Thereafter, it was determined which specific BZD had been prescribed, in which dose, for how long, as well as the specific social and demographic characteristics of patients to whom the drugs were prescribed. Results: The results showed that 38.47% of patients used the BZDs for a period longer than six months. The most frequent BZDs prescribed were the intermediate-acting BZDs, primarily bromazepam (58.69%). Two thirds of patients were women. The average age of the patients was 60, 60.46% of patients were single, and 69.68% lived in urban areas. The longer uses of BZDs were recorded in women, the elderly, single people and those who lived in urban areas, while higher doses of BZDs were prescribed to men, as well as younger and married people. The highest positive correlation was found between the dose and length of use of BZD. Conclusions: A significant percentage of patients used BZDs for a time period longer than recommended. Caution is necessary when prescribing BZDs to women, the elderly, patients that live in urban areas and patients who are single. When prescribing BZDs, family physicians should be aware of their potential interactions and addictive potentials.

Background/Aim: Coma is the most severe disturbance of consciousness from which the patient cannot wake up and in which there is no verbal and motor response or opening of the eyes. The aim of the research was to establish the frequency of occurrence of coma and the aetiology of coma in the Banja Luka Emergency Department (ED). Also, the goal was to analyse the accuracy of the referral diagnosis and potential factors that can help the doctor in making a correct diagnosis. Methods: A retrospective cross-sectional study was conducted. In the ED database, in the period from January to September 2022, all patients diagnosed with coma have been found. The gender and age of the patient, vital parameters, performed diagnostic methods and therapy were recorded. The referral diagnosis, the department to which the patient was referred, as well as the final diagnosis determined in hospital conditions were recorded. Results: In the period from January to September 2022 there were 95 patients who were diagnosed with coma. The average age of the patients was 67.76 ± 16.56 years, there were 56 (58.9 %) men and 39 (41.1 %) women. Of that number, 41 (43.2 %) patients were diagnosed with hypoglycaemic coma and those patients were treated in the field. Out of 54 patients, 32 (59.3 %) patients had a confirmed referral diagnosis, while 22 (40.7 %) patients had another diagnosis established at the hospital. All patients with suspected intracranial bleeding or stroke were correctly diagnosed and adequately referred, while all patients with a confirmed diagnosis of sepsis and shock were incorrectly referred (ch2 = 30.563, p < 0.001). Conclusion: The most frequent were coma caused by hypoglycaemia and coma caused by brain ischaemia and non-traumatic bleeding, which were adequately recognised and treated and/or referred. Coma caused by sepsis and shock of different aetiology was not recognised as such and was referred to a neurologist, where precious time was wasted. In order to reduce errors in the field, it is necessary to pay more attention to the anamnestic data on diseases and perform a somatic and neurological examination adequately.

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.

Background / Aim: The concept of general balanced anaesthesia was devised in order to assure cardiovascular stability and fast post-anaesthesia recovery. This clinical trial was organised in order to investigate the parameters of cardiovascular function and emergence from anaesthesia in elective ear, nose and throat (ENT) surgery patients. Methods: A total of 40 ASA I and II patients of both sexes scheduled for elective ENT surgery were randomly divided into two equal groups. Both groups received a continuous IV infusion of glucose 5 % solution and in the esmolol group this infusion also contained esmolol. Esmolol infusion rate was 0.3 mg/kg/min during the first 5 min and thereafter 0.1 mg/kg/min. In critical phases of anaesthesia and operation (induction, intubation, first incision, surgical manipulations, wound suture, extubation), systolic and diastolic blood pressure were monitored. Recovery after anaesthesia was assessed based on times of eye opening on command, spontaneous eye opening and regaining of full orientation. Increases in cardiovascular parameters by 20 % of the baseline values or more were treated with IV boluses of fentanyl, alone or with droperidol and, if necessary, by adding isoflurane 0.5 % to the inhalational mixture. Consumption of drugs was recorded. Results: Esmolol assured stable values of cardiovascular parameters that were in most critical phases of anaesthesia and operation lower than in the control group. The duration of anaesthesia did not differ between the groups. In the esmolol group, lower consumption of fentanyl, droperidol and sevoflurane was registered. Patients in the esmolol group emerged from anaesthesia faster than patients in the control group. Conclusion: Continuous IV infusion of esmolol assures better cardiovascular stability, necessitates lower consumption of analgesics and anaesthetics and results in faster emergence from general anaesthesia in elective ENT surgery.

Abstract Pesticide poisonings, intentional as well as accidental, are common, especially in undeveloped and developing countries. The goal of this study was to analyze the clinical presentation of patients hospitalized due to acute organophosphate (OPP) or carbamate pesticide (CP) poisoning as well as to analyze the factors that potentially influenced the severity and outcome of the poisonings. A retrospective cross-sectional study was performed. The age and gender of each patient were recorded, the type of ingested pesticide, whether the poisoning was intentional or accidental, number of days of hospitalization, the severity of the poisoning, and the outcome of the treatment (i.e., whether the patient survived or not). Clinical aspects of poisonings were analyzed, as well as the therapeutic measures performed. 60 patients were hospitalized due to acute OPP or CP poisoning, out of 51 (85.00%) were cases of intentional self-poisoning. The majority of patients were poisoned by OPPs (76.67%), in one-third the causative agent was malathion, followed in frequency by chlorpyrifos and diazinon. Dimethoate poisonings were manifested with the most severe clinical picture. A 70% or lower activity of reference values of acetylcholinesterase and butyrylcholinesterase was found in 50% and 58% of patients, respectively. The most common symptom was miosis (58.33%), followed by nausea and vomiting. Pralidoxime reactivated acetylcholinesterase inhibited by chlorpyrifos or diazinon, but not with malathion or dimethoate. Impairment of consciousness and respiratory failure, as well as the degree of acetylcholinesterase and butyrylcholinesterase inhibition, were prognostic signs of the severity of poisoning. The lethal outcome was more often found in older patients (t = 2.41, p = 0.019). The type of ingested pesticide significantly affects the severity and outcome of poisoning as well as the effectiveness of antidotes.

Background/Aim: Organophosphorus compounds (OP) bind to acetylcholinesterase (AChE) causing an irreversible inhibition of the enzyme. When doing in vivo studies of OP intoxication, to precisely measure AChE activity in the brain tissue it is necessary to remove as much blood from the brain as possible. By doing so, interference of the OPs present in the blood is avoided. Usually this demands expensive equipment, therefore, the aim of this study was to find a simple and economical method to eliminate the blood from brain blood vessels. Methods: Wistar albino rats were divided into four groups named Control (C), Control washout (CW), Paraoxon (Pox) and Paraoxon washout (PoxW) group. Rats in Pox and PoxW were treated with 0.25 mg/kg paraoxon subcutaneously (sc), while C and CW received 1 mL/kg sc saline instead. The "Marinković-Maksimović" ("MM") method was performed in rats from PoxW and CW groups. Activity of AChE was measured both in erythrocyte lysate and in brain tissue using spectrophotometry. Results: Macroscopic examination revealed that the elimination of blood was achieved in CW and PoxW groups. Activity of AChE in homogenised brain tissue was expectedly lower in the Pox and PoxW group, when compared to C and CW group, respectively. The CW group had a lower value of AChE activity in the brain tissue compared to C group, while activity of AChE in the PoxW group was statistically higher than in the Pox group (p = 0.044). Conclusion: The MM method provides good elimination of blood from the brain. Together with blood, present confounding factors that interfere with analysis in homogenised brain tissue, were also eliminated.

Background/Aim: In surgery, and especially in the neurosurgical operations, maintenance of cardiovascular stability during and in the phase of the immediate postoperative recovery is of vital importance. The aim of this study was to investigate the effects of continuous esmolol infusion on the values of cardiovascular parameters and quality of the emergence from anaesthesia in neurosurgical patients. Methods: A total of 40 patients of both sexes scheduled for elective supratentorial surgery were randomly assigned to two groups. Esmolol group received intravenous (iv) infusion of esmolol dissolved in 5 % glucose solution (during the first 5 min at a rate of 0.3 mg/kg/min and thereafter at a rate of 0.1 mg/kg/min), while the ones from the control group received a 5 % glucose solution without esmolol at the same volume and rate. Cardiovascular parameters were registered at critical phases of anaesthesia and operation (induction, intubation, placement of Mayfield frame, craniotomy, skull closure, extubation). Recovery after anaesthesia was assessed based on times of eye opening on command, spontaneous eye opening and regaining of full orientation. Results: Values of systolic blood pressure and heart rate were significantly lower in the esmolol than in the control group of patients. Although the durations of anaesthesia did not differ, patients from the esmolol group required significantly less opioids and isoflurane and recovered after the anaesthesia significantly faster than the patients in the control group. Conclusion: Ultrashort-acting beta-adrenergic receptor antagonist esmolol, administered as a continuous iv infusion, assures better cardiovascular stability and smoother emergence from the balanced inhalation general anaesthesia than the control glucose infusion in elective neurosurgical patients.

Introduction: Oganophosphorus compounds (OP) bind to acetylcholinesterase (AChE) and inactivate it. In the synaptic cleft, undestroyed and accumulated acetylcholine produce the acute cholinergic effects. The aim of this study was to determine the frequency, speed of onset and intensity of certain signs of paraoxon poisoning depending on dose and outcome of poisoning. Methods: The study was conducted in adult Wistar rats. The median lethal dose (LD50) of paraoxon as well as protective ratio (PR) of atropine (10 mg/kg intramuscularly) was determined. Clinical signs of poisoning were observed: fasciculations, tremor, seizures, ataxia, piloerection, lacrimation, exophthalmos, bizzare/stereotypic behaviour and dyspnoea. The time from paraoxon injection to the first appearance of the sign of poisoning was recorded as well as the intensity of poisoning with evaluation at 10 time intervals throughout the 4 h observational period. Results: The LD50 of paraoxon was 0.33 mg/kg (subcutaneously) and PR of atropine was 2.73. Dose-dependent, piloerection occurred more often (p = 0.009) and at higher intensity (p = 0.016) at higher doses. Fasciculations, tremor, seizures and ataxia occurred significantly earlier at higher doses of paraoxon (p = 0.015, 0.002, 0.021 and 0.016, respectively), as well as the intensity of seizure, tremor and fasciculation. Piloerection (p = 0.002) and seizures occurred more frequently (p = 0.009) in non-survivors. Fasciculations, tremor, seizures and ataxia occurred significantly earlier and at higher intensity in non-survivors (p < 0.001, for all parameters), as well as dyspnoea (p = 0.009 and p = 0.048). In atropine-protected rats, nicotinic effects persevered, so they were the prognostic parameter of the severity of the poisoning. Conclusion: Seizures and fasciculations followed by tremor were strong prognostic parameters of the probability of lethal outcome of paraoxon poisoning. Also, the mentioned poisoning signs were with their intensity and speed of occurrence in a clear positive correlation with the administered dose of paraoxon. Even at high doses of paraoxon, atropine blocked the muscarinic (but not nicotinic) effects and somewhat mitigated the CNS toxic effects.