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.

Introduction. Combustible tobacco smoking accounts for nearly 30% of all cancer deaths in the United States of America and about 7 million deaths worldwide each year. Nowadays, e-cigarettes are increasingly used, especially among young people, but nicotine addiction that develops by such smoking easily converts to smoking combustible tobacco. Therefore, public health efforts must be directed to the prevention of initiation of smoking all nicotine-containing products. Role of Physicians. Medical doctors are very influential in smoking-related changes in local society, especially those who work in primary care, and they have an important role in both prevention and cessation of tobacco smoking. Tobacco smoking should be eliminated among medical doctors, yet many of them still smoke. The lowest percentage of smoking among physicians is in Oceania and North America (less than 11%) and the highest in Eurasia (25%). Smoking prevalence among medical students is higher than 35% in Georgia, Greece, Spain, and Italy, but less than 5% in the United States of America and Australia. In Serbia, 23% of physicians smoke. The age of physicians does not affect the number of smokers, but gender has a significant effect; women smoke less than men. Smoking Prevention and Cessation. Education about the effects of combustible tobacco smoking is a critical issue for successful smoking prevention and cessation; the best way is to provide educational programs on smoking at medical schools by introducing a mandatory course on combustible tobacco smoking at the beginning of the first year of study, especially in societies with a large percentage of smokers. Conclusion. In this paper, we showed how smoking can be eliminated among physicians and how they can affect the patients, public health policies, and antismoking campaigns.

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.

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.

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.

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.

Psoriasis is an autoimmune and inflammatory skin disease. Psoriatic patients express higher levels of plasma homocysteine (Hcy) concentration and pro-inflammatory mediators than healthy people; this is frequently associated with vitamin D deficiency. The aim of this clinical study was to investigate the effects of high doses of vitamin D supplementation on the parameters of Hcy metabolism and cytokines in sera of psoriatic patients. This prospective study was conducted on 40 psoriatic patients who had the vitamin D deficiency. All patients received vitamin D 5000 IU/day for three months. Clinical and biochemical measurements were taken at baseline and at follow up (3 months). The results showed that the severity of clinical features, measured by the psoriasis area severity index (PASI) score, were considerably improved in patients after vitamin D supplementation. After vitamin D supplementation, most of the patients (n = 25 or 62.5%) had mild clinical form (p < 0.001). After twelve weeks of intervention period, there were significant increases in vitamin D and B12 serum levels in comparison to the levels that had been measured at the beginning of the study (56.77 ± 14.66 nmol/L and 301.08 ± 95.02 pg/mL vs. 103.85 ± 32.20 nmol/L and 362.81 ± 118.56 pg/mL, respectively; p < 0.001). Moreover, serum levels of Hcy and folate were significantly lower at the end of the study in comparison with the initial levels (12.45 ± 1.92 µmol/L and 8.01 ± 3.88 mg/mL vs. 10.38 ± 1.66 µmol/L and 6.27 ± 2.60 mg/mL, respectively). High doses of vitamin D supplementation led to a significant decrease in pro-inflammatory cytokines (IFN-ɤ, TNF-α, IL-1β, IL-6, IL-8, and IL-17) and high-sensitivity C-reactive protein (hsCRP), whereas the production of anti-inflammatory cytokines (IL-10, IL-5) was up-regulated. In conclusion, supplementation with high doses of vitamin D could be one of the possible preventive and therapeutic measures to reduce systemic inflammation in psoriatic patients.

Pharmacists are often the first healthcare professionals that patients contact with their illnesses and requests for medical information, which is enhanced following the recent COVID-19 pandemic. Community pharmacists are expected and required to possess a broad spectrum of knowledge and skills. Self-assessment of these competencies is needed for their self-improvement. To assess pharmacists’ clinical knowledge and practice in the safe use of contraceptives, and to compare the scores obtained by external observation with pharmacists’ self-assessment of their knowledge as well as investigate the significance of preceptorship experiences. Contraceptives was chosen as the subject area in view of high rates of abortions as a means of contraception in Bosnia and Herzegovina. A questionnaire approach was used. The questionnaire included the following: the first domain contained two case scenarios (safe use of contraceptives), which evaluated clinical knowledge, a second domain in which pharmacists self-assessed their knowledge to resolve cases from the first domain and a third domain that measured the demographics of pharmacists (including experience in preceptorship). Dispensing practice was evaluated in the second domain. The questionnaires were distributed to a convenient sample of 100 pharmacists at the Annual Meeting of Bosnia and Herzegovina Pharmacists. The results were presented as counts (%). The groups (preceptors and non-preceptors) were compared using Mann-Whitney U test, paired assessments were analyzed by Wilcoxon signed-rank test and Spearman’s correlation was used to assess the correlation between variables. Of the 100 pharmacists invited to participate, 84 completed the questionnaire (84 % response rate). There was no agreement between pharmacists’ real knowledge (average score - case 1: 2.71, case 2: 3.3) and their self-assessment (average score - case 1: 3.77, case 2: 3.91). There was no statistically significant difference in the actual knowledge of pharmacists (experienced/non-experienced in precepting), while the difference in the self-assessment was significant between these two groups. Pharmacists appear to overrate themselves, which leads to self-enhancement bias, in which the experience in precepting has some influence. Pharmacists’ capability in performing an objective self-assessment of their clinical knowledge needs to be carefully studied in the future to fully benefit patients.

Background Pharmacists are often the first healthcare professionals that patients contact with their illnesses and requests for medical information, which is enhanced following the recent COVID-19 pandemic. Community pharmacists are expected and required to possess a broad spectrum of knowledge and skills. Self-assessment of these competencies is needed for their self-improvement. Purpose of the study To assess pharmacists’ clinical knowledge and practice in the safe use of contraceptives, and to compare the scores obtained by external observation with pharmacists’ self-assessment of their knowledge as well as investigate the significance of preceptorship experiences. Contraceptives was chosen as the subject area in view of high rates of abortions as a means of contraception in Bosnia and Herzegovina. Methods A questionnaire approach was used. The questionnaire included the following: the first domain contained two case scenarios (safe use of contraceptives), which evaluated clinical knowledge, a second domain in which pharmacists self-assessed their knowledge to resolve cases from the first domain and a third domain that measured the demographics of pharmacists (including experience in preceptorship). Dispensing practice was evaluated in the second domain. The questionnaires were distributed to a convenient sample of 100 pharmacists at the Annual Meeting of Bosnia and Herzegovina Pharmacists. The results were presented as counts (%). The groups (preceptors and non-preceptors) were compared using Mann-Whitney U test, paired assessments were analyzed by Wilcoxon signed-rank test and Spearman’s correlation was used to assess the correlation between variables. Results Of the 100 pharmacists invited to participate, 84 completed the questionnaire (84 % response rate). There was no agreement between pharmacists’ real knowledge (average score - case 1 : 2.71, case 2 : 3.3) and their self-assessment (average score - case 1 : 3.77, case 2 : 3.91). There was no statistically significant difference in the actual knowledge of pharmacists (experienced/non-experienced in precepting), while the difference in the self-assessment was significant between these two groups. Conclusion Pharmacists appear to overrate themselves, which leads to self-enhancement bias, in which the experience in precepting has some influence. Pharmacists’ capability in performing an objective self-assessment of their clinical knowledge needs to be carefully studied in the future to fully benefit patients.

Abstract The enzymes of the cytochrome P450 superfamily play a critical role in phase I drug metabolism. Among them, CYP2C9 and CYP2C19 are clinically important, as they can mediate severe toxicity, therapy failure, and increased susceptibility to cancer and other diseases caused by chemicals. The aim of this study was to determine the prevalence of pharmacologically most important allelic variants of the CYP2C9 and CYP2C19 genes in the general population of the Republic of Srpska (Bosnia and Herzegovina) and to compare them with other populations. For this purpose we determined the genotype profile and allele frequency of 216 randomly selected healthy volunteers using real-time polymerase chain reaction (RT-PCR). The prevalence of the CYP2C9 *2 and *3 alleles was 13.6 and 7.4 %, respectively. Based on these frequencies, of the 216 participants four (1.86 %) were predicted to be poor metabolisers, 78 (36.11 %) intermediate, and the remaining 134 (62.03 %) normal metabolisers. Based on the prevalence of CYP2C19 *2 and *17 variants – 16.2 and 20.4 %, respectively – nine (4.17 %) were predicted to be poor, 57 (26.39 %) rapid, and nine (4.17 %) ultra-rapid metabolisers. We found no significant differences in allele frequencies in our population and populations from other European countries. These findings suggest that genetically determined phenotypes of CYP2C9 and CYP2C19 should be taken into consideration to minimise individual risk and improve benefits of drug therapy in the Republic of Srpska.

Background/Aim: The prevention of cardiovascular risk factors and cardiovascular disease management contributes to the cardiovascular mortality reduction. The effects of these activities have been measured by quality indicators. The aim of this study was to determine the effects of family medicine team training workshop and implementation of clinical guidelines on the cardiovascular risk factors and diseases management in primary health care in the Republic of Srpska/Bosnia and Herzegovina. Methods: The "CardioVascular Risk Assessment and Management" study included a sample of 373 teams from 41 primary health care centres trained to provide adequate services and to compare the quality of cardiovascular risk management before and after the training workshop and implementation of clinical guidelines. The comparison was based on nine project defined performance indicators related to hypertension, type 2 diabetes mellitus, hyperlipidaemia, tobacco smoking and obesity. Results: Significant improvements were observed in six indicators after the training workshop and implementation of guidelines. Target values for blood pressure and HbA1c were achieved in over 80 % of patients (82.12 ± 15.81 vs 84.49 ± 12.71 and 84.49 ± 12.71 vs 85.49 ± 24.55; before and after the training workshop, respectively), while the target values for LDL cholesterol were achieved in 54.98 % ± 20.33 before and 57.64 % ± 16.66 after the training workshop. The number of teams that had less than 20 % of recorded data significantly decreased after the training workshop and guidelines implementation, and adequate recording of all indicators was improved. Conclusion: The training workshop of family medicine teams and implementation of clinical guidelines resulted in significant quality improvement of cardiovascular diseases management in primary health care.

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.