Comprehensive Analysis of Antioxidant and Hepatoprotective Properties of Morus nigra L.

The framework of this study was a comprehensive investigation of Morus nigra L. extracts, with the aim to establish the correlation between chemical composition and antioxidant/hepatoprotective activity of a series of black mulberry extracts obtained from aerial parts of the plant. Black mulberry leaf (MLEE), bark (MBEE), juice (MJ) and fresh fruit (MFEE) extracts were obtained using the conventional Soxhlet extraction, while the supercritical CO2 extraction procedure was employed for preparation of the seed oil (MSO). Analysis of the chemical composition was performed using spectrophotometric, HPLC and GC methods. For the evaluation of antioxidant activity, in vitro FRAP and DPPH assays were applied. In Haan strain NMRI mice with streptozotocin-induced oxidative stress, in vivo antioxidant activity and liver tissue integrity were examined. The content of polyphenolic compounds was the highest in MBEE (68.3 ± 0.7 mgGAE/g) with the most abundant compounds being polyphenolic acids, followed by MLEE (23.4 ± 0.5 mgGAE/g) with the flavonoids isoquercetin and rutin being present in a significant amount. An analysis of MSO revealed a high content of γ-linoleic acid. The highest antioxidant activity in vitro (FRAP and DPPH) was observed for MLEE, MBEE and MSO. Beneficial effects were confirmed in vivo, with lower values of hepatosomatic index, potentiation of the activity of the enzymes superoxide dismutase and catalase, a lower rate of lipid peroxidation and reduced positivity for the P450 enzyme in animals treated with MLEE, MBEE and MSO. Black mulberry leaf and bark extracts as well as seed oil exhibited significant antioxidant activity. Apart from the confirmed biological properties of the fruit and leaf extracts, the observed activities of black mulberry seed oil and bark extract imply its importance as a sustainable source of phytochemicals.

Economic burden of breast cancer in northern Serbia.

Introduction: Breast cancer is the most common cancer in terms of incidence and mortality among all cancers in women in Vojvodina, the northern region of Serbia. In addition to the effectiveness and safety of therapy, it is important to put emphasis on the cost of treatment, as well as on the optimal allocation of limited resources. Objectives: This study aimed to assess the overall economic burden of breast cancer in Vojvodina, as well as the ratio of direct and indirect costs in 2019. Materials and methods: Costs were estimated using Cost of Illness (COI) evaluation, from a social perspective, based on the prevalence of the disease. The total costs included both direct and indirect expenditures. Direct costs associated with breast cancer comprised expenses linked to screening, hospital treatment, outpatient care, and prescribed medications. Indirect costs were estimated using a human capital approach, encompassing expenditures tied to lost productivity arising from sick leave, early retirement, and premature death. Results: The total cost of breast cancer in Vojvodina during 2019 was estimated to be 15 million euros. Among the total cost, direct costs accounted for 5 million euros, representing 34% of the overall expenses. Hospital treatment costs accounted for 76% of the direct costs, while screening costs represented 1%. Indirect costs amounted to 10 million euros, constituting 66% of the total cost. The primary driver was attributed to production losses caused by premature retirement, which accounted for 50% of the indirect costs. Conclusion: Breast cancer is a huge financial burden on both the health system and society in Vojvodina, accounting for 0.12% GDP. The dominance of indirect costs in total costs, can provide significant guidance to decision-makers in the healthcare system in terms of better allocation of limited resources to breast cancer prevention and early detection strategies.

Identification of patient-related, healthcare-related and knowledge-related factors associated with inadequate blood pressure control in outpatients: a cross-sectional study in Serbia.

OBJECTIVES: To determine rate of blood pressure (BP) control and to analyse patient-related, medication-related and healthcare system-related factors associated with poor BP control in outpatients with hypertension (HT). DESIGN: Cross-sectional study. SETTING: Two study sites with different levels of healthcare (primary healthcare (PHC) and secondary level of healthcare (SHC)) in Vojvodina, Northern Serbia. PARTICIPANTS: A total of 581 patients (response rate 96.8%) visiting their primary care physician between July 2019 and June 2020 filled out a pretested semistructured questionnaire and had a BP reading during their regular appointments. PRIMARY AND SECONDARY OUTCOME MEASURES: Data on demographics, medication, BP control (target systolic BP≤140 mm Hg and∕ or diastolic BP≤90 mm Hg) and knowledge on HT was collected. Based on the median of knowledge score, patients were classified as having poor, average and adequate knowledge. RESULTS: Majority of the respondents (74.9%) had poorly controlled BP and had HT longer than 10 years. Larger number of patients at PHC site was managed with monotherapy while at the SHC majority received three or more antihypertensive drugs. Respondents from SHC showed a significantly lower knowledge score (9, 2-15) compared with the respondents from PHC (11, 4-15, p=0.001). The share of respondents with adequate knowledge on HT was significantly higher in the group with good BP control (26% and 9.2%, respectively). In a multivariate regression analysis, factors associated with poor BP control were knowledge (B=-1.091; p<0001), number of drugs (B=0536; p<0001) and complications (B=0898; p=0004). CONCLUSIONS: Poor BP control is common in outpatients in Serbia, irrespective of the availability of different levels of healthcare. Patients with poor knowledge on HT, with complications of HT and those with multiple antihypertensive drugs, were at particular risk of poor BP control. Our study could serve as a basis for targeted interventions to improve HT management.

Survey of the Knowledge, Attitudes and Practice towards Antibiotic Use among Prospective Antibiotic Prescribers in Serbia.

The complex issue of antibacterial resistance (ABR) requires actions taken with the One Health approach, involving both human and veterinarian medicine. It can spread from animals to humans through the food chain or through direct contact. Health profession students, as the future antibiotic providers, can greatly impact antibiotic-related issues in the future. The study was conducted to evaluate knowledge, attitudes and practice of future antibiotic prescribers in relation to judicious use of antibiotics. This cross-sectional, questionnaire-based study was performed on 400 students of health professions who were allowed to prescribe antibiotics of the University of Novi Sad, Serbia. Students of medicine and students of dentistry showed a significantly higher knowledge score compared to students of veterinary medicine (p = 0.001). Multivariate regression identified predictors of adequate antibiotic knowledge: being a female student (B = 0.571; p = 0.020), higher grade average (B = 1.204; p = 0.001), students of medicine (B = 0.802; p = 0.006) and dentistry (B = 0.769; p = 0.026), and students who used a complete package of antibiotics during the last infection (B = 0.974; p = 0.001) or for the period recommended by the doctor (B = 1.964; p = 0.001). Out of the total sample, self-medication was reported among 42.8% of students. The identified predictors of self-medication were: more frequent (B = 0.587; p = 0.001) and irregular (B = 0.719; p = 0.007) antibiotic use, taking antibiotics until symptoms disappeared (B = 2.142; p = 0.001) or until the bottle was finished (B = 1.010; p = 0.001) during the last infection. It seems prudent to reevaluate the educational curricula regarding antibiotic use and ABR of prospective prescribers in Serbia.

Community pharmacists' challenges regarding adverse drug reaction reporting: a cross-sectional study.

OBJECTIVE: The effectiveness of the national drug safety monitoring program directly depends on the active participation of healthcare professionals in reporting suspected adverse drug reactions (ADRs). The aim of the study was to explore community pharmacists' comprehension of pharmacovigilance, their perspectives toward reporting ADRs and investigate the current practice of ADR reporting among pharmacists in Serbia. METHODS: This descriptive cross-sectional study was performed on a sample of pharmacists in Serbia between November 2019 and March 2020 using a pre-tested questionnaire distributed online. Eligible participants were community pharmacists in Serbia who were willing to participate in the study during the data collection period. Non-parametric statistical tests were performed in the analysis of knowledge, perspectives and ADR reporting. The validity and reliability of the survey were measured by exploratory factor analysis. RESULTS: The median knowledge score was 6 out of 10 (interquartile range 5-7, range 2-10). No significant differences in the knowledge scores of pharmacists were found based on weekly working hours (U = 24,805, p = .374), working experience (χ2 = 4.011, DF = 2, p = .135), being a member of a professional organization (U = 24,312, p = .209), or highest level of pharmacy qualification obtained (χ2 = 3.233, DF = 3, p = .506). Only 28.8% of pharmacists reported ADR at least once a year, while the majority of them have never reported any ADRs. CONCLUSIONS: Despite the community pharmacists' positive attitude toward adverse drug reporting and their role in the process, they show limited knowledge regarding the issue and highly prevalent under-reporting of ADRs. Educational programs are necessary to increase ADRs reporting.

Self-Medication Perceptions and Practice of Medical and Pharmacy Students in Serbia.

BACKGROUND: Attitudes towards conventional and complementary medicine among future healthcare professionals can impact their future pharmacotherapy practice. This study aimed to determine the prevalence and predisposing factors related to self-medication among medical and pharmacy students. METHODS: This cross-sectional questionnaire-based study was performed at the Faculty of Medicine, University of Novi Sad, Serbia, on first- and final-year students of medicine and pharmacy. The multivariate Poisson regression model with robust variance was used to identify the main predictors of self-medication. RESULTS: The overall self-medication prevalence in the past year was 81.3%. Independent risk factors for self-medication identified in the regression analysis were the final study year, housing condition, i.e., living in a leased apartment or in a student dormitory in comparison to living with parents, and cigarette consumption. The conventional drugs were the most frequently used, mostly for the symptoms of cold and pain. Final-year students had more confidence in conventional medicines than in herbal drugs and were more aware of the risks of their concomitant use. CONCLUSION: Self-medication is highly prevalent among students of medical sciences, especially among final-year students. Increased medical knowledge led to the higher awareness of the drug interaction risks.

Increase and Change in the Pattern of Antibiotic Use in Serbia (2010-2019).

The aim of this study was to determine and describe trends in antibiotics utilization in Serbia over a ten-year period. Data were retrieved from publicly available annual reports (2010-2019). The results were expressed as Defined Daily Dose (DDD) per 1000 inhabitants per day (DID). All calculations were performed using the DDD values for the 2020 Anatomical Therapeutic Chemical/Defined Daily Dose (ATC/DDD) version for each year of the study, to account for the DDD changes during the study period. Antibiotics were classified using the WHO Access, Watch, Reserve (AWaRe) classification. Total utilization of antibacterials for systemic use increased from 17.25 DID in 2010 to 28.65 DID in 2019. A statistically significant increasing trend in the use of the Watch category antibiotics was observed. A tendency towards use of broad-spectrum antibiotics, apparent by a statistically significant increase in the rate of utilization of broad-spectrum macrolides, quinolones and third-generation cephalosporins vs. narrow-spectrum ones, as well as a significant increasing trend in the use of quinolones was identified. Total antibiotic utilization was found to be well above the European average. Several specific problem areas were identified, which requires further efforts to improve antibiotic prescribing. The present study provides the information needed to facilitate antibiotic stewardship in Serbia further and proposes specific interventions to optimize antibiotic use in Serbia.

Serbian students' knowledge, attitudes and behaviour towards antibiotic use: is there room for improvement?

OBJECTIVES: This study has been aimed at evaluating knowledge, attitudes and behaviour of university students regarding the usage of antibiotics focusing on differences between medical and nonmedical students. METHODS: This cross-sectional questionnaire-based study was performed on 800 students of the University of Novi Sad, Serbia. RESULTS: The identified predictors of adequate antibiotic knowledge were enrolled in medical program, higher grade average and appropriate use of antibiotics during last infection. Multivariate regression identified following predictors of self-medication: being medical student (B = 0.715; p < 0.001), more frequent (B = 0.628; p < 0.001) and irregular (B = 0.584; p = 0.001) antibiotic use, a family member engaged in medical profession (B = 0.789; p < 0.001), living in dormitory (B = 0.679; p = 0.007) or rented apartment (B = 0.621; p = 0.002), using antibiotics until symptoms resolved (B = 1.616; p < 0.001) or until the bottle was finished (B = 0.628; p < 0.001) during the last infection. CONCLUSIONS: Although a high number of students showed adequate knowledge about antibiotics, numerous misconceptions were recorded, including self-medication. Further educational interventions are necessary to improve their understanding, perceptions as well as their behaviour towards antibiotic use.

Consumer willingness to pay for a pharmaceutical disposal program in Serbia: A double hurdle modeling approach.

Proper collection and disposal of pharmaceutical waste from households can reduce the negative influence of medicines on the environment. The aim of this paper is to examine the current methods of disposal of unused medicines from households, as well as the willingness of Serbian residents to participate and bear the costs of an organized collection program. Moreover, this research aims to define factors contributing to an individual's willingness to participate and pay for a medicine collection program. The survey included randomly selected patients older than 18 years visiting private pharmacies in the four largest Serbian cities. The questionnaire included information regarding the presence of unwanted medicines within the household, general medicine disposal practices, the likelihood to participate in a medicine take-back program, willingness to pay for a medicine disposal program (per prescription and per visit), importance to the environment, and demographic variables from participants. Approximately 80% of surveyed respondents are very or somewhat likely to participate, however less than half of the respondents are willing to pay for the collection of their unused medicines. The factors that influenced willingness to participate are environmental awareness and income, while the factors affecting willingness to pay, are previously received advice about proper disposal, education level, number of unwanted medicines in the household and gender. The majority of Serbian people dispose unused medicines improperly, mostly into household garbage. Well-organized and easily accessible collection programs are essential in order to enable the general public to return unused medicines for proper disposal.

The influence of standardized dry ivy leaf extract on the proportion of nasal secretion after post-septoplasty nasal packing removal.

INTRODUCTION: After post-septoplasty nasal packing removal, a certain proportion of nasal secretion occurs, leading to local and sometimes systemic infections. OBJECTIVE: The aim was to determine if standardized dry ivy leaf extract application after nasal packing removal influences the reduction of nasal secretion and diminish the occurrence of local infections. METHODS: The study included 70 post-septoplasty patients (divided into two equal groups) whose nasal packing was removed on the third day after the procedure. Group I was treated with standardized dry ivy leaf extract syrup along with regular nasal irrigation for the five days after the nasal packing removal whereas the Group II had only nasal lavage. On the sixth day after nasal packing removal, the quantity of nasal secretion was determined using a visual analog scale and nasal endoscopic examination. RESULTS: The group treated with standardized dry ivy leaf extract syrup had significantly lesser nasal secretion both by subjective patients' assessment (p<0.001) and by nasal endoscopic examination (p=0.003). The post-surgical follow up examination on the sixth day after nasal packing removal showed no development of local infection in the Group I, while in the Group II a local infection was evident in five patients (14.29%) and antibiotic therapy was required. CONCLUSION: The use of the standardized dry ivy leaf extract after nasal packing removal significantly lowers the proportion of nasal secretion.

Hepatoprotective and antioxidant potential of Pycnogenol® in acetaminophen-induced hepatotoxicity in rats.

Pycnogenol® (PYC) has already being used as a food supplement and herbal medicine due to its potent antioxidant properties. The aim of the present study was to examine the protective effect of PYC on acetaminophen-induced acute liver injury in rats. The effect of PYC on acetaminophen-induced hepatotoxicity in rats was examined by determining biochemical parameters, in vitro antioxidant activity, histological assessment, and oxidative status in liver homogenates. The best antioxidant properties were demonstrated in methanolic extracts. Seven-day pretreatment with PYC suppressed elevation of CYP2E1 protein expression induced by administration of toxic dose of acetaminophen. PYC at 50 mg/kg showed the ability to significantly decrease malondialdehyde (MDA) level compared with the group received acetaminophen. Xanthine oxidase (XOD) enzyme activity was significantly elevated in acetaminophen-treated group compared with control, whereas concomitant administration of PYC in a dose of 50 mg/kg significantly reduced activity of this enzyme. Significant decrease of glutathione (GSH) hepatic content in acetaminophen-intoxicated rats compared with the control rats was improved by concomitant administration of PYC at 50 mg/kg. Protective effect of PYC on acetaminophen-induced acute liver injury in rats has showed the best in vitro antioxidant potential expressed in methanolic extract and consequent histological assessment and oxidative status in liver homogenates.

Factors associated with non-adherence among type 2 diabetic patients in primary care setting in eastern Bosnia and Herzegovina.

AIMS: The aims of this study were to assess patients' non-adherence and associated factors to antidiabetic medication in the primary care setting in the eastern part of Bosnia and Herzegovina (BiH). METHODS: We conducted a retrospective chart review of 323 patients with type 2 diabetes mellitus (T2DM) attending the primary health care center of the Foca municipality in eastern part of BiH and measured adherence to antidiabetic medication. Adherence was measured using a pill count method. RESULTS: The majority of patients were treated with oral therapy (84.21%). Half of the patients (48%) treated pharmacologically were non-adherent and patients on oral and insulin combination therapy showed better adherence than those on oral therapy. Age (B=-0.749; p=0.004), copayment (B=0.549; p=0.028) and oral therapy (B=0.827; p=0.045) were the strongest predictors of poor adherence. CONCLUSION: About half of the patients were non-adherent to antidiabetic medication. Interventions oriented towards policy changes regarding availability of antidiabetic medication through copayment reductions, and providing healt education to younger population and patients on oral therapy could lead to better adherence among T2DM patients in eastern part of BiH.

Is the level of knowledge a predictor of rational antibiotic use in Serbia?

INTRODUCTION: The objective of this study was to investigate the knowledge, attitudes and behavior regarding antibiotics of the general population. METHODS: The study sample consisted of adult subjects who consulted general practitioners at health centers in Serbia and agreed to complete the questionnaire. A total of 668 questionnaires were distributed; 500 respondents completed the entire questionnaire (response rate 74.85%). RESULTS: The average age was 51.65 ± 16.56 years, 60.80% of the respondents were women. The median antibiotic knowledge score was 9. Predictors of adequate antibiotic knowledge were higher education level and a family member whose ocuppation was related to health-care. Overall, 58.4% of respondents believed that antibiotics could be used to treat common cold. Around a half of the respondents (47.2%) self-medicated with antibiotics at least once during their life-time, and around a quarter (24.2%) during the last treatment of infection. Patients with inadequate knowledge had 3 times higher chances of self-medicating with antibiotics compared to those with adequate knowledge. Although 98.20% of respondents claimed that antibiotic treatment should be started after a visit to a doctor and receiving a prescription, only 65.8% obtained antibiotics with prescription from a doctor during the last infection. CONCLUSIONS: Although these results demonstrate that respondents had a relatively adequate level of knowledge regarding antibiotics use, some areas of misconceptions and improper behavior were identified. Therefore, further rationalization should be focused on educational campaigns targeting the behavior of patients with regard to antibiotic use.

Self-medication with antibiotics in Serbian households: a case for action?

Background Irregular antibiotic use, including self-medication contributes to the development of antibiotic resistance. One method of accessing antibiotic use in the community is through obtaining an in house inventory of drugs. Objective The aim of this study was to investigate the extent of storage and self-medication with antibiotics agents in households in Novi Sad, Serbia. Setting Households in Novi Sad. Method The study was performed during a 4-month period (October 2015-January 2016) using a sample of 112 households in Novi Sad, Serbia. Two trained interviewers performed the survey by visiting each household. The study consisted of making an inventory of all drugs in household and a semi-structured interview about drug use practices and perceptions. Main outcome measure Number of antibiotics obtained without prescription. Results Out of 112 surveyed households, antibiotics were encountered in 55 (49.1%). Antibiotics constituted 11.98% (92/768) of total number of drug items in households. Out of all antibiotics in households, 41 (44.57%) were not in current use, and presented left-overs from previous treatment. Antibiotics were usually acquired with prescription (67, 67.7%), while about a quarter of packages were used for self-medication-purchased at pharmacy without prescription (19, 20.65%) or obtained through friends or family member (6, 6.52%).The most commonly used antibiotics for self-medication was amoxicillin (reported indications included common cold, cough, pharyngitis and tooth-ache). Conclusion Antibiotics were present in large share of households in Novi Sad. Self-medication with antibiotics and sale of antibiotics without prescription represent an important problem in Serbia.

Antioxidative and Protective Actions of Apigenin in a Paracetamol-Induced Hepatotoxicity Rat Model.

BACKGROUND AND OBJECTIVES: Apigenin is known to have various pharmacological properties without causing significant toxicity; however, hepatoprotective effect of apigenin is not often reported. The aim of our study was to investigate if the alterations in lipid peroxidation and antioxidant status are in favor to prove the efficacy of apigenin against paracetamol-induced hepatotoxicity. METHODS: The effect of apigenin on paracetamol-induced hepatotoxicity in rats was examined by determining biochemical parameters, histological assessment and oxidative status in liver homogenates. RESULTS: The treatment of animals with both apigenin and paracetamol attenuates the parameters of hepatotoxicity, especially for ALT and ALP activity which was significantly lower compared to groups of animals treated with saline and paracetamol. Hepatotoxicity induced by toxic dose of paracetamol was revealed also by notable histopathological alterations, which were not observed in the group treated with paracetamol together with apigenin. Apigenin also prevented paracetamol-induced increase in malondialdehyde (MDA) level. The activities of both CAT (catalase) and GR (glutathione reductase) enzymes after the toxic dose of paracetamol were significantly increased in the liver homogenates, compared to control group. Apigenin reversed these parameters near to values of control group. CONCLUSIONS: The result of our study indicates that apigenin inhibits the level of lipid peroxidation and significantly increases the enzyme antioxidant defense mechanisms in paracetamol-induced hepatotoxicity in rats.

Disposal of Unused Drugs: Knowledge and Behavior Among People Around the World.

The purpose of this systematic review was to determine the practice of medication disposal around the world and get insight into possible association between environmental awareness and people's behavior regarding this issue. A literature search (2005-2015) was performed to identify reports with quantitative data on disposal practices published in peer-reviewed literature. The most common method for disposal of unused medications in households is disposal in the garbage (Kuwait, United Kingdom, Lithuania, Qatar, Serbia, Ghana, Bangladesh, Malta and Saudi Arabia). The practice of flushing drugs into the sewage system still takes place in New Zealand, USA and Bangladesh. Only in Sweden and Germany, practice of returning drugs to pharmacy was practiced to a larger extent. The environmental impact of improper medication disposal is expected in countries with poorly functioning waste management schemes (Middle Eastern, Asian and African countries). Lack of the adequate information and clear instructions on proper manners of drug disposal was reported in many surveyed countries (USA, New Zealand, Bangladesh, Malta and Ireland). Clear and definite connection between knowledge about environmental detrimental effects of improper drug disposal and the preference towards disposal methods could not be established. Many respondents were generally concerned with issues of inadequate medicines discarding but the behavior regarding disposal of unused drugs often did not equate the awareness (Serbia, USA, Kuwait, Malta and UK). The current data emphasizes the global issue of improper medicine disposal, prevalent in environmentally-aware people.

Analysis of expired medications in Serbian households.

INTRODUCTION: An ongoing issue of expired medications accumulating in some households is a universal problem around the world. The aim of the study was to investigate the extent and structure of expired medications in Serbian households, and to determine which therapeutic groups generated the most waste. METHODS: This was an observational, cross-sectional study conducted in households in the city of Novi Sad, Serbia. The study had been performed over 8 month period (December 2011 - July 2012) and it consisted of personal insights into the medication inventory in households. RESULTS: Of 1008 families, 383 agreed to participate and complete the questionnaire (38.3% response rate). In almost a half of households (44.4%), expired medications were maintained. The amount of expired medications was 402 items, corresponding to 9.2% of total medications presented in surveyed households. The majority of expired medications (64.7%) was in solid dosage (tablets, capsules, granules, lozenges), following semisolid (ointments, creams, gel, suppositories) and liquid dosage forms (drops, syrups). Expired medications in the households belonged mostly to 3 categories: antimicrobials for systemic use (16.7%), dermatological preparation (15.9%) and medications for alimentary tract and metabolism (14.2%). CONCLUSIONS: This study revealed that there were relatively large quantities of expired medications in Serbian households, with a high prevalence of antibiotics for systemic use, anti-inflammatory and antirheumatic products, and medications for alimentary tract and metabolism.