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Determination of anthocyanins content in three samples of herbal teas with cranberry, Vaccinium macrocarpon Aiton
No full textHerbal and fruit teas are very popular because of their ease of preparation and their refreshing taste and smell, as well as their positive effects on health. They are a good source of various polyphenolic compounds, especially anthocyanins, which have significant pharmacological effects (antioxidant, cardioprotective, anti-inflammatory, antitumor, antidiabetic, etc.) Anthocyanins are flavonoid compounds present in plants, especially in fruit and vegetables, from which red, purple and blue color is derived (blueberries, blackberries, raspberries, hibiscus flowers, etc). However, their use is limited, because they are extremely unstable compounds, and the main factors of instability are pH value, light, temperature and the presence of enzymes.15th International Congress on Nutrition "Food, nutrition and health within sustainable development", 20-22nd November 2024, Belgrade, Serbia15. Конгрес исхране "Храна, исхрана и здравље у оквиру одрживог развоја", 20-22. новембар 2024, Београд, Србиј
Historical evolution of training and skills development at BENU Pharmacies
No full textThe evolution of training and skills development at BENU pharmacies can be traced through
distinct phases, each reflecting advancements in both hard and soft skills aligned with
evolving organizational needs and industry trends. Initiated in 2004, BENU's commitment to
operational excellence began with a focus on hard skills training, ensuring robust technical
competencies across its pharmacy network.
Phase I (2004-2014): Foundation of Operational Excellence
During the initial phase, BENU pharmacies established a framework centered on hard skills
training. This period saw the implementation of rigorous training programs aimed at
enhancing technical proficiencies and operational efficiency. The emphasis was on equipping
pharmacy staff with the necessary competencies to uphold high standards of service delivery
and pharmaceutical care.
Phase II (2014-2019): Integration of Soft Skills
Building upon its foundation, BENU transitioned into the integration of soft skills training.
Recognizing the pivotal role of interpersonal dynamics and customer relations in
pharmaceutical service delivery, the organization introduced programs focusing on
communication, customer service, and team collaboration. This phase marked a significant
shift towards holistic training approaches that addressed not only technical prowess but also
the softer aspects of pharmacy operations.
Phase III (Post-2019): Adaptive Training for Contemporary Challenges
In response to evolving market dynamics and the increasing complexity of healthcare
environments, BENU pharmacies entered a new phase of training strategies. Emphasizing
resilience, emotional intelligence, and psychological safety, current training initiatives are
designed to empower employees to navigate challenges with agility and empathy. These
programs reflect BENU's commitment to fostering a supportive workplace culture that values
both individual well-being and organizational effectiveness.
Assessments and Research for Continuous Improvement
In tandem with its comprehensive training initiatives, BENU pharmacies prioritize
assessments and ongoing research to drive continuous improvement. Regular assessments of
employee competencies and customer satisfaction metrics inform targeted training
interventions and operational enhancements. Moreover, robust research endeavors explore
emerging trends in pharmaceutical care and customer expectations, guiding strategic
decisions and ensuring relevance in a competitive market. By leveraging data-driven insights
and fostering a culture of innovation, BENU remains committed to advancing its service
quality and maintaining its position as a leader in the pharmacy industry.
Conclusion
The historical evolution of training and skill development at BENU pharmacies underscores a
progressive journey from foundational hard skills to integrated soft skills and contemporary
adaptive training practices. By aligning training programs with evolving industry demands
and employee needs, BENU continues to cultivate a workforce equipped to deliver
exceptional pharmaceutical services in a dynamic healthcare landscape
Molecular dynamics examination of the cryptic subpocket of sirtuin 2
No full textRecently described alternative conformational state of sirtuin 2 (SIRT2) characterized by a cryptic
subpocket paved the way for this study which investigates the significance of the newly identified
cryptic subpocket in designing a group of SIRT2 inhibitors, derivatives of 4-(4-
pyridylmethyl)aniline. With this aim, molecular dynamics simulations were conducted, initiating
from two distinct conformational states of SIRT2 defined by the absence, or presence of the cryptic
subpocket. Based on the analysis of the generated trajectories and estimated free energies of binding
for reference and designed inhibitor, it has been shown that studied ligands were able to stabilize
protein in both conformational states. Furthermore, the results suggest that the further design of
novel 4-(4-pyridylmethyl)anilines could be focused on finding optimal substitution pattern to
facilitate interactions with residue Phe132 within the cryptic subpocket.17th International Conference on Fundamental and Applied Aspects of Physical Chemistry, September 23-27, 2024 Belgrade, Serbi
Characterization of Chokeberry Pomace Extract and its Utilization for Dyeing and Functionalization of Fabrics
No full textBerry pomaces, which are waste products from the food industry, contain
a significant amount of colored bioactive polyphenolic compounds. These
compounds are known for their excellent antioxidant and antimicrobial activities.
Given these properties, bioactive compounds from chokeberry pomace (CBP)
extract were utilized for the simultaneous dyeing and functionalization of fabrics
of different chemical compositions. After the preparion, CBP extract was
characterized1
from the aspect of total polyphenolic content (204.61 mg/g of CBP),
total flavonols and flavonones content (14.74 mg/g of CBP), and total anthocyanin
content (14.62 mg/g of CBP). The antioxidant activity of the extract, determined
by the DPPH and ABTS assays, was found to be 66.44% and 99.70%, respectively.
This characterized extract was then used for dyeing and functionalizing of fabrics
of different chemical compositions brought together in a multifiber fabrics. The
carried out experiments indicated that cotton and viscose exhibited excellent
antioxidant activity (99.99%) and antibacterial efficacy against Escherichia coli
and Staphylococcus aureus. Colorimetric measurements showed that the fabric
color strength values ranged from 2.06 to 18.93. These results suggest that the
treated fabrics are suitable for the production of protective textiles
Determination of Total Phenolic Content, Antioxidant, and Antimicrobial Activities of Green Vegetables
No full textModern trends in nutrition imply the daily intake of fresh fruits and
vegetables, with the statement that they are important natural antioxidants that
protect the body from oxidative stress. Green vegetables with a high total phenolic
content (TPC), are especially highlighted. The TPC values of several types of green
vegetables (brussels sprouts, cabbage, broccoli, parsley, borecole, and spinach)
were determined by the Folin-Ciocalteu method. The antioxidative ability of
chosen green vegetables were determined using DPPH and ABTS methods. The
same samples were tested for antimicrobial activity against seven laboratory
control strains of bacteria and one yeast. The obtained results indicate that there is
a significant correlation between TPC and the antioxidant and antimicrobial
potential of methanol-water extracts of selected green vegetables. i.e., the high
total phenolic content does influence the antioxidant activity of tested green
vegetables from the Brassicaceae, Amaranthaceae, and Apiacaae families.
Overall, these everyday consumed vegetables were shown as a good source of
antioxidants for regulating free radicals in our body
GLP-1 Receptor Agonists Attenuate Pain-Like Behavior in an Animal Model of Chronic Migraine
No full textBackground & Aims
Migraine stands as the second leading cause of global disability, particularly affecting females under 50 [1]. Nearly 70% of migraine sufferers are dissatisfied with conventional prophylactic therapies [2], prompting exploration into alternative treatment approaches. Recent preclinical investigations have shown that liraglutide (a GLP-1 receptor agonist) is effective against mechanical hypersensitivity associated with chronic migraine [3, 4]. Building on this, the hypothesis that GLP-1 receptor agonists might be useful for migraine prophylaxis arose. To add on existing knowledge, we aimed to investigate the effects of semaglutide and liraglutide, both long-acting GLP-1 receptor agonists, through an extended battery of antinociceptive tests including well-being assessment in a murine model of chronic migraine. In order to increase the translational relevance of our study, propranolol (a well-established migraine prophylactic drug) served as a positive control.
Methods
A model of chronic migraine was established by repeated intraperitoneal (i.p.) administration of nitroglycerin (NTG; 10 mg/kg; every second day over 9 days) in female C57BL/6 mice. Semaglutide (subcutaneous, s.c.), liraglutide (s.c.), and propranolol (i.p.) were given daily all over the study course. To evaluate pain hypersensitivity and the antinociceptive effects of treatments, both stimulus-evoked (orofacial glutamate test) and non-evoked (burrowing test) nociceptive tests were used. The orofacial glutamate test was performed by injecting glutamate solution (s.c.) into the orofacial region. This chemical stimulus induces specific nociceptive behavior that was quantified during 15 min (two hours post-NTG injection, all over the observing period). The burrowing test served as a paradigm for spontaneous nociceptive behavior and overall animal welfare (performed on the 8th day of the protocol). Data were analyzed using one-way/two-way repeated measures ANOVA (Tukey post hoc analysis).
Results
Repeated NTG administration caused significant chemical hypersensitivity and spontaneous nociceptive behavior in treated mice in comparison with the vehicle group (all P < 0.01; P < 0.05; respectively). In the orofacial glutamate test, prophylactic repeated administration of semaglutide (50 and 100 µg/kg/day, s.c.), liraglutide (400 and 800 µg/kg/day, s.c.), as well as propranolol (20 mg/kg/day, i.p.) significantly reduced the development of chemical pain hypersensitivity in female mice with NTG-induced chronic migraine, characterized by a decrease in total time spent in nociceptive behavior (all P < 0.05; two-way repeated measures ANOVA with Tukey post hoc test). In the burrowing test, prophylactic administration of both GLP-1 receptor agonists, contrasting the reference drug, statistically significantly increased the amount of burrowed material in comparison with the NTG-control group (all P < 0.05; one-way ANOVA with Tukey post hoc test).
Conclusions
The presented results showed that GLP-1 receptor agonists, semaglutide and liraglutide, attenuated provoked pain-like behavior in a comparable manner to propranolol, the referent drug, in the chronic migraine model in female C57BL/6 mice. Unlike propranolol, GLP-1 receptor agonists beneficially affect spontaneous pain-like behavior and animal well-being. Assuming the high predictive value of the employed chronic pain model, semaglutide and liraglutide might represent useful alternatives for chronic migraine prophylaxis. Further exploration of GLP-1 agonists in clinical settings is essential to ascertain their potential applicability.
References
[1] Steiner, T.J., Stovner, L.J., Jensen, R., Uluduz, D., Katsarava, Z., 2020. Migraine remains second among the world’s causes of disability, and first among young women: findings from GBD2019. J Headache Pain 21, 137.
[2] Pascual, J., Panni, T., Dell’Agnello, G., Gonderten, S., Novick, D., Evers, S., 2023. Preventive treatment patterns and treatment satisfaction in migraine: results of the OVERCOME (EU) study. J Headache Pain. 24(1):88.
[3] Jing, F., Zou, Q., Wang, Y., Cai, Z., Tang, Y., 2021. Activation of microglial GLP-1R in the trigeminal nucleus caudalis suppresses central sensitization of chronic migraine after recurrent nitroglycerin stimulation. J Headache Pain. 22(1):86.
[4] Jing, F., Zou, Q., Pu, Y., 2023. GLP-1R agonist liraglutide attenuates pain hypersensitivity by stimulating IL-10 release in a nitroglycerin-induced chronic migraine mouse model. Neurosci Lett. 812:137397
Review and External Evaluation of Population Pharmacokinetic Models for Vedolizumab in Patients with Inflammatory Bowel Disease: Assessing Predictive Performance and Clinical Applicability
No full textBackground/Objectives: Several population pharmacokinetic models of vedolizumab (VDZ) are available for inflammatory bowel disease (IBD) patients. However, their predictive performance in real-world clinical settings remains unknown. This study aims to externally evaluate the published VDZ pharmacokinetic models, focusing on their predictive performance and simulation-based clinical applicability. Methods: A literature search was conducted through PubMed to identify VDZ population pharmacokinetic models. A total of 114 VDZ concentrations from 106 IBD patients treated at the University Medical Center “Zvezdara”, Republic of Serbia, served as the external evaluation cohort. The predictive performance of the models was assessed using prediction- and simulation-based diagnostics. Furthermore, the models were utilized for Monte Carlo simulations to generate concentration–time profiles based on 24 covariate combinations specified within the models. Results: Four published pharmacokinetic models of VDZ were included in the evaluation. Using the external dataset, the median prediction error (MDPE) ranged from 13.82% to 25.57%, while the median absolute prediction error (MAPE) varied between 41.64% and 47.56%. None of the models fully met the combined criteria in the prediction-based diagnostics. However, in simulation-based diagnostics, pvcVPC showed satisfactory results, despite wide prediction intervals. Analysis of NPDE revealed that only the models by Rosario et al. and Okamoto et al. fulfilled the evaluation criteria. Simulation analysis further demonstrated that the median VDZ concentration remains above 12 μg/mL at week 22 during maintenance treatment for approximately 45–60% of patients with the best-case covariate combinations and an 8-week dosing frequency. Conclusions: None of the published models satisfied the combined criteria (MDPE, MAPE, percentages of prediction error within ±20% and ±30%), rendering them unsuitable for a priori predictions. However, two models demonstrated better suitability for simulation-based applications
Heuristička analiza odnosa strukture, aktivnosti i selektivnosti derivata izokumarina kao potencijalnih antifungalnih agenasa
No full textA series of recently synthetized and biologically evaluated isocoumarin derivatives (n=16,
including voriconazole as standard) were used for heuristic analysis of structure, activity and
selectivity relationships. While research of isocoumarins found in the literature was mainly
focused on antifungal properties of 3-alkyl/aryl compounds, this study used structures synthetized
by a strategy merging antifungal properties of isocoumarins with some known fungal
pharmacophores. Rationalization of activity and selectivity was performed using the results of
testing against C. albicans (CA) and testing on a normal human lung fibroblast cell line (MRC5).
Structures were created and optimized using the ChemDraw Ultra 8.0 and MOPAC software.
Calculation of molecular descriptors and the heuristic method, using the Codessa software, were
applied for the selection of the most significant descriptors for activity against CA, as well as
selectivity against CA versus MRC5. Biological tests for determination of activity against CA
used in studies include inhibition of hyphal growth, so the activity against resistant cells was also
considered. The supposed mechanisms of action, including lacton opening and electrophilic
attack on nucleophiles, as well as inhibition of lanosterol 14α-demethylase (CYP51), were in
agreement with the results obtained. The results could serve as a basis for further optimization of
isocoumarin derivatives with respect to better activity, selectivity and action against resistant
species.Serija skorašnje sintetisanih i biološki testiranih derivata izokumarina (br. 16, uključujući
vorikonazol kao standard) korišćena je za heurističku analizu odnosa strukture, aktivnosti i
selektivnosti. Istraživanja izokumarina pronađena u literaturi su uglavnom fokusirana na
antifungalne osobine 3-alkil/aril derivata, dok su u ovim studijama korišćene strukture sintetisane
strategijom kombinovanja antifungalnih osobina izokumarina sa nekim poznatim fungalnim
farmakoforama. Racionalizacija aktivnosti i selektivnosti vršena je korišćenjem rezultata
testiranja protiv C. albicans (CA) i na normalne humane ćelije plućnog fibroblasta (MRC5).
Strukture su kreirane i optimizovane korišćenjem ChemDraw Ultra 8.0 i MOPAC softvera.
Izračunavanje molekulskih deskriptora i heuristička metoda, korišćenjem Codessa softvera,
primenjeni su za selekciju najznačajnijih deskriptora za aktivnost protiv CA, kao i selektivnost
protiv CA u odnosu na MCR5. Biološki testovi za određivanje aktivnosti protiv CA korišćeni u
studijama uključuju inhibiciju hifalnog rasta, te je razmatrana i aktivnosti protiv rezistentnih
ćelija. Pretpostavljeni mehanizmi aktivnosti, uključujući otvaranje laktona i elektrofilni napad na
nukleofile, kao i inhibiciju lanosterol 14α-demetilaze (CYP51), u saglasnosti su sa dobijenim
rezultatima. Rezultati mogu da posluže kao osnova za buduću optimizaciju derivata izokumarina
u cilju postizanja bolje aktivnosti, selektivnosti i dejstva protiv rezistentnih vrsta
Integrating Clopidogrel’s First-Pass Effect in a Joint Semi-Physiological Population Pharmacokinetic Model of the Drug and Its Inactive Carboxylic Acid Metabolite
No full textClopidogrel (CLO), a pro-drug for preventing thrombotic events, undergoes rapid absorption and extensive metabolism, with approximately 85–90% converted to an inactive carboxylic acid metabolite (CLO-CA) and the remaining to an active thiol (CLO-TH). Few pharmacokinetic models for the drug and its metabolites exist, with most focusing on CLO-TH. Although CLO-CA is inactive, its predominant (compared to its parent drug and metabolites) presence in plasma underscores the importance of characterizing its formation and pharmacokinetic profile. This study aimed to characterize the process of the absorption of CLO and its conversion to CLO-CA via developing a population pharmacokinetic model. Individual participants’ data from two bioequivalence studies were utilized. Extensive blood samples were collected at predetermined intervals, including 841 concentrations of CLO and 1149 of CLO-CA. A nonlinear, mixed-effects modelling approach using NONMEM® software (v 7.5) was applied. A one-compartment model was chosen for CLO, while a two-compartment proved optimal for CLO-CA. Absorption from the depot compartment was modeled via two transit compartments, incorporating transit rate constants (Ktr). A semi-physiological model explained the first-pass effect of CLO, integrating a liver compartment. The estimated mean transit times (MTTs) for the studies were 0.470 and 0.410 h, respectively. The relative bioavailability for each study’s generic medicine compared to the reference were 1.08 and 0.960, respectively. Based on the estimated parameters, the fractions metabolized to inactive metabolites (FiaM_st1 and FiaM_st2) were determined to be 87.27% and 86.87% for the two studies, respectively. The appropriateness of the final model was confirmed. Our model offers a robust framework for elucidating the pharmacokinetic profiles of CLO and CLO-CA
Perceived importance of emotional intelligence for clinical pharmacy practice and suggested improvements: a focus group study of postgraduate pharmacists
No full textBackground: Emotional intelligence (EI) is a critical set of skills that impacts clinical pharmacists’ well-being and positively influences high-level patient-centred care. Describing pharmacists’ perceptions may support the integration of EI development approaches into their professional development continuum. Aim: The aim of this study was to analyse pharmacists’ perceptions of the characteristics of emotionally intelligent clinical pharmacists, the importance of EI in clinical practice, and educational models and approaches to enhancing EI. Method: A qualitative study with a focus group methodology was conducted with pharmacy practitioners using a semi-structured guide grounded in the EI competency framework and existing qualitative research methodology practices. Purposive sampling was conducted until information and meaning saturation occurred. The focus group recordings were transcribed and independently coded by two researchers. The conventional content analysis of qualitative data was applied with the inductive thematic approach at its core. Results: According to the 17 focus group participants, emotionally intelligent clinical pharmacists are perceived as self-confident communicators who control and manage emotions, work well under pressure, and handle every situation effectively. Emotional self-control, self-awareness, awareness of others, tolerance, understanding, and empathy have emerged as key EI competencies required for challenges in clinical practice. EI lectures with reflections from clinical applications, behaviour modelling, and behaviour-changing methods were perceived to be of particular importance for pharmacist education and development programmes. Conclusion: Postgraduate pharmacy practitioners perceived EI competencies as necessary for their professional success and high-quality patient-centred care. They suggested that EI competencies be a focal point in pharmacy professional development programmes