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Determination of paraoxonase activity and prooxidant-antioxidant balance in the brain tissue of rats following subacute administration of different K-oximes
No full textThis study aimed to determine the paraoxonase activity and prooxidant-antioxidant balance in the brain tissue of Wistar rats following subacute treatment with selected K-oximes. Each K-oxime was administered intramuscularly (0.1 LD50/kg) twice per week for four weeks, and 7 days after the last treatment, the paraoxonase activity (PON1), the prooxidant-antioxidant balance (PAB), the levels of superoxide anion radical (O2•–), the concentration of nitrite (NO2−) and the content of free protein thiol groups in the brain homogenates were evaluated. The PON1 and PAB activity were significantly reduced in almost all oxime-treated groups (p < 0.01 and p < 0.001, respectively). The concentrations of O2•– were significantly increased in the obidoxime-, K048-, K074- and K075-treated groups (p < 0.001), while the levels of NO2− was significantly decreased in asoxime-, obidoxime-, K074 and K075-treated rats (p < 0.01, p < 0.001, respectively). The content of Thiol groups was significantly elevated in all oxime-treated groups (p < 0.001). Continuing our previously published data, these results confirmed that applied K-oximes improved the oxidative status and further harmful systemic effects of rats after subacute administration
Surveillance of Corrected QT Interval-Prolonging Medications upon Admission throughout Hospitalization in a Tertiary Care Geriatric Ward
No full textObjective: Long QT syndrome (LQTS) poses a significant risk of torsade de pointes, particularly in older patients due to age-related changes in cardiac repolarization and increased susceptibility to medication-induced QTc interval prolongation. Despite the increased risk, data on medication-related LQTS remain limited, leading to this study on its prevalence, characteristics, and risk factors, along with QT-prolonging drug use in older patients. The study aimed to identify clinical and medication-related predictors of LQTS and evaluate the burden of co-prescribed QT-prolonging medications in this population. Subjects and Methods: This prospective study at a tertiary care hospital included initial and follow-up ECGs, with medication details were collected. Statistical analyses compared variables, including QTc intervals and medication use, between patients with and without LQTS. Results: The study included 128 adults aged 65 or older, with 27.3% presenting LQTS on admission, increasing to 42.2% after 7 days of hospitalization. Patients with LQTS had a higher prevalence of QTc interval-prolonging medications, list 1 medications, and atrial fibrillation. Laboratory changes and medication use were observed, with significant increases in QTc interval and list 1 medication administration. Male sex and amiodarone use were identified as predictors of LQTS during hospitalization. Conclusion: The study reports a high prevalence of prolonged QTc interval and LQTS in older inpatients. Proton pump inhibitors were frequently prescribed despite their QTc-prolonging potential. This underscores the need of close monitoring and awareness of QTc prolongation risks in older patients, advocating for routine ECG assessments and vigilant management of modifiable risk factors, especially the electrolytes.Peer-reviewed manuscript: [https://farfar.pharmacy.bg.ac.rs/handle/123456789/6024
Pioneering first-in-class HDAC-ROCK inhibitors as potential multitarget anticancer agents
No full textAim: With the aim of simultaneously modulating the epigenetic system and the protein kinase path
way, we selected the enzyme histone deacetylase (HDAC) and the Rho-associated protein kinases
(ROCK) as desired targets to develop potential multitarget anticancer agents with additional antimeta
static properties. We report here the rational design, synthesis, and biological evaluation of the first-in-
class HDAC/ROCK multitarget inhibitors in pancreatic ductal adenocarcinoma (PDAC) and triple-
negative breast cancer (TNBC).
Materials and methods: A molecular docking study performed with the Gold software was used to
develop HDAC/ROCK multitarget inhibitors. IC50 values were determined by enzyme assays. The
cytotoxicity, anti-migratory and anti-invasive properties of the inhibitors were evaluated using triple-
negative breast cancer cells (MDA-MB-231 and HCC 1973) and pancreatic ductal adenocarcinoma cells
(Panc-1 and MiaPaCa-2).
Results: C-9 showed significant inhibition of HDAC6, ROCK1 and ROCK2. At the same time, this compound
showed strong antiproliferative effects on MDA-MB-231, MiaPaCa-2 and Panc-1 cell lines with IC50 values of
5.81 μM, 3.87 μM and 19.57 μM. In addition, it demonstrated great anti-invasive and anti-migratory effects.
Conclusion: The findings of this study strongly suggest that the simultaneous inhibition of ROCK and
HDACs holds significant potential as a promising therapeutic strategy in the advancement of cancer
treatment
Treatment of urinary tract infections: study on patients' beliefs and attitudes
No full textThe present study investigated patients' opinions and attitudes regarding the use of antibiotics and plant-based products in the treatment of urinary tract infections (UTIs). The research was conducted as a cross-sectional study, using a validated questionnaire for data collection. The results indicate that the majority of respondents considered antibiotics (74.3%) and plant-based products (87.9%) to be effective in treating UTIs, while approximately half of the participants evaluated plant-based products as being more effective than antibiotics. Additionally, over 50% of respondents believed that plant-based products could be administered concomitantly with other medications. Regarding the treatments used, patients who exhibited UTI symptoms were treated with antibiotics in 63.9% of cases, while 78.6% also used plant-based products. Data analysis revealed that patients who perceived plant-based products as more effective than antibiotics were 40.4% less likely to use antibiotics and 138.2% more likely to opt for plant-based products. Furthermore, positive beliefs regarding the efficacy, safety, and compatibility of concomitant administration with other medications, along with access to adequate information, significantly increased the use of plant-based products.Studiul de față a investigat opiniile și poziția pacienților referitor la utilizarea antibioticelor și a produselor pe bază de plante
în tratamentul infecțiilor tractului urinar (ITU). Cercetarea a fost realizată sub forma unui studiu transversal, utilizând un
chestionar validat pentru colectarea datelor. Rezultatele indică faptul că majoritatea respondenților au considerat că
antibioticele (74,3%) și produsele din plante (87,9%) sunt eficiente în tratamentul ITU, în timp ce aproximativ jumătate dintre
participanți au evaluat produsele din plante ca fiind mai eficiente decât antibioticele. De asemenea, peste 50% dintre respondenți
au fost de părere că produsele din plante pot fi administrate concomitent cu alte medicamente.În ceea ce privește tratamentele
utilizate, pacienții care au prezentat simptome de ITU au fost tratați cu antibiotice în proporție de 63,9%, iar 78,6% dintre aceștia
au utilizat și produse din plante. Analiza datelor a evidențiat că pacienții care percep produsele din plante ca fiind mai eficiente decât
antibioticele au avut o probabilitate cu 40,4% mai mică de a utiliza antibiotice și cu 138,2% mai mare de a opta pentru produse
pe bază de plante. În plus, convingerile pozitive legate de eficacitatea, siguranța și compatibilitatea administrării concomitente cu
alte medicamente, alături de accesul la informații adecvate, au determinat o creștere semnificativă a utilizării produselor din plante
Antinociceptivni efekat P-cimena i cinamaldehida: povezanost sa L-arginin-no putem kod pacova
No full textBased on the previously known therapeutic properties of the active principles from
essential plant oils, we investigated the antinociceptive effects of p-cymene (PC) and
cinnamaldehyde (CNA) on carrageenan (CG)-induced inflammatory hyperalgesia
in female Wistar rats, as well as their relationship with the L-arginine-nitric oxide
pathway. Hyperalgesia was induced by intraplantar administration of CG (500 μg)
into the rat hind paw, lasting 6 hours. The electronic von Frey apparatus measured
the paw withdrawal threshold induced by pressure. Motor coordination in PC-treated
animals was assessed using the Rota-rod test. PC and CNA (5, 25, 50 mg/kg BW),
administered orally 50 minutes before CG, reduced CG-induced hyperalgesia, with
PC showing a significantly dose-dependent (p<0.05, p<0.01, p<0.001) and stronger
antinociceptive effect (p<0.001) than CNA. Compared to diclofenac (10 mg/kg), PC
(50 mg/kg) demonstrated superior antinociceptive activity (p<0.001), while CNA (50
mg/kg) had a lower effect (p<0.05, p<0.01, p<0.001). Co-administration of PC (5
mg/kg) or CNA (5 mg/kg) with NOS inhibitors L-NAME (5 mg/kg) or AG (0.3 mg/
kg) significantly enhanced the antinociceptive effect (p<0.01, p<0.001), with PC+L-
NAME showing greater potentiation (p<0.001) than PC+AG. L-ARG (10 mg/kg),
an NO donor, significantly reduced or reversed the antinociceptive effect of PC/
CNA+NOS inhibitors (p<0.05, p<0.01, p<0.001). In the Rota-rod test, PC (100 mg/
kg BW) did not impair motor coordination or cause CNS depression in female rats.
Given their significant antinociceptive effects on CG-induced hyperalgesia, the close
relationship between the L-arginine-NO system and their mechanism of action, and
the fact that PC does not adversely affect the CNS, both PC and CNA are promising
candidates for the development of new analgesic drugs in veterinary practiceNa osnovu prethodno poznatih terapeutskih svojstava aktivnih principa iz esencijal-
nih biljnih ulja, ispitivali smo antinociceptivne efekte p-cimena (PC) i cinamaldehida
(CNA) na karagenanom (CG)-indukovanu inflamatornu hiperalgeziju kod ženki paco-
va soja Wistar, kao i njihov odnos sa L-arginin-NO putem. Hiperalgezija je izazvana in-
traplantarnom aplikacijom CG (500μg) u zadnju šapu pacova, u trajanju od 6 sati. Prag
povlačenja šape, usled pritiska, merio se elektronskim von Frey aparatom. Motorička
koordinacija kod pacova tretiranih PC-om procenjivana je Rota-rod testom. PC i CNA
(5, 25, 50mg/kg TM), primenjeni oralno, 50 minuta pre CG, smanjili su CG-induko-
vanu hiperalgeziju, pri čemu je PC pokazao značajan dozno-zavisan (p<0.05, p<0.01,
p<0.001) i jači antinociceptivni efekat (p<0,001) u poređenju sa CNA. U poređenju
sa diklofenakom (10mg/kg), PC (50mg/kg) je pokazao superiornu antinociceptiv-
nu aktivnost (p<0,001), dok je CNA (50mg/kg) imao slabiji efekat (p<0,05, p<0,01,
p<0,001). Istovremena primena PC (5mg/kg) ili CNA (5mg/kg) sa NOS inhibitorima L-NAME (5mg/kg) ili AG (0,3mg/kg) značajno je pojačala antinociceptivni efekat
(p<0,01, p<0,001), pri čemu je PC+L-NAME pokazao veće pojačanje (p<0,001) u
poređenju sa PC+AG. L-ARG (10mg/kg), NO donor, značajno je smanjio ili poni-
štio antinociceptivni efekat PC/CNA+NOS inhibitora (p<0,05, p<0,01, p<0,001). U
Rota-rod testu, PC (100mg/kg TM) nije narušio motoričku koordinaciju niti izazvao
depresiju CNS-a kod ženki pacova. S obzirom na njihove značajne antinociceptivne
efekte na CG-indukovanu hiperalgeziju, blisku povezanost njihovog mehanizma de-
lovanja sa L-arginin-NO sistemom, kao i činjenicu da PC nema štetne efekte na CNS,
PC i CNA su obećavajući kandidati za razvoj novih analgetika u veterinarskoj praksi
Global DNA Methylation in Poorly Controlled Type 2 Diabetes Mellitus: Association with Redox and Inflammatory Biomarkers
No full textAlthough emerging evidence suggests that epigenetic mechanisms contribute to the pathogenesis and progression of type 2 diabetes mellitus (T2DM), data remain limited for patients with suboptimal metabolic control. The aim of this study was to assess global DNA methylation in patients with poorly controlled T2DM and to identify diabetes-related factors associated with DNA methylation levels. The study included 107 patients and 50 healthy controls. Global DNA methylation (5mC) was measured by UHPLC-DAD method. Pro-oxidant and antioxidant biomarkers, advanced glycation end-products, high-sensitivity C-reactive protein (hsCRP) and complete blood count were determined and leukocyte indices calculated. Patients had a significantly lower 5mC than controls (3.56 ± 0.31% vs. 4.00 ± 0.68%; p < 0.001), with further reductions observed in those with longer disease duration and diabetic foot ulcers. Oxidative stress and inflammatory biomarkers were higher in the patient group. DNA hypomethylation was associated with a higher monocyte-to-lymphocyte ratio and hsCRP, pro-oxidant–antioxidant balance, ischemia-modified albumin, and advanced oxidation protein products levels. Conversely, 5mC levels showed positive correlations with total antioxidant status and total sulfhydryl groups. Principal component analysis identified five key factors: proinflammatory, pro-oxidant, aging, hyperglycemic, and antioxidant. The pro-oxidant factor emerged as the sole independent predictor of global DNA hypomethylation in T2DM (OR = 2.294; p = 0.027). Our results indicate that global DNA hypomethylation could be a biomarker of T2DM progression, reflecting the complex interactions between oxidative stress, inflammation, and epigenetic modifications in T2DM
Promoting safe medication use during breastfeeding: uncontrolled interventional before-after study in community pharmacies
No full textBackground: Due to a lack of information or unreasonable fear of the effects of medication, breastfeeding mothers either stop taking medication or discontinue/interrupt breastfeeding while taking medication. Aim: The aim of the study was to investigate and evaluate the role of community pharmacists in promoting safe medication use among breastfeeding mothers through evidence-based interventions. Methods: The prospective uncontrolled interventional before- and after- study was conducted in 2022. The first phase involved a one-day comprehensive training session for community pharmacists. The second phase involved the provision and documentation of pharmaceutical care services. Findings and discussion: A total of 1243 breastfeeding mothers participated in the study. Allergy, pain, sore throat, cough and urinary tract infections were the most common complaints. A total of 746 mothers (60.0 %) had been prescribed a medication while breastfeeding. The most commonly used medications were anti-infectives (15.1 %) and medications for respiratory system (10.9 %). Just over half of mothers stated that they had not received specific advice from their doctor about taking medication while breastfeeding (52.8 %). Pharmacists offered various interventions, such as dispensing a prescribed medication accompanied by breastfeeding counselling (41.8 %), recommending a change to a medication or supplement for safety reasons (15.3 %) and tailored recommendations for monitoring the infant (40.1 %). Pharmacist interventions, including the use of alternative medications/supplements, resulted in a decrease in the frequency of high-risk medications (from 1 % to 0.3 %, p < 0.001). Conclusion: Community pharmacists play an important role in the care of breastfeeding mothers. In addition to providing breastfeeding counselling and support, community pharmacists significantly improved the safety of medications taken by using relevant sources of information
Towards Sustainable Food Waste Management in Serbia: A Review of Challenges, Gaps, and Future Perspectives
No full textFood waste is a pressing global problem with significant environmental, economic and social impacts. This review examines the state of food waste management in Serbia and contextualizes the challenges and opportunities in a global and EU framework. In the Republic of Serbia, an estimated 247,000 tons of food is wasted annually, indicating critical gaps in waste management infrastructure, consumer awareness and missing legislation. While existing policies address general waste management, there is a lack of targeted measures for food waste prevention and resource recovery. The overview recommends aligning Serbian policy with an EU legislative frame, introducing extended producer responsibility and promoting public–private cooperation to improve food donation and recycling. This is the first comprehensive study specifically addressing food waste management in Serbia and assessing its compliance with European and global best practices. By comparing Serbia’s current status with established international models, this paper identifies critical gaps and proposes actionable strategies to improve the efficiency and sustainability of the food waste management system in Serbia. These include investment in infrastructure, public awareness campaigns and the use of innovative digital tools to reduce waste and support a circular economy
Glucosinolate-Derived Metabolites from Barbarea vulgaris (Brassicaceae): Evaluation of Antimicrobial, Antioxidant, and Anti-Inflammatory Potentials
No full textGlucosinolate-derived metabolites play central roles in plant defense and are increasingly recognized for their pharmacological importance. Barbarea vulgaris produces a structurally diverse set of such compounds, yet their biological activities remain insufficiently explored. In this study, natural metabolites and their synthetic analogues were evaluated for antimicrobial, antibiofilm, antioxidant, and anti-inflammatory properties. Antimicrobial activity was assessed against human and plant pathogens by determining minimum inhibitory and minimum microbicidal concentrations, antibiofilm potential was examined using microplate assays, and radical scavenging activity was measured by DPPH and ABTS assays. In addition, the compounds were screened for inhibitory effects on lipoxygenase (LOX) and cyclooxygenase-2 (COX-2). Phenolic derivatives, particularly methyl-4-hydroxyphenylethyl dithiocarbamate (2) and 2-(4-hydroxyphenyl)ethyl isothiocyanate (8), exhibited notable in vitro antibacterial activity (MIC 0.312–1.25 mg mL−1 against E. coli ATCC 25922 and S. aureus ATCC 25923) and detectable antibiofilm effects. Racemic barbarin (4) preferentially inhibited LOX, underscoring its potential as an anti-inflammatory scaffold, whereas COX-2 inhibition was weak across all tested compounds. None of the metabolites showed radical scavenging activity, suggesting that their effects rely on enzyme inhibition or microbial interactions rather than nonspecific antioxidant mechanisms. This study provides an integrated evaluation of B. vulgaris metabolites, highlighting their ecological role in plant defense and their potential as scaffolds for novel antimicrobial and anti-inflammatory agents
Transcriptomic, Redox Status and Adipocytokine Profiles in Metabolic Dysfunction-Associated Steatotic Liver Disease: Impact of Coexisting Type 2 Diabetes
No full textBackground: Metabolic dysfunction-associated steatotic liver disease (MASLD) commonly
coexists with type 2 diabetes (T2D), but their independent contributions to redox imbalance,
inflammation and immune signaling remain uncertain. Objectives: This study aimed to
evaluate whether the presence of MASLD alone, and the presence of T2D within MASLD,
are independently associated with high-risk profiles of oxidative/antioxidant markers,
peripheral blood mononuclear cell (PBMC) gene expression and adipocytokines. Methods:
A total of 190 participants were categorized via abdominal ultrasound as controls ( n = 46 ),
MASLD (n = 83) or MASLD with T2D (n = 61). Measurements included advanced oxidation
protein products (AOPP) and paraoxonase-1 (PON1) activity in serum; messenger ribonu-
cleic acids expression of cluster of differentiation 36 (CD36), Toll-like receptor 9 (TLR9),
and glutathione peroxidase-1 in PBMC; and adiponectin, leptin, and resistin in plasma.
Biomarker values were adjusted and statistical comparisons among groups were performed
using the Quade test. Subsequently, biomarkers were stratified into tertiles to examine
associations between high-risk biomarker levels and the presence of MASLD or T2D in
patients with MASLD using multivariate binary logistic regression. Results: Multivariate
analysis showed that MASLD presence was independently associated with both increased
AOPP and decreased resistin levels in the circulation. Furthermore, T2D presence in pa-
tients with MASLD was independently associated with increased CD36 and decreased
TLR9 gene expression in PBMCs, as well as elevated circulating leptin levels. Conclusions:
Collectively, these findings underscore the complex interplay between oxidative stress,
insulin resistance, inflammation, and immune signaling in the pathogenesis of MASLD,
which are fundamental factors contributing to this condition