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Potential QT-prolonging drug-drug interactions in cardiovascular disease patients
No full textThe study aimed to assess the prevalence and characteristics of potential drug-drug interactions (pDDIs) that increase the risk of QT prolongation, in a population of cardiovascular disease patients. An observational retrospective study was conducted at a cardiology ward. A total of 351 patients were included in the analysis, with almost equal gender distribution (female 48.4%) and mean age 70±10 years. In the total set of tested drug pairs (5620), QT-prolonging pDDIs were identified in 13 drug pairs on admission. The highest frequency was observed for ciprofloxacin (involved in 5 pDDIs), followed by propafenone (4 pDDIs) and beta2-agonists (4 pDDIs). The pharmacodynamic mechanism was involved in all pDDIs. The study revealed a low prevalence of QT-prolonging pDDIs on admission to the cardiology ward, about 3% in the studied population. However, given that underlying heart disease is a significant risk factor for the occurrence of QTc prolongation, the additional risk for acquired QT prolongation should not be neglected. Due to serious consequences caused by QT prolongation and TdP, the key role of health professionals is to identify predisposed patients and to recognize pDDIs involving QT-prolonging agents. Hence, patients’ modifiable risk factors for QT prolongation should be minimized, if not eliminated
Endothelial-Protective Actions of Diethylether Extract from Gentiana kochiana and Xanthone Gentiacaulein Against Oxidized LDL-Induced Injury—In Vitro Evaluation
No full textEndothelial dysfunction is an early pathophysiological event in atherosclerosis. The endothelial-protective abilities of diethylether extract (EE) from the Gentiana kochiana (Gentianaceae) herb and its main component, xanthone aglycone gentiacaulein (GC), were evaluated in an oxidized low-density lipoprotein (oxLDL)-treated EA.hy926 endothelial cell line. The EE and GC actions were assessed using cell viability assays, flow cytometry, immunoblot, DPPH, NBT, TBARS, conjugated diene formation, and Griess tests. Both EE and GC prevented oxLDL-induced apoptosis by reducing intracellular reactive oxygen species levels, mitochondrial depolarization, and caspase activation in EA.hy926 cells. EE and GC dose-dependently diminished oxLDL-induced cellular lipid peroxidation. In cell-free conditions, EE moderately scavenged superoxide anions and had no affinity toward DPPH radicals, GC did not interact with either of investigated free radicals, while both EE and GC effectively delayed Cu²⁺-induced LDL oxidation. EE and GC upregulated oxLDL-suppressed protective Akt/CREB/eNOS and ERK signals and restored oxLDL-reduced nitric oxide levels. Therefore, EE and GC effectively counteract oxLDL-induced endothelial apoptosis by reducing oxidative stress, promoting mitochondrial recovery, and enhancing the prosurvival Akt/CREB/eNOS axis and ERK activity. Our study is the first to demonstrate that xanthone-rich EE from aerial parts of G. kochiana and xanthone GC alleviate oxLDL-induced endothelial cell injury, underscoring their potential for cardiovascular protection
Nivoi galektina-3 u serumu i faktora rasta fibroblasta-23 u odnosu na dijabetes tip 2 i kardiovaskularni rizik
No full textBackground: The clinical utility of galectin-3 and fibroblast
growth factor 23 (FGF-23) needs to be further explored
since previous studies show divergent results in relation to
type 2 diabetes (T2D) and cardiovascular risk. Hence, the
aim of this research was to explore galectin-3 and FGF-23
in relation to T2D, as well as to examine the potential asso-
ciation of these biomarkers with atherosclerotic
cardiovascular disease (ASCVD) risk score in Montenegrin
adults.
Methods: A total of 35 T2D patients and 36 controls were
consecutively enrolled. Serum galectin-3 and FGF-23 were
determined by ELISA. The ASCVD risk score was calculat-
ed.
Results: Higher serum galectin-3 levels were shown in T2D
patients (p=0.016) in comparison with the control group.
The increase in galectin-3 levels for 1 ng/mL showed an
8.5% higher probability of T2D occurrence (OR=1.085,
p=0.015). FGF-23 levels did not differ between the control
and the T2D group. Serum galectin-3 correlated with FGF-
23 (r=0.390, p=0.001). Both galectin-3 (r=0.306,
p=0.010) and FGF-23 (r=0.332, p=0.005) correlated
with ASCVD risk score in bivariate Spearman’s correlation
analysis, but these correlations were not retained in binary
logistic regression analysis.
Conclusions: Serum galectin-3 levels but not FGF-23 are
higher in T2D patients. Serum galectin-3 correlated with
FGF-23. Although both biomarkers were correlated with
the ASCVD risk score, further statistical analysis did not
confirm their independent associations with cardiovascular
risk. Studies with a large sample size are needed to further
explore this issue.Uvod: Klinička primena galektina-3 i fibroblastnog faktora rasta-23 (FGF-23) zahteva dodatna istraživanja s obzirom da su dosadašnje studije pokazale oprečne rezultate u odnosu na dijabetes tip 2 i kardiovaskularni rizik. S tim u vezi, cilj ovog istraživanja je bio da ispita galektin-3 i FGF-23 kod pacijenata sa dijabetesom tip 2, kao i da se ispita potencijalna povezanost ovih biomarkera sa skorom aterosklerotskog kardiovaskularnog rizika (ASCVD) u adultnoj crnogorskoj populaciji. Metode: Ukupno 35 pacijenata obolelih od dijabetesa i 36 ispitanika koji su činili kontrolnu grupu su konsekutivno uključeni u istraživanje. Serumske vrednosti galektina-3 and FGF-23 su merene ELISA metodom. ASCVD skor rizika je izračunat. Rezultati: Veče serumske vrednosti galektina-3 su zabeležene kod pacijenata obolelih od dijabetesa tip 2 (p=0,016) u poređenju sa kontrolnom grupom. Porast nivoa galektina-3 za 1 jedinicu pokazao je 8,5% veču vjerovatnoču za pojavu dijabetesa (OR=1,085, p=0,015). Vrednosti FGF-23 se nisu razlikovale među ispitivanim grupama. Serumske vrednosti galektina-3 su korelirale sa FGF-23 (p=0,390, p= 0,001 ). I galektin-3 ( p = 0,306, p= 0,01 0) i FGF-23 (p =0,332, p=0,005) su korelirali sa AscVd skorom rizika u Spearman-ovoj korelacionoj analizi, ali ove korelacije nisu zadržane u binarnoj logističkoj regresionoj analizi. Zaključak: Serumske vrednosti galektina-3, ali ne i FGF-23 su veče kod pacijenata obolelih od dijabetesa tip 2. Serumske vrednosti galektina-3 su korelirale sa FGF-23. Premda su oba biomarkera korelirala sa ASCVD skorom rizika, dublja statistička analiza nije potvrdila nezavisnu povezanost ovih biomarkera sa kardiovaskularnim rizikom. Potrebna su istraživanja na večem broju ispitanika da dodatno istraže ulogu ovih biomarkera u dijabetesu tip 2
The influence of the loading procedure on the properties of nanoemulsions with the patented ligand GL-II-73
No full textPassive API loading is a loading technique that is particularly useful in early formulation development when screening potential carriers. It also enables material savings, ..
A Comprehensive Overview of Antibacterial Agents for Combating Multidrug-Resistant Bacteria: The Current Landscape, Development, Future Opportunities, and Challenges
No full textBackground/Objectives: Antimicrobial resistance poses a major public health challenge. The World Health Organization has identified 15 priority pathogens that require prompt development of new antibiotics. This review systematically evaluates the antibacterial resistance of the most significant bacterial pathogens, currently available treatment options, as well as complementary approaches for the management of infections caused by the most challenging multidrug-resistant (MDR) bacteria. For carbapenem-resistant Gram-negative bacteria, treatment options include combinations of beta-lactam antibiotics and beta-lactamase inhibitors, a novel siderophore cephalosporin, known as cefiderocol, as well as older antibiotics like polymixins and tigecycline. Treatment options for Gram-positive bacteria are vancomycin, daptomycin, linezolid, etc. Although the development of new antibiotics has stagnated, various agents with antibacterial properties are currently in clinical and preclinical trials. Non-antibiotic strategies encompass antibiotic potentiators, bacteriophage therapy, antivirulence therapeutics, antimicrobial peptides, antibacterial nanomaterials, host-directed therapy, vaccines, antibodies, plant-based products, repurposed drugs, as well as their combinations, including those used alongside antibiotics. Significant challenges exist in developing new antimicrobials, particularly related to scientific and technical issues, along with policy and economic factors. Currently, most of the alternative options are not part of routine treatment protocols. Conclusions and Future Directions: There is an urgent need to expedite the development of new strategies for treating infections caused by MDR bacteria. This requires a multidisciplinary approach that involves collaboration across research, healthcare, and regulatory bodies. Suggested approaches are crucial for addressing this challenge and should be backed by rational antibiotic use, enhanced infection control practices, and improved surveillance systems for emerging pathogens
The converging roles of microRNAs and lipid metabolism in atherosclerotic cardiovascular disease and cancer
No full textCancer and atherosclerotic cardiovascular disease (ASCVD) are the main causes of mortality worldwide. The complex relationship between these two diseases has long puzzled scientists, with lipid metabolism emerging as a promising area for research and therapy of both diseases. Cholesterol accumulation promotes the formation of atherosclerotic plaques, while dysregulated lipid metabolism favours the progression of tumours. MicroRNAs (miRNAs) have been identified as key post-transcriptional regulators of lipid metabolism, influencing cholesterol synthesis and efflux, fatty acid oxidation and lipoprotein function. MiR-33, miR-144 and miR-122 modulate important target proteins such as sterol regulatory element-binding proteins (SREBPs), ATP-binding cassette transporter A1 (ABCA1) and peroxisome proliferator-activated receptor gamma (PPARγ) and thus control metabolic reprogramming in both cancer and ASCVD. In cancer, miRNA-mediated lipid reprogramming promotes proliferation, immune evasion and metastasis, whereas dysregulated miRNAs in ASCVD contribute to foam cell formation, chronic inflammation and vascular dysfunction. The dual role of miRNAs, acting either as tumour suppressors or oncogenes, highlights their complex impact on lipid-related pathophysiology. Moreover, miRNA-based therapeutic strategies, including antagomirs and miRNA mimics, hold promise for targeted intervention in both diseases, which could reduce ASCVD risk in cancer patients and improve long-term outcomes. Understanding the intricate interactions between miRNAs, lipid metabolism and disease progression provides new insights into the overlapping molecular mechanisms of cancer and ASCVD and opens new therapeutic opportunities in the field of cardio-oncology
Composition and genotoxic activity of methanolic extracts of Teucrium montanum L.
No full textTeucrium montanum L. (Lamiaceae) is a perennial plant rich in biologically active components
such as polyphenolic compounds and terpenoids. Previous studies have confirmed the
beneficial effects of phenolic acids and flavonoids, which are known for their strong antioxidant
activity, as well as the antimicrobial, antifungal, antiproliferative and anti-inflammatory
effects of T. montanum. In this study, methanolic extracts of T. montanum from the flowering
aerial parts collected from two ecologically different localities were used. The composition was
determined by high performance liquid chromatography (HPLC). The potential genotoxic activity
of different concentrations (12.5, 25, 50, 100 and 200 μg/mL) of both extracts on human
peripheral blood mononuclear cells (PBMCs) was tested in vitro using the comet assay.
The HPLC results showed the presence of various phenolic acids, chlorogenic and caffeic acid,
the flavonoids luteolin and luteolin glucoside, quercetin glucoside and quercetin heteroside,
and apigenin. The dominant component in sample 1 was phenolic acid, which was not identified
in the second sample. In sample 2, the flavonoid luteolin glucoside was the most abundant
component, which could not be detected in sample 1. Quercetin heteroside was found
in sample 1, while it was only present in trace amounts in sample 2. The results of our study
show that there was no increase in DNA damage in the samples of PBMCs treated with both
extracts of T. montanum at any of the concentrations used. The results obtained suggest further
investigation of the composition of T. montanum extracts and the quantification of their
components, as well as an investigation of their antigenotoxic potential
Genotoxic and antigenotoxic assessment of functionalized TiO2 powder with Dihydroquercetin
No full textTitanium dioxide (TiO2), a widely studied wide-bandgap photocatalyst, has broad applications
in the biomedical field. Dihydroquercetin (DHQ), a naturally occurring flavonoid, is an efficient
scavenger of reactive oxygen species, with a wide range of therapeutic effects. This study’s
objective was to screen potential adverse/beneficial impacts on the genome sensitivity of
TiO2-based ICT complex with DHQ. Genotoxicity assessment, by using the comet assay,
demonstrated that pristine TiO2 at various concentrations (1, 2, 5, 10, and 20 mg/mL) induced
statistically significant DNA damage in MRC-5 cells, while TiO2/DHQ did not, indicating that
DHQ mitigates the genotoxic potential of TiO2. Furthermore, 1, 2, 5, 10, and 20 mg/mL
TiO2/DHQ showed antigenotoxic effects by reducing H2O2-induced DNA damage in MRC-5
cells and by supporting its protective role against oxidative stress. These findings suggest that
TiO2-based ICT complex with DHQ can potentially serve as a safe, non-toxic agent. Further
assessment of its bioactivity is required
Nonchemotherapy drug-induced cytopenias: A cost-of-illness study using the microcosting methodology based on real-world data
No full textAims: Our study aimed to determine the healthcare utilization and costs of nonchemotherapy drug-induced cytopenias and analyse the main drivers of costs. Methods: This cost-of-illness study was conducted using the microcosting (bottom-up) approach based on real-world data. Data on the patients who developed leucopenia, anaemia or thrombocytopenia as nonchemotherapy drug-induced blood disorders were extracted from records of the inpatients treated in a tertiary care university hospital. Results: The study included 46, 71 and 80 cases of leucopenia, anaemia and thrombocytopenia, respectively. Leucopenia had the highest costs per case (average: 200 928.4, median: 176 078.4 Serbian dinars [RSD], interquartile range: 171 223.4 RSD), followed by thrombocytopenia (average: 115 065.2, median: 89 732.4 RSD, interquartile range: 77 755.9 RSD) and anaemia (average: 109 502.5, median: 90 267.3 RSD, interquartile range: 74 225.1 RSD). These costs expressed as Gross Domestic Product per capita based on purchasing power parity were 6.97, 2.85 and 2.84% for leucopenia, anaemia and thrombocytopenia, respectively. In leucopenia, 48.9% of the costs were the costs of drugs, while in anaemia and thrombocytopenia, the majority of the costs were due to the length of hospitalization (38.6 and 34.7%, respectively). The factors with the greatest influence on the total costs of anaemia and thrombocytopenia were the length of hospitalization and the number of computed tomography scans, while the cost of leucopenia treatment was most influenced by survival status, age and the number of laboratory tests. Conclusions: Our study showed that the use of healthcare services and costs caused by nonchemotherapy drugs are considerable. Proactive strategies to manage and prevent drug-induced cytopenias should be considered
Efficacy of individualized escitalopram dosing based on plasma level monitoring: findings from a cross-sectional study
No full textEscitalopram, a widely used antidepressant, exhibits considerable interindividual variability in
metabolism and response, which is primarily influenced by CYP2C19 and CYP2D6
polymorphisms. The therapeutic plasma range is 15-80 ng/ml, with optimal exposure at 25-50
ng/ml. With the standard dosage of 10 mg/day, genetic variability is often neglected, leading to
suboptimal results. The aim of this prospective cross-sectional study is to investigate the impact
of TDM-guided and pharmacogenetically adjusted dosing of escitalopram on patient outcomes
in real-life clinical practice. In addition, the study will investigate the impact of CYP2C19 and
CYP2D6 genotypes on optimizing drug exposure. The study involved 89 patients (18-65 years)
diagnosed with depression and treated at the Institute of Mental Health in Belgrade. After two
weeks of taking 10 mg/day of escitalopram, plasma levels were measured and the dose was
adjusted based on TDM. In patients with levels <25 ng/ml, the dose was increased, while in
patients with levels >50 ng/ml, the dose was reduced. Plasma levels were quantified by
HPLC-MS/MS. Genotyping is planned for the next study phase. At baseline, only 19 patients
were in the therapeutic range, 28 were slightly underdosed, 41 were significantly underdosed
and one was overdosed. After TDM-based adjustments, 37 patients reached the ideal exposure,
the proportion of underdosed patients decreased by 3.4-fold, and the proportion of optimally
dosed patients almost doubled (1.9-fold). A standard dose of 10 mg/day is insufficient for most
patients. TDM-guided dosing significantly improved target exposure and reduced underdosing.
Further genetic and biochemical analyzes will improve personalized antidepressant therapy