Apigenin (4′,5,7-trihydroxyflavone) (Api) is an important component of the human diet, being distributed in a wide number of fruits, vegetables and herbs with the most important sources being represented by chamomile, celery, celeriac and parsley. This study was designed for a comprehensive evaluation of Api as an antiproliferative, proapoptotic, antiangiogenic and immunomodulatory phytocompound. In the set experimental conditions, Api presents antiproliferative activity against the A375 human melanoma cell line, a G2/M arrest of the cell cycle and cytotoxic events as revealed by the lactate dehydrogenase release. Caspase 3 activity was inversely proportional to the Api tested doses, namely 30 μM and 60 μM. Phenomena of early apoptosis, late apoptosis and necrosis following incubation with Api were detected by Annexin V-PI double staining. The flavone interfered with the mitochondrial respiration by modulating both glycolytic and mitochondrial pathways for ATP production. The metabolic activity of human dendritic cells (DCs) under LPS-activation was clearly attenuated by stimulation with high concentrations of Api. Il-6 and IL-10 secretion was almost completely blocked while TNF alpha secretion was reduced by about 60%. Api elicited antiangiogenic properties in a dose-dependent manner. Both concentrations of Api influenced tumour cell growth and migration, inducing a limited tumour area inside the application ring, associated with a low number of capillaries.
Background Geriatric falls are leading causes of hospital trauma admissions and injury-related deaths. Medication use is a crucial element among extrinsic risk factors for falls. To reduce fall risk and the prevalence of adverse drug reactions, potentially inappropriate medication (PIM) lists are widely used. Objective Our aim was to investigate the possible predictors of geriatric falls annualized over a 5-year-long period, as well as to evaluate the medication use of nursing home residents. Setting Nursing home residents were recruited from the same institution between 2010 and 2015 in Szeged, Hungary. Method A retrospective epidemiological study was performed. Patient data were analysed for the first 12 months of residency. Chi-squared test and Fisher's-test were applied to compare the categorical variables, Student's t test to compare the continuous variables between groups. Binary logistic regression analysis was carried out to determine the association of falls with other variables found significant in univariate analysis. Microsoft Excel, IBM SPSS Statistics (version 23) and R (3.2.2) programs were used for data analysis. Main outcome measure Falls affected by age, gender, number of chronic medications, polypharmacy, PIM meds. Results A total of 197 nursing home residents were included, 150 (76.2%) women and 47 (23.8%) men, 55 fallers (annual fall prevalence rate was 27.9%) and 142 non-fallers. Gender was not a predisposing factor for falls (prevalence in males: 23.4 vs 29.3% in females, p > 0.05). Fallers were older (mean years ± SD; 84.0 ± 7.0) than non-fallers (80.1 ± 9.3, p < 0.01). The age ≥80 years was a significant risk factor for falls (p < 0.001). The number of chronic medications was higher in male fallers (12.4 ± 4.0) than in non-fallers (6.9 ± 4.2, p < 0.001). Polypharmacy (taking four or more chronic medications) was a significant risk factor of falls (p < 0.01). Those PIMs carrying fall risk were taken by 70.9% of fallers and 75.3% of non-fallers (p > 0.05). Taking pantoprazole, vinpocetine or trimetazidine was a significant risk factor for falls. Conclusion Older age, polypharmacy and the independent use of pantoprazole, vinpocetine, and trimetazidine were found to be major risk factors for falls. Further real-life epidemiological studies are necessary to confirm the role of particular active agents, and to help professionals prescribe, evaluate and review geriatric medication use.
Ephedra alata Decne. belongs to the Ephedraceae family. It is a species of Ephedra that grows mostly in the desert. Today, the main importance of Ephedra species in the medical field is due to the presence of the alkaloids derived from phenyl-alanine, which act on the sympathetic nervous system as a sympathomimetic. The aim of this study was to conduct a phytochemical characterization of the hydroalcoholic extract of the aerial part of Ephedra alata Decne., which is indigenous to Tunis, that involves the total phenolic content, individual phenolic content, and antioxidant activity as well as a biological screening for the evaluation of the antimicrobial, antifungal, antiproliferative, pro-apoptotic, and cytotoxic potential against the MCF-7 breast cancer cell line. The results show that the hydroalcoholic extract contains polyphenolic phytocompounds (156.226 ± 0.5 mgGAE/g extract) and elicits antioxidant activity (7453.18 ± 2.5 μmol Trolox/g extract). The extract acted as a bacteriostatic agent against all tested bacterial strains, but was bactericidal only against the Gram-positive cocci and Candida spp. In the set experimental parameters, the extract presents antiproliferative, pro-apoptotic, and cytotoxic potential against the MCF-7 human breast cancer cell line.
Chamomile, parsley, and celery represent major botanical sources of apigenin, a well-known flavone with chemopreventive properties. The aim of this study was to assess the phytochemical composition, antioxidant, and anti-inflammatory potential of methanol extracts obtained from chamomile, parsley, and celery collected from Romania, as well as the biological activity against A375 human melanoma and human dendritic cells. Results have shown that all three extracts are rich in polyphenolic compounds and flavonoids, and they generate a radical scavenger capacity, iron chelation potential, as well as lipoxygenase inhibition capacity. Chamomile and celery extracts present weak antiproliferative and pro-apoptotic properties in the set experimental conditions, while parsley extract draws out significant pro-apoptotic potential against A375 human melanoma cells. Parsley and chamomile extracts affected the fibroblast-like morphology of the screened tumor cell line. On the other hand, chamomile and celery extracts abrogated the expansion of LPS-activated dendritic cells, while the metabolic activity was attenuated by stimulation with celery extract; chamomile and parsley extracts had no effect upon this parameter. Chamomile and parsley extracts incubation with naive dendritic cells did not trigger cytokine secretion (TNF-alpha, IL-6, IL-10), but celery extract stimulation significantly reduced the anti-inflammatory, cytokine IL-10.
Aims To analyse glucose‐lowering drug utilization, focusing on the novel glucose‐lowering drug groups dipeptidyl peptidase‐4 inhibitors, glucagon‐like peptide‐1 receptor agonists and sodium‐glucose co‐transporter‐2 inhibitors, and the financial burden they entail. Methods Crude reimbursed national drug utilization and expenditure data for the entire population of Hungary were obtained from the National Health Insurance Fund for the study period: 2008 to 2017. Data were analysed using the WHO's Anatomical Therapeutic Chemical Classification/defined daily dose system and were expressed in defined daily dose per 1000 inhabitants per day. Results Total glucose‐lowering drug consumption in Hungary showed an 18% increase over the study period, reaching 74.7 defined daily doses per 1000 inhabitants per day, while novel glucose‐lowering drug use increased to 11.7 defined daily doses per 1000 inhabitants per day (16% of total glucose‐lowering drug use) by 2017. Dipeptidyl‐peptidase 4 inhibitor consumption grew to 7.4 defined daily doses per 1000 inhabitants per day by 2017. The most widely used dipeptidyl‐peptidase 4 inhibitor was sitagliptin. Glucagon‐like peptide‐1 receptor agonists were used the least, but by 2017 rose to 1.5 defined daily doses per 1000 inhabitants per day, led by liraglutide. Sodium‐glucose co‐transporter‐2 inhibitors appeared in the utilization data in 2014 and their consumption, mainly empagliflozin, reached 2.8 defined daily doses per 1000 inhabitants per day by 2017. The total expenditure on glucose‐lowering drugs increased 94% between 2008 and 2017, and the total cost of novel glucose‐lowering drug utilization comprised 44% of the total glucose‐lowering drug expenditure in 2017. Conclusions Both the use of and the financial burden posed by novel glucose‐lowering drugs in Hungary increased steadily between 2008 and 2017. This increase is expected to continue.
The aging population in developed countries is a growing problem nowadays. The burden on healthcare is particularly high, since the prevalence of the diseases, especially chronic diseases increases with age. Prevalence of polypharmacy is common among elderly patients. While comorbidities require usage of several active agents with evidence based indication, polypharmacy increases the likelihood of interactions and adverse drug reactions, reduces patient compliance, affects quality of life and puts a significant financial burden on the patient and society. In order to reduce drug-related problems among the elderly, different lists of potentially inappropriate drugs and doses were created. One of the earliest known lists is the "Beers criteria". The use of listed drugs is risky and not recommended for elderly patients. Following foreign examples, a list was compiled and adapted to the Hungarian drug spectrum based on the main concerns and alternative therapeutic suggestions.
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