Acta Pharmaceutica最新文献

Glucocorticoids are a group of drugs increasingly used in modern medical practice due to their pronounced anti--inflammatory and immunosuppressive properties. In this study, prednisolone disodium phosphate and prednisolone acetate were analysed, with the aim of developing and validating an HPLC method in accordance with ICH Q2(R2) guidelines and quantifying their content in the active pharmaceutical ingredient powder and a model in--house sample. By applying the HPLC-DAD method with gradient elution, effective separation of the analytes was achieved. The method met all validation parameter requirements. The obtained results showed that the content of both analytes in the tested samples (bulk API powders and in-house prepared model formulation) was within the prescribed limits according to current pharmacopoeial standards. The proposed HPLC-DAD method was assessed for its applicability and environmental profile utilizing a range of green and blue metric tools. This comprehensive evaluation confirms that the method adheres to green analytical principles, making it suitable for sustainable pharmaceutical analysis.

This double-blind randomised controlled trial aimed to evaluate the efficacy of an emollient cream with and without 1 % supercritical CO₂ extract of Calendula officinalis in contact dermatitis. Twenty healthy volunteers without pre-existing dermatological conditions participated in this single-centre study. Each participant's forearm was divided into three test sites: control (no treatment), placebo (base emollient), and intervention (calendula cream). The study employed random allocation of test sites using Microsoft Excel software. Both investigators and participants were blinded to the treatment assignments. The main outcomes were changes in skin hydration and transepidermal water loss (TEWL), measured with non-invasive probes (Corneometer CM 825, Tewameter TM 300), and erythema measured by Mexameter MX 18. Following irritant exposure, all sites showed increased TEWL and reduced hydration, confirming skin barrier impairment. The intervention site demonstrated significantly greater hydration compared with both the control (p = 0.017) and placebo sites (p = 0.035) on day 4, with this improvement persisting on day 8 (p = 0.043). TEWL values at the intervention site were significantly lower than control on day 3 (p = 0.022), indicating faster barrier recovery. No significant differences in erythema were observed between groups, and no adverse events occurred. Results of this study indicate that the addition of 1 % Calendula officinalis extract to an emollient cream enhanced skin hydration and accelerated recovery after irritant exposure, suggesting potential benefit in managing contact dermatitis with non-pharmacological skincare formulations.

This study aimed to examine the motility, biofilm production, endotoxin release, and antibiotic resistance of 81 Ralstonia pickettii isolates collected from different pharmaceutical water systems in Croatia. Swimming and twitching motility were detected in all isolates, while swarming was not observed. Biofilm production was detected in approximately 40 % of the isolates under the tested conditions. Notably, extracellular polymeric substance (EPS) production was a common trait among all isolates. Endotoxin production was detected with the Limulus Amoebocyte Lysate test. Antibiotic susceptibility testing revealed consistent resistance to colistin, as well as significant resistance rates to β-lactam antibiotics, ertapenem, amoxicillin/clavulanic acid, ticarcillin and ampicillin. High susceptibility to first-generation cephalosporins, cephalexin, cefoxitin and chloramphenicol was observed. All isolates were susceptible to tigecycline and tetracycline. The isolates were grouped into three genetically closely related clusters, yet notable phenotypic diversity in biofilm production and antibiotic susceptibility persisted within these groups. The study highlights R. pickettii's adaptability in pharmaceutical water systems, marked by its motility, biofilm-forming capabilities, and multidrug resistance. These results emphasise the importance of rigorous monitoring of water systems to reduce transmission risks and prevent the emergence of resistant strains in clinical environments.

Methyl caffeate (MC), a naturally occurring methyl ester of caffeic acid (CA), exhibits potent antioxidant activity and a broad spectrum of biological effects. This study investigates the antioxidant mechanism of MC through its reaction with the stable radical DPPH•, employing both experimental and computational approaches. Kinetic measurements were conducted in a predo minantly nonpolar medium (1,4-dioxane with phosphate buffer), revealing concerted proton and electron transfer. This experimental evidence was supported by values of kinetic isotope effects (KIEs) and thermodynamic activation parameters. Analysis of the intrinsic bond orbitals (IBOs) along the calculated intrinsic reaction coordinate (IRC) trajectories supported the proposed proton- coupled electron transfer (PCET) reaction mechanism. Additionally, the Fe(II) complexation ability of MC was evaluated spectrophotometrically, demonstrating stable complex formation at pH 7.0, suggesting potential for mitigating hydroxyl radical generation in physiological conditions. These findings offer new insights into the antioxidant behaviour of MC and its potential applications in pharmaceutical and nutraceutical formulations.

The aim of this study was to evaluate the antibacterial and antibio-film potential of two naturally occurring naphthoquinones, 2-hydroxy-1,4-naphthoquinone (2-HNQ) and 2-methoxy-1,4-naphthoquinone (2-MNQ), against the Gram-negative bacterium Escherichia coli strain ATCC 25922. In the first step of the study, the minimum inhibitory concentrations (MICs) of 2-HNQ and 2-MNQ were determined using the microdilution method. Subsequently, possible mechanisms underlying the antibacterial activity of 2-HNQ and 2-MNQ against E. coli were investigated by assessing intracellular reactive oxygen species (ROS) production and membrane permeability. Finally, the impact of 2-HNQ and 2-MNQ on swarming motility and on pre- and post-biofilm formation of E. coli was evaluated. The MIC of 2-HNQ against E. coli was 500 µg mL-1, while that of 2-MNQ was 100 µg mL^-1. Both compounds increased intracellular ROS production and altered the membrane permeability of E. coli. Moreover, 2-HNQ and 2-MNQ reduced swarming motility and inhibited both pre- and post-biofilm formation. The results of this study indicate that both naphthoquinones possess antibacterial potential, with 2-MNQ showing greater potency against E. coli. Their antibacterial activity appears to involve ROS generation and disruption of membrane permeability. Importantly, both tested naphthoquinones also impaired E. coli motility and bio-film formation, suggesting potential applications in the treatment of infections caused by E. coli.

Optimising medication adherence is essential for effective heart failure (HF) management, yet nonadherence remains common, particularly among hospitalised and advanced-stage patients. This study evaluated the internal consistency reliability and score association of the Medication Adherence Report Scales, MARS-5 and MARS-10, self-report questionnaires in clinical pharmacist-led adherence assessments in hospitalised HF patients. Tools were administered during structured pharmacist-led interviews. To complement quantitative findings, four clinical cases were presented to illustrate the clinical relevance of adherence assessment in real--world HF management. Results showed a strong association between MARS-5 and MARS-10 (n = 70) responses (unweighted Cohen's kappa 0.820 (95 % CI 0.683-0.957; p < 0.001) for categorizing patients as nonadherent or adherent and Pearson's r coefficient of 0.899 (95 % CI 0.847-1.000; p < 0.001) for continuous score correlation), supporting score association and flexible use in clinical settings, with MARS-5 reliably identifying nonadherence (defined as score < 20 for MARS-5 and ≤ 8 for MARS-10), with potentially reduced respondent burden due to fewer items. Serious clinical complications were documented in nonadherent patients (41.43 % by MARS-5 and 35.71 % by MARS-10), illustrated through selected cases including stent thrombosis, embolic stroke, graft dysfunction, and deterioration in glycaemic control. These findings indicate the potential of MARS-5 as a practical, time-efficient tool for routine adherence assessment in acute settings. Case analyses underscore the critical role of the clinical pharmacist in proactively identifying nonadherence and enabling timely, targeted interventions to mitigate risk and improve patient outcomes in HF care.

Preeclampsia (PE) is a complex pregnancy disorder that may cause adverse outcomes for mother and baby. Combining risk factors with clinical, laboratory, and ultrasonographic data can help identify women at risk. This study investigated the relationship between maternal risk factors, soluble fms-like tyro-sine kinase 1 (sFlt-1), placental growth factor (PlGF), their ratio, and pregnancy outcomes, involving 68 women with PE risk factors and 21 controls. There were no significant differences in the frequency of adverse outcomes (PE, foetal death, and infants with abnormal birth weight), sFlt-1, PlGF, the sFlt-1/PlGF ratio, or birth weight centiles between the PE-risk and control groups. The most frequently recorded high-risk factor was gestational diabetes mellitus, whereas moderate risk was a pre-pregnancy body mass index of over 30 kg m^-2. The most prominent difference was observed in the subgroups with gestational hypertension and first-time pregnant women as risk factors, with significantly higher sFlt-1/PlGF ratios compared to the control group. Combining multiple risk factors increased the sFlt-1/PlGF ratio compared to both the control group and the group with only one risk factor. The study documented PE risk factors and outcomes at a Croatian hospital where angiogenic markers are not routinely used in screening. Findings highlighted the importance of integrating PE screening into standard practice.

l-Met-enkephalin is a neuropeptide known to exert protective effects in various experimental models of autoimmune and inflammatory diseases. These effects are mediated through opioid receptors and can be abolished by the opioid receptor antagonist naltrexone. Investigation of peptide enantiomerism and the incorporation of d-amino acids are crucial for designing novel peptides with altered structural and biological properties compared with their native l-forms. Since no data are currently available on the properties or biological activity of the d-Met-enkephalin enantiomer, we evaluated its hepatoprotective potential in a mouse model of acetaminophen-induced hepatotoxicity. Male CBA mice were treated with d-Met-enkephalin, and hepatoprotection was assessed by measuring plasma alanine aminotransferase (ALT) and aspartate amino-transferase (AST) activities, along with histological liver necrosis scores. The peptide's secondary structure and antisense peptide binding were analysed using circular dichroism and fluorescence spectroscopy, respectively. d-Met-enkephalin demonstrated dose-dependent hepatoprotective effects within the range of 0.5-20 mg kg-1, with maximal protection observed at 5 mg kg^-1, a dose comparable to that of the l-enantiomer (7.5 mg kg^-1). This preservation of biological activity may be attributed to the presence of the achiral amino acid glycine at positions 2 and 3, which maintains the functional conformation of the d-enantiomer. The role of opioid receptor involvement was further examined through direct receptor blockade using naltrexone and indirect inhibition with the antisense peptide IPPKY.

Antibiotic resistance is a growing global health threat, with patient non-adherence to prescribed antibiotic regimens representing an important contributing factor. This prospective interventional study investigated the impact of clinical pharmacist counselling at hospital discharge on adherence to oral antibiotic therapy. The study was conducted at the Department of Nephrology and Endocrinology, General Hospital "Dr. Tomislav Bardek", Koprivnica, between March 2022 and July 2025. A total of 98 participants aged ≥18 years who were prescribed oral antibiotics at discharge were randomised into intervention (counselling) and non-intervention groups. Baseline socio-demographic and clinical data were collected, and adherence was assessed following treatment completion using a structured questionnaire developed by the authors. Of the 98 participants, 94 were included in the final analysis. Non-adherence was significantly lower in the intervention group, compared to the non-intervention group (2.1 % vs. 36.2 %, p < 0.001). Urinary tract infections represented the most common indication for antibiotic therapy, with ciprofloxacin and amoxicillin-clavulanic acid being the most frequently prescribed medicines. This study demonstrates that pharmacist-led discharge counselling markedly improves adherence to short-term antibiotic therapy. These findings provide preliminary evidence supporting integration of clinical pharmacists into hospital discharge processes to promote rational antibiotic use and combat antimicrobial resistance.

The COVID-19 pandemic introduced substantial changes to clinical practice, including widespread antibiotic use. These changes raised concerns about a potential rise in healthcare-associated infections, particularly Clostri dioi des difficile infection (CDI). This study aimed to investigate the hidden impact of COVID-19 treatment strategies on the incidence of CDI, with a specific focus on antibiotic use, advanced age, comorbidities, and the administration of proton pump inhibitors (PPIs) and corticosteroids. A retrospective observational study was conducted using anonymised patient data from the University Clinical Hospital Mostar. The number of CDI cases significantly increased during the COVID-19 peak in 2021, showing a perfect positive correlation with COVID-19 incidence (ρ = 1.0, p < 0.05). Antibiotic use was strongly associated with CDI (69 % vs. 12 %; p < 0.05), as was advanced age (≥ 65 years; 71 %; p < 0.05). The combined use of proton pump inhibitors and corticosteroids was significantly more frequent in the CDI group (54 % vs. 24 %; p < 0.05). The findings highlight how COVID-19 treatment strategies can unintentionally raise CDI risk, stressing the need for prudent antibiotic use, careful drug management and targeted prevention for elderly and high-risk patients.