Acta Pharmaceutica Feed

Gastrointestinal risk profile of tigecycline, omadacycline and eravacycline: Evidence from the FDA adverse event reporting system

Wed, 25 Mar 2026 00:00:00 GMT

This study assessed the gastrointestinal (GI) safety profiles of tigecycline, omadacycline, and eravacycline through a retrospective disproportionality analysis of reports submitted to the FDA Adverse Event Reporting System (FAERS) between the second quarter of 2005 and the first quarter of 2024. Among 3,261 adverse event reports associated with these agents, 809 (24.8 %) involved gastrointestinal disorders, with tigecycline accounting for the largest proportion (588 reports), followed by omadacycline (197) and eravacycline (24). Disproportionality analysis revealed that gastrointestinal disorders ranked among the top three system organ classes for all three drugs, with positive signals observed for tigecycline (ROR = 1.63), omadacycline (ROR = 3.04), and eravacycline (ROR = 1.79), the strongest association being with omadacycline. While most GI events were consistent with known safety information, several unexpected signals were identified, including gastrointestinal haemorrhage, melena, small-intestinal obstruction, tongue discolouration, and intestinal perforation for tigecycline, as well as lip swelling and tongue discolouration for omadacycline. The median onset times of GI events were 4, 0, and 2.5 days for tigecycline, omadacycline, and eravacycline, respectively, with nearly half of the events occurring within three days of treatment initiation. These findings reveal distinct GI safety patterns among newer tetracycline-derived antibiotics and underscore the importance of early and route-specific monitoring in clinical practice.

Pan-Cdk inhibitor ZK304709 suppresses Cdc20 expression and potentiates the anticancer activity of apcin in HeLa cervical cancer cells

Wed, 25 Mar 2026 00:00:00 GMT

Cell division cycle 20 homologue (Cdc20), a key regulator of the anaphase-promoting complex/cyclosome (APC/C), is frequently overexpressed in human cancers and represents a promising therapeutic target. However, monotherapy targeting Cdc20 has shown limited efficacy, partly due to compensatory activation of cyclin-dependent kinase 1 (Cdk1). In this study, we investigated the combinatorial potential of the pan-Cdk inhibitor ZK304709 with the Cdc20 inhibitor apcin in HeLa cervical cancer cells. Transcriptomic analysis revealed that both CDC20 and CDK1 are upregulated in cervical cancer tissues. Mechanistically, apcin treatment induced cyclin B1 accumulation and enhanced Cdk1 phosphorylation at Thr161, suggesting feedback activation. In contrast, ZK304709 reduced p-Cdk1(T161) levels and suppressed Cdc20 expression at both protein and mRNA levels. Functionally, the combination of apcin and ZK304709 synergistically inhibited cell proliferation and induced G2/M phase arrest in HeLa cells. These findings demonstrate that dual inhibition of Cdk1 and Cdc20 disrupts compensatory signalling pathways and enhances antitumour efficacy in HeLa cells, providing a rational strategy for combination therapy in cervical cancer.

Sedation management in mechanically ventilated intensive care unit patients: Meta-analysis review

Wed, 25 Mar 2026 00:00:00 GMT

Sedation is crucial for managing mechanically ventilated intensive care unit (ICU) patients, but agents differ in their effects. Propofol, benzodiazepines and α2-agonists are commonly used, yet their comparative impact remains unclear. This review searched OVID MEDLINE and Embase from January 2006 to June 2025 for randomised controlled trials in adult ICU patients. The primary outcome was duration of mechanical ventilation; secondary outcomes were ICU length of stay, delirium and mortality. Twenty-six trials (N = 4,993) were included. Dexmedetomidine significantly shortened mechanical ventilation (mean difference [MD] –0.60 days; 95 % CI –0.89 to –0.31), with larger effects versus midazolam (MD –1.25 days) and mixed comparators (MD –1.23 days), but not versus propofol (MD –0.34 days). ICU stay was also reduced (MD –0.94 days; 95 % CI –1.49 to –0.39). Delirium risk decreased (odds ratio [OR] 0.58; 95 % CI 0.38–0.87). No mortality difference was found. Dexmedetomidine is therefore associated with a modest but clinically meaningful reduction in ventilation time, ICU stay and delirium, particularly when compared with benzodiaze-pines, though benefits over propofol are less certain.

Comparative biodistribution analysis of umbilical cord mesenchymal stromal cells via different administration routes in rabbit models

Wed, 25 Mar 2026 00:00:00 GMT

Umbilical cord mesenchymal stem cells (UC-MSCs) have shown therapeutic potential in renal diseases due to their homing ability. This study compared the effects of three administration routes (intravenous, local renal injection, and interventional injection) on UC-MSC distribution in kidney tissue. Eighteen New Zealand rabbits were assigned to the three groups (n = 6 each), and DiI-labelled UC-MSCs were tracked using confocal microscopy to evaluate their distribution in the kidney, lung, and brain. Local renal injection led to high MSC concentrations at the injection site, but distribution to the contralateral kidney was minimal and comparable to that of intravenous injection. Intravenous delivery via the marginal ear vein was simple and convenient but resulted in limited renal homing (< 1 %) and no significant difference between kidneys. Interventional injection achieved the highest delivery efficiency (12.4 %) and a more uniform renal distribution. Notably, inflammatory cytokine levels (IL-6, TNF-α, IL-10) were significantly elevated in the local injection group (p < 0.05). These results indicated that the choice of administration route critically affects MSC targeting and therapeutic potential, and interventional injection may offer the most effective strategy for precise UC-MSC delivery in renal therapy.

Sexually dimorphic and time-dependent influence of active avoidance learning by vilazodone in C57BL/6J mice

Wed, 25 Mar 2026 00:00:00 GMT

The effects of vilazodone (VZD) on the acquisition of active avoidance behavior were examined in C57BL/6J mice. Both female and male mice were assigned to three groups (n = 8 per group per sex): the vehicle control group (VEH), the 0.5 mg kg–1 vilazodone lower dose group (VZD0.5) and the 1 mg kg–1 vilazodone higher dose group (VZD1.0). Spontaneous locomotion and anxiety-like behaviour were assessed after drug administration intraperitoneally in an open field test (OFT). Another cohort of mice was trained in a three-day shuttle box active avoidance test (AAT) after drug administrations with the aim of evaluating the effects of VZD on the acquisition of active avoidance behaviour. In the OFT, VZD decreased freezing time in the corner area in both female and male mice, indicating reduced anxiety-like behaviours. In the AAT, the active avoidance rate was significantly improved on day 1 in female mice and day 2 in male mice, suggesting that VZD facilitated active avoidance learning with sexual dimorphism. Furthermore, the increased active avoidance rates were negatively correlated with freezing time during training. Interestingly, these group differences and correlations diminished on day 3, implying that the facilitation was restricted to early training phases. Collectively, VZD facilitates the acquisition of active avoidance behaviour in mice with distinct sexual dimorphism and temporal dynamics.

Predictive analytical workflow for rapid structure elucidation and in silico toxicological qualification of an unidentified impurity in cefixime granules for oral suspension

Wed, 25 Mar 2026 00:00:00 GMT

During in-use stability testing of cefixime granules for oral suspension, an impurity with a relative retention time of 0.19 was consistently detected and increased during storage. To ensure regulatory compliance and patient safety, the impurity was structurally identified and toxicologically qualified. A laboratory-scale formulation and commercial products were studied under refrigerated and ambient conditions. The impurity was isolated by automated fraction collection and characterised by liquid chromatography-mass spectrometry and tandem mass spectrometry. Kinetic evaluation showed pseudo-first-order formation, with faster accumulation at ambient temperature. The impurity was identified as a γ-lactone degradation product of cefixime, present as multiple stereoisomers stabilised under acidic conditions. In silico toxicological assessment using complementary platforms indicated no additional structural alerts, no mutagenic potential, and negligible acute toxicity. The impurity forms only after prolonged storage of reconstituted suspensions and is classified as an ICH M7 Class 5 impurity, requiring no further genotoxicity testing. The applied analytical-computational workflow provides an efficient approach for impurity qualification in β-lactam antibiotics.

H3 relaxin mediated neuroprotection in Alzheimer’s disease pathology induced by streptozotocin in mouse models: Impact on memory improvement, autophagy and PI3K/Akt-mTOR signalling pathway

Wed, 25 Mar 2026 00:00:00 GMT

Alzheimer’s disease (AD) is characterised by β-amyloid (Aβ) plaque accumulation and tau hyperphosphorylation. H3 relaxin, a neuro-peptide, is known to exert neuroprotective effects. In this study, we investigated how H3 relaxin confers neuroprotection in a streptozotocin (STZ)-induced mouse model and modulates PI3K/Akt-mTOR signalling. Mice were divided into four groups (n = 6 per group): control (saline), STZ, STZ + H3 relaxin, and STZ + donepezil. Following STZ induction, H3 relaxin (1 µg per day) was administered intracerebro ventricularly (ICV) for 14 consecutive days, whereas donepezil (2.5 mg kg–1 per day) was administered orally for the same duration. Cognitive performance was assessed using the Morris water maze (MWM) test. Aβ deposition in the cortex was evaluated through immunohistochemistry. Western blotting was conducted for tau phospho rylation, PI3K/Akt/mTOR signalling, and autophagy markers in the hippocampus. Oxidative stress and inflammation markers were measured using ELISA. H3 relaxin markedly improved memory by decreasing escape latency and duration while spending more time in the target quadrant in the MWM test. Additionally, H3 relaxin reduced Aβ plaque burden and tau phosphorylation (Ser396/404) while enhancing PI3K/Akt-mTOR signalling. Oxidative stress was attenuated, as evidenced by increased GSH and HO-1 levels and reduced MDA and H2O2 concentrations. Moreover, markers of inflammation, NF-κB and TNF-α were suppressed. Overall, H3 relaxin ameliorated cognitive deficits in STZ-induced AD mice through modulation of impaired PI3K/Akt-mTOR signalling, reduction of Aβ and tau pathology, and promotion of autophagy.

Beneficial effect of omega-3 fatty acids supplementation on leaky gut, inflammation and oxidative stress in propionic acid-induced autism in aged rats

Wed, 25 Mar 2026 00:00:00 GMT

This study examined the effects of omega-3 fatty acids supplementation on gut barrier integrity, systemic inflammation, neurotrans-mission and oxidative stress, in an aged rat model of propionic acid (PPA)-induced neurotoxicity. Twenty-four aged male rats were divided into four groups: control, omega-3, PPA and PPA + omega-3. Serum cytokines, tight-junction proteins (TJP1), dopamine, serotonin, short-chain fatty acids (SCFAs), oxidative stress markers, and histopathology of the brain and small intestine were evaluated. PPA exposure significantly increased tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and reduced TJP1 expression, confirming gut barrier disruption and systemic inflammation. Omega-3 fatty acids supplementation selectively reduced IL-6 but did not reverse PPA-induced TNF-α elevation or oxidative stress. CLDN2 expression increased in PPA + omega-3 rats, suggesting a compensatory but incomplete barrier response. Dopamine, serotonin, and SCFA levels showed upward trends with supplementation but were not statistically significant. Histological analysis demonstrated partial preservation of neuronal and intestinal structure in the PPA + omega-3 group. Overall, omega-3 fatty acids exerted modest anti-inflammatory effects but failed to fully restore oxidative balance or barrier integrity in aged rats, suggesting that omega-3 fatty acids may be more effective as a preventive rather than restorative intervention in ageing-related gut-brain axis disruption.

The effect of astragaloside IV on a model of isoproterenol-induced hypertrophic injury in H9c2 cells

Wed, 25 Mar 2026 00:00:00 GMT

The objective of this study was to explore the protective effect of astragaloside IV on a model of isoproterenol-induced (ISO) hyper-trophic injury in rat cardiomyocytes H9c2 (cell line derived from embryonic BD1X rat heart tissue). A cell hypertrophy injury model was established (H9c2 cells treated with 100 μmol L–1 ISO). The cells were divided into normal control, a model group, and an astragalo-side IV group at several concentrations. Astragaloside IV was pre-administered for 2 hours, followed by ISO treatment for 24 hours. Cell viability, cell surface area, apoptosis rate, lactate dehydrogenase (LDH) activity, reactive oxygen species (ROS), superoxide dismutase (SOD), the mRNA levels of Bcl-2, Bax, p62, and LC3, the protein expressions of Sirt1, p62, caspase-3, beclin, and p53 and the LC3II/LC3I ratio were detected. Astragaloside IV significantly alleviated ISO-induced hypertrophy injury in H9c2 cells, reduced cell surface area and LDH release, decreased apoptosis rate and intracellular ROS levels, increased SOD levels, upregulated the expressions of autophagy-related mRNA and proteins, and downregulated the expressions of apoptosis-related mRNA and proteins. Astragaloside IV can effectively inhibit ISO-induced hypertrophy and apoptosis in H9c2 cells, and its mechanism may be related to promoting auto-phagy and reducing oxidative stress.

Antibacterial and antibiofilm activities of naturally occurring naphthoquinones 2-hydroxy-1,4-naphthoquinone and 2-methoxy-1,4-naphthoquinone against Escherichia coli

Tue, 13 Jan 2026 00:00:00 GMT

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.

Motility, biofilm, and endotoxin in Ralstonia pickettii isolates obtained from purified and ultrapure pharmaceutical water systems

Tue, 13 Jan 2026 00:00:00 GMT

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.

Impact of clinical pharmacist counselling at discharge on adherence to oral antibiotics: A pilot study

Tue, 13 Jan 2026 00:00:00 GMT

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.

Antioxidant activity of methyl caffeate: Evidence of proton-coupled electron transfer reaction mechanism

Tue, 13 Jan 2026 00:00:00 GMT

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.

Peptide chirality and opioid receptor modulation: Hepatoprotective effect of d-Met-enkephalin in acetaminophen-induced liver injury

Tue, 13 Jan 2026 00:00:00 GMT

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.

Investigating preeclampsia risk factors and angiogenic profiles in low-screening area

Tue, 13 Jan 2026 00:00:00 GMT

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.

The hidden impact of COVID-19 treatment strategies on the spread of Clostridioides difficile infection

Tue, 13 Jan 2026 00:00:00 GMT

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.

Application of green analytical principles in the HPLC analysis of prednisolone derivatives: Method optimization and validation for nasal powder formulations

Tue, 13 Jan 2026 00:00:00 GMT

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.

MARS-5 vs. MARS-10: Optimizing pharmacist-led adherence assessment in clinical heart failure practice

Tue, 13 Jan 2026 00:00:00 GMT

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.

Double-blind randomised controlled trial of an emollient cream with and without 1 % supercritical CO2 extract of Calendula officinalis in contact dermatitis

Tue, 13 Jan 2026 00:00:00 GMT

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.

Development of two different eco-friendly label-free platforms for analysis of selumetinib

Fri, 10 Oct 2025 00:00:00 GMT

Selumetinib (SEL) is a recently approved medication for paediatric patients who have neurofibromatosis type 1. It is the first approved therapy for this rare, debilitating, and disfiguring disease. Development of proper analytical platforms for SEL analysis in its marketed pharmaceutical formulation (Koselugo® capsules) and blood plasma is highly warranted. Availability of such analytical tools would ensure SEL capsules’ quality and effective therapy. This study introduces, for the first time, the development of two label-free and sensitive platforms for SEL quantification in capsules and human plasma. These platforms are microwave-assisted with an ultraviolet absorbance microplate reader (MW-UV) and reverse-phase high-performance liquid chromatography with a photodiode-array detector (HPLC-PDA). Both platforms employed the SEL native UV absorption as an analytical signal. The MW-UV measured the UV absorption in 96-well transparent plates at 255 nm. The HPLC-PDA involved chromatographic separation of SEL and tozasertib (TOZ), internal standard, on a C18 column both were detected at 255 nm. The optimum procedures of both platforms were established and validated following the ICH guidelines. The linearity ranges were 15–500 µg mL–1 and 0.8–100 µg mL–1, with limits of quantification of 15.3 and 3.5 µg mL–1, for MW-UV and HPLC-PDA, resp. Both platforms displayed high precision with relative standard deviation values ≤ 1.8 %, and high accuracy with recovery ranging from 98.3 to 102.3 %. The platforms were successfully applied to quantify SEL in bulk form, Koselugo® capsules, and were preliminarily applied to human plasma analysis. Eco-friendliness assessment confirmed the adherence of both platforms to green analytical approaches. MW-UV and HPLC-PDA are simple and fast, enabling high-throughput analysis, thus introducing valuable tools for routine use in quality control and clinical laboratories for SEL quantification.