Search Results (1,835)

The increasing consumption of pharmaceuticals associated with global population growth has intensified concerns regarding their release into aquatic environments and potential ecotoxicological effects. In this context, this study evaluated the ecotoxicity and biodegradation of the widely used corticosteroid prednisone. Ecotoxicity assays were performed using aquatic organisms representing different trophic levels: Artemia salina (microcrustacean), Aliivibrio fischeri (marine bacterium), and the cyanobacterium Microcystis novacekii. Biodegradation assays were conducted using M. novacekii. Prednisone was tested at concentrations ranging from 5 to 100 mg/L, corresponding to its maximum solubility in water. All experiments were carried out in accordance with standardized protocols (ABNT NBR 16530, ABNT NBR 15411-3, ISO 11348-3, and OECD 201). No toxic effects were observed for prednisone in any of the tested organisms, as responses at all tested concentrations, including the highest, were not significantly different from the control. Therefore, it was not possible to estimate EC50 values within the tested concentration range. According to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS), substances with effect concentrations above 100 mg/L are considered non-toxic to aquatic organisms. During biodegradation assays, a reduction in prednisone concentration was observed during the growth of M. novacekii, which was associated with an increase in the pH of the culture medium. These results suggest that prednisone degradation occurred indirectly through pH changes caused by cyanobacterial growth rather than through direct metabolic pathways. Full article

Background: Amorphous drug formulations are commonly used to improve the solubility and bioavailability of poorly soluble molecular pharmaceuticals, yet less is known about their molecular conformations and local bonding interactions than their crystalline phases. Methods: High-energy X-ray diffraction structure factor measurements have been made on liquid and glassy nifedipine (NIF), felodipine (FEL), NIF 1:3 polyvinylpyrrolidone (PVP), and FEL 1:3 PVP wt.% mixtures. The corresponding X-ray pair distribution functions have been interpreted using empirical potential structure refinement using different models and density functional theory conformer calculations. Results: In both NIF and FEL, the NH···O inter-molecular hydrogen bonds between the pyridyl nitrogen and ester carbonyls are found to be considerably weaker than those observed in the crystalline polymorphs. For nifedipine, it is proposed that either inter-molecular NH…ON nitro bonds are present and/or a fraction (<20%) of conformational changes, with the aryl ring flipped, occur in the liquid state. For felodipine, the models indicate significant disorder associated with the methyl and ethyl side chains in the liquid state, with the main peak intensity at 3.0 Å arising from intra-molecular Cl-Cl atom pairs. When nifedipine molecules are incorporated into PVP, our models show they possess stronger NH···O bonds to the PVP polymer than felodipine molecules, which have stronger affinity for bonding to the polymer than to other felodipine molecules. Conclusions: The amorphous forms of both NIF and FEL show much weaker hydrogen bonding than found in their crystalline phases. Liquid NIF also exhibits configurations which are not observed in the crystal phases. Full article

In vitro cell barrier models have been increasingly integrated into pharmaceutical and academic research pipelines to evaluate drug safety and drug delivery due to a shift towards New Approach Methodologies (NAMs) in research and regulatory safety assessment. Such models require reliable and interpretable functional readouts. Bioimpedance-based monitoring, particularly transepithelial/endothelial electrical resistance (TEER), is a widely adopted readout due to its non-invasive and real-time capabilities. However, substantial variability arises from differences in measurement settings, frequency selection, electrode configuration, impedance measuring techniques, and data analysis strategies. In numerous studies, TEER is approximated from single-frequency impedance magnitude measurements, which do not isolate the resistive component associated with tight junction-mediated paracellular transport but instead reflect the combined response of a coupled electrochemical system. This review clarifies impedance measuring techniques and systematically analyzes impedance-based measurement and analysis strategies for in vitro biological cell barrier integrity. We compare mono-frequency and broadband acquisition approaches, examine the influence of electrode–electrolyte interfaces, electrode geometry, and culture configuration, and evaluate equivalent circuit modeling and phase-resolved electrical impedance spectroscopy (EIS). Based on this comparison, we propose a three-level analytical hierarchy adapted to experimental objectives and instrumentation constraints. We conclude that phase-informed impedance analysis and harmonized reporting are essential to improve measurement reproducibility, inter-platform comparability, and integration of impedance-derived cell barrier assessment within NAMs-oriented research workflows. Full article

Leucomisine is a major component of renewable plant raw material Artemisia leucodes Schrenk, a sesquiterpene γ-lactone exhibiting antioxidant, hypoglycemic, antiparasitic, and hepatoprotective activities. However, the use of leucomisine in pharmaceuticals is limited by its insufficient bioavailability associated with low aqueous solubility. Therefore, the effect of solid-state synthesis based on leucomisine using the methods of “solvent removal”, “simple mixing”, and “mixture heating”, with disodium glycyrrhizinate as a carrier, on the aqueous solubility of leucomisine was investigated. It was established that the synthesized solid dispersions exhibit increased solubility (7–19-fold) and dissolution rate (36–100-fold) of leucomisine released from the carrier. The most pronounced stimulation of the dissolution process was observed for samples obtained using the “simple mixing” method. Based on physicochemical studies (visible-range spectrophotometry, microcrystalloscopy, investigation of optical properties of solutions, and X-Ray phase analysis), it was determined that the enhancement of solubility is attributed to the loss of crystalline state, micronization, and the solubilization process of leucomisine by the carrier, as well as to the formation of a colloidal solution of leucomisine stabilized by disodium glycyrrhizinate. Full article

Introduction: Peanut oral immunotherapy (P-OIT) is an emerging treatment strategy for peanut allergy (PA). Although a standardized pharmaceutical product, Peanut (Arachis hypogaea) Allergen Powder-dnfp, has been approved in several countries, it is not universally available. In such contexts, real-world protocols using readily utilizable peanut products may represent an alternative approach. This study aimed to describe the feasibility, safety, and clinical outcomes of P-OIT using toasted peanuts in a real-world effort in a pediatric population. Methods: This single-center retrospective cohort study enrolled children who initiated P-OIT at our tertiary pediatric hospital Allergy Unit between April 2015 and December 2024. Demographic and clinical features, allergy test results, and information about P-OIT were recorded. Desensitization was defined as tolerance of 630 mg of peanut protein (PP). Results: Sixty patients (51.7% male; median age 8.2 years) were included. 22/60 (36.7%) achieved desensitization within a median time of 22.7 months. 21/60 (35%) were still undergoing P-OIT at a median tolerated dose of 100 mg of PP, and 17/60 (28.3%) discontinued treatment, most commonly due to loss to follow-up (44%). At least one adverse reaction occurred in 43/60 (71.7%) patients, predominantly mild and self-limiting (68.3% resolved spontaneously, 39.5% occurred at home). However, 11/60 (18.3%) showed anaphylaxis, and 3/60 (5%) received adrenaline. A reduction in Ara h 2 serum-specific IgE levels compared to the baseline was observed in patients completing escalation (p = 0.03). Conclusions: In this real-world single-center cohort, P-OIT using toasted peanuts was feasible in a subset of patients and was associated predominantly with mild adverse reactions, although systemic reactions were also recorded. Treatment discontinuation and adherence remain relevant challenges. These findings highlight the need for prospective, controlled studies to better define the role, safety profile, and patient selection criteria for food-based P-OIT protocols in settings where standardized products are not available. Full article

The improper disposal of household pharmaceuticals is a global public health concern, posing risks to both human health and the environment and highlighting the need to raise public awareness. This study aimed to identify individual characteristics associated with the inappropriate disposal of household pharmaceuticals and to determine which individuals may require greater awareness. This cross-sectional study included 310 participants who completed an online questionnaire collecting sociodemographic and clinical information, as well as data regarding the participants’ use, storage, and disposal of medications. Most participants were female (74%), single (57%), had a university degree (81%), and were 34 ± 12 years old; 37% had some non-communicable disease (NCD), 85% used some medication, and 62% disposed of pharmaceuticals inappropriately. Having no undergraduate degree (OR = 4.4; 95% CI = 2.01–9.8), an absence of NCDs (OR = 2.5; 95% CI = 1.1–5.6), a lack of knowledge about reverse logistics (OR = 3.6; 95% CI = 1.7–7.6) or environmental risks (OR = 13.5; 95% CI = 1.5–125), and a lack of guidance from healthcare professionals (OR = 3.6; 95% CI = 1.2–10.6) were associated with inappropriate disposal. Although most respondents (88.6%) were aware of the negative environmental impacts of improper disposal, 69.7% did not know what reverse logistics was or where to find collection points (73.5%). These findings highlight the importance of environmental education for the effective implementation of reverse logistics for household pharmaceuticals. Full article

Mid-high-frequency ultrasound (375 kHz) and anodic oxidation at low current intensity (<50 mA, NaCl as the supporting electrolyte) were employed to treat sulfonamide antibiotics (sulfamethoxazole—SMX and sulfacetamide—SAM). The sonodegradation involved HO•, while electrogenerated HClO was mainly responsible for the antibiotics’ elimination in the electrochemical process. A comparison of the processes evidenced that the degradation of SMX by ultrasound was faster due to its higher hydrophobicity. In contrast, in the electrochemical system, the SAM degradation was more efficient, which was associated with a higher reactivity of its acetamide moiety toward HClO. Interestingly, SMX was selectively sonodegraded in synthetic hospital wastewater and seawater, whereas the matrix components strongly accelerated the electrochemical degradation but affected the process performance in the hospital wastewater. On the other hand, theoretical analyses of atomic charge indicated that the central S-N bond, the N and aromatic ring in the aniline moiety, the C=C bond, and methyl groups in the isoxazole groups on SMX are the most susceptible moieties to the attacks by HO• and HClO. Furthermore, for the typical byproducts, calculations of the probability of being active against bacteria were slightly lower than that of the parent pharmaceutical, even being much lower for the byproducts from the electrochemical treatment. Full article

Background: Air pollution, antimicrobial use, and population ageing are increasingly recognised as co-occurring pressures shaping population health. This study explores their ecological association with mortality patterns in the province of Messina (Southern Italy), within a One Health-informed framework. Methods: An ecological analysis was conducted using district-by-year data (2015–2024), integrating environmental monitoring (PM₁₀, PM_2.5, NO₂, O₃), outpatient antibiotic consumption, and cause-specific mortality rates. Multivariable regression models were used to assess associations between exposures and mortality outcomes. A post-2020 indicator was included to account for COVID-19-related disruption. Results: Marked geographic variability in pollutant concentrations was observed, with higher levels in urban-industrial districts. Infectious disease mortality increased from 13.8 to 44.6 per 100,000 inhabitants between the pre-pandemic and post-pandemic periods. In Poisson regression models, particulate matter showed a small and non-significant association with respiratory mortality (RR = 1.02, 95% CI: 0.89–1.18), while antibiotic consumption was not independently associated with mortality (RR = 0.99, 95% CI: 0.94–1.05). The post-2020 period was associated with higher mortality estimates (RR = 1.15, 95% CI: 0.72–1.83), although with wide confidence intervals. Conclusions: The findings suggest the co-occurrence of environmental, demographic, and pharmaceutical pressures within the same territories, rather than demonstrating formal synergistic interaction. The observed post-pandemic increase in mortality highlights the importance of accounting for COVID-19-related disruption. These results should be interpreted as exploratory, given the ecological design and limited sample size, but support the need for integrated surveillance approaches within a One Health perspective. Full article

Nalca (Gunnera tinctoria Mol.) is traditionally consumed for its edible petioles and valued for medicinal properties associated with its bioactive compounds. In this study, natural deep eutectic solvents (NADESs) were synthesized and applied for the ultrasound-assisted extraction of phenolic compounds and alkaloids from Nalca leaves. NADES synthesis was confirmed using ¹H NMR, and their physicochemical properties were evaluated to assess their influence on extraction efficiency. The extracts showed total phenolic contents ranging from 6.8 to 142.6 mg GAE/g DW and total alkaloid contents ranging from 0.2 to 3.2 mg OXIE/g DW, depending on solvent composition. Antioxidant activity, evaluated using DPPH and FRAP assays, confirmed that most NADES extracts exhibited significant radical-scavenging and ferric-reducing capacities, generally correlating with phenolic content. The extraction yields obtained with specific NADES formulations were comparable or superior to those achieved with conventional solvents, demonstrating their efficiency. These results demonstrate that NADESs are effective and environmentally friendly alternatives to conventional solvents for extracting bioactive compounds from Nalca leaves. The physicochemical properties of NADESs enable the selective extraction of different metabolite classes, highlighting their potential for green extraction processes in food, nutraceutical, and pharmaceutical applications. Full article

Pharmaceuticals are increasingly recognized as emerging contaminants with potential impacts on agroecosystems. Among these, antibiotics such as ciprofloxacin (CPX) persist in wastewater and may enter agricultural soils through irrigation or fertilization practices, yet their effects on crop plants remain poorly understood. This study evaluated the phytotoxic effects of ciprofloxacin on early growth and photosynthetic pigment content in purple maize (Zea mays L.), a variety of nutritional and cultural importance. Seeds were germinated in an agar-based medium (0.5%) and exposed to three concentrations of ciprofloxacin (3, 10, and 30 mg·L⁻¹) for seven days under controlled conditions. Germination percentage, seedling fresh weight, organ length (root, stem, and leaf), and photosynthetic pigment concentrations (chlorophylls a and b, and carotenoids) were determined. Ciprofloxacin exposure resulted in dose-dependent reductions in germination (from 83% at 3 mg·L⁻¹ to 50% at 30 mg·L⁻¹) and root elongation, while stem length remained unaffected. Chlorophyll content decreased with increasing ciprofloxacin concentration, with the lowest values observed at 30 mg·L⁻¹, while carotenoid levels remained stable, with no statistically significant differences observed. Although ciprofloxacin is typically detected in environmental matrices at ng–µg L⁻¹ levels, higher concentrations may occur in localized contamination hotspots; ciprofloxacin affected early developmental and physiological processes in maize under these elevated exposure conditions. These findings highlight the importance of integrating phytotoxicity assessments into agricultural ecopharmacovigilance strategies and contribute to understanding the risks associated with pharmaceutical contamination in crop production systems. Full article

Multidrug resistance (MDR) and chemotherapy-associated toxicity remain major challenges limiting the success of cancer treatments. In this context, berberine (BBR), an isoquinoline derivative belonging to the barberry family, has emerged as a promising adjuvant that can enhance the efficacy of chemotherapy while potentially mitigating its side effects. The findings indicate that berberine enhances the therapeutic effect of several drugs, such as doxorubicin, cisplatin, tamoxifen, and 5-fluorouracil, through multiple mechanisms including the inhibition of ABC transporters, regulation of autophagy, and synergistic enhancement of reactive oxygen species generation. Advanced pharmaceutical and nanotechnological formulations, including cyclodextrin complexes, solid dispersions, liposomes, solid lipid nanoparticles, nanostructured lipid carriers, polymeric nanoparticles, chitosan-based systems, and inorganic nanoplatforms, have demonstrated significant improvements in the solubility, stability, cellular uptake, and oral bioavailability of berberine. However, knowledge gaps remain regarding optimal dosage determination, safety assessment in combination therapy, and establishing efficacy in large-scale clinical trials. Incorporating berberine into combination therapy strategies may improve treatment outcomes, overcome drug resistance, and potentially reduce the toxic burden associated with chemotherapy. Therefore, this review provides a comprehensive analytical framework for berberine’s potential as an adjuvant, elucidates its mechanistic synergistic interactions with standard therapies, explores pharmaceutical strategies to overcome bioavailability limitations, and suggests future research avenues to further its clinical development. Full article

Advanced oxidation processes based on photo-Fenton chemistry have gained increasing attention as effective treatment alternatives for the removal of pharmaceutical contaminants from water and wastewater systems. However, large-scale implementation remains constrained by operational requirements, limited mineralization efficiency, and challenges associated with process stability and selectivity. This review provides a critical assessment of recent advances (2022–2025) in conventional photo-Fenton and hybrid systems, including photocatalysis/photo-Fenton and sono-photo-Fenton processes, with emphasis on their performance in water and wastewater treatment applications. The removal of non-steroidal anti-inflammatory drugs, antibiotics, pharmaceutical mixtures, and real wastewater matrices is analyzed considering catalyst configuration, irradiation sources, oxidant utilization, and operating conditions relevant to practical treatment scenarios. Conventional homogeneous Fe²⁺/H₂O₂ systems enable rapid contaminant degradation but typically require acidic conditions and show limited mineralization efficiency. In contrast, iron-complexed and heterogeneous catalysts allow operation under near-neutral pH and visible-light irradiation, improving applicability in realistic water treatment systems. Hybrid photocatalysis/photo-Fenton processes enhance treatment efficiency through synergistic generation of reactive oxygen species, while ultrasound-assisted systems further intensify oxidation rates and contaminant removal. Special attention is given to oxidation mechanisms, catalyst stability, transformation products, and toxicity evolution to identify the key factors controlling treatment performance. Finally, current technological limitations, operational challenges, and design considerations for process integration, scale-up, and sustainable implementation in water and wastewater treatment are discussed. Full article

(1) Background: Aristolochia spp. are plants spread around the world and are cautiously used for medicinal purposes due to their toxic compounds. Because of their content of aristolochic acid I (AAI), a major carcinogenic compound, these plant preparations can cause acute and chronic kidney disease, which is associated with cancer. These compounds also contaminate the environment where Aristolochia plants grow, leading to indirect exposure of the population. (2) Methods: The study provides a practical solution for minimizing the toxic effects of AAI using activated charcoal (AC). An ultra-high-pressure liquid chromatography (UHPLC) coupled with a diode array detector (DAD) was used for the AAI qualitative and quantitative evaluation at different time points. Also, the greenness of the chromatographic analysis was evaluated with the AGREE method. (3) Results: A medical pill of 250 mg AC removed 125 µg/mL AAI from a methanolic solution in 30 min with 97.65% efficiency. The greenness for the analytical evaluation was 58%. (4) Conclusions: This study offers, for the first time, a low-cost medical and environmental solution for AAI contamination. The UHPLC–DAD method seems to be an environmentally responsible platform for the AAI routine analysis. AC shows efficient removal, which could be used both for Aristolochia sp. pharmaceutical preparations as well as in environmental decontamination. Full article

Introduction: The growing demand for traditional medicines and health supplements (TMHS) in Malaysia has raised concerns regarding microbial contamination in hard-shell capsule products. Despite regulatory oversight, recurring recalls highlight persistent non-compliance with Good Manufacturing Practice (GMP) standards. This study examines the risks of microbial contamination, recall patterns, and encapsulation practices among TMHS hard-shell capsule manufacturers in Malaysia. Methods: A cross-sectional approach was employed, comprising a review of regulatory guidelines, analysis of NPRA recall data from 2020 to 2024, and a structured survey of 86 TMHS manufacturers on equipment and production parameters. Results: Review of GMP guidance indicated that greater automation and reduced manual handling in capsule-filling processes help minimise microbial contamination. In line with this, TMHS products were recalled at a rate of 4.73%, more than 4 times the pharmaceutical recall rate (1.09%). Among the 245 TMHS recalls, 68 involved hard-shell capsule products that failed microbial testing, primarily total aerobic microbial count (73.53%). Additionally, manufacturers with 50–100 registered products had significantly higher odds of recall (OR = 10.0, 95% CI: 2.35–42.47). However, no significant associations were found between recall status and equipment type, capsule size, or production frequency. Conclusions: Microbial contamination remains a critical issue in TMHS hard-shell capsule products. Regulatory efforts should focus on medium-scale manufacturers and reinforce risk-based GMP adherence to enhance product safety and public health protection. Full article

Introduction: Adolescent suicide behavior is a global concern and a leading cause of morbidity and mortality in this age group. Pharmaceutical ingestion is a frequent method of suicide attempts, requiring toxicology and psychiatric interventions. This study analyzed data from a pediatric tertiary hospital to elucidate the trends, demographics, and methods used. Methods: This retrospective study was conducted at a single tertiary pediatric hospital in Romania and included adolescents aged 10–18 years admitted for suicide attempts between 2014 and 2024. Data extracted from electronic medical records included age, sex, residence, suicide method, psychiatric history, and clinical outcomes. Temporal trends were analyzed using regression-based methods, and group comparisons were performed using chi-square tests, with statistical significance set at p < 0.05. Results: The study included 1840 adolescents, with a significant increasing trend over time (p < 0.0001), but with a transient decline in 2020. The female-to-male ratio was 5.4:1 (p < 0.0001). The median age of the patients was 15.2 years. The suicide attempt methods were pharmaceutical poisoning (95%), chemical ingestion (4%), and violent methods (1%). Females were more prone to pharmaceutical poisoning, while males were associated with chemical ingestion and violent methods (p < 0.0001). Previously documented psychiatric disorders were present in 32.8% of patients, while 9.6% had a history of prior suicide attempts. Two fatalities (0.1%) were recorded, both involving defenestration. Conclusions: Hospital-treated suicide attempts among Romanian adolescents increased over time, mainly affecting females through pharmaceutical poisoning. Adolescents without prior psychiatric diagnoses reveal gaps in early identification and prevention. These findings highlight important patterns among hospital-treated adolescents and may inform targeted prevention efforts. Full article