Search Results (689)

An in-line process analytical technology that measures drag force exerted by wet mass in a high-shear granulator on a thin cylindrical probe enabled real-time identification of distinct stages in high-shear wet granulation of acetaminophen. The technology known as Lenterra in-line rheometer outputs two parameters, the mean force pulse magnitude (MFPM) and the coefficient of variation of force pulse magnitude (CVFPM), that characterize granule densification and size uniformity in real time, providing a process fingerprint. The MFPM and CVFPM evolutions measured during granulation of acetaminophen formulations for varied amounts of added water were compared with the results of particle size distribution (PSD) analysis of the powder released after granulation and with the tablet dissolution tests. The comparison demonstrated a correlation between salient features of the MFPM and CVFPM evolutions and particle size distributions for different water amounts. Based on the measured process fingerprints, it was possible to identify the water amount optimal for best granulation output. In addition, MFPM and CVFPM evolutions allowed for the prediction of a granulation endpoint. The results indicate that in-line rheometry can be a useful tool for formulation development and scale-up of high-shear wet granulation processes. Full article

Poly(glycidyl methacrylate) (PGMA) is a polymer containing epoxy groups in its side chains, which makes it a suitable platform for the development of functional materials. In this study, crosslinked PGMA-based microspheres were synthesized by suspension polymerization using N,N′-methylenebisacrylamide as a crosslinker, and the effect of incorporating inorganic additives (InAds) (NaCl, CaCO₃, and MgO nanoparticles) during synthesis was evaluated. In all cases, solid microspheres were obtained, exhibiting variations in particle size, sphericity, and aggregation depending on the type and amount of InAds. Thermal stability was characteristic of crosslinked PGMA (i.e., a single broad thermal transition in ~80–110 °C), while water absorption remained within a narrow range (80–120% for t = 40 min). In addition, the number of epoxy groups per gram of sample was 4.83 ± 0.02 mmol g⁻¹. Selected microspheres were subsequently functionalized with polyethyleneimine (PEI) to obtain graft polymers (PGMA–PEI) and evaluated for the adsorption of three model contaminants: Acid Red 27 (AR-27), nitrites, and acetaminophen. PGMA–PEI showed high affinity toward AR-27 and nitrites, achieving high removal efficiencies at acidic and neutral pH, with rapid adsorption kinetics consistent with a pseudo-second-order model, attributed to electrostatic interactions between protonated amine groups and anions. At pH 11, anion desorption was promoted, enabling partial material regeneration. The results highlight the potential of PGMA–PEI microspheres for the removal of AR-27 (maximum retention ~0.25 mg of dye/g of polymer) and nitrites (maximum retention ~0.023 mg of ${NO}_2^{-}$/g of polymer), whereas acetaminophen removal was not evidenced. Full article

The administration of specific immunoglobulin G-based antivenoms is a key strategy for treating snakebite envenoming victims. However, serious adverse reactions, such as anaphylaxis or serum sickness, are frequently observed following such administration. In addition, inflammation associated with delayed wound healing considerably drives the irrational use of antibiotics or anti-inflammatory agents, which may be linked to adverse reactions following antivenom treatment. In this study, we evaluated the factors contributing to adverse effects following the administration of snake antivenom, especially pharmacological treatment and premedication intended to prevent adverse reactions. Our retrospective study was conducted by healthcare professionals in Narathiwat, the southernmost province in Thailand, and it involved 980 patients confirmed to have been snakebitten from 2016 to 2021. Of these cases, 513 were treated with antivenom. Prevalence rates and 95% confidence intervals were calculated, and univariate and multivariate analyses were performed to determine the correlation between adverse reactions and medications. Following antivenom administration, the majority of the patients exhibited no adverse reactions (86.7%). Nevertheless, skin rash, itching, wheezing, angioedema, chest tightness, and fever were observed in 13.3% of those receiving snake antivenom. After the administration of antivenom for Malayan pit viper bite, adverse reactions occurred in 11.7% of the sample, especially among referral patients (p < 0.001). Epinephrine and antihistamines were prescribed as prevention and treatment for hypersensitivity due to antivenom administration. Antibiotics, Non-steroidal Anti-inflammatory drugs (NSAIDs), and acetaminophen were not associated with antivenom-induced adverse reactions. Interestingly, tramadol and antihistamines significantly reduced the occurrence of adverse reactions after antivenom administration (p < 0.05). Well-trained staff, close monitoring alongside resuscitation equipment and medications that can minimise the severity of anaphylactic reactions must be promptly available whenever antivenom is administered. Full article

The management of patent ductus arteriosus (PDA) in premature infants remains a significant debate in neonatology. Interventions aimed at accelerating ductal closure, often using nonsteroidal anti-inflammatory drugs (NSAIDs) or acetaminophen, are common practice. However, recent evidence increasingly challenges this approach. Pharmacological agents for PDA closure demonstrate limited efficacy and carry significant risks of systemic toxicity, affecting renal, gastrointestinal, vascular, and pulmonary systems. Multiple recent randomized controlled trials (RCTs) and meta-analyses have largely failed to demonstrate that early active treatment improves crucial clinical outcomes such as mortality, bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH), or necrotizing enterocolitis (NEC). Some studies even suggest potential harm, particularly an increased risk of BPD and mortality in vulnerable extremely preterm infants. Procedural closure methods (surgical ligation, transcatheter techniques), while achieving anatomical closure, also pose significant risks and lack evidence of improved clinical outcomes. Given the high rates of spontaneous PDA closure, especially in extremely preterm infants, and the lack of proven benefit alongside potential harm from interventions, a paradigm shift towards expectant or conservative management is gaining support. This approach emphasizes supportive care, minimizing interventions, and may be complemented by the judicious use of postnatal corticosteroids in selected infants with significant lung disease, which might indirectly facilitate ductal closure by addressing underlying inflammation. Full article

Emerging pharmaceutical pollutants such as acetaminophen (ACE) pose health and environmental risks. Solar photocatalysis provides a sustainable and efficient treatment option. In this study, UiO-66-NH₂ metal–organic framework was immobilized on cotton fabrics to enable their application in both batch and continuous flow systems. Cotton, a biodegradable and low-cost support, was first functionalized by two strategies: hydroxylation (-OH) and carboxylation (-COOH), to promote MOF anchoring. Cotton fabric functionalization and MOF growth were confirmed by ATR and X-ray diffraction, while SEM and EDX analyses revealed that carboxylated fibers achieved higher MOF loading. Photocatalytic experiments under simulated solar irradiation demonstrated significantly higher degradation of acetaminophen when the carboxylated cotton fabric-based catalyst (F-COOH-UiO-66-NH₂) was used. Mott–Schottky analysis and band alignment revealed that, under the applied reaction conditions, hydroxyl radical generation was not favored due to the position of the valence band. Studies with scavengers identified the superoxide radical as the dominant oxidative agent responsible for the photodegradation process. In particular, the F-COOH-UiO-66-NH₂ system demonstrated its suitability for application in continuous flow systems, achieving acetaminophen conversion of up to 50% under simulated solar irradiation. This confirms its potential for scalable application in practical water treatment technologies. These results reinforce the feasibility of immobilizing MOF-based photocatalysts on functionalized textile waste, offering a dual-purpose solution that combines the removal of pharmaceutical pollutants with the valorization of waste materials. The synergistic integration of high photocatalytic efficiency, sunlight harvesting and recyclability of the materials underlines the eco-friendly and cost-effective nature of the proposed strategy. Full article

A rapid method for the early diagnosis of fatal mushroom poisoning is not available. Therefore, in our region, symptomatic patients are admitted to intensive care units (ICUs) for close monitoring and treatment. This retrospective study evaluated ICU patients with mushroom poisoning to assess clinical and laboratory trends, treatment characteristics, and outcomes and determine the necessity of level 3 ICU admission. Fifty-four patients were included in this study, and the duration of ICU stay was 5.5 ± 3.9 days. Acute liver failure (ALF) was observed in 7% of patients. Eight patients (14.8%) only received symptomatic treatment, whereas two patients underwent liver transplantation, and one of whom died. The overall mortality rate was 5.6%. A significant decrease was observed in alanine aminotransferase, aspartate aminotransferase, bilirubin, urea, creatinine, lactate dehydrogenase, international normalized ratio, and prothrombin time values on the day of discharge from the ICU compared with the day of admission (p < 0.05). Mushroom poisoning cases thought to be at risk of developing ALF can be transferred to transplant centers early to avoid wasting time. However, to ensure that ICU resources are used effectively, we believe that monitoring and treatment in a level 3 ICU should be reserved for patients progressing to liver failure rather than all symptomatic patients. Full article

Dendrobium officinale exhibits hepatoprotective potential against acetaminophen-induced liver injury (AILI). Fermentation has been proposed as a strategy to enhance the utilization and efficacy of herbal medicines. However, whether yeast fermentation improves the hepatoprotective effects of D. officinale remains unclear. This study investigated whether fermentation of D. officinale flower extract with Saccharomyces cerevisiae (1002S) enhances its protective effects against AILI, compared with a nonfermented extract (DOFE). Hepatoprotective efficacy was evaluated in male C57BL/6 mice, which received 1002S or DOFE (500 mg/kg, oral gavage) for 7 days before an acute acetaminophen challenge. Untargeted metabolomics and network pharmacology analyses were used to characterize fermentation-associated metabolic alterations and to explore potential pathways related to the observed effects. Metabolomic profiling revealed distinct metabolic differences between 1002S and DOFE. Network pharmacology analysis indicated predicted targets of fermentation-associated metabolites were associated with the phosphoinositide 3-kinase (PI3K)/ protein kinase B (Akt) and Janus kinase (JAK)/signal transducer and activator of transcription proteins (STAT) signaling pathways. In vivo, 1002S more effectively alleviated hepatocellular necrosis and significantly reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. Increased expression of nuclear factor erythroid 2-related factor 2 (Nrf2), superoxide dismutase 2 (SOD2), solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) was observed in liver tissues. Molecular docking suggested hemsleyanoside may contribute to these effects. Collectively, S. cerevisiae fermentation enhanced the antioxidant and hepatoprotective efficacy of D. officinale flower extract, supporting its potential development for AILI prevention. Full article

In this study, we evaluated the physiological effects of fermented metabolites derived from puffed grains (z), fermented using Bacillus amyloliquefaciens NPKE6, a strain isolated from Korean water kimchi. In vitro assays showed that NPKE6-FM significantly increased antioxidant enzyme activities (SOD, CAT, GPx) and digestive enzyme activities (α-amylase, protease), suggesting its strong biofunctional potential. To confirm its in vivo efficacy, we established two inflammatory disease models—ulcerative colitis and liver injury—in male C57BL/6 mice. Colitis was induced by oral administration of 1% dextran sodium sulfate (DSS, 1 mL), while liver injury was induced by intraperitoneal injection of acetaminophen (APAP, 300 mg/kg) three times per week for 4 weeks. In disease-induced control groups, elevated serum biomarkers (AST, ALT, ALP) and reduced antioxidant activity were observed. Experimental groups received 10 or 50 mg/kg/day of NPKE6-FM for 4 weeks. Treatment significantly restored antioxidant enzyme levels and reduced inflammatory markers such as TNF-α and IL-6. In the colitis model, NPKE6-FM alleviated DSS-induced tissue damage, evidenced by improved colon length, weight, and histological scores. Gene expression analysis showed downregulation of iNOS and COX-2 in colon tissues and Akt and MCP-1 in liver, indicating molecular anti-inflammatory effects. Although liver histopathology did not show marked improvement, biochemical and gene expression results supported its protective role. In summary, NPKE6-FM demonstrated potent antioxidant and anti-inflammatory activities in vitro and in vivo, indicating its potential as a functional food additive to prevent or alleviate inflammatory conditions such as colitis and liver injury. Full article

Background/Objective: Patent Ductus Arteriosus (PDA) is a common congenital heart defect causing high morbidity and mortality in preterm neonates. IV ibuprofen is the standard treatment, with acetaminophen as a potential alternative when ibuprofen is contraindicated. However, evidence for acetaminophen’s effectiveness is inconclusive. This study aimed to compare the efficacy and safety of IV acetaminophen versus IV ibuprofen as the initial treatment for PDA closure in preterm neonates. Methods: A retrospective cohort study was conducted at a tertiary Saudi hospital. This study included preterm neonates with a gestational age of ≤32 weeks diagnosed with PDA and treated with IV ibuprofen or IV acetaminophen. The primary outcome was to evaluate the efficacy of ibuprofen versus acetaminophen for treating PDA. Results: A total of 95 courses were included. Of these, 49 neonates received ibuprofen, and 18 neonates received acetaminophen as first therapy. The mean age at the initial course was 5.47 ± 10.30 days for the ibuprofen group and 5.22 ± 6.43 days for the acetaminophen group. In most neonates, the hemodynamic significance of the PDA was confirmed by ultrasound examination. As a result, 35 of 49 neonates treated with ibuprofen experienced successful full PDA closure, with a rate of 71.4%, compared to 10 of 18 in the acetaminophen group, which had a rate of 55.6%. However, this difference was not statistically significant (p-value = 0.35). Conclusions: A trend toward higher PDA closure with ibuprofen was observed compared to acetaminophen, without a statistically significant difference. Both treatments showed comparable safety. Further studies are needed to confirm these findings and optimize acetaminophen dosing. Full article

Acetaminophen (APAP) overdose is a major global cause of drug-induced liver injury (DILI), and the rising incidence of APAP-induced hepatotoxicity has raised substantial concern in the medical community, highlighting an urgent need for effective therapeutic approaches. Coptidis Rhizoma alkaloids (CRAs) have shown hepatoprotective effects in multiple hepatic disease models. This study aimed to investigate the therapeutic efficacy and the underlying mechanisms of CRA in acetaminophen (APAP)-induced acute liver injury. After identifying 18 alkaloid components in CRA, we employed an integrated strategy of untargeted metabolomics and network pharmacological analysis to investigate the underlying mechanisms. The potential mechanisms were subsequently validated through histopathological examination and molecular biology assays. Our results showed that CRA exerted dose-dependent protection against APAP-induced liver injury in vitro and in vivo. This protective effect was mediated by enhanced hepatic glutathione (GSH) biosynthesis via increased intracellular cysteine (Cys) availability. In the mouse model, hepatic Cys and GSH levels were increased by 2.2-fold and 1.8-fold, respectively, relative to the model group, which consequently attenuated oxidative stress damage. Furthermore, CRA suppressed APAP-induced activation of ERK and NF-κB, reducing the phosphorylation levels by 39.2% and 38.0%, respectively. Accordingly, it also downregulated the subsequent expression of inflammatory mediators in the TNF signaling pathway. These findings provide crucial mechanistic insights into the hepatoprotective role of CRA against APAP-induced toxicity, establishing a valuable foundation for developing novel therapeutic or preventive strategies for APAP-induced liver injury. Full article

Precise control and measurement of the cellular microenvironment, particularly oxygen concentration, are crucial for developing physiologically relevant in vitro models. However, current methods often lack the spatial resolution and throughput needed to investigate complex, oxygen-dependent biological mechanisms in 3D cell cultures. Here, we present an advanced platform based on microcavity arrays featuring integrated, ratiometric oxygen sensors, so-called SensoSpheres. A unique bevel design at the cavity entrance enables the non-invasive, real-time measurement of pericellular oxygen concentration and oxygen gradients. We established protocols for generating spheroids from various cell lines (e.g., HepG2, HeLa) and characterized their metabolic responses under precisely controlled hypoxic, normoxic, and hyperoxic conditions. Using a dose–response assay, we demonstrate the platform’s sensitivity in capturing distinct metabolic shifts in response to acetaminophen and cisplatin. Furthermore, we introduce the Oxygen Consumption Recovery Rate (OCRR) as a novel parameter to quantify cellular resilience after exposure to toxic compounds such as cisplatin and acetaminophen. This high-throughput-compatible platform represents a significant methodological advancement, enabling detailed studies of oxygen-dependent cellular processes, drug toxicity, and metabolic adaptation. Its potential for integration into microfluidic systems paves the way for more sophisticated organ-on-chip models, ultimately improving the predictive power of preclinical research. Full article

Acetaminophen (APAP) overdose can induce potentially fatal nephrotoxicity. Micromeria frivaldszkyana (M. frivaldszkyana), an endemic plant to Bulgaria, has demonstrated significant antioxidant activity. This study represents the first evaluation of the nephroprotective effects of a methanolic extract of M. frivaldszkyana in an APAP-induced rat model of kidney injury. The aim of the study was to investigate the protective potential of orally administered M. frivaldszkyana methanolic extract against APAP-induced nephrotoxicity. Male Wistar rats received a one-week treatment with saline, M. frivaldszkyana extract (250, 400, or 500 mg/kg), rosmarinic acid (100 mg/kg), or silymarin (125 mg/kg). On day 7, renal injury was induced by oral administration of APAP (2000 mg/kg). Forty-eight hours later, blood and kidney samples were collected for biochemical and histological analyses. The extract at 500 mg/kg significantly reduced the elevated levels of serum urea (1.83 ± 0.24 vs. 3.49 ± 0.75, p < 0.05), creatinine (59.51 ± 2.30 vs. 72.27 ± 3.92, p < 0.05), and uric acid (477.55 ± 52.48 vs. 898.33 ± 65.30, p < 0.001), while restoring renal glutathione (GSH) levels (4.43 ± 0.19 vs. 2.64 ± 0.10, p < 0.001) and catalase activity (3802.78 ± 142.05 vs. 2485.03 ± 143.23, p < 0.01), compared with APAP-treated rats. Malondialdehyde levels were significantly reduced by the extract (25.19 ± 0.95 vs. 69.66 ± 4.11, p < 0.001), with similar effects observed across all tested doses. In conclusion, M. frivaldszkyana methanolic extract confers significant protection against APAP-induced nephrotoxicity, likely through antioxidant-mediated mechanisms, enhanced GSH restoration, and attenuation of lipid peroxidation, highlighting its potential as a nephroprotective agent. Full article

This study developed a sonoseeding strategy for controlling the crystal size of acetaminophen during cooling crystallization by introducing sonication into a supersaturated solution, thereby inducing nucleation. Based on the synthetic route of acetaminophen, crystallization behavior in both water and acetic acid aqueous solutions was investigated, along with the influence of a structurally related additive, p-aminophenol, on nucleation. To establish the sonoseeding approach, the solubility of acetaminophen in water and an aqueous solution of acetic acid, with and without the additive, was measured over a temperature range of 10–70 °C using a titration method. In parallel, the nucleation temperatures and metastable zone widths of acetaminophen were systematically determined during cooling crystallization under varying operating conditions. Results demonstrate that sonication effectively induces nucleation and significantly narrows the metastable zone width, particularly in aqueous solutions of acetic acid. Guided by the determined solubility and nucleation behavior, sonoseeding crystallization experiments were conducted at various supersaturation levels, allowing for the efficient control of acetaminophen crystal size, which ranged from 27 μm to 95 μm, with narrower particle size distributions compared to spontaneous nucleation. Furthermore, the recrystallized acetaminophen was confirmed as Form I using PXRD, DSC, and FTIR analysis. This study demonstrates that the sonoseeding approach is an efficient method for controlling crystal size during the crystallization of active pharmaceutical ingredients. Full article

Background: Effective postoperative analgesia after laparoscopic cholecystectomy (LC) should facilitate rapid recovery while minimizing exposure to opioid-related adverse events, a central goal of enhanced recovery after surgery (ERAS). Although intravenous patient controlled analgesia (IV-PCA) remains widely used, its gastrointestinal and mobilization-impairing side effects may hinder early recovery. Methods: This retrospective cohort study included adult patients who underwent elective laparoscopic cholecystectomy, all performed using a standardized three-port technique, between January 2025 and December 2025. Patients with conversion to open surgery, concurrent procedures, incomplete medical records, or American Society of Anesthesiologists physical status ≥ IV were excluded. Patients received either a single-shot ultrasound-guided subcostal transversus abdominis plane (TAP) block with 0.19% ropivacaine or conventional fentanyl-based IV-PCA. Postoperative analgesic requirements, functional recovery outcomes, and safety profiles were evaluated. Results: All patients in the Group TAP (n = 60) required no rescue analgesia during the first 12 postoperative hours and did not require nonsteroidal anti-inflammatory drugs or IV-PCA within 24 h. Early recovery milestones were consistently achieved, including preserved early ambulation, prompt tolerance of oral intake, and smooth transition to oral acetaminophen 650 mg orally three times daily from postoperative day 1. All Group TAP patients met the discharge criteria by postoperative day 2 without opioid-related adverse events or signs of local anesthetic systemic toxicity. In contrast, the Group IV-PCA (n = 60) exhibited a high incidence of opioid-related adverse effects, frequent PCA interruption or discontinuation, delayed functional recovery, and prolonged hospitalization. Conclusions: A single-shot ultrasound-guided subcostal TAP block using low-concentration ropivacaine can function as a reliable, opioid-free primary analgesic strategy after laparoscopic cholecystectomy, effectively supporting ERAS-consistent early recovery. This approach represents a practical and clinically meaningful alternative to conventional IV-PCA in routine LC. Full article

Conventional gelatin capsules deliver a rapid drug release in the stomach, which is suboptimal for therapies requiring controlled and delayed release, emphasizing the need for customizable drug delivery systems for precision medicine. This study’s objective was to optimize 3D-printed capsule shells formulated with pH-responsive polymer blends—hydroxypropyl methylcellulose acetate succinate (HPMC-AS), PEG-4000, and PVA—to achieve controlled and sustained drug release, comparing profiles against a commercial enteric capsule. Capsule shells were produced via fused filament fabrication (FFF) at two ratios (80:15:5 and 70:20:10), filled with acetaminophen (250 mg), and tested using a two-stage dissolution method (simulated gastric fluid (SGF) for 2 h followed by simulated intestinal fluid (SIF) for 4–5 h). Results showed negligible drug release in SGF (≤5%) for both printed and commercial capsules. However, in SIF, the commercial capsule released its payload rapidly (>80% within 15 min), while the 3D-printed capsules achieved a prolonged, gradual release. The higher HPMC-AS content significantly extended the release duration. All capsules met the pharmacopeial weight uniformity criteria. In conclusion, the 3D-printed shells provided a controllable, sustained drug release profile, underscoring 3D printing’s potential to create tunable, patient-specific dosage forms. Full article