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Background: Paracetamol is one of the most used antipyretics and analgesics among pediatrics, and its overdose is highly encountered among pediatrics especially in the pre-school age. While it is well-known that paracetamol overdose may lead to toxicities including severe hepatic toxicity, some recent reports have highlighted its "in situ" toxicity on brain tissue at high doses, even in the absence of hepatotoxicity. This can result in acute leukoencephalopathy (AL), coma, or even death. This report describes a case of a child who developed cortical blindness-complicated AL, following a paracetamol overdose. Case presentation: An 18-month-old previously healthy girl accidentally ingested 300 mg/kg of paracetamol suspension. After ingestion, the child was in an initial bad condition that has gradually improved. Several days after ingestion, the patient lost her vision, and she remained blind since then despite a newer appreciation to light. The initial brain magnetic resonance imaging (MRI) suggested AL demonstrated as a faint high T2/fluid-attenuated inversion recovery (FLAIR) signal intensity in the cortical and subcortical regions of both parieto-occipital lobes with sulcal effacement and restricted diffusion. After around 3 months, the subsequent brain MRI showed involutional changes that were manifested as a brain volume loss in the same areas with evidence of gyri-form laminar necrosis in both parieto-occipital regions without restricted diffusion. Other brain MRI findings include right cerebral convexity hyperacute subdural hematoma with prominent subarachnoid spaces. Conclusions: The child developed cortical blindness-complicated AL following a paracetamol overdose. It is well- known that AL may result from several toxins by their direct and/or indirect effect on the cerebral white matter. However, there is still no enough data in the literature clearly explaining the relation of paracetamol overdose to AL. The generally proposed effect of paracetamol on the brain is mainly justified by the excessive oxidative stress. Further studies at the cellular and genetic levels are still needed to investigate the exact association between paracetamol overdose and AL, as well as the underlying mechanisms involved. [ABSTRACT FROM AUTHOR]

Paracetamol‐based bis 1,2,3‐triazole analogues were synthesized involving copper‐catalyzed click chemistry protocol. The new compounds were characterized by 1H NMR, 13C NMR, and mass spectral techniques. All the compounds were evaluated for their in vitro anti‐inflammatory properties using diclofenac as standard reference. The compound 6b with chlorine and fluorine functions displayed outstanding activity with IC50 values of 7.34 ± 0.45 µM and 7.84 ± 0.47 µM, respectively. Compound 6g with methyl and fluorine functions displayed best activity with IC50 values of 9.34 ± 0.22 µM and 9.40 ± 0.35 µM, respectively. Compound 6i, 6k, 6f, 6a, 6e, 6h, 6j, and 6l exhibited promising activity with respect to diclofenac. Using PyRx tool, the molecular docking study against crystal structure of COX‐2 proved the binding efficacies with notable binding interactions. [ABSTRACT FROM AUTHOR]

The photochemical pathways of acetanilide and paracetamol were investigated using the XMS‐CASPT2 quantum chemical method and the cc‐pVDZ (correlation consistent polarized valence double‐ζ$$ \zeta $$) basis set. In both compounds, the bright state is the second excited state, designated as a 1(ππ*$$ {}^1\Big({\pi \pi}^{\ast } $$La) state. Through a detailed exploration of the potential energy profile and the conical intersection structure between the 1(ππ*$$ {}^1\Big({\pi \pi}^{\ast } $$La) and ground states, we gained a better understanding of how cleavage might occur in both molecules upon photoexcitation. Other potential relaxation mechanisms, including crossings with the dark 1nπ*$$ {}^1\left(n{\pi}^{\ast}\right) $$ and 1(ππ*$$ {}^1\Big({\pi \pi}^{\ast } $$La) states, are also discussed in detail. [ABSTRACT FROM AUTHOR]

Introduction: While factors like high serum paracetamol (acetaminophen) concentration and delayed acetylcysteine treatment increase hepatotoxicity risk, existing predictive tools, such as the paracetamol concentration aminotransferase activity multiplication product and the psi (ψ) parameter, lack definitive accuracy. This study evaluated the paracetamol psi parameter multiplication product addition against the psi parameter and the paracetamol concentration aminotransferase activity multiplication product for predicting hepatotoxicity following an acute paracetamol overdose. Methods: A retrospective analysis of patients with acute paracetamol overdose from January 2007 to December 2016 was conducted. The paracetamol psi parameter multiplication product addition, calculated by summing the psi parameter (mmol/L × h) and the paracetamol concentration aminotransferase activity multiplication product (g U/L2), was used. Hepatotoxicity was defined as aspartate or alanine aminotransferase activities ≥1,000 U/L. Diagnostic accuracy was assessed through sensitivity, specificity, the area under the receiver operating characteristic curve, and their corresponding 95% CI, with the optimal cutoff determined using the maximum Youden index method. Results: The study comprised 421 patients, mostly female (82.9%) with a median age of 23 years. Hepatotoxicity occurred in 13.5% (57 patients). The paracetamol psi parameter multiplication product addition showed an area under the receiver operating characteristic curve of 0.989 (95% CI: 0.974–0.997), with an optimal cutoff at 9.723, providing 96.5% sensitivity and 97.3% specificity. The paracetamol psi parameter multiplication product addition demonstrated superior performance in area under the receiver operating characteristic curve compared to the individual assessments of the psi parameter (0.916; 95% CI: 0.885–0.941) and the paracetamol concentration aminotransferase activity multiplication product (0.901; 95% CI: 0.868–0.928). Discussion: The paracetamol psi parameter multiplication product addition appears to be a more effective diagnostic tool than the psi parameter or the paracetamol concentration aminotransferase activity multiplication product alone. Conclusion: Incorporating the paracetamol psi parameter multiplication product addition into clinical protocols could improve paracetamol overdose management by enabling precise identification of individuals at heightened risk for hepatotoxicity, thereby facilitating the customization of treatment approaches. [ABSTRACT FROM AUTHOR]

Introduction: In 2015, Australia and New Zealand treatment guidelines recommended a 2 h paracetamol serum concentration for risk assessment of unintentional paracetamol liquid exposures. We assess our experience with this approach. Methods: Retrospective case review of children <6 years-old with liquid paracetamol overdoses referred to a regional poisons information centre January 2017 to August 2022. We extracted data on the exposure and management from the poisons information centre and hospital medical records. We identified additional cases with two paracetamol concentrations obtained from September 2022 to June 2024. Results: Of 437 paediatric poisonings, 271 were eligible for inclusion. The median age was 24 months, the median time to presentation was 120 min, and paracetamol was the sole ingestant in 92% of cases. Blood testing was recommended in 131 patients (48.3%), occurring at 2 h post-ingestion in 62 patients (47.3%). Testing at a later time was mostly due to delayed presentation, including to hospitals unable to measure paracetamol concentrations. Eighteen patients (16.7%) had repeat blood testing, and five additional cases were identified in the subsequent period. Overall, the concentration decreased in 19 patients (83%), but in three patients it increased, from 73 mg/L to 81 mg/L (0.49–0.54 mmol/L), from 154 mg/L to 179 mg/L (1.03–1.19 mmol/L), and from 56 mg/L to 115 mg/L (0.37–0.77 mmol/L). Symptomatic patients were more likely to receive a second blood test or acetylcysteine while awaiting investigations. Of 19 patients administered acetylcysteine, it was discontinued in five due to low paracetamol serum concentrations. All patients recovered. Discussion: Guidelines were followed in >90% of patients and this testing regimen shortened length of stay. Based on these data, Australian treatment guidelines now recommend repeat testing for 2 h paracetamol serum concentrations >100 mg/L (0.67 mmol/L). Conclusion: A paracetamol serum concentration between 2 h and 4 h post-ingestion in children <6 years-old with unintentional poisonings of paracetamol liquid can facilitate medical discharge. [ABSTRACT FROM AUTHOR]

This study aimed to compare the analgesic effectiveness of intravenous (IV) dexketoprofen trometamol, IV meperidine and IV paracetamol in patients with renal colic at the Emergency Department of Erciyes University Medical School. Ninety patients, aged 18-65, were enrolled in a double-blind, randomized trial and divided into three groups of 30. Each group received either 50 mg IV dexketoprofen trometamol, 50 mg IV meperidine or 1000 mg IV paracetamol, administered in 250 mL saline over 15 minutes. Pain intensity was assessed at 15, 30 and 60 minutes using a 100-mm visual analog scale (VAS) and a 4-point verbal rating scale (VRS). A successful treatment outcome was defined as a =50% reduction in VAS at 30 minutes and patients with a VAS score =40 mm at 30 minutes were given fentanyl as rescue analgesia. Results showed significant reductions in VAS scores (±Standard deviation (SD): 53.9 ± 17.6 mm in the dexketoprofen trometamol group, 62.8 ± 14.6 mm in the meperidine group, and 41.7 ± 19.8 mm in the paracetamol group (Probability value, p < 0.001). The percentage reduction in VAS scores (±SD), was 67.3 ± 20.2% for dexketoprofen trometamol, 71.7 ± 14.2% for meperidine and 51.3 ± 21.0% for paracetamol (p < 0.001). Both dexketoprofen trometamol and meperidine were more effective than paracetamol, but there was no significant difference between them. Rescue analgesia was required in 4 (13.3%) of dexketoprofen trometamol patients, 2 (6.7%) of meperidine patients, and 11 (36.7%) of paracetamol patients. Adverse effects were more common in the meperidine group (33.3%) compared to paracetamol (3.3%) and dexketoprofen trometamol (none) (p < 0.05). In conclusion, IV dexketoprofen trometamol and IV meperidine are equally effective for renal colic and superior to IV paracetamol. [ABSTRACT FROM AUTHOR]

This study examined the effect of acute acetaminophen (ACTP) ingestion on physical performance during the 5 m shuttle run test (5mSRT), attention, mood states, and the perception of perceived exertion (RPE), pain (PP), recovery (PRS), and delayed onset of muscle soreness (DOMS) in well-trained female athletes. In a randomized, placebo-controlled, double-blind, crossover trial, fifteen well-trained female athletes (age 21 ± 2 years, height 165 ± 6 cm, body mass 62 ± 5 kg) swallowed either 1.5 g of ACTP or 1.5 g of placebo. The profile of mood states (POMS) and digit cancellation (DCT) were assessed 45 min postingestion, and 5mSRT was performed 60 min postingestion. The RPE and PP were determined immediately after each 30-s repetition of the 5mSRT, and the PRS and DOMS were recorded at 5 min and 24 h post-5mSRT. For the 5mSRT, ACTP ingestion improved the greatest distance (+ 10.88%, p < 0.001), total distance (+ 11.33%, p = 0.0007) and fatigue index (+ 21.43%, p = 0.0003) compared to PLA. Likewise, the DCT score was better on the ACTP (p = 0.0007) than on the PLA. RPE, PP, PRS, and DOMS scores were improved after ACTP ingestion (p < 0.01 for all comparisons) compared to PLA. POMS scores were enhanced with ACTP ingestion compared to PLA (p < 0.01). In conclusion, this study indicates that acute acetaminophen ingestion can improve repeated high intensity short-term maximal performance, attention, mood states, and perceptions of exertion, pain, recovery, and muscle soreness in well-trained female athletes, suggesting potential benefits for their overall athletic performance and mood state. [ABSTRACT FROM AUTHOR]

The interactions of naturally occurring polymers and medicaments, sodium carboxymethyl cellulose (Na-CMC) and Paracetamol (PCM), have attracted the interest of researchers in a variety of biomedical and pharmaceutical applications areas, such as drug delivery, cosmetics and tissue engineering. In our research described here, the effects of temperature and concentration of Na-CMC/PCM/water (W) mixed solutions were studied at various temperatures ranging from 20 °C to 45 °C. We highlighted that different regions can be distinguished in the aqueous Na-CMC/PCM/W complexes, depending on the composition and electrostatic interactions of the solutions, which are associated with significantly different phase behaviors. [ABSTRACT FROM AUTHOR]

Layered double hydroxides (LDH) exhibit macromolecular behavior due to their layered structure, providing unique properties that make them suitable for various applications. Their crystal structure allows for intercalation of various species, demonstrating excellent thermal stability and mechanical strength. Synthesis methods, such as co-precipitation, ion exchange, and hydrothermal techniques, enable the preparation of well-defined LDH macromolecules with tailored characteristics. These materials find applications in catalysis, drug delivery systems, environmental remediation processes, and energy storage devices. Our research described here an LDH material based on nickel, copper, and aluminum was synthesized, characterized and used as a catalyst for the oxidation of Acetaminophen (Ac) using H2O2. Our materials were created using the co-precipitation process at a constant pH. Fourier Transform infrared spectroscopy (FTIR), Raman spectroscopy (RAMAN), X-Ray Diffraction (XRD), Scanning Electron Microscopy (SEM), and Energy-Dispersive X-ray Spectroscopy (EDS) were used to characterize the synthesized material. The material was crystalline and devoid of contaminants, according to the characterization. The CuNiAl-CO3 material was used to catalyze the elimination of the Ac (1 g.L−1) from an aqueous solution. The amount of the LDH, the molar ratio (oxidant/pollutant), the temperature, and the pH were among the experimental factors that were modified to get superior results. The kinetic analysis revealed that using 3 g L−1 of LDH with a molar ratio (oxidant/pollutant) of 2.5 for 3 h at room temperature and without modification of the pH of the solution resulted in a complete degradation of the Ac, and that our LDH performed best in acidic conditions. [ABSTRACT FROM AUTHOR]

Copyright of Microbes & Infectious Diseases is the property of Microbes & Infectious Diseases and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The escalating use of pharmaceuticals, particularly analgesic and antipyretic drugs, due to the rise of emerging ailments has led to a significant environmental concern, that is, increased presence of paracetamol in various water sources. This surge is predominantly linked to heightened paracetamol consumption by individuals seeking relief from COVID-19 symptoms. Consequently, the contamination poses health risk to those consuming affected water, primarily due to the production of toxic compound such as 4-aminophenol, known for its liver damaging effects. This review addresses the surging production and consumption of paracetamol to mitigate water contamination. Essential measures for efficient paracetamol removal from water sources are emphasized. The wastewater is the most affected by paracetamol, with a high concentration compared to the other sources. A few other contemporary treatment methods are covered, with an emphasis on the adsorption process. Adsorption is one of the predominant approaches that has been extensively researched and applied to treat pharmaceutical pollutants, with a high removal percentage reaching 98% by using activated carbon as an adsorbent. The use of efficient adsorbents that have previously been employed for paracetamol elimination will be discussed. The paper also provides a concise interpretation of the mechanisms involved in paracetamol adsorption, presenting an innovative perspective on the efficacy of this process as an excellent method for removal. [ABSTRACT FROM AUTHOR]

High‐performance sensors are in constant demand for health care and environmental protection. In this study, a sensitive paracetamol (PCM) sensor was designed by modifying glassy carbon electrode (GCE) with carbon‐doped boron nitride (BCN/GCE) nanosheets. The BCN nanosheets were synthesized using a molten‐salt method, which ensured the uniformity of size distribution. X‐ray diffraction and transmission electron microscopy results suggested that the carbon‐doping hardly changed the crystal structure and morphology of hexagonal boron nitride (HBN). However, the carbon‐doping can reduce the bandgap, increase the specific surface area and improve the electrical conductivity, which is attributed to the formation of abundant point defects in the BN crystal. These point defects modulate electronic structure and surface activity, and further improve the electrocatalytic properties of BN. The BCN nanosheets exhibited outstanding electrocatalytic activity in the oxidation of paracetamol (PCM). With the help of square wave voltammetry (SWV) method, the BCN/GCE demonstrated linear current response towards PCM covering the concentrations of 0.05–70 μM and 70–200 μM with a detection limit (LOD) of 0.0086 μM. The developed method also showed excellent selectivity and high stability. In addition, the BCN/GCE sensor worked well when it was applied to quantify PCM in actual samples. [ABSTRACT FROM AUTHOR]

Paracetamol is one of the most commonly used painkillers. Its significant production and consumption result in its presence in the environment. For that reason, paracetamol has a negative impact on the organisms living in ecosystems. Therefore, it is necessary to develop effective methods to remove paracetamol from sewage. One of the methods is the bioaugmentation of activated sludge with organisms with increased degradation potential in relation to paracetamol. This study determined the effectiveness of paracetamol degradation by activated sludge augmented with a free or immobilised Pseudomonas moorei KB4. To immobilise the strain, innovative capsules made of cellulose acetate were used, the structure of which provides an optimal environment for the development of bacteria. Augmentation with both a free and immobilised strain significantly improves the efficiency of paracetamol biodegradation by activated sludge. Over a period of 30 days, examined systems allowed ten doses of paracetamol decomposition, while the unaugmented system degraded only four. At the same time, using the immobilised strain does not significantly affect the functioning of the activated sludge, which was reflected in the stability of processes such as nitrification. Due to the high stability of the preparation, it can become a valuable tool in wastewater treatment processes. [ABSTRACT FROM AUTHOR]

Anodic TiO2 nanotube arrays decorated with Ni, Cu, and NiCu alloy thin films were investigated for the first time for the photocatalytic degradation of paracetamol in water solution under UV irradiation. Metallic co-catalysts were deposited on TiO2 nanotubes using magnetron sputtering. The influence of the metal layer composition and thickness on the photocatalytic activity was systematically studied. Photocatalytic experiments showed that only Cu-rich co-catalysts provide enhanced paracetamol degradation rates, whereas Ni-modified photocatalysts exhibit no improvement compared with unmodified TiO2. The best-performing material was obtained by sputtering a 20 nm thick film of 1:1 atomic ratio NiCu alloy: this material exhibits a reaction rate more than doubled compared with pristine TiO2, enabling the complete degradation of 10 mg L−1 of paracetamol in 8 h. The superior performance of NiCu-modified systems over pure Cu-based ones is ascribed to a Ni and Cu synergistic effect. Kinetic tests using selective holes and radical scavengers unveiled, unlike prior findings in the literature, that paracetamol undergoes direct oxidation at the photocatalyst surface via valence band holes. Finally, Chemical Oxygen Demand (COD) tests and High-Resolution Mass Spectrometry (HR-MS) analysis were conducted to assess the degree of mineralization and identify intermediates. In contrast with the existing literature, we demonstrated that the mechanistic pathway involves direct oxidation by valence band holes. [ABSTRACT FROM AUTHOR]

Introduction: Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used in the pediatric age group as pain relievers, antipyretics and anti-inflammatory drugs. Since NSAIDs are used in many medical conditions, there is a need for alternative NSAIDs to be used safely in people with hypersensitivity reactions. Selective and partially selective COX-2 inhibitors and weak COX-1 inhibitors are generally used as safe alternative drugs. The aim of this study was to evaluate safe NSAIDs determined by oral provocation tests (OPTs) according to phenotypes in children with NSAID hypersensitivity reactions. Methods: The results of the oral provocation test performed with alternative NSAIDs (paracetamol, meloxicam, nimesulide, celecoxib) in patients followed up with the diagnosis of NSAID hypersensitivity reaction in the Pediatric Immunology and Allergy Department between January 2015 and February 2023 were evaluated retrospectively. Results: During the study period, 91 patients underwent OPTs with 109 alternative drugs 48 (52.7%) of whom were girls, with a median age of 15 years. 91 patients had a history of reactions to 117 drugs. As an alternative NSAID; OPT was performed with paracetamol in 58 patients, meloxicam in 44 patients, nimesulide in 5 patients, and celecoxib in 2 patients. Since 15 patients used paracetamol safely at home, no tests were performed with paracetamol. Reactions were observed in 3 of the 73 patients (4.1%) who underwent OPT with paracetamol and in 2 of the 44 (4.5%) who underwent OPT with meloxicam. Reactions to nimesulide were also observed in the latter 2 patients (2/5, 40%), but they appeared to tolerate celecoxib. No reaction was observed in the 2 patients who were tested with celecoxib. Conclusion: Paracetamol, meloxicam, and nimesulide can be used as safe alternative drugs in most children with NSAID hypersensitivity. Selective COX-2 inhibitors should be tried as an alternative in patients who cannot tolerate them. [ABSTRACT FROM AUTHOR]

Post-operative pain is one of the main causes of chronic pain, and it is the most representative form of acute pain that can be debilitating, reduce the standard of living, and generate economic implications. When patients undergo a craniotomy, they could face severe consequences such as increased blood pressure, tachycardia, intracranial hypertension, agitation, and chronic cephalgia, which can lead to an increase in mortality. Post-craniotomy pain falls into the moderate to critical category; thus, the anesthesiologist requires the knowledge and skill to achieve adequate pain control during the intraoperative and immediate postoperative periods without interfering with the patient's neurological status. This literature mini-review informs us about the different options available to prevent post-craniotomy pain, such as medications like acetaminophen, nonsteroidal analgesics, gabapentinoids, and dexmedetomidine, among others, or even invasive procedures such as scalp block, which aim to provide analgesia during and after the surgery procedure. [ABSTRACT FROM AUTHOR]

In the present study, electrochemical sensing electrode based on uniform poly(arginine)-modified carbon nanotube paste electrode (PAMCNTPE) is introduced for concurrent determination of caffeic acid and paracetamol. Scanning electron microscopy (SEM) and electrochemical impedance spectroscopy (EIS) were used to characterize the surface of the sensor. In addition, cyclic voltammetry (CV) and differential pulse voltammetry (DPV) were used to investigate the performance of PAMCNTPE. The redox optimum current of caffeic acid was increased dramatically at the PAMCNTPE surface alongside bare carbon nanotube paste electrode (BCNTPE) and their overpotentials decreased. SEM images shows the morphological differences between bare and modified electrode which shows the evidence of modification. The effects of pH, polymerization cycle, and potential were investigated on the electrochemical redox response of caffeic acid based on response surface methodology. In addition, scan rate technique showed the process is adsorption controlled. Under the optimized conditions, linear response was obtained over the range of 10–200 μM, and also, detection limits were found to be 0.13 μM by DPV method on the surface of PAMCNTPE. The PAMCNTPE showed good stability, reproducibility, and repeatability as well as high recovery. The practical application of the PAMCNTPE was demonstrated by measuring the concentration of caffeic acid in apple juice as real sample. The proposed technique is simple, rapid, and cost-effective, serving as an important analytical tool for quality control in the pharmaceutical industry. [ABSTRACT FROM AUTHOR]

Copyright of Medicina Pro Praxi is the property of SOLEN sro and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The study successfully produced a hybrid nanocomposite of silver nanoparticles embedded with end-of-life battery-derived sheets-like nitrogen and sulfur-doped reduced-graphene oxide (AgNPs@NSG), which was utilized to remove methylene blue (MB) and paracetamol (PC) from aqueous solutions. The AgNPs@NSG nanocomposite was analyzed using various techniques. Several conditions, including pH value, adsorbent dose, initial concentration, and contact time, were studied to improve the removal efficiency of MB and PC. The pseudo-second-order model was the best fit for both MB and PC adsorption kinetics. The Langmuir model effectively described the experimental data for the adsorption isotherm, with maximum adsorption capacities of 61.72 and 52.6 mg/g for MB and PC, respectively, at room temperature. Additionally, the AgNPs@NSG nanocomposite demonstrated promising antibacterial activity against Gram-positive and Gram-negative bacteria. The nanocomposite showed inhibition zone diameters of 12.00 mm for Bacillus subtilis, 10.33 mm for Staphylococcus aureus, 9.67 mm for Streptococcus mutans, 10.00 mm for Escherichia coli, 11.33 mm for Proteus vulgaris, 9.67 mm for Serratia marcescens, and 10.67 mm for Vibrio parahaemolyticus. These results indicate the potential of AgNPs@NSG for reducing microorganism infections, especially in wastewater treatment. Overall, this study presents a simple and cost-effective process for producing an efficient material to remove harmful pollutants from wastewater. It also demonstrates its additional antimicrobial properties, highlighting its potential for versatile applications in environmental cleanup and infection control. [ABSTRACT FROM AUTHOR]

The main objective of this study was to improve the aqueous solubility of Paracetamol and Domperidone using hydrotropic agents and to develop a validated method for their simultaneous estimation in pharmaceutical formulations using UV spectrophotometry. Paracetamol and Domperidone were sourced from Sigma Pharmaceuticals and Akums Pharma, respectively. Urea, sodium benzoate, niacinamide, sodium acetate, and sodium citrate were used as hydrotropic agents. The solubility of the drugs was determined using hydrotropic solutions and UV-visible spectrophotometry was employed to assess drug concentrations. Calibration curves for both drugs were prepared and regression equations were derived. The method was validated through statistical analysis of precision, recovery, and repeatability. The solubility of both Paracetamol and Domperidone improved significantly in the presence of hydrotropic agents, particularly urea (8 M). The solubility enhancement ratios were calculated, confirming the improved solubility. UV-visible spectrophotometric analysis showed linearity for Paracetamol (r² = 0.997) and Domperidone (r² = 0.995) in their respective concentration ranges. The regression equations were Y = 0.030 conc. + 0.014 for Paracetamol and Y = 0.098 conc. + 0.030 for Domperidone. The method was validated according to ICH guidelines. Recovery studies showed over 99% recovery for both drugs, indicating accuracy. Intra-day and inter-day precision, as well as analyst-to-analyst variability, were within acceptable limits (RSD < 1%). The solubility of Paracetamol and Domperidone was significantly enhanced using hydrotropic agents, with urea providing the best results. The developed UV spectrophotometric method allowed for the simultaneous estimation of both drugs, showing high precision and accuracy. The method was robust, with consistent results across different conditions and analysts. In conclusion, the study successfully enhanced the solubility of Paracetamol and Domperidone using hydrotropic agents. The developed UV spectrophotometric method for their simultaneous estimation was found to be simple, accurate and precise, making it suitable for routine analysis of pharmaceutical formulation. [ABSTRACT FROM AUTHOR]

Paracetamol is an important analgesic and antipyretic drug showing poor tabletability. Among the various approaches used to improve this property, understanding the forces that govern the crystal packing is revealed to be crucial. We prepared three stable compounds: (par)2∙(nap) (1), (par)∙(quin) (2), and (par)∙(acr) (3) (nap—naphthalene, quin—quinoline, acr—acridine) being cocrystals or solvate. The structural studies showed that all the reported compounds are composed of alternately arranged layers of paracetamol and coformer. Several supramolecular motifs in the paracetamol layer were identified: R 4 4 (22) in (1); R 6 4 (20) and R 2 2 (8) in (2); and R 2 2 (8), R 4 2 (12), and R 4 4 (26) rings in (3). The stability of the crystal network was studied by interactions analysis performed by Hirshfeld surface and fingerprint approaches and the energy between the closest units in the crystal network was calculated. It showed that the strongest interactions were found between blocks connected by N-H⋯O=C and O-H⋯O/N hydrogen bonds due to an important coulombic factor. The dispersive energy becomes important for tail-to-tail (and head-to-tail) arranged paracetamol units, and it prevails in the case of stacking interactions between coformer molecules. The importance of dispersive forces increases with the size of the aromatic system of the coformer. XAS studies confirmed the successful preparation of compounds and provided some details about electron structure. [ABSTRACT FROM AUTHOR]

In the present study, a glassy carbon electrode (GCE) modified with Pd nanoparticles deposited on poly(acrylamide) gel brush‐grafted magnetic particles (Pd/PAAmGB@Fe3O4) with core‐shell structure was fabricated for simultaneous electrochemical detection of dopamine (DA) and paracetamol (PA). Electrochemical performance of Pd/PAAmGB@Fe3O4/GCE was evaluated using cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), and differential pulse voltammetry (DPV). The fabricated sensor exhibited voltammetric sensing with a satisfactory linear determination range from 0.4–41 μM for DA and from 0.5–95 μM for PA. The limit of detection (LOD) was 0.1 μM for DA and 0.17 μM for PA based on signal to noise ratio of 3. The proposed sensor also had excellent reusability and selectivity, good reproducibility and stability, and satisfactory recovery in biomedical examples. It is believed that metal nanoparticles deposited on polymer gel brush composites may offer promising new horizons for sensor growth. [ABSTRACT FROM AUTHOR]

Background: A number of advancements have been implemented in recent years to reduce pain during office hysteroscopy and boost completion rates, for reduction of this pain, many drugs are offered as Non-steroidal anti-inflammatory drugs (NSAIDs) and paracetamol. Paracetamol act centrally by inhibition of brain cyclooxgynase (Cox). This study aimed to assess the analgesic effect of paracetamol and ipubrofen tablets in pain perception during and after outpatient diagnostic hysteroscopy without anaesthesia. Methods: This was a Prospective, Randomized-Controlled clinical trial, conducted at the endoscopy unit of obstetrics and gynecology department at Zagazig university hospitals. Sixty patients included in our trial. The included women were divided into 3 groups; control group: did not receive any medication before the procedure. Group 2 (Paracetamol group): included 20 women received a 1000-mg oral paracetamol tablet, Group 3 (Ibuprofen group): included 20 women received a ibuprofen 600-mg tablet of the same appearance. The treatment was given one hour before the hysteroscopy. Results: The main indication for hysteroscopy was abnormal uterine bleeding in paracetamol group 12(60%), ibuprofen group 10(50%) and control group 7(35%). We found that uterine polyps were the major findings. In paracetamol group 8(40%), ibuprofen group 8(40%) and control group 5(25%). The pain scores, which comprised the VAS before hysteroscopy (p=0.976) and the VAS following hysteroscopy (p=0.832). Conclusions: The injection of ibuprofen and paracetamol one hour before to an office hysterscopy did not lessen pain during the procedure. [ABSTRACT FROM AUTHOR]

This study explored the efficacy of activated carbon derived from rice straw and treated with ZnCl2 (ZnCl2-RS) for the removal of diclofenac sodium (DCF) and paracetamol (PCM) through an adsorption process. The investigation included examining the variations in removal efficiency at different pH levels and ZnCl2-RS doses. The characteristics of the ZnCl2-RS, prepared for the study, were determined through SEM and FTIR analyses, revealing a composition of 49.4% carbon and 8.3% zinc. At pH 5, the adsorption efficiency for DCF and PCM was enhanced, achieving removal rates of 92.2% for DCF and 89.1% for PCM with 0.2 g of ZnCl2-RS. The adsorption of DCF and PCM by ZnCl2-RS followed pseudo-second-order kinetic and adhered to the Langmuir isotherm model. The maximum adsorption capacities were calculated as 26.04 mg/g for DCF and 19.05 mg/g for PCM. In conclusion, the cost-effective production of activated carbon from agricultural waste like rice straw yielded a promising adsorbent material for efficiently removing pharmaceuticals such as diclofenac sodium and paracetamol. This approach not only contributes to waste reduction but also promotes the repurposing of agricultural waste materials. NOVELTY STATEMENT: This study is about the preparation of rice straw, which is produced as agricultural waste, by ZnCl2 activation and the usability of the prepared adsorbent material in the purification of drugs used as analgesics such as diclofenac sodium and paracetamol. Although there are studies on the use of activated carbon produced from rice straw in the removal of pollutants such as dye, studies on drug removal are quite limited. [ABSTRACT FROM AUTHOR]

N‐acetylcysteine (NAC) is regarded as an effective treatment of paracetamol overdoses. However, in cases of "massive" paracetamol overdoses, recent studies indicate that patients may not be sufficiently treated with the standard dose of NAC (300 mg/kg over 20–21 h). The subject is further complicated because "massive overdoses" and "high‐risk" are defined differently; some studies use the ingested amount (e.g., >40 g), and some studies use blood concentrations of paracetamol and transaminases. This narrative review investigates whether high‐dose NAC significantly decreases the risk of hepatotoxicity in patients with massive paracetamol overdoses. Three observational studies were analysed; one study with 373 patients found no significant difference (odds ratio [OR]: 1.27, 95% confidence interval [CI]: 0.49–3.29). One study with 79 patients found a significant difference (OR: 0.27, 95% CI: 0.08–0.94). The third study with 89 patients found a significant difference in hepatoxicity between the groups (p = 0.043). There are no solid evidence to support that treatment with high‐dose NAC significantly reduces the rate of hepatotoxicity in patients presenting with massive paracetamol overdoses. Differences in inclusion criteria in the included studies make the studies incomparable. This paper shows that standardized inclusion is needed to determine whether a high‐dose NAC regimen should be included in clinical practice. [ABSTRACT FROM AUTHOR]

Fixed drug eruptions (FDEs) are dermatological manifestations characterized by recurrent lesions at the same site upon re-exposure to the causative drug. We present a novel case of a 32-year-old female who developed bilateral symmetrical erythematous papules on her thighs following the use of chlorzoxazone for chronic back pain. This case is particularly significant as it underscores the potential for this specific drug, which is commonly prescribed, to induce FDE—a reaction previously unreported in the literature. The findings emphasize the necessity for clinicians to maintain a high index of suspicion for drug-induced skin reactions, even with medications considered safe and routinely used. This case serves as a critical reminder of the importance of thorough medication history assessments and the potential implications of drug interactions in dermatological care. [ABSTRACT FROM AUTHOR]

Developing new products that satisfy performance and durability expectations while also addressing environmental concerns is possible through the reuse of residues produced by industrial processes, aiming to fulfill the principles of circular economy. In this study, we improved the performance of a carbon paste sensor by incorporating untreated (RC) and regranulated/thermally treated (RGC) cork, which are considered biomass residues from the cork industry. We explored the electroanalytical behavior of paracetamol in sulfuric acid solutions using cyclic voltammetry and differential pulse techniques. The cork-modified carbon paste sensors showed greater sensitivity towards paracetamol. Both modified sensors allowed for an excellent resolution in distinguishing the voltammetric responses of paracetamol in sulfuric acid, showing for both an increase in peak currents compared to the unmodified carbon paste electrode. The quantification of paracetamol without interference has proved to be a feasible operation for the RC- and RGC-modified carbon paste sensors; notably, the first showed the most favorable limits of detection (LD = 2.4112 µM) and quantification (LQ = 8.0373 µM) for paracetamol in the sulfuric acid solution, performing significantly better than the second (LD = 10.355 µM, and LQ = 34.518 µM). Finally, the practical utility of the proposed sensors was assessed by analyzing paracetamol in pharmaceutical samples, obtaining satisfactory results that were in line with those obtainable using high-performance liquid chromatography. [ABSTRACT FROM AUTHOR]

Paracetamol (PCT) in aquatic environments has become a global concern due to its potential harm to humans and environments. However, conventional water treatment was only able to degrade PCT partially. It was necessary to treat PCT contaminated water with tertiary technologies in particular by combination approach, such as Fenton oxidation and membrane filtration process. This combined approach enabling mitigation of large chemical footprint and iron residue associated with Fenton oxidation, as well as reducing fouling tendency of the membrane. The aim of this study was to evaluate the PCT removal efficiency by hybrid technology Fenton oxidation and membrane filtration. The membrane performance during the filtration process was also analyzed. As an important parameter for Fenton process, concentration of H2O2/Fe2+ with ratio of 1:0.5 resulted in optimal removal of 45% PCT in terms of COD removal. However, separation using flat sheet Polyethersulfone Ultrafiltration (UF) with constant flux of 120 L/m²·h resulted in insignificant of COD removal. Nevertheless, the UF process was able to remove up to 54% of Fe2+ at pH in alkaline condition with 8.5. In addition, a decrease in membrane permeability down to 0.2 L/m²h/bar over time, according to the filtered specific volume during the UF process, indicates fouling of the UF membrane during the 120 minutes of filtration. While the combined approach does not show significant improvement in COD removal, it does help to reduce the chemical footprint of the process, which is an important factor for the applicability of the selected water treatment method. [ABSTRACT FROM AUTHOR]

Abstract Background Paracetamol is one of the most used antipyretics and analgesics among pediatrics, and its overdose is highly encountered among pediatrics especially in the pre-school age. While it is well-known that paracetamol overdose may lead to toxicities including severe hepatic toxicity, some recent reports have highlighted its “in situ” toxicity on brain tissue at high doses, even in the absence of hepatotoxicity. This can result in acute leukoencephalopathy (AL), coma, or even death. This report describes a case of a child who developed cortical blindness-complicated AL, following a paracetamol overdose. Case presentation An 18-month-old previously healthy girl accidentally ingested 300 mg/kg of paracetamol suspension. After ingestion, the child was in an initial bad condition that has gradually improved. Several days after ingestion, the patient lost her vision, and she remained blind since then despite a newer appreciation to light. The initial brain magnetic resonance imaging (MRI) suggested AL demonstrated as a faint high T2/fluid-attenuated inversion recovery (FLAIR) signal intensity in the cortical and subcortical regions of both parieto-occipital lobes with sulcal effacement and restricted diffusion. After around 3 months, the subsequent brain MRI showed involutional changes that were manifested as a brain volume loss in the same areas with evidence of gyri-form laminar necrosis in both parieto-occipital regions without restricted diffusion. Other brain MRI findings include right cerebral convexity hyperacute subdural hematoma with prominent subarachnoid spaces. Conclusions The child developed cortical blindness-complicated AL following a paracetamol overdose. It is well- known that AL may result from several toxins by their direct and/or indirect effect on the cerebral white matter. However, there is still no enough data in the literature clearly explaining the relation of paracetamol overdose to AL. The generally proposed effect of paracetamol on the brain is mainly justified by the excessive oxidative stress. Further studies at the cellular and genetic levels are still needed to investigate the exact association between paracetamol overdose and AL, as well as the underlying mechanisms involved.

Abstract Detecting and quantifying pharmaceutical compounds in various environmental matrices is complex and challenging. This difficulty stems from the trace levels at which these compounds are found and the lack of analytical methods that are rapid, cost-effective, and portable. To address these challenges, this study aimed to develop microfluidic paper-based analytical devices (μ-PADs) using beeswax screen printing for fabrication. Key parameters, including reaction time, concentration, reagent volume, and channel length, were optimized using response surface methodology. Under optimal conditions of 5 ppm sample concentration, 10 μL reagent volume, 10 min reaction time, and 2 cm channel length, the analytical performance of the μPAD was evaluated and compared with the standard UV–Vis spectrophotometry method. The microfluidic analytical device demonstrated detection limits at 0.03 μg/ml, compared to 0.01 μg/ml for the UV–Vis spectrophotometer. Although the sensitivity of µ-PADs in this study (0.03 μg/ml) is lower than that of UV–Vis (0.01 μg/ml), it represents an improvement over the previous µ-PAD report (1 μg/ml) on the same analytes. Both methods exhibited commendable precision, with a relative standard deviation below 2%. Additionally, recovery rates were acceptable and comparable, ranging from 86.8 to 99.6% for µ-PADs and 96.5–99% for UV–Vis. The analytical performance evaluation suggests that µPADs provide excellent sensitivity, precision, and accuracy for trace-level paracetamol analysis. A paired t-test further confirmed no statistically significant difference between the two methods, underscoring the promising potential of µ-PADs for trace-level paracetamol quantification in water samples without conventional analytical instruments.

Acute heat injury (AHI) is a serious condition caused by an excessive increase in body temperature, usually due to prolonged exposure to high environmental temperatures or intense physical activity in the heat. Without timely treatment, heat stroke can lead to severe damage to the central nervous system with cerebral edema, profound disturbances in the water-salt balance and internal organs, coma and death. Since the effectiveness of drugs for the treatment of thermal injuries has not been proven, the search for new thermoprotective agents with different mechanisms of action, in particular inhibitors of the arachidonic acid cascade, is urgent. In a preliminary screening study on the AHI model in rats, it was found that among cyclooxygenase (COX) inhibitors, the highly selective COX-2 inhibitor celecoxib and the analgesic-antipyretic para­cetamol are the most effective in preventing hyperthermia and improving the course of the recovery period. The purpose of this study was to determine the impact of the specified screening leaders on the functional state of the central nervous system, pain sensitivity and physical endurance in the recovery period of heat injury. The AHI model was reproduced on adult white male rats according to the previously proposed and validated method by means of a 30-minute exposure at +55°C. Animals were divided into 4 groups with 8 rats in each group: intact control, control pathology, paracetamol group and celecoxib group. Based on the results of the study, it was established that celecoxib exhibits a pronounced thermoprotective effect, probably improves the state of the central nervous system in terms of behavioral reactions and physical endurance of animals in the recovery period after acute heat injury. At the same time, paracetamol after acute heat injury does not have a distinct positive effect on the functional state of the central nervous system, moderately improves the physical endurance of rats and is inferior to celecoxib in all the studied parameters. These results open new opportunities for the development of approaches to the treatment of AHI and confirm the different effectiveness of the use of celecoxib and paracetamol in thermal injuries.

Abstract Reduced functional connectivity of physiological systems is associated with poor prognosis in critically ill patients. However, physiological network analysis is not commonly used in clinical practice and awaits quantitative evidence. Acute liver failure (ALF) is associated with multiorgan failure and mortality. Prognostication in ALF is highly important for clinical management but is currently dependent on models that do not consider the interaction between organ systems. This study aims to examine whether physiological network analysis can predict survival in patients with ALF. Data from 640 adult patients admitted to the ICU for paracetamol-induced ALF were extracted from the MIMIC-III database. Parenclitic network analysis was performed on the routine biomarkers using 28-day survivors as reference population and network clusters were identified for survivors and non-survivors using k-clique percolation method. Network analysis showed that liver function biomarkers were more clustered in survivors than in non-survivors. Arterial pH was also found to cluster with serum creatinine and bicarbonate in survivors compared with non-survivors, where it clustered with respiratory nodes indicating physiologically distinctive compensatory mechanism. Deviation along the pH-bicarbonate and pH-creatinine axes significantly predicts mortality independent of current prognostic indicators. These results demonstrate that network analysis can provide pathophysiologic insight and predict survival in critically ill patients with ALF.

The electrooxidation of acyclovir (ACv) and paracetamol (PC) on a glassy carbon electrode (GCE) coated with reduced graphene oxide (GOred) and electrodeposited gold particles (Au/GOred/GCE) was studied. The separation of the oxidation peaks of PC and ACv on the Au/GOred/GCE was achieved by decreasing overvoltage. А selective and highly sensitive voltammetric method for the simultaneous determination of PC and ACv was developed. The linear dynamic range of PC and ACv was from 5×10-3 to 5×10-8 M. The proposed method was successfully applied to detect non-metabolized forms of PC and ACv in the presence of human urine.

This study investigates the paracetamol removal efficiency by multi-tip pulsed corona discharges, highlighting the conditions avoiding mutual effects between two consecutive streamer branching discharges generated by each tip. The results show that the production of reactive oxygen and nitrogen species (RONS) in the liquid phase and the efficiency of paracetamol removal are influenced by the distance between two contiguous tips due to the mutual effects for small inter-tip distances between 4 mm and 8 mm in the case of a fixed inter-electrode distance of 5 mm (i.e. distance between the tip summit and the water surface). Beyond an inter-tip distance of 12 mm (over twice the gap distance), the mutual effects of branching discharges were no longer observed since the field lines did not overlap, making the production and absorption of liquid-phase species more efficient. Furthermore, RONS production was almost linear when moving from one to four tip electrodes: [H2O2]1tip: 0.52 mg l–1 versus [H2O2]4tips: 1.99 mg l–1, a ratio of 3.82. Optimum values were reached for an inter-tip distance of 16 mm. In this case, the enhancement factor in this reactor configuration is the surface integration between the plasma and the liquid surface to be treated. Furthermore, the results show a quasi-exponential increase in the percentage of paracetamol degradation as a function of the number of electrodes, from 4% with a mono-tip configuration to over 78% for a treatment with a four tip one. [ABSTRACT FROM AUTHOR]

In this study, experimental carry out of liquid–vapor and solid–liquid phase transitions were conducted for the ternary system {CO2 (1) + ethanol (2) + acetaminophen (3)} at different concentrations of paracetamol in ethanol for temperatures from 313 to 333 K and pressures up to 12 MPa. Experimental high pressure phase transition data were obtained using the static method in a variable volume view cell. Experimental data were compared with the literature for systems containing acetaminophen in a saturated solution. The presence of paracetamol in the binary system {CO2 (1) + ethanol (2)} significantly alters the behavior of the phase under the conditions of temperature and concentration studied. It was observed that in the ternary system {CO2 (1) + ethanol (2) + acetaminophen (3)} with a saturated solution at the lowest temperature, 313 K, CO2 acts as a cosolvent for mole fractions lower than 0.6. Thermodynamic simulations employing the Perturbed Chain Statistical Associating Fluid Theory (PC-SAFT) Equations of State (EoS) aligned the experimental results adequately. The observed minimal deviations in pressure and temperature validate the efficacy of the thermodynamic models applied in this study. [ABSTRACT FROM AUTHOR]

Pharmaceuticals account for 19–32% of healthcare greenhouse gas (GHG) emissions. Paracetamol is a common perioperative analgesic agent. We estimated GHG emissions associated with i.v. and oral formulations of paracetamol used in the perioperative period. Life-cycle assessment of GHG emissions (expressed as carbon dioxide equivalents CO 2 e) of i.v. and oral paracetamol preparations was performed. Perioperative paracetamol prescribing practices and costs for 26 hospitals in USA, UK, and Australia were retrospectively audited. For those surgical patients for whom oral formulations were indicated, CO 2 e and costs of actual prescribing practices for i.v. or oral doses were compared with optimal oral prescribing. The carbon footprint for a 1 g dose was 38 g CO 2 e (oral tablet), 151 g CO 2 e (oral liquid), and 310–628 g CO 2 e (i.v. dependent on type of packaging and administration supplies). Of the eligible USA patients, 37% received paracetamol (67% was i.v.). Of the eligible UK patients, 85% received paracetamol (80% was i.v.). Of the eligible Australian patients, 66% received paracetamol (70% was i.v.). If the emissions mitigation opportunity from substituting oral tablets for i.v. paracetamol is extrapolated to USA, UK, and Australia elective surgical encounters in 2019, ∼5.7 kt CO 2 e could have been avoided and would save 98.3% of financial costs. Intravenous paracetamol has 12-fold greater life-cycle carbon emissions than the oral tablet form. Glass vials have higher greenhouse gas emissions than plastic vials. Intravenous administration should be reserved for cases in which oral formulations are not feasible. [ABSTRACT FROM AUTHOR]

Objective: Utilizing two-sample Mendelian randomization (TSMR) analysis, this study aims to explore the potential bidirectional causal relationship between common nonsteroidal anti-inflammatory drugs (paracetamol, ibuprofen, aspirin) and major depression (MD) from a genetic standpoint. Methods: We employed summarized data from a Genome-Wide Association Study (GWAS) of European populations. The inverse variance weighted (IVW) method was used for TSMR analysis; outcomes were evaluated based on p -value, OR (Odds Ratio), and 95% confidence interval (95% CI). Results: From a genetic perspective, the study found that the use of paracetamol and ibuprofen increased the risk of MD (IVW (MRE): OR = 2.314, 95% CI: 1.609–3.327; p = 6.07E-06) and (IVW (MRE): OR = 2.308, 95% CI: 1.780–3.653; p = 0.002), respectively. No significant causal relationship was found between aspirin and MD (p > 0.05). Reverse TSMR analysis found that MD increased the genetic predisposition to use paracetamol, ibuprofen, and aspirin (IVW (MRE): OR = 1.042, 95% CI: 1.030–1.054, p = 3.07E-12), (IVW (FE): OR = 1.015, 95% CI: 1.007–1.023, p = 1.13E-04), (IVW (MRE): OR = 1.019, 95% CI: 1.009–1.030, p = 4.22E-04), respectively. Other analytical methods and sensitivity analyses further supported the robustness and reliability of these findings. Conclusion: This study provides preliminary genetic evidence through bidirectional TSMR analysis that MD increases the genetic predisposition to use paracetamol, ibuprofen, and aspirin, aiding clinicians in devising preventive strategies against the misuse of non-steroidal anti-inflammatory drugs. Moreover, we found that the use of paracetamol and ibuprofen increases the risk of MD, whereas aspirin did not. This suggests a crucial clinical implication: clinicians treating MD patients could opt for the relatively safer aspirin over paracetamol and ibuprofen. [ABSTRACT FROM AUTHOR]

BACKGROUND: The design of new‐generation flexible sensors for medical applications has gained considerable interest in the research community in recent past years. Herein, a free‐standing flexible electrode was developed for the electrochemical determination of Paracetamol (PC). This graphene‐based paper electrode was prepared using graphene and MnCo2O4 dispersion with a mold‐casting method followed by chemical reduction. The morphology and structure of our flexible paper electrode (MnCo2O4/GP) were characterized by scanning electron microscopy, energy‐dispersive, X‐ray diffraction, X‐ray photoelectron, and Raman spectroscopy. RESULTS: The as‐prepared flexible MnCo2O4/GP showed outstanding sensing performance for PC, as compared to GP, due to the excellent electrochemical properties of MnCo2O4. The proposed sensor exhibited a wide linear range of 4.64–1000 μM for electrochemical determination of PC with a low detection limit of 1.39 μM. Furthermore, MnCo2O4/GP was successfully applied for PC syrup and tablets with good accuracy results. CONCLUSIONS: For the first time, the present study demonstrated the fabrication and utilization of MnCo2O4‐modified graphene paper to develop a flexible and sensitive electrode for monitoring PC. © 2024 The Author(s). Journal of Chemical Technology and Biotechnology published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry (SCI). [ABSTRACT FROM AUTHOR]

Abstract Background Pyroglutamic acidosis is a rare cause of high anion gap metabolic acidosis. Most cases of paracetamol related pyroglutamic acidosis are described in malnourished women and patients with kidney/liver failure, alcohol use or severe sepsis. In this report, we describe how pyroglutamic acidosis could be related to the use of chronic therapeutic paracetamol with only malnutrition as an associated risk factor. Case presentation We report a case of a 67-year-old male patient developing a pyroglutamic acidosis. The patient was initially admitted to hospital for infectious osteoarthritis and developed a metabolic acidosis during his hospital stay. Analgesics included daily therapeutic doses of paracetamol. What makes our case unusual is that our malnourished male patient did not have renal or hepatic failure. The diagnosis of paracetamol related pyroglutamic acidosis was made after ruling out the main causes of metabolic acidosis. It was further confirmed by urine organic acids measurement showing a markedly elevated level of pyroglutamic aciduria. Paracetamol was discontinued allowing a prompt correction of the anion gap. Conclusion This case is a representative of pyroglutamic acidosis related to chronic therapeutic paracetamol with only malnutrition as an associated risk factor. Physicians should be aware of such unusual cause of metabolic acidosis, which may be more common than expected in hospitalized patients. A high clinical suspicion is needed when urine organic acids analysis is not available.

Abstract Metal-organic frameworks (MOFs) with their exceptional properties have the potential to revolutionize the field of electrochemistry and pave the way for new and exciting applications. MOFs is an excellent choice as an active electrocatalyst component in the fabrication of electrochemical sensors. Here, bimetallic NiCo-MOFs, monometallic Ni-MOFs, and Co-MOFs were fabricated to modify the carbon paste electrode. Moreover, the ratio between Co and Ni within the bimetallic MOFs was optimized. Our aim in this work is to synthesize different compositions from bimetallic MOFs and systematically compare their catalytic activity with mono-metallic MOFs on paracetamol. The structure and properties of the 2D NiCo-MOFs were characterized by scanning electron microscope, X-ray photoelectron spectroscopy, Fourier transform infrared, and electrochemical method. Bimetallic Ni0.75Co0.25-MOFs modified carbon paste sensor displayed the optimum sensing performance for the electrochemical detection of paracetamol. A linear response over the range 6.00 × 10− 7 to 1.00 × 10− 4 M with a detection limit of 2.10 × 10− 8 M was obtained. The proposed method was applied to detect paracetamol in spiked human plasma and to determine paracetamol in the presence of its major toxic impurity, p-aminophenol. These findings suggest the considerable potential use of the newly developed sensor as a point-of-care tool for detecting paracetamol and p-aminophenol in the future.

Escherichia coli is a major cause of serious infections, with antibiotic resistance rendering many treatments ineffective. Hence, novel strategies to combat this pathogen are needed. Anti-virulence therapy is a promising new approach for the subsequent era. Recent research has examined the impact of sub-inhibitory doses of ascorbic acid and paracetamol on Escherichia coli virulence factors. This study evaluated biofilm formation, protease production, motility behavior, serum resistance, expression of virulence-regulating genes (using RT-PCR), and survival rates in a mouse model. Ascorbic acid significantly reduced biofilm formation, protease production, motility, and serum resistance from 100% in untreated isolates to 22–89%, 10–89%, 2–57%, and 31–35% in treated isolates, respectively. Paracetamol also reduced these factors from 100% in untreated isolates to 16–76%, 1–43%, 16–38%, and 31–35%, respectively. Both drugs significantly down-regulated virulence-regulating genes papC, fimH, ompT_m, stcE, fliC, and kpsMTII. Mice treated with these drugs had a 100% survival rate compared with 60% in the positive control group control inoculated with untreated bacteria. This study highlights the potential of ascorbic acid and paracetamol as anti-virulence agents, suggesting their use as adjunct therapies alongside conventional antimicrobials or as alternative treatments for resistant Escherichia coli infections.

Ajeng Diantini,1,2,&ast; Mohammed Alfaqeeh,3,&ast; Lanny Indah Permatasari,3,&ast; Mirna Nurfitriani,3,&ast; Lela Durotulailah,3,&ast; Wening Wulandari,3,&ast; Truly Deti Rose Sitorus,4 Gofarana Wilar,1,2 Jutti Levita1,2,&ast; 1Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Padjadjaran. University, Sumedang, West Java, 45363, Indonesia; 2Center of Excellence in Higher Education for Pharmaceutical Care Innovation, Padjadjaran University, Sumedang, West Java, 45363, Indonesia; 3Master Program in Clinical Pharmacy, Faculty of Pharmacy, Padjadjaran University, Sumedang, West Java, 45363, Indonesia; 4Department of Pharmacology and Therapy, Faculty of Medicine, Padjadjaran University, Sumedang, West Java, 45363, Indonesia&ast;These authors contributed equally to this workCorrespondence: Jutti Levita, Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Padjadjaran University, Sumedang, West Java, 46363, Indonesia, Tel +6222-84288888 Ext 3510, Email jutti.levita@unpad.ac.idAbstract: Cough and cold symptoms (CCS) are common pediatric conditions often treated with over-the-counter (OTC) medications. However, the available knowledge regarding the safety and toxicity of these medications in children is inadequate. Therefore, understanding their clinical toxicology is crucial for safeguarding children’s well-being. This narrative review highlights the importance of clinical toxicology in evaluating the safety and toxicity profile of OTC medications for treating CCS in pediatric patients. The pharmacology, clinical features, and adverse effects of various drug classes commonly found in cough and cold medications are briefly discussed. Pharmacokinetic and pharmacodynamic parameters are also examined to understand the interactions between these drugs and the body. OTC cough and cold medications often contain active ingredients such as antihistamines, decongestants, antitussives, expectorants, and analgesics-antipyretics. The combination of multiple ingredients in these products significantly increases the risk of adverse effects and unintentional overdoses. Several case studies have reported significant toxicity and even fatalities associated with the use of these medications in children. This review underscores the critical importance of clinical toxicology in evaluating the safety and toxicity profile of OTC medications employed for treating CCS in pediatric patients. The findings highlight the significance of informed clinical practice and public health policies to ensure the well-being of children using OTC cough and cold medications.Keywords: bromhexine, chlorpheniramine maleate, dextromethorphan, glyceryl guaiacolate, paracetamol, pseudoephedrine

Corrosion is one of the main problems causing damage to metals. The occurrence of a reaction with the surrounding environment accompanied by several factors cause deterioration so that corrosion causes damage to the material. Therefore, researchers added inhibitors as a way to control corrosion. This study used paracetamol as an inhibitor against corrosion protection of AISI 1020 steel with 3% NaCl as the media. The method used for the corrosion test was the weight loss and toughness test using the Charpy method of impact testing. This study obtained the lowest corrosion rate value at the addition of 220 ppm inhibitor concentration with immersion time for 7 days of 1.078 mpy. The efficiency observed in this study showed that adding an inhibitor concentration of 220 ppm with the immersion time of 7 days had the highest value reaching 71.42%. Moreover, the impact test results got the highest value on the 220 ppm inhibitor variation with the immersion time of 7 days, reaching 0.0817 J/

Background: Drug overdose is a common health problem and recently, deliberate self-poisoning using medicinal drugs is becoming popular in both urban and rural areas of Sri Lanka. This study aimed to describe the epidemiology and clinical manifestations following drug overdose in adults.Methods: A prospective clinical study was conducted in Teaching Hospital Ratnapura, Sri Lanka over one year commencing from September 2018 including all adult patients with drug overdose.Results: There were 202 (21%) adult patients with drug overdose from which deliberate self-poisonings were 200 (99%) and accidental poisonings were 2 (1%). Females were 124 (61%) and the commonly affected age group was 15-30 years (158;78%). The commonest overdosing agent was paracetamol (109:54%). Most patients (96;47.5%) were admitted to the hospital within 1-4 hours of the ingestion (IQR 2-4 hrs). Most of the patients (86;42.5%) were treated at hospital for 2 days (1QR 2-3 days). Decontamination was done for 151 (75%) of patients. Gastrointestinal symptoms including nausea and vomiting occurred prominently and they were 42% (n=89) and 53 % (n=113) respectively. Complications were detected in 15 (7.4%) cases from which ECG changes 6 (3%), respiratory failure 5 (2.5%), acute liver failure 4 (2%), acute kidney injury 3 (1.5%) and hypotension 3 (1.5%). Six (3%) were treated at the intensive care unit from which 5 (2.5%) were intubated. There were 2 (1%) deaths and the case fatality rate of drug overdose was 1%.Conclusions: Drug overdoses are common in intentional type. Young females are mostly affected and the commonest overdosing agent is paracetamol.

The use of paracetamol in excessive doses can increase the hepatotoxicity effect, which causes acute hepatocellular injury. Dewa leaves (Gynura pseudochina (L.) DC) contain flavonoids, saponin, and tannin. This study aimed to determine the effect of ethanol extract from dewa leaves in reducing the impact of paracetamol induction on SGPT and SGOT levels and liver histology of white rats (Rattus norvegicus). The test was grouped into five treatment groups, namely: normal control; negative control with paracetamol induction 315mg/KgBW; Dewa leaf extract was administered with three variations in dosage, namely 3.15mg/KgBW, 3.50mg/KgBW and 3.85mg/KgBW and each treatment group consisted of 5 rats as replications. Dewa leaf extract was administered to the experimental animal, followed by the administration of paracetamol 8 hours after the extract was given orally; both treatments were given for 14 days. Measurement of SGPT and SGOT levels uses the photometric method. The hepatoprotective effect was further verified by histopathology of the liver. Liver histology was made using the paraffin method. SGPT levels, SGOT levels, and Hepatocyte Damage Scores were analyzed using Analysis of Variance (ANOVA); if the results are significant, continue with the Least Significance Difference (LSD) test at a significance level of 5%. The results of this study show that the administration of dewa leaf extract was not able to significantly reduce SGPT and SGOT levels in rats. The administration of dewa leaf extract at doses of 3.50mg/KgBW and 3.85mg/KgBW significantly prevented histological damage to rat livers.

NSAIDs and paracetamol are commonly used as antipyretic treatments, which may impair renal and hepatic function, respectively. Both organ systems are also negatively affected by COVID-19. In two retrospective case–control studies, we investigated whether COVID-19 is a risk factor for the development of renal or hepatic function impairment after NSAID and paracetamol use, respectively. In the NSAID study, we defined cases as patients with a decrease of ≥15% in the estimated glomerular filtration rate (eGFR). We matched them using a 1:2 ratio with controls who did not show a decrease in the eGFR. For the paracetamol study, we matched patients with ALT or ALP ≥ 3x, the upper limits of normal, using a 1:3 ratio with controls whose liver enzymes did not increase. In both studies, we selected demographic data, comorbidities, drug doses, and laboratory values as predictors in addition to SARS-CoV-2 test status. We applied different machine learning models to predict renal and hepatic function impairment. From the cohort of 12,263 unique adult inpatients, we found 288 cases of renal function impairment, which were matched with 576 controls, and 213 cases of liver function impairment, which were matched with 639 controls. In both case–control studies, testing positive for SARS-CoV-2 was not an independent risk factor for the studied adverse drug effects.

Background In acute settings around the globe, renal/ureteric colic remains one of the most common diagnoses for patients presenting with loin-to-groin pain. Even though management spans from medical expulsive therapies to surgical options, pain as a significant component of a patient’s presentation must be dealt with quickly, decisively, and safely, as it can be excruciating and its effects on overall health are dire. This study aimed to explore compliance with the National Institute for Health and Care Excellence (NICE) guidelines for pain management in patients with suspected renal/ureteric colic. It includes the use of nonsteroidal anti-inflammatory drugs (NSAIDs), intravenous paracetamol, and opioids as first-, second-, and third-line analgesics, respectively, and does not offer antispasmodics. In the event of deviations from the standard, the aim was to put in corrective measures, followed by re-exploration of compliance with patient care. Methods This study involved a single healthcare facility with the study type being retrospective before interventions and prospective after interventions. In the first cycle, we retrieved and analysed 78 patients records whom had been suspected to have renal/ureteric colic between July and September 2022. The inclusion criteria were documented complaints of “flank/loin-to-groin pain” and diagnosis prior to performing diagnostic tests. We surveyed the first-, second-, and third-line painkillers issued, and whether an antispasmodic was given. We collected and entered data into a Microsoft Excel file and correlated it with NICE standards. Having found deviations from the standard, we conducted interventions, allowed time for clinicians to adapt, and re-explored compliance using patient case records [n=58] between February and May 2023. Results In the 1 st cycle, 78 patients were suspected of having renal/ureteric colic. M: F = 1.2:1. Non-contrast computerized tomography of the kidney ureters and bladder (NC-CTKUB) confirmed 87% of patients with stones and 3% had no stones. NC-CTKUB was not performed in 9% of patients because they were young, and urinalysis showed no microscopic hematuria. One patient had discharged against medical advise before the NC-CTKUB was performed. Compliance with the NICE pain management guidelines for suspected renal/ureteric colic was full in 23% of cases but unsatisfactory in 78% of cases. In the 2 nd cycle, M: F = 1.5:1, NC-CTKUB was not re-audited, as the first cycle study yielded excellent results, and our action plan resulted in an NICE pain management compliance rate of 56%. Although our interventions resulted in improvements of more than twice the initial results, work still needs to be performed. Conclusion Clinicians’ ability to correctly diagnose renal/ureteric colic is remarkable. However, the pain management compliance rate indicates room for improvement. This may be due to the limited awareness of the NICE guideline or the fact that the clinical team has an affinity for certain analgesics compared to others. We propose the need to consider select variables to existing standard guidelines to enhance compliance for improved patient care.

Background and Purpose: The analgesic action of paracetamol involves KV7 channels, and its metabolite N‐acetyl‐p‐benzo quinone imine (NAPQI), a cysteine modifying reagent, was shown to increase currents through such channels in nociceptors. Modification of cysteine residues by N‐ethylmaleimide, H2O2, or nitric oxide has been found to modulate currents through KV7 channels. The study aims to identify whether, and if so which, cysteine residues in neuronal KV7 channels might be responsible for the effects of NAPQI. Experimental Approach: To address this question, we used a combination of perforated patch‐clamp recordings, site‐directed mutagenesis, and mass spectrometry applied to recombinant KV7.1 to KV7.5 channels. Key Results: Currents through the cardiac subtype KV7.1 were reduced by NAPQI. Currents through all other subtypes were increased, either by an isolated shift of the channel voltage dependence to more negative values (KV7.3) or by such a shift combined with increased maximal current levels (KV7.2, KV7.4, KV7.5). A stretch of three cysteine residues in the S2‐S3 linker region of KV7.2 was necessary and sufficient to mediate these effects. Conclusion and Implication: The paracetamol metabolite N‐acetyl‐p‐benzo quinone imine (NAPQI) modifies cysteine residues of KV7 subunits and reinforces channel gating in homomeric and heteromeric KV7.2 to KV7.5, but not in KV7.1 channels. In KV7.2, a triple cysteine motif located within the S2‐S3 linker region mediates this reinforcement that can be expected to reduce the excitability of nociceptors and to mediate antinociceptive actions of paracetamol. [ABSTRACT FROM AUTHOR]

Background: Pyroglutamic acidosis is a rare cause of high anion gap metabolic acidosis. Most cases of paracetamol related pyroglutamic acidosis are described in malnourished women and patients with kidney/liver failure, alcohol use or severe sepsis. In this report, we describe how pyroglutamic acidosis could be related to the use of chronic therapeutic paracetamol with only malnutrition as an associated risk factor. Case presentation: We report a case of a 67-year-old male patient developing a pyroglutamic acidosis. The patient was initially admitted to hospital for infectious osteoarthritis and developed a metabolic acidosis during his hospital stay. Analgesics included daily therapeutic doses of paracetamol. What makes our case unusual is that our malnourished male patient did not have renal or hepatic failure. The diagnosis of paracetamol related pyroglutamic acidosis was made after ruling out the main causes of metabolic acidosis. It was further confirmed by urine organic acids measurement showing a markedly elevated level of pyroglutamic aciduria. Paracetamol was discontinued allowing a prompt correction of the anion gap. Conclusion: This case is a representative of pyroglutamic acidosis related to chronic therapeutic paracetamol with only malnutrition as an associated risk factor. Physicians should be aware of such unusual cause of metabolic acidosis, which may be more common than expected in hospitalized patients. A high clinical suspicion is needed when urine organic acids analysis is not available. [ABSTRACT FROM AUTHOR]

Metal-organic frameworks (MOFs) with their exceptional properties have the potential to revolutionize the field of electrochemistry and pave the way for new and exciting applications. MOFs is an excellent choice as an active electrocatalyst component in the fabrication of electrochemical sensors. Here, bimetallic NiCo-MOFs, monometallic Ni-MOFs, and Co-MOFs were fabricated to modify the carbon paste electrode. Moreover, the ratio between Co and Ni within the bimetallic MOFs was optimized. Our aim in this work is to synthesize different compositions from bimetallic MOFs and systematically compare their catalytic activity with mono-metallic MOFs on paracetamol. The structure and properties of the 2D NiCo-MOFs were characterized by scanning electron microscope, X-ray photoelectron spectroscopy, Fourier transform infrared, and electrochemical method. Bimetallic Ni0.75Co0.25-MOFs modified carbon paste sensor displayed the optimum sensing performance for the electrochemical detection of paracetamol. A linear response over the range 6.00 × 10− 7 to 1.00 × 10− 4 M with a detection limit of 2.10 × 10− 8 M was obtained. The proposed method was applied to detect paracetamol in spiked human plasma and to determine paracetamol in the presence of its major toxic impurity, p-aminophenol. These findings suggest the considerable potential use of the newly developed sensor as a point-of-care tool for detecting paracetamol and p-aminophenol in the future. [ABSTRACT FROM AUTHOR]