Kinetic modeling of the photocatalytic degradation of acetaminophen and its main transformation products.

In this study, a kinetic model of the heterogeneous photocatalytic degradation of acetaminophen and its main transformation products is presented. Kinetic photocatalytic modeling and photon absorption rate modeling were included. Monte Carlo method was used to model the photon absorption process. Experiments were carried out in a reactor operated in batch mode and TiO2 nanotubes were used as photocatalyst irradiated with 254 nm UVC. Kinetic parameters were estimated from the experiments data by applying a non-linear regression procedure. Intrinsic expressions to the kinetics of acetaminophen degradation and its main transformation products were derived. Model, kinetics and photon absorption formulations and parameters proved to be affordable for describing the photocatalytic degradation of acetaminophen, but improvements should be done for better description of formation and oxidation kinetics of main transformation products. The model should be tested with other pharmaceuticals and emergent pollutants to calibrate it and evaluate its applicability in a wide range of compounds.

Safety of metamizole (dipyrone) for the treatment of mild to moderate pain-an overview of systematic reviews.

Metamizole, as known as dipyrone or novaminsulfone is widely used, especially in Latin America, for its analgesic and antipyretic function. However, several countries have banned it due to the risk of agranulocytosis, skin necrosis, and other serious adverse effects. To assess the safety of metamizole compared to other commonly used non-opioid analgesics (paracetamol, ibuprofen, and acetylsalicylic acid). An overview of systematic reviews. The searches were performed in the PubMed, Cochrane Library, Embase, Scopus and LILACS databases. Systematic reviews of randomized and nonrandomized clinical trials with adult patients with mild to moderate pain that assessed the adverse effects of metamizole were included. A methodological quality assessment was performed through ROBIS. The protocol of this systematic review was submitted to the International Prospective Register of Systematic Reviews (Prospero, CRD42021295272). Of 387 identified studies, four were included, with a total of 20,643 participants, all submitted to a single dose by oral, intramuscular, or intravenous route. No study reported a serious adverse effect. However, 60 of 778 patients (7.7%) who used metamizole; 120/828 (14.5%) who used acetylsalicylic acid; 56/443 (12.6%) who used paracetamol; and 27/213 (12.7%) who used ibuprofen had mild adverse effects. A complementary statistical analysis showed that metamizole, at any dose, has a 38.8% lower chance of adverse effects compared to paracetamol and 46.8% compared to acetylsalicylic acid. The results shows that metamizole is a safe drug with evidence of a lower incidence of adverse effects compared to paracetamol and acetylsalicylic acid.

[Liver transplantation as treatment for acetaminophen poisoning]. / Trasplante hepático como tratamiento de intoxicación por paracetamol.

Acetaminophen is a commonly used analgesic and antipyretic drug, which has experienced an increase in its consumption in recent years in our environment. There has also been an increase in the number of accidental and intentional overdoses that were treated by the health system. Its toxicity is dose-dependent and can cause fulminant liver failure, becoming one of the main reasons for liver transplantation in English-speaking countries. The case of a 28-year-old woman with a history of major depression and five previous suicide attempts, who deliberately ingested a significant amount of paracetamol tablets, is here presented. She developed fulminant liver failure and metabolic acidosis, for which she underwent an emergency liver transplant due to the severity of her condition, from which she evolved favorably. The decision to perform a liver transplant in serious cases like this and under a condition of severe psychiatric vulnerability is challenging and must be carefully considered. This particular case illustrates the importance of multidisciplinary care including psychiatric evaluation in patients with acetaminophen poisoning.

El paracetamol es una droga analgésica y antipirética comúnmente utilizada, que ha experimentado un aumento en su consumo en los últimos años en nuestro medio. También se ha observado un incremento en el número de sobredosis accidentales e intencionales que fueron atendidas por el sistema de salud. Su toxicidad es dosis dependiente y puede causar falla hepática fulminante, convirtiéndose en una de las principales razones de trasplante hepático en países angloparlantes. Se presenta el caso de una mujer de 28 años con antecedentes de depresión mayor y cinco intentos de suicidio previos, quien ingirió deliberadamente una cantidad significativa de comprimidos de paracetamol. Desarrolló una falla hepática fulminante y acidosis metabólica, por lo que fue sometida a un trasplante hepático de emergencia debido a la gravedad de su condición evolucionando favorablemente. La decisión de realizar un trasplante hepático en casos graves como este y bajo una condición de vulnerabilidad psiquiátrica grave, es un desafío y debe considerarse cuidadosamente. Este caso en particular ilustra la importancia de la atención multidisciplinaria incluyendo la evaluación psiquiátrica en pacientes con intoxicación por paracetamol.

Efficacy of different routes of acetaminophen administration for postoperative pain in children: a systematic review and network meta-analysis.

PURPOSE: Acetaminophen is the most common drug used to treat acute pain in the pediatric population, given its wide safety margin, low cost, and multiple routes for administration. We sought to determine the most efficacious route of acetaminophen administration for postoperative acute pain relief in the pediatric surgical population. METHODS: We conducted a systematic review of randomized controlled trials (RCTs) that included children aged between 30 days and 17 yr who underwent any type of surgical procedure and that evaluated the analgesic efficacy of different routes of administration of acetaminophen for the treatment of postoperative pain. We searched MEDLINE, CENTRAL, Embase, CINAHL, LILACs, and Google Scholar databases for trials published from inception to 16 April 2023. We assessed the risk of bias in the included studies using the Cochrane Risk of Bias 1.0 tool. We performed a frequentist network meta-analysis using a random-effects model. Our primary outcome was postoperative pain using validated pain scales. RESULTS: We screened 2,344 studies and included 14 trials with 829 participants in the analysis. We conducted a network meta-analysis for the period from zero to two hours, including six trials with 496 participants. There was no evidence of differences between intravenous vs rectal routes of administration of acetaminophen (difference in means, -0.28; 95% confidence interval [CI], -0.62 to 0.06; very low certainty of the evidence) and intravenous vs oral acetaminophen (difference in means, -0.60; 95% CI, -1.20 to 0.01; low certainty of the evidence). For the comparison of oral vs rectal routes, we found evidence favouring the oral route (difference in means, -0.88; 95% CI, -1.44 to -0.31; low certainty of the evidence). Few trials reported secondary outcomes of interest; when comparing the oral and rectal routes in the incidence of nausea and vomiting, there was no evidence of differences (relative risk, 1.20; 95% CI, 0.81 to 1.78). CONCLUSION: The available evidence on the effect of the administration route of acetaminophen on postoperative pain in children is very uncertain. The outcomes of postoperative pain control and postoperative vomiting may differ very little between the oral and rectal route. Better designed and executed RCTs are required to address this important clinical question. STUDY REGISTRATION: PROSPERO (CRD42021286495); first submitted 19 November 2021.

RéSUMé: OBJECTIF: Compte tenu de sa large marge de sécurité, de son faible coût et de ses multiples voies d'administration, l'acétaminophène est le médicament le plus couramment utilisé pour traiter la douleur aiguë dans la population pédiatrique. Nous avons cherché à déterminer la voie d'administration d'acétaminophène la plus efficace pour le soulagement de la douleur aiguë postopératoire dans la population chirurgicale pédiatrique. MéTHODE: Nous avons réalisé une revue systématique d'études randomisées contrôlées (ERC) qui ont inclus des enfants âgé·es de 30 jours à 17 ans ayant bénéficié de n'importe quel type d'intervention chirurgicale et qui ont évalué l'efficacité analgésique de différentes voies d'administration d'acétaminophène pour le traitement de la douleur postopératoire. Nous avons mené des recherches dans les bases de données MEDLINE, CENTRAL, Embase, CINAHL, LILAC et Google Scholar pour en tirer les études publiées depuis leur création jusqu'au 16 avril 2023. Le risque de biais dans les études incluses a été évalué à l'aide de l'outil de Risque de biais 1.0 de Cochrane. Nous avons réalisé une méta-analyse de réseau fréquentiste à l'aide d'un modèle à effets aléatoires. Notre critère d'évaluation principal était la douleur postopératoire mesurée à l'aide d'échelles de douleur validées. RéSULTATS: Nous avons passé en revue 2344 études et inclus 14 études incluant un total de 829 enfants dans l'analyse. Nous avons mené une méta-analyse en réseau pour une période allant de zéro à deux heures, comprenant six études avec 496 participant·es. Il n'y avait aucune preuve de différences entre les voies d'administraion intraveineuse vs rectale de l'acétaminophène (différence de moyennes, −0,28; intervalle de confiance [IC] à 95 %, −0,62 à 0,06; très faible certitude des données probantes) et entre les voies intraveineuse vs orale (différence de moyennes, −0,60; IC 95 %, −1,20 à 0,01; faible certitude des données probantes). Pour la comparaison des voies orale vs rectale, nous avons trouvé des données probantes en faveur de la voie orale (différence de moyennes, −0,88; IC 95 %, −1,44 à −0,31; faible degré de certitude des données probantes). Peu d'études ont rapporté des résultats secondaires d'intérêt; en comparant les voies orale et rectale dans l'incidence des nausées et des vomissements, il n'y avait aucune preuve de différences (risque relatif, 1,20; IC 95 %, 0,81 à 1,78). CONCLUSION: Les données probantes disponibles sur l'effet de la voie d'administration de l'acétaminophène sur la douleur postopératoire chez les enfants sont très incertaines. Les résultats de contrôle de la douleur postopératoire et de vomissements postopératoires peuvent différer très peu entre la voie orale et la voie rectale. Des ERC mieux conçues et mieux exécutées sont nécessaires pour répondre à cette importante question clinique. ENREGISTREMENT DE L'éTUDE: PROSPERO (CRD42021286495); première soumission le 19 novembre 2021.

Exposure to Paracetamol in Early Pregnancy and the Risk of Developing Cerebral Palsy: A Case-Control Study Using Serum Samples.

OBJECTIVE: To investigate whether maternal paracetamol use in early pregnancy is associated with cerebral palsy (CP) in offspring. STUDY DESIGN: We conducted a registry and biobank-based case-control study with mother-child pairs. We identified CP cases (n = 322) born between 1995 and 2014 from a nationwide CP-registry. Randomly selected controls (n = 343) and extra preterm controls (n = 258) were obtained from a birth registry. For each mother, a single serum sample from early pregnancy (gestation weeks 10-14) was retrieved from a biobank and analyzed for serum concentrations of paracetamol, categorized into unexposed (<1 ng/ml), mildly exposed (1-100 ng/ml), and highly exposed (>100 ng/ml), and in quartiles. Analyses were performed using logistic regression and adjusted for potential confounders. Separate analyses were conducted including only those children born preterm and only those born term. RESULTS: Of the 923 participants, 36.8% were unexposed, 53.2% mildly exposed, and 10% highly exposed to paracetamol. Overall, prenatal exposure to paracetamol was not associated with CP. Sensitivity and subgroup analyses showed no clear associations between paracetamol and CP across strata of term/preterm birth as well as subtypes of CP. CONCLUSIONS: The present study does not support an association between intrauterine exposure to paracetamol in early pregnancy and the risk of CP. However, it is important to stress that the exposure estimate is based on a single serum sample.

Improvement of ferrioxalate assisted Fenton and photo-Fenton processes for paracetamol degradation by hydrogen peroxide dosage.

This work aimed to investigate the impact of hydrogen peroxide (HP) punctual dosage on paracetamol (PCT) degradation, through Fenton and photo-Fenton processes under near-neutral pH conditions, using ferrioxalate and artificial sunlight. The assays were performed using a D-optimal experimental design, to statistically evaluate the influence of radiation (ON or OFF), HP concentration (94.5-756 mg L-1), and HP dosage (YES or NO), on PCT conversion. The optimal conditions determined from the study were: HP = 378 mg L-1, DOS = YES, and RAD = ON, achieving a predicted PCT conversion of 99.68% in 180 min. This result obtained from the model was very close to the experimental one (98.80%). It was verified that HP dosage positively influenced the iron catalytic cycle since higher Fe2+ concentrations were reached at shorter reaction times, accelerating not only PCT conversion but also its by-products hydroquinone and 1,4-benzoquinone, leading to better performances of Fenton and photo-Fenton reactions. Under optimal conditions and employing real water matrices (an artificial matrix with inorganic anions, a real groundwater sample, and a synthetic industrial wastewater), HP dosage demonstrated the ability to mitigate the negative effects caused by the content of different ions and other organic compounds and significantly improve HP consumption in challenging wastewater conditions.

Unraveling kinetic and synergistic effects during ultrasound-enhanced carbocatalysis for water remediation as a function of ultrasonic frequency.

The ability of the ultrasound (US) combined with peroxymonosulfate (PMS), and a carbonaceous material (BC) was evaluated in the degradation of a model pollutant (acetaminophen, ACE). The US/BC/PMS system was compared with other possible systems (US, oxidation by PMS, BC adsorption, BC/PMS, US/PMS, and US/BC. The effect of the ultrasonic frequency (40, 375, and 1135 kHz) on the kinetics and synergy of the ACE removal was evaluated. In the US system, kinetics was favored at 375 kHz due to the increased production of hydroxyl radicals (HO•), but this did not improve in the US/PMS and US/BC systems. However, synergistic and antagonistic effects were observed at the low and high frequencies where the production of radicals is less efficient but there is an activation of PMS through mechanical effects. US/BC/PMS at 40 kHz was the most efficient system obtaining ∼95% ACE removal (40 µM) in the first 10 min of treatment, and high synergy (S = 10.30). This was promoted by disaggregation of the carbonaceous material, increasing the availability of catalytic sites where PMS is activated. The coexistence of free-radical and non-radical pathways was analyzed. Singlet oxygen (1O2) played the dominant role in degradation, while HO• and sulfate radicals (SO4•-), scarcely generated at low frequency, play a minimum role. Performance in hospital wastewater (HWW), urine, and seawater (SW) evidenced the competition of organic matter by BC active sites and reactive species and the removal enhancement when Cl- is present. Besides, toxicity decreased by ∼20% after treatment, being the system effective after three cycles of reuse.

Photocatalytic and antifouling performance of titania-coated alumina membranes produced using a facile sol-gel dip-coating approach.

Photocatalytic membranes (PM) have been investigated as an antifouling strategy for membrane separation processes. Coating ceramic membranes with photocatalytic layers can provide a highly active surface capable of degrading foulants and smaller molecules improving the membrane's performance when the surface is irradiated by a suitable light. Nevertheless, the coating process often leads to pore blockage due to the formation or deposition of thick layers of photocatalyst on membrane surfaces, which modifies the original membranes' average pore size and reduces membrane permeability. A facile sol-gel dip coating process was used to produce PM without modifying the original surface morphology of alumina microfiltration membranes. A 3.7-fold increase in permeate volume after 90 minutes of permeation of an acetaminophen solution in continuous filtration mode under UV light (λ = 365 nm LED, 10W) using titania as photocatalyst compared to the bare alumina membrane without irradiation. Furthermore, fouling modeling proved a reduction in the fouling constant, while fouling mechanisms were not modified. Raman analysis showed 100% anatase formed on the membrane surface. Although membranes could remove up to 87% TOC for oily wastewater filtration, antifouling capabilities for this type of effluent were not observed for the photocatalytic membranes mainly due to fouling inside the pores and light attenuation due to the thick fouling layer on the membrane surface.

Hepatoprotective Effects of Four Brazilian Savanna Species on Acetaminophen-Induced Hepatotoxicity in HepG2 Cells.

We investigated four Cerrado plant species, i.e., Cheiloclinium cognatum (Miers) A.C.Sm, Guazuma ulmifolia Lam., Hancornia speciosa Gomes, and Hymenaea stigonocarpa Mart. ex Hayne, against acetaminophen toxicity using an in vitro assay with HepG2 cells. The activity against acetaminophen toxicity was evaluated using different protocols, i.e., pre-treatment, co-treatment, and post-treatment of the cells with acetaminophen and the plant extracts. HepG2 cell viability after treatment with acetaminophen was 39.61 ± 5.59% of viable cells. In the pre-treatment protocol, the extracts could perform protection with viability ranging from 50.02 ± 15.24% to 78.75 ± 5.61%, approaching the positive control silymarin with 75.83 ± 5.52%. In the post-treatment protocol, all extracts and silymarin failed to reverse the acetaminophen damage. In the co-treatment protocol, the extracts showed protection ranging from 50.92 ± 11.14% to 68.50 ± 9.75%, and silymarin showed 77.87 ± 4.26%, demonstrating that the aqueous extracts of the species also do not increase the toxic effect of acetaminophen. This protection observed in cell viability was accompanied by a decrease in ROS. The extracts' hepatoprotection can be related to antioxidant compounds, such as rutin and mangiferin, identified using HPLC-DAD and UPLC-MS/MS. The extracts were shown to protect HepG2 cells against future APAP toxicity and may be candidates for supplements that could be used to prevent liver damage. In the concomitant treatment using the extracts with APAP, it was demonstrated that the extracts do not present a synergistic toxicity effect, with no occurrence of potentiation of toxicity. The extracts showed considerable cytoprotective effects and important antioxidant characteristics.

Systematic study of the synergistic and kinetics effects on the removal of contaminants of emerging concern from water by ultrasound in the presence of diverse oxidants.

The enhancement of the ultrasound system by adding diverse oxidants to remove a model contaminant (acetaminophen, ACE) in water was investigated. Different parameters were evaluated to study their effect on both the degradation kinetics and the synergy of the combination. The variables studied were the ultrasonic frequency (575, 858, and 1135 kHz), type of oxidant (hydrogen peroxide, sodium peroxydisulfate (or persulfate, PDS), and potassium peroxymonosulfate (PMS)), ACE concentration (4, 8, and 40 µM), and oxidant concentration (0.01, 0.1, 1, and 5 mM). Particular interest was placed on synergistic effects, implying that one process (or both) is activated by the other to lead to greater efficiency. Interestingly, the parameters that led to the higher synergistic effects did not always lead to the most favorable degradation kinetics. An increase in ACE removal of 20% was obtained using the highest frequency studied (1135 kHz), PMS 0.1 mM, and the highest concentration of ACE (40 µM). The intensification of degradation was mainly due to the ability of ultrasound to activate oxidants and produce extra hydroxyl radicals (HO•) or sulfate radicals (SO4•-). Under these conditions, treatment of ACE spiked into seawater, hospital wastewater, and urine was performed. The hospital wastewater matrix inhibited ACE degradation slightly, while the urine components inhibited the pollutant degradation completely. The inhibition was mainly attributed to the competing organic matter in the effluents for the sono-generated radical species. On the contrary, the removal of ACE in seawater was significantly intensified due to "salting out" effects and the production of the strong oxidant HOCl from the reaction of chloride ions with PMS.

Detection of Acetaminophen in Groundwater by Laccase-Based Amperometric Biosensors Using MoS2 Modified Carbon Paper Electrodes.

The use of enzyme-based biosensors for the detection and quantification of analytes of interest such as contaminants of emerging concern, including over-the-counter medication, provides an attractive alternative compared to more established techniques. However, their direct application to real environmental matrices is still under investigation due to the various drawbacks in their implementation. Here, we report the development of bioelectrodes using laccase enzymes immobilized onto carbon paper electrodes modified with nanostructured molybdenum disulfide (MoS2). The laccase enzymes were two isoforms (LacI and LacII) produced and purified from the fungus Pycnoporus sanguineus CS43 that is native to Mexico. A commercial purified enzyme from the fungus Trametes versicolor (TvL) was also evaluated to compare their performance. The developed bioelectrodes were used in the biosensing of acetaminophen, a drug widely used to relieve fever and pain, and of which there is recent concern about its effect on the environment after its final disposal. The use of MoS2 as a transducer modifier was evaluated, and it was found that the best detection was achieved using a concentration of 1 mg/mL. Moreover, it was found that the laccase with the best biosensing efficiency was LacII, which achieved an LOD of 0.2 µM and a sensitivity of 0.108 µA/µM cm2 in the buffer matrix. Moreover, the performance of the bioelectrodes in a composite groundwater sample from Northeast Mexico was analyzed, achieving an LOD of 0.5 µM and a sensitivity of 0.015 µA/µM cm2. The LOD values found are among the lowest reported for biosensors based on the use of oxidoreductase enzymes, while the sensitivity is the highest currently reported.

Polyester resin and graphite flakes: turning conductive ink to a voltammetric sensor for paracetamol sensing.

The development of a disposable electrochemical paper-based analytical device (ePAD) is described using a novel formulation of conductive ink that combines graphite powder, polyester resin, and acetone. As a proof of concept, the proposed sensor was utilized for paracetamol (PAR) sensing. The introduced ink was characterized via morphological, structural, and electrochemical analysis, and the results demonstrated appreciable analytical performance. The proposed ePAD provided linear behavior (R2 = 0.99) in the concentration range between 1 and 60 µmol L-1, a limit of detection of 0.2 µmol L-1, and satisfactory reproducibility (RSD ~ 7.7%, n = 5) applying a potential of + 0.81 V vs Ag at the working electrode. The quantification of PAR was demonstrated in different pharmaceutical formulations. The achieved concentrations revealed good agreement with the labeled values, acceptable accuracy (101% and 106%), and no statistical difference from the data obtained by HPLC at the 95% confidence level. The environmental impact of the new device was assessed using AGREE software, which determined a score of 0.85, indicating that it is eco-friendly. During the pharmacokinetic study of PAR, it was found that the drug has a maximum concentration of 23.58 ± 0.01 µmol L-1, a maximum time of 30 min, and a half-life of 2.15 h. These results are comparable to other studies that utilized HPLC. This suggests that the combination of graphite powder and polyester resin can transform conductive ink into an effective ePAD that can potentially be used in various pharmaceutical applications.

Gestational paracetamol exposure induces core behaviors of neurodevelopmental disorders in infant rats and modifies response to a cannabinoid agonist in females.

Paracetamol (PAR) is an over-the-counter analgesic/antipyretic used during pregnancy worldwide. Epidemiological studies have been associating gestational PAR exposure with neurobehavioral alterations in the progeny resembling autism spectrum disorders and attention-deficit hyperactivity disorder symptoms. The endocannabinoid (eCB) dysfunction was previously hypothesized as one of the modes of action by which PAR may harm the developing nervous system. We aimed to evaluate possible effects of gestational exposure to PAR on male and female rat's offspring behavior and if an acute injection of WIN 55,212-2 (WIN, 0.3 mg/kg), a non-specific cannabinoid agonist, prior to behavioral tests, would induce different effects in PAR exposed and non-exposed animals. Pregnant Wistar rats were gavaged with PAR (350 mg/kg/day) or water from gestational day 6 until delivery. Nest-seeking, open field, apomorphine-induced stereotypy, marble burying and three-chamber tests were conducted in 10-, 24-, 25- or 30-days-old rats, respectively. PAR exposure resulted in increased apomorphine-induced stereotyped behavior and time spent in the central area of the open field in exposed female pups. Additionally, it induced hyperactivity in the open field and increased marble burying behavior in both male and female pups. WIN injection modified the behavioral response only in the nest seeking test, and opposite effects were observed in control and PAR-exposed neonate females. Reported alterations are relevant for the neurodevelopmental disorders that have been associated with maternal PAR exposure and suggest that eCB dysfunction may play a role in the action by which PAR may harm the developing brain.

Prospective Protective Effects of Arthrospira platensis Against Acetaminophen Induced Hepato-Renal Toxicity in Rats / Efectos Protectores Prospectivos de Arthrospira platnesis Contra la Toxicidad Hepatorrenal Inducida por Paracetamol en Ratas

SUMMARY: The toxic effects of acetaminophen appear primarily in the liver and kidney. The protective effect of blue green alga Arthrospira platensis on hepato-renal toxicity caused by acetaminophen was evaluated in male rats. The obtained results showed that subcutaneous injection of acetaminophen at a dose 120 &240 սl acetaminophen/kg by weight resulted in an observed elevation in the enzyme activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and Alkaline phosphatase (ALP), serum total lipids, total cholesterol, creatinine, total bilirubin, urea, nitric oxide (NO), L- malondialdehyde (MDA) and interleukins (IL-2 &IL-6). However, there is a decrease in the serum total protein, albumin and loss in antioxidant enzyme activities in liver including; superoxide dismutase (SOD), catalase (CAT) and glutathione reductase (GSH). This effect was found to be dose and time dependent. In spite of, pre- oral administration of Arthrospira platensis 1000 mg/kg .b. wt. prior acetaminophen injection succeeded to modulate the effect of the observed abnormalities caused by acetaminophen. Moreover, there were no remarkable changes in serum biomarkers of rats received Arthrospira platensis only at a dose of 1000 mg/kg by weight (group 2). The histopathological findings confirm the biochemical results that indicates the safety use of Arthrospira platensis at the selected dose in this study. Therefore, the present results clarified the protective effect of blue green alga Arthrospira platensis on oxidative stress, hepatic and nephrotoxicity induced by acetaminophen in male Wister rats.

Los efectos tóxicos del paracetamol aparecen principalmente en el hígado y el riñón. Se evaluó en ratas macho Wistar el efecto protector del alga verde azulada Arthrospira platensis sobre la toxicidad hepatorrenal causada por paracetamol. Los resultados obtenidos mostraron que la inyección subcutánea de paracetamol a dosis de 120 y 240 µl de paracetamol/kg, resultó en una elevación en las actividades enzimáticas de la aspartato aminotransferasa (AST), alanina aminotransferasa (ALT) y fosfatasa alcalina (ALP), lípidos séricos totales, colesterol total, creatinina, bilirrubina total, urea, óxido nítrico (NO), L- malondialdehído (MDA) e interleucinas (IL-2 e IL-6). Sin embargo, hay una disminución en la proteína sérica total, albúmina y pérdida en las actividades de las enzimas antioxidantes en el hígado, incluyendo; superóxido dismutasa (SOD), catalasa (CAT) y glutatión reductasa (GSH). Se encontró que este efecto era dependiente de la dosis y el tiempo. A pesar de la administración preoral de Arthrospira platensis 1000 mg/kg, la inyección previa de acetaminofeno logró modular el efecto de las anormalidades observadas causadas por el acetaminofeno. Además, no hubo cambios notables en los biomarcadores séricos de ratas que recibieron Arthrospira platensis solo a una dosis de 1000 mg/kg (Grupo 2). Los hallazgos histopatológicos confirman los resultados bioquímicos que indican la seguridad del uso de Arthrospira platensis a la dosis seleccionada en este estudio. Por lo tanto, los presentes resultados aclararon el efecto protector del alga verde azulada Arthrospira platensis sobre el estrés oxidativo, la toxicidad hepática y la nefrotoxicidad inducida por paracetamol en ratas Wistar macho.

Is Acetaminophen Beneficial in Patients With Cancer Pain Who are on Strong Opioids? A Randomized Controlled Trial.

CONTEXT: Pain is common among cancer patients. The evidence recommends using strong opioids in moderate to severe cancer pain. No conclusive evidence supports the effectiveness of adding acetaminophen to patients with cancer pain who are already using this regime. OBJECTIVES: To assess the analgesic efficacy of acetaminophen in hospitalized cancer patients with moderate to severe pain receiving strong opioids. METHODS: In this randomized blinded clinical trial, hospitalized cancer patients with moderate or severe acute pain managed with strong opioids were randomized to acetaminophen or placebo. The primary outcome was pain intensity difference between baseline and 48 hours using the Visual Numeric Rating Scales (VNRS). Secondary outcomes included change in morphine equivalent daily dose (MEDD), and patients' perception of improved pain control. RESULTS: Among 112 randomized patients, 56 patients received placebo, 56 acetaminophen. Mean (standard deviation [SD]) decrease in pain intensity (VNRS) at 48 hours were 2.7 (2.5) and 2.3 (2.3), respectively (95% Confidence Interval (CI) [-0.49; 1.32]; P = 0.37). Mean (SD) change in MEDD was 13.9 (33.0) mg/day and 22.4 (57.7), respectively (95% CI [-9.24; 26.1]; P = 0.35). The proportion of patients perceiving pain control improvement after 48 hours was 82% in the placebo and 80% in the acetaminophen arms (P = 0.81). CONCLUSION: Among patients with cancer pain on strong opioid regime, acetaminophen may not improve pain control, or decrease total opioid use. These results add to the current evidence available suggesting not to use acetaminophen as an adjuvant for advanced cancer patients with moderate to severe cancer pain who are on strong opioids.

Comparación: acetaminofén vs ibuprofeno para el tratamiento de los síntomas en pacientes con infección por SARS-CoV-2 / Comparação: paracetamol vs ibuprofeno para o tratamento de sintomas em pacientes com infecção por SARS-CoV-2 / Comparison: acetaminophen vs ibuprofen for the treatment of symptoms in patients with SARS-CoV-2 infection

La propagación del COVID-19 fue expedita y tras varios informes la eficacia de algunos medicamentos antiinflamatorios no esteroideos, como el ibuprofeno, estuvo bajo sospecha. Mientas que el paracetamol (acetaminofén) se sugirió como una alternativa segura y recomendable para el manejo temprano y domiciliario del dolor y fiebre en pacientes. Objetivo. Comparar el uso del acetaminofén vs ibuprofeno para tratamiento de los síntomas en pacientes con infección por SARS-COV-2". Metodología. La investigación es una revisión sistemática, donde, se analizaron artículos científicos publicados en revistas vinculadas a áreas de salud, disponibles en buscadores y plataformas digitales tales, como Scienedirect, Pubmed, Elsevier y Springer Link. Las búsquedas se realizaron utilizando las palabras claves previamente definidas. Conclusión. El uso del ibuprofeno ha estado en duda desde sus inicios, en pacientes con COVID-19. Sin embargo, ningún estudio afirma asociar el uso del mismo con aumentos importantes en estadía hospitalaria, ingresos en UCI, necesidad de ventilación mecánica, ni mortalidad. Sin embargo, el acetaminofén ha sido utilizado desde un principio, su uso no estuvo en duda, pero los hallazgos recientes parecen indicar que no es tan eficaz como se pensaba en un principio. Siendo bastante inferior en la comparación directa con el ibuprofeno.

The spread of COVID-19 was expeditious and after several reports the efficacy of some non-steroidal anti-inflammatory drugs, such as ibuprofen, was under suspicion. While paracetamol (acetaminophen) was suggested as a safe and recommended alternative for early and home management of pain and fever in patients. Objective. To compare the use of acetaminophen vs ibuprofen for symptom management in patients with SARS-COV-2 infection". Methodology. The research is a systematic review, where scientific articles published in journals related to health areas, available in search engines and digital platforms such as Scienedirect, Pubmed, Elsevier and Springer Link, were analyzed. Searches were performed using previously defined keywords. Conclusion. The use of ibuprofen has been in question since its inception in patients with COVID-19. However, no study claims to associate its use with significant increases in hospital stay, ICU admissions, need for mechanical ventilation, or mortality. However, acetaminophen has been used from the beginning, its use was not in doubt, but recent findings seem to indicate that it is not as effective as originally thought. It is quite inferior in direct comparison with ibuprofen.

A disseminação da COVID-19 foi rápida e, após vários relatos, a eficácia de alguns anti-inflamatórios não esteroides, como o ibuprofeno, ficou sob suspeita. Já o paracetamol (acetaminofeno) foi sugerido como uma alternativa segura e recomendada para o tratamento precoce e domiciliar da dor e da febre nos pacientes. Objetivo. Comparar o uso de acetaminofeno versus ibuprofeno para o controle dos sintomas em pacientes com infecção por SARS-COV-2". Metodologia. A pesquisa é uma revisão sistemática, onde foram analisados artigos científicos publicados em periódicos relacionados às áreas de saúde, disponíveis em sites de busca e plataformas digitais como Scienedirect, Pubmed, Elsevier, e Springer Link. As buscas foram realizadas por meio de palavras-chave previamente definidas. Conclusões. O uso do ibuprofeno tem sido questionado desde sua criação em pacientes com COVID-19. No entanto, nenhum estudo afirma associar seu uso a aumentos significativos na permanência hospitalar, internações em UTI, necessidade de ventilação mecânica ou mortalidade. No entanto, o acetaminofeno tem sido usado desde o início, seu uso não foi questionado, mas descobertas recentes parecem indicar que ele não é tão eficaz quanto se pensava originalmente. Ele é muito inferior em comparação direta com o ibuprofeno.

Rosemary (Rosmarinus officinalis L.) Glycolic Extract Protects Liver Mitochondria from Oxidative Damage and Prevents Acetaminophen-Induced Hepatotoxicity.

Rosmarinus officinalis L. (rosemary) is an aromatic culinary herb. Native to the Mediterranean region, it is currently cultivated worldwide. In addition to its use as a condiment in food preparation and in teas, rosemary has been widely employed in folk medicine and cosmetics. Several beneficial effects have been described for rosemary, including antimicrobial and antioxidant activities. Here, we investigated the mechanisms accounting for the antioxidant activity of the glycolic extract of R. officinalis (Ro) in isolated rat liver mitochondria (RLM) under oxidative stress conditions. We also investigated its protective effect against acetaminophen-induced hepatotoxicity in vivo. A crude extract was obtained by fractionated percolation, using propylene glycol as a solvent due to its polarity and cosmeceutical compatibility. The quantification of substances with recognized antioxidant action revealed the presence of phenols and flavonoids. Dereplication studies carried out through LC-MS/MS and GC-MS, supported by The Global Natural Product Social Molecular Networking (GNPS) platform, annotated several phenolic compounds, confirming the previous observation. In accordance, Ro decreased the production of reactive oxygen species (ROS) elicited by Fe2+ or t-BOOH and inhibited the lipid peroxidation of mitochondrial membranes in a concentration-dependent manner in RLM. Such an effect was also observed in liposomes as membrane models. Ro also prevented the oxidation of mitochondrial protein thiol groups and reduced glutathione (GSH). In model systems, Ro exhibited a potent scavenger activity toward 2,2'-diphenyl-1-picrylhydrazyl (DPPH) radicals and superoxide anions. It also demonstrated an Fe2+ chelating activity. Moreover, Ro did not exhibit cytotoxicity or dissipate the mitochondrial membrane potential (∆Ψ) in rat liver fibroblasts (BRL3A cells). To evaluate whether such antioxidant protective activity observed in vitro could also be achieved in vivo, a well-established model of hepatotoxicity induced by acute exposure to acetaminophen (AAP) was used. This model depletes GSH and promotes oxidative-stress-mediated tissue damage. The treatment of rats with 0.05% Ro, administered intraperitoneally for four days, resulted in inhibition of AAP-induced lipid peroxidation of the liver and the prevention of hepatotoxicity, maintaining alanine and aspartate aminotransferase (ALT/AST) levels equal to those of the normal, non-treated rats. Together, these findings highlight the potent antioxidant activity of rosemary, which is able to protect mitochondria from oxidative damage in vitro, and effects such as the antioxidant and hepatoprotective effects observed in vivo.

Sobredosis de acetaminofén y comportamientos relacionados con suicidio / Acetaminophen overdose and suicide-related behaviors / Overdose de paracetamol e comportamentos suicidas

Objetivo: este trabajo busca caracterizar el comportamiento relacionado con el suicidio en la población admitida al Hospital San Vicente Fundación, Rionegro, con sobredosis de acetaminofén entre enero 2019 y diciembre 2020 y detectar factores asociados con la dosis tóxica. Metodología: análisis descriptivo con información obtenida de historias clínicas. Resultados: 63 individuos presentaron ingestión aguda de dosis tóxica de acetaminofén como comportamiento relacionado con suicidio. Cuarenta y tres eran mujeres, 60% tenía antecedente de enfermedad psiquiátrica, 35% reportó al menos un intento suicida previo y 22% consumieron 25g o más. La lesión hepática aguda se asoció con una dosis tóxica. Conclusiones: evidenciamos una alta prevalencia de antecedente de enfermedad psi­quiátrica y comportamiento relacionado con suicidio y casi un tercio de los pacientes ingirió dosis mayores al umbral de riesgo para falla hepática. Además, la impulsividad e ingesta en casa sugiere que políticas públicas restrictivas pueden no impactar en la reducción de estos eventos en la población.

Objective: this work seeks to characterize the behavior related to suicide in the po­pulation admitted to the Hospital San Vicente Fundación, Rionegro, with an overdose of acetaminophen between January 2019 and December 2020, and to identify factors associated with the toxic dose. Methodology: descriptive analysis with information obtained from medical records. Results: 63 individuals presented acute ingestion of a toxic dose of acetaminophen as behavior related to suicide. Forty-three were women, 60% had a history of psychiatric illness, 35% reported at least one previous suicide attempt, and 22% consumed 25g or more. Acute liver injury was associated with a toxic dose. Conclusions: we evidenced a high prevalence of a history of psychiatric illness and beha­vior related to suicide; almost a third of the patients ingested doses greater than the risk threshold for liver failure. In addition, impulsiveness and eating at home suggests that res­trictive public policies may not have an impact on reducing these events in the population.

Objetivo: Este trabalho busca caracterizar o comportamento relacionado ao suicídio na população internada no Hospital San Vicente Fundación, Rionegro, com overdose de acetaminofeno entre janeiro de 2019 e dezembro de 2020 e detectar fatores associados à dose tóxica. Metodologia: análise descritiva com informações obtidas dos prontuários. Resultados: 63 indivíduos apresentaram ingestão aguda de dose tóxica de paracetamol como comportamento relacionado ao suicídio. Quarenta e três eram mulheres, 60% tinham histórico de doença psiquiátrica, 35% relataram pelo menos uma tentativa de suicídio anterior e 22% consumiram 25g ou mais. A lesão hepática aguda foi associada a uma dose tóxica. Conclusões: evidenciamos alta prevalência de história de doença psiquiátrica e com-portamento relacionado ao suicídio e quase um terço dos pacientes ingeriu doses superiores ao limiar de risco para insuficiência hepática. Além disso, a impulsividade e a alimentação em casa sugerem que políticas públicas restritivas podem não ter impacto na redução desses eventos na população.

Removal of pharmaceuticals from aqueous medium by alginate/polypyrrole/ZnFe2O4 beads via magnetic field enhanced adsorption.

The physicochemical and structural characteristics of the magnetic materials can be modulable due to exposition to a magnetic field, which allows, for example, to enhance its adsorption performance. In this sense, this study describes the preparation of magnetic beads of alginate/polypyrrole/ZnFe2O4 (Alg/PPy/ZnFe2O4) and investigates the effect of an external magnetic field (EMF) on their adsorption performance towards two overconsumed drugs, acetaminophen (ACT) and ibuprofen (IBU). Characterization analyses confirmed the composite formation and magnetic nature of Alg/PPy/ZnFe2O4. Conversely to the pristine beads (Alg/PPy), the presence of an EMF altered the swelling and pHPZC behavior of the magnetic beads, indicating that these properties are affected by this external stimulus. Batch experiments revealed that the amount of ACT and IBU adsorbed by Alg/PPy/ZnFe2O4 in 60-70 min is appreciably high (106.7 ad 108.2 mg/g). The presence of an EMF modulated the structure of Alg/PPy/ZnFe2O4 beads enhancing their adsorption capacity towards ACT and IBU by 14% and 12% compared to Alg/PPy. Kinetic analysis revealed that the adsorption of both drugs on Alg/PPy/ZnFe2O4 followed a pseudo-second-order. Besides, the adsorption mechanism was fitted by the Freundlich isotherm. Reuse experiments showed that the magnetic beads keep a high adsorption capacity for both drugs even after ten consecutive reuse cycles. The results presented here suggest that magnetic-responsive materials like Alg/PPy/ZnFe2O4 are prominent and modulable tools for improving the treatment of water/wastewater containing this class of contaminants.

Uso del esquema Scottish and Newcastle Anti-Emetic Pretreatment (SNAP) en la recuperación de una intoxicación por sobredosis masiva de acetaminofén (paracetamol) con injuria hepática aguda - Reporte de caso

Acetaminophen is a drug widely used in the world and easily accessible due to its antipyretic, analgesics characteristics, among others (1); however, exposure to toxic doses causes organic damage and even death. We present the case of an 18-year-old female patient who ingested 40 grams of acetaminophen and developed severe liver dysfunction, being treated with N-acetylcysteine (NAC) antidotal therapy according to the simplified scheme: Scottish and Newcastle Anti-emetic Pretreatment Paracetamol Poisoning Study Regimen (SNAP), presenting improvement in the clinical course and decrease in liver profiles, coagulation disorder, INR and resolution of the condition.

El acetaminofén es un fármaco ampliamente usado en el mundo y de fácil acceso por sus características antipiréticas, analgésicas, entre otras (1); sin embargo la exposición a dosis tóxicas produce daños a nivel orgánico e incluso la muerte. Presentamos el caso de una paciente mujer de 18 años que ingirió 40 gramos de acetaminofén y desarrolló injuria hepática severa, siendo tratada con terapia antidotal de N-acetilcisteína (NAC) según el esquema simplificado: Scottish and Newcastle Anti-Emetic Pretreatment Paracetamol Poisoning Study Regimen (SNAP), presentando mejoría del curso clínico y disminución de los perfiles hepáticos, trastorno de coagulación, INR y resolución del cuadro.