Administration Of Paracetamol Research Articles

Mitigating of Paracetamol-induced Hepatotoxicity in Albino Mice Using Boerhaavia diffusa Extracts

Boerhaavia diffusa, renowned for its therapeutic efficacy in chronic liver diseases, operates through multifaceted mechanisms to uphold internal homeostasis. Its pivotal roles encompass modulation of intermediary metabolism of macromolecules, synthesis of crucial plasma proteins, enzymatic activities, and bile excretion.In this investigation, we aimed to evaluate the hepatoprotective potential of Boerhaavia diffusa against paracetamol-induced hepatotoxicity in rats. Our study revealed promising outcomes as the extracts obtained from Boerhaavia diffusa demonstrated a significant hepatoprotective role in albino rats subjected to hepatotoxicity induced by paracetamol administration. During the study, the animals were administered doses of 1g/kg b.wt and 2 g/kg b.wt of the plant extracts. Following paracetamol administration, conspicuous changes were observed in hepatocyte biochemical markers, indicative of hepatotoxicity. However, treatment with Boerhaavia diffusa extracts ameliorated these alterations, underscoring their potential to mitigate paracetamol-induced liver injury. These findings underscore the significant hepatoprotective properties inherent in the plant extracts derived from Boerhaavia diffusa. which can be utilized as a potential therapeutic avenue for the management of paracetamol-induced liver damage. These findings hold promise for the development of novel therapeutic interventions aimed at safeguarding liver health and mitigating the adverse effects of hepatotoxic insults.

Mitigating of Paracetamol-induced Hepatotoxicity in Albino Mice Using Boerhaavia diffusa Extracts

Boerhaavia diffusa, renowned for its therapeutic efficacy in chronic liver diseases, operates through multifaceted mechanisms to uphold internal homeostasis. Its pivotal roles encompass modulation of intermediary metabolism of macromolecules, synthesis of crucial plasma proteins, enzymatic activities, and bile excretion.In this investigation, we aimed to evaluate the hepatoprotective potential of Boerhaavia diffusa against paracetamol-induced hepatotoxicity in rats. Our study revealed promising outcomes as the extracts obtained from Boerhaavia diffusa demonstrated a significant hepatoprotective role in albino rats subjected to hepatotoxicity induced by paracetamol administration. During the study, the animals were administered doses of 1g/kg b.wt and 2 g/kg b.wt of the plant extracts. Following paracetamol administration, conspicuous changes were observed in hepatocyte biochemical markers, indicative of hepatotoxicity. However, treatment with Boerhaavia diffusa extracts ameliorated these alterations, underscoring their potential to mitigate paracetamol-induced liver injury. These findings underscore the significant hepatoprotective properties inherent in the plant extracts derived from Boerhaavia diffusa. which can be utilized as a potential therapeutic avenue for the management of paracetamol-induced liver damage. These findings hold promise for the development of novel therapeutic interventions aimed at safeguarding liver health and mitigating the adverse effects of hepatotoxic insults.

Effects of repeated doses of paracetamol administration during pregnancy on lung, kidney, and liver tissues of pregnant rats.

Paracetamol is one of the most widely used analgesics and antipyretics in the world. It is the most commonly used analgesic and antipyretic agent in pregnancy. Paracetamol is known to have toxic effects on the liver, lung, and kidney. In this study, we investigated the effects of long-term chronic paracetamol exposure on the lung, liver, and kidney in newborn rats at different trimesters of pregnancy. In our study, we formed control (group C), first trimester (group A), and third trimester (group B) groups. Group A had the first seven days of pregnancy and group B had days 15-21. Paracetamol was given orally during the specified periods. On the third postnatal day, pups were euthanized by applying 50 mg/kg ketamine intraperitoneally, and then lung, liver, and kidney tissues were kept under appropriate conditions for examination. A total of 70 pups underwent histopathological examination. The lung revealed congestion (p<0.0001), and erythrocytes (p<0.0001), the liver revealed significant histopathological findings in terms of the presence of inflammation (p<0.0001), vacuolar degeneration (p<0.0001), and sinusoidal dilatation in groups A and B compared to the control group under light microscopy. MDA and free radical metabolism enzyme activities, CAT, GSH, and SOD were evaluated. While there were no significant differences between the groups in lung and kidney tissues, oxidant parameters were significant in liver tissues. Our data point out that subacute doses of paracetamol used chronically in different trimesters caused damage to the lung, liver, and kidney tissues of pups.

Strategies for Treating Acute Migraines and Identifying Triggers. Literature review

Introduction Migraine, a prevalent neurological disorder affecting a substantial portion of the global population, poses a significant burden on individuals' overall quality of life. While the exact pathophysiological mechanisms underlying migraine headache attacks remain elusive, the involvement of trigeminal pathway activation is well-documented. A multitude of factors, collectively termed triggers, have been identified as capable of precipitating migraine episodes, ranging from dietary components to environmental stimuli such as bright lights and weather fluctuations. Migraine headaches typically manifest as throbbing pain localized predominantly on one side of the head and are often accompanied by a constellation of additional symptoms including photophobia, phonophobia, and nausea. The management of migraine involves a diverse array of therapeutic modalities tailored to the specific characteristics of the pain experienced. These may include the administration of non-steroidal anti-inflammatory drugs (NSAIDs), paracetamol, triptans, and antiemetics, among others. This study endeavors to explore the most prevalent triggers implicated in migraine onset, as well as contemporary treatment strategies, with an emphasis on incorporating the latest research findings and therapeutic advancements in this evolving field. Aim of the study This review aims to identify symptoms, triggers of acute migraine and solutions in its treatment process, including latest developments. Material and method This article presents the current state of knowledge about acute migraine, triggers and treatment options in various scientific articles. Publications describing acute migraine attacks and treatments including the most recent reports in the field were reviewed using the PubMed platform. The search included the keywords ‘migraine, 'migraine triggers', 'triptans', 'migraine with aura'.

Intermittent intravenous paracetamol versus continuous morphine in infants undergoing cardiothoracic surgery: a multi-center randomized controlled trial

BackgroundTo determine whether intermittent intravenous (IV) paracetamol as primary analgesic would significantly reduce morphine consumption in children aged 0–3 years after cardiac surgery with cardiopulmonary bypass.MethodsMulti-center, randomized, double-blinded, controlled trial in four level-3 Pediatric Intensive Care Units (PICU) in the Netherlands and Belgium. Inclusion period; March 2016–July 2020. Children aged 0–3 years, undergoing cardiac surgery with cardiopulmonary bypass were eligible. Patients were randomized to continuous morphine or intermittent IV paracetamol as primary analgesic after a loading dose of 100 mcg/kg morphine was administered at the end of surgery. Rescue morphine was given if numeric rating scale (NRS) pain scores exceeded predetermined cutoff values. Primary outcome was median weight-adjusted cumulative morphine dose in mcg/kg in the first 48 h postoperative. For the comparison of the primary outcome between groups, the nonparametric Van Elteren test with stratification by center was used. For comparison of the proportion of patients with one or more NRS pain scores of 4 and higher between the two groups, a non-inferiority analysis was performed using a non-inferiority margin of 20%.ResultsIn total, 828 were screened and finally 208 patients were included; parents of 315 patients did not give consent and 305 were excluded for various reasons. Fourteen of the enrolled 208 children were withdrawn from the study before start of study medication leaving 194 patients for final analysis. One hundred and two patients received intermittent IV paracetamol, 106 received continuous morphine. The median weight-adjusted cumulative morphine consumption in the first 48 h postoperative in the IV paracetamol group was 5 times lower (79%) than that in the morphine group (median, 145.0 (IQR, 115.0–432.5) mcg/kg vs 692.6 (IQR, 532.7–856.1) mcg/kg; P < 0.001). The rescue morphine consumption was similar between the groups (p = 0.38). Non-inferiority of IV paracetamol administration in terms of NRS pain scores was proven; difference in proportion − 3.1% (95% CI − 16.6–10.3%).ConclusionsIn children aged 0–3 years undergoing cardiac surgery, use of intermittent IV paracetamol reduces the median weight-adjusted cumulative morphine consumption in the first 48 h after surgery by 79% with equal pain relief showing equipoise for IV paracetamol as primary analgesic.Trial Registration Clinicaltrials.gov, Identifier: NCT05853263; EudraCT Number: 2015-001835-20.

Protective effects of jervine purified from Veratrum album on paracetamol-induced liver toxicity in rats

Purpose: Since paracetamol toxicity is a very common type of poisoning, we planned to investigate whether Jervine has an effect on paracetamol toxicity by utilizing its anti-inflammatory effect.&#x0D; Materials and Methods: In our study, 42 Sprague Dawley rats of 8 weeks of age were used. Seven groups were formed with 6 animals in each group. At the 24th hour of the study, all groups underwent laparotomy under anesthesia, and liver dissection was performed. Hematoxylin and Eosin (H&amp;E) staining was performed to evaluate liver histopathology. SOD, CAT, GSH, and MDA levels were analyzed biochemically.&#x0D; Results: Histopathological, while liver tissues were normal in the control group, we observed degeneration areas, inflammation, and hemorrhage in the paracetamol group. Jervine reduced the severity of paracetamol toxicity and prevented liver damage. Jervine significantly increased SOD levels. Paracetamol administration significantly decreased CAT levels. Paracetamol significantly decreased GSH levels compared to the control group. &#x0D; Conclusion: Jervine reduced the adverse effects of paracetamol toxicity on liver tissue, such as degeneration, inflammation, and hemorrhage. Jervine increased antioxidant activity and reduced the harmful effects of NAPQI, the toxic metabolite of paracetamol, on liver tissue.

The effect of paracetamol on care dependency and daily functioning in persons with advanced dementia living in long-term care facilities

BackgroundPain medication may have an impact on the quality of life (QoL) in persons with dementia, but may also influence care dependency and daily functioning. The aim of this study is to investigate the effect of regularly scheduled paracetamol on care dependency and daily functioning in persons with advanced dementia with low QoL living in long-term care facilities.MethodsThe Quality of life and Paracetamol In advanced Dementia (Q-PID) study was a (block) randomized double-blind placebo-controlled crossover trial with paracetamol and placebo across seventeen long-term care facilities across 9 care organizations in the western region of the Netherlands. Participants were ≥ 65 years, had advanced dementia (Global Deterioration Scale 5–7), and low QoL (QUALIDEM-6D score ≤ 70). Measurements were performed by nursing staff at the start and at the end of each treatment period of six weeks. Repeated linear mixed models were used to compute differences between randomization groups, with adjustment for period and order effects, and psychotropic use.ResultsNinety-five persons (mean age of 83.9 years, 57.4% female) were enrolled in the Q-PID study. The mean Care Dependency Scale total score was 37.8 (Standard Deviation [SD] 12.9) and the mean Katz-15 total score was 11.9 (SD 2.4). Repeated linear mixed models showed no difference in mean differences of care dependency (paracetamol − 1.0 [95% Confidence Interval (CI) -2.4-0.3], placebo + 0.1 [-1.3-1.5]), and daily functioning (paracetamol + 0.2 [95% CI -0.2-0.6], placebo + 0.1 [-0.3-0.4]).ConclusionsCompared to placebo, no effect of scheduled administration of paracetamol was found on care dependency and daily functioning in persons with advanced dementia with low QoL. Future research should focus on which specific items of care dependency need special attention to improve the care for persons with advanced dementia. A multi-domain approach is needed to enhance and/or maintain QoL of persons with advanced dementia.Trial registrationNetherlands Trial Register (NTR6766); http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=6766; Trial registration date: 20/10/2017.

Comparative Analysis of Machine Learning Algorithms Evaluating the Single Nucleotide Polymorphisms of Metabolizing Enzymes with Clinical Outcomes Following Intravenous Paracetamol in Preterm Neonates with Patent Ductus Arteriosus.

Pharmacogenomics has been identified to play a crucial role in determining drug response. The present study aimed to identify significant genetic predictor variables influencing the therapeutic effect of paracetamol for new indications in preterm neonates. Paracetamol has recently been preferred as a first-line drug for managing Patent Ductus Arteriosus (PDA) in preterm neonates. Single Nucleotide Polymorphisms (SNPs) in CYP1A2, CYP2A6, CYP2D6, CYP2E1, and CYP3A4 have been observed to influence the therapeutic concentrations of paracetamol. The purpose of this study was to evaluate various Machine Learning Algorithms (MLAs) and bioinformatics tools for identifying the key genotype predictor of therapeutic outcomes following paracetamol administration in neonates with PDA. Preterm neonates with hemodynamically significant PDA were recruited in this prospective, observational study. The following SNPs were evaluated: CYP2E1*5B, CYP2E1*2, CYP3A4*1B, CYP3A4*2, CYP3A4*3, CYP3A5*3, CYP3A5*7, CYP3A5*11, CYP1A2*1C, CYP1A2*1K, CYP1A2*3, CYP1A2*4, CYP1A2*6, and CYP2D6*10. Amongst the MLAs, Artificial Neural Network (ANN), C5.0 algorithm, Classification and Regression Tree analysis (CART), discriminant analysis, and logistic regression were evaluated for successful closure of PDA. Generalized linear regression, ANN, CART, and linear regression were used to evaluate maximum serum acetaminophen concentrations. A two-step cluster analysis was carried out for both outcomes. Area Under the Curve (AUC) and Relative Error (RE) were used as the accuracy estimates. Stability analysis was carried out using in silico tools, and Molecular Docking Studies (MDS) were carried out for the above-mentioned enzymes. Two-step cluster analyses have revealed CYP2D6*10 and CYP1A2*1C to be the key predictors of the successful closure of PDA and the maximum serum paracetamol concentrations in neonates. The ANN was observed with the maximum accuracy (AUC = 0.53) for predicting the successful closure of PDA with CYP2D6*10 as the most important predictor. Similarly, ANN was observed with the least RE (1.08) in predicting maximum serum paracetamol concentrations, with CYP2D6*10 as the most important predictor. Further MDS confirmed the conformational changes for P34A and P34S compared to the wildtype structure of CYP2D6 protein for stability, flexibility, compactness, hydrogen bond analysis, and the binding affinity when interacting with paracetamol, respectively. The alterations in enzyme activity of the mutant CYP2D6 were computed from the molecular simulation results. We have identified CYP2D6*10 and CYP1A2*1C polymorphisms to significantly predict the therapeutic outcomes following the administration of paracetamol in preterm neonates with PDA. Prospective studies are required for confirmation of the findings in the vulnerable population.

Investigation of catalytic properties of glutathione reductase obtained by chromatographic methods from the liver of rats with paracetamol-induced liver damage upon administration of 6-hydroxy-2,2,2,4-trimethyl-1,2-dihydroquinoline

The aim of the present study was to analyze some catalytic and regulatory properties of the enzyme preparation of glutathione reductase (GR, EC 1.6.4.2.) obtained from rat liver using gel filtration and ion exchange chromatography under conditions of paracetamol-induced liver injury (PILI) and administration of 6-hydroxy-2,2,4-trimethyl-1,2-dihydroquinoline (DHQ). Laboratory animals (Rattus norvegicus rats of the Wistar line) were divided into 3 groups. The animals of the control group were orally administered vaseline oil. The second group consisted of rats with PILI induced by a single oral administration of paracetamol at a dose of 1000 mg/kg body weight dissolved in 1 cm3 of vaseline oil. Animals of the third group were modeled by PILI and orally administered with DHQ at a dose of 50 mg per 1 kg body weight dissolved in 1 cm3 of 1% starch, 1 hour and 12 hours after paracetamol administration. Liver and serum were collected 24 hours after paracetamol administration. GR activity was measured on a spectrophotometer at 340 nm wavelength. The enzyme was purified from rat liver by ammonium sulfate fractionation, gel filtration through Sephadex G-25, and ion exchange chromatography on DEAE-cellulose. The total amount of protein in the samples was measured using the BCA protein assay kit. GR was obtained from the liver of rats treated with DHQ on the background of PILI with a 32-fold purification degree. Using the method of double inverse Lineweaver-Burk coordinates it was shown that administration of DHQ to rats was accompanied by a decrease in the affinity of the enzyme for NADPH, as compared to the indicators at pathology. The introduction of isocitrate into the spectrophotometric medium resulted in a less pronounced increase in the activity of GR from the liver of animals treated with DHQ on the background of PILI, compared to the second group of rats. The enzyme from the liver of animals of the third group was characterized by a more significant decrease in activity when glucose-6-phosphate was introduced into the reaction medium. Citrate had a less pronounced regulatory effect on GR from the liver of rats treated with DHQ on the background of pathology, relative to the indicators of animals with PILI. The changes in enzyme properties demonstrated may be due to conformational changes in the molecule resulting from the inhibition effect of DHQ on the intensity of free radical-induced oxidation, which develops against the background of the toxic effect of paracetamol metabolites.

Postoperative Pain in the General Surgery Department of Fousseyni Daou Hospital in Kayes

Goal: To study the management of postoperative pain in the general surgery department of the Fousseyni DAOU hospital in Kayes. Patients and Method: We conducted a prospective 6-month study from November 2022 to May 2023, involving 107 surgical patients, aged 15 to 81 years, who met the inclusion criteria. We assessed pain using the Visual Analogue Scale (VAS) at patient admission, at the second hour, and then every eight hours until seventy- second hours after analgesic use. Multimodal analgesia was the most widely used in the study. Administration of paracetamol alone and/or in combination with nefopam and/or ketoprofen and/or morphine. The evolution of pain as well as adverse effects after administration of analgesics were investigated. Results: The mean age of our patients was 35.9 years with extremes of 15 and 81 years. Male sex was the most represented at 64.5% with a sex ratio of 1.82 and the majority of patients were classified as ASA 1 (82.2%). VAS less than 3 (VAS≤ 4) was most observed during the first 2 hours postoperatively, i.e. 41.1% for VAS 0-2 and 28.9% VAS 3-4 at rest, respectively, and respectively 33.6% and 30.8% for no pain and mild pain. At 24 hours postoperatively, 87.2% of patients did not feel pain after the resting assessment, this figure increased from 89.8% at the 48th postoperative hour at rest, still after the use of analgesics. At the 72nd hour, we observed cases of pain, i.e. 0.9% of patients, which was related to a postoperative complication. The average cost of pain management was estimated at 23580 FCFA. Side effects observed were vomiting in 3 patients and drowsiness in one patient. Conclusion: Postoperative pain is still understudied, the evaluation with the visual analogue scale of patients before and after the use of analgesics has allowed us to better understand patients' pain and to improve pain management in the surgical department.

Perioperative pain management in thoracic surgery and side effects in the early postoperative period

Aim. To study the impact of various methods of perioperative pain management on the frequency of postoperative complications in patients with lung cancer after thoracotomy. Materials and methods. The study involved 157 patients who were divided into 4 groups. Multimodal analgesia (MA) group: according to the concept of preemptive analgesia, patients received 1000 mg paracetamol IV 1 hour before surgery and 50 mg dexketoprofen IV; in the postoperative period, dexketoprofen and paracetamol were administered every 8 hours as well as epidural analgesia: 40 mg of 2 % lidocaine solution after a catheter was placed and continuous ropivacaine infusion at a dose of 2 mg/ml (6–14 ml/h) in the postoperative period. Thoracic epidural analgesia (TEA) group: epidural analgesia: administration of 40 mg of 2 % lidocaine solution after catheter placement, continuous ropivacaine infusion in the postoperative period at a dose of 2 mg/ml (6–14 ml/h). Preemptive analgesia (PA) group: according to the concept of preemptive analgesia – 1000 mg IV paracetamol 1 hour before surgery as well as 50 mg IV dexketoprofen; in the postoperative period, dexketoprofen and paracetamol were administered every 8 hours. Control group (C): patients received 50 mg IV dexketoprofen for postoperative analgesia. If the severity of the pain syndrome was more than 50 mm according to the visual analogue scale (VAS), patients of all groups were given 10 mg IV morphine. The study involved the registration of side effects in the postoperative period. Results. Among 157 patients, complications in the postoperative period were observed in 61 patients (38.85 %). The frequency of complications in MA group was 10.8 % of the total number of patients, in TEA group – 12.7 %, PA – 6.4 %, and in C group – 8.9 %. The most common complaint among TEA group patients was injection-site itching (13.5 %). PA group patients had a significantly lower number of complications compared to TEA group (p = 0.035). There was no statistically significant difference in the frequency of nausea or urinary retention in patients of all groups (p &gt; 0.05). No difference was noted in the number of pulmonary complications depending on the method of perioperative analgesia (p &gt; 0.05). 31 patients (75.6 %) of PA group did not have any complications, that was significantly different from TEA (p = 0.021) and MA (p = 0.039) patient groups. Conclusions. The use of paracetamol and dexketoprofen combination in the perioperative period allows to reduce (p = 0.035) the total number of postoperative anesthetic complications compared to the use of only thoracic epidural analgesia. The use of a multimodal approach combining epidural analgesia and administration of paracetamol and dexketoprofen does not reduce (p &gt; 0.05) the overall frequency of complications compared to patients without epidural analgesia.

Use of Preoperative Oral Paracetamol

Paracetamol is a widely used analgesic in the perioperative period. Studies have shown that there is no significant difference between intravenous and oral preparations in postoperative pain outcomes. We proposed moving towards routine administration of oral paracetamol before surgery to reduce the use of IV preparations, with benefits of carbon and cost reduction.

Flaxseed Lignan Alleviates the Paracetamol-Induced Hepatotoxicity Associated with Regulation of Gut Microbiota and Serum Metabolome.

This study examined the protective effect of flaxseed lignans on liver damage caused by an overdose of paracetamol (PAM). The findings demonstrated that administering 800 mg/kg/d flaxseed lignan prior to PAM significantly decreased the serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin (TBi) levels, while it increased liver superoxide dismutase (SOD) and glutathione (GSH) levels in mice. Flaxseed lignan renovated the gut microbiota dysbiosis induced by PAM by promoting the proliferation of sulfonolipid (SL) producing bacteria such as Alistipes and lignan-deglycosolating bacteria such as Ruminococcus while inhibiting the growth of opportunistic pathogen bacteria such as Acinetobacter and Clostridium. Furthermore, flaxseed lignan modulated the serum metabolomic profile after PAM administration, specifically in the taurine and hypotaurine metabolism, phenylalanine metabolism, and pyrimidine metabolism. The study identified eight potential biomarkers, including enterolactone, cervonyl carnitine, acutilobin, and PC (20:3(5Z, 8Z, 11Z)/20:0). Overall, the results suggest that flaxseed lignan can alleviate PAM-induced hepatotoxicity and may be beneficial in preventing drug-induced microbiome and metabolomic disorders.

Pharmacokinetic profile of oral and subcutaneous administration of paracetamol in the koala (Phascolarctos cinereus) and prediction of its analgesic efficacy.

The pharmacokinetic profile of paracetamol in koalas is described when administered orally at 15 mg/kg; followed by the same dose, administered every 12 hours (hrs), repeated five times. After the initial oral administration, the median (range) maximal plasma concentration (Cmax), the time Cmax was reached (Tmax) and elimination half-life (t1/2) were 16.93 μg/mL (13.66 to 20.25 μg/mL); 4 hrs (4 to 8 hrs) and 5.54 hrs (4.66 to 7.67 hrs), respectively. When paracetamol was administered orally at 15 mg/mL every 12 hrs, the trough total plasma concentration range remained comparable to the therapeutic range in humans i.e. 4 to 20 μg/mL that is known to provide some analgesia. However, there is a smaller proportion of free drug (i.e. not bound to plasma proteins; and the active form) available in koala plasma (approximately 40% unbound) compared to human plasma (approximately 80% unbound). Consequently, even when there are similar total drug plasma concentrations in both koala and human plasma, the therapeutic efficacy may be reduced in koalas compared to humans. The initial oral dose and subsequent twice daily doses resulted in no obvious adverse effects in any koala. Haematology, plasma electrolyte and biochemical analyte values remained within their reference ranges eight hrs after the last dose but there was a significant change in alanine transaminase (ALT) levels (an increase), and in total protein (a decrease) (both p = 0.03). A dose of 15 mg/kg was also administered as a subcutaneous injection, diluted 50:50 with saline, to two koalas. As the oral formulation and the subcutaneous administration resulted in comparable absorption, the study focused on the oral profile. Based on these results there is an argument to recommend a slight increase in the oral paracetamol dose for the koala, however further investigation is required to confirm whether repeated administration of a slightly higher dose may be associated with more severe or additional significant changes in haematology, electrolytes or biochemical analytes. However, a preferable recommendation would be to administer this dosage of paracetamol in combination with another analgesic such as tramadol, as a subcutaneous injection, to improve efficacy.

Effects of repeated doses of paracetamol administration during pregnancy on lung, kidney, and liver tissues of pregnant rats.

Paracetamol is one of the most widely used analgesics and antipyretics in the world. It is the most commonly used analgesic and antipyretic agent in pregnancy. Paracetamol is known to have toxic effects on the liver, lung, and kidney. In this study, we investigated the effects of long-term chronic paracetamol exposure on the lung, liver, and kidney in newborn rats at different trimesters of pregnancy. In our study, we formed control (group C), first trimester (group A), and third trimester (group B) groups. Group A had the first seven days of pregnancy and group B had days 15-21. Paracetamol was given orally during the specified periods. On the third postnatal day, pups were euthanized by applying 50 mg/kg ketamine intraperitoneally, and then lung, liver, and kidney tissues were kept under appropriate conditions for examination. A total of 70 pups underwent histopathological examination. The lung revealed congestion (p<0.0001), and erythrocytes (p<0.0001), the liver revealed significant histopathological findings in terms of the presence of inflammation (p<0.0001), vacuolar degeneration (p<0.0001), and sinusoidal dilatation in groups A and B compared to the control group under light microscopy. MDA and free radical metabolism enzyme activities, CAT, GSH, and SOD were evaluated. While there were no significant differences between the groups in lung and kidney tissues, oxidant parameters were significant in liver tissues. Our data point out that subacute doses of paracetamol used chronically in different trimesters caused damage to the lung, liver, and kidney tissues of pups.

Effects of paracetamol/acetaminophen on the expression of solute carriers (SLCs) in late-gestation fetal rat brain, choroid plexus and the placenta.

Solute carriers (SLCs) regulate transfer of a wide range of molecules across cell membranes using facilitative or secondary active transport. In pregnancy, these transporters, expressed at the placental barrier, are important for delivery of nutrients to the fetus, whilst also limiting entry of potentially harmful substances, such as drugs. In the present study, RNA-sequencing analysis was used to investigate expression of SLCs in the fetal (embryonic day19) rat brain, choroid plexus and placenta in untreated control animals and following maternal paracetamol treatment. In the treated group, paracetamol (15mg/kg) was administered to dams twice daily for 5 days (from embryonic day15 to 19). In untreated animals, overall expression of SLCs was highest in the placenta. In the paracetamol treatment group, expression of several SLCs was significantly different compared with control animals, with ion, amino acid, neurotransmitter and sugar transporters most affected. The number of SLC transcripts that changed significantly following treatment was the highest in the choroid plexus and lowest in the brain. All SLC transcripts that changed in the placenta following paracetamol treatment were downregulated. These results suggest that administration of paracetamol during pregnancy could potentially disrupt fetal nutrient homeostasis and affect brain development, resulting in major consequences for the neonate and extending into childhood.

Effect of timing of intraoperative administration of paracetamol on postoperative shivering: A randomised double-blind controlled trial.

Paracetamol (PCM) has an anti-shivering effect and may also exacerbate intraoperative hypothermia. This study compares the incidence of shivering as the primary outcome and the incidence of perioperative hypothermia (<36°C) and the time to the analgesic requirement as secondary outcomes when PCM was administered after induction of anaesthesia or towards the end of surgery. In this randomised study, 225 adult patients of either gender undergoing elective surgical procedures under general anaesthesia with an expected duration of surgery of 1-4 h were studied. They received intravenous (IV) PCM 15 mg/kg (maximum 1 g) immediately after anaesthesia induction (Early PCM group), 30 min before completion of surgery (Late PCM group) or no PCM (Control group). IV morphine 0.1 mg/kg was administered for analgesia in all three groups. The Chi-square test and repeated measures analysis of variance followed by Tukey's test were used for statistical analysis. The incidence of shivering was lower in Late PCM (12%) than in Early PCM (29.3%) (P = 0.009) and Control groups (30.6%) (P = 0.005). The incidence of postoperative hypothermia was also significantly lower in the Late PCM group than in the Early PCM (P = 0.002) and Control groups (P = 0.016). Early PCM and Control groups did not significantly differ. The number of patients requiring postoperative analgesia was smaller, and the time to the analgesic requirement was longer in Late PCM compared to other groups. Administration of IV PCM 30 min before completion of surgery results in a lower incidence of postoperative shivering and hypothermia when compared to PCM administered after induction of anaesthesia or no PCM.

Hippocratea africana Root Extract and Fractions Ameliorates Paracetamol (PCM)-Induced Oxidative Stress and Liver Injuries in Rats

Aim: The antidotal potential of Hippocratea africana root, which is used locally to cure poisoning, was studied in rats.&#x0D; Methodology: The hepatoprotective activity of the root extract (200-600 mg/kg), fractions (dichloromethane (DCM) and aqueous, 400 mg/kg) and Silymarin (100 mg/kg), were investigated against paracetamol-induced liver injury in rats. Assay of liver function parameters, markers of antioxidative stress in addition to liver histological analysis were employed to evaluate the hepatoprotective potential of root extract and fractions.&#x0D; Results: Administration of the root extract (200-600 mg/kg) caused significant (P &lt; .05-.001) increases in the blood levels of total protein and decreases in direct and total bilirubin, and the liver biomarker enzymes ALT, AST, and ALP caused by paracetamol administration. Most of the time, the effects were dose-dependent. When compared to the negative control group of animals (organotoxic-treated animals), the histology of the liver sections from animals treated with extract, fractions, and silymarin revealed a decrease in pathological characteristics. These histological observations suggest significant hepatoprotective potentials which were in line with the chemical pathological alterations.&#x0D; Conclusion: The outcome of the study indicated that root extract and fractions of Hippocratea africana have antioxidative stress potentials and hepatoprotective action against harmful substances, maybe as a result of its phytochemical constituents' activity.

Adverse events following immunization (AEFIs) with anti-meningococcus type B vaccine (4CMenB): Data of post-marketing active surveillance program. Apulia Region (Italy), 2019–2023

The four-component recombinant-DNA anti-meningococcus B vaccine (4CMenB) has been approved by the European Medicines Agency in 2013. In Italy, 4CMenB is recommended since 2017 for use in infants under one year of age. Due to the strong evidence of increased risk of fever after administration, surveillance of adverse events following immunization (AEFIs) is a priority for 4CMenB.This cross-sectional prospective study aims at investigating 4CMenB’s safety profile. The study population is represented by infants under twelve months of age vaccinated with 4CMenB in selected ambulatories in Apulia, a region in South-Eastern Italy, from October 1st, 2020, to March 31st, 2023. Parents were provided with a post-vaccination diary covering up to seven days after immunization and were contacted one week after the vaccination day. Information about AEFIs was collected, and reactions were classified following World Health Organization guidelines. For serious AEFIs, causality assessment was carried out. AEFI risk determinants were investigated via logistic regression.A total of 4,773 diaries were completed, with 78.13 % of them (3,729/4,773) containing one or more AEFI reports. Systemic reactions such as malaise, drowsiness/insomnia and fatigue were the most common ones, followed by fever and local pain, tenderness, redness and swelling.Twenty-three cases of serious AEFIs were reported. Following causality assessment, 78.26 % of serious adverse events (18/23) were deemed to have a consistent causal association with the administration of 4CMenB (reporting rate: 0.38 %). Three infants were hospitalized following vaccination, but no cases of death or permanent/severe impairment were reported. Prophylactic paracetamol administration showed a significant protective effect against the risk of manifesting fever within the first 24 h after administration (OR: 0.75; p < 0.005).Our data confirms existing evidence regarding the safety of 4CMenB vaccination in babies under 2 years of age, but also highlight a significant risk of fever after vaccination. Prophylactic paracetamol administration could represent a protective factor against fever, especially during the first 24 h after vaccination.

Impact of α-Tocopherol and Ascorbic Acid Pre-Treatment on Paracetamol Induced Liver Injury in Wistar Albino Male Rats

Background: Liver injury may occur by toxic dose of paracetamol administration where liver function markers are elevated and centrilobular hepatic necrosis is visible under a microscopic observation in hepatic lobule configuration. α-tocopherol and ascorbic acid are known antioxidant and they may have hepatoprotective effect against paracetamol induced liver damage. Aim of the study: The aim of this study was to evaluate the effects of α-tocopherol and ascorbic acid on paracetamol induced liver damage in Wistar albino male Rats. Methods: This was an animal model experimental study which was conducted in the Department of Physiology, Sir Salimullah Medical College, Dhaka, Bangladesh from 1st January to 31st December, 2017. Although primarily healthy Wister albino male rats, 90-120 days old, weighing from 160 to 200g were selected for this study, finally data were analyzed on 30 rats. Finalized 30 samples were divided into three groups Group I (baseline control group, n=10), Group II (paracetamol treated control group, n=10) and Group III (combined α-tocopherol with ascorbic acid pretreated &amp; paracetamol treated group n=10). The dose of α-tocopherol 100 mg/kg Body weight and ascorbic acid 200 mg/kg Body weight per day orally were selected as pre-exposure prophylaxis. The statistical analyses were done by one-way ANOVA and Bonferroni test, paired ‘t’ test and Fisher’s Exact test as applicable. Results: The mean serum total bilirubin, ALT and AST were significantly increased in group II and III in comparison to that of group I except the serum levels of total bilirubin and ALT of group III which were increased than that of group I but it was not statistically significant. Again, the mean MDA concentration in liver was significantly increased in group II in comparison to that of group I whereas though this level was increased in group III than that of group I but it was statistically not significant. Furthermore, the mean serum levels of total bilirubin, ALT, AST and ...