Ecotoxicological effects of paracetamol on the biochemical and molecular responses of spinach (Spinacia oleracea L.).

The widespread use of pharmaceuticals, including paracetamol, has raised concerns about their impact on the environment and non-target species. The aim of this study was to investigate the biochemical and molecular responses of Spinacia oleracea (spinach) to high paracetamol concentrations in order to understand the plant's stress responses and underlying mechanisms. Under controlled conditions, spinach plants were exposed to different paracetamol concentrations (0, 50, 100, and 200 mg/L). The study evaluated the impact of paracetamol exposure on biochemical parameters such as oxidative stress markers (H2O2, MDA), activities of antioxidant enzymes (APX, CAT, GPOD, SOD), levels of non-enzymatic components (phenolics and flavonoids), and phytohormones (ABA, SA, and IAA). Furthermore, the study assessed molecular impacts by analyzing stress-related genetic variation and alterations in the gene expression of the antioxidant enzymes. Results showed that paracetamol exposure significantly increased oxidative stress in spinach, which was evident through the elevated H2O2 and MDA levels. However, the antioxidant defense mechanisms were activated to counteract this effect, as evidenced by increased activity of antioxidant enzymes and higher phenolics and flavonoid levels. Moreover, induction in the phytohormone levels indicated a stress response in paracetamol-treated plants compared to control plants. RAPD analysis revealed polymorphism indicating the DNA damage, and the Real-time qRT-PCR method showed significant upregulation of stress-responsive genes, highlighting the severe impact of paracetamol at the molecular level. The study concludes that high paracetamol concentrations pose a significant threat to spinach growth by affecting both biochemical and molecular processes. These findings underscore the need for strict environmental management practices to mitigate the possible impact of continuous release, accumulation, and long-term exposure of pharmaceutical contaminants to the environment and implement policies to reduce pharmaceutical pollutants to preserve ecological health and biodiversity.

Application of physiological network mapping in the prediction of survival in critically ill patients with acute liver failure.

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.

Chitosan supported hetero-metallic bio-nanocomposites for paracetamol removal from homogeneous solutions and heterogeneous mixtures with focused antibacterial studies.

Biopolymers infused with bimetallic nanoparticles exhibit a wide range of functionalities necessary for efficiently eliminating diverse water contaminants. However, the protracted production process requires further exploration. As such, present study seeks to optimize microwave-assisted technique for the facile synthesis of cross-linked chitosan (CTS) supported bimetallic-oxide nanoparticles, specifically zinc oxide (ZnO) and iron-oxide (Fe3O4), denoted as CTS-TTP/Zn-Fe. The primary objective is to investigate the efficacy of these beads in the removal of Paracetamol (PCM) from single and complex water matrices while also assessing their antibacterial properties. Characterization includes chemical composition, surface structures, thermal stability, and magnetic properties. The experimental results demonstrated that CTS-TPP/Zn-Fe beads achieved a remarkable PCM removal efficiency of ~99 % (qm = 4.98 mg g-1), with a Zn:Fe mole ratio of 1:1. The experimental data showed good applicability with Freundlich isotherm and chemisorption-supported rate models (R2 > 0.9). To evaluate the long-term viability and practicality of these beads, three crucial field applicability tests were conducted. These encompassed competition studies with other pharmaceuticals, desorption investigations for repeated use, and efficiency evaluations in an ionic solution. Collectively, this research provides a comprehensive understanding, spanning from material design to practical applications, with potential relevance for large-scale wastewater treatment when coupled with appropriate flux control measures.

Evaluation, optimization study, and life cycle assessment of novel eco-friendly PVA-based nanocomposite hydrogel adsorbents for methylene blue and paracetamol removal.

In this study, an eco-friendly and novel hydrogel based on a crosslinked polyvinyl alcohol (PVA), iota carrageenan (IC) and polyvinylpyrrolidone (PVP) scaffold, containing a large amount (10-50 wt%) of nanoscale palm fronds (NPF) as additives, for water purification was demonstrated. A life cycle assessment (LCA) findings on NPF as biomass waste incorporated into PVA_PVP_IC polymer matrix was presented, and the results highlight the necessity of focused actions to reduce environmental impact and support the palm waste utilization in a sustainable manner. The multicomponent nanocomposite hydrogels were examined as adsorbents in a system work in batches for methylene blue (MB) and paracetamol (PCT) removal. The results show that, the presence of NPF, which dispersed in the hydrogel PVA_PVP_IC scaffolds containing both covalent and non-covalent cross-linking bonds, greatly enhanced the MB and PCT adsorption efficiency. A response surface methodology (RSM) model was used to find the best operating parameters of contaminant adsorption, including time, adsorbent dose, and starting concentration of pollutants. By using this statistical model, it was found that the optimal conditions for the adsorption reaction to achieve the complete removal of MB are 66.7 h adsorption time duration, 98.5 mg L-1 starting concentration, and an adsorbent dose of 5.9 mg, while for the complete removal of PCT, it is 57.6 h adsorption time duration, 80 mg L-1 starting concentration, and an adsorbent dose of 6 mg. The reusability of the nanocomposite hydrogels were tested for 5 cycles, all showed high adsorption capacity, indicating the potential for practical application of this nanocomposite hydrogel system. This study indicates that the prepared nanocomposite hydrogel raises the standard used for treatment of wastewater and also gives a solution to protect the environment and mitigate global warming.

Aspirin may be more suitable for patients with major depression: Evidence from two-sample Mendelian randomization analysis.

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.

Driving Forces in the Formation of Paracetamol Cocrystals and Solvate with Naphthalene, Quinoline and Acridine.

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: R44(22) in (1); R64(20) and R22(8) in (2); and R22(8), R42(12), and R44(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.

Self-poisoning with paracetamol in England: short report of characteristics of individuals and their overdoses according to source of tablets.

Self-poisoning with paracetamol is the most frequently used overdose method in the UK. Psychosocial assessments were conducted by mental health clinicians with 127 consecutive individuals who presented with pure paracetamol overdoses to a large general hospital over 8 months, including asking about the source of the tablets and scoring the patients' acts on the Beck Suicide Intent scale (BSI). Patients were predominantly female (86%) and young (79% aged 12-24 years). Most had used paracetamol which was available in the home (77%). Those who purchased paracetamol for the act took double the number of tablets compared with those who used paracetamol available in the home (37 v. 18), had higher suicidal intent (mean BSI: 11 v. 7) and more often required treatment with N-acetyl cysteine (71% v. 43%). These results highlight the need for safer home storage of paracetamol and consideration of reducing pack size limits on paracetamol that can be purchased.

Assessment the Combining Medications with Tobacco during Water-Pipe Smoking among the University Students in Jordan.

BACKGROUND: Water-pipe smoking, popularly known as "hookah" or "shisha," is a widespread social activity in the Middle East, involving the use of a water-filtered device to vaporize flavored tobacco. A concerning trend has emerged as individuals add various drugs to the tobacco mixture, complicating the health implications. AIMS: This study aimed to explore the prevalence, demographic factors, and motivations behind drug mixing with tobacco in shisha among university students in Jordan. METHODS: In this descriptive cross-sectional study, a structured questionnaire was used to collect data on participants' demographics, shisha smoking habits, drug mixing practice and the motivations behind it. Four hundred and sixty-nine (469) students, aged 18-30 years, including medical and non-medical students, from two universities in Jordan participated in this study. RESULTS: Approximately 18% of participants reported mixing drugs with tobacco in shisha, with paracetamol being the predominant choice (80%). Motivations varied, with 42% seeking euphoric effects, 46% a relaxing experience, and 12% a sedative outcome. Males (73%) showed a higher frequency of drug mixing compared to females (27%). In addition, non-medical reported mixing drugs with the tobacco of water-pipe more than medical students. CONCLUSIONS: This study provides valuable insights into the complex phenomenon of drug mixing with tobacco in water-pipe smoking among university students in Jordan. The findings highlight the need for further research on clinical implications and interventions to address this emerging trend.

Efficacy and safety of serrapeptase on ankle sprain cases: A single center prospective comparative study.

Background: Non-steroid anti-inflammatory drugs (NSAIDs) rank among the frequently prescribed medications for addressing pain and inflammation. Although they are powerful pain relievers, their side effects are indisputable. Serrapeptase, a serine protease, exhibits anti-inflammatory and anti-oedemic activity without the side effects of NSAIDs. We aim to assess the efficacy and safety of serrapeptase in the treatment of pain and edema in ankle sprains. Methods: In a single-centre prospective comparative study, 76 patients aged 18-53 with Grade II ankle sprains were assigned to either a serrapeptase intervention group (n = 38) receiving 5 mg serrapeptase (two tablets, three times per day) for ten days, or a control group (n = 38) receiving 500 mg paracetamol (three times per day) for the same duration. Ankle joint edema was assessed using both Figure-of-Eight and water-displacement methods. Pain was assessed with Visual Analogue Scale (V.A.S.). Within-groups and between-groups analyses were performed in the 3rd and 10th day. Results: Both groups exhibited reduced edema and pain over time. Serrapeptase demonstrated a superior reduction in ankle joint edema on the third and tenth day compared to paracetamol, while pain management did not differ significantly. Conclusion: Serrapeptase exhibited better efficacy than paracetamol in reducing ankle joint edema, highlighting its potential as an alternative treatment. Level of evidence: Level II, prospective comparative trial without randomization.

The Assessment of Knowledge, Attitude, and Practice of Paracetamol and Ibuprofen Administration Among Saudi Parents in the Makkah Region.

Introduction Paracetamol and ibuprofen, widely used for pediatric fever and pain, are safe when administered correctly. However, the caregiver's lack of understanding poses risks such as overdose. Addressing knowledge gaps is crucial due to reported variations in over-the-counter medication practices. "Fever phobia" underscores parental anxiety, stressing the ongoing need for research in this healthcare domain. Methodology This is a descriptive cross-sectional design targeting Saudi parents and caregivers from the Makkah region who have children aged 0-10 years. Data was collected via a self-administered validated online questionnaire in the Arabic language using a convenient sampling technique. The data was cleaned in Excel and analyzed using SPSS version 29 (IBM Inc., Armonk, New York). Results Our study included 449 parents and caregivers in the Makkah Region, of whom 337 (75.1%) were female, 179 (39.9%) were aged 18-29, and 425 (94.7%) were Saudi nationals. Knowledge assessment revealed gaps; e.g., only 86 (26.6%) identified baby weight as a dosage factor. Attitudes varied, with 152 (47.1%) associating paracetamol/ibuprofen with liver harm. Logistic regression showed no significant predictors for high-level knowledge, positive attitudes, or good practices, except for gender-influencing good practices (p=0.035, aOR=1.839). Significantly, males exhibited better practices regarding using of paracetamol. Conclusion Our study highlights knowledge gaps among parents and caregivers in the Makkah Region regarding pediatric fever management with paracetamol and ibuprofen. Attitudes varied, and gender significantly influenced good practices, with males demonstrating better adherence to the proper practice of managing children using paracetamol and ibuprofen.

Exploring the impact of curcumin on osteoarthritis symptomatology: correlations and insights from a Bulgarian cohort.

INTRODUCTION: Osteoarthritis is a prevalent degenerative joint disorder associated with pain and functional impairment. Curcumin, a natural anti-inflammatory compound, has garnered attention for its potential therapeutic benefits in osteoarthritis management.

Chlorzoxazone-Induced Fixed Drug Eruption: A Clinical Case Report.

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.

Hepatoprotective potential of coconut inflorescence sap against paracetamol induced toxicity in hep G2 cell lines.

Coconut Inflorescence Sap (CIS) is the sweet, oyster-white colored, non-fermented juice obtained from the immature inflorescence of the Coconut tree. Acetaminophen (N-acetyl-p-aminophenol, or paracetamol) is one of the most frequently used drugs worldwide as an antipyretic or analgesic. HepG2 cell lines were used as an experimental model for studying in vitro hepatotoxicity induced by Paracetamol. The present study aims to identify biologically active compounds of CIS using LCMS analysis and to elucidate the ameliorative potential of CIS in alleviating paracetamol-induced hepatotoxicity. LC-MS analysis revealed the presence of 17 bioactive compounds. HepG2 cells were pretreated with Paracetamol (20 mM) for inducing toxicity, and Silymarin at a concentration of 50 µg/ml was used as a standard drug. The morphological analysis and MTT assay showed effective recovery from toxicity in cells treated with CIS in a dose-dependent manner. CIS at 25 µg/ml potentially showed the highest percentage of inhibitory activity against the toxicity induced by paracetamol. The treatment with paracetamol significantly increased the indicators of liver toxicity - LDH, SGOT, SGPT, and Glut.S Transferase in the media.CIS administration also increased the total protein levels, SOD, and Catalase activity. The morphological analysis, MTT assay, cytocompatibility studies, determination of enzymatic activities, etc., confirms the significant hepatoprotective efficacy of CIS.

Comparison of the Magnesium Sulphate With Paracetamol Combination vs the Fentanyl With Lignocaine Combination in Attenuating the Hemodynamic Response During Laryngoscopy and Intubation: A Prospective, Double-Blinded Randomized Controlled Study.

Background and aims Laryngoscopy and intubation cause an increased sympatho-adrenergic pressor response, which can be detrimental to patients with coronary artery disease, hypertension, etc. Various drugs and manoeuvres have been tried to reduce the pressor response with acceptable results but the quest for the ideal drug still continues. Hence, we planned to compare the effects of magnesium sulfate with paracetamol and fentanyl with lignocaine on attenuating the hemodynamic responses due to direct laryngoscopy and intubation and to note the complications of these drugs. Methods We studied 60 adult patients of the American Society of Anaesthesiologists (ASA) physical status I and II of either sex, scheduled for elective surgery under general anaesthesia. The patients were randomly divided into two groups. Group A received 25 mg/kg magnesium sulphate mixed with paracetamol 1 gram IV (100 ml) given over 10 minutes before induction and Group B received 2 mcg/kg fentanyl and 1.5 mg/kg lignocaine, 3 minutes before intubation. All patients were uniformly pre-medicated, induced, and intubated as per standard protocol. Heart rate (HR) and systemic arterial pressures were recorded at baseline, after study drug infusion, after induction, and 1, 3, 5, 10, and 15 mins after intubation. Hemodynamic parameters were compared using repeated measures analysis of variance (ANOVA). In the post-hoc tests, p value < 0.05 was considered statistically significant. Results We observed the mean pre-op HR (p = 0.161) and mean HR one-minute post-induction (p = 0.144). The percentage change from baseline at one-minute post-induction was 9.7 in Group A and 15.2 in Group B. We observed the mean pre-op mean arterial pressure (MAP) (p = 0.119) and mean MAP one minute post-induction (p = 0.585). The percentage change from baseline at one-minute post-induction was 3.3 in Group A and 2.8 in Group B. The percentage change from baseline was found to be within 15%, for HR in Group A and for systolic blood pressure (SBP), diastolic blood pressure (DBP), and MAP in Group B. However, there was no statistically significant difference (p > 0.05) between the mean HR, SBP, DBP, and MAP between the time points. Conclusion In our study, both the combinations of drugs, magnesium sulphate with paracetamol (Group A drugs) and fentanyl with lignocaine (Group B drugs) were found to be equally effective (i.e. neither group was superior to the other) in attenuating the hemodynamic response to laryngoscopy and intubation.

Synthesis of Copper Molybdate and Its Electrochemical Sensing of Paracetamol.

Background In recent years, significant advancements have been made in various scientific sectors, particularly in healthcare and pharmaceutical research. This progress has been driven by the development of enhanced sensing materials and methodologies. Electrochemical sensing has become an important tool in detecting and analyzing drug molecules due to its high sensitivity, specificity, and rapid response times. Among various drugs, paracetamol, also known as acetaminophen, is widely used for its analgesic and antipyretic properties. Accurate detection of paracetamol is crucial due to its widespread use and potential for overdose, which can lead to severe liver damage. Copper molybdate (CuMoO4) is a transition metal oxide that has garnered attention for its excellent electrical conductivity and electrochemical stability. These properties make it a promising candidate for use in electrochemical sensors. The ability of CuMoO4 to act as a sensor material is enhanced by its unique structural and morphological characteristics, which can be tailored during synthesis. Aim This study aimed to synthesize CuMoO4 and investigate its electrochemical sensing capability for the detection of drug molecules, specifically paracetamol. Materials and method CuMoO4 was synthesized using a precipitation method that did not involve any surfactants. This approach was chosen to simplify the synthesis process and avoid potential contamination from surfactants. The morphology of the synthesized CuMoO4 nanoparticles was investigated using a field emission scanning electron microscope (FE-SEM). Energy-dispersive X-ray spectroscopy (EDX) confirmed the purity of the CuMoO4 nanomaterial. Structural analysis was performed using X-ray diffraction (XRD). To evaluate the electrochemical sensing capability of CuMoO4 for paracetamol, Differential pulse voltammetry (DPV) was employed. DPV is a sensitive electrochemical technique that can detect changes in current response corresponding to the presence of analytes. Results The synthesized CuMoO4 exhibited a rock-like structure, as revealed by FE-SEM imaging. This morphology is advantageous for electrochemical applications due to the increased surface area available for interaction with analytes. EDX confirmed the purity of the CuMoO4 nanomaterial, showing no significant impurities. XRD analysis indicated that the CuMoO4 nanoparticles were crystalline in nature, which is beneficial for consistent and reproducible electrochemical behavior. The DPV analysis demonstrated that the CuMoO4 sensor exhibited a linear increase in current response with increasing concentrations of paracetamol. This linear relationship indicates that CuMoO4 is capable of detecting paracetamol effectively, with a strong and quantifiable signal response. Conclusion The CuMoO4 nanomaterial was successfully synthesized using a simple precipitation method and was characterized by its rock-like morphology and crystalline structure. Electrochemical testing using DPV showed that CuMoO4 has excellent sensing capabilities for detecting paracetamol, with a clear and linear current response. These findings suggest that CuMoO4 is a promising electrochemical sensing material for drug detection, potentially offering a reliable and efficient method for monitoring paracetamol and possibly other pharmaceuticals in various settings.

Bimetallic MOF-based electrochemical sensor for determination of paracetamol in spiked human plasma.

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.

Acetaminophen effects upon formalin-evoked flinching, postformalin, and postincisional allodynia and conditioned place preference.

Introduction: We explored in mice, the analgesic, tolerance, dependency, and rewarding effects of systemic acetaminophen (APAP). Methods: Studies employed adult mice (C57Bl6). (1) Intraplantar formalin flinching + post formalin allodynia. Mice were given intraperitoneal APAP in a DMSO (5%)/Tween 80 (5%) or a water-based formulation before formalin flinching on day 1 and tactile thresholds assessed before and after APAP at day 12. (2) Paw incision. At 24 hours and 8 days after hind paw incision in male mice, effects of intraperitoneal APAP on tactile allodynia were assessed. (3) Repeated delivery. Mice received daily (4 days) analgesic doses of APAP or vehicle and tested upon formalin flinching on day 5. (4) Conditioned place preference. For 3 consecutive days, vehicle was given in the morning in either of 2 chambers and in each afternoon, an analgesic dose of morphine or APAP in the other chamber. On days 5 and 10, animals were allowed to select a "preferred" chamber. Results: Formalin in male mice resulted in biphasic flinching and an enduring postformalin tactile allodynia. Acetaminophen dose dependently decreased phase 2 flinching, and reversed allodynia was observed postflinching. At a comparable APAP dose, female mice showed similarly reduced phase 2 flinching. Incision allodynia was transiently reversed by APAP. Repeated APAP delivery showed no loss of effect after sequential injections or signs of withdrawal. Morphine, but not APAP or vehicle, resulted in robust place preference. Conclusions: APAP decreased flinching and allodynia observed following formalin and paw incision and an absence of tolerance, dependence, or rewarding properties.

A case report of Paracetamol related pyroglutamic acidosis: mind the gap in a malnourished patient.

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.

Study on Differences of Metabolites among Different Ganoderma Species with Comprehensive Metabolomics.

In traditional Chinese medicine, Ganoderma is a kind of edible and medicinal mushroom, which is widely used because of its significant pharmacological activity. There are many species within the Ganoderma genus, each with different material bases and applications. However, detailed studies on these species are still lacking. In this study, we investigated the metabolites of G. leacontextum (B), G. lucidum (C), G. tsugae (S) from Changbai Mountain, and G. tsugae (M) from Mongolia using metabolomics. The PCA results indicated minimal differences between M and S, whereas B and S exhibited significant variations. A total of 708 differential metabolites were identified in this study, with steroids, triterpenoids, phenols, and quinones being the major metabolites. Specifically, triterpenoids and steroids were higher in C. Meanwhile, phenolic compounds were more abundant in B. Additionally, quinones were more abundant in M and S. We validated some of the main compounds, and the results showed that paracetamol was most abundant in B, making paracetamol a potential marker for identifying B. Additionally, vitamin K3 was found to be more abundant in M and S, which can serve as a marker for their identification. This study provides new insights and a theoretical basis for the development and utilization of the genus Ganoderma.