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Veterinary Research Forum : An... 2024In this study, the effects of nanocurcumin on acetaminophen-induced acute hepatorenal toxicity in domestic pigeons () were investigated. Fifteen pigeons were randomly...
In this study, the effects of nanocurcumin on acetaminophen-induced acute hepatorenal toxicity in domestic pigeons () were investigated. Fifteen pigeons were randomly assigned into three groups. Group I was served as a negative control group and received tap water as a placebo. Pigeons in groups II and III were administered acetaminophen at the beginning of the experiment (hr 0). Group III was further treated with nanocurcumin, at 12 hr after acetaminophen administration, being continued every 12 hr for two days. The birds were observed for clinical signs of acute drug toxicity. Blood samples were collected from the pigeons at hr 0, 12, 24 and 48 of the experiment for biochemical analysis of the serum. The results showed that acetaminophen toxicity increased the serum levels of aspartate aminotransferase, alanine aminotransferase, urea and uric acid in the pigeons. Nanocurcumin treatment of acetaminophen intoxicated pigeons attenuated increases in biomarkers of the liver and kidney functions towards control levels. Also, the consumption of nanocurcumin minimized histopathological changes in the liver and kidney. A mortality of 60.00% was seen in the acetaminophen-induced toxicity group; while, none of the birds treated with nanocurcumin died. It can be concluded that nanocurcumin alleviates the acetaminophen-induced acute toxic liver and kidney damages, which can lead to pigeon mortality.
PubMed: 38770380
DOI: 10.30466/vrf.2024.2011585.4009 -
Biochemistry and Biophysics Reports Jul 2024-acetyl--benzoquinoneimine (NAPQI), a toxic byproduct of paracetamol (Acetaminophen, APAP), can accumulate and cause liver damage by depleting glutathione and forming...
BACKGROUND AND AIM
-acetyl--benzoquinoneimine (NAPQI), a toxic byproduct of paracetamol (Acetaminophen, APAP), can accumulate and cause liver damage by depleting glutathione and forming protein adducts in the mitochondria. These adducts disrupt the respiratory chain, increasing superoxide production and reducing ATP. The goal of this study was to provide computational proof that succinate dehydrogenase (SDH), a subunit of complex II in the mitochondrial respiratory chain, is a favorable binding partner for NAPQI in this regard.
METHOD
Molecular docking, molecular dynamics simulation, protein-protein interaction networks (PPI), and KEGG metabolic pathway analysis were employed to identify binding characteristics, interaction partners, and their associations with metabolic pathways. A lipid membrane was added to the experimental apparatus to mimic the natural cellular environment of SDH. This modification made it possible to develop a context for investigating the role and interactions of SDH within a cellular ecosystem that was more realistic and biologically relevant.
RESULT
The molecular binding affinity score for APAP and NAPQI with SDH was predicted -6.5 and -6.7 kcal/mol, respectively. Furthermore, RMSD, RMSF, and Rog from the molecular dynamics simulations study revealed that NAPQI has slightly higher stability and compactness compared to APAP at 100 ns timeframe with mitochondrial SDH.
CONCLUSION
This study serves to predict the mechanistic process of paracetamol toxicity by using different computational approaches. In addition, this study will provide information about the drug target against APAP hepatotoxicity.
PubMed: 38766381
DOI: 10.1016/j.bbrep.2024.101727 -
Clinical, Cosmetic and Investigational... 2024Although the use of biologics has led to great improvement in psoriasis patients, the treatment of psoriasis during pregnancy still faces many challenges. We herein...
Although the use of biologics has led to great improvement in psoriasis patients, the treatment of psoriasis during pregnancy still faces many challenges. We herein report on a 29-year-old pregnant woman treated with ustekinumab for generalized pustular psoriasis. Upon becoming pregnant, the woman underwent continued treatment with ustekinumab in the first trimester. We also considered the need for neonatal vaccination. The patient discontinued ustekinumab therapy in the second trimester, and during the period of drug discontinuation we noted a slight rash recurrence. The patient was treated with ultraviolet B phototherapy and topical corticosteroids, and the rash was localized to the abdomen. However, in the 27th week of pregnancy, the patient was infected with COVID-19, which made the condition worse. The rash erupted rapidly and spread throughout her body, and she experienced a high fever with her blood count showing augmented numbers of white blood cells. The patients self-administered 0.3 g of acetaminophen three times per day, and after four days her core body temperature was 38.0°C; the rash, however, did not diminish. We diagnosed an outbreak of generalized pustular psoriasis and treated the patient with ustekinumab. The rash resolved quickly, and a healthy newborn was delivered by caesarean section at 39 weeks.
PubMed: 38765193
DOI: 10.2147/CCID.S451738 -
Journal of Ethnopharmacology Oct 2024Scutellaria baicalensis Georgi (SBG), a widely used traditional Chinese medicine, exhibits anti-inflammatory and antioxidant properties. Wogonin is one of the primary...
ETHNOPHARMACOLOGICAL RELEVANCE
Scutellaria baicalensis Georgi (SBG), a widely used traditional Chinese medicine, exhibits anti-inflammatory and antioxidant properties. Wogonin is one of the primary bioactive components of SBG. Acetaminophen (APAP)-induced liver injury (AILI) represents a prevalent form of drug-induced liver damage and is primarily driven by inflammatory responses and oxidative stress.
AIM OF STUDY
To investigate the therapeutic effects of Wogonin on AILI and the underlying mechanisms.
MATERIALS AND METHODS
C57BL/6 J mice were pre-treated with Wogonin (1, 2.5, and 5 mg/kg bodyweight) for 3 days, followed by treatment with APAP (300 mg/kg bodyweight). The serum and liver tissue samples were collected at 24 h post-APAP treatment. Bone marrow-derived macrophages and RAW264.7 cells were cultured and pre-treated with Wogonin (5, 10, and 20 μM) for 30 min, followed by stimulation with lipopolysaccharide (LPS; 100 ng/mL) for 3 h. To examine the role of the PI3K/AKT signaling pathway in the therapeutic effect of Wogonin on AILI, mice and cells were treated with LY294002 (a PI3K inhibitor) and MK2206 (an AKT inhibitor).
RESULTS
Wogonin pre-treatment dose-dependently alleviated AILI in mice. Additionally, Wogonin suppressed oxidative stress and inflammatory responses. Liver transcriptome analysis indicated that Wogonin primarily regulates immune function and cytokines in AILI. Wogonin suppressed inflammatory responses of macrophages by inhibiting the PI3K/AKT signaling pathway. Consistently, Wogonin exerted therapeutic effects on AILI in mice through the PI3K/AKT signaling pathway.
CONCLUSIONS
Wogonin alleviated AILI and APAP-induced hepatotoxicity in mice through the PI3K/AKT signaling pathway.
Topics: Animals; Flavanones; Acetaminophen; Mice, Inbred C57BL; Mice; Chemical and Drug Induced Liver Injury; Proto-Oncogene Proteins c-akt; Signal Transduction; Male; RAW 264.7 Cells; Phosphatidylinositol 3-Kinases; Liver; Oxidative Stress; Anti-Inflammatory Agents; Macrophages; Scutellaria baicalensis
PubMed: 38763368
DOI: 10.1016/j.jep.2024.118364 -
Environmental Science and Pollution... May 2024Water pollution due to emerging contaminants, e.g., pharmaceuticals, is one of the most frequently discussed issues. Among them, paracetamol received great attention due...
Water pollution due to emerging contaminants, e.g., pharmaceuticals, is one of the most frequently discussed issues. Among them, paracetamol received great attention due to its physico-chemical properties, persistence, and adverse environmental effects. Different techniques were employed for its degradation and, among them, photodegradation is considered one of the most suitable to pursue the aim. This work aimed to synthesize mesoporous TiO, even with the presence of iron, through a one-pot method, with an enhanced ability to abate paracetamol. Precisely, pure and iron-containing (3.5 wt%) TiO were successfully obtained employing an uncommon procedure for this kind of material, mainly solution combustion synthesis (SCS). Moreover, a traditional hydrothermal method and a commercial Degussa P25 were also investigated for comparison purposes. The samples were characterized through N-physisorption at - 196 °C, XRD, XPS, EDX, DR UV-Vis, and FESEM analysis. The catalytic activity was investigated for the abatement of 10 ppm of paracetamol, under UV irradiation in acidic conditions (pH = 3) and in the presence of HO. As a whole, the best-performing catalysts were those obtained through the SCS procedure, highlighting a complete removal of the organic pollutant after 1 h in the case of Fe/TiO_SCS, thanks to its highly defective structure and the presence of metal Fe. To better investigate the performance of both pure and Fe-containing SCS samples, further oxidation tests were performed at pH = 7 and in the absence of HO. Noteworthy, in these conditions, the two samples exhibited different behaviors, highlighting different mechanisms depending on the presence or absence of iron in the structure. Finally, a kinetic study was conducted, demonstrating that a first order is suitable for its abatement.
Topics: Titanium; Acetaminophen; Catalysis; Photolysis; Iron; Water Pollutants, Chemical; Hydrogen Peroxide
PubMed: 38758438
DOI: 10.1007/s11356-024-33575-5 -
Orthopaedic Journal of Sports Medicine May 2024Although several studies have noted that patients are routinely overprescribed opioids, few have reported usage after arthroscopic surgery.
BACKGROUND
Although several studies have noted that patients are routinely overprescribed opioids, few have reported usage after arthroscopic surgery.
PURPOSE
To determine opioid consumption and allocation for unused opioids after common arthroscopic surgeries.
STUDY DESIGN
Case series; Level of evidence, 4.
METHODS
Patients between the ages of 15 and 40 years who were scheduled to undergo anterior cruciate ligament reconstruction (ACLR), labral repair of the hip or shoulder, meniscectomy, or meniscal repair were prospectively enrolled. Patients were prescribed either 5 mg hydrocodone-325 mg acetaminophen or 5 mg oxycodone-325 mg acetaminophen based on surgeon preference. Patients completed a daily opioid usage survey during the 2-week postoperative period. In addition, patients completed a survey on postoperative day 21 inquiring about continued opioid use and medication disposal, if applicable. Opioid medication consumption was converted to morphine milligram equivalents (MMEs).
RESULTS
Of the 200 patients who were enrolled in the study, 176 patients had sufficient follow-up after undergoing 85 (48%) ACLR, 26 (14.8%) hip labral repair, 34 (19.3%) shoulder labral repair, 18 (10.2%) meniscectomy, and 13 (7.4%) meniscal repair procedures. Mean age was 26.1 years (SD, 7.38); surgeons prescribed a mean of 26.6 pills whereas patients reported consuming a mean of 15.5 pills. The mean MME consumption in the 14 days after each procedure was calculated: ACLR (95.7; 44% of prescription), hip labral repair (84.8; 37%), shoulder labral repair (57.2; 35%), meniscectomy (18.4; 27%), and meniscal repair (32.1; 42%). This corresponded to approximately 39% of the total opioid prescription being utilized across all procedures. Mean MME consumption was greatest on postoperative day 1 in hip, shoulder, and meniscal procedures and on postoperative day 2 in ACLR. Only 7.04% of patients reported continued opioid use in the third postoperative week. Patients had a mean of 11 unused pills or 77.7 MMEs remaining. Of the patients with remaining medication, 24.7% intended to keep their medication for future use.
CONCLUSION
The results of our study indicate that patients who undergo the aforementioned arthroscopic procedures consume <75 MMEs in the 2-week postoperative period, translating into a mean of 10 to 15 pills consumed. Approximately 60% of total opioids prescribed went unused, and one-fourth of patients intended to keep their remaining medication for future usage. We have provided general prescribing guidelines and recommend that surgeons carefully consider customizing their opioid prescriptions on the basis of procedure site to balance optimal postoperative analgesia with avoidance of dissemination of excess opioids.
PubMed: 38757068
DOI: 10.1177/23259671241249688 -
Cureus Apr 2024Background Nasal obstruction due to inferior turbinate hypertrophy is a common medical complaint among ENT clinic patients, which can significantly affect the patient's...
Background Nasal obstruction due to inferior turbinate hypertrophy is a common medical complaint among ENT clinic patients, which can significantly affect the patient's quality of life, and some are compelled to use topical intranasal decongestants. Conservative management is the first line of treatment; however, surgical reduction of the inferior turbinate becomes necessary if the symptoms persist after three months of treatment. The optimal surgical technique is controversial. High-intensity focused ultrasound (HIFU) is a minimally invasive surgical option that targets tissue volume precisely and minimally impacts surrounding tissue. This study aimed to assess the effectiveness and safety of HIFU in treating patients suffering from nasal obstruction due to inferior turbinate hypertrophy. Methods This prospective study was conducted from February to December 2016. The study lasted over six months. Patients with a history of allergic and non-allergic rhinitis participated in this study. It included 43 patients who had been experiencing chronic nasal obstruction due to bilateral inferior turbinate hypertrophy and had not shown improvement after three months of medical treatment. The patients underwent Ultrasound Volumetric Tissue Reduction (UVTR) surgery using the D & A Ultrasurg device (Diamant Medical Equipment Ltd., Amman, Jordan) under local anesthesia. The effectiveness, safety, and tolerance of HIFU were assessed subjectively for six months using a well-designed questionnaire utilizing a visual analog scale (VAS) and nasal endoscopy after the surgery. Results The study included 43 patients, 22 male and 21 female, aged 13 to 65 years. The study found that 40 (93%) patients showed significant improvement in nasal obstruction within a month of the surgery. However, three (7%) patients continued to experience persistent nasal obstruction even after six months of follow-up. The procedure was well-tolerated, with low rates of complications after surgery and reasonable pain control. During the surgery, 20 (46.5%) patients reported mild pain described as a pressure-like sensation, and 10 out of 43 patients (23%) required paracetamol after the procedure. Four patients (9.3%) had mild bleeding, which was treated with an ultrasound nasal probe without nasal packing. All patients experienced crusting of the nasal cavity during the first week, but no crustation was observed after the first month. There were no reported cases of synechia among the patients. Conclusion This study confirms that HIFU treatment is a reliable and effective treatment for improving short-term nasal obstruction caused by inferior turbinate hypertrophy. The procedure is easily applied and well-tolerated in outpatient clinics.
PubMed: 38756284
DOI: 10.7759/cureus.58348 -
The Journal of Clinical Pediatric... May 2024Postoperative pain is generally a novel experience among paediatric patients. Topical anaesthetics, distraction procedures, and buffering of anaesthetic solutions have...
Postoperative pain is generally a novel experience among paediatric patients. Topical anaesthetics, distraction procedures, and buffering of anaesthetic solutions have been used in reducing the postoperative pain. In this review, the authors assessed various modalities used to alleviate postoperative pain in children's dental treatment under general anaesthesia. Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) protocol were strictly adhered to in this systematic review. Specific keywords including postoperative pain, general anaesthesia, children, and dental extraction were used in the search for relevant randomized control trial studies in Web of Science, Scopus and PubMed, and included articles published until June 2021. From a total of 191 abstracts, 21 were reviewed. From the six studies with the usage of non-steroidal anti-inflammatory drugs (NSAIDs) alone or in combination with paracetamol, four observed that the preoperative use of NSAIDs alone or in combination was better than paracetamol alone, one discovered preoperative intravenous paracetamol was better than postoperative intravenous paracetamol, and the remaining study found no difference among various groups. Of two studies comparing the usage of non-steroidal anti-inflammatory drugs with opioid analgesics, one stated intravenous fentanyl in combination was better, while the other study found no difference among groups. The results obtained in this review can be utilized by physicians to control postoperative pain in children undergoing dental treatment under general anaesthesia.
Topics: Humans; Pain, Postoperative; Anesthesia, General; Child; Anti-Inflammatory Agents, Non-Steroidal; Dental Care for Children; Acetaminophen; Analgesics, Opioid; Anesthesia, Dental; Tooth Extraction
PubMed: 38755977
DOI: 10.22514/jocpd.2024.054 -
Cureus Apr 2024Background Patients with sickle cell disease (SCD) often present in the Emergency Department (ED) with acute and debilitating pain and other SCD-related complications....
Background Patients with sickle cell disease (SCD) often present in the Emergency Department (ED) with acute and debilitating pain and other SCD-related complications. Objectives The objective is to analyze the causes of ED visits of pediatric patients with SCD, assess the burden of ED admission due to SCD in relation to other pediatric diseases, the treatment given, and the outcomes. Methods A prospective analytical study was conducted on children and adolescents with SCD, 1-14 years old who had been admitted to the ED at Basrah Maternity and Children Hospital over a six-month period. Patient's sociodemographic and clinical data, drug history, length of ED stay, complications, outcome, and readmissions were recorded. Results A total of 422 patients with SCD were admitted to ED during the study period representing 4.10% of the total admitted cases; 276(65.40%) of them were recruited in this study, and their mean age was 7.84 ±3.47 years. The main cause for ED admission was pain (73.91%), followed by infection (10.14%) and hemolytic crisis (6.15%). The mean duration of stay at ED was 6.11±1.87 hours. All admitted SCD patients had received analgesia; non-steroidal anti-inflammatory drugs (NSAIDs) were the commonest (80.4%), followed by acetaminophen (39.5%), and opioid narcotic (18.5%). Readmission within 30-days was reported in 82(29.71%) patients and was associated with the number of ED visits/last year (B=0.151, P=0.023), length of stay at ED (B=0.140, P=0.034) and severe disease (B=0.253, P<0.001). Conclusions Acute painful episodes were the main cause of ED admission. Although most patients with pain did receive NSAIDs, only a small percentage of them did receive opioids. About one-third of patients have been readmitted within 30 days, and readmission was associated with the number of ED visits/last year, disease severity, and length of ED stay. These findings can help in establishing local guidelines for managing such patients in the ED especially pain management.
PubMed: 38752095
DOI: 10.7759/cureus.58277 -
Frontiers in Pharmacology 2024Administration of high doses of acetaminophen (APAP) results in liver injury. Oxidative stress and iron overload play roles in the pathogenesis of APAP-induced...
Administration of high doses of acetaminophen (APAP) results in liver injury. Oxidative stress and iron overload play roles in the pathogenesis of APAP-induced hepatotoxicity. The present study assessed the potential hepatoprotective effects of phytic acid (PA), a natural antioxidant and iron chelator, on APAP-induced hepatotoxicity and the possible underlying mechanism through its effects on gene expression, iron homeostasis, oxidative stress, and -1 expression levels. Twenty-four adult male albino mice were used in this study. Mice were divided into four groups (six mice in each group): control, APAP-treated, PA-treated and APAP + PA-treated groups. Liver function tests, serum and liver tissue iron load were evaluated in all the study groups. Hepatic tissue homogenates were used to detect oxidative stress markers, including malondialdehyde (MDA) and reduced glutathione (GSH). Histological hepatic evaluation and immunohistochemistry of -1 were performed. Quantitative real-time PCR was used for the assessment of and SIRT-1 gene expressions. APAP-induced biochemical and structural hepatic changes were reported. PA administration showed beneficial effects on APAP-induced hepatotoxicity through improvements in liver functions, decreased gene expression, decreased serum and liver iron load, decreased MDA, increased GSH, increased -1 expression level and improvement in hepatic architecture. Conclusively, PA can be considered a potential compound that can attenuate acetaminophen-induced hepatotoxicity through its role as an iron chelator and antioxidant, as well as the up-regulation of -1 and down-regulation of
PubMed: 38751780
DOI: 10.3389/fphar.2024.1384834