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Theranostics 2024Acetaminophen (APAP) overdosing is a major cause of acute liver failure worldwide and an established model for drug-induced acute liver injury (ALI). While studying gene...
Acetaminophen (APAP) overdosing is a major cause of acute liver failure worldwide and an established model for drug-induced acute liver injury (ALI). While studying gene expression during murine APAP-induced ALI by 3'mRNA sequencing (massive analysis of cDNA ends, MACE), we observed splenic mRNA accumulation encoding for the neutrophil serine proteases cathepsin G, neutrophil elastase, and proteinase-3 - all are hierarchically activated by cathepsin C (CtsC). This, along with increased serum levels of these proteases in diseased mice, concurs with the established phenomenon of myeloid cell mobilization during APAP intoxication. In order to functionally characterize CtsC in murine APAP-induced ALI, effects of its genetic or pharmacological inhibition were investigated. We report on substantially reduced APAP toxicity in CtsC deficient mice. Alleviation of disease was likewise observed by treating mice with the CtsC inhibitor AZD7986, both in short-term prophylactic and therapeutic protocols. This latter observation indicates a mode of action beyond inhibition of granule-associated serine proteases. Protection in CtsC knockout or AZD7986-treated wildtype mice was unrelated to APAP metabolization but, as revealed by MACE, realtime PCR, or ELISA, associated with impaired expression of inflammatory genes with proven pathogenic roles in ALI. Genes consistently downregulated in protocols tested herein included , , and . Moreover, , a positive regulator of the toll-like receptor/interferon-axis, was reduced by targeting CtsC. This work suggests CtsC as promising therapeutic target for the treatment of ALI, among others paradigmatic APAP-induced ALI. Being also currently evaluated in phase III clinical trials for bronchiectasis, successful application of AZD7986 in experimental APAP intoxication emphasizes the translational potential of this latter therapeutic approach.
Topics: Animals; Acetaminophen; Cathepsin C; Mice; Chemical and Drug Induced Liver Injury; Mice, Inbred C57BL; Mice, Knockout; Male; Disease Models, Animal
PubMed: 38855187
DOI: 10.7150/thno.96092 -
RSC Advances Jun 2024A novel magnetic composite bead was synthesized using carbon 18, paracetamol and alginate (mC18/Pa/Alg). The bead was applied to simultaneously adsorb butylated...
A novel magnetic composite bead was synthesized using carbon 18, paracetamol and alginate (mC18/Pa/Alg). The bead was applied to simultaneously adsorb butylated hydroxytoluene, butylated hydroxyanisole, and bisphenol A from water samples by magnetic solid-phase extraction (MSPE). The adsorbed analytes were determined by gas chromatography-flame ionization detection. The morphology and composition of the bead were examined by field emission scanning electron microscopy, energy-dispersive X-ray spectrometry, X-ray diffraction analysis, Fourier transform infrared spectroscopy and Brunauer-Emmett-Teller surface analysis. The best condition of MSPE included an adsorbent bead made with 0.8% sodium alginate, a 0.3 g adsorbent dose, a sample solution pH of 7, and a desorption time of 20 min in methanol. The proposed method exhibited linearity at concentrations between 0.015 and 1.00 μg mL of analytes. Limits of detection ranged from 6.86 to 9.66 ng mL. Recoveries from 80.3 to 100.1% were achieved with interday and intraday precisions (RSDs) of 0.4-4.3%.
PubMed: 38854826
DOI: 10.1039/d4ra02720e -
SAGE Open Medical Case Reports 2024Primary psoas abscess is an uncommon yet critical factor contributing to postpartum sepsis. This report is of a case of postpartum primary psoas abscess in a 24-year-old...
Primary psoas abscess is an uncommon yet critical factor contributing to postpartum sepsis. This report is of a case of postpartum primary psoas abscess in a 24-year-old Moroccan woman. After an uncomplicated vaginal delivery, a 24-year-old primiparous Moroccan woman presented to our hospital with a 3-week history of severe left-sided lower abdominal pain that radiated to the anterior aspect of the left thigh. She had been taking ciprofloxacin, metronidazole, and paracetamol for a week without any improvement. On examination, she was febrile and pale. The laboratory analysis revealed the presence of microcytic anemia, an elevated erythrocyte sedimentation rate, and an increased level of C-reactive protein. Computed tomography scans of the abdomen, and pelvis were conducted, revealing a substantial left psoas abscess. Under the guidance of computed tomography, anterior abdominal percutaneous drainage of the abscess was successfully performed. A pan-sensitive strain was identified through culture of the specimen. The patient showed a favorable response to treatment with amoxicillin/clavulanate and gentamicin. This case illustrates that primary psoas abscess should be considered in cases of any postpartum infectious presentation.
PubMed: 38854677
DOI: 10.1177/2050313X241260184 -
Cureus May 2024Postpartum hemorrhage (PPH) remains the leading cause of maternal mortality, primarily attributed to uterine atony. Both the World Health Organization (WHO) and the...
Postpartum hemorrhage (PPH) remains the leading cause of maternal mortality, primarily attributed to uterine atony. Both the World Health Organization (WHO) and the International Federation of Gynecology and Obstetrics (FIGO) endorse the use of misoprostol not only for the prevention but also for the treatment of PPH. However, the administration of misoprostol is commonly associated with transient pyrexia, attributed to a shift in the hypothalamic set point observed in certain animal studies. Misoprostol-induced hyperpyrexia can occasionally manifest with a prodrome of shivering, particularly when administered via the sublingual route, which achieves a higher and faster maximum plasma concentration compared to vaginal and rectal routes. General management strategies to reduce fever involve removing clothing and blankets, applying cool compresses, administering oral acetaminophen, and ensuring adequate hydration. While some cases have reported misoprostol-induced convulsions, hyperpyrexia leading to convulsions and subsequent rhabdomyolysis is a rare and potentially lethal side effect. In this case presentation, we emphasize a scenario where misoprostol was employed for the treatment of PPH but led to rhabdomyolysis. Our goal is to highlight the side effects of misoprostol and the significance of considering the initial combination of misoprostol with anti-pyretic management to minimize the risk of hyperthermia-related side effects and prevent additional severe complications.
PubMed: 38854268
DOI: 10.7759/cureus.59874 -
Cureus May 2024The routine use of multimodal analgesic modality results in lower pain scores with minimum side effects and opioid utilization.
BACKGROUND
The routine use of multimodal analgesic modality results in lower pain scores with minimum side effects and opioid utilization.
MATERIALS AND METHODS
A prospective, cross-sectional, observational study was conducted among orthopedicians practicing across India to assess the professional opinions on using analgesics to manage orthopedic pain effectively.
RESULTS
A total of 530 orthopedicians participated in this survey. Over 50% of the participants responded that tramadol with or without paracetamol was the choice of therapy for acute pain. Nearly 50% of the participants mentioned that multimodal interventions can sometimes help to manage pain. A total of 55.6% of participants mentioned that using Non-steroidal anti-inflammatory drugs was the most common in their clinical practice, while 25.7% of participants mentioned that they used tramadol more commonly in their clinical practice. As per clinical efficacy ranking, the combination of tramadol plus paracetamol (44.3%) was ranked first among analgesic combinations, followed by aceclofenac plus paracetamol (40.0%). The severity of pain (62.6%) followed by age (60.6%) and duration of therapy (52.6%) were the most common factors that should be considered while prescribing tramadol plus paracetamol combination. Gastrointestinal and renal are reported as the most common safety concerns encountered with analgesics.
CONCLUSION
The combination of tramadol and paracetamol was identified as the most preferred choice of analgesics for prolonged orthopedic pain management.
PubMed: 38854259
DOI: 10.7759/cureus.59935 -
Cureus May 2024Acute liver failure (ALF) exemplifies a rapid decline in liver function among individuals with previously healthy livers, often manifesting through symptoms such as...
Acute liver failure (ALF) exemplifies a rapid decline in liver function among individuals with previously healthy livers, often manifesting through symptoms such as jaundice, confusion, and potentially life-threatening complications. Timely medical intervention, and, in severe instances, liver transplantation, are essential for enhancing outcomes and averting further deterioration. While the causes of ALF are multifaceted, in developed nations, it predominantly arises from drug-induced liver injury. Treatment primarily revolves around supportive measures, with severe cases necessitating liver transplantation. In instances where acute overdose with acetaminophen serves as the instigating factor, N-acetylcysteine (NAC) emerges as a pivotal component of management, as indicated by the Rumack-Matthew nomogram. The Rumack-Matthew nomogram guides treatment for acetaminophen overdose by correlating serum levels with the risk of liver damage. If levels exceed a set threshold, NAC is administered to prevent toxicity by replenishing glutathione. The decision to administer NAC is typically guided by this clinical tool, which aids healthcare providers in determining the appropriate course of action. NAC assumes a critical role in ameliorating the detrimental effects of acetaminophen overdose, particularly in averting liver damage, thus holding significant importance in patient care and recovery. While chronic acetaminophen overdose cases leading to ALF may also benefit from NAC, the supporting evidence remains weak. In this context, we present a case of ALF stemming from chronic acetaminophen ingestion, managed with NAC when liver transplantation was not a viable option.
PubMed: 38854233
DOI: 10.7759/cureus.59883 -
IET Systems Biology Jun 2024Acute ischemic stroke (AIS) is caused by cerebral ischemia due to thrombosis in the blood vessel. The purpose of this study is to identify key genes related to...
OBJECTIVES
Acute ischemic stroke (AIS) is caused by cerebral ischemia due to thrombosis in the blood vessel. The purpose of this study is to identify key genes related to metabolism to aid in the mechanism research and management of AIS.
MATERIALS AND METHODS
Gene expression data were downloaded from the Gene Expression Omnibus database. Weighted gene co-expression network analysis, Gene Ontology and kyoto encyclopedia of genes and genomes analysis were used to identify metabolism-related genes that may be involved in the regulation of AIS. A protein protein interaction network was mapped using Cytoscape based on the STRING database. Subsequently, hub metabolism-related genes were identified based on Cytoscape-CytoNCA and Cytoscape-MCODE plug-ins. Least absolute shrinkage and selection operator algorithm and differential expression analysis. In addition, drug prediction, molecular docking, ceRNA network construction, and correlation analysis with immune cell infiltration were performed to explore their potential molecular mechanisms of action in AIS. Finally, the expression of hub gene was verified by real-time PCR.
RESULTS
Metabolism-related genes FBL, HEATR1, HSPA8, MTMR4, NDUFC1, NDUFS8 and SNU13 were identified. The AUC values of FBL, HEATR1, HSPA8, MTMR4, NDUFS8 and SNU13 were all greater than 0.8, suggesting that they had good diagnostic accuracy. Correlation analysis found that their expression levels were also related to the infiltration levels of multiple immune cells, such as Activated.CD8.T.cell and Activated.dendritic.cell. It was found that only HSPA8 was successfully matched to drugs with literature support, and these drugs were acetaminophen, bupivacaine, dexamethasone, gentamicin, tretinoin and cisplatin. Moreover, it was also identified that the ENSG000000218510-hsa-miR-330-3p-HEATR1 axis may be involved in regulating AIS.
CONCLUSIONS
The identification of FBL, HEATR1, HSPA8, MTMR4, NDUFC1, NDUFS8 and SNU13 provides a new research direction for exploring the molecular mechanisms of AIS, which can help in clinical management and diagnosis.
PubMed: 38850201
DOI: 10.1049/syb2.12095 -
Critical Care (London, England) Jun 2024
Topics: Humans; Pain, Postoperative; Cardiac Surgical Procedures; Analgesics, Opioid; Pain Management; Infant
PubMed: 38849911
DOI: 10.1186/s13054-024-04983-3 -
BMC Anesthesiology Jun 2024We aimed to compare the analgesic effects of intravenous ibuprofen to ketorolac after open abdominal hysterectomy. (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
BACKGROUND
We aimed to compare the analgesic effects of intravenous ibuprofen to ketorolac after open abdominal hysterectomy.
METHODS
This randomized double-blinded controlled trial included adult women scheduled for elective open abdominal hysterectomy. Participants were randomized to receive either 30 mg ketorolac (n = 50) or 800 mg ibuprofen (n = 50) preoperatively, then every 8 h postoperatively for 24 h. All participants received paracetamol 1 gm/6 h. Rescue analgesic was given if the visual analogue scale (VAS) for pain assessment was > 3. The primary outcome was the mean postoperative dynamic VAS during the first 24 h. Secondary outcomes were static VAS, intraoperative fentanyl consumption, postoperative morphine consumption, time to independent movement, and patient's satisfaction.
RESULTS
Forty-six patients in the ibuprofen group and fifty patients in the ketorolac group were analyzed. The 24-h dynamic and static VAS were similar in the two groups. The median (quartiles) dynamic VAS was 1.1 (0.9, 1.9) in the ibuprofen group versus 1.0 (0.7, 1.3) in the ketorolac group, P-value = 0.116; and the median (quartiles) static VAS was 0.9 (0.6, 1.3) in the ibuprofen group versus 0.7 (0.4, 1.1) in the ketorolac group, P-value = 0.113. The intra- and postoperative analgesic requirements were also similar in the two groups. However, patient satisfaction was slightly higher in the ketorolac group than that in the ibuprofen group (median [quartiles]: 6 [5, 7] versus 5 [4, 7], respectively), P-value: 0.009.
CONCLUSION
The two drugs, intravenous ibuprofen and ketorolac produced similar analgesic profile in patients undergoing open abdominal hysterectomy receiving multimodal analgesic regimen. NCT05610384, Date of registration: 09/11/2022 CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05610384. https://clinicaltrials.gov/ct2/show/NCT05610384.
Topics: Humans; Ketorolac; Ibuprofen; Female; Hysterectomy; Double-Blind Method; Pain, Postoperative; Middle Aged; Anti-Inflammatory Agents, Non-Steroidal; Adult; Administration, Intravenous; Pain Measurement; Analgesics, Non-Narcotic; Patient Satisfaction
PubMed: 38849734
DOI: 10.1186/s12871-024-02571-0 -
Journal of Clinical Anesthesia Jun 2024Necrotizing enterocolitis (NEC) is a life-threatening intestinal illness mostly affecting preterm infants, which commonly requires surgery. Anesthetic care for these...
STUDY OBJECTIVE
Necrotizing enterocolitis (NEC) is a life-threatening intestinal illness mostly affecting preterm infants, which commonly requires surgery. Anesthetic care for these patients is challenging, due to their prematurity and critical illness with hemodynamic instability. Currently, there are no guidelines for anesthetic care for these vulnerable patients. Therefore, this study aimed to describe current anesthesia practices across Europe for infants undergoing surgery for NEC.
DESIGN
Cross-sectional survey study.
PARTICIPANTS
Anesthesiologists working in centers where surgery for NEC is performed across Europe.
MEASUREMENTS
A 46-item questionnaire assessing protocols for anesthesia practice, preoperative care, intraoperative care, postoperative care, and the respondent's opinion on the adequacy of anesthetic care for patients with NEC in their center.
MAIN RESULTS
Out of the 173 responding anesthesiologists from 31 countries, approximately a third had a written standard protocol for anesthetic care in infants. Three quarters of the respondents screened all patients with NEC preoperatively, and a third structurally performed preoperative multidisciplinary consultation. For induction of general anesthesia, most respondents opted for intravenous anesthesia (n = 73, 43%) or a combination of intravenous and inhalation anesthesia (n = 57, 33%). For intravenous induction, they mostly used propofol (n = 58, 44%), followed by midazolam (n = 43, 33%) and esketamine (n = 42, 32%). For maintenance of anesthesia, inhalation anesthetic agents were more commonly used (solely: n = 71, 41%; in combination: n = 37, 22%), almost exclusively with sevoflurane. Postoperative analgesics mainly included paracetamol and/or morphine. Sixty percent of the respondents (n = 104) considered their anesthetic care for patients with NEC adequate. Suggestions for further improvement mainly revolved around monitoring, protocols, and collaboration.
CONCLUSIONS
Anesthesia practice for infants undergoing surgery for NEC was highly variable. Most respondents considered the provided anesthetic care for patients with NEC adequate, but also recognized opportunities for further improvement, especially with regards to monitoring, protocols, and interdisciplinary collaboration.
PubMed: 38843649
DOI: 10.1016/j.jclinane.2024.111508