-
International Journal of Molecular... May 2024Acetaminophen overdose is a leading cause of acute liver failure (ALF), and effective treatment depends on early prediction of disease progression. ALF diagnosis...
Acetaminophen overdose is a leading cause of acute liver failure (ALF), and effective treatment depends on early prediction of disease progression. ALF diagnosis currently requires blood collection 24-72 h after APAP ingestion, necessitating repeated tests and hospitalization. Here, we assessed earlier ALF diagnosis using positron emission tomography (PET) imaging of translocator proteins (TSPOs), which are involved in molecular transport, oxidative stress, apoptosis, and energy metabolism, with the radiotracer [F]GE180. We intraperitoneally administered propacetamol hydrochloride to male C57BL/6 mice to induce ALF. We performed in vivo PET/CT imaging 3 h later using the TSPO-specific radiotracer [F]GE180 and quantitatively analyzed the PET images by determining the averaged standardized uptake value (SUV) in the liver parenchyma. We assessed liver TSPO expression levels via real-time polymerase chain reaction, Western blotting, and immunohistochemistry. [F]GE180 PET imaging 3 h after propacetamol administration (1500 mg/kg) significantly increased liver SUV compared to controls ( = 0.001). Analyses showed a 10-fold and 4-fold increase in TSPO gene and protein expression, respectively, in the liver, 3 h after propacetamol induction compared to controls. [F]GE180 PET visualized and quantified propacetamol-induced ALF through TSPO overexpression. These findings highlight TSPO PET's potential as a non-invasive imaging biomarker for early-stage ALF.
Topics: Animals; Liver Failure, Acute; Acetaminophen; Male; Mice; Mice, Inbred C57BL; Receptors, GABA; Positron-Emission Tomography; Liver; Positron Emission Tomography Computed Tomography; Fluorine Radioisotopes; Radiopharmaceuticals; Disease Models, Animal; Carbazoles
PubMed: 38892130
DOI: 10.3390/ijms25115942 -
Cell Communication and Signaling : CCS Jun 2024Balloon flower root-derived exosome-like nanoparticles (BDEs) have recently been proposed as physiologically active molecules with no cytotoxicity. However, the...
A novel approach to alleviate acetaminophen-induced hepatotoxicity with hybrid balloon flower root-derived exosome-like nanoparticles (BDEs) with silymarin via inhibition of hepatocyte MAPK pathway and apoptosis.
INTRODUCTION
Balloon flower root-derived exosome-like nanoparticles (BDEs) have recently been proposed as physiologically active molecules with no cytotoxicity. However, the therapeutic effects of drug-induced hepatotoxicity of BDEs have not been elucidated. BDEs contain a large amount of platycodin D, which is widely known to be effective in regulating inflammation and ameliorating systemic toxicity. Thus, the main therapeutic activity of BDEs is attributed to inhibiting the inflammatory response and alleviating toxicity. In this study, we fabricated the hybrid BDEs fused with liposomes containing silymarin (SM) to enhance the synergistic effect on inhibition of acetaminophen-induced hepatotoxicity (APAP).
OBJECTIVE
Considering the potential therapeutic effects of BDEs, and the potential to achieve synergistic effects to improve therapeutic outcomes, we constructed hybrid BDEs with a soy lecithin-based liposome loaded with SM. Since liposomes can provide higher thermal stability and have greater structural integrity, these might be more resistant to clearance and enzymatic degradation of drug molecules.
METHODS
Hybrid BDEs with liposome-loaded SM (BDEs@lipo-SM) were fabricated by thin-film hydration and extrusion. BDEs@lipo-SM were characterized using dynamic light scattering and high-performance liquid chromatography. After confirmation of the physical properties of BDEs@lipo-SM, various therapeutic properties were evaluated.
RESULTS
BDEs@lipo-SM were internalized by hepatocytes and immune cells and significantly decreased mRNA expression of apoptosis and inflammation-relevant cytokines by inhibiting the hepatocyte MAPK pathway. BDEs@lipo-SM significantly induced an increase in glutathione levels and inhibited APAP-induced hepatotoxicity.
CONCLUSION
From this study, we know that BDEs are reliable and safe nanovesicles containing natural metabolites derived from balloon flower, and they can facilitate intercellular communication. BDEs are also easily modified to enhance drug loading capacity, targeting effects, and long-term accumulation in vivo. BDEs@lipo-SM have therapeutic benefits for acute liver injury and can alleviate cell death and toxicity. They can be efficiently delivered to the liver and effectively inhibit APAP-induced hepatotoxicity by inhibiting the MAPK signaling pathway and apoptosis, which accelerates liver recovery in the APAP-induced acute liver injury model. These findings highlight that BDEs represent an attractive delivery vehicle for drug delivery.
Topics: Acetaminophen; Apoptosis; Animals; Nanoparticles; Exosomes; Hepatocytes; Silymarin; MAP Kinase Signaling System; Mice; Chemical and Drug Induced Liver Injury; Humans; Liposomes; Male; Plant Roots; Mice, Inbred C57BL
PubMed: 38890646
DOI: 10.1186/s12964-024-01700-z -
AAPS PharmSciTech Jun 2024Unexpected cross-contamination by foreign components during the manufacturing and quality control of pharmaceutical products poses a serious threat to the stable supply...
Unexpected cross-contamination by foreign components during the manufacturing and quality control of pharmaceutical products poses a serious threat to the stable supply of drugs and the safety of customers. In Japan, in 2020, a mix-up containing a sleeping drug went undetected by liquid chromatography during the final quality test because the test focused only on the main active pharmaceutical ingredient (API) and known impurities. In this study, we assessed the ability of a powder rheometer to analyze powder characteristics in detail to determine whether it can detect the influence of foreign APIs on powder flow. Aspirin, which was used as the host API, was combined with the guest APIs (acetaminophen from two manufacturers and albumin tannate) and subsequently subjected to shear and stability tests. The influence of known lubricants (magnesium stearate and leucine) on powder flow was also evaluated for standardized comparison. Using microscopic morphological analysis, the surface of the powder was observed to confirm physical interactions between the host and guest APIs. In most cases, the guest APIs were statistically detected due to characteristics such as their powder diameter, pre-milling, and cohesion properties. Furthermore, we evaluated the flowability of a formulation incorporating guest APIs for direct compression method along with additives such as microcrystalline cellulose, potato starch, and lactose. Even in the presence of several additives, the influence of the added guest APIs was successfully detected. In conclusion, powder rheometry is a promising method for ensuring stable product quality and reducing the risk of unforeseen cross-contamination by foreign APIs.
Topics: Powders; Rheology; Drug Contamination; Excipients; Acetaminophen; Cellulose; Pharmaceutical Preparations; Quality Control; Aspirin; Chemistry, Pharmaceutical; Lactose; Drug Compounding; Lubricants; Bulk Drugs
PubMed: 38890193
DOI: 10.1208/s12249-024-02856-0 -
Clinical Toxicology (Philadelphia, Pa.) Jun 2024Chlorpromazine, one of the oldest antipsychotic medications, remains widely available and is still taken in overdose. We aimed to investigate the clinical effects of...
INTRODUCTION
Chlorpromazine, one of the oldest antipsychotic medications, remains widely available and is still taken in overdose. We aimed to investigate the clinical effects of chlorpromazine overdose and determine if there is a relationship between the reported dose ingested and intensive care unit admission or endotracheal intubation.
METHODS
We performed a retrospective analysis of patients admitted to our toxicology tertiary referral hospital with chlorpromazine overdose (reported dose ingested greater than 300 mg) between 1987 and 2023. We extracted demographic information, details of ingestion, clinical effects and complications (Glasgow Coma Scale, hypotension [systolic blood pressure less than 90 mmHg], delirium, dysrhythmias), length of stay, intensive care unit admission, and endotracheal intubation.
RESULTS
There were 218 chlorpromazine overdose cases, with presentations decreasing in frequency over the 36 years. The median age at presentation was 32 years (interquartile range: 25-40 years) and 143 (61 per cent) were female. The median reported dose ingested was 1,250 mg (interquartile range; 700-2,500 mg). The majority of presentations (135; 62 per cent) involved reported co-ingestion of other medications, typically benzodiazepines, paracetamol or antipsychotics. There were 76 (35 per cent) chlorpromazine alone ingestions in which there was a slightly higher median reported dose ingested of 1,650 mg (interquartile range: 763-3,000 mg) compared to the reported co-ingestion group, median reported dose ingested of 1,200 mg (interquartile range: 700-2,100 mg). Of all presentations, 36 (27 per cent) had a Glasgow Coma Scale less than 9, 50 (23 per cent) were admitted to the intensive care unit, and 32 (15 per cent) were endotracheally intubated. There was a significant difference in the median reported dose ingested between patients intubated (2,000 mg; interquartile range: 1,388-3,375 mg) and those not intubated (1,200 mg; interquartile range: 644-2,050mg; < 0.001), and between those admitted to the intensive care unit and not admitted to the intensive care unit ( < 0.0001). The median reported dose ingested in seven chlorpromazine alone presentations who were intubated was 2,500 mg (interquartile range: 2,000-8,000 mg, range: 1,800-20,000 mg). Eighteen (8 per cent) patients developed delirium, eight (4 per cent) had hypotension, three had seizures, and there was one death.
DISCUSSION
Almost one quarter of cases were admitted to the intensive care unit and over half of these were intubated. Whist the decision to admit to an intensive care unit or intubate a patient is based on clinical need, there was a significant association between reported dose ingested and requirement for endotracheal intubation. Both the frequency of presentation and reported dose ingested declined after 2013. The major limitations of the study were a retrospective design and no analytical confirmation of ingestion.
CONCLUSIONS
We found that the most common effect of chlorpromazine overdose was central nervous system depression and that endotracheal intubation was associated with larger reported doses ingested, particularly in single chlorpromazine ingestions.
PubMed: 38889430
DOI: 10.1080/15563650.2024.2367672 -
Naunyn-Schmiedeberg's Archives of... Jun 2024Metamizole, as known as dipyrone or novaminsulfone is widely used, especially in Latin America, for its analgesic and antipyretic function. However, several countries... (Review)
Review
Metamizole, as known as dipyrone or novaminsulfone is widely used, especially in Latin America, for its analgesic and antipyretic function. However, several countries have banned it due to the risk of agranulocytosis, skin necrosis, and other serious adverse effects. To assess the safety of metamizole compared to other commonly used non-opioid analgesics (paracetamol, ibuprofen, and acetylsalicylic acid). An overview of systematic reviews. The searches were performed in the PubMed, Cochrane Library, Embase, Scopus and LILACS databases. Systematic reviews of randomized and nonrandomized clinical trials with adult patients with mild to moderate pain that assessed the adverse effects of metamizole were included. A methodological quality assessment was performed through ROBIS. The protocol of this systematic review was submitted to the International Prospective Register of Systematic Reviews (Prospero, CRD42021295272). Of 387 identified studies, four were included, with a total of 20,643 participants, all submitted to a single dose by oral, intramuscular, or intravenous route. No study reported a serious adverse effect. However, 60 of 778 patients (7.7%) who used metamizole; 120/828 (14.5%) who used acetylsalicylic acid; 56/443 (12.6%) who used paracetamol; and 27/213 (12.7%) who used ibuprofen had mild adverse effects. A complementary statistical analysis showed that metamizole, at any dose, has a 38.8% lower chance of adverse effects compared to paracetamol and 46.8% compared to acetylsalicylic acid. The results shows that metamizole is a safe drug with evidence of a lower incidence of adverse effects compared to paracetamol and acetylsalicylic acid.
PubMed: 38888755
DOI: 10.1007/s00210-024-03240-2 -
Pain and Therapy Jun 2024Most patients undergoing the Nuss procedure reported moderate to severe pain after surgery. This study aimed to investigate the efficacy and safety of ultrasound-guided...
INTRODUCTION
Most patients undergoing the Nuss procedure reported moderate to severe pain after surgery. This study aimed to investigate the efficacy and safety of ultrasound-guided serratus anterior plane block (SAPB) combined with transversus thoracic muscle plane (TTMP) block for relieving acute pain in patients undergoing the Nuss procedure.
METHODS
The enrolled patients in our study were allocated to either receive combined nerve blocks with ropivacaine (NB group) or saline (CON group). The primary outcome of this study was postoperative pain at 2, 4, 8, 16, 24, 36, and 48 h during rest and movement (coughing). Secondary outcomes included intraoperative dosage of remifentanil, the time to extubation and the length of stay in the post-anesthesia care unit (PACU), the total acetaminophen and codeine tablet consumption, time to first bowel movement, time to first flatus, opioid-related adverse events, and the length of hospital stay.
RESULTS
Patients in the NB group had significantly lower Numerical Rating Scale (NRS) pain scores compared with the CON group. The NB group required significantly less postoperative acetaminophen consumption and lower dosages of perioperative sufentanyl and remifentanil compared with the CON group. The length of stay in the PACU and time to extubation were significantly increased in the CON group compared with the NE group. Time to first bowel movement and time to first flatus were earlier in the NB group. But there were no significant differences between the groups in terms of the length of hospital stay and codeine tablet consumption.
CONCLUSION
Ultrasound-guided SAPB and TTMP blocks in patients undergoing the Nuss procedure could provide effective analgesia.
TRIAL REGISTRATION
This study was registered in the Chinese Clinical Trial Registry (ChiCTR2000038506).
PubMed: 38888719
DOI: 10.1007/s40122-024-00627-0 -
Scandinavian Journal of Pain Jan 2024Chronic pain is highly prevalent in nursing home residents and often occurs with depression as well as cognitive impairment, which can severely influence and limit the...
OBJECTIVES
Chronic pain is highly prevalent in nursing home residents and often occurs with depression as well as cognitive impairment, which can severely influence and limit the expression of pain.
METHODS
The present cross-sectional study aimed to estimate the prevalence of pain, depressive mood, and cognitive impairment in association with pharmacological treatment against pain and depressive symptoms among Swedish nursing home residents.
RESULTS
We found an overall pain prevalence of 52.8%, a prevalence of 63.1% for being in a depressive mood, and a prevalence of cognitive impairment of 68.3%. Among individuals assessed to have depressive mood, 60.5% were also assessed to have pain. The prevalence of pharmacological treatment for pain was 77.5 and 54.1% for antidepressants. Prescription of pharmacological treatment against pain was associated with reports of currently having pain, and paracetamol was the most prescribed drug. A higher cognitive function was associated with more filled prescriptions of drugs for neuropathic pain, paracetamol, and nonsteroidal anti-inflammatory drugs (NSAIDs), which could indicate an undertreatment of pain in those cognitively impaired.
CONCLUSION
It is important to further explore the relationship between pain, depressive mood, and cognitive impairment in regard to pain management in nursing home residents.
Topics: Humans; Nursing Homes; Sweden; Male; Female; Cross-Sectional Studies; Prevalence; Depression; Aged, 80 and over; Aged; Cognitive Dysfunction; Pain Management; Antidepressive Agents; Chronic Pain; Acetaminophen; Analgesics
PubMed: 38887790
DOI: 10.1515/sjpain-2024-0007 -
PloS One 2024Photobiomodulation is a safe option for controlling pain, edema, and trismus when applied postoperatively in third molar surgery. However, administration prior to... (Randomized Controlled Trial)
Randomized Controlled Trial
Assessment of the pre-emptive effect of photobiomodulation in the postoperative period of impacted lower third molar extractions: A randomized, controlled, double-blind study protocol.
Photobiomodulation is a safe option for controlling pain, edema, and trismus when applied postoperatively in third molar surgery. However, administration prior to surgery has been under-explored. This study aims to explore the effectiveness of pre-emptive photobiomodulation in reducing postoperative edema in impacted lower third molar extractions. Two groups of healthy individuals undergoing tooth extraction will be randomly assigned: Control group receiving pre-emptive corticosteroid and simulated photobiomodulation, and Photobiomodulation Group receiving intraoral low-intensity laser and extraoral LED cluster application. The primary outcome will be postoperative edema after 48 h. The secondary outcomes will be pain, trismus dysphagia, and analgesic intake (paracetamol). These outcomes will be assessed at baseline as well as two and seven days after surgery. Adverse effects will be recorded. Data will be presented as means ± SD and a p-value < 0.05 will be indicative of statistical significance.
Topics: Humans; Molar, Third; Tooth Extraction; Low-Level Light Therapy; Tooth, Impacted; Double-Blind Method; Pain, Postoperative; Edema; Female; Male; Postoperative Period; Postoperative Complications; Adult
PubMed: 38885236
DOI: 10.1371/journal.pone.0300136 -
Indian Journal of Otolaryngology and... Jun 2024We presented a case of a 46-year-old woman from Saudi Arabia with a persistent buccal ulcer, measuring 0.4 × 0.4 × 0.3 cm. After surgical excision of the...
UNLABELLED
We presented a case of a 46-year-old woman from Saudi Arabia with a persistent buccal ulcer, measuring 0.4 × 0.4 × 0.3 cm. After surgical excision of the lesion was performed using both general and local anesthesia, its microscopic examination revealed keratinized squamous epithelium with surface ulcerations in the buccal mucosa. Beneath the epithelium, there was granulation tissue, scattered and clustered lymphoid tissue, and reactive germinal centers with tingible body microphages. These lymphoid clusters infiltrated the adjacent skeletal muscles and fat. The final diagnosis was ectopic oral tonsillar tissue overlaid by an inflammatory ulcer, most likely attributed to friction. Importantly, no evidence of malignancy were observed in the biopsy. The surgical removal of the lesion was performed to rule out malignancy. The surgical excision was performed using both general and local anesthesia. Following surgery and during follow-up visits, the indicated instructions were provided. Pain was effectively managed with acetaminophen, and the patient fully recovered in approximately ten days. Neither recurrence nor post-operative complications were hitherto reported.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s12070-024-04536-8.
PubMed: 38883445
DOI: 10.1007/s12070-024-04536-8 -
Cureus May 2024The purpose of this study was to assess the awareness of ototoxicity among medical doctors in Arar City, Saudi Arabia.
OBJECTIVES
The purpose of this study was to assess the awareness of ototoxicity among medical doctors in Arar City, Saudi Arabia.
METHODS
This is a cross-sectional study based on a pre-formed validated questionnaire (Appendix) that included three sections covering participants' demographic data (three questions), their attitudes (five questions), and knowledge (13 questions) regarding drug-induced ototoxicity.
RESULTS
After obtaining their informed consent, 213 physicians from government and private sector health facilities in Arar were enrolled in the study. Interns and general practitioners represented 57.8% of the participants; consultants represented 17.8%. Only 71.8% of participants were interested in drug-induced ototoxicity, while 26.3% considered ototoxicity a rare complication. Approximately 90% of the participants were knowledgeable about the adverse effects of drugs on the vestibulocochlear system, and 26.7% reported having experienced cases of drug-induced ototoxicity in their practice. Participants showed an overall knowledge score about ototoxicity of 9.3±3.27 (out of 14). The knowledge score was significantly higher (p-value=0.0007) for participants with more years of clinical experience. The most widely known ototoxic drug for participants was frusemide (72.3%), followed by aminoglycoside (68.5%), while acetaminophen (44.1%) ototoxicity was the least known among participants.
CONCLUSION
Awareness of drug-induced ototoxicity is satisfactory among physicians in the Northern Borders region. However, workshops about all types of drugs with ototoxic effects and the main lines for the management of drug-induced ototoxicity are recommended to increase awareness.
PubMed: 38882992
DOI: 10.7759/cureus.60429