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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 -
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 -
Tropical Medicine & International... Jun 2024Many children in sub-Saharan Africa die from infectious diseases like malaria, pneumonia, and diarrhoea that can be prevented by early diagnosis, effective and targeted...
OBJECTIVE
Many children in sub-Saharan Africa die from infectious diseases like malaria, pneumonia, and diarrhoea that can be prevented by early diagnosis, effective and targeted treatment. This study aimed to gain insights into case management practices by parents before they present their children to hospital.
METHODS
We conducted a cross-sectional study among 332 parents attending a district hospital with their under-fives symptomatic with fever and/or diarrhoea between November 2019 and July 2020 in rural Tanzania. Timely and targeted treatment was defined as seeking health care within 24 h of fever onset, and continued fluid intake in case of diarrhoea.
RESULTS
The main admission diagnoses were acute respiratory infections (61.8%), malaria (25.3%), diarrhoea (18.4%) and suspected sepsis (8.1%). The majority of children (91%) received treatment prior to admission, mostly antipyretics (75.6%), local herbal medicines (26.8%), and antibiotics (17.8%)-half of them without prescription from a clinician. For diarrhoea, the use of oral rehydration solution was rare (9.0%), although perceived as easily accessible and affordable. 49.4% of the parents presented their children directly to the hospital, 23.2% went to a pharmacy/drug shop and 19.3% to a primary health facility first. Malaria symptoms began mostly 3 days before the hospital visit; only 25.4% of febrile children visited any health facility within 24 h of disease onset. Prior use of local herbal medicine (AOR = 3.2; 95% CI 1.4-7.3), visiting the pharmacy (adjusted Odds Ratio [AOR] = 3.1; 95% confidence interval [CI]: 1.0-9.8), the dispensary being the nearest health facility (AOR = 3.0; 95% CI: 1.5-6.2), and financial difficulties (AOR = 2.2; 95% CI 1.1-4.5) were associated with delayed treatment.
CONCLUSION
This study suggests that antipyretics and antibiotics dispensed at pharmacies/drug shops, as well as use of local herbal medicines, delay early diagnosis and treatment, which can be life-threatening. Pharmacies/drug shops could be integrated as key focal points for sensitising community members on how to respond to paediatric illnesses and encourage the use of oral rehydration solutions.
PubMed: 38888511
DOI: 10.1111/tmi.14022 -
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 -
Journal of Advanced Nursing Jun 2024The research was conducted to determine the practices of parents regarding the fever management of their children and reveal the relationship between their health...
AIMS
The research was conducted to determine the practices of parents regarding the fever management of their children and reveal the relationship between their health literacy (HL) and fever management of their children.
DESIGN
Cross-sectional study was used.
METHODS
This study was carried out with 242 parents. The data were collected using the Parent Descriptive Information Form, Turkish HL Scale-32 and Parents' Fever Management Scale between September 2021 and September 2022. The data were evaluated with the SPSS program, using percentages, averages, Pearson's correlation and regression analysis.
RESULTS
The mean age of the parents was 31.87 ± 6.59. The parents' mean Parents' Fever Management Scale score was 36.22. It means that parents had high fever management practice. Their mean Turkish HL Scale-32 total score was 34.43. 51.6% of the parents had a problematic or insufficient HL level. In the cases of fever, 61.2% of the parents stated that they took off the child's clothes, 69.0% measured temperature from the armpit, and 55.4% gave antipyretics according to the doctor's prescription. There is a statistically significant positive correlation between the Parents' Fever Management Scale and Turkish HL Scale-32. It is observed that 8.2% of the change in parents' fever management is explained by HL.
CONCLUSION
The study found that with an increase in parents' HL, fever management of their children also increased.
IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE
Emerging evidence showed that developing parents' HL knowledge and skills could be an option/approach in fever management. It should be a basic nursing skill that to provide HL support to parents.
REPORTING METHOD
This study adhered to the relevant cross-sectional STROBE (the Strengthening the Reporting of Observational Studies in Epidemiology) guidelines.
PATIENT OR PUBLIC CONTRIBUTION
No patient or public contribution.
PubMed: 38887109
DOI: 10.1111/jan.16275 -
Cureus May 2024Chenopodium ambrosioides L. is a plant belonging to the Chenopodiaceae family, known for its use in traditional medicine as a remedy for its antiseptic, analgesic,...
Chenopodium ambrosioides L. is a plant belonging to the Chenopodiaceae family, known for its use in traditional medicine as a remedy for its antiseptic, analgesic, antipyretic, antispasmodic, and anti-inflammatory properties. It is used for its therapeutic properties internally as an infusion or externally as a vermifuge. Its use can be responsible for serious, even fatal, side effects and intoxications, particularly in infants and children. These may include neurological, digestive, hepatic, or renal complications. We present a case of Chenopodium ambrosioides L. intoxication in a four-year-old girl, resulting from repeated high-dose infusions of this plant for antipyretic purposes. She was admitted to the pediatric emergency department for management of a disorder of consciousness four hours after ingesting Chenopodium ambrosioides L. to treat acute fever.
PubMed: 38883026
DOI: 10.7759/cureus.60351 -
Journal of Pharmacy & Bioallied Sciences Apr 2024also known as the "King of Bitters" is a herbal medicine of the family which is native to India and Sri Lanka. is a very useful medicinal plant as it has antioxidant,...
also known as the "King of Bitters" is a herbal medicine of the family which is native to India and Sri Lanka. is a very useful medicinal plant as it has antioxidant, antidiabetic, antipyretic, anticancer properties. The main antibacterial activity of is due to the presence of andrographolide and arabinogalactan proteins. The medicinal properties of rose are mostly due to their abundance in phenolic compounds. They have many pharmacological properties like antibacterial, antioxidant, thrombolytic, and anticancer properties. The hips of the rose plant have Vitamin C in a concentration that is three times more than a citrus fruit that can be used in the treatment of a flu or a cold. Mueller-Hinton agar was utilized for this activity to determine the zone of inhibition. The plant extracts with different concentrations were loaded, and the plates were incubated for 24 hours at 37°C. After the incubation time, the zone of inhibition was measured. The results of this study are significant because they demonstrate the antibacterial activity of against three bacterial pathogens. This suggests that the formulation of has potential as a natural antibacterial agent. Further studies are needed to explore the mechanism of action and potential applications of this formulation. In conclusion, the study shows that the formulation of has significant antibacterial activity against , , . This suggests that the formulation of has potential as a natural antibacterial agent that could be further explored for its potential use in the treatment of bacterial infections.
PubMed: 38882789
DOI: 10.4103/jpbs.jpbs_574_23 -
Clinical and Translational Science Jun 2024This cohort study aims to assess the connection between cytochrome P450 family 2 subfamily C member 19 (CYP2C19) genotyping, platelet aggregability following oral...
This cohort study aims to assess the connection between cytochrome P450 family 2 subfamily C member 19 (CYP2C19) genotyping, platelet aggregability following oral clopidogrel administration, and the occurrence of postoperative atrial fibrillation (POAF) after off-pump coronary artery bypass graft (CABG) surgery. From May 2017 to November 2022, a total of 258 patients undergoing elective first-time CABG surgery, receiving 100 mg/day oral aspirin and 75 mg/day oral clopidogrel postoperatively, was included for analysis. These patients were categorized based on CYP2C19 genotyping. Platelet aggregability was assessed serially using multiple-electrode aggregometry before CABG, 1 and 5 days after the procedure, and before discharge. The incidences of POAF were compared using the log-rank test for cumulative risk. CYP2C19 genotyping led to categorization into CYP2C19*1*1 (WT group, n = 123) and CYP2C19*2 or *3 (LOF group, n = 135). Baseline characteristics and operative data showed no significant differences between the two groups. The incidence of POAF after CABG was 42.2% in the LOF group, contrasting with 22.8% in the WT group (hazard risk [HR]: 2.061; 95% confidence interval [CI]: 1.347, 3.153; p = 0.0013). Adenosine diphosphate-stimulated platelet aggregation was notably higher in the LOF group compared to the WT group 5 days after CABG (30.4% ± 6.5% vs. 17.9% ± 4.1%, p < 0.001), remaining a similar higher level at hospital discharge (25.6% ± 6.1% vs. 12.2% ± 3.5%, p < 0.001). The presence of CYP2C19 LOF was linked to a higher incidence of POAF and relatively elevated platelet aggregation after CABG surgery under the same oral clopidogrel regimen.
Topics: Humans; Cytochrome P-450 CYP2C19; Atrial Fibrillation; Male; Female; Aged; Coronary Artery Bypass; Middle Aged; Clopidogrel; Postoperative Complications; Genotype; Platelet Aggregation Inhibitors; Platelet Aggregation; Incidence; Aspirin
PubMed: 38877696
DOI: 10.1111/cts.13862 -
Biomolecules & Therapeutics Jun 2024Gefitinib is the well-tolerated first-line treatment of non-small cell lung cancer. As it need for analgesics during oncology treatment, particularly in the context...
Gefitinib is the well-tolerated first-line treatment of non-small cell lung cancer. As it need for analgesics during oncology treatment, particularly in the context ofthe coronavirus disease, where patients are more susceptible to contract high fever and sore throat. This has increased the likelihood of taking both gefitinib and antipyretic analgesic acetaminophen (APAP). Given that gefitinib and APAP overdose can predispose patients to liver injury or even acute liver failure, there is a risk of severe hepatotoxicity when these two drugs are used concomitantly. However, little is known regarding their safety at therapeutic doses. This study simulated the administration of gefitinib and APAP at clinically relevant doses in an animal model and confirmed that gefitinib in combination with APAP exhibited additional hepatotoxicity. We found that gefitinib plus APAP significantly exacerbated cell death, whereas each drug by itself had little or minor effect on hepatocyte survival. Mechanistically, combination of gefitinib and APAP induces hepatocyte death via the apoptotic pathway obviously. Reactive oxygen species (ROS) generation and DNA damage accumulation are involved in hepatocyte apoptosis. Gefitinib plus APAP also promotes the expression of Kelch-like ECH-associated protein 1 (Keap1) and downregulated the antioxidant factor, Nuclear factor erythroid 2-related factor 2 (Nrf2), by inhibiting p62 expression. Taken together, this study revealed the potential ROS-mediated apoptosis-dependent hepatotoxicity effect of the combination of gefitinib and APAP, in which the p62/Keap1/Nrf2 signaling pathway participates and plays an important regulatory role.
PubMed: 38871446
DOI: 10.4062/biomolther.2023.209