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Nanomaterials (Basel, Switzerland) May 2024Hydrophilic nanofibers offer promising potential for the delivery of drugs with diverse characteristics. Yet, the effects of different drugs incorporated into these...
Hydrophilic nanofibers offer promising potential for the delivery of drugs with diverse characteristics. Yet, the effects of different drugs incorporated into these nanofibers on their properties remain poorly understood. In this study, we systematically explored how model drugs, namely ibuprofen, carvedilol, paracetamol, and metformin (hydrochloride), affect hydrophilic nanofibers composed of polyethylene oxide and poloxamer 188 in a 1:1 weight ratio. Our findings reveal that the drug affects the conductivity and viscosity of the polymer solution for electrospinning, leading to distinct changes in the morphology of electrospun products. Specifically, drugs with low solubility in ethanol, the chosen solvent for polymer solution preparation, led to the formation of continuous nanofibers with uniform diameters. Additionally, the lower solubility of metformin in ethanol resulted in particle appearance on the nanofiber surface. Furthermore, the incorporation of more hydrophilic drugs increased the surface hydrophilicity of nanofiber mats. However, variations in the physicochemical properties of the drugs did not affect the drug loading and drug entrapment efficiency. Our research also shows that drug properties do not notably affect the immediate release of drugs from nanofibers, highlighting the dominant role of the hydrophilic polymers used. This study emphasizes the importance of considering specific drug properties, such as solubility, hydrophilicity, and compatibility with the solvent used for electrospinning, when designing hydrophilic nanofibers for drug delivery. Such considerations are crucial for optimizing the properties of the drug delivery system, which is essential for achieving therapeutic efficacy and safety.
PubMed: 38869574
DOI: 10.3390/nano14110949 -
European Journal of Pharmaceutical... Jun 2024Drug-induced liver injury (DILI) is prevalent in the treatment of chronic kidney disease (CKD). Advanced oxidation protein products (AOPPs) are markers of CKD...
Drug-induced liver injury (DILI) is prevalent in the treatment of chronic kidney disease (CKD). Advanced oxidation protein products (AOPPs) are markers of CKD progression and participate in the occurrence and development of liver diseases. However, the mechanisms underlying the regulation of DILI in CKD have not been established. Herein, we demonstrate the involvement of Cytochrome p450 2E1 (CYP2E1) in DILI induced by AOPPs is exacerbated by exposure to acetaminophen (APAP). We used a adenine-induced CKD model, a model of DILI induced by APAP, and the AOPPs model was generated by intraperitoneal injection. The decline in renal function was associated with a significantly increased concentration of Scr, BUN and AOPPs, and renal tissue fibrosis. The ALT, AST, and AOPPs levels and liver tissue necrosis increased significantly in CKD model group compared with the sodium carboxymethyl cellulose (CMCNa) group. In the AOPPs model, compared to the PBS controls, ALT, AST, and AOPP levels, and liver tissue necrosis increased significantly. In HepG2 or L0-2 cell lines, cell survival was significantly reduced in the AOPP + APAP treatment and CYP2E1 protein expression was increased. FPS-ZM1 or NAC attenuated the hepatocyte toxicity induced by AOPP + APAP and suppression of CYP2E1 expression. AOPPs exacerbated APAP-induced DILI through CYP2E1 signaling pathways. Protein uremic toxins, such as AOPPs, can modify drug toxicity in patients with CKD. This study provides new a rationale to reduce the generation of DILIs in clinical treatment in patients with CKD. AOPPs targeting may present a novel approach to reduce the occurrence of DILI.
PubMed: 38866111
DOI: 10.1016/j.ejps.2024.106829 -
Cureus May 2024We present an atypical case of risedronate-induced chronic fever in an 85-year-old woman with Parkinson's disease, with a dosage regimen of 17.5 mg/week. Our patient had...
We present an atypical case of risedronate-induced chronic fever in an 85-year-old woman with Parkinson's disease, with a dosage regimen of 17.5 mg/week. Our patient had been administered an analgesic/antipyretic drug, acetaminophen, at a rate of 600 mg/day for treatment of a vertebral fracture that occurred relatively frequently, which might have masked the fever caused by risedronate. We noted two clinically significant indications. Firstly, blood test results do not necessarily show the cause of risedronate-induced fever, as white blood cell counts and C-reactive protein levels vary. A simple way to diagnose risedronate-induced fever is to suspend risedronate for a certain period and observe if the patient's fever lowers. Secondly, in general, cases receiving polypharmacy tend to include an analgesic antipyretic agent, which may mask the drug-induced fever. Even in patients with Parkinson's disease whose body temperature is generally unstable due to autonomic nerve system disorder, if they are administered risedronate and experience chronic fever of unknown cause, the possibility of drug fever may be considered. This study concludes that risedronate-induced chronic fever, as observed in our case, represents a rare phenomenon, and it may be necessary to reconsider treatment methods for osteoporosis.
PubMed: 38864058
DOI: 10.7759/cureus.60117 -
The Journal of Pediatric Pharmacology... Jun 2024Acetaminophen (APAP) is an alternative to indomethacin and ibuprofen for treatment of patent ductus arteriosus (PDA). The side effect profile of non-steroidal...
OBJECTIVE
Acetaminophen (APAP) is an alternative to indomethacin and ibuprofen for treatment of patent ductus arteriosus (PDA). The side effect profile of non-steroidal anti-inflammatory drugs (NSAIDs) presents enteral feeding safety concerns; however, the safety of enteral feeding on APAP is largely unknown. Optimal feeding strategies during pharmacological PDA treatment are unknown, leading to practice variation. This study aims to assess the incidence of adverse gastrointestinal (GI) outcomes in neonates treated with APAP for PDA closure while receiving enteral feedings.
METHODS
Single-center retrospective cohort study of 59 extremely low birth weight (ELBW), premature neonates who received APAP for PDA treatment divided into Low Volume (LV; ≤ 20 mL/kg/day) and High Volume (HV; > 20 mL/kg/day) enteral feeding groups. The primary outcome was the incidence of any suspected or confirmed necrotizing enterocolitis (NEC). Timing of nutrition milestones, parenteral nutrition (PN) days, and adverse outcomes (feeding intolerance, liver dysfunction, death prior to discharge) were evaluated.
RESULTS
The incidence of suspected or confirmed NEC was 19.5% in the LV group and 13.3% in the HV group (p = 0.593). The HV group reached full feeds 6 days sooner (18 vs 24 days, p = 0.024) and had fewer PN days (17 vs 23.5 days, p = 0.044) with no difference in adverse outcomes.
CONCLUSIONS
Provision of > 20 mL/kg/day of enteral feeds during APAP treatment of PDA decreased time to full feeds and PN days compared to trophic feedings (≤ 20 mL/kg/day) with no difference in adverse GI outcomes. Continuing enteral feeding during APAP PDA treatment appears safe while improving achievement of nutritional milestones.
PubMed: 38863856
DOI: 10.5863/1551-6776-29.3.278 -
Upsala Journal of Medical Sciences 2024Standard dosages of analgesic and sedative drugs are given to intensive care patients. The resulting range of blood concentrations and corresponding clinical responses...
BACKGROUND
Standard dosages of analgesic and sedative drugs are given to intensive care patients. The resulting range of blood concentrations and corresponding clinical responses need to be better examined. The purpose of this study was to describe daily dosages, measured blood concentrations, and clinical responses in critically ill patients. The purpose was also to contribute to establishing whole blood concentration reference values of the drugs investigated.
METHODS
A descriptive study of prospectively collected data from 302 admissions to a general intensive care unit (ICU) at a university hospital. Ten drugs (clonidine, fentanyl, morphine, dexmedetomidine, ketamine, ketobemidone, midazolam, paracetamol, propofol, and thiopental) were investigated, and daily dosages recorded. Blood samples were collected twice daily, and drug concentrations were measured. Clinical responses were registered using Richmond agitation-sedation scale (RASS) and Numeric rating scale (NRS).
RESULTS
Drug dosages were within recommended dose ranges. Blood concentrations for all 10 drugs showed a wide variation within the cohort, but only 3% were above therapeutic interval where clonidine (57 of 122) and midazolam (38 of 122) dominated. RASS and NRS were not correlated to drug concentrations.
CONCLUSION
Using recommended dose intervals for analgesic and sedative drugs in the ICU setting combined with regular monitoring of clinical responses such as RASS and NRS leads to 97% of concentrations being below the upper limit in the therapeutic interval. This study contributes to whole blood drug concentration reference values regarding these 10 drugs.
Topics: Humans; Hypnotics and Sedatives; Analgesics; Male; Female; Middle Aged; Aged; Intensive Care Units; Prospective Studies; Adult; Midazolam; Critical Care; Dexmedetomidine; Fentanyl; Critical Illness; Propofol; Clonidine; Ketamine; Morphine; Aged, 80 and over; Dose-Response Relationship, Drug; Thiopental; Acetaminophen
PubMed: 38863729
DOI: 10.48101/ujms.v129.10560 -
Drug Metabolism and Disposition: the... Jun 2024Acetaminophen (APAP) is the most used non-prescription drug throughout the world. At therapeutic doses, APAP has potent analgesic and antipyretic effects. The efficacy...
Acetaminophen (APAP) is the most used non-prescription drug throughout the world. At therapeutic doses, APAP has potent analgesic and antipyretic effects. The efficacy and safety of APAP are influenced by multi-factorial processes that are dependent upon dosing, namely frequency and total dose. APAP poisoning by repeated ingestion of supratherapeutic doses, depletes glutathione (GSH) stores in liver and other organs capable of metabolic bioactivation, leading to hepatocellular death due to exhausted antioxidant defenses. Numerous genes, encompassing transcription factors and signaling pathways, have been identified as playing pivotal roles in APAP toxicity, with the liver being the primary organ studied due to its central role in APAP metabolism and injury. Nuclear factor erythroid 2-related factor 2 (Nrf2) and its array of downstream responsive genes are crucial in counteracting acetaminophen APAP toxicity. Nrf2, along with its negative regulator Kelch-like ECH-associated protein 1 (Keap1), plays a vital role in regulating intracellular redox homeostasis. This regulation is significant in modulating the oxidative stress, inflammation, and hepatocellular death induced by APAP. In this review, we provide an updated overview of the mechanisms through which Nrf2 activation and signaling critically influence the threshold for developing APAP toxicity. We also describe how genetically modified rodent models for Nrf2 and related genes have been pivotal in underscoring the significance of this antioxidant response pathway. While Nrf2 is a primary focus, the article comprehensively explores other genetic factors and related pathways that contribute to APAP toxicity, thereby providing a holistic understanding of the genetic landscape influencing susceptibility to this condition. This review scrutinizes the genetic elements and signaling pathways underlying acetaminophen (APAP)-induced liver toxicity, with a focus on the crucial protective role of the transcription factor NRF2. This review also delves into the genetic intricacies influencing APAP safety and potential liver harm and it emphasizes the need for deeper insight into the molecular mechanisms of hepatotoxicity, especially the interplay of NRF2 with other pathways.
PubMed: 38857948
DOI: 10.1124/dmd.124.001282 -
World Journal of Emergency Medicine 2024To describe trends in oxycodone and oxycodone-containing analgesic prescribing for the treatment of back pain among adults in emergency departments (EDs) in the USA from...
BACKGROUND
To describe trends in oxycodone and oxycodone-containing analgesic prescribing for the treatment of back pain among adults in emergency departments (EDs) in the USA from 2007 to 2018.
METHODS
Data were gathered from the National Hospital Ambulatory Medical Care Survey (NHAMCS) from 2007 to 2018. The study population included individuals of all ages presenting to USA EDs. The NHAMCS reasons for visit and oxycodone drug ID codes were used to isolate patients with back pain. The main outcome was the proportion of oxycodone and oxycodone-containing analgesics prescribed for back pain in the EDs over the specified time period.
RESULTS
There was a relative decrease in the overall administration of oxycodone for back pain in the EDs by 62.3% from 2007 (244,000 visits) to 2018 (92,000 visits). The proportion of ED patients prescribed with oxycodone-containing analgesics for back pain increased among patients aged 45 years and older (from 43.8% to 57.6%), female patients (from 54.5% to 62.0%), black patients (from 22.5% to 30.4%), and Hispanic/Latino patients (from 9.4% to 19.6%). Oxycodone/acetaminophen was most prescribed and accounted for 90.2% of all oxycodone-containing analgesics in 2007, with a decrease to 68.5% in 2018. Pure oxycodone was the second most prescribed medication, accounting for 6.1% in 2007 and 31.5% in 2018.
CONCLUSION
The overall number of oxycodone-containing analgesics decreased significantly from 2007 to 2018. However, that number trended upward in 45-year-old and older, female, black, or Hispanic/Latino patients from 2007 to 2018. The total amount of pure oxycodone increased significantly from 2007 to 2008.
PubMed: 38855375
DOI: 10.5847/wjem.j.1920-8642.2024.002 -
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