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Antioxidants (Basel, Switzerland) May 2024Acetaminophen (APAP) overdose triggers a cascade of intracellular oxidative stress events, culminating in acute liver injury. The clinically used antidote,...
Acetaminophen (APAP) overdose triggers a cascade of intracellular oxidative stress events, culminating in acute liver injury. The clinically used antidote, N-acetylcysteine (NAC), has a narrow therapeutic window, and early treatment is essential for a satisfactory therapeutic outcome. For more versatile therapies that can be effective even at late presentation, the intricacies of APAP-induced hepatotoxicity must be better understood. Accumulation of advanced glycation end products (AGEs) and the consequent activation of the receptor for AGEs (RAGE) are considered one of the key mechanistic features of APAP toxicity. Glyoxalase 1 (Glo-1) regulates AGE formation by limiting the levels of methylglyoxal (MEG). In this study, we studied the relevance of Glo-1 in the APAP-mediated activation of RAGE and downstream cell death cascades. Constitutive Glo-1-knockout mice (GKO) and a cofactor of Glo-1, ψ-GSH, were used as tools. Our findings showed elevated oxidative stress resulting from the activation of RAGE and hepatocyte necrosis through steatosis in GKO mice treated with high-dose APAP compared to wild-type controls. A unique feature of the hepatic necrosis in GKO mice was the appearance of microvesicular steatosis as a result of centrilobular necrosis, rather than the inflammation seen in the wild type. The GSH surrogate and general antioxidant ψ-GSH alleviated APAP toxicity irrespective of the Glo-1 status, suggesting that oxidative stress is the primary driver of APAP toxicity. Overall, the exacerbation of APAP hepatotoxicity in GKO mice suggests the importance of this enzyme system in antioxidant defense against the initial stages of APAP overdose.
PubMed: 38929087
DOI: 10.3390/antiox13060648 -
Biomedicines Jun 2024Fibromyalgia, a chronic pain condition marked by abnormal pain processing, impacts a significant part of the population, leading to reduced quality of life and function.... (Review)
Review
Fibromyalgia, a chronic pain condition marked by abnormal pain processing, impacts a significant part of the population, leading to reduced quality of life and function. Hallmark symptoms include widespread persistent pain, sleep disturbances, fatigue, cognitive dysfunction, and mood changes. Through this updated review, we aim to contribute to the evolving understanding and management of fibromyalgia, offering insights into the diverse tools available to improve the lives of those affected by this challenging condition. Management begins with educating patients to ultimately relieve them of unnecessary testing and provide reassurance. Treatment emphasizes a comprehensive approach, combining nonpharmacological interventions such as aforementioned education, exercise, and psychotherapy, alongside pharmacologic management-namely duloxetine, milnacipran, pregabalin, and amitriptyline-which have consistent benefits for a range of symptoms across the spectrum of fibromyalgia. Notably, drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen are generally not recommended due to limited efficacy and associated risks. Lastly, a variety of other medications have shown promise, including NMDA-receptor antagonists, naltrexone, and cannabinoids; however, they should be used with caution due to a small amount of evidence and potential for adverse effects.
PubMed: 38927473
DOI: 10.3390/biomedicines12061266 -
Biomedicines May 2024Previous studies have identified metabolites as biomarkers or potential therapeutic targets for traumatic brain injury (TBI). However, the causal association between...
Previous studies have identified metabolites as biomarkers or potential therapeutic targets for traumatic brain injury (TBI). However, the causal association between them remains unknown. Therefore, we investigated the causal effect of serum metabolites and cerebrospinal fluid (CSF) metabolites on TBI susceptibility through Mendelian randomization (MR). Genetic variants related to metabolites and TBI were extracted from a corresponding genome-wide association study (GWAS). Causal effects were estimated through the inverse variance weighted approach, supplemented by a weighted median, weight mode, and the MR-Egger test. In addition, sensitivity analyses were further performed to evaluate the stability of the MR results, including the MR-Egger intercept, leave-one-out analysis, Cochrane's Q-test, and the MR-PRESSO global test. Metabolic pathway analysis was applied to uncover the underlying pathways of the significant metabolites in TBI. In blood metabolites, substances such as 4-acetaminophen sulfate and kynurenine showed positive links, whereas beta-hydroxyisovalerate and creatinine exhibited negative correlations. CSF metabolites such as N-formylanthranilic acid were positively related, while kynurenate showed negative associations. The metabolic pathway analysis highlighted the potential biological pathways involved in TBI. Of these 16 serum metabolites, 11 CSF metabolites and metabolic pathways may serve as useful circulating biomarkers in clinical screening and prevention, and may be candidate molecules for the exploration of mechanisms and drug targets.
PubMed: 38927385
DOI: 10.3390/biomedicines12061178 -
Talanta Jun 2024Effective monitoring of acetaminophen (APAP) dosage is crucial for preventing antipyretic abuse, ensuring therapeutic efficacy, and minimizing toxic effects. However,...
Effective monitoring of acetaminophen (APAP) dosage is crucial for preventing antipyretic abuse, ensuring therapeutic efficacy, and minimizing toxic effects. However, existing self-monitoring methods are limited. In this study, we designed a plasmonic microneedle (MN) sensor for real-time nondestructive monitoring of acetaminophen levels in dermal interstitial fluid (ISF) by employing a handheld Raman spectrometer. The fabricated MN sensor incorporated a high-density plasmonic MOFs known as HDPM, which unique structure of large specific surface area, specific pore structure as well as high density gold nanospheres packing enabled the excellent performance of selective ISF drug enrichment and surface-enhanced Raman scattering (SERS). The maximum electric field enhancement factor of the HDPM nanostructure could be calculated as 5.73 × 10. The developed HDPM@MNs was characterized with a core-shell type "soft on the outside and rigid on the inside" structure, which exhibited sufficient hardness and flexibility to penetrate the dermal tissue with little damage, and robust SERS enhancement effect in APAP detection without any interfering peaks. Through a hydrogel drug simulation experiment, the sensor demonstrated robust capabilities for acetaminophen enrichment and monitoring, exhibiting excellent stability and repeatability. The quantitative detection window spanned from 1 to 100 μM, with a low detection limit reaching 0.45 μM. Furthermore, by monitoring the concentration of acetaminophen in the interstitial fluid of rat skin at different doses and for different administration times, the HDPM@MNs can be used to determine the pharmacokinetics of acetaminophen in rats and the physiological characteristics associated with various dosage regimens. This work not only holds promise for drug monitoring but also provides a novel approach for nondestructive monitoring of other crucial low-abundance physiological markers.
PubMed: 38924988
DOI: 10.1016/j.talanta.2024.126463 -
Reviews in Medical Virology Jul 2024Liver involvement is an unusual yet frequently overlooked dengue complication. Pivotal for an efficient clinical management, the early diagnosis of dengue-associated...
Liver involvement is an unusual yet frequently overlooked dengue complication. Pivotal for an efficient clinical management, the early diagnosis of dengue-associated liver involvement relies on an accurate description of its clinical and biological characteristics, its prognosis factors, its association with severe dengue and its clinical management. We conducted a systematic review by searching PubMed and Web of Science databases for original case reports, cohort and cross-sectional studies reporting the clinical and/or biological features of dengue-associated liver involvement. The study was registered in PROSPERO (CRD42021262657). Of the 2552 articles identified, 167 were included. Dengue-associated liver involvement was characterised by clinical features including abdominal pain, hepatomegaly, jaundice, nausea/vomiting, and an echogenic liver exhibiting hepatocellular necrosis and minimal inflammation. Elevated Aspartate Aminotransferase and Alanine Aminotransferase but also elevated bilirubin, Alkaline Phosphatase, gamma-glutamyl transferase, increased International Normalised Ratio, creatinine and creatine kinase, lower albumin and prolonged prothrombin and activated partial thromboplastin time were prevalent in dengue-associated liver involvement. Cardiovascular and haematological systems were frequently affected, translating in a strong association with severe dengue. Liver involvement was more common in males and older adults. It was associated with dengue virus serotype-2 and secondary infections. Early paracetamol intake increased the risk of liver involvement, which clinical management was mostly conservative. In conclusion, this systematic review demonstrates that early monitoring of transaminases, clinical assessment, and ultrasound examination allow an efficient diagnosis of dengue-associated liver involvement, enabling the early identification and management of severe dengue.
Topics: Humans; Dengue; Dengue Virus; Liver; Liver Diseases
PubMed: 38923215
DOI: 10.1002/rmv.2564 -
Journal of Xenobiotics Jun 2024The monitoring of contaminants in fish species is pivotal for fishes' health and reproduction, as well as for human health. In the specific work, three major categories...
The monitoring of contaminants in fish species is pivotal for fishes' health and reproduction, as well as for human health. In the specific work, three major categories of contaminants, pesticides, pharmaceuticals, and macro and trace elements, were investigated in two major fish species, and , collected from Thermaikos Gulf, in Greece. To achieve this goal, three analytical methods using LC-MS/MS, GC-MS/MS, and ICP-MS were developed, validated, and applied to the collected fish samples. The results indicated a very low prevalence of caffeine and acetaminophen, both not exceeding 3.8 μg/kg fish. Similarly, thiabendazole, cypermethrin, and tricyclazole (pesticides) were found in a concentration range of 0.9 to 13.7 μg/kg fish, while in one sample, traces of the metabolite of organochlorine pesticide DDT, -DDE were detected. Al, Mn, Fe, Zn, and Sr were the predominant trace elements in a concentration range of 500-20,000 μg/kg fish. Macro elements levels varied from 280 to 5405 mg/kg fish. Health risk assessment did not unveil an unacceptable risk for the human health of adults, apart from one sample presenting Hg above the regulatory levels. On the contrary, for children, the calculated hazard quotient values for Hg in all cases and for two As detections were higher than the threshold value of 1, indicating a potential risk.
PubMed: 38921650
DOI: 10.3390/jox14020041 -
Hospital Pharmacy Aug 2024Each month, subscribers to receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to... (Review)
Review
Each month, subscribers to receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to Pharmacy & Therapeutics Committees. Subscribers also receive monthly 1-page summary monographs on agents that are useful for agendas and pharmacy/nursing in-services. A comprehensive target drug utilization evaluation/medication use evaluation (DUE/MUE) is also provided each month. With a subscription, the monographs are available online to subscribers. Monographs can be customized to meet the needs of a facility. Through the cooperation of publishes selected reviews in this column. For more information about , contact Wolters Kluwer customer service at 866-397-3433.
PubMed: 38919758
DOI: 10.1177/00185787241236439 -
Journal of Anaesthesiology, Clinical... 2024Moderate-to-severe intensity pain is reported on the first day following lower abdominal surgery. No study has compared transversus abdominis plane (TAP) block with...
BACKGROUND AND AIMS
Moderate-to-severe intensity pain is reported on the first day following lower abdominal surgery. No study has compared transversus abdominis plane (TAP) block with retrolaminar block (RLB) in laparoscopic inguinal hernia surgery for postoperative pain relief.
MATERIAL AND METHODS
In this prospective, randomized trial, 42 patients of American Society of Anesthesiologists (ASA) physical status I and II, aged 18-65 s, and having a BMI <40 kgm received TAP or RLB following laparoscopic inguinal hernia surgery. A standard general anesthetic technique was performed. Patients were randomized into two groups: single-shot TAP block (gp I) (n 21) or the RLB (gp II) (n 21) with bilateral 20 ml of 0.375% ropivacaine. Postoperatively, IV paracetamol 1 was administered as rescue analgesia. Postoperative cumulative Visual Analogue Scale (VAS) score 24 hours after surgery was considered as the primary outcome.
RESULTS
Postoperative cumulative VAS score at rest at 24 , represented as mean ± S.D (95% CI), in the TAP block group was 3.54 3.04 2.16-4.93) and in the RLB group was 6.09 4.83 3.89-8.29). value was 0.112 and VAS on movement was 7.95 3.41 6.39-9.50 [2.5-15.0]) in TAP block group, whereas value was 0.110 and VAS on movement was 10.83 5.51 8.32-13.34) in the RLB group.
CONCLUSION
Similar postoperative cumulative pain score on movement at 24 was present in patients receiving TAP block or RLB. However, VAS score at rest and on movement was reduced in patients receiving TAP block at 18 and 24 postoperatively.
PubMed: 38919452
DOI: 10.4103/joacp.joacp_424_22 -
Journal of Anaesthesiology, Clinical... 2024Erector spinae plane block (ESPB) has been found to be simple, safe, and effective at thoracic and lumbar levels. There is no randomized controlled trial evaluating its...
BACKGROUND AND AIMS
Erector spinae plane block (ESPB) has been found to be simple, safe, and effective at thoracic and lumbar levels. There is no randomized controlled trial evaluating its effectiveness at sacral level. The present study was conducted to evaluate its effectiveness at sacral level for postoperative analgesia in pediatric patients undergoing hypospadias repair.
MATERIAL AND METHODS
Forty children of 2-7 years with ASA grade I or II were included. They were randomly allocated to one of the two groups of 20 patients each. After induction of general anesthesia, patients of group I were given ultrasound-guided sacral ESPB with 1 ml/kg of 0.25% bupivacaine, and patients of group II were not given block. Postoperatively, pain was assessed using face, legs, activity, cry, consolability (FLACC) scale at 0 hour, every 15 min up to 1 hour, every half an hour up to 2 hours, 2 hourly up to 12 hours, and at 18 hour and 24 hour postoperatively. At FLACC score ≥4, rescue analgesia was given using 15 mg/kg paracetamol infusion. Primary objective was to compare postoperative analgesic (paracetamol) consumption, and secondary objective was time to first rescue analgesia.
RESULTS
Mean postoperative paracetamol consumption was 360 ± 156.60 mg in group I and 997.50 ± 310.87 mg in group II ( = 0.001). Time to first rescue analgesia was 906 ± 224.51 min in group I and 205.00 ± 254.92 min in group II ( = 0.001).
CONCLUSION
Sacral ESPB has been found to be effective in reducing postoperative analgesic consumption in pediatric patients undergoing hypospadias repair.
PubMed: 38919450
DOI: 10.4103/joacp.joacp_418_22 -
Cureus May 2024Dengue, an arboviral illness, is notorious for inducing thrombocytopenia, leading to bleeding and heightened mortality risk. leaf extract has shown efficacy in...
Dengue, an arboviral illness, is notorious for inducing thrombocytopenia, leading to bleeding and heightened mortality risk. leaf extract has shown efficacy in elevating platelet counts. A 35-year-old male presented with fever, fatigue, and body pain persisting for four days. Additionally, he complained of severe back pain, ocular discomfort, and brief episodes of nosebleeds. Testing revealed a positive NS1 antigen, prompting the initiation of intravenous normal saline, paracetamol, and papaya extract tablets. Despite initial platelet levels of 74,000, a subsequent decline to 30,650 was observed following another nosebleed. Subsequently, the patient's spouse administered freshly prepared papaya leaf extract orally three to four times daily, resulting in a platelet count of 120,320 on day 14. Timely recognition of declining platelet levels and the commencement of leaf extract contributed significantly to averting mortality risks.
PubMed: 38919218
DOI: 10.7759/cureus.61090