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Nature Food Feb 2024
Topics: Oryza; Cadmium; Charcoal; Soil Pollutants
PubMed: 38365911
DOI: 10.1038/s43016-024-00934-x -
World Journal of Emergency Medicine 2024Chlorfenapyr is used to kill insects that are resistant to organophosphorus insecticides. Chlorfenapyr poisoning has a high mortality rate and is difficult to treat.... (Review)
Review
BACKGROUND
Chlorfenapyr is used to kill insects that are resistant to organophosphorus insecticides. Chlorfenapyr poisoning has a high mortality rate and is difficult to treat. This article aims to review the mechanisms, clinical presentations, and treatment strategies for chlorfenapyr poisoning.
DATA RESOURCES
We conducted a review of the literature using PubMed, Web of Science, and SpringerLink from their beginnings to the end of October 2023. The inclusion criteria were systematic reviews, clinical guidelines, retrospective studies, and case reports on chlorfenapyr poisoning that focused on its mechanisms, clinical presentations, and treatment strategies. The references in the included studies were also examined to identify additional sources.
RESULTS
We included 57 studies in this review. Chlorfenapyr can be degraded into tralopyril, which is more toxic and reduces energy production by inhibiting the conversion of adenosine diphosphate to adenosine triphosphate. High fever and altered mental status are characteristic clinical presentations of chlorfenapyr poisoning. Once it occurs, respiratory failure occurs immediately, ultimately leading to cardiac arrest and death. Chlorfenapyr poisoning is difficult to treat, and there is no specific antidote.
CONCLUSION
Chlorfenapyr is a new pyrrole pesticide. Although it has been identified as a moderately toxic pesticide by the World Health Organization (WHO), the mortality rate of poisoned patients is extremely high. There is no specific antidote for chlorfenapyr poisoning. Therefore, based on the literature review, future efforts to explore rapid and effective detoxification methods, reconstitute intracellular oxidative phosphorylation couplings, identify early biomarkers of chlorfenapyr poisoning, and block the conversion of chlorfenapyr to tralopyril may be helpful for emergency physicians in the diagnosis and treatment of this disease.
PubMed: 38855374
DOI: 10.5847/wjem.j.1920-8642.2024.046 -
Current Opinion in Anaesthesiology Apr 2024The advent of direct oral anticoagulants (DOACs) marks a significant milestone in anticoagulant treatment. However, DOACs can exacerbate bleeding, which is challenging... (Review)
Review
PURPOSE OF REVIEW
The advent of direct oral anticoagulants (DOACs) marks a significant milestone in anticoagulant treatment. However, DOACs can exacerbate bleeding, which is challenging for the treating clinician, especially when combined with traumatic injury.
RECENT FINDINGS
In major bleeding associated with DOACs, rapid reversal of the anticoagulant effects is crucial. Recent observational and nonrandomized interventional trials have demonstrated the effectiveness of the specific antidotes andexanet alfa and idarucizumab as well as the unspecific prothrombin complex concentrates (PCCs) to counteract the anticoagulant effects of DOACs. The European Society of Anaesthesiology and Intensive Care guideline for severe perioperative bleeding and the European trauma guideline propose divergent recommendations for the use of andexanet alfa and PCC to obtain hemostasis in Factor Xa inhibitor-related bleeding. The conflicting recommendations are due to limited evidence from clinical studies and the potential increased risk of thromboembolic complications after the administration of andexanet. Regarding dabigatran-associated major bleeding, both guidelines recommend the specific reversal agent idarucizumab as first-line therapy.
SUMMARY
Current guidelines recommend specific antidots and PCCs in DOAC-related major bleeding. Prospective randomized trials comparing specific vs. nonspecific hemostatic agents in the perioperative setting are needed to evaluate the effectiveness and safety of the hemostatic agents.
Topics: Humans; Administration, Oral; Anticoagulants; Antidotes; Hemorrhage; Hemostatics; Prospective Studies; Wounds and Injuries
PubMed: 38390922
DOI: 10.1097/ACO.0000000000001349 -
Biochemical Pharmacology Feb 2024Liver injury and acute liver failure caused by an acetaminophen (APAP) overdose is a significant clinical problem in western countries. With the introduction of the... (Review)
Review
Liver injury and acute liver failure caused by an acetaminophen (APAP) overdose is a significant clinical problem in western countries. With the introduction of the mouse model of APAP hepatotoxicity in the 1970 s, fundamental mechanisms of cell death were discovered. This included the recognition that part of the APAP dose is metabolized by cytochrome P450 generating a reactive metabolite that is detoxified by glutathione. After the partial depletion of glutathione, the reactive metabolite will covalently bind to sulfhydryl groups of proteins, which is the initiating event of the toxicity. This insight led to the introduction of N-acetyl-L-cysteine, a glutathione precursor, as antidote against APAP overdose in the clinic. Despite substantial progress in our understanding of the pathomechanisms over the last decades viable new antidotes only emerged recently. This review will discuss the background, mechanisms of action, and the clinical prospects of the existing FDA-approved antidote N-acetylcysteine, of several new drug candidates under clinical development [4-methylpyrazole (fomepizole), calmangafodipir] and examples of additional therapeutic targets (Nrf2 activators) and regeneration promoting agents (thrombopoietin mimetics, adenosine A2B receptor agonists, Wharton's Jelly mesenchymal stem cells). Although there are clear limitations of certain therapeutic approaches, there is reason to be optimistic. The substantial progress in the understanding of the pathophysiology of APAP hepatotoxicity led to the consideration of several drugs for development as clinical antidotes against APAP overdose in recent years. Based on the currently available information, it is likely that this will result in additional drugs that could be used as adjunct treatment for N-acetylcysteine.
PubMed: 38346541
DOI: 10.1016/j.bcp.2024.116056 -
NEJM Evidence Sep 2023Maintaining independence is the top health-related priority reported by older patients with advanced kidney disease. Unfortunately, functional losses such as fatigue,...
Maintaining independence is the top health-related priority reported by older patients with advanced kidney disease. Unfortunately, functional losses such as fatigue, skeletal muscle loss, infection, cognitive decline, and diminished aerobic capacity are very common among patients receiving hemodialysis for chronic kidney failure. Such functional losses are associated with higher mortality and affect patients' physical activity level and overall quality of life. Indeed, symptom burden and mortality in patients receiving hemodialysis rival those in patients with cancer. Nephrology societies, clinicians, and above all patients and families are therefore interested in preserving quality of life and function for patients on dialysis.
Topics: Humans; Renal Dialysis; Antidotes; Quality of Life; Kidney Failure, Chronic; Exercise
PubMed: 38320189
DOI: 10.1056/EVIDe2300178 -
Biomedicine & Pharmacotherapy =... Oct 2023Patients receiving high-dose methotrexate (HDMTX) for malignancies are exposed to diverse complications, including nephrotoxicity, hepatotoxicity, mucositis,... (Review)
Review
Patients receiving high-dose methotrexate (HDMTX) for malignancies are exposed to diverse complications, including nephrotoxicity, hepatotoxicity, mucositis, myelotoxicity, neurological symptoms, and death. Glucarpidase is a recombinant carboxypeptidase G2 (CPG2) that converts MTX into nontoxic metabolites. In this study, the role of vector type, gene optimization, orientation, and host on the expression of CPG2 is investigated. The effectiveness of various therapeutic regimens containing glucarpidase is classified and perspectives on the dose adjustment based on precision medicine are provided. Conjugation with cell-penetrating peptides, human serum albumin, and polymers such as PEG and dextran for delivery, higher stability, and production of the biobetter variants of CPG2 is highlighted. Conjugation of CPG2 to F(ab՜) or scFv antibody fragments against tumor-specific antigens and the corresponding prodrugs for tumor-targeted drug delivery using the antibody-directed enzyme prodrug therapy (ADEPT) is communicated. Trials to reduce the off-target effects and the possibility of repeated ADEPT cycles by adding pro-domains sensitive to tumor-overexpressed proteases, antiCPG2 antibodies, CPG2 mutants with immune-system-unrecognizable epitopes, and protective polymers are reported. Intracellular cpg2 gene expression by gene-directed enzyme prodrug therapy (GDEPT) and the concerns regarding the safety and transfection efficacy of the GDEPT vectors are described. A novel bifunctional platform using engineered CAR-T cell micropharmacies, known as Synthetic Enzyme-Armed KillER (SEAKER) cells, expressing CPG2 to activate prodrugs at the tumor niche is introduced. Taken together, integrated data in this review and recruiting combinatorial strategies in novel drug delivery systems define the future directions of ADEPT, GDEPT, and SEAKER cell therapy and the placement of CPG2 therein.
Topics: Humans; Methotrexate; gamma-Glutamyl Hydrolase; Prodrugs; Antidotes; Neoplasms; Antibodies; Polymers
PubMed: 37579696
DOI: 10.1016/j.biopha.2023.115292 -
CJEM Oct 2023
PubMed: 37737538
DOI: 10.1007/s43678-023-00569-0 -
Toxics May 2024From 2019 to 2020, antihistamines were found in 15% of all US drug overdose deaths, often co-administered with fentanyl, with 3.6% of overdose deaths due to... (Review)
Review
From 2019 to 2020, antihistamines were found in 15% of all US drug overdose deaths, often co-administered with fentanyl, with 3.6% of overdose deaths due to antihistamines alone. The most common antihistamine found in all these reported deaths is diphenhydramine, a ubiquitous, over-the-counter and clinically important medication. Currently, there is no antidote for diphenhydramine overdose. This review summarizes the adverse health effects and current emergency medicine treatments for diphenhydramine. Several emergency medicine case reports are reviewed, and the efficacy and outcomes of a variety of treatments are compared. The treatments reviewed include the more traditional antihistamine overdose therapeutics physostigmine and sodium bicarbonate, as well as newer ones such as donepezil, dexmedetomidine, and lipid emulsion therapy. We conclude that more study is needed to determine the ideal therapeutic approach to treating antihistamine overdoses.
PubMed: 38922056
DOI: 10.3390/toxics12060376 -
The Science of the Total Environment Dec 2023The development of carbonaceous materials such as biochar has triggered a hot spot in materials application. Carbon material derived from biomass could be a vital... (Review)
Review
The development of carbonaceous materials such as biochar has triggered a hot spot in materials application. Carbon material derived from biomass could be a vital platform for energy storage and conversion. Biochar-based materials deliver a novel approach to deal with the current energy-related challenges. To design and utilize the maximum potential of biochar for environmentally sustainable applications, it is crucial to understand the recent progress and advancement in molecular structures of biochar to discover a new possible field to simplify structural application networks. However, most of the studies demonstrated the application of biochar in the form of soil enhancers and bio-adsorbents, reducing soil emissions of greenhouse gases and as fertilizers. The present review on biochar highlighted the application of biochar-based materials in various energy storage and conversion sectors, comprising different types of conversion technologies, biochar formation mechanisms, modification techniques on biochar surface chemistry and its functionality, catalysts, biochar application in energy storage gadgets such as supercapacitors and nanotubes, bio-based composite materials and inorganic based composites materials. Finally, this review addressed some vital outlooks on the prospect of the functionalization and best utilization of biochar-supported materials in numerous energy storage and conversion fields. After reviewing the literature, it was directed that advanced and in-depth research is essential for structural analysis and separation, considering the macroscopic and microscopic evidence of the formed structural design of biochar for specific applications.
Topics: Biomass; Charcoal; Carbon; Soil
PubMed: 37741418
DOI: 10.1016/j.scitotenv.2023.167171 -
The Journal of Pharmacology and... Jan 2024There do not appear to be any established therapeutics for treating azide poisoning at this time, and presently available antidotes to cyanide poisoning are far from...
There do not appear to be any established therapeutics for treating azide poisoning at this time, and presently available antidotes to cyanide poisoning are far from ideal, being particularly impractical for use if multiple victims present. The cobalt (II/III) complex of the Schiff-base ligand -[14]-diene (5,7,7,12,14,14-hexamethyl-1,4,8,11-tetraazacyclotetradeca-4,11-diene (CoN[14]) is shown to act as an effective antidote to both azide and cyanide toxicity in mice. Groups of animals challenged with an LD dose of NaCN (100 µmol/kg i.p.) exhibited significantly faster recovery from knockdown and fewer (zero) deaths if given CoN[14] (50 μmol/kg i.p.) 2 minutes after the toxicant. Groups of animals challenged with an essentially lethal dose of NaCN (1.5 x LD = 150 µmol/kg i.p.) all survived if given the CoN[14] (75 μmol/kg i.p.) 5 minutes before the toxicant dose. These data represent improved antidotal capability over the Food and Drug Administration-approved cobalt-based cyanide antidote hydroxocobalamin. Recovery of animals challenged sublethally with NaN (415 μmol/kg i.p.) was assessed employing a modified pole-climbing test. Mice given the CoN[14] antidote (70 μg/kg i.p.) 5 minutes after the toxicant dose recovered twice as fast as the controls given no antidote. The interactions of cyanide and azide with CoN[14] in vitro (buffered aqueous solutions) have been further investigated by a combination of spectroscopic approaches. The Co(II) form of the complex is able to bind two CN anions while only binding a single N , providing a reasonable explanation for the difference between their therapeutic abilities. SIGNIFICANCE STATEMENT: The Schiff-base complex CoN[14] is shown to be an effective antidote to cyanide in mice, with improved therapeutic capabilities compared to the Food and Drug Administration-approved cobalt-containing hydroxocobalamin. CoN[14] is also antidotal in mice toward azide poisoning, for which there is seemingly no approved therapy currently available. The activity toward cyanide involves a "redox-switching" mechanism that could be a common, but largely unrecognized, feature of all cobalt-based cyanide antidotes in use and under development.
Topics: United States; Animals; Mice; Antidotes; Hydroxocobalamin; Azides; Cobalt; Cyanides; Schiff Bases
PubMed: 38182416
DOI: 10.1124/jpet.123.001719