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Diabetologia Oct 2023
Topics: Antidotes; Incretins; Venoms
PubMed: 37594570
DOI: 10.1007/s00125-023-05987-4 -
International Journal of Toxicology Dec 2023The Expert Panel for Cosmetic Ingredient Safety reviewed newly available studies since their original assessment in 1982, along with updated information regarding...
The Expert Panel for Cosmetic Ingredient Safety reviewed newly available studies since their original assessment in 1982, along with updated information regarding product types and concentrations of use, and confirmed that Quaternium-18 and Quaternium-18 Bentonite are safe as cosmetic ingredients in the practices of use and concentration as described in this report.
Topics: Bentonite; Cosmetics; Consumer Product Safety
PubMed: 37772402
DOI: 10.1177/10915818231204280 -
Nanoscale Aug 2023Prussian Blue Nanozymes (PBNZs) have emerged as highly efficient agents for reactive oxygen species (ROS) elimination, owing to their multiple enzyme-like properties... (Review)
Review
Prussian Blue Nanozymes (PBNZs) have emerged as highly efficient agents for reactive oxygen species (ROS) elimination, owing to their multiple enzyme-like properties encompassing catalase (CAT), peroxidase (POD), and superoxide dismutase (SOD) activities. As a functional nanomaterial mimicking enzyme, PBNZs not only surmount the limitations of natural enzymes, such as instability and high manufacturing costs, but also exhibit superior stability, tunable activity, low storage expenses, and remarkable reusability. Consequently, PBNZs have gained significant attention in diverse biomedical applications, including disease diagnosis and therapy. Over the past decade, propelled by advancements in catalysis science, biotechnology, computational science, and nanotechnology, PBNZs have witnessed remarkable progress in the exploration of their enzymatic activities, elucidation of catalytic mechanisms, and wide-ranging applications. This comprehensive review aims to provide a systematic overview of the discovery and catalytic mechanisms of PBNZ, along with the strategies employed to modulate their multiple enzyme-like activities. Furthermore, we extensively survey the recent advancements in utilizing PBNZs for scavenging ROS in various biomedical applications. Lastly, we analyze the existing challenges of translating PBNZs into therapeutic agents for clinical use and outline future research directions in this field. By presenting a comprehensive synopsis of the current state of knowledge, this review seeks to contribute to a deeper understanding of the immense potential of PBNZs as an innovative therapeutic agent in biomedicine.
Topics: Reactive Oxygen Species; Nanostructures; Nanotechnology; Ferrocyanides; Catalysis
PubMed: 37496423
DOI: 10.1039/d3nr01741a -
Biochemical and Biophysical Research... Sep 2023The therapeutic effects and application of radiotherapy are restricted to some extent due to low radiosensitivity of tumor tissues and adverse effects by excess dosage....
The therapeutic effects and application of radiotherapy are restricted to some extent due to low radiosensitivity of tumor tissues and adverse effects by excess dosage. Current radiosensitizers are confronted with problems in clinical translation because of complicated manufacture technique and high cost. In this research, we have synthesized a radiosensitizer with advantages in low cost and mass production, which could be applied to CT imaging and enhanced radiotherapy in breast cancer, namely Bi-DTPA. It not only enhanced tumor CT imaging which resulted in better therapeutic accuracy, but also realized radiotherapy sensitization by producing massive ROS and inhibit tumor proliferation, providing a sound perspective in the clinical translation of the radiosensitizer.
Topics: Humans; Radiation-Sensitizing Agents; Radiation Tolerance; Neoplasms; Pentetic Acid; Tomography, X-Ray Computed
PubMed: 37302294
DOI: 10.1016/j.bbrc.2023.05.065 -
Cureus Oct 2023Methemoglobinemia is a potentially life-threatening condition in which there is diminution of the oxygen-carrying capacity of circulating hemoglobin. It can result from...
Methemoglobinemia is a potentially life-threatening condition in which there is diminution of the oxygen-carrying capacity of circulating hemoglobin. It can result from either congenital or acquired processes. Methemoglobin forms when hemoglobin is oxidized to contain iron in the ferric (Fe3+) rather than the normal ferrous (Fe2+) state. Methemoglobinemia is a clinical diagnosis and is suspected in the presence of hypoxemia refractory to supplemental oxygen and the presence of chocolate-colored blood. Symptoms are usually dependent on methemoglobin levels; at levels higher than 35%, systemic symptoms from tissue hypoxia may be fatal. A high index of suspicion is required in patients with refractory hypoxia or cyanosis when treated with oxygen. Treatment options involve the removal of the inciting agent and treatment with the antidote methylene blue. Here we present a case of methemoglobinemia in a young patient who attended a college rave party.
PubMed: 38021620
DOI: 10.7759/cureus.47752 -
Clinical Toxicology (Philadelphia, Pa.) Dec 2023Fifty years ago, basic scientific studies and the availability of assay methods made the assessment of risk in paracetamol (acetaminophen) poisoning possible. The use of... (Review)
Review
Fifty years of paracetamol (acetaminophen) poisoning: the development of risk assessment and treatment 1973-2023 with particular focus on contributions published from Edinburgh and Denver.
INTRODUCTION
Fifty years ago, basic scientific studies and the availability of assay methods made the assessment of risk in paracetamol (acetaminophen) poisoning possible. The use of the antidote acetylcysteine linked to new methods of risk assessment transformed the treatment of this poisoning. This review will describe the way in which risk assessment and treatments have developed over the last 50 years and highlight the remaining areas of uncertainty.
METHODS
A search of PubMed and its subsidiary databases revealed 1,166 references published in the period 1963-2023 using the combined terms "paracetamol", "poisoning", and "acetylcysteine". Focused searches then identified 170 papers dealing with risk assessment of paracetamol poisoning, 141 with adverse reactions to acetylcysteine and 114 describing different acetylcysteine regimens. To manage the extensive literature, we focused mainly on contributions made by the authors during their time in Edinburgh and Denver.
DOSE AND CONCENTRATION RESPONSE
The key relationship between paracetamol dose and toxicity risk was established in 1971 and led to the development of the Rumack-Matthew nomogram from data collected in Edinburgh.
MECHANISMS OF TOXICITY
A series of papers on the mechanisms of toxicity were published in 1973, and these showed that paracetamol hepatotoxicity was caused by the formation of a toxic intermediate epoxide metabolite normally detoxified by glutathione but which, in excess, was bound covalently to hepatic enzymes and proteins. An understanding of the relationship between the rate of paracetamol metabolism, paracetamol concentration, and toxic hazard in humans soon followed.
ANTIDOTE DEVELOPMENT AND EFFICACY IN PATIENTS
These discoveries were followed by the testing of a range of sulfhydryl-donors in animals and "at risk" patients. Acetylcysteine was developed as the lead intravenous antidote in the United Kingdom. The license holder in the United States refused to make an intravenous formulation. Thus, oral acetylcysteine became the antidote trialed in the United States National Multicenter Study. Intravenous acetylcysteine regimens used initially in the United Kingdom and subsequently in the United States used loading doses of 150 mg/kg over 15 minutes or one hour, 50 mg/kg over four hours, and 100 mg/kg over 16 hours. These regimens were associated with adverse drug reactions (nausea, vomiting and anaphylactoid reactions) and hence, treatment interruption. Newer dosing regimens now give loading doses more slowly. One, the Scottish and Newcastle Anti-emetic Pretreatment protocol, using an acetylcysteine regimen of 100 mg/kg over two hours followed by 200 mg/kg over 10 hours, has been widely adopted in the United Kingdom. A cohort comparison study suggests this regimen has comparable efficacy to standard regimens and offers opportunities for selective higher acetylcysteine dosing.
RISK ASSESSMENT AT PRESENTATION
No dose-ranging studies with acetylcysteine were done, and no placebo-controlled studies were performed. Thus, there is uncertainty regarding the optimal dose of acetylcysteine, particularly in patients ingesting very large overdoses of paracetamol. The choice of intervention concentration on the Rumack-Matthew nomogram has important consequences for the proportion of patients treated. The United States National Multicenter Study used a "treatment" line starting at 150 mg/L (992 µmol/L) at 4 hours post overdose, extending to 24 hours with a half-life of 4 hours, now standard there, and subsequently adopted in Australia and New Zealand. In the United Kingdom, the treatment line was initially 200 mg/L (1,323 µmol/L) at 4 hours (the Rumack-Matthew "risk" line). In 2012, the United Kingdom Medicines and Healthcare products Regulatory Agency lowered the treatment line to 100 mg/L (662 µmol/L) at 4 hours for all patients, increasing the number of patients admitted and treated at a high cost. Risk assessment is a key issue for ongoing study, particularly following the development of potential new antidotes that may act in those at greatest risk. The development of biomarkers to assess risk is ongoing but has yet to reach clinical trials.
CONCLUSION
Even after 50 years, there are still areas of uncertainty. These include appropriate acetylcysteine doses in patients who ingest different paracetamol doses or multiple (staggered) ingestions, early identification of at-risk patients, and optimal treatment of late presenters.
Topics: Humans; Acetaminophen; Antidotes; Acetylcysteine; Antiemetics; Risk Assessment; Drug Overdose; Analgesics, Non-Narcotic; Chemical and Drug Induced Liver Injury; Multicenter Studies as Topic
PubMed: 38197864
DOI: 10.1080/15563650.2023.2293452 -
BioRxiv : the Preprint Server For... Jun 2024Toxin-antidote systems are selfish genetic elements composed of a linked toxin and antidote. The toxin-antidote system in consists of a transmembrane toxin protein...
Toxin-antidote systems are selfish genetic elements composed of a linked toxin and antidote. The toxin-antidote system in consists of a transmembrane toxin protein PEEL-1 which acts cell autonomously to kill cells. Here we investigate the molecular mechanism of PEEL-1 toxicity. We find that PEEL-1 requires a small membrane protein, PMPL-1, for toxicity. Together, PEEL-1 and PMPL-1 are sufficient for toxicity in a heterologous system, HEK293T cells, and cause cell swelling and increased cell permeability to monovalent cations. Using purified proteins, we show that PEEL-1 and PMPL-1 allow ion flux through lipid bilayers and generate currents which resemble ion channel gating. Our work suggests that PEEL-1 kills cells by co-opting PMPL-1 and creating a cation channel.
PubMed: 38915716
DOI: 10.1101/2024.06.11.598564 -
International Journal of Molecular... Apr 2024Due to a large number of harmful chemicals flowing into the water source in production and life, the water quality deteriorates, and the use value of water is reduced or... (Review)
Review
Due to a large number of harmful chemicals flowing into the water source in production and life, the water quality deteriorates, and the use value of water is reduced or lost. Biochar has a strong physical adsorption effect, but it can only separate pollutants from water and cannot eliminate pollutants fundamentally. Photocatalytic degradation technology using photocatalysts uses chemical methods to degrade or mineralize organic pollutants, but it is difficult to recover and reuse. Woody biomass has the advantages of huge reserves, convenient access and a low price. Processing woody biomass into biochar and then combining it with photocatalysts has played a complementary role. In this paper, the shortcomings of a photocatalyst and biochar in water treatment are introduced, respectively, and the advantages of a woody biochar-based photocatalyst made by combining them are summarized. The preparation and assembly methods of the woody biochar-based photocatalyst starting from the preparation of biochar are listed, and the water treatment efficiency of the woody biochar-based photocatalyst using different photocatalysts is listed. Finally, the future development of the woody biochar-based photocatalyst is summarized and prospected.
Topics: Water Purification; Charcoal; Catalysis; Wood; Carbon; Water Pollutants, Chemical; Photochemical Processes; Adsorption
PubMed: 38731960
DOI: 10.3390/ijms25094743 -
Netherlands Heart Journal : Monthly... Feb 2024Digoxin-specific antibodies (digoxin-Fabs) are of value in the treatment of a strongly suspected or a known, potentially life-threatening digoxin toxicity. These... (Review)
Review
Digoxin-specific antibodies (digoxin-Fabs) are of value in the treatment of a strongly suspected or a known, potentially life-threatening digoxin toxicity. These antibodies are not registered for use in Europe; therefore Dutch hospital pharmacies are not allowed to keep them in stock. In the Netherlands, digoxin-Fabs are stored in a national calamity stock of emergency medicines at the National Institute for Public Health and the Environment. In the case of a medical emergency, digoxin-Fabs are available after contact with the Dutch Poisons Information Centre. Recent studies have shown that the dose of digoxin-Fabs required to effectively treat digoxin toxicity is lower than previously thought. In this article, we present the adjusted digoxin-Fab dosing strategy currently recommended by the Dutch Poisons Information Centre ( www.vergiftigingen.info ). This new dose titration strategy is safe and effective and has a cost-saving side-effect.
PubMed: 37861975
DOI: 10.1007/s12471-023-01814-y -
Nature Communications Dec 2023Killer meiotic drivers (KMDs) skew allele transmission in their favor by killing meiotic progeny not inheriting the driver allele. Despite their widespread presence in...
Killer meiotic drivers (KMDs) skew allele transmission in their favor by killing meiotic progeny not inheriting the driver allele. Despite their widespread presence in eukaryotes, the molecular mechanisms behind their selfish behavior are poorly understood. In several fission yeast species, single-gene KMDs belonging to the wtf gene family exert selfish killing by expressing a toxin and an antidote through alternative transcription initiation. Here we investigate how the toxin and antidote products of a wtf-family KMD gene can act antagonistically. Both the toxin and the antidote are multi-transmembrane proteins, differing only in their N-terminal cytosolic tails. We find that the antidote employs PY motifs (Leu/Pro-Pro-X-Tyr) in its N-terminal cytosolic tail to bind Rsp5/NEDD4 family ubiquitin ligases, which ubiquitinate the antidote. Mutating PY motifs or attaching a deubiquitinating enzyme transforms the antidote into a toxic protein. Ubiquitination promotes the transport of the antidote from the trans-Golgi network to the endosome, thereby preventing it from causing toxicity. A physical interaction between the antidote and the toxin enables the ubiquitinated antidote to translocate the toxin to the endosome and neutralize its toxicity. We propose that post-translational modification-mediated protein localization and/or activity changes may be a common mechanism governing the antagonistic duality of single-gene KMDs.
Topics: Schizosaccharomyces; Antidotes; Ubiquitination; Golgi Apparatus; Ubiquitin; Endosomal Sorting Complexes Required for Transport; Ubiquitin-Protein Ligases
PubMed: 38097609
DOI: 10.1038/s41467-023-44151-9