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Current Opinion in Biotechnology Dec 2008Receptor-ligand interactions are fundamental to the regulation of cell physiology, enabling the communication between cells and their environment via signal... (Review)
Review
Receptor-ligand interactions are fundamental to the regulation of cell physiology, enabling the communication between cells and their environment via signal transduction. Receptors are also exploited by toxins and infectious agents to mediate pathogenesis. Over the past 20 years, however, this bi-partite paradigm for cellular regulation, that is, receptors and their ligands, has been revised to include an unforeseen participant namely, soluble receptors or molecular decoys. Decoys function as nature's modifiers of potent responses such as inflammation, stimulation of cell proliferation and triggering apoptosis. Decoys not only provide the means to fine tune the regulation of these phenomena; they also serve as potential leads for the development of recombinant anti-toxins, anti-viral agents and novel therapeutics for combating cancer and inflammatory disease.
Topics: Animals; Antidotes; Immunologic Factors; Molecular Mimicry
PubMed: 18977299
DOI: 10.1016/j.copbio.2008.10.001 -
Current Opinion in Insect Science Feb 2022Wolbachia endosymbionts commonly induce cytoplasmic incompatibility, making infected males' sperm lethal to the embryos unless these are rescued by the same bacterium,... (Review)
Review
Wolbachia endosymbionts commonly induce cytoplasmic incompatibility, making infected males' sperm lethal to the embryos unless these are rescued by the same bacterium, inherited from their mother. Causal genes were recently identified but two families of mechanistic models are still opposed. In the toxin-antidote model, interaction between the toxin and the antidote is required for rescuing the embryos. In host modification models, a host factor is misregulated in sperm and rescue occurs through compensation or withdrawal of this modification. While these models have been thoroughly discussed, the multiplicity of compatibility types, that is, the existence of many mutually incompatible strains, as seen in Culex mosquitoes, has not received sufficient attention. To explain such a fact, host modification models must posit that the same embryonic defects can be induced and rescued through a large variety of host targets. Conversely, the toxin-antidote model simply accommodates this pattern in a lock-key fashion, through variations in the toxin-antidote interaction sites.
Topics: Animals; Antidotes; Genomics; Male; Models, Molecular; Phenotype; Wolbachia
PubMed: 34954414
DOI: 10.1016/j.cois.2021.12.005 -
Critical Care (London, England) Jun 2019In light of an aging population with increased cardiovascular comorbidity, the use of oral anticoagulation (OAC) is steadily expanding. A variety of pharmacological... (Review)
Review
In light of an aging population with increased cardiovascular comorbidity, the use of oral anticoagulation (OAC) is steadily expanding. A variety of pharmacological alternatives to vitamin K antagonists (VKA) have emerged over recent years (direct oral anticoagulants, DOAC, i.e., dabigatran, rivaroxaban, apixaban, and edoxaban) which show a reduced risk for the occurrence of intracerebral hemorrhage (ICH). Yet, in the event of ICH under OAC (OAC-ICH), hematoma characteristics are similarly severe and clinical outcomes likewise substantially limited in both patients with VKA- and DOAC-ICH, which is why optimal acute hemostatic treatment in all OAC-ICH needs to be guaranteed. Currently, International Guidelines for the hemostatic management of patients with OAC-ICH are updated as several relevant large-sized observational studies and recent trials have established treatment approaches for both VKA- and DOAC-ICH. While the management of VKA-ICH is mainly based on the immediate reversal of elevated levels of international normalized ratio using prothrombin complex concentrates, hemostatic management of DOAC-associated ICH is challenging requiring specific antidotes, notably idarucizumab and andexanet alfa. This review will provide an overview of the latest studies and trials on hemostatic reversal agents and timing and summarizes the effects on hemorrhage progression and clinical outcomes in patients with OAC-ICH.
Topics: Administration, Oral; Anticoagulants; Antidotes; Antithrombins; Blood Coagulation; Cerebral Hemorrhage; Factor Xa; Factor Xa Inhibitors; Humans; Recombinant Proteins; Tranexamic Acid
PubMed: 31171018
DOI: 10.1186/s13054-019-2492-8 -
British Journal of Anaesthesia Dec 1989
Review
Topics: Animals; Antidotes; Humans; Insecticides; Organophosphorus Compounds; Organothiophosphorus Compounds
PubMed: 2692674
DOI: 10.1093/bja/63.6.736 -
Current Opinion in Pharmacology Aug 2007Glutathione (GSH) deficiency is associated with numerous pathological conditions. Administration of N-acetylcysteine (NAC), a cysteine prodrug, replenishes intracellular... (Review)
Review
Glutathione (GSH) deficiency is associated with numerous pathological conditions. Administration of N-acetylcysteine (NAC), a cysteine prodrug, replenishes intracellular GSH levels. NAC, best known for its ability to counter acetaminophen toxicity, is a safe, well-tolerated antidote for cysteine/GSH deficiency. NAC has been used successfully to treat GSH deficiency in a wide range of infections, genetic defects and metabolic disorders, including HIV infection and COPD. Over two-thirds of 46 placebo-controlled clinical trials with orally administered NAC have indicated beneficial effects of NAC measured either as trial endpoints or as general measures of improvement in quality of life and well-being of the patients.
Topics: Acetaminophen; Acetylcysteine; Antidotes; Controlled Clinical Trials as Topic; Cysteine; Cystic Fibrosis; Free Radical Scavengers; Glutathione; HIV Infections; Humans; Prodrugs; Quality of Life
PubMed: 17602868
DOI: 10.1016/j.coph.2007.04.005 -
British Journal of Clinical Pharmacology Mar 2016The alcohols, methanol, ethylene glycol and diethylene glycol, have many features in common, the most important of which is the fact that the compounds themselves are... (Review)
Review
The alcohols, methanol, ethylene glycol and diethylene glycol, have many features in common, the most important of which is the fact that the compounds themselves are relatively non-toxic but are metabolized, initially by alcohol dehydrogenase, to various toxic intermediates. These compounds are readily available worldwide in commercial products as well as in homemade alcoholic beverages, both of which lead to most of the poisoning cases, from either unintentional or intentional ingestion. Although relatively infrequent in overall occurrence, poisonings by metabolically-toxic alcohols do unfortunately occur in outbreaks and can result in severe morbidity and mortality. These poisonings have traditionally been treated with ethanol since it competes for the active site of alcohol dehydrogenase and decreases the formation of toxic metabolites. Although ethanol can be effective in these poisonings, there are substantial practical problems with its use and so fomepizole, a potent competitive inhibitor of alcohol dehydrogenase, was developed for a hopefully better treatment for metabolically-toxic alcohol poisonings. Fomepizole has few side effects and is easy to use in practice and it may obviate the need for haemodialysis in some, but not all, patients. Hence, fomepizole has largely replaced ethanol as the toxic alcohol antidote in many countries. Nevertheless, ethanol remains an important alternative because access to fomepizole can be limited, the cost may appear excessive, or the physician may prefer ethanol due to experience.
Topics: Acidosis; Antidotes; Ethanol; Ethylene Glycol; Ethylene Glycols; Fomepizole; Humans; Methanol; Pyrazoles
PubMed: 26551875
DOI: 10.1111/bcp.12824 -
Annales de Biologie Clinique Feb 2019Many neutralizing agents of anticoagulant effect of factor Xa or thrombin inhibitors (xabans and dabigatran, respectively) have been developed since the... (Review)
Review
Many neutralizing agents of anticoagulant effect of factor Xa or thrombin inhibitors (xabans and dabigatran, respectively) have been developed since the commercialization of direct oral anticoagulants (DOAC) in 2008. Idarucizumab is a specific antidote of dabigatran commercialised since 2016. An antidote of xabans, andexanet-α, was very recently approved by the Food and Drug Administration (FDA). Other antidotes of DOAC are under pre-clinical or clinical development; the most advanced being the aripazine in addition to γ-thrombine S195A and GDFXa-αM complex. Prothrombin complex concentrates activated or not, are part of the pro-hemostatic agents suggested for DOAC handling in case of haemorrhage or preceeding urgent surgery or invasive procedures. Other pro-hemostatic agents (FXa, FX (a)-C, FVa) are in pre-clinical stage. The efficacy of these different agents in DOAC reversal and mortality reduction is still controversal in the light of the sparse results of in vitro, ex vivo, pre-clinical and clinical studies.
Topics: Administration, Oral; Anticoagulants; Antidotes; Antithrombins; Dabigatran; Factor Xa; Factor Xa Inhibitors; Hemorrhage; Humans; Recombinant Proteins; Rivaroxaban
PubMed: 30591426
DOI: 10.1684/abc.2018.1400 -
Current Biology : CB Mar 2021Toxin-antidote elements (TAs) are selfish genetic dyads that spread in populations by selectively killing non-carriers. TAs are common in prokaryotes, but very few...
Toxin-antidote elements (TAs) are selfish genetic dyads that spread in populations by selectively killing non-carriers. TAs are common in prokaryotes, but very few examples are known in animals. Here, we report the discovery of maternal-effect TAs in both C. tropicalis and C. briggsae, two distant relatives of C. elegans. In C. tropicalis, multiple TAs combine to cause a striking degree of intraspecific incompatibility: five elements reduce the fitness of >70% of the F hybrid progeny of two Caribbean isolates. We identified the genes underlying one of the novel TAs, slow-1/grow-1, and found that its toxin, slow-1, is homologous to nuclear hormone receptors. Remarkably, although previously known TAs act during embryonic development, maternal loading of slow-1 in oocytes specifically slows down larval development, delaying the onset of reproduction by several days. Finally, we found that balancing selection acting on linked, conflicting TAs hampers their ability to spread in populations, leading to more stable genetic incompatibilities. Our findings indicate that TAs are widespread in Caenorhabditis species and target a wide range of developmental processes and that antagonism between them may cause lasting incompatibilities in natural populations. We expect that similar phenomena exist in other animal species.
Topics: Animals; Antidotes; Caenorhabditis; Female; Male; Repetitive Sequences, Nucleic Acid; Toxins, Biological
PubMed: 33417886
DOI: 10.1016/j.cub.2020.12.013 -
American Family Physician Aug 2009N-acetylcysteine is the acetylated variant of the amino acid L-cysteine and is widely used as the specific antidote for acetaminophen overdose. Other applications for... (Review)
Review
N-acetylcysteine is the acetylated variant of the amino acid L-cysteine and is widely used as the specific antidote for acetaminophen overdose. Other applications for N-acetylcysteine supplementation supported by scientific evidence include prevention of chronic obstructive pulmonary disease exacerbation, prevention of contrast-induced kidney damage during imaging procedures, attenuation of illness from the influenza virus when started before infection, treatment of pulmonary fibrosis, and treatment of infertility in patients with clomiphene-resistant polycystic ovary syndrome. Preliminary studies suggest that N-acetylcysteine may also have a role as a cancer chemopreventive, an adjunct in the eradication of Helicobacter pylori, and prophylaxis of gentamicin-induced hearing loss in patients on renal dialysis.
Topics: Acetaminophen; Acetylcysteine; Antidotes; Expectorants; Female; Free Radical Scavengers; Hearing Loss; Humans; Influenza, Human; Neoplasms; Polycystic Ovary Syndrome; Respiratory Tract Diseases
PubMed: 19621836
DOI: No ID Found -
Molecules (Basel, Switzerland) Mar 2020Poisoning is the greatest source of avoidable death in the world and can result from industrial exhausts, incessant bush burning, drug overdose, accidental toxication or... (Meta-Analysis)
Meta-Analysis Review
Poisoning is the greatest source of avoidable death in the world and can result from industrial exhausts, incessant bush burning, drug overdose, accidental toxication or snake envenomation. Since the advent of Albert Calmette's cobra venom antidote, efforts have been geared towards antidotes development for various poisons to date. While there are resources and facilities to tackle poisoning in urban areas, rural areas and developing countries are challenged with poisoning management due to either the absence of or inadequate facilities and this has paved the way for phyto-antidotes, some of which have been scientifically validated. This review presents the scope of antidotes' effectiveness in different experimental models and biotechnological advancements in antidote research for future applications. While pockets of evidence of the effectiveness of antidotes exist and with ample biotechnological developments, the utilization of analytic assays on existing and newly developed antidotes that have surpassed the proof of concept stage, as well as the inclusion of antidote's short and long-term risk assessment report, will help in providing the required scientific evidence(s) prior to regulatory authorities' approval.
Topics: Animals; Antidotes; Biotechnology; Disease Models, Animal; Drug Development; Drug Evaluation, Preclinical; Humans; Phytochemicals; Poisoning; Treatment Outcome
PubMed: 32225103
DOI: 10.3390/molecules25071516