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Circulation Oct 2023In this focused update, the American Heart Association provides updated guidance for resuscitation of patients with cardiac arrest, respiratory arrest, and refractory... (Review)
Review
2023 American Heart Association Focused Update on the Management of Patients With Cardiac Arrest or Life-Threatening Toxicity Due to Poisoning: An Update to the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care.
In this focused update, the American Heart Association provides updated guidance for resuscitation of patients with cardiac arrest, respiratory arrest, and refractory shock due to poisoning. Based on structured evidence reviews, guidelines are provided for the treatment of critical poisoning from benzodiazepines, β-adrenergic receptor antagonists (also known as β-blockers), L-type calcium channel antagonists (commonly called calcium channel blockers), cocaine, cyanide, digoxin and related cardiac glycosides, local anesthetics, methemoglobinemia, opioids, organophosphates and carbamates, sodium channel antagonists (also called sodium channel blockers), and sympathomimetics. Recommendations are also provided for the use of venoarterial extracorporeal membrane oxygenation. These guidelines discuss the role of atropine, benzodiazepines, calcium, digoxin-specific immune antibody fragments, electrical pacing, flumazenil, glucagon, hemodialysis, hydroxocobalamin, hyperbaric oxygen, insulin, intravenous lipid emulsion, lidocaine, methylene blue, naloxone, pralidoxime, sodium bicarbonate, sodium nitrite, sodium thiosulfate, vasodilators, and vasopressors for the management of specific critical poisonings.
Topics: Humans; Adrenergic beta-Antagonists; American Heart Association; Benzodiazepines; Cardiopulmonary Resuscitation; Digoxin; Heart Arrest; United States
PubMed: 37721023
DOI: 10.1161/CIR.0000000000001161 -
Autophagy Sep 2023Mitophagy, which selectively eliminates the dysfunctional and excess mitochondria by autophagy, is crucial for cellular homeostasis under stresses such as hypoxia....
Mitophagy, which selectively eliminates the dysfunctional and excess mitochondria by autophagy, is crucial for cellular homeostasis under stresses such as hypoxia. Dysregulation of mitophagy has been increasingly linked to many disorders including neurodegenerative disease and cancer. Triple-negative breast cancer (TNBC), a highly aggressive breast cancer subtype, is reported to be characterized by hypoxia. However, the role of mitophagy in hypoxic TNBC as well as the underlying molecular mechanism is largely unexplored. Here, we identified GPCPD1 (glycerophosphocholine phosphodiesterase 1), a key enzyme in choline metabolism, as an essential mediator in hypoxia-induced mitophagy. Under the hypoxic condition, we found that GPCPD1 was depalmitoylated by LYPLA1, which facilitated the relocating of GPCPD1 to the outer mitochondrial membrane (OMM). Mitochondria-localized GPCPD1 could bind to VDAC1, the substrate for PRKN/PARKIN-dependent ubiquitination, thus interfering with the oligomerization of VDAC1. The increased monomer of VDAC1 provided more anchor sites to recruit PRKN-mediated polyubiquitination, which consequently triggered mitophagy. In addition, we found that GPCPD1-mediated mitophagy exerted a promotive effect on tumor growth and metastasis in TNBC both and . We further determined that GPCPD1 could serve as an independent prognostic indicator in TNBC. In conclusion, our study provides important insights into a mechanistic understanding of hypoxia-induced mitophagy and elucidates that GPCPD1 could act as a potential target for the future development of novel therapy for TNBC patients.: ACTB: actin beta; 5-aza: 5-azacytidine; BNIP3: BCL2 interacting protein 3; BNIP3L: BCL2 interacting protein 3 like; CCCP: carbonyl cyanide m-chlorophenyl hydrazone; ChIP: chromatin immunoprecipitation; co-IP: co-immunoprecipitation; CQ: chloroquine; CsA: cyclosporine; DOX: doxorubicin; FIS1: fission, mitochondrial 1; FUNDC1: FUN14 domain containing 1; GPCPD1: glycerophosphocholine phosphodiesterase 1; HAM: hydroxylamine; HIF1A: hypoxia inducible factor 1 subunit alpha; HRE: hypoxia response element; IF: immunofluorescence; LB: lysis buffer; LC3B/MAP1LC3B: microtubule associated protein 1 light chain 3 beta; LC-MS: liquid chromatography-mass spectrometry; LYPLA1: lysophospholipase 1; LYPLA2: lysophospholipase 2; MDA231: MDA-MB-231; MDA468: MDA-MB-468; MFN1: mitofusin 1; MFN2: mitofusin 2; MKI67: marker of proliferation Ki-67; OCR: oxygen consumption rate; OMM: outer mitochondrial membrane; OS: overall survival; PalmB: palmostatin B; PBS: phosphate-buffered saline; PINK1: PTEN induced kinase 1; PRKN: parkin RBR E3 ubiquitin protein ligase; SDS: sodium dodecyl sulfate; TOMM20: translocase of outer mitochondrial membrane 20; TNBC: triple-negative breast cancer; VBIT-4: VDAC inhibitor; VDAC1: voltage dependent anion channel 1; WT: wild type.
Topics: Humans; Autophagy; Lysophospholipase; Mitophagy; Neurodegenerative Diseases; Phospholipases; Proto-Oncogene Proteins c-bcl-2; Triple Negative Breast Neoplasms; Ubiquitin-Protein Ligases; Ubiquitination; Voltage-Dependent Anion Channel 1
PubMed: 36803235
DOI: 10.1080/15548627.2023.2182482 -
Journal of Education & Teaching in... Jul 2022The goal of this simulation is to educate emergency medicine students, residents, attending physicians, and mid-level practitioners to recognize, diagnose, and manage...
AUDIENCE
The goal of this simulation is to educate emergency medicine students, residents, attending physicians, and mid-level practitioners to recognize, diagnose, and manage acute cyanide toxicity.
INTRODUCTION
Cyanide has an almond scent and is a naturally occurring compound. It is present within many different types of plants and fruits including apricots, apples, peaches, lima beans, and cassava plants but is harmless.1 The trace amounts of cyanide found within organic materials is of little concern because its high reactivity causes it to be metabolized rapidly and create other compounds. However, modern synthetic materials such as plastics, papers, textiles, and machinery can release a much greater concentration of hydrogen cyanide when exposed to high temperatures.1 As the use of contemporary nitrogen-containing synthetic polymers has expanded, the possibility of cyanide toxicity has become increasingly common and severe. Hydrogen cyanide is especially dangerous to humans because the gaseous form reacts quickly upon inhalation.2When cyanide enters the body via inhalation, it blocks the cells from utilizing oxygen by binding to the cytochrome oxidase in the mitochondria.2 The inability of the cell to use oxygen forces cells from aerobic metabolism into anaerobic metabolism. Anaerobic metabolism results in the production of lactic acid, which causes metabolic acidosis.3 The human body cannot sustain itself with the lack of oxygen and anaerobic metabolism for a prolonged period of time. Ultimately, the body will suffer cardiorespiratory arrest.1Symptoms of cyanide toxicity include headache, nausea, shortness of breath, and altered mental status.1 These are similar to those of carbon monoxide and carbon dioxide inhalation. However, symptoms of cyanide toxicity cannot be treated with supplemental oxygen as carbon monoxide and carbon dioxide are. Cyanide toxicity must be treated with an antidote - sodium thiosulfate, sodium nitrite, and hydroxocobalamin.4 Each of the antidotes works by binding with the highly reactive cyanide, neutralizing the compound, and converting it into a water-soluble product that will be cleared through renal excretion.4Fire victims often present to the emergency department critically ill. They will likely have obvious external thermal burns and traumatic injuries; however, it is important for emergency personnel to recognize the respiratory distress and metabolic derangements that are most likely occurring due to toxic gas inhalation. People who are trapped within a burning structure are exposed to carbon monoxide, carbon dioxide, and cyanide from the combustion of contents within the building. These toxic gasses will cause severe tissue hypoxia without significant vital sign changes.5 The respiratory distress and metabolic compromise will be acutely more fatal than the obvious external injuries and burns. The challenge in treating these patients is for the healthcare team to know the differential diagnoses, prioritize airway, breathing and circulation, and to empirically treat the patient as if they have a confirmed exposure.It is estimated that 35% of all fire victims have toxic levels of cyanide upon arrival to the emergency room.2 Acute cyanide toxicity can become fatal within minutes; however, a prompt diagnosis and treatment can be lifesaving. Unfortunately, due to the limited amount of time the human body can sustain anaerobic metabolism and tissue hypoxia, blood test results are not available in time to be clinically applicable.2 Rather, the emergency room personnel must begin treatment immediately upon recognizing that toxic smoke inhalation may have occurred.We understand the importance of knowing how to treat fire victims. Therefore, the goal of this simulation case is to expose the emergency providers to cyanide poisoning and educate emergency providers about the critical steps of how to approach, diagnose, and treat cyanide toxicity.
EDUCATIONAL OBJECTIVES
After the completion of this simulation, participants will have learned how to: 1) identify clues of smoke inhalation based on a physical examination; 2) identify smoke inhalation-induced airway compromise and perform definitive management; 3) create a differential diagnosis for victims of fire cyanide poisoning, carbon monoxide, and carbon dioxide; 4) appropriately treat cyanide poisoning; 5) demonstrate the importance of preemptively treating for cyanide poisoning; 6) perform an initial physical examination and identify physical marks suggesting the patient is a fire and smoke inhalation victim; and 7) familiarize themselves with the Cyanokit and treatment with hydroxocobalamin.
EDUCATIONAL METHODS
This is a high-fidelity simulation case in which participants work through a case of a patient who has been exposed to fire. The participants will be able to work hands-on to evaluate, diagnose, and treat cyanide poisoning in an emergency event. Afterwards, there will be a small group discussion and debriefing of the case in order to review patient care skills, interpersonal and communication skills, medical knowledge, and system-based practice.
RESEARCH METHODS
The participants were instructed to complete a survey before and after the simulation case. A quality Likert Scale was used to assess the participants' comfort level of diagnosing, treating, and managing a patient with toxic smoke inhalation. A score of 1 represented a negative experience and 5 represented a very positive experience. The surveys were then reviewed by the research team to determine if the simulation case improved the participants' comfort level. The survey answers were compared collectively, as well as individually, and were analyzed between the pre-simulation and post-simulation results.
RESULTS
Our simulation involved 25 participants: 20 participants were emergency medicine resident physicians and 5 were 4th-year medical students. In the pre-simulation survey, participants reported a mean of 2.7 out of 5 when asked to rate their confidence in their ability to treat a smoke inhalation victim. The post-simulation survey showed a significant increase to a mean of 3.5 out of 5. Participants were also asked to evaluate the usefulness of the simulation: 15 participants rated the case as a 5, which represented "very useful," and the other 10 participants rated the case as a 4, which represented "useful." The mean value when asked to assess the simulation case's usefulness and applicability in emergency medicine was 4.6 out of 5.
DISCUSSION
This simulation allows providers to focus on victims of fire. Fire victims are often critically ill and require time sensitive treatment. This simulation gives providers a chance to review their knowledge and prepare them for real life cases. Based on the survey results, the simulation improved awareness and understanding of the symptoms of acute cyanide toxicity and improved the participant's ability to recognize, diagnose, and treat cyanide poisoning.
TOPICS
Cyanide toxicity, carbon monoxide toxicity, cyanide antidote, fire victim, intubation, airway intervention, oxygen treatment, history taking, lab testing ordering, symptom identification, interpretation of lab results, emergency medicine simulation.
PubMed: 37465777
DOI: 10.21980/J80W76 -
Autophagy Sep 2019Mitochondria are key organelles for cellular metabolism, and regulate several processes including cell death and macroautophagy/autophagy. Here, we show that...
Mitochondria are key organelles for cellular metabolism, and regulate several processes including cell death and macroautophagy/autophagy. Here, we show that mitochondrial respiratory chain (RC) deficiency deactivates AMP-activated protein kinase (AMPK, a key regulator of energy homeostasis) signaling in tissue and in cultured cells. The deactivation of AMPK in RC-deficiency is due to increased expression of the AMPK-inhibiting protein FLCN (folliculin). AMPK is found to be necessary for basal lysosomal function, and AMPK deactivation in RC-deficiency inhibits lysosomal function by decreasing the activity of the lysosomal Ca channel MCOLN1 (mucolipin 1). MCOLN1 is regulated by phosphoinositide kinase PIKFYVE and its product PtdIns(3,5)P, which is also decreased in RC-deficiency. Notably, reactivation of AMPK, in a PIKFYVE-dependent manner, or of MCOLN1 in RC-deficient cells, restores lysosomal hydrolytic capacity. Building on these data and the literature, we propose that downregulation of the AMPK-PIKFYVE-PtdIns(3,5)P-MCOLN1 pathway causes lysosomal Ca accumulation and impaired lysosomal catabolism. Besides unveiling a novel role of AMPK in lysosomal function, this study points to the mechanism that links mitochondrial malfunction to impaired lysosomal catabolism, underscoring the importance of AMPK and the complexity of organelle cross-talk in the regulation of cellular homeostasis. : ΔΨ: mitochondrial transmembrane potential; AMP: adenosine monophosphate; AMPK: AMP-activated protein kinase; ATG5: autophagy related 5; ATP: adenosine triphosphate; ATP6V0A1: ATPase, H+ transporting, lysosomal, V0 subbunit A1; ATP6V1A: ATPase, H+ transporting, lysosomal, V0 subbunit A; BSA: bovine serum albumin; CCCP: carbonyl cyanide-m-chlorophenylhydrazone; CREB1: cAMP response element binding protein 1; CTSD: cathepsin D; CTSF: cathepsin F; DMEM: Dulbecco's modified Eagle's medium; DMSO: dimethyl sulfoxide; EBSS: Earl's balanced salt solution; ER: endoplasmic reticulum; FBS: fetal bovine serum; FCCP: carbonyl cyanide-p-trifluoromethoxyphenolhydrazone; GFP: green fluorescent protein; GPN: glycyl-L-phenylalanine 2-naphthylamide; LAMP1: lysosomal associated membrane protein 1; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MCOLN1/TRPML1: mucolipin 1; MEF: mouse embryonic fibroblast; MITF: melanocyte inducing transcription factor; ML1N*2-GFP: probe used to detect PtdIns(3,5)P based on the transmembrane domain of MCOLN1; MTORC1: mechanistic target of rapamycin kinase complex 1; NDUFS4: NADH:ubiquinone oxidoreductase subunit S4; OCR: oxygen consumption rate; PBS: phosphate-buffered saline; pcDNA: plasmid cytomegalovirus promoter DNA; PCR: polymerase chain reaction; PtdIns3P: phosphatidylinositol-3-phosphate; PtdIns(3,5)P: phosphatidylinositol-3,5-bisphosphate; PIKFYVE: phosphoinositide kinase, FYVE-type zinc finger containing; P/S: penicillin-streptomycin; PVDF: polyvinylidene fluoride; qPCR: quantitative real time polymerase chain reaction; RFP: red fluorescent protein; RNA: ribonucleic acid; SDS-PAGE: sodium dodecyl sulfate polyacrylamide gel electrophoresis; shRNA: short hairpin RNA; siRNA: small interfering RNA; TFEB: transcription factor EB; TFE3: transcription factor binding to IGHM enhancer 3; TMRM: tetramethylrhodamine, methyl ester, perchlorate; ULK1: unc-51 like autophagy activating kinase 1; ULK2: unc-51 like autophagy activating kinase 2; UQCRC1: ubiquinol-cytochrome c reductase core protein 1; v-ATPase: vacuolar-type H+-translocating ATPase; WT: wild-type.
Topics: AMP-Activated Protein Kinases; Animals; Autophagosomes; Calcium; Cell Death; Electron Transport Complex I; Fibroblasts; HEK293 Cells; HeLa Cells; Humans; Lysosomes; Mice; Mitochondria; Mitochondrial Diseases; Phosphatidylinositol 3-Kinases; Phosphatidylinositol Phosphates; Proto-Oncogene Proteins; Transient Receptor Potential Channels; Tumor Suppressor Proteins
PubMed: 30917721
DOI: 10.1080/15548627.2019.1586256 -
Indian Journal of Critical Care... Dec 2019Antidotes are agents that negate the effect of a poison or toxin. Antidotes mediate its effect either by preventing the absorption of the toxin, by binding and...
INTRODUCTION
Antidotes are agents that negate the effect of a poison or toxin. Antidotes mediate its effect either by preventing the absorption of the toxin, by binding and neutralizing the poison, antagonizing its end-organ effect, or by inhibition of conversion of the toxin to more toxic metabolites. Antidote administration may not only result in the reduction of free or active toxin level, but also in the mitigation of end-organ effects of the toxin by mechanisms that include competitive inhibition, receptor blockade or direct antagonism of the toxin.
MECHANISM OF ACTION OF ANTIDOTES
Reduction in free toxin level can be achieved by specific and non-specific agents that bind to the toxin. The most commonly used non-specific binding agent is activated charcoal. Specific binders include chelating agents, bioscavenger therapy and immunotherapy. In some situations, enhanced elimination can be achieved by urinary alkalization or hemadsorption. Competitive inhibition of enzymes (e.g. ethanol for methanol poisoning), enhancement of enzyme function (e.g. oximes for organophosphorus poisoning) and competitive receptor blockade (e.g. naloxone, flumazenil) are other mechanisms by which antidotes act. Drugs such as N-acetyl cysteine and sodium thiocyanate reduce the formation of toxic metabolites in paracetamol and cyanide poisoning respectively. Drugs such as atropine and magnesium are used to counteract the end-organ effects in organophosphorus poisoning. Vitamins such as vitamin K, folic acid and pyridoxine are used to antagonise the effects of warfarin, methotrexate and INH respectively in the setting of toxicity or overdose. This review provides an overview of the role of antidotes in poisoning.
HOW TO CITE THIS ARTICLE
Chacko B, Peter JV. Antidotes in Poisoning. Indian J Crit Care Med 2019;23(Suppl 4):S241-S249.
PubMed: 32020997
DOI: 10.5005/jp-journals-10071-23310 -
Adipocyte Dec 2020The diabetes medication canagliflozin (Cana) is a sodium glucose cotransporter 2 (SGLT2) inhibitor acting by increasing urinary glucose excretion and thus reducing...
UNLABELLED
The diabetes medication canagliflozin (Cana) is a sodium glucose cotransporter 2 (SGLT2) inhibitor acting by increasing urinary glucose excretion and thus reducing hyperglycaemia. Cana treatment also reduces body weight. However, it remains unclear whether Cana could directly work on adipose tissue. In the present study, the pharmacological effects of Cana and the associated mechanism were investigated in adipocytes and mice. Stromal-vascular fractions (SVFs) were isolated from subcutaneous adipose tissue and differentiated into mature adipocytes. Our results show that Cana treatment directly increased cellular energy expenditure of adipocytes by inducing mitochondrial biogenesis independently of SGLT2 inhibition. Along with mitochondrial biogenesis, Cana also increased mitochondrial oxidative phosphorylation, fatty acid oxidation and thermogenesis. Mechanistically, Cana promoted mitochondrial biogenesis and function via an Adenosine monophosphate-activated protein kinase (AMPK) - silent information regulator 1 (Sirt1) - peroxisome proliferator-activated receptor γ coactivator-1α (Pgc-1α) signalling pathway. Consistently, study demonstrated that Cana increased AMPK phosphorylation and the expression of Sirt1 and Pgc-1α. The present study reveals a new therapeutic function for Cana in regulating energy homoeostasis.
ABBREVIATIONS
Ucp-1, uncoupling protein 1; cAMP, cyclic adenosine monophosphate; PKA, cAMP-dependent protein kinase A; SGLT, sodium glucose cotransporter; Cana, canagliflozin; T2DM: type 2 diabetes; Veh, vehicle; Pgc-1α, peroxisome proliferator-activated receptor γ coactivator-1α; SVFs, stromal-vascular fractions; FBS, bovine serum; Ad, adenovirus; mtDNA, mitochondrial DNA; COX2, cytochrome oxidase subunit 2; RT-PCR, real-time PCR; SDS-PAGE, sodium dodecyl sulphate-polyacrylamide gel electrophoresis; Prdm16, PR domain zinc finger protein 16; Cidea, cell death inducing DFFA-like effector A; Pgc-1β, peroxisome proliferator-activated receptor γ coactivator-1β; NRF1, nuclear respiratory factor 1; Tfam, mitochondrial transcription factor A; OXPHOS, oxidative phosphorylation; FAO, fatty acid oxidation; AMPK, Adenosine monophosphate-activated protein kinase; p-AMPK, phosphorylated AMPK; Sirt1, silent information regulator 1; mTOR, mammalian target of rapamycin; WAT, white adipose tissue; Fabp4, fatty acid binding protein 4; Lpl, lipoprotein lipase; Slc5a2, solute carrier family 5 member 2; ERRα, oestrogen related receptor α; Uqcrc2, ubiquinol-cytochrome c reductase core protein 2; Uqcrfs1, ubiquinol-cytochrome c reductase, Rieske iron-sulphur polypeptide 1; Cox4, cytochrome c oxidase subunit 4; Pparα, peroxisome proliferator activated receptor α; NAD, nicotinamide adenine dinucleotide; Dio2, iodothyronine deiodinase 2; Tmem26, transmembrane protein 26; Hoxa9, homeobox A9; FCCP, carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone; Rot/AA, rotenone/antimycin A; OCR, oxygen consumption rate; Pparγ, peroxisome proliferator activated receptor γ; C/ebp, CCAAT/enhancer binding protein; LKB1, liver kinase B1; AUC, area under the cure; Vd, apparent volume of distribution.
Topics: AMP-Activated Protein Kinases; Adipocytes; Animals; Canagliflozin; Energy Metabolism; Fatty Acids; Gene Expression Regulation; Male; Mice; Mitochondria; Models, Biological; Organelle Biogenesis; Oxidation-Reduction; Oxidative Phosphorylation; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Signal Transduction; Sirtuin 1; Thermogenesis
PubMed: 32835596
DOI: 10.1080/21623945.2020.1807850 -
Clinical Toxicology (Philadelphia, Pa.) Mar 2022Hydrogen cyanide and methanethiol are two toxic gases that inhibit mitochondrial cytochrome oxidase. Cyanide is generated in structural fires and methanethiol is...
CONTEXT
Hydrogen cyanide and methanethiol are two toxic gases that inhibit mitochondrial cytochrome oxidase. Cyanide is generated in structural fires and methanethiol is released by decaying organic matter. Current treatments for cyanide exposure do not lend themselves to treatment in the field and no treatment exists for methanethiol poisoning. Sodium tetrathionate (tetrathionate), a product of thiosulfate oxidation, could potentially serve as a cyanide antidote, and, based on its chemical structure, we hypothesized it could react with methanethiol.
RESULTS
We show that tetrathionate, unlike thiosulfate, reacts directly with cyanide under physiological conditions, and based on rabbit studies where we monitor cyanide poisoning in real-time, tetrathionate likely reacts directly with cyanide . We found that tetrathionate administered by intramuscular injection rescues >80% of juvenile, young adult, and old adult mice from exposure to inhaled hydrogen cyanide gas that is >80% lethal. Tetrathionate also rescued young adult rabbits from intravenously administered sodium cyanide. Tetrathionate was reasonably well-tolerated by mice and rats, yielding a therapeutic index of ∼5 in juvenile and young adult mice, and ∼3.3 in old adult mice; it was non-mutagenic in Chinese Hamster ovary cells and by the Ames bacterial test. We found by gas chromatography-mass spectrometry that both tetrathionate and thiosulfate react with methanethiol to generate dimethyldisulfide, but that tetrathionate was much more effective than thiosulfate at recovering intracellular ATP in COS-7 cells and rescuing mice from a lethal exposure to methanethiol gas.
CONCLUSION
We conclude that tetrathionate has the potential to be an effective antidote against cyanide and methanethiol poisoning.
Topics: Animals; Antidotes; CHO Cells; Cricetinae; Cricetulus; Cyanides; Humans; Mice; Rabbits; Rats; Sulfhydryl Compounds; Tetrathionic Acid; Thiosulfates
PubMed: 34328378
DOI: 10.1080/15563650.2021.1953517 -
Drugs in Context 2021Poisoning causes significant morbidity and sometimes mortality in children worldwide. The clinical skill of toxidrome recognition followed by the timely administration... (Review)
Review
BACKGROUND
Poisoning causes significant morbidity and sometimes mortality in children worldwide. The clinical skill of toxidrome recognition followed by the timely administration of an antidote specific for the poison is essential for the management of children with suspected poisoning. This is a narrative review on antidotes for toxidromes in paediatric practice.
METHODS
A literature search was conducted on PubMed with the keywords "antidote", "poisoning", "intoxication", "children" and "pediatric". The search was customized by applying the appropriate filters (species: humans; age: birth to 18 years) to obtain the most relevant articles for this review article.
RESULTS
Toxidrome recognition may offer a rapid guide to possible toxicology diagnosis such that the specific antidote can be administered in a timely manner. This article summarizes toxidromes and their respective antidotes in paediatric poisoning, with an emphasis on the symptomatology and source of exposure. The antidote and specific management for each toxidrome are discussed. Antidotes are only available for a limited number of poisons responsible for intoxication. Antidotes for common poisonings include N-acetyl cysteine for paracetamol and sodium thiosulphate for poisoning by cyanide.
CONCLUSION
Poisoning is a common cause of paediatric injury. Physicians should be familiar with the recognition of common toxidromes and promptly use specific antidotes for the management of childhood toxidromes.
PubMed: 34122588
DOI: 10.7573/dic.2020-11-4 -
Toxics Nov 2021Biomarkers in exposure assessment are defined as the quantifiable targets that indicate the exposure to hazardous chemicals and their resulting health effect. In this...
Biomarkers in exposure assessment are defined as the quantifiable targets that indicate the exposure to hazardous chemicals and their resulting health effect. In this study, we aimed to identify, validate, and characterize the mRNA biomarker that can detect the exposure of sodium cyanide. To identify reliable biomarkers for sodium cyanide exposure, critical criteria were defined for candidate selection: (1) the expression level of mRNA significantly changes in response to sodium thiocyanate treatment in transcriptomics results (fold change > 2.0 or <0.50, adjusted -value < 0.05); and (2) the mRNA level is significantly modulated by sodium cyanide exposure in both normal human lung cells and rat lung tissue. We identified the following mRNA biomarker candidates: , , , , , , , , , , , , , and The expression levels of these candidates were commonly downregulated by sodium cyanide exposure both in vitro and in vivo. We functionally characterized the biomarkers and established the impact of sodium cyanide on transcriptomic profiles using in silico approaches. Our results suggest that the biomarkers may contribute to the regulation and degradation of the extracellular matrix, leading to a negative effect on surrounding lung cells.
PubMed: 34822678
DOI: 10.3390/toxics9110288