Toxicology

2020 ◽  
pp. 187-225
Author(s):  
Jonathan P. Wyatt ◽  
Robert G. Taylor ◽  
Kerstin de Wit ◽  
Emily J. Hotton ◽  
Robin J. Illingworth ◽  
...  
Keyword(s):  
Tricyclic Antidepressant ◽  
Accidental Poisoning ◽  
Novel Psychoactive Substances ◽  
Recreational Drugs ◽  
Converting Enzyme ◽  
Gas Poisoning ◽  
Tear Gas ◽  
Body Packers ◽  
Chemical Incidents ◽  
Button Batteries

This chapter in the Oxford Handbook of Emergency Medicine encompasses toxicology in the emergency department (ED). It examines poisons in general, including diagnosis, supportive care, reducing absorption, and antidotes. Specific poisoning is explored in detail, through opioid, salicylate, paracetamol, tricyclic antidepressant, benzodiazepine, clomethiazole, phenothiazine, barbiturate, lithium, sulfonylurea, beta-blocker, calcium channel antagonist, digoxin, angiotensin-converting enzyme (ACE) inhibitor, theophylline, salbutamol, iron, ethanol, methanol, ethylene glycol, paraquat, petrol, paraffin, organophosphate, cyanide, carbon monoxide, chlorine, and CS gas (tear gas) poisoning. Chemical incidents are discussed, as well as accidental poisoning from plants, berries, mushrooms, and button batteries. It also examines novel psychoactive substances (NPS), recreational drugs, serotonin syndrome, and body packers.

scholarly journals Clomipramine suppresses ACE2-mediated SARS-CoV-2 entry

2021 ◽  
Author(s):  
Yuri Kato ◽  
Shigeru Yamada ◽  
Kazuhiro Nishiyama ◽  
Ayano Satsuka ◽  
Suyong Re ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Metabolic Disorder ◽  
Myocardial Damage ◽  
Tricyclic Antidepressant ◽  
Host Cells ◽  
Converting Enzyme ◽  
Susceptibility To Infection ◽  
Potential Inhibitor ◽  
Combined Use ◽  
Approved Drugs

Myocardial damage caused by the newly emerged coronavirus (SARS-CoV-2) infection is one of key determinants of COVID-19 severity and mortality. SARS-CoV-2 entry to host cells are initiated by binding with its receptor, angiotensin converting enzyme (ACE) 2, and the ACE2 abundance is thought to reflect the susceptibility to infection. Here, we found that clomipramine, a tricyclic antidepressant, potently inhibits SARS-CoV-2 infection and metabolic disorder in human iPS-derived cardiomyocytes. Among 13 approved drugs that we have previously identified as potential inhibitor of doxorubicin-induced cardiotoxicity, clomipramine showed the best potency to inhibit SARS-CoV-2 spike glycoprotein pseudovirus-stimulated ACE2 internalization. Indeed, SARS-CoV-2 infection to human iPS-derived cardiomyocytes (iPS-CMs) and TMPRSS2-expressing VeroE6 cells were dramatically suppressed even after treatment with clomipramine. Furthermore, the combined use of clomipramine and remdesivir was revealed to synergistically suppress SARS-CoV-2 infection. Our results will provide the potentiality of clomipramine for the breakthrough treatment of severe COVID-19.

Substrate specificity and inducibility of TACE (tumour necrosis factor α-converting enzyme) revisited: the Ala-Val preference, and induced intrinsic activity

2003 ◽  
Vol 70 ◽  
pp. 39-52 ◽  
Author(s):  
Roy A. Black ◽  
John R. Doedens ◽  
Rajeev Mahimkar ◽  
Richard Johnson ◽  
Lin Guo ◽  
...  
Keyword(s):  
Substrate Specificity ◽  
Recent Work ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Transforming Growth Factor ◽  
Intrinsic Activity ◽  
Converting Enzyme ◽  
Tumour Necrosis Factor Α ◽  
Factor Α ◽  
Necrosis Factor

Tumour necrosis factor α (TNFα)-converting enzyme (TACE/ADAM-17, where ADAM stands for a disintegrin and metalloproteinase) releases from the cell surface the extracellular domains of TNF and several other proteins. Previous studies have found that, while purified TACE preferentially cleaves peptides representing the processing sites in TNF and transforming growth factor α, the cellular enzyme nonetheless also sheds proteins with divergent cleavage sites very efficiently. More recent work, identifying the cleavage site in the p75 TNF receptor, quantifying the susceptibility of additional peptides to cleavage by TACE and identifying additional protein substrates, underlines the complexity of TACE-substrate interactions. In addition to substrate specificity, the mechanism underlying the increased rate of shedding caused by agents that activate cells remains poorly understood. Recent work in this area, utilizing a peptide substrate as a probe for cellular TACE activity, indicates that the intrinsic activity of the enzyme is somehow increased.

The New Forest Suicide Prevention Initiative (NFSPI)

Crisis ◽  
2005 ◽  
Vol 26 (1) ◽  
pp. 25-33 ◽  
Author(s):  
Elizabeth King ◽  
Neil Frost
Keyword(s):  
Environmental Issues ◽  
Exhaust Gas ◽  
Telephone Number ◽  
Forestry Commission ◽  
Car Exhaust ◽  
Gas Poisoning ◽  
Car Park ◽  
Annual Total ◽  
New Forest ◽  
Car Exhaust Gas

Abstract. A retrospective suicide study revealed that the Forestry Commission car parks in the New Forest in southern England were a previously unrecognized magnet for nonlocal suicides, attracting as high a proportion of “visitors” (35/43 in 1993-97) as among suicides who jumped from the cliffs at the infamous Beachy Head (39/48 in 1993-97). Over 95% of the car park suicides died from car exhaust gas poisoning. A multiagency initiative aimed to reduce the number of suicides in the 140 New Forest car parks where restricting access was impossible, and environmental issues paramount. Signs displaying the Samaritans' national telephone number were erected in the 26 car parks in which 50% of the car park suicides had occurred. Numbers, location, and residence of all car park deaths were monitored for 3 years. Corresponding changes in other forest registration districts were also monitored. During the 3-year intervention period the number of car park suicides fell significantly from 10/year, 1988-1997, to 3.3/year. The average annual total number of suicides in the New Forest registration district also decreased. No significant changes were found in comparable forest districts. The number of suicides in the New Forest car parks remained low during the 2 years following the evaluation.

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