ABSTRACT
BACKGROUND: Diethylene glycol (DEG) is an industrial solvent with many uses, including brake fluids. It has also caused mass poisonings after use as an inappropriate substitute for propylene glycol or glycerin, though individual ingestions are rare. Like other toxic alcohols, DEG is metabolized by alcohol dehydrogenase and aldehyde dehydrogenase, with toxicity likely mediated by the resulting metabolites. Fomepizole, an alcohol dehydrogenase inhibitor, is used to prevent metabolite formation with other toxic alcohol exposures. Fomepizole is recommended for DEG poisoning, though supporting clinical evidence is limited. CASE REPORT: A 31-year-old man presented after ingestion of DEG-containing brake fluid and hydrocarbon-containing "octane booster." He was noted to be clinically intoxicated, with a mildly elevated anion gap metabolic acidosis and no osmolar gap. DEG level was later found to be elevated, consistent with his ingestion. He was treated with fomepizole alone, with resolution of metabolic acidosis and clinical findings over the next 2 days. No delayed neurologic sequelae were present at 52-day follow-up. Our case provides additional evidence supporting the use of fomepizole for DEG poisoning. Consistent with other toxic alcohols, DEG poisoning, especially early presentations, may benefit from empiric fomepizole administration. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: DEG poisoning is potentially life threatening, but treatable if identified early. An ingestion can be toxic despite a normal osmolar gap, leading to false reassurance. Finally, it is rare, so emergency physicians must be made aware of its potential dangers.
Subject(s)
Acidosis , Poisoning , Acidosis/chemically induced , Acidosis/drug therapy , Adult , Alcohol Dehydrogenase/therapeutic use , Aldehyde Dehydrogenase/therapeutic use , Antidotes/pharmacology , Antidotes/therapeutic use , Eating , Ethylene Glycol , Ethylene Glycols , Fomepizole/therapeutic use , Glycerol/therapeutic use , Humans , Male , Octanes/therapeutic use , Poisoning/therapy , Propylene Glycols/therapeutic use , Pyrazoles/pharmacology , Pyrazoles/therapeutic use , Solvents/therapeutic useABSTRACT
Limited treatment options exist to combat infections caused by multidrug-resistant (MDR) Gram-negative bacteria possessing broad-spectrum ß-lactamases. The design of novel ß-lactamase inhibitors is of paramount importance. Here, three novel diazabicyclooctanes (DBOs), WCK 5153, zidebactam (WCK 5107), and WCK 4234 (compounds 1-3, respectively), were synthesized and biochemically characterized against clinically important bacteria. Compound 3 inhibited class A, C, and D ß-lactamases with unprecedented k2/ K values against OXA carbapenemases. Compounds 1 and 2 acylated class A and C ß-lactamses rapidly but not the tested OXAs. Compounds 1-3 formed highly stable acyl-complexes as demonstrated by mass spectrometry. Crystallography revealed that 1-3 complexed with KPC-2 adopted a "chair conformation" with the sulfate occupying the carboxylate binding region. The cefepime-2 and meropenem-3 combinations were effective in murine peritonitis and neutropenic lung infection models caused by MDR Acinetobacter baumannii. Compounds 1-3 are novel ß-lactamase inhibitors that demonstate potent cross-class inhibition, and clinical studies targeting MDR infections are warranted.
Subject(s)
Azabicyclo Compounds/pharmacology , Bridged Bicyclo Compounds/pharmacology , Cyclooctanes/pharmacology , Gram-Negative Bacteria/drug effects , Octanes/pharmacology , Piperidines/pharmacology , beta-Lactam Resistance/drug effects , beta-Lactamase Inhibitors/pharmacology , beta-Lactamases/metabolism , beta-Lactams/pharmacology , Animals , Azabicyclo Compounds/chemistry , Azabicyclo Compounds/therapeutic use , Bridged Bicyclo Compounds/chemistry , Bridged Bicyclo Compounds/therapeutic use , Cyclooctanes/chemistry , Cyclooctanes/therapeutic use , Drug Synergism , Lung/drug effects , Lung/microbiology , Mice , Octanes/chemistry , Octanes/therapeutic use , Peritonitis/drug therapy , Peritonitis/microbiology , Piperidines/chemistry , Piperidines/therapeutic use , beta-Lactamase Inhibitors/chemistry , beta-Lactamase Inhibitors/therapeutic useABSTRACT
A series of novel azobicyclo[3.3.0]octane derivatives were synthesized and evaluated as dipeptidyl peptidase 4 (DPP-4) inhibitors. The effort resulted in the discovery of inhibitor 2a, which exhibited excellent efficacies in an oral glucose tolerance test. Introduction of methyl group (2j) could prolong the inhibition of serum DPP-4 activity.
Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Dipeptidyl-Peptidase IV Inhibitors/chemical synthesis , Hypoglycemic Agents/chemical synthesis , Octanes/chemical synthesis , Octanes/therapeutic use , Animals , Azo Compounds/chemical synthesis , Bridged Bicyclo Compounds/chemical synthesis , Dipeptidyl Peptidase 4/blood , Dipeptidyl Peptidase 4/metabolism , Dipeptidyl-Peptidase IV Inhibitors/pharmacology , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Glucose Tolerance Test , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/therapeutic use , Mice , Mice, Inbred ICR , Octanes/pharmacology , Pharmacokinetics , Rats , Rats, Sprague-Dawley , Structure-Activity RelationshipABSTRACT
PURPOSE: To describe a solvent that removes silicone oil adhesions on intraocular lenses (IOLs). METHOD: The solvent O44 is a partially fluorinated alcane that dissolves silicone oil. Silicone oil adhesions on silicone and poly(methyl methacrylate) IOLs were treated with O44. The extent of silicone oil adhesions and the effectiveness of O44 were studied by gross microscopy. RESULTS: The solvent O44 removed silicone oil adhesions from both IOL types. CONCLUSION: The substance O44 may be a successful intraoperative tool to remove silicone oil IOL adhesions, avoiding IOL explantation.
