Early ECMO initiation in the emergency department for refractory hypoxemic respiratory failure caused by NaDCC intoxication.

We describe a case of acute respiratory failure caused by inhalation of gas formed from a reaction of intentional dissolution of sodium dichloroisocyanurate (NaDCC) tablets in water. A patient had refractory respiratory failure despite the use of conventional therapy, including lung-protective mechanical ventilation. Early veno-venous extracorporeal membrane oxygenation (VV-ECMO) support was initiated in the emergency department (ED). The patient was weaned from ECMO on hospital day 6 and discharged from the ICU on hospital day 27. Cases of severe inhalation injury with acute respiratory failure refractory to conventional treatments and mechanical ventilator support may benefit from VV-ECMO. Literature on early initiation of ED-VV-ECMO in NaDCC-induced refractory respiratory failure is rare. This case may be used as a guide in the management of subsequent cases as it shows that early initiation of ED-VV-ECMO was beneficial to the patient.

Analysis of rocuronium in human whole blood and tissues using liquid chromatography-tandem mass spectrometry.

A rapid, accurate and sensitive liquid chromatography-tandem mass spectrometry method has been developed for the determination of a quaternary nitrogen muscle relaxant, rocuronium, in human blood. The procedure involves protein precipitation with chloroform and trichloroacetic acid, and purification using methanol. The chromatography was performed using a phenyl-hexyl column (150 × 2.0 mm i.d., 3 µm; Phenomenex) with a mobile phase consisting of 5 mM ammonium formate (pH 3.0) and acetonitrile. Multiple reaction monitoring was used for quantification. The assay was linear over a concentration range of 4-500 ng/mL for rocuronium with R(2) ≥ 0.998. The recoveries for this compound ranged from 96.0 to 109.1%. The intra-day and inter-day precision was less than 10.5% and the accuracy ranged from 106.6 to 114.9%. The validated method was applied to quantify the content of rocuronium in blood and a variety of tissues of a victim suspected of overdose. In conclusion, the method was successfully applied for the analysis of rocuronium in biological samples for forensic toxicology.

The identification of ingested dandelion juice in gastric contents of a deceased person by direct sequencing and GC-MS methods.

DNA and chemical analysis of gastric contents of a deceased person were handled in this work. The body of the victim was discovered in his car, submerged in a lake. We were asked to determine whether or not the gastric contents of the victim harbored drugs and dandelion material. It was suspected that the victim had been murdered by poisoning with an excess amount of sleeping medication (doxylamine), which had been homogenized with dandelion. The concentrations of 11.4 and 27.5 mg/kg of doxylamine detected from spleen and liver of the victim were far higher than the assumed therapeutic concentration. Via gas chromatography-mass spectrometry (GC-MS) analysis and direct sequencing analysis of plant genetic markers such as intergenic transcribed spacer, 18S ribosomal RNA (rRNA), rbcL and trnLF, it was confirmed that the gastric contents of the victim contained taraxasterol, which is one of the marker compounds for dandelion and contained dandelion species-specific rbcL and trnL-trnF IGS (trnLF) sequences. The initial PCR of the genomic DNA isolated from the gastric contents showed insufficient quantity, and the second PCR, of which the template was a portion of the initial PCR products, exhibited a sufficient quantity for direct sequencing. rbcL and trnLF located in the cpDNA resulted in the successful determination of dandelion DNA in a decedent's stomach contents. GC-MS identifies the actual presence of a taraxasterol at 28.4 min. Raw dandelion was assumed to be used as a masking vehicle for excess sleeping drug (doxylamine).

Simultaneous analysis of d-3-methoxy-17-methylmorphinan and l-3-methoxy-17-methylmorphinan by high pressure liquid chromatography equipped with PDA.

d-3-Methoxy-17-methylmorphinan (Dextromethorphan, DXM), which is a structural analog of morphine and codeine, has been widely used as a non-narcotic antitussive agent. It is a safe drug in therapeutic dose and does not produce analgesic effects, while its enantiomer, l-3-methoxy-17-methylmorphinan called levomethorphan (LXM) is a potent narcotic analgesic. DXM has been widely abused in Korea due to its hallucinogenic effect in large doses; therefore, the health authorities have regulated its use as a psychotropic agent since 2003. As its abuse has been serious, a possibility that DXM would be smuggled into Korea has also increased. Moreover, it has been suspected that there was the possibility of the adulteration or substitution of DXM with LXM due to their chemical similarities. Therefore, it was necessary for us to establish the enantiomeric separation of DXM and LXM. In this study, a liquid chromatographic method using a chiral column capable of separating stereoisomers of DXM as well as analyzing the major metabolites of DXM, 3-methoxymorphinan, 3-hydroxymorphinan, and 17-hydroxymethylmorphinan was developed. The validation of a method was studied through repeatability of retention times. Using this method, 32 confiscated DXM samples were analyzed to identify the enantiomers of DXM. As a result, DXM was detected in all samples and there was no evidence of the adulteration or substitution of DXM with LXM. Nevertheless, the stereochemical analysis of DXM and LXM is important not only to identify starting materials for illegal drug manufacture but also to understand the trends of abused drugs.

Caspase-3-dependent apoptosis in vascular smooth muscle cell by proteasome inhibition.

The effects of a number of substances on neointima formation following angioplasty have been investigated in animal models. It was suggested that delivering of proteasome inhibitor to the site of vascular injury would be a potential therapeutic approach in prevention of vascular restenosis. But the mechanisms underlying biologic activities of proteasome inhibition in vascular smooth muscle cells (VSMCs) are largely unknown. We have investigated effects of proteasome inhibition on VSMCs using proteasome inhibitor MG115. MG115 induced apoptotic death in VSMCs as determined by viability, morphology, and DNA fragmentation. Proteasome inhibition was accompanied by up-regulation of p53, p21, and p27. In contrast, there were no appreciable alterations in the levels of Bcl-2 and Bax. Proteasome inhibition was followed by activation of caspase-3 but not of -8. The induction of apoptosis was suppressed by treatment with a selective inhibitor of the caspase-3 family, z-DEVD-fmk but not by NG-monomethyl-L-arginine. These results indicate that proteasome inhibition induces apoptosis in VSMCs by activation of caspase-3.