Enhancement effect of ethanol on lipopolysaccharide-induced procoagulant status in human umbilical endothelial cells.

In spite of the inhibitory effects of ethanol (EtOH) on platelet function, soft blood clots are often observed in cadaveric blood in cases of sudden death after alcohol ingestion. In order to resolve this discrepancy, we have focused on the role of vascular endothelial cells. We tried to investigate the effects of EtOH and LPS on endothelial cells from various perspectives; thrombogenic factor (Von Willebrand factor, VWF), fibrinolytic factor (tissue plasminogen activator, tPA) and inflammatory factor (Interleukin-6, IL-6). Human umbilical vein endothelial cells (HUVECs) were incubated with various concentrations of EtOH (0-160 mM) with or without LPS. Treatment with EtOH and LPS increased VWF release from HUVECs without enhancement mRNA expression. Treatment with 40 mM of EtOH also increased IL-6 release from HUVECs without enhancement mRNA expression. Although EtOH inhibited LPS-induced IL-6 mRNA expression, 20 mM of EtOH still had an increasing effect on the release of IL-6. These doses of EtOH are consistent with a moderate drunkenness level in a normal person. On the other hand, mRNA expression and release reaction of tPA were not affected by EtOH and LPS addition. In conclusion, EtOH enhances procoagulant status via VWF release and IL-6 production cooperation with LPS and may contribute to soft blood clot formation in cadaveric blood.

Analysis of the tracheal contents using headspace gas chromatography-mass spectrometry to screen for accelerant use.

We describe here the usefulness of analysis of tracheal contents in a case of death by fire, which revealed that the deceased had used the accelerants. The analysis of tracheal contents provides useful information for the determination of the circumstances of the scene.

An autopsy case of poisoning with ethanol and psychotropic drugs.

A case of fatal poisoning involving ethanol with psychotropic drugs is presented. Quantitative toxicological analysis showed that the concentrations of ethanol, amoxapine and phenobarbital in the femoral blood were 2.86 mg/ml, 0.41 microg/ml and 6.80 microg/ml, respectively. We concluded that the cause of death was due to the combination use of ethanol, amoxapine and phenobarbital.

Forensic toxicological implication of an autopsy case of mixed drug overdose involving clomipramine, chlorpromazine and flunitrazepam.

A case of fatal poisoning involving clomipramine, chlorpromazine and flunitrazepam is presented. Quantitative toxicological analysis showed that the concentrations of clomipramine, chlorpromazine and 7-aminoflunitrazepam (a metabolite of flunitrazepam) in the femoral blood were 3.24 microg/ml, 0.36 Kg/ml and 0.61 microg/ml, respectively, and large amounts of drugs were also detected from the stomach contents. We concluded that the cause of death was due to the combined use of clomipramine, chlorpromazine and flunitrazepam.

Antitumor effects of inhibitors of nitric oxide synthase or cyclooxygenase-2 on human KB carcinoma cells overexpressing COX-2.

Inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 are major inflammatory mediators. Nitric oxide (NO) produced by iNOS has been shown to have an important role in carcinogenesis. Recent studies have suggested that COX-2 expression also contributes to carcinogenesis, as well as tumor growth, invasion, and metastasis. COX-2 inhibitors such as celecoxib are widely recognized to have antitumor activity, but can cause adverse effects. We investigated possible relations between COX-2 and NO with the use of a human epidermoid carcinoma cell line, designated KB, in which overexpression of COX-2 protein was induced by gene transfer. We also assessed the possibility of using NOS inhibitor as an antitumor drug. We isolated a COX-2 transfected clone (KB/COX-2) and used a neomycin-transfected clone (KB/neo) as control. NG-nitro-L-arginine-methyl ester (L-NAME) was used as a NOS inhibitor, dihydrochloride (1400W) as an iNOS inhibitor, and celecoxib as a selective COX-2 inhibitor. All agents inhibited the cell growth of both clones to similar extents in a dose-dependent manner. Prostaglandin E2 (PGE2) production and COX-2 expression in KB/COX-2 were inhibited not only by celecoxib, but also by L-NAME and 1400W. The decreases in PGE2 production and COX-2 expression were most prominent with celecoxib and L-NAME. In vivo, L-NAME and celecoxib significantly inhibited the proliferation of KB/COX-2-xenografted tumors. Tumor weight was reduced by L-NAME (60.6% decrease), 1400W (38.0% decrease), and celecoxib (74.5% decrease) as compared with the control after 21 days of treatment. Immunohistochemically, xenografted tumors expressed COX-2, iNOS, and eNOS. Such expression was suppressed by treatment with L-NAME and celecoxib. These results suggest that L-NAME and celecoxib significantly inhibit the proliferation of murine squamous cell carcinoma in vivo. L-NAME as well as celecoxib might thus be useful for the design and development of new antitumor drugs.

Application of energy dispersive X-ray fluorescent spectrometry (EDXRF) in drug-related cases.

We applied here energy dispersive X-ray fluorescent spectrometry (EDXRF) to two medico-legal autopsy cases of bromvalerylurea ingestion. Rapid elemental analysis using EDXRF identified bromide in blood, urine and stomach contents of victims during autopsy. The present cases indicate that screening with EDXRF, an instrument suitable for non-destructive, rapid elemental analysis, provides useful information for identification of drugs.

An autopsy case of asthmatic death--usefulness of biochemical examination.

BACKGROUND: Asthma is the one of the major causes of sudden death in Japan. Postmortem diagnosis of asthma has been based on morphological findings in lungs, but it histological evidence, was also reported that the biochemical markers such as total and specific immunoglobulin E (IgE) are useful. CASE REPORT: We present here a case of fatal asthmatic death. A Japanese male in his thirties, complaining of dyspnea, collapsed suddenly. He was taken by ambulance to hospital, but cardiopulmonary resuscitation was ineffective. From autopsy findings, we concluded that the cause of death was asphyxia due to asthma attack. Biochemical findings indicated that the deceased had a severe asthmatic condition. CONCLUSION: In the presented case, the biochemical examination of the serum obtained at autopsy gave helpful information for the diagnosis that asthmatic attack was a cause of death.