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Red imported fire ants, Solenopsis invicta Buren (Hymenoptera: Formicidae), which are among the most harmful alien ants, were first detected in Japan in a shipping container from China in May 2017, and continue to enter Japan via this trade pathway. Fumigation is one of the most effective ways to eliminate S. invicta from goods transported in containers. The present study is the first to evaluate the effect of fumigation with allyl isothiocyanate (AITC) against S. invicta. Fumigation using microencapsulated AITC pellets in a gas-barrier bag for 24 h completely killed S. invicta. Furthermore, our fumigation system was able to maintain a high concentration of AITC vapor for at least 13 days. AITC, a naturally occurring compound in wasabi [Eutrema japonicum (Miq.) Koidz], has been demonstrated to be safe for humans and the environment, but its use as a fumigant is limited by its strong volatility and pungency. However, its encapsulation solves this problem by allowing controlled vapor release. Thus, the use of microencapsulated AITC in combination with a gas-barrier bag has considerable potential to provide an effective and easy-to-use protocol for fumigation of S. invicta.

Sea container has been identified as a major pathway for the unintended entry and spread of alien ant species. In Japan, red imported fire ants, Solenopsis invicta Buren (Hymenoptera: Formicidae), which are among the most harmful alien ants, were first detected in a shipping container from China in May 2017, and the invasion into Japan via the trade pathway is still continuing. To prevent containers contaminated with S. invicta and its establishment in Japan, control measures, such as repellents, are urgently required. The present study is the first to evaluate repellency of microencapsulated allyl isothiocyanate (AITC) against S. invicta, as a preliminary step to use the innovative equipment for invasive species management in sea containers. In a field in Taiwan heavily infested with S. invicta, a repellent test of microencapsulated AITC using bait traps showed that the equipment completely prevents S. invicta from accessing the bait. Due to its volatility and irritancy, AITC, a safe natural repellant in wasabi (Eutrema japonicum (Miq.) Kiudz), has not been used for pest management in containerized cargo. However, the encapsulation of AITC solves this problem by allowing controlled vapor release. Microencapsulated AITC has considerable potential as an effective measure to stop the spread of S. invicta through global trade.

For the purpose of application for structural members such as the automobile, effect of carbon modification to the AZ91D magnesium alloy chip surface on fatigue property was examined by the rotary bending test. The carbon modification to the chip surface was quite useful for the control of the internal defect for the thick part on the thixomolding process. The depression of the internal defect by the carbon nanoparticle modification is closely related to the improvement of flowability, and that is presumed to be based on promoting the filling of the molten metal into the metal die inside. The tensile strength and elongation were respectively improved by the carbon addition. In addition, the fatigue strength also improved over 15%. This improvement of the mechanical property is based on the refinement of the crystal grain as well as the depression of the internal defects.

Solubility of flavone, 6-methoxyflavone and anthracene in supercritical CO 2 with an ethanol co-solvent ranging from 0.05 to 0.40 were measured at 333 K and 22.0 MPa. Solubility of each compound increased with increasing mole fraction of ethanol. Solubility data were correlated with Chrastil equation considering a relationship between fluid density and solubility and compared with newly proposed relations that use an entropy-based solubility parameter (SSP). Among proposed relations, one relation taking temperature dependence into consideration, that included two fitting parameters had absolute relative deviation (ARD) of 3.9% compared to the experimental data and were much more reliable than a relation not taking temperature dependence into consideration within ARD of 7.6%. The expression similar to Chrastil model that included three fitting parameters and considered SSP was the best ARD within 3.6% among the proposed relations. From these correlation results, the SSP can be applied to determine the solubility of substances at high pressure with multicomponent solvent mixtures.

Background and Aim An intention-to-treat prospective randomized study was carried out to compare the potentiation of antiviral efficacies between cholecalciferol, non-activated vitamin D3 supplement, and alfacalcidol, activated 1α-Hydroxyvitamin D3 [1α (OH)-vitamin D3]. Methods Chronic hepatitis patients with genotype 1b hepatitis C virus (HCV) infection showing serum HCV-RNA levels greater than 5 Log IU/mL received oral administration of cholecalciferol (2000 IU/day) or alfacalcidol (0.5 μg/day) for 4 weeks, and then they were given pegylated interferon (Peg-IFN)-α2a plus ribavirin therapy in combination with either vitamin D3 for 48 or 72 weeks according to the response-guided manner. Results A total of 36 patients were evaluated. Serum 25-hydroxyvitamin D3 [25(OH)-D3] levels were increased only in patients in the cholecalciferol group during the lead-in vitamin D administration, and the levels at 4 weeks were higher in these patients than in those in the alfacalcidol group (P

Aim To optimize the therapeutic efficacy of NS3/4A protease inhibitors, a multicenter prospective study was performed according to an algorithm based on the Adherence, IL-28B Gene Allele and Viral Response Trial (AG & RGT). Methods A total of 340 patients with genotype 1b hepatitis C virus (HCV) showing serum RNA levels of >5 log were enrolled. The duration of ribavirin/pegylated interferon (PEG IFN)-α-2b therapy was prolonged to 48 weeks in patients with unfavorable IL28B alleles showing adherence rates of less than 80% for either drug during the first 12 weeks even if RVR had been achieved, and in those in whom cEVR, but not RVR, was achieved; furthermore, to 72 weeks in those showing partial early viral response. Results The therapeutic outcomes were assessed in 282 patients, and the therapy was set to complete at 24 weeks in 181 patients (64%) and to prolong to 48 weeks or 72 weeks in 71 patients (25%). The former group showed a SVR rate of 84%, while the latter group showed an SVR rate of 69% with a relapse rate of 7%. The SVR rate was 33% in the 30 patients (11%) in whom the therapy had to be discontinued in less than 12 weeks. Thus, the results of intention-to-treat analysis revealed an overall SVR rate of 75%. Multivariate analysis identified prolongation of the duration of therapy as a significant factor associated with SVR. Conclusion Triple therapy yielded a high SVR rate in the AG & RGT trial via attenuation of viral relapse by prolonged ribavirin/PEG IFN-α-2b administration. © 2015 The Japan Society of Hepatology

Pristine topological insulators (TIs) with no carrier doping principally suffer from a lack of magnetic ordering. We create a nanomesh structure, a honeycomblike array of hexagonal nanopores with extremely high density, on a nondoped two-dimensional (2D) thin TI (Bi2Te3). We observe antiferromagnetism (AFM) in completely hydrogen-terminated nanomeshes, while it is eliminated by ferromagnetism (FM) in completely O-terminated nanomeshes. Interplay between the AFM and FM is observed in partially O-terminated nanomeshes. As a possible origin for the observed magnetisms, Kramers doublets, which may exist around nanopore edges, for AFM and those eliminated by FM spin alignment due to O-Te coupling along pore edges are discussed based on the structure and annealing dependence of the magnetisms. The nondoped 2D nanomesh formed on a TI will lead to new avenues of research on topological magnetisms and spintronics.

Although postmortem production of γ-hydroxybutyric acid (GHB) has been confirmed, its production pathways and substrates have not been sufficiently clarified. To confirm that the residual enzymes are involved in GHB production during the early postmortem period, endogenous GHB concentrations in the postmortem blood and liver samples obtained from charred cadavers were compared with those from noncharred cadavers within 50 h after death. The endogenous GHB concentrations in blood and the livers of charred cadavers were significantly lower than those of noncharred cadavers, showing that heat denaturation of enzyme proteins had prevented the postmortem GHB production. In addition, in vitro experiments with rabbit liver homogenates were carried out for inhibition of postmortem GHB production by specific enzyme inhibitors; N-formylglycine (succinic semialdehyde dehydrogenase inhibitor), valproic acid [γ-aminobutyric acid (GABA) aminotransferase inhibitor], pyrazole (alcohol dehydrogenase inhibitor), or N,N-diethyldithiocarbamic acid (aldehyde dehydrogenase inhibitor) was added and incubated, and the inhibition of GHB production was then measured. The results showed that the inhibition ratios by N-formylglycine, valproic acid, and pyrazole were 74.0%, 10.4%, and 17.7%, respectively. This suggests that the contribution ratios of the GHB-producing pathways originating from succinic acid, GABA/putrescine, and 1,4-butanediol are about 70%, 10%, and 20%, respectively.

To investigate the effect of oxidative stress on the survival of two Brachionus species of rotifer, we examined the effective dose of juglone, which generates reactive oxygen species, and compared survival times between the two species. First, we observed that juglone affected survival in the rotifers in a dose-dependent manner between 0.02 to 20 μM, and that treatment at above 2 μM showed acute toxicity causing the animals to die within a few hours. Next, we found the difference in survival time between the two species exposed to 20 μM juglone: B. rotundiformis was significantly more tolerant against the substance than the allied species B. plicatilis. The findings suggest that exploring the basis of species-specific abilities to persist under oxidative stress will be of great interest to uncover the underlying mechanisms governing the stress resistance of the rotifer, as well as contributing to their stable mass production for aquaculture.

Cigarette smoking is associated with a higher risk for suicide. The present study was conducted on the hypothesis that suicide smokers show higher nicotine and cotinine levels in blood and urine than non-suicide smokers. We determined nicotine and cotinine levels in blood and urine of 87 deceased individuals (18 suicides and 69 non-suicides) by gas chromatography. The smoking rate was 77.8% for individuals who committed suicide and 42.0% for those who did not commit suicide. Average nicotine and cotinine levels in blood were significantly higher in the suicide smokers than in the non-suicide smokers (nicotine: 93.2 ± 46.6 ng/ml versus 25.8 ± 14.4 ng/ml, p < 0.0001 and cotinine: 378 ± 235 ng/ml versus 201 ± 137 ng/ml, p < 0.005). Average levels of urinary nicotine and cotinine were also significantly higher in the suicide smokers than in the non-suicide smokers (nicotine: 1980 ± 2210 ng/ml versus 394 ± 376 ng/ml, p < 0.005 and cotinine: 1170 ± 1330 ng/ml versus 414 ± 290 ng/ml, p < 0.05). Twenty-six decedents were intoxicated with alcohol, and they included 7 suicides (7 smokers) and 19 non-suicides (15 smokers). Our data suggest that cigarette smokers who commit suicide smoke more heavily than other cigarette smokers.

We describe a mysterious fatal case of poisoning by fenitrothion of a male adult. No typical external signs of organophosphate poisoning were found; we observed patchy mucosal hemorrhages of the bronchi and slight parenchymal hemorrhages of the lower lobe of the left lung at autopsy. The stomach contained 10 g of a faintly purplish/reddish viscous fluid with no chemical smell. Gas chromatography and gas chromatography-mass spectrometry analyses of blood specimens revealed substantial amounts of fenitrothion. The concentrations in cerebrospinal fluid, vitreous humor, and urine are also presented. We concluded that the victim probably died of delayed respiratory insufficiency caused by acute fenitrothion poisoning.

We have observed hysteretic behavior of magnetoresistance with slow dynamics in a GaAs/AlGaAs two-dimensional hole system (2DHS) in quantum Hall regime. The relaxation towards the stable state exhibits a distinct change in behaviour between the filling ranges ν > 1 and ν < 1, suggesting a spin-related mechanism. The relaxation time scale on the order of an hour was observed at the lowest temperature. (© 2006 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

THz radiation emission from GaMnAs samples grown on (001) GaAs substrates is observed in a transmission configuration in a direction normal to the surface. The samples are excited with pump pulses having a 400 nm center wavelength. The radiation is only observed in the presence of a ferromagnetic phase and increases with the sample magnetization. The THz emission is explained by the strong influence of the magnetization on the photogenerated carrier acceleration path. (© 2006 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

Apolipoprotein (apo) E plays a key role in lipoprotein metabolism and has been proposed to modulate triglyceride (TG) lipolysis. However, no systematic investigation on lipolysis using all 3 isoforms of apoE has been performed. To clarify the role of common human apoE isoforms in the lipolysis of very low-density lipoprotein (VLDL) TGs, we overexpressed human apoE isoforms in apoE and low-density lipoprotein receptor-deficient mice using adenoviral-mediated gene transfer and used VLDL particles obtained from these mice for in vitro lipolysis assay. Overexpression of apoE, regardless of its isoforms, increased the TG content of VLDL in mice in vivo. In vitro analysis of the effect of apoE on lipolysis revealed that irrespective of its isoforms, apoE did inhibit TG lipolysis at every concentration of apoE examined, and this inhibitory effect became more pronounced as the apoE content of VLDL increased. No difference was observed in TG lipolysis activity among isoforms at low apoE/TG ratio; however, intermediate ratios of apoE/TG, which reflect physiologic VLDL apoE/TG ratios, demonstrated a significantly greater level of lipolysis inhibition in apoE2, but less so in apoE4 compared with other isoforms. This differential effect by apoE isoforms on lipolysis was attenuated at higher apoE/TG ratios; nevertheless, apoE2 still inhibited lipolysis significantly more than did apoE4. Enrichment of VLDL with apoE decreased both the apoC contents and apoC-II/C-III ratios of VLDL, contributing, at least in part, to the inhibitory function of apoE on lipolysis. The present study clarifies the differential lipolysis-modulating effect of apoE isoforms, which would help explain the difference in pre- and postprandial TG levels among humans carrying different apoE isoforms.

The goal of this study was to determine how the postmortem interval and duration of storage of blood at 4 degrees C affect endogenous gamma-hydroxybutyric acid (GHB) levels in blood. Forty-three autopsy cases of non-users of GHB were involved. The postmortem interval ranged from 8 to 132 h. Blood samples were collected and stored without any preservatives at 4 degrees C for 1 day up to 15 months until analysis. In some cases, samples were also stored at -20 degrees C for 10 days to 7 months to determine GHB levels at autopsy. Blood GHB concentrations were measured by headspace gas chromatography after GHB was converted to gamma-butyrolactone. Blood GHB concentrations ranged from 0 to 43.0 microg/ml and averaged 9.80 microg/ml. A positive correlation was observed between concentration and postmortem interval (r = 0.571) but no correlation was found between concentration and storage interval at 4 degrees C. In 14 blood samples stored at -20 and 4 degrees C for 10 days, GHB concentrations were 4.55+/-3.88 and 6.06+/-4.27 microg/ml, respectively. In another eight blood samples stored at -20 and 4 degrees C for 1-7 months, GHB concentrations were 3.77+/-2.76 and 5.49+/-2.97 microg/ml, respectively. A large portion of endogenous GHB detected in blood of corpses may be produced during the interval between death and autopsy, rather than during storage of blood at 4 degrees C until analysis. In an additional experiment, it was suggested that glycolysis by bacteria may enhance endogenous GHB production.

Probucol, an antioxidative and hypolipidemic agent, has been postulated to increase reverse cholesterol transport by enhancing cholesteryl ester transfer protein (CETP) activity. However, its clinical implication in CETP deficient patients has not been fully defined. To characterize the effects of probucol in the absence of CETP, we evaluated the changes in lipid profile, lipid peroxidation, and paraoxonase 1 (PON1) activity in two complete CETP deficient patients, caused by treatment with probucol. When the patients were not receiving probucol, low-density lipoprotein (LDL) particles were smaller and high-density lipoprotein (HDL) particles were larger in these patients than in controls. Treatment with probucol (500 mg/day) resulted in the decrease in the levels of HDL-C and apolipoprotein (apo) A-I up to 22%. The size of HDL particles became smaller. LDL cholesterol concentration did not change in one patient, while it decreased by 47% in the other. PON1 activity/HDL-C, which was about 40% lower in the patients before treatment than in controls with the matching PON1 genotype, increased by 30% during the treatment. Lag time for LDL and HDL in both cases became prolonged more than 1.8 times after administration of probucol. This study demonstrated for the first time that probucol reduces HDL-C even in humans with complete CETP deficiency. Probucol treatment in these patients was also associated with protection of lipoproteins against oxidative stress, suggesting a clinical benefit of this drug even in such a state.

Objective— Plasma platelet-activating factor (PAF) acetylhydrolase (AH) is an enzyme bound with lipoproteins that degrades not only PAF but also PAF-like oxidized phospholipids that are proposed to promote atherosclerosis. In this study, we investigated the distribution of PAF-AH protein among lipoprotein classes by using adenovirus-mediated gene transfer in mice, and we examined its effects on lipoprotein oxidation and foam cell formation of macrophages. Methods and Results— Adenovirus-mediated overexpression of PAF-AH in mice resulted in a 76- to 140-fold increase in plasma PAF-AH activity. Contrary to the previous report, overexpressed human PAF-AH protein was bound to very low density lipoprotein, intermediate density lipoprotein, low density lipoprotein, and high density lipoprotein (HDL). All the lipoproteins with overexpressed human PAF-AH revealed more resistance against oxidative stress, which was associated with lower levels in autoantibody against oxidized low density lipoprotein in the plasma. In addition, HDL with human PAF-AH inhibited foam cell formation and facilitated cholesterol efflux in macrophages. Conclusions— These results suggest that human plasma PAF-AH exerts an antiatherogenic effect by binding to all the lipoproteins and thereby protecting them from oxidation, producing less proatherogenic lipoproteins and preserving HDL functions.

Objective— Apolipoprotein E (apoE) mediates cellular cholesterol efflux and plays a crucial role in the inhibition of atherogenesis. We investigated whether there is an isoform-specific difference in its function for cholesterol efflux from cholesterol-loaded RAW264.7 cells, a murine macrophage cell line that lacks endogenous apoE expression. Methods and Results— When human apoE was expressed in RAW264.7 cells, apoE2 reduced cellular total cholesterol (TC) and esterified cholesterol (EC) levels significantly, whereas apoE3 and apoE4 had no effect. However, treatment of cells with 4-methylumbelliferyl-7-β- d -xyloside (β-DX) resulted in all 3 isoforms’ reducing cellular TC and EC contents significantly. We also investigated the effect of exogenously derived apoE on cholesterol efflux by utilizing the medium harvested from HeLa cells expressing apoE. ApoE2 and E3 reduced both cellular TC and EC contents significantly, whereas apoE4 did not. However, treatment of the cells with β-DX resulted in all 3 exogenously derived apoE isoforms’ reducing TC and EC contents significantly. The binding ability of apoE to heparan sulfate proteoglycans examined by heparinase I treatment revealed less binding ability of apoE2 compared with that of apoE3 or apoE4. Conclusions— The present study clarified the differential cellular cholesterol-modulating effect of apoE isoforms in macrophages, which would be due to the difference in their binding to proteoglycans.

Detailed measurement of transport very close to two metal–insulator critical points in a diluted magnetic semiconductor (Ga, Mn)As is reported. The first metal–insulator transition (MIT) at the dilute-side of the metallic phase is associated with the appearance of the ferromagnetism and the effect of correlation between the electrons (holes) cannot be ignored. On the other hand, the second MIT at higher concentration is purely driven by disorder and disorder-modified Coulomb interaction. It is shown experimentally that the difference in the characters of these two MITs clearly appears in the width of region in which two-parameter scaling works well. This result gives an important suggestion to the long-debated ‘exponent puzzle’ in the MIT of doped semiconductors.

Low-temperature annealing after molecular-beam epitaxial growth of III–V-based diluted magnetic semiconductors, (Ga,Mn)As and (In,Mn)As have been found to improve the crystallinity of the films. That is, the Curie temperature and the conductivity are greatly enhanced. This effect is probably due to the removal of excess As atoms which passivate doped Mn acceptors. The present method provides a way for carrying out reproducible systematic studies of these materials.

We evaluated the synergistic effect of zinc supplementation on the response to interferon (IFN) therapy in patients with intractable chronic hepatitis C in a pilot study using natural IFN-alpha with or without zinc. No clinical differences were observed between patients treated with IFN alone (n=40) and IFN with polaprezinc (IFN + Zn, n=35). All patients were positive for HCV genotype Ib and had more than 105 copies of the virus/mL serum. Ten million units of natural IFN-alpha was administered daily for 4 weeks followed by the same dose every other day for 20 weeks. In the IFN + Zn group, patients received an additional dose of 150 mg/day polaprezinc orally throughout the 24-week IFN course. No additional side-effects of polaprezinc were noted but four out of 40 IFN alone treatment and three out of 35 IFN + Zn group withdrew because of side-effects. Complete response (CR) was defined as negative HCV RNA in the serum on PCR and normal aminotransferase level 6 months after therapy. Incomplete response (IR) was normal liver enzyme and positive serum HCV RNA. Both of them were evaluated at the 6 months after the completion of the treatment. Patients with higher levels of serum HCV (more than 5 x 105 copies/mL) had little response in both treatment groups. Patients with moderate amount of HCV (105 to 4.99 x 105/mL) showed high response rates in combination group (CR: 11/27, 40.7%; CR + IR 15/27, 64.3%), better than IFN alone (CR: 2/15, 18.2%; CR + IR: 2/15, 18.2%). Serum zinc levels were higher in patients with IFN + Zn group than in the IFN group. Our results indicate that zinc supplementation enhances the response to interferon therapy in patients with intractable chronic hepatitis C.

A rapid and accurate method, combining solid-phase extraction and second-order derivative spectrophotomety approaches, is developed for the simultaneous determination of diquat (DQ) and paraquat (PQ) in blood, tissue and urine samples. Supernatant resulting from the precipitation of protein (with trichloroacetic acid) in plasma and tissue or Amberlite IRA-401 resin treated urine are passed through a mini-column packed with Wakogel gel (Silica gel). Analytes are then eluted with a non-organic solvent, 0.2mol/l HCl solution containing 2mol/l NH(4)Cl. UV spectrum of the eluent in 220-350nm range provides effective screen to detect the presence of DQ and/or PQ. In the presence of DQ or PQ alone, the analyte present is quantitated by conventional zero- or second-order derivative spectrophotometry. The calibration curve in the 0.1-5.0mg/l range for either analyte obeys Beer's law. When both DQ and PQ are present, their concentrations are determined by the peak amplitudes of their respective second-derivative spectra after the addition of alkaline dithionite reagent. Interference is negligible when the DQ/PQ concentration ratio is within the 5.0-0.2 range. Using a 2-ml of sample size, the detection limits for DQ and PQ in plasma are 0.02 and 0.005mg/l. The corresponding detection limits for urine samples (10ml sample size) are 0.004 and 0.001mg/l. Recoveries of DQ and PQ in triplicate plasma and urine samples spiked with 0.5mg/l of analytes are 93 and 85%. The precision of the proposed method resulting from triplicate study of spiked urine samples varies from 3.2 to 4.6% at 0.5mg/l of DQ and PQ, respectively.

A cross-sectional study was conducted in 3660 male workers to examine whether the weekly frequency of alcohol intake affected serum lipids and blood pressure, which are risk factors for coronary heart disease, independently of the weekly alcohol consumption. Information regarding life-style habits and current medication was obtained by questionnaire. The effects of the frequency were examined using Tukey's test in the groups of drinkers divided according to their alcohol consumption. In moderate (189–377 ml/week) drinkers, a higher frequency of drinking was related to a higher level of HDL-cholesterol, and a lower level of triglycerides. In light (1–188 ml/week) and heavy (378–566 ml/week) drinkers, a higher frequency of drinking was also related to a higher level of HDL-cholesterol. There were no significant relations between the frequency of drinking and total cholesterol, or blood pressure in these three groups. Similar results were obtained when values were adjusted for age, body-mass index, smoking, physical activity and weekly alcohol consumption. Multiple regression analysis in the whole drinkers also showed that the weekly frequency of drinking was associated with HDL-cholesterol, but not with triglycerides (p = 0.052), total cholesterol, or blood pressure. The results suggest that the weekly frequency of drinking may affect the levels of HDL-cholesterol independently of the weekly alcohol consumption.

Enantiomeric determination of L- and D-lactate in human cerebrospinal fluid (CSF) was achieved by HPLC on a chiral stationary phase with UV detection. Samples were submitted to a solid-phase extraction procedure using Oasis HLB Plus Extraction Cartridge and L- and D-lactate in the extract were separated by Shodex ORpac CRX-453 B column, a ligand exchange column for chiral separation, using a mobile phase containing copper (II) ion. L- and D-lactate were determined in 25 min. Intra-assay precision in CSF was 4.98% (mean 1.85 mmol/L) for L-lactate and 10.1% (mean 4.96 micromol/L) for D-lactate (n = 5). Detection limits were between 1.0 (L-lactate) and 1.5 (D-lactate) pmol. The mean values (n = 3) of analytical recovery for L- and D-lactate were 95% and 107%, respectively. The mean +/- SD of concentrations of L- and D-lactate in CSF (n = 20) were 1.52 +/- 0.54 mmol/L and 10.98 +/- 5.15 micromol/L, respectively.

We have measured concentrations of morphine, codeine and 6-monoacetylmorphine in urine of people admitted to the Los Angeles County + University of Southern California Medical Center. Of 60 patients positive for morphine and/or codeine, 10 were judged to be heroin abusers based on positive results for 6-monoacetylmorphine, a specific metabolite of heroin. In nine of these ten patients, 0.028-39.4 microg/ml free codeine and 0.070-307 microg/ml total codeine were detected along with 1.74-218 microg/ml of free morphine and 11.2-2870 microg/ml of total morphine; the morphine-to-codeine ratios were 3.65-228 and 2.27-207 for the free forms and total amounts of these opiates, respectively. In the one patient who was negative for codeine, the concentrations of free and total morphine were 0.114 and 2.22 microg/ml, respectively. Based on our data and literature data available, the following criteria are proposed for judging heroin use from the results of urinalysis, especially when no 6-monoacetylmorphine is detected: (1) a detectable amount of free morphine exists and the concentration of total morphine is higher than 10 microg/ml; (2) a detectable amount of codeine exists; and (3) the morphine-to-codeine ratio is higher than 2 for both the free forms and total amounts of these opiates.

This paper describes the tissue distributions of dichlorvos, an organophosphate, and chlorpyrifos-methyl, an organophosphorothioate, in a male individual who died after ingesting an insecticidal preparation containing these chemicals and the results of an in vitro stability study on dichlorvos and chlorpyrifos-methyl in blood and buffers. Tiny amounts of dichlorvos, 0.067 and 0.027 mg/L, were detected in the vitreous humor and cerebrospinal fluid, respectively. Although dichlorvos (0.082-8.99 mg/L or mg/kg) was detected in the thoracic aortic blood, thoracic inferior vena caval blood, pericardial fluid, bile, and spleen, it was strongly suggested that it had diffused postmortem from the stomach, which contained 879 mg, because no dichlorvos was detected in the other blood samples and tissues tested. Substantial amounts (0.615-4.15 mg/L) of chlorpyrifos-methyl were detected in all blood samples, and the order of its concentrations was as follows: pulmonary vessel blood > thoracic inferior vena caval blood > blood in the right cardiac chambers > blood in the left cardiac chambers approximately thoracic aortic blood > right femoral venous blood. The total amount of chlorpyrifos-methyl in the stomach was 612 mg. However, it was strongly suggested that virtually no chlorpyrifos-methyl diffused from the stomach into surrounding fluids and tissues postmortem because no chlorpyrifos-methyl was detected in the bile and little was found in the pericardial fluids. Neither compound was detected in the urine. In vitro experiments showed that dichlorvos (10 mg/L) almost disappeared from fresh (pH 7.4) and acidified (pH 6.2) blood samples within 24 and 72 h, respectively. However, 53 and 77% of the original amount of dichlorvos in 0.05M phosphate buffers at pH 7.4 and 6.2 were detected 72 h later. Chlorpyrifos-methyl (1 mg/L) was very stable in blood samples, regardless of the pH, during the 72-h study period, but in the pH 7.4 and 6.2 phosphate buffers, approximately 80% of the original amount had degraded after 72 h. These results indicate that organophosphates are degraded more rapidly by esterase activities than by chemical mechanisms and that organophosphorothioates are hydrolyzed chemically in aqueous solutions but are very stable in biological specimens and not metabolized by esterases. When sodium fluoride was added to blood samples, dichlorvos degraded completely within 15 min, and chlorpyrifos-methyl became very unstable. Thus, when analyzing samples to detect organophosphorus chemicals, this common preservative should not be added to fluid specimens.

Advanced glyco-oxidation end products (AGEs) generate oxygen free radicals that potentiate the development of atherosclerosis. Thus, AGEs may potentiate the aggregation of human platelets through oxidative stress. AGE-bovine serum albumin (BSA) and AGE-poly-L-lysine were evaluated for aggregation of human platelets. Superoxide in platelet-rich plasma (PRP) was measured using lucigenin-derived chemiluminescence. The platelet aggregation induced by ADP or U46619 was potentiated by preincubation with AGE-BSA, by 40% and by 59%, P < .05, respectively, vs BSA. Aggregation was increased by AGEs in a dose-dependent manner. The production of superoxide was significantly greater in PRP incubated with AGE-BSA vs BSA. The other Maillard reaction products, such as Amadori-, pentosidine-, and carboxymethyl lysine (CML)-BSA had no effect. Superoxide dismutase or indomethacin abolished the enhancing effect of AGEs on the platelet aggregation. AGEs potentiate platelet aggregation possibly with superoxide anions and prostanoids. AGE-induced potentiation of platelet aggregation may be involved in the development of atherosclerosis.

We have studies zinc deficiency in hepatitis C patients (complete responder [CR] 22, nonresponder [NR] 25) with relation to the therapeutic effect of interferon-alpha (IFN-alpha). Circadian variations in serum zinc levels were high in the morning (basal level) and then gradually decreased during the day in both chronic hepatitis C patients and healthy controls. Basal zinc levels in serum were significantly lower in chronic hepatitis C patients (73 +/- 3 micrograms/dL, n = 12) than in controls (93 +/- 5 micrograms/dL). An injection of 10 MU of IFN-alpha to hepatitis C patients augmented the serum zinc reductions, up to 40% in 8 h. Serum cortisol levels were significantly elevated 8 h (25.6 +/- 2.3 micrograms/dL) after IFN-alpha dose. Forty-seven chronic hepatitis C patients were treated with IFN-alpha for 24 wk, and serum zinc and copper levels were determined 12 and 24 wk during and after the completion of IFN-alpha therapy. Serum zinc levels and zinc/copper ratio were higher in CRs than in NRs to IFN therapy at each time-point. Hepatic metallothionein staining became prominent after IFN therapy in most of CRs, whereas it diminished NRs. These data suggest that nutritional status of zinc influences the effect of IFN on hepatitis C patients.

To determine the effects of insulin on intracellular calcium and platelet aggregatory responses in hypertensive subjects with insulin resistance, we measured insulin sensitivity in terms of glucose disposal rate (GDR) by the hyperinsulinemic euglycemic clamp technique (GC) in 14 non-diabetic untreated hypertensive subjects, and determined basal ([Ca2+]i) and thrombin-stimulated (T-[Ca2+]i) platelet-free calcium concentrations and thrombin-stimulated platelet aggregatory response (AG) before (PRE[Ca2+]i, T-PRE[Ca2+]i, and PRE AG, respectively) and during (POST[Ca2+]i, T-POST[Ca2+]i, and POST AG, respectively) GC. As a control for GC, vehicle (normal saline) was infused on another day. No significant difference was observed between PRE[Ca2+]i and POST[Ca2+]i, T-PRE[Ca2+]i and T-POST[Ca2+]i, or PRE AG and POST AG, GDR inversely correlated with delta[Ca2+]i (POST [Ca2+]i-PRE[Ca2+]i, r = -0.75, p < 0.02), delta T-[Ca2+]i, (T-POST[Ca2+]i-T-PRE[Ca2+]i, r = -0.63, p < 0.02) and delta AG (POST AG-PRE AG, r = -0.67, p < 0.01). No significant changes were observed in these variables during vehicle infusion. [Ca2+]i, T-[Ca2+]i, and AG decreased during GC as compared with baseline in hypertensive subjects with normal insulin sensitivity, but were unchanged in those with insulin resistance, suggesting that the vasodilatory and anti-platelet aggregatory effects of insulin are impaired in patients with insulin-resistant hypertension.

Among major eicosanoids and their analogs, prostaglandin (PG) F2 alpha > PGD2 > PGE1 > or = PGE2 > iloprost, a stable agonist of PGI2, dose-dependently stimulated DNA synthesis in quiescent NIH-3T3 cells. PGF2 alpha, PGD2, and PGE2, in that order, formed inositol phosphates and elevated intracellular Ca2+ ([Ca2+]i) but did not form cAMP nor inhibit forskolin-induced cAMP formation. Iloprost, PGI2, and PGE1 induced cAMP formation dose dependently with an ED50 of around 10(-7) M, and PGE2 at more than 10(-6) M did it. [3H]PGF2 alpha and [3H]PGD2 bindings membranes from NIH-3T3 cells were displaced in the order of PGF2 alpha > PGD2 > or = PGE2, while [3H]PGE2 binding was displaced by PGE2 > PGD2 > or = PGF2 alpha. Expression of mRNA encoding EP1 and EP4 (EP2) subtypes could be detected by reverse transcription- polymerase chain reaction using primers specific for EP1 and EP4 (EP2) cDNAs, but not that of EP3 subtype mRNA. The dose dependence of cAMP formation on iloprost and PGI2 and that of [Ca2+]i elevation on PGF2 alpha, D2, and E2 were similar to that of [3H]thymidine incorporation on the corresponding agonists. Fluprostenol (1 microM), a PGF2 alpha receptor agonist > 17-phenyl-trinor-PGE2 (1 microM), an EP1 receptor agonist stimulated [3H]thymidine incorporation, but an EP3 receptor agonist, ONO-AP-324 nor an EP4 (EP2) receptor agonist, 11-deoxy-PGE1 (1 microM) did not. Iloprost, dibutyryl cAMP, forskolin, or cholera toxin, when applied alone, enhanced [3H]thymidine incorporation, while they inhibited [3H]thymidine incorporation induced by submaximal concentrations of PGF2 alpha or epidermal growth factor (EGF), when applied within 12 hr after agonist stimulation. These results suggest that the proliferation of NIH-3T3 cells is stimulated by PGs via the PGF2 alpha receptor, EP1 subtype of PGE receptor, and the PGI2/PGE1 receptor through [Ca2+]i- and cAMP-dependent pathways, and that cAMP pathway negatively cross-talks with [Ca2+]i-or receptor tyrosine kinase-mediated DNA synthesis in a cell cycle-dependent manner.

We examined endogenous ethanol and n-propanol levels in the brain in 29 drowning cases in which ethanol consumption was excluded. Based on the stage of putrefaction of the brain, our cases were classified into 4 groups: pulpified brain (PB, n = 11), softened brain (SB, n = 6), discolored brain (DB, n = 2), and normal brain (NB, n = 10). The endogenous ethanol and n-propanol levels (mg/g), respectively, in the brains from these groups were 1.06 +/- 0.401 and 0.076 +/- 0.032 in PB, 0.195 +/- 0.136 and 0.012 +/- 0.009 in SB, and 0.053 +/- 0.032 and 0.001 +/- 0.001 in DB. Ethanol and n-propanol were not detected in NB. The concentration ratios of ethanol to n-propanol were 16.2 +/- 7.1 in specimens with ethanol levels > or = 0.50 mg/g (n = 10), and 17.6 +/- 13.5 in specimens with ethanol levels of 0.10 to 0.49 mg/g (n = 9). Drinking may strongly be suspected when (1) ethanol concentration in the brain is > or = 0.50 mg/g and cerebral ethanol to n-propanol ratio is > or = 40; and (2) the concentration of ethanol is 0.10 to 0.49 mg/g and the ethanol to n-propanol ratio is > or = 60. Language: en

Previously, we characterized the prostaglandin (PG) F2 alpha receptor linked to phospholipase C activation and DNA synthesis in NIH-3T3 cells (Nakao, A., Watanabe, T., Taniguchi, S., Nakamura, M., Honda, Z-I., Shimizu, T., and Kurokawa, K. (1993) J. Cell. Physiol. 155, 257-264). To elucidate intracellular events evoked via this receptor, we examined changes caused by PGF2 alpha stimulation in the phosphotyrosine composition of cellular proteins. The addition of PGF2 alpha to cells in quiescent culture rapidly increased the levels of phosphotyrosine in cellular proteins with Mr values of 70,000 (pp70), 85,000 (pp85), 92,000 (pp92), 100,000 (pp100), and 125,000 (pp125); the latter was immunologically identified as p125 focal adhesion kinase. The PGF2 alpha-induced changes in the level of intracellular Ca2+ ([Ca2+]i) elevation, formation of inositol phosphates, and [3H]thymidine incorporation followed a similar dose dependence as PGF2 alpha-induced tyrosine phosphorylation. This tyrosine phosphorylation was independent of extracellular Ca2+, while a [Ca2+]i chelator, 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (50 microM), completely inhibited the PGF2 alpha-induced elevation of [Ca2+]i, tyrosine phosphorylation, and [3H]thymidine incorporation. Ionomycin (0.1 microM), which induced [Ca2+]i elevation without formation of inositol phosphates, mimicked the PGF2 alpha-induced tyrosine phosphorylation. 12-O-Tetradecanoylphorbol-13-acetate (TPA) also induced [3H]thymidine incorporation in a dose-dependent manner but had no significant effect on tyrosine phosphorylation. The PGF2 alpha-induced tyrosine phosphorylation could be observed even in the cells pretreated with TPA (5 microM, 24 h). PGF2 alpha exhibited an additive effect on TPA-induced [3H]thymidine incorporation but had no effect on the 32P-phosphorylation of a known 80-kDa protein kinase (PK) C substrate. Both staurosporine and H-7 inhibited the PGF2 alpha-induced increase in [3H]thymidine incorporation and tyrosine phosphorylation in a similar dose-dependent manner whether or not cells were pretreated with TPA (5 microM, 24 h). However, W-7 and KN-62 had no effect on these cellular responses even at the concentration for the almost complete inhibition of Ca2+/calmodulin-dependent PKs (20 microM). These results, taken together, indicate that PGF2 alpha receptor-mediated tyrosine phosphorylation is evoked by a [Ca2+]i-dependent mechanism that is sensitive to staurosporine and H-7 but which is independent of PKC or Ca2+/calmodulin PKs. Finally, the data suggest that this PGF2 alpha-induced signaling pathway is linked to the proliferation of cells.

The direct effect of apolipoprotein (apo) E on cholesteryl ester transfer protein (CETP) activity was studied using lipoproteins from a subject with apoE deficiency (Atherosclerosis. 1991. 88: 15-20) as a model system. The transfer of cholesteryl ester (CE) from discoidal bilayer particles (DBP) to very low density lipoprotein (VLDL) was enhanced by incorporation of apoE into VLDL. This enhancement was induced only in the presence of CETP activity. Moreover, after incubation of CETP with VLDL, CETP activity and immunoreactivity were coeluted with apoE-incorporated VLDL (E-VLDL) on a gel filtration column (Sephadex G-150), but there was little CETP activity and immunoreactivity with apoE-free VLDL (C-VLDL), suggesting that E-VLDL had higher affinity for CETP compared to C-VLDL. The supplementation of the apoE-deficient serum with apoE enhanced the CETP-mediated changes of amount of CE and triglyceride (TG) in the high density lipoprotein (HDL) fraction, which were completely inhibited by the addition of the monoclonal antibody against CETP that blocks CETP activity. Our results suggest that 1) apoE enhances the cholesteryl ester and triglyceride transfer between VLDL and HDL via cholesteryl ester transfer protein, and 2) this effect of apoE may be mediated by enhancing the affinity of CETP for VLDL.

We report improvements in the crystallinity of a III–V-based diluted magnetic semiconductor (Ga, Mn)As by heat treatment (annealing) after growth at comparatively low temperatures. This method can be used to raise the Curie temperature to 100 K without the need for severe optimization of growth conditions, as well as to adjust the material parameters to desired values.

We report an autopsy case of postmortem ethanol diffusion into the cardiac blood after aspiration of wood chips, although antemortem ethanol consumption was not evident. A man in his twenties, who was loading a truck with small wood chips in a hot, humid storehouse, was accidentally buried in a heap of chips. At the time the body was discovered, 20h after the accident, rectal temperature was 36°C. Autopsy showed the cause of death to be asphyxia due to obstruction of the airway by aspiration of wood chips. The ethanol and n -propanol levels were significantly higher in the lungs (left, 0.603 and 0.009mg/g; right, 0.571 and 0.006mg/g) than in other tissues. A significant difference in ethanol concentration was observed between the left cardiac blood (0.243mg/g) and the right femoral blood (0.042mg/g). Low levels of ethanol and n -propanol were detected in the stomach contents (0.105 and 0.001mg/g, respectively). In order to determine whether aspiration of wood chips affects postmortem ethanol production in the lung, we measured the ethanol and n -propanol levels of homogenized rabbit lung tissue incubated with autoclaved or non-autoclaved wood chips. Levels of ethanol and n -propanol were significantly higher in the homogenates incubated with non-autoclaved chips for 24h. The results of this animal experiment suggested that the ethanol detected in the lung was produced by putrefactive bacteria within the wood chips. After death, the ethanol produced endogenously in the lung appears to have diffused and affected the ethanol concentration of the left cardiac blood.

The regulation of extracellular Ca2+ entry into fura-2-loaded human platelets was examined following stimulation with thrombin. In the presence of external Ca2+, stimulation of platelets with thrombin resulted in a rapid increase, followed by a plateau, in intracellular Ca2+ concentration ([Ca2+]i). Pretreatment with wortmannin, a specific inhibitor of myosin light chain kinase, suppressed only the plateau phase and had no effect on the initial rapid increase in [Ca2+]i. In Ca(2+)-free EGTA buffer, thrombin induced a transient and relatively small increase in [Ca2+]i caused by Ca2+ release from internal stores. When Ca2+ was added subsequently to the Ca(2+)-free medium within 10 min after thrombin activation, a marked increase in [Ca2+]i was seen, reflecting thrombin-stimulated external Ca2+ entry. With the Ca(2+)-free medium, wortmannin did not affect either the Ca2+ mobilization from the internal stores or the rapid external Ca2+ entry at early time points (within 5 s) after thrombin stimulation, whereas it significantly inhibited Ca2+ entry when Ca2+ was added later (at 3 min). Wortmannin inhibition of this late Ca2+ entry and that of 20-kDa myosin light chain phosphorylation after thrombin stimulation were dose- and preincubation time-dependent and correlated well with each other. These results suggest that two different channels are responsible for Ca2+ entry in human platelets at the early and late phases of thrombin stimulation and that the channel responsible for the late phase of Ca2+ entry may be activated by a mechanism involving myosin light chain kinase.

We show electrical coherent manipulation of quadrupole-split nuclear spin states in a GaAs/AlGaAs heterostructure on the basis of the breakdown of quantum Hall effect. The electric quadrupole splitting in nuclear spin energy levels is intentionally enhanced by applying an external stress to the heterostructure. Nuclear magnetic resonance spectra with clearly separated triple peaks are obtained, and Rabi oscillations are observed between the nuclear spin energy levels. The decay of the spin-echo signal is compared between the cases before and after the enhancement of quadrupole splitting., Comment: 4 pages, 4 figures

We reported previously that blood levels of nicotine in suicidal smokers tend to be significantly higher than those in non-suicidal smokers, and blood level of nicotine seems to be a useful criterion for discriminating suicide from other types of death. In this paper, we report nicotine and cotinine levels in various tissues of an adipocere body found in the sea. The cause of death was drowning, and the postmortem time interval was approximately 5 months at autopsy. His driver's license was concealed in his sock, which seemed to suggest that he committed to suicide. In toxicological analysis by gas chromatography, nicotine and cotinine in the femoral muscle were detected at concentrations of 213 and 488 ng/g, respectively, and these substances were also detected in the brain, liver and kidney. For evaluating the tissue levels of nicotine and cotinine in the adipocere body, we analyzed these levels in blood and various tissues of 13 autopsy cases of smokers. Nicotine and cotinine levels in blood were the most similar to those in skeletal muscle. Although the postmortem time interval, the formation process of adipocere and the environmental condition in water may affect nicotine and cotinine levels in the femoral muscle, the high muscle level of nicotine in the present case seem to implicate suicidal death.

The resistively‐detected NMR experiments have been carried out in the vicinity of filling ν=1 where skyrmion excitations play a crucial role. The NMR lineshape in this region exhibits a dip‐peak structure (dispersive lineshape). The anomalous lineshape evolves to the usual dip structure either by moving further away from ν=1 or by raising temperature above ∼150 mK. The nuclear spin relaxation rate 1/T1 shows a distinct ν‐dependence at the dip and the peak. The temperature dependence of 1/T1 is anomalous in the region where the dispersive lineshape is observed. We compare our result with the conflicting experimental results recently reported.

The aim of this study was to determine if the endogenous levels of gamma-hydroxybutyric acid (GHB) in urine were affected by drinking and smoking. Urine samples were obtained from 20 healthy volunteers (15 males, 21-45 years; 5 females, 22-24 years). This population included four average drinkers (males), 4 average smokers (males), and 12 nonsmokers/nondrinkers (seven males and five females). Urinary levels of GHB were measured by gas chromatography. No gender differences were observed in the urinary levels of endogenous GHB. The urinary levels of GHB in males were 0.52+/-0.37 microg/ml in smokers, 0.28+/-0.21 microg/ml in nonsmokers/nondrinkers, and 0.23+/-0.04 microg/ml in drinkers. Urinary GHB levels were measured three times a day for 5 consecutive days in a male from each group. Large intra-individual differences were observed over the 5-day period in a smoker and a nonsmoker/nondrinker. No significant changes in daily endogenous GHB levels were observed in a drinker during the period. Our preliminary results suggest that stimulatory effects of nicotine on the central nervous system (CNS) may result in an increase in nocturnal formation of GHB and the depressive effects of ethanol on the CNS may not affect, even may inhibit, nocturnal production of GHB.

A 35-year-old male was found lying in a prone position in his room. He was in cardiopulmonary arrest on arrival to hospital and was pronounced dead. There was no attempt at resuscitation. No miosis was observed on admission. At post-mortem his stomach contained 170 g greenish liquid with a small amount of shredded tobacco leaves. The serum cholinesterase activities were 47-90 IU (normal range for male: 200-440 IU). GC and GC-MS analyses showed nicotine (21.8 mg), methomyl (304 mg), and triazolam (1.69 mg) in his stomach. He had consumed tobacco leaves, Lannate containing water soluble methomyl (45%), and Halcion tablets containing 0.25 mg triazolam. Methomyl concentrations in blood were 3-8 ng/ml. Substantial amounts of methomyl (2260-2680 ng/ml) were detected in cerebrospinal fluid and vitreous humor. Nicotine concentrations in blood ranged from 222 to 733 ng/ml. A small amount of triazolam was detected only in bile (176 ng/ml) and liver (23 ng/g). The cause of death was respiratory paralysis produced by the additive effects of methomyl and nicotine shortly after consumption.

We measured nicotine and cotinine levels in blood and urine from 31 forensic autopsy cases. Initially, we developed a sensitive and reproducible gas chromatographic method with a minimum limit of detection of 2.1 ng/ml for both nicotine and cotinine. Calibration curves for nicotine and cotinine were linear in the ranges of 2.1-1030 ng/ml (r2=0.994-0.999) and 2.1-1380 ng/ml (r2=0.998-0.999) respectively. Our population included 13 smokers and eight of these smokers committed suicide. They showed high levels of nicotine and cotinine at 65.1-205 ng/ml (mean: 115 ng/ml) and 31.3-938 ng/ml (mean: 405 ng/ml) in blood, respectively, and 234-7290 ng/ml (mean: 1940 ng/ml) and 143-4620 ng/ml (mean: 1170 ng/ml) in urine, respectively. None of these individuals consumed nicotine preparations or tobacco leaves. In five smokers who did not commit suicide, nicotine and cotinine levels were 4.4-62.1 ng/ml (mean: 33.2 ng/ml) and 49.9-217 ng/ml (mean: 140 ng/ml) in blood, respectively, and 158-314 ng/ml (mean: 246 ng/ml) and 68.9-300 ng/ml (mean: 179 ng/ml) in urine, respectively. Our results suggest that there may be a marked increase in consumption of cigarettes in smokers with suicidal thoughts.

A 57-year-old man was found dead lying down in a bamboo thicket. Moderate to severe petechiae were present on his conjunctivae, buccal mucosa, and laryngeal mucosa at autopsy. Cardiac chambers contained a normal volume of fluid blood. Moderate atherosclerosis and fatty liver were observed. No remarkable changes, other than congestion in other organs, were observed. Gas chromatographic screening of the stomach contents, blood and urine was positive for triazolam and alpha-hydroxytriazolam that were confirmed by gas chromatography-mass spectrometry. Blood concentrations of triazolam and free alpha-hydroxytriazolam were 62-251 and 10-66 ng/ml, respectively. A substantial amount of triazolam was detected in bile (1130 ng/ml), but not in urine. Free and total alpha-hydroxytriazolam concentrations were 3920 and 7050 ng/ml, respectively, in the bile and 3710 and 9670 ng/ml, respectively, in urine. Organs contained 216-583 ng/g triazolam. The concentration of free alpha-hydroxytriazolam in the kidney (246 ng/g) was higher than in any other organ. Free alpha-hydroxytriazolam was not detected in the liver. The concentrations of total alpha-hydroxytriazolam in the liver and kidney were 784 and 381 ng/g, respectively. Free to total ratios of alpha-hydroxytriazolam were 0.14-0.56 in fluid samples and 0.56-0.92 in tissue samples, except for the liver. A large quantity of triazolam (8.4 mg) remained in the stomach. The victim probably died of postural asphyxia caused by triazolam poisoning.

The purpose of this study was to examine the effects of methemoglobinemia caused by fire gases on blood cyanide concentrations in fire victims. Twenty-two fire victims with postmortem intervals of 8-48 h were involved. Blood cyanide concentrations at the time of death (C(0)) were estimated using the formula: C(0)=Ce(0.046 t) (C=blood cyanide concentration detected at autopsy, 0.046=first-order rate constant of cyanide disappearing from blood in corpses, and t=postmortem interval). Total (free and combined with cyanide) methemoglobin (MetHb) content was used to estimate the maximum capacity of MetHb for combining cyanide. Blood cyanide concentrations at the time of death were very high (5.32-6.47 mg/l) in five victims. Three showed high saturation (54.7-63.0%) of carboxyhemoglobin (CO-Hb) and elevated total MetHb contents (2.6-5.0%). MetHb at these levels is capable of scavenging up to 8.6-11.4 mg/l of blood cyanide. Thus, blood cyanide might have been completely combined with MetHb at the time of their death. In the remaining two victims, CO-Hb saturation was not high (30.9 and 37.9%) and no free MetHb was detected. As a result they may have exhibited severe toxic effects of cyanide at the time of their death. Our results indicate that MetHb contents and CO-Hb saturation should be determined to evaluate the toxic effects of cyanide in fire victims.