Comparison of postmortem butane distribution between two fatal butane poisoning cases.

Fatal accidents during butane abuse frequently occur in Japan and in many countries around the world. Although analytical data about butane concentration in postmortem samples is being accumulated, when using the data to determine the cause of death, careful interpretation is required because the gas is easily diffused. Two fatal butane poisoning cases were encountered, and butane quantification of autopsy samples obtained from left and right heart blood, femoral blood, kidney, liver, lung, brain and fatty tissues was performed. In both cases, butane concentration in the left heart blood was lower than in the right heart blood or the femoral blood, despite gas inhalation. These findings may indicate that the deceased individuals interrupted gas inhalation and inhaled room air immediately before their death, therefore ruling out asphyxia due to anoxia as the mechanism of death. Case 1, which was suspected to be a not acute death, showed a very high butane concentration ratio of fatty tissues to femoral blood of over 70. Case 2 was considered an acute death, and the butane concentration ratio of fatty tissues to femoral blood was 8.2. These results are consistent with previously reported findings showing that much higher ratios of fatty tissues to blood are compatible with long survival time. In conclusion, the comparison of butane concentration among different samples, including left heart blood versus right heart blood and fatty tissues versus blood, is useful when interpreting the result of postmortem butane analysis to examine the mechanism of death and survival time.

Postmortem diffusion of n-butane and i-butane used for anticontagious plugging spray.

Blood and tissue samples from a forensic autopsy of a man in his late 60s, who developed dementia and died of multiple head traumas due to a fall from a moving vehicle, contained certain amounts of n-butane and i-butane. The concentration of n-butane was in the range of 0.48-70.5 µL/g, which would be considered as toxic or lethal levels. We had to distinguish whether the cause of his unexplained behavior was due to his pre-existing condition (dementia), or from a confused state induced by butane abuse. No traces of butane use were found at the scene. Police investigation revealed that a propellant used in an anticontagious plugging spray had been administered to him during a postmortem treatment in the emergency hospital. In order to prove the postmortem butane diffusion had resulted from the spray administration and to estimate the diffused concentration, experimental simulation was conducted by using rats. As a result of postmortem treatment with the spray, n-butane at concentrations of 0.54-15.5 µL/mL or g were found in the rat blood and tissues. In this case, we provided further evidence that the postmortem butane diffusion, caused by using the anticontagious plugging spray containing butane gas as a propellant administered to a cadaver during a postmortem procedure prior to forensic autopsy, should be distinguished from cases of actual butane poisoning.

Quantitative determination of n-butane metabolites in three cases of butane sniffing death.

Butane is an addictive volatile substance like toluene. We report three forensic autopsy cases of sudden death that occurred while sniffing n-butane and isobutane from portable gas cartridges. n-Butane and isobutane were detected in all three cases. In cases 1-3, n-butane concentrations in heart blood were 54.3, 25.5, and 30.7µg/mL, respectively. These concentrations were considered fatal according to the previous reports. In addition, n-butane metabolites (2-butanol and 2-butanone) were detected in cases 1 and 3 but not in case 2. Blood levels of 2-butanol and 2-butanone were 6.5 and 1.8µg/mL, respectively, in case 1, and 6.3 and 5.6µg/mL, respectively, in case 3. According to the police investigation, the decedent in case 1 had misused butane gas for more than 6 months in the period leading up to death. The decedent in case 3 also had a history of chronic misuse of butane gas. There was no history of chronic misuse of butane gas by the decedent in case 2. It was suspected that he attempted suicide via inhalation of butane gas using a plastic bag, leading to a rapid death. The presence or absence of n-butane metabolites might reflect the way of butane inhalation, such as the frequency and duration. Although additional experimental and case studies are necessary to establish the forensic applications of n-butane metabolite detection, it may be a useful method to understand the decedents' pattern of butane sniffing before death.

The somatostatin receptor 4 agonist J-2156 reduces mechanosensitivity of peripheral nerve afferents and spinal neurons in an inflammatory pain model.

Somatostatin (SST) is a peptide hormone that regulates the endocrine system and affects neurotransmission via interaction with G protein-coupled SST receptors and inhibition of the release of different hormones. The aim of this study was to investigate whether the analgesic properties of the selective SSTR4 agonist J-2156 are mediated via peripheral and/or spinal receptors. Effect on mechanical hyperalgesia in the Complete Freund׳s Adjuvant (CFA) model was measured after intraperitoneal application of J-2156. Electrophysiological neuronal recordings were conducted 24 h after injection of CFA or vehicle into the paw of Wistar rats. Mechanosensitivity of peripheral afferents of the saphenous nerve as well as of spinal wide dynamic range (WDR) and nociceptive-specific (NS) neurons were measured after systemic or spinal application of J-2156. In CFA animals J-2156 dose dependently reduced hyperalgesia in behavioral studies. The minimal effective dose was 0.1 mg/kg. Mechanosensitivity of peripheral afferents and spinal neurons was significantly reduced by J-2156. NS neurons were dose dependently inhibited by J-2156 while in WDR neurons only the highest concentration of 100 µM had an effect. In sham controls, J-2156 had no effect on neuronal activity. We demonstrated that J-2156 dose-dependently reduces peripheral and spinal neuronal excitability in the CFA rat model without affecting physiological pain transmission. Given the high concentration of the compound required to inhibit spinal neurons, it is unlikely that the behavioral effect seen in CFA model is mediated centrally. Overall these data demonstrated that the analgesic effect of J-2156 is mediated mainly via peripheral SST4 receptors.

Partition of bispyridinium oximes (trimedoxime and K074) administered in therapeutic doses into different parts of the rat brain.

The penetration of acetylcholinesterase reactivators (oximes) into the central nervous system is typically restricted by the blood-brain barrier. Although oximes are highly hydrophilic compounds, some contradictory results confirming permeation into the brain exist. The aim of this study is to verify the penetration of oximes through the blood-brain barrier and to detect their levels achieved in different brain regions 60 min after the administration. It was confirmed that oximes are able to penetrate into the brain after injection of therapeutic doses corresponding with 5% of LD(50). The level in whole brain was 0.58% for trimedoxime and 0.85% for the experimental drug oxime K074 as the percentage of their plasma concentration. The highest concentration was found in frontal cortex (trimedoxime 2.27%; oxime K074 0.95%) and lowest in basal ganglia (trimedoxime 0.86%; oxime K074 0.42%). Entry of oximes into the brain is minimal, but some low reactivation effect should be expected. The reactivation potency of oximes might be higher or lower, depending on the real oxime concentration in a given area.

An autopsy case of butane gas abuse.

A case of fatal butane gas poisoning in a young female is presented. Quantitative toxicological analysis showed that the concentration of butane in the femoral blood was 6.8 microl/ml, and isobutane and propane were also identified. Severe congestion of the lungs and deposition of lipofuscin in the myocardium were also observed. We concluded that the cause of death of the victim was due to cardiac arrhythmia induced by the butane gas abuse.

In vitro metabolism of (nitrooxy)butyl ester nitric oxide-releasing compounds: comparison with glyceryl trinitrate.

We investigated the in vitro metabolism of two (nitrooxy)butyl ester nitric oxide (NO) donor derivatives of flurbiprofen and ferulic acid, [1,1'-biphenyl]-4-acetic acid-2-fluoro-alpha-methyl-4-(nitrooxy)butyl ester (HCT 1026) and 3-(4-hydroxy-3-methoxyphenyl)-2-propenoic acid 4-(nitrooxy)butyl ester (NCX 2057), respectively, in rat blood plasma and liver subcellular fractions compared with (nitrooxy)butyl alcohol (NOBA) and glyceryl trinitrate (GTN). HCT 1026 and NCX 2057 undergo rapid ubiquitous carboxyl ester hydrolysis to their respective parent compounds and NOBA. The nitrate moiety of this latter is subsequently metabolized to inorganic nitrogen oxides (NOx), predominantly in liver cytosol by glutathione S-transferase (GST) and to a lesser extent in liver mitochondria. If, however, in liver cytosol, the carboxyl ester hydrolysis is prevented by an esterase inhibitor, the metabolism at the nitrate moiety level does not occur. In blood plasma, HCT 1026 and NCX 2057 are not metabolized to NOx, whereas a slow but sustained NO generation in deoxygenated whole blood as detected by electron paramagnetic resonance indicates the involvement of erythrocytes in the bioactivation of these compounds. Differently from NOBA, GTN is also metabolized in blood plasma and more quickly metabolized by different GST isoforms in liver cytosol. The cytosolic GST-mediated denitration of these organic nitrates in liver limits their interaction with other intracellular compartments to possible generation of NO and/or their subsequent availability and bioactivation in the systemic circulation and extrahepatic tissues. We show the possibility of modulating the activity of hepatic cytosolic enzymes involved in the metabolism of (nitrooxy)butyl ester compounds, thus increasing the therapeutic potential of this class of compounds.

Tóxicos detectados en muertes relacionadas con fuegos e intoxicaciones por monóxido de carbono / Toxic agents detected in deaths related to fire and intoxications with carbon monoxide

Se presentan en este trabajo las conclusiones del estudio realizado sobre los resultados de los análisis efectuados en muestras de sangre de 882 personas que resultaron fallecidas o intoxicadas en fuegos o a consecuencia de la inhalación de monóxido de carbono y/o de otros gases de combustión. En ellas se investigó la presencia de monóxido de carbono, cianuro y otros tóxicos tales como el alcohol etílico y los psicofármacos. Se realizan dos subgrupos, el de muertes producidas por intoxicación por monóxido de carbono y el de las ocurridas en fuegos. Se puede observar que las concentraciones de carboxihemoglobina alcanzadas en uno y otro grupo difieren sensiblemente, siendo muy superiores las encontradas en el primer grupo, con frecuencias máximas entre 50 per cent y 70 per cent de carboxihemoglobina frente a las detectadas en el segundo grupo cuyas frecuencias máximas se hallan entre 1 per cent y 15 per cent. En las muertes ocurridas en fuegos se detecta además cianuro en concentraciones variables ( 0,2 - 12 µg / ml ) e independientes del nivel de carboxihemoglobina detectado en cada caso. Entre los otros tóxicos más frecuentes se detectan el alcohol etílico, las benzodiacepinas, el butano y los antidepresivos, entre otros. El alcohol etílico se detecta en diferentes concentraciones observándose una mayor concentración en los casos de fuegos, lo que indica que puede tener influencia en la ocurrencia de accidentes relacionados con ellos (AU)

Quantitative determination of n-propane, iso-butane, and n-butane by headspace GC-MS in intoxications by inhalation of lighter fluid.

This report describes a fully elaborated and validated method for quantitation of the hydrocarbons n-propane, iso-butane, and n-butane in blood samples. The newly developed analytical procedure is suitable for both emergency cases and forensic medicine investigations. Its practical applicability is illustrated with a forensic blood sample after acute inhalative intoxication with lighter fluid; case history and toxicological findings are included. Identification and quantitation of the analytes were performed using static headspace extraction combined with gas chromatography-mass spectrometry. In order to reconcile the large gas volumes injected (0.5 mL) with the narrowbore capillary column and thus achieve preconcentration, cold trapping on a Tenax sorbent followed by flash desorption was applied. Adequate retention and separation were achieved isothermally at 35 degrees C on a thick-film capillary column. Sample preparation was kept to a strict minimum and involved simply adding 2.5 microL of a liquid solution of 1,1,2-trichlorotrifluoroethane in t-butyl-methylether as an internal standard to aliquots of blood in a capped vial. Standards were created by volumetric dilution departing from a gravimetrically prepared calibration gas mixture composed of 0.3% of n-propane, 0.7% of iso-butane, and 0.8% of n-butane in nitrogen. In the forensic blood sample, the following concentrations were measured: 90.0 microg/L for n-propane, 246 microg/L for iso-butane, and 846 microg/L for n-butane.

Role of molecular diffusion in conventional and high frequency ventilation.

The influence of molecular diffusion on gas-mixing during conventional mechanical ventilation (CMV) and high frequency ventilation (HFV) was studied by observing the wash-in of six poorly soluble, inert gases in arterial blood. Anesthetized dogs were ventilated either with CMV or HFV. Following a step change in inspired gas composition, the increase in arterial concentrations of hydrogen, helium, methane, ethane, isobutane, and sulfur hexafluoride was determined by gas chromatography. The relative gas diffusivities encompassed a range of almost one order of magnitude. Propane, present in inspired gas during both the control and wash-in phases, served as an internal reference for calculation of blood tracer concentrations. The wash-in of all six inert gases followed a single exponential time course during both CMV and HFV. The rate of wash-in of each gas decreased with increasing molecular weight (MW). The relationship of rate constants to a measure of relative diffusivity (MW-0.5) was significantly different than zero for both types of ventilation. The slope of this relationship was three times larger for CMV than HFV, indicating that molecular diffusion has a greater role in gas mixing during ventilation with large tidal volumes. Diffusion has a minor role in gas mixing during high frequency ventilation with small tidal volumes. Demonstration of the presence of gas separation secondary to molecular diffusion during HFV is enhanced by measuring wash-in, rather than wash-out, of inert gases because gas separation is likely to be obscured as exhaled gases pass through the well-mixed central airways during gas wash-out.

Ventricular tachycardia associated with non-freon aerosol propellants.

A previously well 2-year-old child presented with seizures and ventricular tachycardia shortly after playing with an aerosol can of a well-known proprietary deodorant. She required intensive care and survived without sequelae. The propellants used in this product were isobutane, n-butane, and propane. The propellants have been thought to be safer than the previously used Freons, which were known to be cardiotoxic and neurotoxic. Significant exposure was confirmed by the detection of n-butane and isobutane in the patient's serum. We conclude that unintentional exposure to non-Freon aerosol propellants in a nonconfined space can be hazardous to children. Aerosol cans should be considered to represent toxic hazards and should be kept out of reach of children.