Heroin overdose masquerades as methomyl poisoning: a case report.

BACKGROUND: Methomyl is the most common cause of suicidal death but heroin is the most common cause of accidental death. The problem is to determine the exact cause and manner of death between methomyl or heroin toxicity. The evidence from autopsy includes crime scene investigation, toxicological analysis by liquid chromatography with mass spectrometry, and knowledge of methomyl and heroin intoxication. CASE PRESENTATION: A 35-year-old Thai man and a 30-year-old Thai woman were found showing evidence of cyanosis, with a fine froth around the nose and mouth. Postmortem interval time was 24 hours. According to the police's and hotel owner's records, the couple stayed together for 1 day before being found dead in bed, naked, with a foul and a fine froth around the nose and mouth. A methomyl insecticide sachet and a plastic box containing white powder form of heroin were found at the scene. Laboratory tests of the male corpse identified the presence of methomyl in the blood of the stomach and morphine, codeine, methadone, and tramadol in the systemic blood. Blood cholinesterase enzyme activity and morphine concentration was 3416 U/L or 53% (normal 6400 U/L) and 0.058 µg/ml respectively. Laboratory test of the female corpse identified the presence of methomyl in the stomach and blood, and cholinesterase enzyme activity was 1965 U/L or 30.7%. CONCLUSIONS: Cause of death of the male corpse was deemed to be due to heroin intoxication as the blood concentration of morphine was more than the lethal concentration with a morphine/codeine ratio of more than 1:1. Methomyl intoxication of the male corpse was unlikely to be the cause of death because methomyl systemic blood concentration was found to be very low, < 2.5 µg/ml, and cholinesterase enzyme levels did not indicate lethal activity (< 10-15% of normal). The main problem regarding an insurance claim is that the policy will not pay out in the case of heroin-associated deaths, as it is an addictive drug. The policy would pay out on death by suicide with methomyl insecticide, which was not prohibited by the insurance company after 1 year of insurance. So, it is not clear whether or not the family will receive money from the insurance company.

Determination of Elements in Gymnema inodorum Lour by Particle Induced X-Ray Emission (PIXE).

At present, Thailand uses medicinal plants to treat various diseases. Alternative medicine utilizes Gymnema inodorum Lour for antipyretic and anti-allergic purposes. There are also other research studies to treat diabetes mellitus, coronary artery disease, cataract, rheumatoid arthritis, gout, liver cancer, and stomach cancer. This study used particle-induced X-ray emission (PIXE) technique to analyze the elements in this plant. The advantage of this technique over other methods is the multi-elemental analysis and high sensitivity. The objective of this study was to determine the elemental compositions and to develop new standard methods for analyzing plant elemental compositions in Thailand. A 2-MeV proton beam was used to identify and characterize major and minor elements namely Mg, Al, Si, P, S, Cl, K, Ca, Ti, Mn, Fe, and Zn in Gymnema Inodorum Lour. Results have shown that these elements are present in varying concentrations in the selected parts: roots, stems, and leaves. The data of elemental analysis, applied in recommended quantities that are harmful to the body, describe the relationship between elements and efficacy of this plant in alternative medicine.

Inhibition of Procarcinogen Activating Enzyme CYP1A2 Activity and Free Radical Formation by Caffeic Acid and its Amide Analogues.

OBJECTIVES: Caffeic acid (CAF) and its amide analogues, ethyl 1-(3',4'-dihydroxyphenyl) propen amide (EDPA), phenethyl 1-(3',4'-dihydroxyphenyl) propen amide (PEDPA), phenmethyl 1- (3',4'-dihydroxyphenyl) propen amide (PMDPA) and octyl 1-(3',4'-dihydroxyphenyl) propen amide (ODPA) were investigated for the inhibition of procarcinogen activating enzyme. METHODS: CYP1A2 and scavenging activity on formation of nitric oxide, superoxide anion, DPPH radical and hydroxyl radical. RESULTS: It was found that they inhibited CYP1A2 enzyme by uncompetitive inhibition. Apparent Ki values of CAF, EDPA, PEDPA, PMDPA and ODPA were 0.59, 0.39, 0.45, 0.75 and 0.80 µM, respectively suggesting potent inhibitors of CYP1A2. Moreover, they potentially scavenged nitric oxide radical with IC 50 values of 0.12, 0.22, 0.28, 0.22 and 0.51 mM, respectively. The IC50 values of superoxide anion scavenging were 0.20, 0.22, 0.44, 2.18 and 2.50 mM, respectively. 1, 1- diphenyl-2- picrylhydrazyl (DPPH) radical-scavenging ability, shown as IC50 values, were 0.41, 0.29, 0.30, 0.89 and 0.84 mM, respectively. Moreover, the hydroxyl radical scavenging in vitro model was shown as IC50 values of 23.22, 21.06, 17.10, 17.21 and 15.81 µM, respectively. CONCLUSION: From our results, caffeic acid and its amide analogues are in vitro inhibitors of human CYP1A2 catalytic activity and free radical formation. They may be useful to be developed as potential chemopreventive agents that block CYP1A2-mediated chemical carcinogenesis.

Inhibitory effects of caffeic acid ester analogues on free radicals and human liver microsome CYP1A2 activities.

Ethyl caffeate (EC), octyl caffeate(OC), benzyl caffeate(BC) and phenethyl caffeate(PC) were synthesized and evaluated for scavenging of superoxide anion, nitric oxide radical and 1,1-diphenyl-1-picrylhydrazyl radical (DPPH). Antioxidant activity was investigated with reducing power method. Pooled human liver microsome was used for investigating the effects on cytochrome P450 1A2 (CYP1A2) catalytic activities by using phenacetin as a substrate. Dixon and Cornish-Bowden plots were used for enzyme kinetic analysis. The EC, OC, BC and PC potentially inhibited superoxide anion, nitric oxide and DPPH radicals. IC(50) values of superoxide anion scavenging of EC, OC, BC and PC were 16.42, 79.83, 123.69 and 123.69 µg/ml, respectively. EC was more potent than OC and BC in terms of nitric oxide radical scavenger: IC(50) values of EC, OC and BC were 24.16, 37.34 and 52.64 µg/ml, respectively. In addition, the IC(50) values of EC, OC, BC and PC on DPPH radical scavenging were 70.00, 184.56, 285.34 and 866.54 µg/ ml, respectively. The IC(50) values of EC, OC, BC and PC on phenacetin O-deethylation were 124.98, 111.86, 156.68 and 31.05 µg/ml, respectively. Enzyme kinetics showed that the type of inhibition mechanism was mixed-type. The result of this study shows that caffeic acid ester analogues potentially scavenge free radicals and inhibit catalytic activity of CYP1A2. This may lead to important implications in the prevention of CYP1A2-mediated chemical carcinogenesis.

Study of the normal internal organ weights in Thai population.

The normal adult internal organ weight and the relationship between it with body weight (BW) and body height (BH) have not been studied in Thailand. The 499 corpses of autopsy were performed in Maharajnakorn Chiang Mai Hospital, the center of the northern part of Thailand during 2000-2005. All of these cases were unnatural deaths including accident, homicide and suicide with no organ injuries or pathologic abnormalities and excluded decomposed bodies, diseases and previous medical treatments. These organs were collected from 269 males and 230 females and were aged between 15 and 60 years. The determination of average organ weight (AOW) was made based on the weight of brains, pituitary glands, thymuses, thyroids, hearts, lungs, livers, pancreases, adrenal glands, kidneys, spleens, ovaries, testes and uteruses. The organ weight (OW) was set in relation to sex, age, body weight (BW) and body height (BH). The AOW (g) of male and female was found to be: brain 1311/1170, pituitary gland 0.6/0.6, thymus 23/24, heart 291/246, thyroid 17/17, right lung 321/271, left lung 296/251, liver 1252/1106, pancreas 97/88, right kidney 106/97, left kidney 112/98, spleen 104/77, right adrenal 5/7.9 and left adrenal gland 6/8. It was also found that weight increased in males in relation to higher age, BW and BH adrenal gland increased in females. There was no difference in pituitary, thymus and thyroid gland weight in either sex. These results can be used as standard organ weights to determine abnormal evidences in Forensic and Pathologic corpses.

The incidence of drug abuse in unnatural deaths in northern Thailand.

OBJECTIVE: Study the incidence of drug abuse in persons with unnatural deaths such as traffic accidents, homicide with gunshot wounds, etc. MATERIAL AND METHOD: One hundred and fifty three cases with a mean age of 34 years (range 10 to 76) were studied. The decedents were mostly male (92%), with a variety of occupations including laborers (76.9%), traders (15.4%), and student (7.7%). The causes of death were mainly traffic injuries (33%), gunshot wounds (26%) and others (stab wound, poisoning, asphyxia etc 41%). The manner of death was accidents in 40% and homicides in 28%. RESULTS: Nine percent were positive for methamphetamine or amphetamine derivatives. Tests for Heroin, 6-MAM, morphine, or cocaine were also performed but not detected. The drug positive cases were mostly males (85%) with the most common age range of 21-30 years (35.4%) and 61% with only primary education. Homicide by gunshot wounds was the most common cause of death at 69.2%, followed by hanging (15.4%), electrocution (7.7%), and poisoning (7.7%). The concentration of methamphetamine in urine was between 501-61,147 ng/ml, which cannot be correlated with intoxication. There were no deaths from overdose. Three Benzodiazepine, one toluene, and one meperidine cases were also found in cases of methamphetamine abuse. Alcohol was found mostly in the persons with unnatural deaths (53.6%) from traffic accidents. CONCLUSION: This information helps us understand the marketing strategies, and the trading routes. All data will be used for planning to eradicate these drugs from Thailand in line with government strategies.

The prevalence of detectable blood alcohol concentration among unnatural deaths in northern Thailand.

BACKGROUND: Alcohol is the most common substance abused. It causes many kinds of injuries and death from accidents, homicides, suicides and sudden unexplained natural death (SUND). Traffic accidents especially, have a very close correlation with alcohol concentration levels in the body. MATERIAL AND METHOD: In the present study, there were 1,138 corpses who were sent for autopsy at Chiang Mai University from January to December 2003, in which 78.4% of these cases suffered unnatural death. RESULTS: The incidence of accident was 64.7%, homicide was 22.3% and suicide was 13%. The authors used 153 corpses as a sample. In the sample, 74 (48.4%) were from traffic injuries. There was Blood Alcohol Concentration (BAC) detected in 82 (53.6%) of them, and 99% were male. Their age range was 26-35 years in 42.7% of cases, the employees constituted 48%, 57% were married, 52.4% had traffic injuries for a total of 54.9% who experienced accidental death. The BACs in the accident deaths were very high, with 67 (81.7%) having blood alcohol concentrations of more than 50 mg, 58 (70.7%) with more than 100 mg% and only 15 (18.3%) with less than 50 mg%. The highest BAC detected was 396 mg% in a case that did not die of alcohol toxicity. The most common range of BAC in these cases was 151-200 mg% in 20.7% of cases. CONCLUSION: Alcohol is one of the most common associations with unnatural death in Thailand From the present study the authors found alcohol associated with drugs such as diazepam and chlorpheniramine etc.

The first fatal case of yam bean and rotenone toxicity in Thailand.

The first fatal case of Yam bean and Rotenone toxicity in Thailand was studied at Forensic Medicine, Chiang Mai, Thailand. A Chinese Taiwan man, 59 years old, was found dead after Yam bean ingestion. Yam bean toxicity and death have been found very rarely in the world and has not been reported in Thailand The Yam bean plant is grown widely in Northern Thailand. But many people know that mature pods, seeds and filage of the Yam bean, except the tuberous root, are very toxic. The victim ate a lot of Yam bean seeds and died within 2 hours with respiratory failure. The authors detected Rotenone substance in Yam bean seeds, gastric content and 72 ng/ml blood by HPLC. Also generalized microscopic hemorrhage in the brain, lungs, liver and adrenal glands which were of characteristic pathology were detected. The authors concluded that the cause of death was asphyxia from Yam bean or Rotenone toxicity.

The duration time of urine morphine detection in heroin addicts by radioimmunoassay.

Heroin is one of the most seriously abused drugs and its consumption is illegal. Therefore, the detection of the drug in addicts has to be highly accurate and reliable. Morphine detection in urine is the most common method to confirm consumption. Several methods of morphine detection in urine are described such as Latex Agglutination Inhibition (LAI), Thin Layer Chromatography (TLC), Radioimmunoassay (RIA), High Performance Liquid Chromatography (HPLC) and Gas Chromatography and Mass Spectrophotometry (GC/MS). In this study, we performed Radioimmunoassay (RIA) because it is rapid and cheap. Sixty-three male heroin addicts, average age 32 years, with an average time of heroin administration of about 3 years were studied. They used on average Q.635 grams of heroin per day. The time of detection in the urine after the last heroin administration to the first urine testing was about 8.5 hours, over 3-4 days. The amount of morphine in the urine was 17,897.9 ng/ml. Nevertheless, we found that morphine could be detected in the urine every day for seven days. The decreasing rate of daily morphine detection in the urine was 88.4, 74.2, 64.2, 57.1, 63.3 and 44.8 per cent. But there was no significant difference in the route of administration.