Takehiko Yamamura

Alcohol addiction of methamphetamine abusers in Japan

Fifty-eight methamphetamine (MAMP) abusers were surveyed to demonstrate the types of nature of MAMP abuse. In-depth interviews using psychophysiological techniques assessed the subjects to be truthful or deceptive about their abuse histories. Research diagnostic criteria determined the subjects clinical symptoms. The results show that three factors characterize MAMP abuse: significant correlation was found between the years of abuse; the manifestation of somatic or mental disorders or both, and alcohol (Alc) addiction. MAMP abusers who were nondrinkers or light drinkers developed a tendency to dislike Alc after MAMP abuse, while there was no change in Alc consumption in heavy drinkers. The findings suggest that the combined abuse of MAMP and Alc aggravates somatic and mental disorders and that Alc plays an important role in the fatal effect of MAMP, especially from small doses. This provides support for the synergistic effects between MAMP and Alc. Coadministration of MAMP and Alc appears to produce long-acting and more complicated changes in the brains neurotransmitter function.

Effects of methamphetamine and ethanol on learning and brain neurotransmitters in rats.

The interactions of methamphetamine (MAMP) and ethanol (EtOH) on multiple active/passive avoidance performance and neurotransmitters in different brain regions were examined. After the acquisition schedules, rats were retrained under the influence of MAMP (2 mg/kg/day, IP), EtOH (2 g/kg/day, IP), and in combination over 20 days in rats (n = 6 per group). As a function of progress of drug treatment, MAMP-EtOH mixtures disrupt the learned avoidance performance and produced severe impairment of discriminative behavior caused by enhancement of excitability induced by MAMP when compared with MAMP only. At withdrawal, MAMP-EtOH-induced impairments of performance significantly persisted, whereas MAMP-only-induced impairments slightly recovered. At the eleventh day drug withdrawal, MAMP-only-induced alterations of neurotransmitter levels at different regions were alleviated by EtOH, but these did not return to normal levels. These data provide support for the direct antagonistic and indirect additive interactions following constant daily treatment with a combination of MAMP and EtOH. EtOH may be an important factor in MAMP abuse to MAMP-induced psychosis or neurotoxicity.

Simultaneous analysis of acephate and methamidophos in human serum by improved extraction and GC-MS

A detailed procedure for simple and rapid analysis of acephate, an organophosphorous pesticide, and its metabolite methamidophos in human serum by gas chromatography-mass spectrometry was established. The method included solid-phase extraction with activated charcoal, which gave high recoveries of both analytes. After validation of the method, it was successfully applied to a serum sample obtained from an actual poisoning case. The present method seems very useful, especially in forensic and environmental toxicology.

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.

Effects of daily administration of methamphetamine on multiple active/passive avoidance performance in rats

The effects of daily methamphetamine (M-Amp) treatment with (2 mg/kg/day, i.p.) were examined on multiple active/passive avoidance performance (MAP) in rats. After avoidance training, the animals were given M-Amp every day; on the days of learning sessions, which were on alternate days, the drug was administered at 15 min before the session. Daily administration of M-Amp produced enhancement of the number of respondings (running) as an excitatory dimension of behavior, disruption of immobilities as an inhibitory dimension, and impairment of successes as a discriminatory dimension, when compared with saline-treated rats. Following M-Amp withdrawal, recovery from these damages of learned behavior was observed, except the deterioration in the discriminative dimension. In conclusion, the MAP paradigm is good for assessing the behavioral effects of M-Amp treatment, making it easy to distinct the behavioral effects of M-Amp into excitatory-inhibitory and discriminative dimensions. It is important to distinguish the behavioral components induced by M-Amp, since the damage of learned avoidance performance consists of different dimensions in the M-Amp-treated rats. Impairment of discriminative behavior appears to demonstrate an attentional deficit, which may explain the behavioral disorderliness in M-Amp abusers who display no disturbance of apparent consciousness. These results are discussed with association of brain monoamine alterations.

Determination of acephate and methamidophos in tissues: appearance of matrix effect in gas chromatography–mass spectrometry

A simple and reliable method to determine acephate and methamidophos in mammalian tissues is presented. The method includes solid-phase extraction of tissue extracts with active carbon cartridges followed by gas chromatography–mass spectrometry analysis. During the study, a matrix effect was observed especially at low concentrations of acephate and methamidophos in serum and in brain. To minimize the effect, we prepared calibration curves with relatively short ranges. The validation data, such as the linearity of calibration curves, limits of detection, and coefficients of variation for recovery rates, were generally satisfactory. The present method is useful for determination of acephate and methamidophos in mammalian tissues because of its simplicity and speed, keeping in mind the presence of the matrix effect.

Effects of dopamine antagonists on methamphetamine-induced dopamine release in high and low alcohol preference rats.

The authors have previously shown that high alcohol preference rats (HAP) have a significantly higher sensitivity than low alcohol preference rats (LAP) for methamphetamine (MAP). In this study, changes in dopamine and serotonin release induced by MAP (1 mg/kg, intraperitoneally) after pre-treatment with D1 and D2 receptor antagonists were examined in the striatum of rats with different alcohol preferences to elucidate differences in receptor levels between the two rat strains. D1 receptor antagonist SCH23390 or D2 receptor antagonist haloperidol were administrated intracerebroventricularly 10 min before MAP stimulation. This study investigated the effect of methamphetamine-induced dopamine and serotonin release in striatum using microdialysis of freely moving rats coupled to ECD-HPLC. With haloperidol treatment both strains of rats showed a significantly greater maximum increase on MAP-induced dopamine release compared with respective control rats. However, after SCH23390 treatment only HAP rats showed a significantly greater increase in dopamine release compared with controls. SCH23390 blocks mainly D1 receptors only in the post-synaptic membrane, whereas haloperidol blocks D2 receptors in both the pre-synaptic and post-synaptic membranes. The MAP-induced increase in dopamine release following haloperidol pre-treatment was greater than SCH23390 pre-treatment in both strains. This result indicates that D2 receptors (autoreceptors) in the pre-synaptic membrane were blocked, leading to the elimination of the feedback function that regulates dopamine release. These data suggested that alcohol preference is associated with the action of MAP, and the dopaminergic mechanism, specifically the D1 system in the striatum, might have a different pathway dependent on alcohol preference.

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.

Mthanol: toxicity of the solvent in a commercial product should also be considered

Sir In general, the evaluation of toxicity relies on the toxicity of the main component in a poisoning case involving a commercial product. However, we usually pay little attention to the toxicity of the solvent used. Methanol finds widespread commercial use as a solvent.1 Here we report a case of death due to trichlorfon (O,O-dimethyl 2,2,2-trichloroi-hydroxyethylphosphonate; DEP) dissolved in methanol and phenobarbital ingestion with fatal levels of these components in the blood, and also a detected toxic level of methanol and its metabolite, formic acid.

Hyperpyrexia induced by a multiple antidepressants overdose.

A 23-year old male ingested an excessive amount of antidepressants that had been prescribed. Initially, he was hospitalized near his house. Subsequently, he was transferred to the emergency department (ED) in a university hospital, because of the difficulties in controlling his seizures. At the time of arrival in the ED, he was in cardiopulmonary arrest. His rectal temperature was 41.2°C (106.16°F). Resuscitation was unsuccessful. A number of empty packets of antidepressants were found in his house during the subsequent authorities’ investigation. At autopsy, no remarkable findings were observed except for severe pulmonary edema and congestion. No evidence of brain injury or infectious diseases such as meningitis, encephalitis or pneumonia was observed. Histological study of the skeletal muscle showed hypercontracted fiber appearing as ‘opaque fibres’ and multiple vacuolation (Figure 1). Drug screening testing using a TriageTM (Biosite Diagnostic Inc, San Diego, USA) panel was positive for benzodiazepines, barbiturates and tricyclic antidepressants, but negative for alcohol by gas chromatography. Figure 2 shows the chromatogram of femoral blood using a high performance liquid chromatography (HPLC) drug analysis system (Class VP system, Shimadzu, Kyoto Japan). Clomipramine, amoxapine, maprotiline, amitriptyline and milnacipran were confirmed by each retention time. The drug concentrations in the victim’s femoral blood and their fatal and therapeutic blood level are summarized in Table 1. Blood concentrations of clomipramine and amoxapine were at fatal levels, while the maprotiline and amitriptyline levels were toxic.2 Milnacipran, a newly developed serotonin-noradrenaline reuptake inhibitor, was found to be ten-fold higher than the therapeutic level.3 The positive benzodiazepines and barbiturates detected by the TriageTM screening