Detection of major psychoactive compounds (safrole, myristicin, and elemicin) of nutmeg in human serum via GC-MS/MS using MonoSpin® extraction: Application in a nutmeg poisoning case.

Nutmeg is an inexpensive, readily available spice used in a variety of recipes. However, the use of nutmeg powder as a recreational drug for its hallucinogenic effects is resulting in an increase in overdose rates. We encountered a male patient being hospitalized after ingesting 75 g of commercially available nutmeg powder with the intent of committing suicide. There are no available reports documenting the toxic or comatose-fatal blood concentrations or time-course of drug action in cases of nutmeg poisoning. Therefore, to improve patient management, we endeavored to determine the blood serum levels and time-course of the major psychoactive compounds (safrole, myristicin, and elemicin) present in nutmeg. We designed a simple and reliable method using the MonoSpin® extraction kit and gas chromatography-tandem mass spectrometry to detect the presence of these psychoactive compounds in human serum. The method had detection and quantitation limits of 0.14-0.16 and 0.5 ng/mL (lowest calibration points), respectively. The calibration curves displayed excellent linearity (0.996-0.997) for all three compounds at 0.5-300 ng/mL blood concentrations. The intra- and inter-day precision values for quality assurance were in the ranges of 2.4-11 % and 2.5-11 %, respectively; bias ranged from - 2.6 % to 2.1 %. Blood serum levels of safrole, myristicin, and elemicin were measured at admission (approximately 8 h post-ingestion) and approximately 94 h after a post-admission fluid therapy to evaluate their biological half-lives. We developed this method to obtain information on the psychoactive constituents of nutmeg and, thereby, determine the toxicokinetic parameters of nutmeg in a case of nutmeg poisoning.

Effectiveness of multiple-dose activated charcoal in lamotrigine poisoning: a case series.

INTRODUCTION: Lamotrigine toxicity can cause coma, seizures, and intraventricular conduction disturbances, and treatment options include good supportive care. We report two cases of lamotrigine poisoning in which multiple-dose activated charcoal may have shortened the elimination half-life of lamotrigine. CASE 1: A 21-year-old woman ingested 15.6 g lamotrigine, 14 g levetiracetam, and 15 mg clonazepam. She became comatose and developed generalized tonic seizure. One hour post-ingestion, 50 g activated charcoal was administered. Starting 11 h post-ingestion, 25 g activated charcoal was administered every 4 h for 4 doses. The peak concentration of serum lamotrigine was 49.5 µg/mL, and the elimination half-life after commencement of multiple-dose activated charcoal was 6.5 h. CASE 2: A 46-year-old woman ingested 0.3 g lamotrigine and 0.1 g topiramate twice, 2 h apart. She became drowsy, complained of blurred vision, vertigo, nausea, and vomited. An initial dose of 50 g activated charcoal was administered at 4.5 h post-second ingestion, and subsequent doses of 25 g (total of 3 doses) were administered every 4 h, commencing at 8.5 h post-second ingestion. The peak concentration of serum lamotrigine was 19.9 µg/mL, and the elimination half-life after commencement of multiple-dose activated charcoal was 9.3 h. DISCUSSION: The mean elimination half-life of lamotrigine in healthy volunteers and epileptic patients receiving lamotrigine monotherapy is 22.8-37.4 h. In our two cases, multiple-dose activated charcoal may have shortened the elimination half-life of lamotrigine, possibly by inhibiting enterohepatic circulation. Multiple-dose activated charcoal should be considered an option for treating lamotrigine poisoning.

Wireless biosensor system for real-time L-lactic acid monitoring in fish.

We have developed a wireless biosensor system to continuously monitor L-lactic acid concentrations in fish. The blood L-lactic acid level of fish is a barometer of stress. The biosensor comprised Pt-Ir wire (φ0.178 mm) as the working electrode and Ag/AgCl paste as the reference electrode. Lactate oxidase was immobilized on the working electrode using glutaraldehyde. The sensor calibration was linear and good correlated with L-lactic acid levels (R = 0.9959) in the range of 0.04 to 6.0 mg · dL(-1). We used the eyeball interstitial sclera fluid (EISF) as the site of sensor implantation. The blood L-lactic acid levels correlated closely with the EISF L-lactic acid levels in the range of 3 to 13 mg · dL(-1) (R = 0.8173, n = 26). Wireless monitoring of L-lactic acid was performed using the sensor system in free-swimming fish in an aquarium. The sensor response was stable for over 60 h. Thus, our biosensor provided a rapid and convenient method for real-time monitoring of L-lactic acid levels in fish.

Association between affective temperaments and brain-derived neurotrophic factor, glycogen synthase kinase 3ß and Wnt signaling pathway gene polymorphisms in healthy subjects.

BACKGROUND: There is increased attention towards elucidating genetic factors that underlie both psychiatric diseases as well as healthy psychological phenomena. Recent evidence suggests that temperamental traits, including affective temperaments, are heritable and associated with genetic polymorphisms. Genetic research examining affective temperaments using the Temperament Evaluation of the Memphis, Pisa, Paris, and San Diego Autoquestionnaire (TEMPS-A) may therefore elucidate the concept of a spectrum of mood disorders and the genetic relationship between affective temperaments and mood disorders. The purpose of this study was to examine the association between brain-derived neurotrophic factor (BDNF), glycogen synthase kinase 3ß(GSK3ß) and Wnt signaling pathway (Wnt) gene polymorphisms and affective temperaments in non-clinical Japanese subjects, as measured by TEMPS-A. METHODS: 44 healthy Japanese subjects were recruited through our university hospital and completed the TEMPS-A. We genotyped three SNPs (single nucleotide polymorphisms) from the BDNF, GSK3ßand Wnt genes in order to test the relationship between these gene variants and five affective temperaments measured by the TEMPS-A. RESULTS: No significant difference in the frequency of alleles between affective temperaments (depressive, cyclothymic, hyperthymic, irritable and anxious temperament) and non affective temperaments was shown. One-way analysis of variance (ANOVA) revealed no significant differences among 5 groups (depressive, cyclothymic, hyperthymic, irritable and anxious temperament) in healthy subjects for all the scores of affective temperaments by TEMPS-A. LIMITATIONS: The number of subjects was relatively small. CONCLUSIONS: The variant of BDNF, GSK3ß and Wnt gene polymorphism might not be related to the five temperaments of TEMPS-A and TEMPS-A score in healthy Japanese subjects. The present results suggest that BDNF, GSK3ßand Wnt genes, might not have a major role in the development of personality traits. Further studies with larger sample size are warranted to evaluate the association of affective temperament and gene polymorphisms.