Toxicological Analysis of Victims' Blood and Crime Scene Evidence Samples in the Sarin Gas Attack Caused by the Aum Shinrikyo Cult

Background:Ethyl alcohol is the most popular legal drug, but its excessive consumption causes social problems. Despite many public campaigns against alcohol use, car accidents, instances of aggressive behaviour, sexual assaults and deterioration in labor productivity caused by inebriated people is still commonplace. Fast and easy diagnosis of alcohol consumption is required in order to introduce proper and effective therapy, and is crucial in forensic toxicology analysis. The easiest method to prove alcohol intake is determination of ethanol in body fluids or in breath. However, since ethanol is rapidly metabolized in the human organism, only recent consumption can be detected using this method. Because of that, the determination of alcohol biomarkers was introduced for monitoring alcohol consumption over a wider range of time.Objective:The objective of this study was to review published studies focusing on the sample preparation methods and chromatographic or biochemical techniques for the determination of alcohol biomarkers in whole blood, plasma, serum and urine.Methods:An electronic literature search was performed to discuss possibilities and limitations of application of alcohol biomarkers in toxicological analysis.Results:Authors described the markers of alcohol consumption such as: ethanol, its nonoxidative metabolites (ethyl glucuronide, ethyl sulfate, phosphatidylethanol, ethyl phosphate, fatty acid ethyl esters) and oxidative metabolites (acetaldehyde and acetaldehyde adducts). We also discussed issues concerning the detection window of these biomarkers, and possibilities and limitations of their use in routine analytical toxicology for monitoring alcohol consumption or sobriety during alcohol therapy.

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Biological and Toxicological Evaluation of N-(4methyl-phenyl)-4-methylphthalimide on Bone Cancer in Mice

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520619666190207130732 ◽

2019 ◽

Vol 19 (5) ◽

pp. 667-676

Author(s):

José R. Santin ◽

Gislaine F. da Silva ◽

Maria V.D. Pastor ◽

Milena F. Broering ◽

Roberta Nunes ◽

...

Keyword(s):

Breast Cancer ◽

Bone Metastasis ◽

In Silico ◽

Bone Matrix ◽

Micronucleus Assay ◽

Repeated Treatment ◽

Toxicological Evaluation ◽

Toxicological Analysis ◽

Breast Cancer Bone Metastasis

Background: It was recently demonstrated that the phthalimide N-(4-methyl-phenyl)-4- methylphthalimide (MPMPH-1) has important effects against acute and chronic pain in mice, with a mechanism of action correlated to adenylyl cyclase inhibition. Furthermore, it was also demonstrated that phthalimide derivatives presented antiproliferative and anti-tumor effects. Considering the literature data, the present study evaluated the effects of MPMPH-1 on breast cancer bone metastasis and correlated painful symptom, and provided additional toxicological information about the compound and its possible metabolites. Methods: In silico toxicological analysis was supported by in vitro and in vivo experiments to demonstrate the anti-tumor and anti-hypersensitivity effects of the compound. Results: The data obtained with the in silico toxicological analysis demonstrated that MPMPH-1 has mutagenic potential, with a low to moderate level of confidence. The mutagenicity potential was in vivo confirmed by micronucleus assay. MPMPH-1 treatments in the breast cancer bone metastasis model were able to prevent the osteoclastic resorption of bone matrix. Regarding cartilage, degradation was considerably reduced within the zoledronic acid group, while in MPMPH-1, chondrocyte multiplication was observed in random areas, suggesting bone regeneration. Additionally, the repeated treatment of mice with MPMPH-1 (10 mg/kg, i.p.), once a day for up to 36 days, significantly reduces the hypersensitivity in animals with breast cancer bone metastasis. Conclusion: Together, the data herein obtained show that MPMPH-1 is relatively safe, and significantly control the cancer growth, allied to the reduction in bone reabsorption and stimulation of bone and cartilage regeneration. MPMPH-1 effects may be linked, at least in part, to the ability of the compound to interfere with adenylylcyclase pathway activation.

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