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1.
J Anal Toxicol ; 35(1): 54-9, 2011 Jan.
Article in English | MEDLINE | ID: mdl-21219704

ABSTRACT

A death involving abuse of propylhexedrine and mitragynine is reported. Propylhexedrine is a potent α-adrenergic sympathomimetic amine found in nasal decongestant inhalers. The decedent was found dead in his living quarters with no signs of physical trauma. Analysis of his computer showed information on kratom, a plant that contains mitragynine, which produces opiumlike effects at high doses and stimulant effects at low doses, and a procedure to concentrate propylhexedrine from over-the-counter inhalers. Toxicology results revealed the presence of 1.7 mg/L propylhexedrine and 0.39 mg/L mitragynine in his blood. Both drugs, as well as acetaminophen, morphine, and promethazine, were detected in the urine. Quantitative results were achieved by gas chromatography-mass spectrometry monitoring selected ions for the propylhexedrine heptafluorobutyryl derivative. Liquid chromatography-tandem mass spectrometry in multiple reactions monitoring mode was used to obtain quantitative results for mitragynine. The cause of death was ruled propylhexedrine toxicity, and the manner of death was ruled accidental. Mitragynine may have contributed as well, but as there are no published data for drug concentrations, the medical examiner did not include mitragynine toxicity in the cause of death. This is the first known publication of a case report involving propylhexedrine and mitragynine.


Subject(s)
Drug-Related Side Effects and Adverse Reactions , Propylamines/toxicity , Secologanin Tryptamine Alkaloids/toxicity , Substance-Related Disorders/diagnosis , Acetaminophen/urine , Chromatography, Liquid , Evaluation Studies as Topic , Fatal Outcome , Gas Chromatography-Mass Spectrometry , Humans , Linear Models , Male , Morphine/urine , Promethazine/urine , Propylamines/blood , Propylamines/urine , Secologanin Tryptamine Alkaloids/blood , Secologanin Tryptamine Alkaloids/urine , Substance Abuse Detection/methods , Tandem Mass Spectrometry , Young Adult
2.
J Pediatr Gastroenterol Nutr ; 44(3): 318-25, 2007 Mar.
Article in English | MEDLINE | ID: mdl-17325551

ABSTRACT

OBJECTIVES: Cyclooxygenase-2 (COX-2) expression is increased in colorectal cancers and has been reported to be upregulated in Peutz-Jeghers polyps. To determine whether germline and somatic loss of BMPR1A in polyps from a patient with juvenile polyposis syndrome have altered COX-2 expression, we characterized a patient with juvenile polyposis syndrome for BMPR1A germline mutations and examined the polyps for BMPR1A expression and COX-2 expression. PATIENTS AND METHODS: DNA analysis for BMPR1A was performed on a patient with juvenile polyposis syndrome. Multiple polypectomies were performed, and several polyps showed adenomatous change. Genomic DNA was extracted from polyp material for loss of heterozygosity (LOH) analyses with microsatellite markers. Immunohistochemistry was performed on sections using antibodies for BMPR1A and COX-2. RESULTS: The kindred possessed a germline BMPR1A missense mutation. In polyp domains containing cystic and adenomatous epithelium, no LOH was observed using markers near the BMPR1A locus. Immunostaining indicated decreased expression of phospho-SMAD1 (pSMAD1), functionally downstream of the mutant BMPR1A receptor in the cystic epithelium, with further reduction in adenomatous portions within the polyp. COX-2 protein, normally not expressed in the colon, was present and increased in polyp epithelium. CONCLUSIONS: Decreased expression of pSMAD1 in the cystic epithelium with further reduction in the adenomatous area, and increase in COX-2 expression within polyps from the BMPR1A heterozygote, suggest a potential mechanism for adenomatous pathogenesis in these hamartomatous polyps. This may imply that COX-2 inhibitors could be a means for chemoprevention in this syndrome.


Subject(s)
Bone Morphogenetic Protein Receptors, Type I/genetics , Colonic Polyps/metabolism , Cyclooxygenase 2/biosynthesis , Peutz-Jeghers Syndrome/genetics , Adult , Bone Morphogenetic Protein Receptors, Type I/biosynthesis , Colonic Neoplasms/etiology , Colonic Polyps/complications , Germ-Line Mutation , Humans , Male , Mutation, Missense , Pedigree , Smad1 Protein/biosynthesis
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