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- 1. 本態性振戦の薬理学的治療 pharmacologic treatment of essential tremor
- 2. 血液灌流 hemoperfusion
- 3. 小児における急性中毒性代謝性脳症 acute toxic metabolic encephalopathy in children
- 4. 成人における急性中毒性代謝性脳症 acute toxic metabolic encephalopathy in adults
- 5. 抗てんかん剤と骨疾患 antiepileptic drugs and bone disease
- Effect of aminoglutethimide on neutrophils in rats: implications for idiosyncratic drug-induced blood dyscrasias.
- Ng W1, Uetrecht J.Author information 1Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada M5S 3M2.AbstractAminoglutethimide (AMG) is an aromatic amine aromatase inhibitor associated with a high incidence of idiosyncratic blood dyscrasias, especially agranulocytosis. Animal models of idiosyncratic drug reactions (IDRs) represent essential tools to study these reactions; however, there is currently no valid model of idiosyncratic drug-induced agranulocytosis. Although AMG does not cause agranulocytosis in most animals or humans, drugs associated with serious IDRs generally cause a higher incidence of mild reactions that resolve despite continued treatment. Therefore, the effects of AMG on neutrophils and bone marrow in rats were studied to understand the mechanisms of more serious IDRs. An increase in peripheral blood neutrophils occurred as early as 24 h after AMG treatment with minimal changes to the total leukocyte count. Further investigation using 5-bromo-2'-deoxyuridine (BrdU) found an increased release of neutrophils from the bone marrow. Histologically, this corresponded to an increase in myeloid cells in the bone marrow, which was confirmed by differential staining with CD45 and CD71. AMG treatment stimulated an increase in colony forming unit granulocyte-macrophage and colony forming unit granulocyte ex vivo. There was also a marked increase in the number of activated neutrophils in the circulation expressing the extravasation marker CD62L. These findings indicate that AMG affects neutrophil production, release, and function. Similar effects on neutrophil kinetics in clozapine-treated rats have previously been found, and transient neutrophilia has been observed in patients taking other drugs associated with idiosyncratic agranulocytosis; therefore, the changes observed with AMG may be biomarkers to predict the risk that a drug will cause agranulocytosis.
- Chemical research in toxicology.Chem Res Toxicol.2013 Aug 19;26(8):1272-81. doi: 10.1021/tx400224j. Epub 2013 Aug 9.
- Aminoglutethimide (AMG) is an aromatic amine aromatase inhibitor associated with a high incidence of idiosyncratic blood dyscrasias, especially agranulocytosis. Animal models of idiosyncratic drug reactions (IDRs) represent essential tools to study these reactions; however, there is currently no val
- PMID 23889370
- Efficacy of tamoxifen ± aminoglutethimide in normal weight and overweight postmenopausal patients with hormone receptor-positive breast cancer: an analysis of 1509 patients of the ABCSG-06 trial.
- Pfeiler G1, Stöger H, Dubsky P, Mlineritsch B, Singer C, Balic M, Fitzal F, Moik M, Kwasny W, Selim U, Renner K, Ploner F, Steger GG, Seifert M, Hofbauer F, Sandbichler P, Samonigg H, Jakesz R, Greil R, Fesl C, Gnant M; ABCSG.Author information 1Division of Gynecology and Gynecological Oncology, Department of Obstetrics and Gynecology, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria.AbstractBACKGROUND: There exists evidence that body mass index (BMI) impacts on the efficacy of aromatase inhibitors in patients with breast cancer. The relationship between BMI and the efficacy of tamoxifen is conflicting. We investigated the impact of BMI on the efficacy of single tamoxifen and tamoxifen plus an aromatase inhibitor in the well-defined prospective study population of the ABCSG-06 trial.
- British journal of cancer.Br J Cancer.2013 Apr 16;108(7):1408-14. doi: 10.1038/bjc.2013.114. Epub 2013 Mar 19.
- BACKGROUND: There exists evidence that body mass index (BMI) impacts on the efficacy of aromatase inhibitors in patients with breast cancer. The relationship between BMI and the efficacy of tamoxifen is conflicting. We investigated the impact of BMI on the efficacy of single tamoxifen and tamoxifen
- PMID 23511562
- Changes in gene expression induced by aromatic amine drugs: testing the danger hypothesis.
- Ng W1, Uetrecht J.Author information 1Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Ontario, Canada.AbstractVirtually all drugs that contain a primary aromatic amine are associated with a high incidence of idiosyncratic drug reactions (IDRs), suggesting that this functional group has biological effects that may be used as biomarkers to predict IDR risk. Most IDRs exhibit evidence of immune involvement and the ability of aromatic amines to form reactive metabolites and redox cycle may be responsible for initiation of an immune response through induction of cell stress, as postulated by the Danger Hypothesis. If true, danger signals could be biomarkers of IDR risk. A previous attempt to test the Danger Hypothesis found that sulfamethoxazole (SMX), the only aromatic amine tested, was also the only drug not associated with an increase of cell stress genes in mice. To ensure that these observations were not species-specific, and to determine biomarkers of IDR risk common to aromatic amines, rats were treated with SMX and two other aromatic amine drugs, dapsone (DDS) and aminoglutethimide (AMG), and hepatic gene expression was determined using microarrays. As in mice, SMX induced minimal gene changes in the rat, and none indicated cell stress, whereas DDS and AMG induced several changes including up-regulation of enzymes such as aldo-keto reductase, glutathione-S-transferase, and aldehyde dehydrogenase, which may represent danger signals. Early insulin-induced hepatic gene (Eiih) was up-regulated by all three drugs. Some mRNA changes were observed in the Keap-1-Nrf2-ARE pathway; however, the pattern was significantly different for each drug. Overall, the most salient finding was that the changes in the liver were minimal, even though aromatic amines cause a high incidence of IDRs. The liver generates a large number of reactive species; however, the ability of aromatic amines to be bioactivated by cells of the immune system may be why they cause a high incidence of IDRs.
- Journal of immunotoxicology.J Immunotoxicol.2013 Apr-Jun;10(2):178-91. doi: 10.3109/1547691X.2012.707699. Epub 2012 Sep 12.
- Virtually all drugs that contain a primary aromatic amine are associated with a high incidence of idiosyncratic drug reactions (IDRs), suggesting that this functional group has biological effects that may be used as biomarkers to predict IDR risk. Most IDRs exhibit evidence of immune involvement and
- PMID 22970684
- Investigation of the stereoselective in vitro biotransformation of glutethimide by high-performance liquid chromatography and capillary electrophoresis
- WEINZ Corinna,BLASCHKE Gottfried,SCHIEBEL Hans-Martin
- Journal of chromatography. B, Biomedical sciences and applications 690(1), 233-242, 1997-03-07
- NAID 10024512363
- 南 幸男,三井 利幸,藤村 義和
- 分析化学 31(10), 604-607, 1982-10-05
- … No detectable interference for determination of barbiturates occured with any of the other compounds, such as sulfonal, bromovalerylurea, bromodiethylacetylurea, ethinamate, and glutethimide. …
- NAID 110002908407
- glutethimide glu·teth·i·mide (glōō-těth'ə-mīd') n. A nonbarbiturate sedative and hypnotic drug.
- glutethimide /glu·teth·i·mide/ (gloo-teth´ĭ-mīd) a nonbarbiturate used as a hypnotic and sedative. glu·teth·i·mide (glōō-tĕth′ə-mīd′) n. A nonbarbiturate sedative and hypnotic drug. glutethimide [gloo-teth´ĭ-mīd] a nonbarbiturate sedative and ...