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  • Mice  (2)
  • Mutagenesis, Insertional  (2)
  • bioavailability  (2)
  • *Point Mutation  (1)
  • 2005-2009
  • 1990-1994  (4)
  • 1
    ISSN: 1432-1041
    Keywords: 6-Mercaptopurine ; suppository ; bioavailability ; acute lymphoblastic leukaemia ; children ; interindividual variability ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma levels and the area under the plasma concentration-time curve (AUC) values of 6-mercaptopurine (6-MP) were determined in a balanced crossover study of oral (powder) and rectal (macrogol suppository) administration to 5 children with acute lymphoblastic leukaemia (ALL). The AUC (538.6 ng · h · ml−1) after the rectal dose of 30 mg/m2 was approximately 1.5-times of that (365.5 ng · h · ml−1) after the oral dose of 87.5 mg/m2. The coefficients of variation of interindividual variability of the AUCs were 21.5% and 32.3%, respectively. The relative bioavailability of the macrogol suppository compared to the powder was approximately 4.39. These findings indicate that rectal administration of 6-MP could avoid the first-pass effect of this drug in the alimentary canal and/or liver, resulting in a large AUC of 6-MP, and so could reduce interindividual variability in plasma 6-MP concentrations. Rectal administration of 6-MP may be more effective than empirical oral dosing for the treatment of children with ALL, especially for patients with nausea and/or vomiting.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1573-904X
    Keywords: 6-mercaptopurine ; bioavailability ; macrogol ; Witepsol ; rectal administration ; first-pass effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 3
    Publication Date: 1993-04-30
    Description: A recessive mutation was identified in a family of transgenic mice that resulted in a reversal of left-right polarity (situs inversus) in 100 percent of the homozygous transgenic mice tested. Sequences that flanked the transgenic integration site were cloned and mapped to mouse chromosome 4, between the Tsha and Hxb loci. During early embryonic development, the direction of postimplantation turning, one of the earliest manifestations of left-right asymmetry, was reversed in homozygous transgenic embryos. This insertional mutation identifies a gene that controls embryonic turning and visceral left-right polarity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yokoyama, T -- Copeland, N G -- Jenkins, N A -- Montgomery, C A -- Elder, F F -- Overbeek, P A -- HD25340/HD/NICHD NIH HHS/ -- N01-CO-74101/CO/NCI NIH HHS/ -- New York, N.Y. -- Science. 1993 Apr 30;260(5108):679-82.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Biology, Baylor College of Medicine, Houston, TX 77030.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8480178" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Animals ; Chromosome Mapping ; Cloning, Molecular ; Embryonic and Fetal Development/*genetics ; Female ; *Genes, Recessive ; Homozygote ; Male ; Mice ; Mice, Transgenic ; Mutagenesis, Insertional ; Situs Inversus/*genetics
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 1993-04-02
    Description: Point mutations that activate the Ki-ras proto-oncogene are presented in about 50 percent of human colorectal tumors. To study the functional significance of these mutations, the activated Ki-ras genes in two human colon carcinoma cell lines, DLD-1 and HCT 116, were disrupted by homologous recombination. Compared with parental cells, cells disrupted at the activated Ki-ras gene were morphologically altered, lost the capacity for anchorage-independent growth, grew more slowly both in vitro and in nude mice, and showed reduced expression of c-myc. Thus, the activated Ki-ras gene plays a key role in colorectal tumorigenesis through altered cell differentiation and cell growth.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shirasawa, S -- Furuse, M -- Yokoyama, N -- Sasazuki, T -- New York, N.Y. -- Science. 1993 Apr 2;260(5104):85-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Kyushu University, Fukuoka, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8465203" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Cell Differentiation ; Cell Division ; Codon ; Colonic Neoplasms/*genetics/pathology ; Gene Expression Regulation, Neoplastic ; Genes, myc/genetics ; Genes, ras/*genetics ; Humans ; Infant ; Mice ; Mice, Nude ; Molecular Sequence Data ; Mutagenesis, Insertional ; Nucleic Acid Hybridization ; Plasmids ; *Point Mutation ; Polymerase Chain Reaction ; Restriction Mapping ; Transfection ; Tumor Cells, Cultured
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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