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“Laromustine (VNP40101M, also known as Cloretazine) is a novel sulfonylhydrazine alkylating ( anticancer) agent. Laromustine generates two types of reactive intermediates: 90CE and methylisocyanate. When incubated

with rat, dog, monkey, and human liver microsomes, [(14)C]laromustine was converted to 90CE (C-8) and seven other radioactive components (C-1-C-7). There was little difference in the metabolite profile among the species examined, in part because the formation of most components (C-1-C-6 and 90CE) did not require NADPH but involved decomposition and/or hydrolysis. The exception was C-7, a hydroxylated metabolite, largely formed by CYP2B6 and CYP3A4/5. Laromustine LY294002 solubility dmso caused direct inhibition of CYP2B6 and CYP3A4/5 ( the two enzymes involved in C-7 formation) as well as of CYP2C19. K(i) values were 125 mu M for CYP2B6, 297 mu M for CYP3A4/5, and 349 mu M for CYP2C19 and were greater

than the average clinical plasma C(max) of laromustine ( 25 mu M). There was evidence of time-dependent inhibition of CYP1A2, CYP2B6, and CYP3A4/5. Treatment of primary cultures of human hepatocytes WZB117 with up to 100 mu M laromustine did not induce CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, or CYP3A4/5, but the highest concentration of laromustine decreased the activity and levels of immunoreactive CYP3A4. The results of this study suggest the laromustine has 1) negligible victim potential with respect to metabolism by cytochrome P450 enzymes, 2) negligible enzyme-inducing potential, and 3) the potential in some cases to cause inhibition of CYP2B6, CYP3A4, and possibly CYP2C19 during and shortly after the duration of intravenous administration of this anticancer drug, but the clinical effects of such interactions are likely to be insignificant.”
“Aims To isolate, characterize and identify lactic acid bacteria (LAB) in yan-tsai-shin (fermented broccoli stems), a traditional fermented food in Taiwan. Methods and Results A total of 226 LAB were isolated; 111 cultures were isolated from samples collected from seven different markets and 115 from six fresh broccoli samples. These isolates were characterized phenotypically

and then initially divided into nine Dactolisib concentration groups (r1 to r9) using restriction fragment length polymorphism analysis and sequencing of 16S ribosomal DNA. Some isolates were further divided into four additional groups by other genetic analysis. The most common bacterial genera in yan-tsai-shin and fresh broccoli were Weissella, Lactococcus and Lactobacillus. Regional similarities in the LAB, with differences in diversity, were observed in this study. On the basis of phylogenetic analysis of 16S rRNA, rpoA, rpoB and pheS gene sequences, two strains were included in the genera Enterococcus and Lactococcus, respectively, and identified as potential novel species or subspecies. In addition, the novel enterococcal strain, and 33 L.lactis subsp.