Management of fungal infections following allogeneic stem cell transplantation

Fungal infection remains an important complication in allogeneic stem cell transplantation (allo-SCT). Since the prognosis of fungal infection is poor, prophylaxis is critical for its management; owing to recent progression in allo-SCT management and widespread use of reduced-intensity regimens, the strategy of infectious prophylaxis has also changed. Various antifungals have recently been developed and applied to clinical use. A major change in antifungal management will probably occur in the next few years.     

A study of cancer information for cancer patients on the internet

Background  There have been few studies of the information provided for cancer patients on the internet. Methods  Using the Japanese language, we searched for cancer-related web pages, using the Google search engine, and evaluated the characteristics of the 150 top-ranked search results. We collected information on the operators of the websites, number of links, existence of a search function, and advertisements on the site. According to their contents, the 150 websites were classified into seven categories, of which five (numbers 1, 2, 3, 4, and 6) each accounted for 20% of the websites. The categories were: (1) media-related websites (e.g., newspapers and publishers), and portal sites; (2) patient association websites, patient's diaries, blogs by patients and/or their families (n = 33); (3) websites of medical institutions (e.g., hospitals; n = 27); (4) websites of research institutions (e.g., universities; n = 35); (5) websites of pharmaceutical companies; (6) other websites providing medical information (n = 32); and (7) other websites that did not belong to categories 1–6. Outgoing links were common in websites created by media-related organizations (median, 13) or patients and their families (median, 15), but such links were not common in the other types of websites (median, 0–4). Eight of the 13 cancer based hospitals in Japan, as well as the National Cancer Center were publishing general cancer information on their websites. Of the 13 cancer based hospitals, 12 included a link to the National Cancer Center. The National Cancer Center had the largest amount of information (736 575 words), exceeding the amount provided by the other cancer based hospitals (1 622–155 515 words). Two of the 7 websites of academic associations (included in category 6) had cancer information for patients, but the document sizes were small (3230–44 091 words). Conclusion  The website of the National Cancer Center is the most prominent source of general cancer information for patients, but it still has room for improvement in its usability.     

The mechanism causing the difference in kinetic properties between rat CYP2D4 and human CYP2D6 in the oxidation of dextromethorphan and bufuralol

The capacity to oxidize bufuralol (BF) and dextromethorphan (DEX) was compared kinetically between human CYP2D6 and four rat CYP2D (CYP2D1, -2D2, -2D3 and -2D4) isoenzymes in a yeast cell expression system. In BF 1″-hydroxylation and DEX O-demethylation, only CYP2D4 showed hook-shaped Eadie-Hofstee plots, the other four CYP2D enzymes exhibiting linear plots. In DEX N-demethylation, rat CYP2D2 did not show any detectable activity under the conditions used, whereas the other four enzymes yielded linear Eadie-Hofstee plots. To elucidate the mechanisms causing the nonlinear kinetics, four CYP2D4 mutants, CYP2D4-F109I, -V123F, -L216F and -A486F, were prepared. CYP2D4-V123F, -L216F and -A486F yielded linear or linear-like Eadie-Hofstee plots for BF 1″-hydroxylation, whereas only CYP2D4-A486F exhibited linear plots for DEX O-demethylation. The substitution of Phe-109 by isoleucine did not have any effect on the oxidative capacity of CYP2D4 for either BF or DEX. These results suggest that the introduction of phenylalanine in the active-site cavity of CYP2D4 simplifies complicated interactions between the substrates and the amino acid residues, but the mechanisms causing the simplification differ between BF and DEX.     

Oxidative metabolism of cinnarizine in rat liver microsomes.

The oxidative metabolism of cinnarizine (CZ) [1-(diphenylmethyl)-4-(3-phenyl-2-propenyl)-piperazine] to 1-(diphenylmethyl)piperazine (M-1), 1-(diphenylmethyl)-4-[3-(4'-hydroxyphenyl)-2-propenyl]piperazine (M-2), benzophenone (M-3) and 1-[4'-hydroxyphenyl)-phenylmethyl]-4-(3- phenyl-2-propenyl)piperazine (M-4) has been studied in rat liver microsomes. In Wistar rats, kinetic analysis revealed sex differences (male > female) in the Km values for formation of all the metabolites and the Vmax values for the formation of M-1, M-3 and M-4. The reactions required NADPH, and were inhibited by carbon monoxide and SKF 525-A. Only M-2 formation was suppressed by sparteine or metoprolol, and was significantly lower in female Dark Agouti rats than in Wistar rats of both sexes. The results suggest that CZ is oxidized by cytochrome P450, and M-2 formation is related to debrisoquine/sparteine-type polymorphic drug oxidation.