We have compared the distribution of fluconazole (FLC) with that of itraconazole (ITC) and griseofulvin (GRF) in the abdominal skin tissues after a single oral dose was administered to guinea pigs. The FLC concentrations in the stratum corneum reached a peak at 2 h after administration and were similar to those of ITC and higher than those of GRF in spite of the administration of a lower dose. GRF was eliminated from the stratum corneum faster than FLC and ITC. The FLC concentrations were also remarkably higher than those of ITC and GRF in the epidermis-cutis but lower in the subcutaneous fatty tissue. The distribution characteristics of each drug result from differences in their physicochemical properties. Following the administration of multiple doses, the FLC concentrations in the stratum corneum were highest in the abdominal skin tissues; those at 24 h after each administration increased gradually and were maintained at a level more than 10 times higher than that of the plasma concentrations. The FLC concentrations in the planta pedis stratum corneum and in the nail showed good dose proportionality and obvious accumulation and were 60 and 40 times as high as that in plasma on day 14. The extent of binding of FLC to human corneous keratin in vitro was about 10%, which is lower than those of ITC (94 to 97%) and GRF (36 to 38%). FLC, unlike ITC, therefore, is presumed to exist in the stratum corneum at high concentrations in an active nonbinding form. These excellent intracutaneous pharmacokinetic properties of FLC probably account in large part for the in vivo efficacy of FLC.

Cu 2 ZnSnS 4 thin films were grown epitaxially on GaP substrates by pulsed laser deposition (PLD). The band gap of the films was about 1.5 eV from the absorption spectra. In XRD patterns, two CTZS peaks, (004) and (008), were observed at the vicinity of GaP peaks of (200) and (400), respectively. The Cu 2 ZnSnS 4 thin films deposited at substrate temperatures of 350 and 400 °C were nearly stoichiometric and showed 4 poles observed at about 48° in pole figure measurement, indicating that the samples were oriented in plane.

The annual nitrogen (N) budget was measured in a soybean-cultivated upland field during the first year after conversion from a paddy field on gray lowland soil, which is typically found on the Sea of Japan side of northern Japan. Forage rice was cultivated on lysimeter fields for 4 consecutive years with applications of chemical fertilizer, immature compost, or mature compost (the control, immature compost, and mature compost plots, respectively), and then the fields were converted to upland fields for soybean (Glycine max [L.] Merrill cultivar Ryuho) cultivation. Input (seed, bulk N deposition, and symbiotic dinitrogen [N 2 ] fixation) and output (harvested grain, leached N via drainage water, and nitrous oxide emission) N flows were measured, and the field N budget was estimated from the difference between the input and output. The soybean plants in the immature and mature compost plots grew well and had higher yields (498-511 g m ) in the mature compost plot (27.7) was higher than those in the control (18.1) and immature compost plots (19.9). Percentages of soybean N accumulation derived from N 2 fixation ranged from 53% to 74%. N derived from symbiotic N 2 fixation accounted for more than 90% of the total N input, whereas harvested grain accounted for approximately 85% of the total N output. N leaching mainly occurred during the fallow period, accounting for 13-15% of the total N output. The annual N budgets were negative ()10.0, )14.2, and )6.4 g N m )2 year )1for the control, immature compost, and mature compost plots, respectively). The N loss from the immature compost plot was higher than that of the control plot, because the N output in harvested grain was higher, and the N input by N 2 fixation was similar between plots. While the N loss from the mature compost plot was lower than that of the control plot because the N output in harvested grain was higher, as was the case in the immature compost plot, the N input by N 2 fixation was also higher. Preceding compost application--whether immature or mature compost--to paddy fields increased the subsequent soybean yield during the first year after conversion. This result suggests that N loss and the following decrease in soil N availability in the field could be mitigated by increased N 2 fixation resulting from mature compost application with an appropriate application practice.

Imatinib and nilotinib are inhibitors that selectively target a set of protein tyrosine kinases, including abelson kinase (Abl), together with the chimeric oncoprotein, breakpoint cluster region-abelson kinase (Bcr-Abl), as well as stem cell factor receptor (KIT), platelet-derived growth factor receptor (PDGFR), discoidin domain receptor (DDR), and colony stimulating factor-1 receptor (CSF-1R). The aim of the present study was to investigate whether imatinib or nilotinib was effective against arthritis in the glucose-6-phosphate isomerase (GPI)-induced arthritis mouse model. Imatinib or nilotinib was administered orally to the arthritic mice at different time points. Efficacy was evaluated by visual scoring and by determining the production of anti-GPI antibody. Splenocytes from the arthritic mice were cultured with GPI in the presence of imatinib or nilotinib in vitro, and cytokine levels in the culture supernatants were analyzed. To investigate the effects of imatinib and nilotinib on T-cell proliferation, lymph node cells from the arthritic mice were cultured with GPI in the presence of imatinib or nilotinib in vitro. Interleukin (IL)-17 mRNA expression in the arthritic ankle joints from the onset of arthritis was analyzed by real-time polymerase chain reaction (PCR). The administration of imatinib from day 0 showed suppression of arthritis (P < 0.05), the administration of nilotinib from day 0 resulted in pronounced suppression of arthritis (P < 0.01), and that from day 7 showed significant inhibition of the progression of arthritis (P < 0.05). A reduction in anti-GPI antibodies was correlated with the therapeutic efficacy of imatinib, but not with that of nilotinib. Imatinib dose-dependently inhibited tumor necrosis factor (TNF)-α, IL-6, interferon (IFN)-γ, and IL-17 production by splenocytes in vitro, while nilotinib inhibited only IL-17 and IFN-γ production in a dose-dependent fashion. Imatinib at 3 μM exerted a mild antiproliferative effect on CD4+ T cells (P < 0.05), whereas imatinib at 10 μM and nilotinib at 3 and 10 μM demonstrated a marked antiproliferative effect (P < 0.01). The IL17 gene expression level on day 7 tended to be higher than that on day 14. These findings suggest that imatinib and nilotinib could prevent autoimmune arthritis, essentially via distinct mechanisms, in that imatinib inhibits both inflammatory and T-cell-derived cytokine production, whereas nilotinib suppresses T-cell-derived cytokine production. Imatinib and nilotinib could have therapeutic potential for rheumatoid arthritis (RA) and other inflammatory diseases.

In this study, in addition to studying the efficacy and safety of the once-daily administration of 100-mg capsules of fluconazole over an 8-week administration period with six patients with hyperkeratotic-type tinea pedis, we also measured the serum and horny layer concentrations of fluconazole to study the mobility into the horny layer in diseased areas of the sole skin. The final overall efficacy and overall safety were both 100% (six out of six), and no side-effects, including abnormal laboratory changes, were observed in any of the patients. The drug mobility study revealed that in the horny layer of the skin a steady state was reached after 4 weeks of administration, with the mean concentration being 12.8 micrograms g-1. This concentration was a high concentration that was no less than 13 times the geometric mean MIC (0.972 microgram ml-1) for fresh clinical isolates of Trichophyton rubrum. Based on the above results, fluconazole is considered to be highly useful for treating various kinds of dermatomycosis, including hyperkeratotic-type tinea pedis.

Midkine (MK) is a heparin-binding growth factor and forms a novel protein family together with another member, pleiotrophin (PTN)/heparin-binding growth-associated molecule (HB-GAM). A cDNA clone isolated from Xenopus laevis specifies for the Xenopus counterpart of MK (XMK), and the mode of XMK expression was studied by in situ hybridization and Northern blot analysis. XMK was first expressed at stage 11 (middle gastrula) and was located in the neural anlage at stage 12 (late gastrula). Through stage 13 to 15 (early neurula), XMK expression was restricted to the neural folds. At stage 23 (tailbud stage), XMK was predominantly localized in the brain and neural tube. At the larva stage, XMK expression was again restrictedly observed in the brain, the optic vesicles, the otic vesicle, and the spinal cord, all of which are derivatives of the neural tube, as well as in the branchial arches, derivatives of the cranial neural crest. Comparing the mode of MK expression between Xenopus and the mouse, we propose that MK plays evolutionally conserved roles in neurogenesis and development of the craniofacial architecture of ectomesenchymal origin. We also found that XMK was expressed in various adult organs; strong expression was observed in the brain, the eye and the spinal cord, all of which showed intense MK expression at the larva stage.

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We analyzed the decomposition of Ga(CH3)3 (TMG) during the metal organic vapor phase epitaxy (MOVPE) of GaN on the basis of first-principles calculations and thermodynamic analysis. We performed activation energy calculations of TMG decomposition and determined the main reaction processes of TMG during GaN MOVPE. We found that TMG reacts with the H2 carrier gas and that (CH3)2GaH is generated after the desorption of the methyl group. Next, (CH3)2GaH decomposes into (CH3)GaH2 and this decomposes into GaH3. Finally, GaH3 becomes GaH. In the MOVPE growth of GaN, TMG decomposes into GaH by the successive desorption of its methyl groups. The results presented here concur with recent high-resolution mass spectroscopy results.