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Thermo dynamic cycles in introductory physics courses are usually made up from a small number of permutations of isothermal, adiabatic, and constant-pressure and volume quasistatic strokes, with the working fluid usually being an ideal gas. Among them we find the Carnot, Stirling, Otto, Diesel, and Joule-Brayton cycles; in more advanced courses, steam cycles and refrigerators based on real working fluids are often introduced. Any additional cycles made up from the same simple strokes, and any extended analysis of known cycles, are welcome additions to the teaching repertory, as they provide more opportunities for practice and discussion. Our purpose in this note is to extend the analysis of the zilch cycle, introduced in ref. 1, by presenting its "TS" diagram and by proposing several variations that do not contain adiabatic strokes, thus allowing a simpler mathematical treatment. As a bonus, we also provide results that make it possible to represent practically any elementary ideal-gas cycle in a "TS" diagram.

Background: Zaleplon (ZAL) is a sedative-hypnotic agent, which is mainly metabolized to inactive 5-oxidized zaleplon (5-oxo-ZAL) and N-des-ethylated ZAL (des-ethyl-ZAL) in mice and humans. The former reaction is considered to be catalyzed by aldehyde oxidase present in liver cytosol., Methods: Here, we examined sex and strain differences of ZAL metabolism to 5-oxo-ZAL among four strains of mice, as well as the inter-individual variation in humans, in order to evaluate the variability of 5-oxo-ZAL-forming activity and its relationship with aldehyde oxidase activity. In mice, the activity in C57BL/6J strain was the highest, followed by C3H/He and BALB/c. The activity in DBA/2J was the lowest, being 2.3-fold lower than that of C57BL/6J mice. The activity of male mice was higher than that of female mice. Large inter-individual variations were observed among humans, with a range of 10- fold. Raloxifene, an inhibitor of aldehyde oxidase, markedly decreased the formation of 5-oxo-ZAL by liver cytosol of mice and humans. Further, the plasma level of 5-oxo-ZAL in mice was decreased when raloxifene was co-administered with ZAL., Results: Our results indicate that the formation of 5-oxo-ZAL from ZAL is mainly catalyzed by aldehyde oxidase in mice and humans, and the variability of 5-oxo-ZAL formation is due primarily to differences of aldehyde oxidase activity., Conclusion: High inter-individual variability of ZAL 5-oxidase activity and potential for interaction of ZAL with other medicines that are inhibitors of aldehyde oxidase should be taken into consideration in clinical usage of ZAL., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Patch testing (PT) can be used to identify allergens and irritants responsible for contact allergic and irritant dermatitis, respectively. However, the reproducibility of PT and correlation between PT and use test has not been fully evaluated. The aim of the present study was to examine the reproducibility of PT and its usefulness in assessing the safety of topical drugs. A total of 55 topical drugs were applied to the backs of two groups of subjects for either 24 or 48 h, and skin irritant reactions were graded at 2 and 24 h after patch removal. For the repeat open application test, six topical drugs with different irritation scores were applied to the arms of two groups of subjects twice daily for 3 weeks, and local symptoms were recorded. The mean irritation scores were similar between the two PT groups. The percentage of subjects positive for symptoms provoked by the use tests was similar between the two groups. The mean irritation scores 24 h after patch removal correlated with the skin symptoms provoked by the use test. PT was reproducible and the results correlated with the use test results. PT is a useful method for evaluating the safety of commercial topical drugs., (© 2014 Japanese Dermatological Association.)

1. Human chimeric mice (h-PXB mice) having humanized liver, constructed by transplantation of human hepatocytes, were evaluated as an experimental model for predicting human drug metabolism. Metabolism of zaleplon in h-PXB mice was compared with that in rat chimeric mice (r-PXB mice) constructed by transplantation of rat hepatocytes. 2. Zaleplon is metabolized to 5-oxo-zaleplon by aldehyde oxidase and to desethyl-zaleplon by cytochrome P450 (CYP3A4) in rat and human liver preparations. 3. Liver S9 fraction of h-PXB mice metabolized zaleplon to 5-oxo-zaleplon and desethyl-zaleplon in similar amounts. However, liver S9 fractions of r-PXB and control (urokinase-type plasminogen activator-transgenic severe combined immunodeficient) mice predominantly metabolized zaleplon to desethyl-zaleplon. 5-Oxo-zaleplon was detected as a minor metabolite. 4. Oxidase activity of h-PXB mouse liver cytosol toward zaleplon was about 10-fold higher than that of r-PXB or control mice. In contrast, activities for desethyl-zaleplon formation were similar in liver microsomes from these mice, as well as rat and human liver microsomes. 5. In vivo, the level of 5-oxo-zaleplon in plasma of h-PXB mice was about 7-fold higher than that in r-PXB or control mice, in agreement with the in vitro data. Thus, aldehyde oxidase in h-PXB mice functions as human aldehyde oxidase, both in vivo and in vitro. 6. In contrast, the plasma level of desethyl-zaleplon in r-PXB and control mice was higher than that in h-PXB mice. 7. These results suggest h-PXB mice with humanized liver could be a useful experimental model to predict aldehyde oxidase- and CYP3A4-mediated drug metabolism in humans.

The in vivo and in vitro metabolism of the sedative-hypnotic agent zaleplon (ZAL) to 5-hydroxylated ZAL (5-oxo-ZAL) and N-desethylated ZAL (desethyl-ZAL) was studied in four strains of rats. Incubation of ZAL with liver microsomes afforded desethyl-ZAL via cytochrome P450-catalyzed reaction, with little strain difference. In contrast, incubation of ZAL with liver cytosol afforded 5-oxo-ZAL with marked strain differences. ZAL hydroxylase activity was well correlated with aldehyde oxidase activity in these strains. The highest level of 5-oxo-ZAL and the highest activity of aldehyde oxidase were observed in cytosol from Sea:SD rats, followed by Jcl:SD rats, while Crj:SD and WKA/Sea rats showed low levels. When ZAL was administered to Sea:SD and WKA/Sea rats, both 5-oxo-ZAL and desethyl-ZAL were detected in blood as the major in vivo metabolites. However, the concentration of 5-oxo-ZAL was far higher in Sea:SD rats than in WKA/Sea rats, while that of desethyl-ZAL was far lower in Sea:SD rats. The levels of 5-oxo-ZAL in blood were closely correlated with the strain differences of cytosolic ZAL hydroxylase activity and benzaldehyde oxidase activity. Our results indicate that variability in the formation of 5-oxo-ZAL from ZAL in vivo in various strains of rats is primarily due to strain differences of hepatic aldehyde oxidase activity.

Background: Trichophyton-induced superficial skin mycosis is a common infectious human disease, but the immunological mechanism against Trichophyton infection is unclear with regard to many points. Since Trichophyton cannot colonize mice, guinea pigs were used in previous experiments on Trichophyton infection. However, it is difficult to perform immunological and genetic analyses in guinea pigs., Objective: The objective of this study was to establish a mouse Trichophytin-associated inflammation model of superficial skin mycosis in which immunological and genetic analyses can be performed., Methods: We established a mouse Trichophyton-induced contact hypersensitivity model by applying Trichophytin, the Trichophyton antigen, extracted from Trichophyton mentagrophytes, to mice. Using a Th1-dominant strain, C57BL/6, and a Th2-dominant strain, BALB/c, we investigated the expression of inflammatory cytokines and receptors of the innate immune system for fungi, TLR4, TLR2, and dectin-1, and their influences on responses of the acquired immune system., Results: In C57BL/6 mice, expressions of IFN-γ and IL-17 A in regional lymph nodes and IL-1β, IFN-γ, IL-6, and IL-23 in the inflammatory auricular skin were enhanced by Trichophytin challenge, suggesting that not only Th1 cells but also Th17 cells were induced. In BALB/c mice, expressions of IL-4 in regional lymph nodes, and TSLP and IL-4 in the auricular skin were enhanced by Trichophytin challenge. Interestingly, dectin-1-neutralizing antibody inhibited the promotion of IFN-γ production in C57BL/6 mice, and dectin-1-expressing immune cells had crucial actions in Trichophyton-induced IFN-γ production., Conclusion: These results suggest that inflammatory mediators differently regulate Trichophytin-induced contact hypersensitivity on the basis of the status of host immunity., (Copyright © 2012 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.)

Aldehyde oxidase-mediated oxidation of N(1)-methylnicotinamide to N(1)-methyl-2-pyridine-5-carboxamide (2-PY) and N(1)-methyl-4-pyridone-5-carboxamide (4-PY) in chimeric mice constructed by transplanting human hepatocytes into urokinase-type plasminogen activator-transgenic severe combined immunodeficient mice was examined in vivo and in vitro. The activity in liver cytosol of chimeric mice with a high replacement index was approximately 4-fold higher than that in control mice. Furthermore, the oxidation products in control mice were 2-PY and 4-PY, whereas, in chimeric mice, the major product was 2-PY, as in humans. The aldehyde oxidase in chimeric mouse liver was confirmed to be of human type by immunoblotting analysis. The ratio of pyridones (2-PY/4-PY) excreted in the urine of chimeric mice was closer to that of humans than to that of control mice. Thus, the aldehyde oxidase in chimeric mice has human-type functional characteristics.

The effect of the culture filtrate Gemella haemolysans in enhancing mycobacterial growth has been previously demonstrated. In the present studies, an attempt was made to confirm whether the addition of the filtrate into the medium would be an effective method to promote the rapid detection of mycobacteria in sputum specimens of patients. One-hundred and one sputum specimens pretreated with NaOH were inoculated with various media (Dubos, Dubos-agar, 1% Ogawa, Kudo PD, and Middlebrook 7H9) supplemented with the culture filtrate of Gemella haemolysans grown in blood-BHI or blood-HEM at the dilutions of 1/32 or 1/64. Addition of the filtrate reduced the amount of time required to detect mycobacterial growth (Mycobacterium tuberculosis, M. avium complex, and M. kansassi) by an average of 60-70%. The media containing the filtrate formed significantly larger numbers of colonies compared with the control media, and those colonies inoculated developed more rapidly in size. The findings clearly indicated that the culture filtrate promotes the effective growth of mycobacteria which cannot or only slowly grows in ordinary media. Also indicated was that the addition of the culture filtrate of Gemella haemolysans into media provides as a useful tool to allow the rapid diagnosis of mycobacterial diseases.

The culture filtrate of G. haemolysans enhanced the growth of mycobacteria. The enhancing substance seemed to be effectively produced in BHI broth supplemented with human blood. The mycobacterial growth was inhibited by high concentrations of the culture filtrate, but was markedly enhanced at low concentrations such as 1/32 or 1/64 dilutions. The generation time at log phase was 7 to 9 hours compared with 14 hours for the control, leading to rapid detection of mycobacteria in culture. With sputa specimens from tuberculosis patients, the culture time to visual detection of mycobacterial growth was decreased by 59 to 67%.

The first positive phototropic curvature induced by a pulse of unilateral white irradiation (0.1 watt per square meter, 30 seconds) of etiolated and de-etiolated Sakurajima radish (Raphanus sativus var hortensis f. gigantissimus Makino) hypocotyls was analyzed in terms of differential growth and growth inhibitor contents of the hypocotyls. In both etiolated and de-etiolated hypocotyls, the growth rates at the lighted sides were suppressed whereas those at the shaded ones showed no change. De-etiolation treatment induced a larger difference between the growth rates at the lighted and shaded sides of the hypocotyls, resulting in a larger curvature of de-etiolated seedlings than of etiolated ones. The contents of growth inhibitors, cis- and trans-raphanusanins, increased in the lighted but not in the shaded halves of the hypocotyls of etiolated seedlings. In de-etiolated seedlings, the two inhibitors increased due to the de-etiolation treatment. When de-etiolated seedlings were exposed to a pulse of unilateral irradiation the level of the two inhibitors remained high along the lighted side for 1 h following the light pulse, whereas at the shaded side the contents of the inhibitors abruptly decreased upon transfer to the dark, the difference between their amounts in the lighted and shaded sides being larger than in etiolated seedlings. Another growth inhibitor, raphanusamide, did not respond to the phototropic stimulus, although its amounts increased by the de-etiolation treatment. These data suggest that cis- and trans-raphanusanins are involved in the first positive phototropic response of radish hypocotyls, and that de-etiolation magnifies the phototropic response through induction of a larger lateral gradient of the raphanusanins in the hypocotyls by the phototropic stimulus.