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Excipient allergies are rare and difficult to diagnose. Carboxymethylcellulose (CMC, carmellose sodium) is an anionic water‐soluble polymer derived from native cellulose, that is, used as an excipient. Here, we report a case of urticaria caused by the CMC in lidocaine jelly and dimethicone drops, which had used for upper gastrointestinal endoscopy. CMC is widely used in pharmaceutical preparations, food additives, and other pharmaceuticals, and its use is increasing. However, there are few reports on immediate hypersensitivity reactions because substances containing CMC. Previous reports and our case suggest that excipients, such as CMC, can be potential hidden allergens. [ABSTRACT FROM AUTHOR]

Platelets have diverse roles in immune processes in addition to their key functions in haemostasis and thrombosis. Some studies imply that platelets may be possibly related to the immune tolerance induction. However, the role of platelets in the development of immune tolerance is not fully understood. The purpose of this study was to investigate the role of platelets in the development of regulatory mechanisms responsible for cutaneous inflammation using a mouse model of low zone tolerance (LZT). Mice were treated with 2,4,6‐trinitro‐1‐chlorobenzene (TNCB) 8 times every other day for tolerance induction with administration of anti‐platelet antibody or control antibody during the tolerance induction phase every 3 days. After the treatment for the tolerance induction, mice were sensitized and then challenged with TNCB. The contact hypersensitivity (CHS) was significantly decreased at 24 hours after challenge in the mice with LZT than in those without LZT. Platelet depletion via administration of anti‐platelet antibody reversed the inhibition of CHS and reduced the frequency of Foxp3+ Tregs in the inflamed skin and draining lymph nodes in mice with LZT. In addition, repeated low‐dose skin exposure resulted in elevated plasma levels of transforming growth factor (TGF)‐β1. Interestingly, platelet depletion reduced plasma TGF‐β1 levels of mice with LZT. Furthermore, the CHS response was reduced by administration of recombinant TGF‐β1 during platelet depletion in mice with LZT. Administration of anti‐TGF‐β antibody reversed the inhibition of the CHS responses. These results suggest that platelets are involved in the induction of immune tolerance via the release of TGF‐β1. [ABSTRACT FROM AUTHOR]

The article focuses on Japanese pacifism. Topics discussed include Japanese nationalism, postwar constitution in the country and settling of international disputes. Other topics which includes international peace, use of nuclear weapon by United States on Japan during World War II and U.S. military protection to Japan are also discussed.

A letter to the editor is presented regarding the occurrence of anaphylaxis in a 65-year-old woman due to the presence of γ-cyclodextrin in sugammadex which was administered to her after her maxillary cyst surgery.

The life of the ‘Other Bose’ involves an intriguing story, which complicates many of the general dichotomies of colonial history. Rash Behari Bose (1886–1945) was born in north-eastern Bengal in 1886. From his youth, he engaged in anti-British activities, on account of which he was forced to flee India in 1915. The Bengali independence fighter then escaped to pre-war Japan, befriended a group of influential Japanese Pan-Asianists, married into one of Tokyo's most progressive families, and continued his life as an activist into wartime. The case of Rash Behari Bose and his Japanese supporters constitutes a remarkable chapter in the developmental history of international cooperation among Asian peoples that preceded Japan's wartime Pan-Asianist rhetoric of the ‘Greater East Asia Co-Prosperity Sphere’. The present article argues that such evidence of cross-border cooperation in the modern history of Asia, as embraced by Rash Behari Bose and his supporters in Japan, sheds light on the analysis of an anti-Western transnationalism in its embryonic form. Thus, the aim of this article is two-fold. First, it attempts to introduce the little-known figure of Rash Behari Bose. Second, by considering the function of Pan-Asianism in Bose's story, I will attempt to demonstrate the complexity of Pan-Asianism not usually addressed in the conventional reading of its role simply as a propagandistic tool of Japan's imperial expansion. [ABSTRACT FROM AUTHOR]

1 Melanocortin (MC) receptors are widely distributed throughout the body of chicken, like in mammals, and participate in a wide range of physiological functions. 2 To clarify the pharmacological impact of ligands acting in the MC system, we expressed the chicken MC1, MC2, MC3, MC4 and MC5 (cMC1–5) receptors in eukaryotic cells and performed comprehensive pharmacological characterization of the potency of endogenous and synthetic melanocortin peptides. 3 Remarkably, the cMC mentors displayed high affinity for ACTH-derived peptides and in general low affinity for α-MSH. It is evident that not only the cMC2 receptor but also the other cMC receptors interact with ACTH-derived peptide through an epitope beyond the sequence of α-MSH. 4 The synthetic ligand MTII was found to be a potent agonist whereas HS024 was a potent antagonist at the cMC4 receptor, indicating that these ligands are suitable for physiological studies in chicken. 5 We also show the presence of prohormone convertase 1 (PC1) and PC2 genes in chicken, and that these peptides are coexpressed with proopiomelanocortin (POMC) in various tissues. [ABSTRACT FROM AUTHOR]

Shift work is indispensable in our modern society; therefore, measures for maintaining the health of shift workers are urgently required. In this prospective study observing the effects of different types of scheduled light-dark shift conditions in wild-type mice, we reared mice for 630 days under two chronic jet lag conditions with distinct programs of light and darkness: an 8-h phase delay every 7 days (delay, n = 14) or an 8-h phase advance every 4 days (advance, n = 34). 'Delay' represents a mild condition in which mice are entrained, whereas 'Advance' represents a condition of circadian rhythm disorder in which mice are not entrained. Our results showed that the 26.5% (9/34) mice reared under the 'Advance' shift condition died or were sacrificed by humane endpoint throughout the experiment, whereas the first death under 'Delay' condition occurred on day 611. The mortality rate of the mice reared under 'Advance' condition was higher than the mice under 'Delay' condition [HR (95% CI) 4.26 (0.54-33.6)]. In 'Advance' mice of shorter lifespan, which showed splenomegaly and increased myeloid cells in bone marrow, which indicates that chronic inflammation existed in those mice. Although this study is still preliminary, these findings suggest that prolonged severe circadian rhythm disorder may result in the induction of chronic inflammation and tend to result in a shorter lifespan. Further studies are needed to understand why and how circadian rhythm disorder increases the risk of various dysfunction of physiology and diseases. [ABSTRACT FROM AUTHOR]

Alpha-melanocyte stimulating hormone (α-MSH) added to serum-free primary culture of melanoblasts derived from epidermal cell suspensions of 0.5 d old C57BL/10JHir mice induced their differentiation. Analysis using the reverse transcription-polymerase chain reaction showed that the expression of the melanocyte-specificα-MSH receptor gene, melanocortin receptor-1 (MC1-R), had already been initiated before addition ofα-MSH, and, in addition, no up-regulation of the MC1-R gene was observed after addition ofα-MSH. However, no expression of the proopiomelanocortin (POMC) gene was observed before or after the addition ofα-MSH. The expression of the MC1-R and POMC genes in the epidermis and dermis of the dorsal skin was surveyed from 13 d old embryos to 5.5 d old neonates. The expression of the MC1-R gene was first observed in the epidermis of 13 d old embryos, and gradually increased up to 0.5 d after birth, and thereafter remained constant. By contrast, the expression of the MC1-R gene in the dermis was first observed in 16 d old embryos, and gradually increased up to 3.5 d after birth, and thereafter remained constant. However, no expression of the POMC gene was observed in the epidermis or dermis of the dorsal skin at any age of mice tested. These results suggest that the expression of the MC1-R gene, but not of the POMC gene, plays an important role in the regulation of melanocyte differentiation in mouse skin. [ABSTRACT FROM AUTHOR]

The present study was designed to clarify the role of the agouti gene in the regulation of the proliferation and differentiation of mouse epidermal melanocytes using serum-free primary culture of epidermal melanocytes from 0.5-d-old black (a/a; C57BL/10JHir) mice and congenic, agouti (A/A; C57BL/10JHir-A/A) mice. There was no significant difference in the proliferation or differentiation of melanocytes betweena/aandA/Amice. However, the content of pheomelanin in culture media fromA/Amelanocytes was increased byl-tyrosine compared witha/amelanocytes. In addition, the content of the pheomelanin precursor, 5-S-cysteinyldopa, in culture media fromA/Amelanocytes was dramatically increased byl-tyrosine. Moreover, pheomelanin content in the epidermis from 3.5- and 5.5-d-oldA/Amice was much higher than ina/amice. Analysis of theAgene using reverse transcription-polymerase chain reaction revealed that cultured keratinocytes and melanocytes do not express theAgene. Moreover, theAgene was expressed in theA/Adermis of 0.5-, 3.5- and 5.5-d-old mice, but not in thea/adermis nor in theA/Aora/aepidermis. These results suggest thatA/Aepidermal melanoblasts are influenced by theAgene from the dermis of neonatal mice, and are capable of synthesizing pheomelanin in the culture. Pheomelanin production in the epidermis from 3.5- and 5.5-d-oldA/Amice may be induced by the expression of the agouti gene in the dermis. [ABSTRACT FROM AUTHOR]

1. Buffer conditions inin vitrometabolism studies using human liver microsomes (HLM) have been reported to affect the metabolic activities of several cytochrome P450 (CYP) isozymes in different ways, although there are no reports about the dependence of CYP2C8 activity on buffer conditions. 2. The present study investigated the effect of buffer components (phosphate or Tris-HCl) and their concentration (10–200 mM) on the CYP2C8 and CYP3A4 activities of HLM, using paclitaxel and triazolam, respectively, as marker substrates. 3. TheKm(or S50) andVmaxvalues for both paclitaxel 6α-hydroxylation and triazolam α- and 4-hydroxylation, estimated by fitting analyses based on the Michaelis–Menten or Hill equation, greatly depended on the buffer components and their concentration. 4. The CLintvalues in phosphate buffer were 1.2–3.0-fold (paclitaxel) or 3.1–6.4-fold (triazolam) higher than in Tris-HCl buffer at 50–100 mM. These values also depended on the buffer concentration, with a maximum 2.3-fold difference observed between 50 and 100 mM which are both commonly used in drug metabolism studies. 5. These findings suggest the necessity for optimization of the buffer conditions in the quantitative evaluation of metabolic clearances, such asin vitro–in vivoextrapolation and also estimating the contribution of a particular enzyme in drug metabolism. [ABSTRACT FROM AUTHOR]

Abstract: Higher plants do not ordinarily possess ketocarotenoids due to the absence of a carotenoid ketolase enzyme. We expressed genes coding for marine-bacterial enzymes β-carotene ketolase (CrtW) and β-carotene hydroxylase (CrtZ) in tobacco plants (Nicotiana tabacum) by transplastomic engineering. A novel carotenoid, 4-ketoantheraxanthin, was isolated from the leaves of the tobacco transformants. The structure of 4-ketoantheraxanthin was determined to be (3S,3′S,5′R,6′S)-5′,6′-epoxy-3,3′-dihydroxy-β,β-caroten-4-one by analysis of the MS, NMR, and CD data. This carotenoid was considered to be synthesized by a 4-ketolation reaction by CrtW of antheraxanthin that had been synthesized by the endogenous carotenoid biosynthetic enzymes present in higher plants and CrtZ. 4-Ketoantheraxanthin was also shown to have potent antioxidative activity against a 1O2 suppression model. [Copyright &y& Elsevier]