Emission-Color Control in Polymer Films by Memorized Fluorescence Solvatochromism in a New Class of Totally Organic Fluorescent Nanogel Particles.

In this work, a new class of totally organic fluorescent nanogel particles and their exceptionally specific behaviors based on their unique structures are introduced, which draws a sharp line from conventional fluorophore-doped and fluorophore-branched-type particles. The nanogel particles, the diameter of which could be controlled by adjusting reaction conditions, such as the solvent system, were spontaneously fabricated with a spherical shape by direct polymerization of non-heterocyclic aromatic compounds, such as 2,6-dihydroxyanthracene, 2,6-dihydroxynaphthalene, and 9,9-bis(4-hydroxyphenyl)fluorene with triazinane as the cross-linker. A fluorophoric moiety formed from a polymer main chain was realized in the particle, and consequently, the resultant content of the fluorophoric moiety was around 70-80 wt % per particle. The uniqueness and versatility of the particles can be emphasized by their good compatibility with various solvents due to their amphiphilic and ampholytic swelling properties, but also by their remarkable fluorescent solvatochromism in the dispersion state. Furthermore, these behaviors were preserved even in their polymer composite system. This study also demonstrates that various fluorescent polymer films can be fabricated with emission color control due to memorization of the solvatochromism phenomenon of the dispersed fluorescent nanoparticles.

Investigation of Discoloration of Furosemide Tablets in a Light-Shielded Environment.

We observed that uncoated furosemide tablets turned yellow in a light-shielded automatic packaging machine and discoloration of the furosemide tablets was heterogeneity and occurred on the surface of the tablets only. The machine was equipped with an internal blower to maintain a constant temperature. Therefore, we investigated the effect of air flow on the discoloration of the furosemide tablets using a blower in a dark environment. The color difference (ΔE) of the furosemide tablets increased linearly as the blowing time increased. We performed structural analysis of the yellow compound in the furosemide tablets by LC-MS and identified the compound as a hydrolysate of furosemide. This suggested that furosemide hydrolysis was accelerated by the air flow. The furosemide tablets were prepared with the most stable furosemide polymorph, form I. X-Ray powder diffractometry and IR spectroscopy showed that during tablet preparation, no crystal transition occurred to an unstable furosemide polymorph. Furthermore, IR spectroscopy showed that the crystal form of furosemide in the yellow portion of the tablets was form I. To elucidate the factors producing the discoloration, we investigated the effect of humidity and atmosphere (air, oxygen, and nitrogen) on the discoloration of the furosemide tablets. The results suggested that the discoloration of the furosemide tablets was accelerated by oxidation, although humidity did not affect the hydrolysis. Therefore, we concluded that the discoloration of the furosemide tablets in the automatic packing machine was caused by acceleration of oxidative degradation by air flow.

Identification of Furosemide Photodegradation Products in Water-Acetonitrile Mixture.

The aim of this study was to identify the chemical structure of the photodegradation products of furosemide in a water-acetonitrile mixture (1 : 1). Furosemide solution was irradiated with a D65 fluorescent lamp and the products were isolated by preparative HPLC. The fractions were evaporated to dryness in vacuo. The purity of the photodegradation products was measured by HPLC. The purity of products 1, 3, and 4 was greater than 90%, whereas that of product 2 was 13%, therefore, photodegradation product 2 was unstable. We identified photodegradation products 1 and 3 as 4-chloro-5-sulfamoylanthranilic acid and 4-hydroxy-N-furfuryl-5-sulfamoylanthranilic acid, respectively, by LC/MS and NMR. Additionally, we assumed that photodegradation product 4 was methyl 2-((furan-2-ylmethyl)amino)-4-hydroxy-3-(methyleneamino)-5-sulfamoylbenzoate by LC/MS and NMR. This showed that furosemide underwent hydrolysis and substitution, and reacted with the acetonitrile under the light of a D65 fluorescent lamp. We were furthermore able to determine the elution times of the photodegradation products of furosemide by applying the Japanese Pharmacopoeia chromatographic method for related substances to the isolated products.

Hepatobiliary cystadenocarcinoma with rapid growth: report of a case.

We describe a case of histologically proven hepatobiliary cystadenocarcinoma with an emphasis on the longterm clinical course. The patient was a 75-year-old man who had been diagnosed as having a simple hepatic cyst at our hospital and had been followed up by abdominal sonography (US) for about 10 years. However, the lesion subsequently showed a sudden increase in size and a marked change in US findings, i.e., from a benign hepatic cyst to a complete solid lesion. Contrast-enhanced US revealed the lesion to be filled with fine vessels. This rapid change led us to strongly suspect a hepatobiliary cystadenocarcinoma and, thus, left lateral segmentectomy was performed. The patient is doing well 6 months after the surgical treatment.

Current status of percutaneous endoscopic gastrostomy (PEG) in a general hospital in Japan: a cross-sectional study.

BACKGROUND: There has been debate over the indications for percutaneous endoscopic gastrostomy (PEG) in recent years in Japan. In addition, the level of satisfaction of patients and patient's family after PEG remains unclear. The aim of this study was to investigate the current status of PEG and the level of satisfaction of patients and patients' families after PEG in Japan. METHODS: We reviewed the existing data of all patients who underwent PEG tube insertion at Yuri Kumiai General Hospital (Akita, Japan) between February 2000 and December 2010. We examined the following points: underlying diseases requiring PEG, levels of consciousness, and performance status. We also sent a questionnaire to the patients and patient's families to ask about their satisfaction with and thoughts about PEG. RESULTS: The data of 545 patients who underwent PEG were reviewed. There were 295 men and 250 women, with a mean age of 77.2 ± 11.4 years. PEG was indicated most frequently for cerebrovascular disorders (48.2%, 239/545). There were 515 (94.4%, 515/545) patients showing consciousness disturbance and 444 (81.5%, 444/545) bedridden patients. The questionnaire was answered by one patient himself and 316 patients' families. When asked, "Was performing PEG a good decision?", 57.5% (182/316) of the patients' families answered yes. Meanwhile, when patients' family members were asked if they would wish to undergo PEG if they were in the same condition as the patient, 28.4% (90/316) answered yes, whereas 55.3% (175/316) answered no. CONCLUSIONS: Few patients were able to make their own decision about PEG tube placement because of consciousness disturbance. As a result, many family members of the patients did not want to experience PEG for themselves. Future studies should be performed to clarify the quality of life and ethical aspects associated with PEG.

Generation of a large number of connective tissue type mast cells by culture of murine fetal skin cells.

We describe a novel culture system for generating large numbers of murine skin-associated mast cells and distinguish their characteristics from bone marrow-derived cultured mast cells. Culture of day 16 fetal skin single cell suspensions in the presence of interleukin-3 and stem cell factor allowed expansion and maturation of mast cells in the presence of stromal cells. The average yield of mast cells after 2 wk was 7.3 million cells per fetus at a purity of 96%. These fetal skin-derived cultured mast cells increased their histamine content in a time-dependent manner to 3.6 pg per cell after 2 wk and 6.7 pg per cell after 4 wk. Phenotypic analyses revealed much greater expression of CD49b and CD81 and lesser expression of CD77 and CD102 on fetal skin-derived cultured mast cells as compared with bone marrow-derived cultured mast cells. These findings suggest a close similarity between fetal skin-derived cultured mast cells and freshly isolated cutaneous mast cells. Connective tissue mast cell characteristics of fetal skin-derived cultured mast cells were evidenced by: (1) their greater histamine content than bone marrow-derived cultured mast cells; (2) the presence of heparin; and (3) their degranulation in response to compound 48/80 and substance P. Importantly, fetal skin-derived cultured mast cells secreted greater amounts of interleukin-13 but much less MIP-1beta and interleukin-6 than bone marrow-derived cultured mast cells in response to ionomycin. Thus fetal skin-derived cultured mast cells have many characteristics distinct from bone marrow-derived cultured mast cells and can be used as a model of cutaneous mast cells to discern their functions.

[Effect of admixture of commercially available corticosteroid ointments and/or creams on vasoconstrictor activity].

A commonly used admixture of commercially available ointments and/or creams was selected from the prescribed sheets in our hospital, and questionnaire to dermatologists. To assess the relationship between permeability of corticosteroid through murine skin and clinical effects in human, we attempted to investigate the vasoconstrictor activity of these admixtures of topical corticosteroid by double-blind controlled study. Test samples were occluded at random on the back of 20 healthy volunteers for 4 hours. The vasoconstrictor activity of corticosteroid creams (Lidomex) alone was significantly large as compared with that of ointments alone. The vasoconstrictor activity of corticosteroid in the admixture of Lidomex ointment and urea ointments or heparinoid ointment was 1.5-2 fold significantly larger than that from ointments alone. The extent of the stability of the emulsion after mixing was related to the vasoconstrictor activity. These experiments demonstrated a close relationship between the vasoconstrictor activity of human skin and permeability of hairless mice skin. These results suggested that the vasoconstrictor activity of topical corticosteroids mixed with commercially available ointments and/or creams depends upon their physicochemical characteristics.

The effects of endothelin-1 on degranulation, cytokine, and growth factor production by skin-derived mast cells.

Endothelin-1 (ET-1), originally described as a vasoconstrictor, is now known to be involved in pathogenesis of various disorders including vascular, inflammatory, and fibrotic diseases. Recent studies suggest that mast cells are also involved in the same pathological conditions. In this study, we tested a hypothesis that ET-1 would affect mast cell functions and contribute to such disease conditions, using fetal skin-derived cultured mast cells (FSMC) and bone marrow-derived cultured mast cells (BMMC). FSMC expressed ET receptors (ET(A) and ET(B)) at mRNA and protein levels, whereas BMMC expressed lower levels of ET(A), and little, if any, ET(B). ET-1 induced degranulation by FSMC, but not by BMMC through ET(A)-mediated pathways. ET-1 at different concentrations exerted the reciprocal effects on degranulation by IgE-bound FSMC. Furthermore, ET-1 induced TNF-alpha and IL-6 production by FSMC, but not by BMMC, and significantly enhanced VEGF production and TGF-beta1 mRNA expression by FSMC. Finally, ET-1 was produced by FSMC, but not by BMMC in response to Toll-like receptor ligands. These results indicate contrasting impacts of ET-1 on distinct mast cell populations. We propose that ET-1 may participate in pathological conditions of various disorders via its multi-functional effects on mast cells under certain conditions.

TLR3-, TLR7-, and TLR9-mediated production of proinflammatory cytokines and chemokines from murine connective tissue type skin-derived mast cells but not from bone marrow-derived mast cells.

Recent studies have revealed that murine bone marrow-derived cultured mast cells (BMMC), which are phenotypically immature mast cells, express functional TLR2 and TLR4 that recognize distinct pathogen-associated molecules. However, it remains relatively uncertain whether mast cells express other TLR. We recently established a method to obtain large numbers of murine fetal skin-derived cultured mast cells (FSMC); these cells exhibit important features of connective tissue type mast cells. Working with FSMC and BMMC, the TLR mRNA expression profiles were compared between both cell types. Although TLR2 and TLR4 mRNA were detected in both cells at comparable levels, TLR3, TLR7, and TLR9 mRNA were expressed by FSMC at higher levels than by BMMC, suggesting distinct TLR expression profiles among different mast cell populations. With respect to their functional aspects, FSMC, but not BMMC, dose dependently produced proinflammatory cytokines (TNF-alpha and IL-6) and chemokines (RANTES, MIP-1alpha, and MIP-2) in response to poly(I:C), R-848, and CpG oligodeoxynucleotide, which are TLR3, TLR7, and TLR9 activators, respectively. Interestingly, these TLR activators failed to induce degranulation and IL-13 production by both mast cells, although peptidoglycan and LPS (TLR2 and TLR4 activators, respectively) induced IL-13 production by both cells. Mast cells, thus, may have potential to recruit other immune cells to the infected sites by responding to various bacterial and viral components through TLR signaling pathways, presumably being involved in initiating innate immunity and subsequently linking innate and acquired immune responses.

Aromatic hydrocarbon-catalyzed direct reaction of sulfur and sodium in a heterogeneous system: selective and facile synthesis of sodium monosulfide and disulfide.

Sodium disulfide and monosulfide were selectively formed via the direct reaction of sulfur and an equimolar amount of sodium in 1,2-dimethoxyethane at 70 degrees C in the presence of a catalytic amount of aromatic hydrocarbons and ketone.