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The 11β-hydroxysteroiddehydrogenase type 1(11β-HSD1), acortisolregenerating enzyme that amplifies tissue glucocorticoidlevels, plays an important role in diabetes, obesity, and glaucoma and is recognized as a potential therapeutic target for various disease conditions. Moreover, a recent study demonstrated that selective 11β-HSD1 inhibitor can attenuate ischemic brain injury. This prompted us to optimize cyclic sulfamide derivative for aiming to treat ischemic brain injury. Among the synthesized compounds, 6e has an excellent in vitro activivity with an IC 50 value of 1 nM toward human and mouse 11β-HSD1 and showed good 11β-HSD1 inhibition in ex vivo study using brain tissue isolated from mice. Furthermore, in the transient middle cerebral artery occlusion model in mice, 6e treatment significantly attenuated infarct volume and neurological deficit following cerebral ischemia/reperfusion injury. Additionally, binding modes of 6e for human and mouse 11β-HSD1 were suggested., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: The prevalence of community-associated meticillin-resistant Staphylococcus aureus (CA-MRSA) is increasing throughout the world and is an important cause of skin and soft tissue infection (SSTI) in children and neonates., Aim: To describe the successful control of an outbreak caused by a new strain of CA-MRSA in a newborn nursery., Methods: The investigation of the outbreak in July 2012 is reported with the control measures taken. Molecular typing of the MRSA isolates was performed., Findings: An outbreak of SSTI caused by CA-MRSA occurred in a newborn nursery. Six neonates were infected in a one-month period [infection rate: 8.5% (6/71)]. A new variant of CA-MRSA was responsible, which was characterized as USA300-related, Panton-Valentine Leucocidin (PVL) positive, arginine catabolic mobile element (ACME) negative, sequence type 8 (ST8), staphylococcal cassette chromosome mec (SCCmec) type IVa, agr type I and spa type t008. The outbreak among term neonates followed a rapid transmission pattern and was successfully controlled by implementing various outbreak control measures, including universal chlorhexidine bathing., Conclusion: This is the first report of a hospital outbreak caused by a USA300-related CA-MRSA clone in Korea. Early recognition and reinforcement of infection control measures are important in decreasing transmission of CA-MRSA in a hospital setting., (Copyright © 2014 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

A new series of cyclic sulfamide derivatives were synthesized and evaluated for their ability to inhibit 11β-HSD1. Among this series, 18e showed good in vitro activity toward human 11β-HSD1, selectivity against 11β-HSD2, microsomal stability, and pharmacokinetic and safety profiles (hERG, CYP, and acute toxicity). Additionally, 18e exhibited good in vivo efficacy in rat and monkey models.

Purpose: To determine the diagnostic utility of a frozen section biopsy in patients undergoing endoscopic submucosal dissection (ESD) for early gastric neoplasms with obscure margins even with chromoendoscopy using acetic acid and indigo carmine (AI chromoendoscopy)., Materials and Methods: The lateral spread of early gastric neoplasms was unclear even following AI chromoendoscopy in 38 patients who underwent ESD between June 2007 and May 2011. Frozen section biopsies were obtained by agreement of the degree of lateral spread between two endoscopists. Thus, frozen section biopsies were obtained from 23 patients (FBx group) and not in the other 15 patients (AI group)., Results: No significant differences were observed for size, histology, invasive depth, and location of lesions between the AI and FBx groups. No false positive or false negative results were observed in the frozen section diagnoses. Adenocarcinoma was revealed in three patients and tubular adenoma in one, thereby changing the delineation of lesion extent and achieving free lateral margins. The rates of free lateral resection margins and curative resection were significantly higher in the FBx group than those in the AI group., Conclusions: Frozen section biopsy can help endoscopists perform more safe and accurate ESD in patients with early gastric neoplasm.

A new series of thiazolidine derivatives with an adamantyl group was synthesized and evaluated for their ability to inhibit 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1). Our initial compound 5a showed a weak inhibitory activity. Significant improvements in potency were achieved by substituent modification. The potent compound 8g (E) showed good in vitro inhibitory activity toward human 11β-HSD1, selectivity toward 11β-HSD2, metabolic stability, pharmacokinetic, and safety profile. Furthermore, this compound significantly inhibited 11β-HSD1 activity in rat and monkey models, and showed improved glycemic control in KKAy mice., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

[reaction: see text] Calixarene-based fluorescent chemosensor 1 with two fluorogenic pyrene units conjugated to amide groups as guest recognition sites is synthesized. Complexation of F(-) by 1 causes a red shift of its absorption band to 400 nm (Deltalambda = 54 nm) and a blue shift of the excimer emission to 470 nm (Deltalambda = 12 nm) together with enhanced fluorescence intensity. The blue-shifted excimer emission is attributed to a pyrene dimer formed in the ground state, a so-called static excimer.

Selective removal of t-Boc protecting groups in a polymer film imbedded, pyrene-containing calixarene derivative results in the generation of a patterned fluorescence image without employing wet developing processes.

A series of novel tetrahomodioxacalix[4]biscrowns with crown-2, crown-3, crown-4, crown-5, and crown-6 units were synthesized. Conformations of each product are dependent on the base used and their conformation stabilities. All conformations were proven by NMR spectra and/or X-ray crystal structures. The 1,3-alternate homodioxacalix[4]biscrown-4 (4b) shows the best selectivity for K+, whereas the 1,3-alternate homodioxacalix[4]crown-5 (5) does for Cs+. Those selectivities are attributable to electrostatic interaction between the metal ion and the crown ring, as well as a pi-metal complexation. However, the C-1,2-alternate conformation does not take the metal ions regardless of the crown species as a result of steric hindrance from the methylene bridge of an ArCH2Ar unit., (Copyright 2004 American Chemical Society)