Efficacy and safety of luseogliflozin added to various oral antidiabetic drugs in Japanese patients with type 2 diabetes mellitus

Introduction: Two studies were carried out to investigate the efficacy and safety of luseogliflozin added to existing oral antidiabetic drugs (OADs) in Japanese type 2 diabetic patients inadequately controlled with OAD monotherapy. Materials and Methods: In the trial involving add‐on to sulfonylureas (study 03‐1), patients were randomly assigned to receive luseogliflozin 2.5 mg or a placebo for a 24‐week double‐blind period, followed by a 28‐week open‐label period. In the open‐label trial involving add‐on to other OADs; that is, biguanides, dipeptidyl peptidase‐4 inhibitors, thiazolidinediones, glinides and α‐glucosidase inhibitors (study 03‐2), patients received luseogliflozin for 52 weeks. Results: In study 03‐1, luseogliflozin significantly decreased glycated hemoglobin at the end of the 24‐week double‐blind period compared with the placebo (–0.88%, P < 0.001), and glycated hemoglobin reduction from baseline at week 52 was –0.63%. In study 03‐2, luseogliflozin added to other OADs significantly decreased glycated hemoglobin from baseline at week 52 (–0.52 to –0.68%, P < 0.001 for all OADs). Bodyweight reduction was observed in all add‐on therapies, even with agents associated with weight gain, such as sulfonylureas and thiazolidinediones. Most adverse events were mild in severity. When added to a sulfonylurea, incidences of hypoglycemia during the double‐blind period were 8.7% and 4.2% for luseogliflozin and placebo, respectively, but no major hypoglycemic episodes occurred. The frequency and incidences of adverse events of special interest for sodium glucose cotransporter 2 inhibitors and adverse events associated with combined OADs were acceptable. Conclusions: Add‐on therapies of luseogliflozin to existing OADs improved glycemic control, reduced bodyweight and were well tolerated in Japanese type 2 diabetic patients. These trials were registered with the Japan Pharmaceutical Information Center (add on to sulfonylurea: JapicCTI‐111507; add on to other OADs: JapicCTI‐111508)

Acute Encephalitis Caused by Intrafamilial Transmission of Enterovirus 71 in Adult

Enterovirus 71 (EV71) is a common cause of hand, foot, and mouth disease and sometimes causes severe neurologic complications, mainly in children. We report a case of adult-onset encephalitis caused by intrafamilial transmission of a subgenogroup C4 strain of EV71. This case elucidates the risk for EV71 encephalitis even in adults

The Constrained Maximal Expression Level Owing to Haploidy Shapes Gene Content on the Mammalian X Chromosome.

X chromosomes are unusual in many regards, not least of which is their nonrandom gene content. The causes of this bias are commonly discussed in the context of sexual antagonism and the avoidance of activity in the male germline. Here, we examine the notion that, at least in some taxa, functionally biased gene content may more profoundly be shaped by limits imposed on gene expression owing to haploid expression of the X chromosome. Notably, if the X, as in primates, is transcribed at rates comparable to the ancestral rate (per promoter) prior to the X chromosome formation, then the X is not a tolerable environment for genes with very high maximal net levels of expression, owing to transcriptional traffic jams. We test this hypothesis using The Encyclopedia of DNA Elements (ENCODE) and data from the Functional Annotation of the Mammalian Genome (FANTOM5) project. As predicted, the maximal expression of human X-linked genes is much lower than that of genes on autosomes: on average, maximal expression is three times lower on the X chromosome than on autosomes. Similarly, autosome-to-X retroposition events are associated with lower maximal expression of retrogenes on the X than seen for X-to-autosome retrogenes on autosomes. Also as expected, X-linked genes have a lesser degree of increase in gene expression than autosomal ones (compared to the human/Chimpanzee common ancestor) if highly expressed, but not if lowly expressed. The traffic jam model also explains the known lower breadth of expression for genes on the X (and the Z of birds), as genes with broad expression are, on average, those with high maximal expression. As then further predicted, highly expressed tissue-specific genes are also rare on the X and broadly expressed genes on the X tend to be lowly expressed, both indicating that the trend is shaped by the maximal expression level not the breadth of expression per se. Importantly, a limit to the maximal expression level explains biased tissue of expression profiles of X-linked genes. Tissues whose tissue-specific genes are very highly expressed (e.g., secretory tissues, tissues abundant in structural proteins) are also tissues in which gene expression is relatively rare on the X chromosome. These trends cannot be fully accounted for in terms of alternative models of biased expression. In conclusion, the notion that it is hard for genes on the Therian X to be highly expressed, owing to transcriptional traffic jams, provides a simple yet robustly supported rationale of many peculiar features of X's gene content, gene expression, and evolution

Similarity on algebraic specifications toward specification databases

リサーチレポート（北陸先端科学技術大学院大学情報科学研究科）本文は図書館に配架されています。 / This material is stored in the JAIST library

Hyperbranched 5,6-glucan as reducing sugar ball

The ring-opening polymerization of 5,6-anhydro-1,2-O-isopropylidene-α-D-glucofuranose (1) as a latent cyclic AB2-type monomer was carried out using potassium tert-butoxide (t-BuOK) or boron trifluoride diethyletherate (BF3・OEt2) as an initiator in order to synthesize a novel hyperbranched glycopolymer. The anionic and cationic polymerizations proceeded via the proton-transfer reaction mechanism to produce the hyperbranched poly(5,6-anhydro-1,2-O-isopropylidene-α-D-glucofuranose) (2). In particular, the cationic polymerization with the slow-monomer-addition strategy is a facile method leading to the hyperbranched glycopolymers with high molecular weights and highly branched structures. The weight-average molecular weight (Mw,SEC-MALLs) values of 2 measured by multi-angle laser light scattering (MALLS) varied in the range from 7,400 to 122,400, which were significantly higher than the weight-average molecular weight (Mw,SEC) values determined by size exclusion chromatography (SEC). The intrinsic viscosities ([η]) of these polymers were very low in the range of 3.3-4.6 mL g^[-1] and the Mark-Houwink-Sakurada exponents α were calculated to be 0.08-0.27. These results of the MALLS, SEC, and viscosity measurements suggested that these polymers exist in a compact spherical conformation in solution because of their highly branched structure. The synthesis of the hyperbranched 5,6-glucan (3) by hydrolysis of polymer 2 was also demonstrated. Polymer 3 is a novel water-soluble hyperbranched glycopolymer arranged with numerous reducing D-glucose units on the peripheries of the polymer, and has a higher reducing ability than D-glucose because of the glycocluster effect or the multivalent effect of the reducing D-glucose units. Therefore, polymer 3 should be called a "reducing sugar ball"