Enzymatic synthesis of glucan dendrimer for pharmaceutical applications

Bio-macromolecules (e.g. protein, peptide, antibody DNA or RNA) present in our bodies are now widely utilized in pharmaceuticals. Carbohydrates, on the other hand, have been receiving increasing attention as drug candidates, but the pharmaceutical usage of carbohydrates is limited to few glycosaminoglycans (e.g. heparin, hyaluronan or chondroitin sulfate), which are all endogenous polysaccharides. Glycogen is another polysaccharide present in our bodies as energy reserves, and its application for pharmaceuticals is not evident either. Glycogen is a highly branched polysaccharide of glucose with a very attractive structure and characteristics. It is a single molecular nano-sized spherical particle with dendritic architecture where numerous non-reducing ends constitute the surface of the molecule. Dendrimers and nano-sized particles have received interest as carriers for drug delivery system because such carriers can enhance the performance and efficacy of drug molecules. From this context, we consider glycogen as potentially a promising polysaccharide as drug carriers; therefore we are currently attempting to develop synthetic glucan dendrimers suitable for drug carriers. Such attempts have been scarce in the recent research of drug candidates. We have developed an enzymatic system to produce glucan dendrimer (GD) from sucrose by combined action of sucrose phosphorylase (EC: 2.4.1.7), glucan phosphorylase (EC: 2.4.1.1) and branching enzyme (EC: 2.4.1.18). This system enables us to produce GDs with strictly controlled molecular size (Mw/Mn value less than 1.1) and particle size ranging from 10 nm to 40 nm. Furthermore, we have developed non-reducing end specific glycosylation technology of GD by using glucan phosphorylase and its substrate analogs. Glucan phosphorylase from Aquifex aeolicus can use not only its original substrate, glucose 1-phosphate, but also other hexose 1-phosphates as substrate and transfer these hexoses moieties (glucuronic acid, glucosamine, N-acetyl glucosamine, galactose and mannose) to the non-reducing end of glucan. Using this enzymatic reaction, we can produce GDs whose surface is modified with these hexose residues. GDs having glucuronic acid and/or glucosamine residues are especially useful since they can be covalently conjugated with functional substances such as sugar chains, peptides, nucleotides and others. It is possible to control the conjugate ratio of the functional substance on the surface of GD. Surface engineered GD is a novel and versatile platform for carbohydrate drugs and drug carriers, and its application will be described

Organized and Sustainable Education Program for Drug Abuse Prevention by Yogo-teachers

　学校における喫煙・飲酒・薬物乱用防止教育の充実には，問題行動が顕在化する中学校期だけでなく小学校期 における指導の推進が重要であり，系統的な指導計画を立て，指導者や時間の確保，教材作成などに組織的に取 組み，継続可能なプログラム開発を行う必要がある。そこで，地区内12 校の養護教諭が協働して，発達段階に応 じた系統的・組織的かつ継続可能な地区共通の指導計画を開発し，各校の教育課程・年間計画に位置付けた実践 研究を行った。その結果，指導計画の実施状況は，小学校11 校中，学級活動10 校，ミニ保健指導10 校，長期 休業前指導6 校，広報活動9 校となり，特別支援学校1 校では広報活動のみを行うことができた。小学校におけ る喫煙・飲酒・薬物乱用防止教育の推進には，学校保健活動の中核的役割を担う養護教諭が専門性を活かし協働 して，系統的な指導計画を各校の教育課程に位置付け組織的で継続可能なプログラムとする取組が有効であった

Genesis and development processes of fractures in granite: Petrographic indicators of hydrothermal alteration.

Biotites occur with varying degrees of alteration within a granite. This study analyzes the relationships among alteration indicators, areal microvoid fractions in chloritized biotite, and macroscopic fracture frequencies in the Toki granite, central Japan, to establish the genesis and development processes of fractures in granite. Appropriate characterizations for the frequency distribution of macroscopic fractures in granite can assist in understanding potential hydrogeological applications, which contributes to safety evaluations for geological disposal and storage. Borehole 06MI03, drilled to a depth of 191 m, was used to obtain samples for the analysis. In total, 24 samples that depicted variations in the macroscopic fracture frequency were selected. Petrographic alteration indicators using biotite chloritization as innovative methods are proposed to evaluate the extent of hydrothermal alteration and fracture frequency within granites. The alteration indicators are defined as the ratio between the alteration product area and the original mineral area. Furthermore, the volume of microscopic fractures and micropores in the mineral was quantitatively characterized by the areal fraction of microvoids in minerals through image analysis. Samples with high macroscopic fracture frequencies correspond to a high number of areal microvoid fractions and large alteration indicators. Microvoids, which are the source of macroscopic fractures, occurred at temperatures between 350 and 780°C and can be evaluated by intrinsic factors, such as alteration indicators. Subsequent faulting and unloading (extrinsic factors) developed microvoids into macroscopic fractures. Intrinsic factors are used to evaluate the source of macroscopic fractures, and therefore contribute to the characterization of present and future distributions of macroscopic fracture frequencies