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Biomedical subjects

I Sugiyama

Publications and source records attributed to I Sugiyama.

At least 19 recordsLinked to original sources

Therapeutic efficacy of sustained drug release from chitosan gel on local inflammation.

The model anti-inflammatory drug prednisolone (PS) was retained in chitosan (CS) gel beads, which were prepared in a 10% aqueous amino acid solution (pH 9.0). Sustained release of PS from the CS gel beads was observed. Carrageenan solution was injected into air pouches (AP), which were prepared subcutaneously on the dorsal surface of mice, in order to induce local inflammation. CS gel beads retaining PS were then implanted into the AP to investigate the therapeutic efficacy of sustained PS release against local inflammation. In vivo PS release from CS gel beads was governed by both diffusion of the drug and degradation of the gel matrix. Sustained drug release by CS gel beads allowed the supply of the minimum effective dose and facilitated prolonged periods of local drug presence. Inflammation indexes were significantly reduced after implantation of CS gel beads when compared with injection of PS suspension. Thus, extension of the duration of drug activity by CS gel beads resulted in improved therapeutic efficacy. These observations indicate that CS gel beads are a promising biocompatible and biodegradable vehicle for treatment of local inflammation.

Adjuvants, Pharmaceutic↗

Expression of matrix metalloproteinases during ascorbate-induced differentiation of osteoblastic MC3T3-E1 cells.

The mouse calvarial osteoblast MC3T3-E1 cells released 92 kDa and 68 kDa of gelatinase activities into the conditioned media (CMs) from undifferentiated cells. When differentiation was induced by cultivating cells with ascorbate-2-phosphate (AscP), 68-kDa activity increased significantly in parallel with production of 60-kDa activity. These enzymes required Ca2+ and Zn2+ ions for their proteolytic activities. The 68-kDa activity was immunologically identified as latent matrix metalloproteinase 2 (MMP-2). The 92-kDa activity was deduced to be latent MMP-9 based on its molecular mass. The 60-kDa activity band was found to possess both gelatin and beta-casein hydrolyzing activities, indicating that this activity band might comprise the active form of MMP-2 and latent MMP-13. MC3T3-E1 cells were found to express MMP-2, MMP-13, and membrane type (MT)1-MMP genes by Northern blotting. MMP-2 was expressed constitutively. MMP-13 was up-regulated during the growth with AscP. MT1-MMP expression also was modulated by AscP; at the early stage of differentiation, its messenger RNA (mRNA) level increased and then decreased gradually to the control level. These changes in the profiles of MMPs observed here could be attributed to the maturation of collagenous extracellular matrix (ECM) induced by AscP.

3T3 Cells↗

Fyn tyrosine kinase participates in the compact myelin sheath formation in the central nervous system.

The cellular mechanisms for spiral wrapping and compaction of myelin sheaths by oligodendrocytes are not known yet. In this study, we examined the role of fyn tyrosine kinase, which could be responsible for molecular events during the stage of myelination in the CNS. Western blot and immunohistochemical analyses revealed that fyn-deficient mice have significantly lower levels of myelin basic protein (MBP), which is required for intracellular membrane adhesion parts so-called major dense line (MDL) and thought to be essential for the stability of myelin sheath. Electron microscopy verified that the myelin ultrastructure could be used to distinguish fyn-deficient mice from wild-type mice, showing a thin and redundant myelin sheath in the corpus callosum. Further, the electron-dense 'major' line in myelin from the purified myelin fractions remained condensed, and myelin compaction was split opened in fyn-deficient mice. To determine whether there was a change in the microheterogeneity of MBP due to a post-translational event we first investigated peptidylarginine deiminase (PAD), which is an enzyme that converts arginine residues in peptides to citrulline residues. PAD immunoreactivity was observed both in the myelin from fyn-deficient and wild-type mice. By Western blot analysis we found an increase of the citrullined form of MBP. In addition, MBP from fyn-deficient mice did weakly induce vesicle aggregation properties of MBP-mediated adhesion. We concluded that although oligodendrocytes from fyn-deficient mice are able to wrap around the axon, they are unable to form compact myelin due to decreased MBP level and the presence of increased citrullinated MBP.

Animals↗

Suppression of glial tumor growth by expression of glial fibrillary acidic protein.

We examined the effect of expression of glial fibrillary acidic protein (GFAP) on the tumor growth of astrocytoma in vivo. When rat astrocytoma C6 cells were injected subcutaneously in athymic mice, the cells produced tumors that grew rapidly. The tumor growth of C6 cells transfected with GFAP cDNA was significantly reduced compared to that of control NeoC6 cells transfected only with the neomycin resistant gene. After implantation of C6 cells transfected with mutated GFAP cDNA at the phosphorylation sites, the tumor growth was suppressed similar to that of the wild GFAP transfectants. To determine whether the cell growth suppression by GFAP is specific for astroglial cells, we assessed the effect of GFAP on the cell growth of an L cell of fibroblast origin in vitro. By GFAP cDNA transfection, L cells showed morphological changes, but the cell growth was not reduced. These results suggest that GFAP is a critical regulator of the tumor growth of astrocytoma.

Amino Acid Sequence↗

[Development of "assessment guideline of family power for healthy life"].

The purpose of this study is to develop "assessment guideline of family power for healthy life" aiming at expanding self-care power of family in community nursing practice. The subjects of this study covered those families in one hundred and fifty six instances that we had seized as subject for nursing care and study. The method of this study had constructed assessment guideline inductively out of each case, and modified it by applying to cases of families with health problems and others. As a result, we had formed nine items of "family power for healthy life" and three items of "conditions influencing family power for healthy life" for "assessment guideline of family power for healthy life".

Community Health Nursing↗

Studies on orally active cephalosporins. I. Synthesis and structure-activity relationships of new 3-substituted carbamoyloxymethyl cephalosporins.

The synthesis and antibacterial activities of 7 beta-[2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetamido]-3-N,N - dimethylcarbamoyloxymethyl-3-cephem-4-carboxylic acid (E1100) and its analogs are described, as well as oral absorbability and in vivo activities of the 1-(isopropoxycarbonyloxy)ethyl ester (E1101) and its analogous esters. The introduction of acyclic and cyclic lower alkyl groups at the N-position of 3-carbamoyloxymethyl cephems influences antibacterial activities, especially against H. influenzae, and oral absorbability of their prodrug esters. The structure-activity relationships are also discussed.

Administration, Oral↗

Studies on orally active cephalosporins. II. Synthesis and structure-activity relations of new [(E) or (Z) 3-substituted carbamoyloxy]-1-propenyl cephalosporins.

In an effort to find a new oral cephalosporin with well-balanced antibacterial spectrum, good oral absorbability and long plasma half-life, a series of oxyimino aminothiazolyl 3-[(E)- or (Z)-N-substituted carbamoyloxy]propenyl cephems was synthesized and evaluated for antibacterial activity and oral absorbability. The substituents of the carbamoyloxy group affected their in vitro activity and bioavailability after oral administration of their pivaloyloxymethyl esters at the C-4 position. The compound possessing an N,N-dimethylcarbamoyloxy moiety at the C-3 position showed good oral absorption and well-balanced antibacterial activity. In this report, the structure-activity relationships and the structure-oral absorbability relationships of 3-(N-substituted carbamoyloxy)-propenyl cephems are described.

Administration, Oral↗

Application of a shape memory alloy to hand splinting.

This paper describes new passive splints which have been developed using a shape memory alloy. The peculiar feature of the splints is that the way in which they change shape in use conforms to the stretching motion which it would be desirable to apply in certain conditions of deformity. The alloy consists of 55.66% by weight Nickel and 44.34% Titanium. The heat treatment of the alloy for memorising shape was implemented at 500 degrees C for one hour. This alloy was easily bent when cool, but the original shape was recovered on heating. It was used as the supporting structure of the reverse knuckle bender splint and the cock-up splint. The new splints could be easily attached to the deformed limb after cooling. The splints avoided the development of spasticity, because they gradually recovered their original shapes and corrected the deformities when the heat of the room or body heat warmed the splints. Since the shape memory alloy has the dual function of thermal sensor and kinetic power source it was a simple device. The splint was, as a result, small and smart. It was apparent from clinical use that the splint was easy to wear and could be worn with comfort for an extended period. The design of the splints and the fabrication process are described and their application is indicated.

Adult↗

Synthesis and structure-activity relationships of a new series of cephalosporins, E1040 and related compounds.

The synthesis and in vitro antibacterial activity of a series of 7-[(Z)-2-aminoaryl-2-oxyiminoacetamido]-3-ammoniomethyl++ +-3-cephems are described. Variation of an oxyimino moiety with aminoaryl at the C-7 side chain and a quaternary ammonium moiety at the C-3 side chain were examined and structure-activity relationships were studied. E1040, the 3-(4-carbamoylquinuclidinio)methyl derivative of the 7-alpha-methoxyimino series of aminothiadiazolyl cephalosporins, exhibited excellent activity against both Gram-positive and Gram-negative bacteria, particularly against Pseudomonas aeruginosa, and possessed high stability to beta-lactamases.

Bacteria↗

Role of the aminothiadiazolyl group in the antipseudomonal activity of cefclidin.

Cefclidin (E1040), which has an aminothiadiazolyl group in the 7 beta-side chain, showed about four-fold higher activity against Pseudomonas aeruginosa than its aminothiazolyl counterpart. Cefclidin had lower affinity and a higher Vmax value for the chromosomal type I beta-lactamase (cephalosporinase) from P. aeruginosa than its aminothiazolyl counterpart. No differences between the affinities of both compounds for the most of the sensitive essential PBPs were observed. Hydrophilicity of cefclidin was higher than that of its counterpart. The antipseudomonal activity of cefclidin, which was increased by the introduction of the aminothiadiazolyl group, was suggested to have resulted mainly from higher resistance to cephalosporinase hydrolysis at pharmacologically relevant low concentrations due to its low affinity for cephalosporinase, and secondarily from good penetration of cefclidin through the outer membrane due to increased hydrophilicity.

Bacterial Proteins↗

White blood cell plugging and blood flow maldistribution in the capillary network of cat cerebral cortex in acute hemorrhagic hypotension: an intravital microscopic study.

The behavior of white blood cells (WBCs) in the capillary network of the cat brain was studied under normal conditions and during acute hemorrhagic hypotension. A small transilluminated area of the cerebral cortex was observed directly, and blood cells flowing through the capillary network were recorded on cinefilm using a high-speed cinecamera. The cell motion was analyzed on the projection screen using a frame-by-frame method. The time during which a single WBC remained at a capillary branching, ie, stagnant time (ST) was examined in detail. In hemorrhagic hypotension, ST was much longer than that in the normal condition. WBC plugging occurred at capillary branchings, and a nonuniform flow pattern (plasma-WBC-accumulated red blood cells [RBCs]) appeared in perfused capillaries. RBC velocity in capillaries was reduced. The ST level was increased significantly with a decrease in RBC velocity. These findings suggest that acute hemorrhagic hypotension may induce flow maldistribution in cerebral microcirculation.

Animals↗

Structure of blood flow through a curved vessel with an aneurysm.

A fine structure of blood flow through a curved vessel with an aneurysm was studied in in vitro experiments in relation to rheological factors of arterial diseases such as arteriosclerosis or thrombosis. On the basis of the in vivo data related to cerebral circulation, red blood cell suspension was flowed through curved vessel models with an asymmetrical aneurysm. Flow visualization was made with a microscope 16 mm cinecamera-TV monitor system, and the velocity profile was measured using the laser Doppler velocimeter. Vortices induced in aneurysm influenced flow structure and velocity at the presence of the secondary flow due to the vessel curvature. This suggests strongly that blood flow in curved arteries with an aneurysm must be understood under the influence of the secondary flow.

Blood Flow Velocity↗