Biomedical subjects

Y Ikada

Publications and source records attributed to Y Ikada.

At least 253 records · Page 14Linked to original sources

PubMed1990

Enzymatic hydrolysis of copoly-(N-hydroxyalkyl L-glutamine/gamma-methyl L-glutamate) fibres.

Fibres from random copolypeptides consisting of N-hydroxyalkyl L-glutamine and gamma-methyl L-glutamate with different monomer ratios were prepared by aminoalcoholysis of a poly(gamma-methyl L-glutamate) fibre with 2-amino-1-ethanol or 5-amino-1-pentanol, both with 1,8-octamethylenediamine as cross-linking agent. The initial tensile properties as well as the in vitro hydrolysis of these hydrophilic fibres were highly dependent on the degree of swelling in phosphate buffer solution. The in vitro hydrolysis was carried out using pronase E as protease. The kinetic study on the weight loss of the fibre accompanying the enzymatic hydrolysis suggested that the degradation of these fibres proceeds gradually from the surface of the fibres into their core. Scanning electron microscopy also supported the surface, not bulk, hydrolysis. The weight loss of the fibres in the course of hydrolysis took place almost in parallel with the strength loss of the fibres.

Biodegradation, Environmental↗

PubMed1990

Influence of glycosaminoglycans on the collagen sponge component of a bilayer artificial skin.

A bilayer artificial skin composed of a silicone membrane and a collagen sponge layer containing glycosaminoglycans (GAGs) was first developed by Yannas and Burke. They reported that GAGs contained in the collagen sponge layer contributed to the function of the artificial skin. In an attempt to assess the effect of GAGs in the collagen sponge layer, the electron microscopic structure, mechanical strength of collagen sponges, and cell proliferation were examined in vitro, using four kinds of collagen sponges containing: no GAG, chondroitin 6-sulphate (C6S), dermatan sulphate (DER), and hyaluronic acid (HYA). The results indicated that: (1) addition of GAGs scarcely affected the mechanical structure of collagen sponges; (2) addition of C6S and DER reinforced mechanical strength, while addition of HYA did not; (3) addition of C6S and DER significantly decreased cell proliferation.

Artificial Organs↗

PubMed1990

Experimental study of a newly developed bilayer artificial skin.

A bilayer artificial skin composed of an outer layer of silicone polymer and an inner sponge layer of collagen containing chondroitin 6-sulphate was developed by modifying the technique proposed by Yannas et al. The artificial skin was placed on the skin defects on the backs of rats. Histological observation indicated that fibroblasts and capillaries infiltrated into the pores and filled in lattice spaces, resulting in synthesis of the connective tissue matrix and absorption of the original network of collagen and chondroitin 6-sulphate. Epidermal cells migrated from the edge of the wound between the two layers. Post-operative contracture in the wound with the artificial skin was significantly less than in the control.

Animals↗

PubMed1990

Development of an artificial articular cartilage.

We have attempted to develop an artificial articular cartilage on the basis of a new viewpoint of joint biomechanics in which lubrication and load-bearing mechanisms of natural and artificial joints are compared. We investigated poly(vinyl alcohol)-hydrogel (PVA-H) which has been recognized as a rubber-like gel and have improved the mechanical properties of this gel through a new synthetic process. In this article we report the biocompatibility and various mechanical properties of the new, improved PVA-H from the aspect of its usefulness as artificial articular cartilage. As regards the lubrication, we measured the change of thickness and fluid pressure of the gap formed between a glass plate and the specimen under loading and found that the PVA-H had a thicker fluid film under higher pressure than polyethylene (PE). The momentary stress transmitted through the specimen revealed that PVA-H had a lower peak stress and a longer duration of sustained stress than PE, suggesting a better damping effect. The wear factor of PVA-H was approximately five times as large as that of PE. Histological findings of the articular cartilage and synovial membranes around the PVA-H implanted for 8-52 weeks showed neither inflammatory nor degenerative changes. The PVA-H artificial articular cartilage could be attached to the underlying bone using an osteochondral composite material. Although there remain still some problems to solve, PVA-H seems to be a very interesting and promising material which meets the requirements of artificial articular cartilage.

Animals↗

PubMed1990

Macrophage activation for antitumour function by muramyl dipeptide-protein conjugates.

A muramyl dipeptide (MDP) has been conjugated directly with various proteins by means of a water-soluble carbodiimide. The enhancement of the antitumour activity of mouse peritoneal macrophages by the MDP-protein conjugates has been investigated to assess the ability of the proteins for targeting MDP to the macrophages. These were activated to inhibit the in-vitro growth of tumour cells much more effectively, when immunoglobulin (IgG), fibronectin (FN), and gelatin conjugates were used than when MDP was used alone. The minimum amount of MDP in both the MDP-gelatin and the MDP-IgG conjugates necessary for macrophage activation was approximately 2000 times lower than the amount of free MDP needed. The macrophages activated by the conjugates exhibited growth inhibitory activity against phenotypically diverse tumour cells. The activity induced by the MDP-gelatin conjugate was higher than that of the MDP-IgG conjugate over the range of MDP concentrations, regardless of the isoelectric point of the gelatin used. When MDP was conjugated with bovine serum albumin (BSA), the antitumour activity of macrophages was reduced as the amount of BSA conjugated increased. With both free MDP and MDP-protein conjugates, the macrophages were more strongly activated, the longer they were pretreated. However, less pretreatment time was needed to potentiate macrophage activation by the MDP-gelatin conjugate than by free MDP. Also, the macrophages pretreated with the MDP-gelatin conjugate could maintain their activated state for longer than those pretreated with free MDP. It is concluded that gelatin is an effective carrier protein for the targeting MDP to macrophages, resulting in their activation.

Acetylmuramyl-Alanyl-Isoglutamine↗

PubMed1990

Design of a polyvinyl alcohol hydrogen containing phospholipid as controlled-release vehicle for rectal administration of (+/-)-propranolol HCl.

Polyvinyl alcohol hydrogels which contained phospholipid, egg yolk lecithin or hydrogenated soya lecithin were designed as a transrectal delivery system for propranolol hydrochloride. The hydrogel preparations containing phospholipid were prepared by a low-temperature crystallization method. The release profile of propranolol from hydrogel preparations containing phospholipid complied with Fickian diffusion (Higuchi model). The release of propranolol from the hydrogel preparation decreased with higher contents of phospholipid (approximately 2% w/w). In rats plasma concentrations of propranolol after rectal administration of hydrogel preparations containing phospholipid (1 and 2% w/w) were prolonged compared with those of rats receiving preparations without phospholipid.

Administration, Rectal↗

PubMed1990

Enzyme-catalyzed synthesis of a bioactive oligopeptide in nearly anhydrous solvents with polyethylene glycol-modified proteases.

An oligopeptide, L-arginyl-glycyl-L-aspartyl-L-serine, having cell attachment activity was synthesized from the respective aminoacids carrying suitable protecting residues, by using carboxymethyl polyethylene glycol (PEG)-modified proteases in organic solvents. Papain, trypsin, and alpha-chymotrypsin were modified with PEG. Organic solvents used were 1,1,1-trichloroethane, chloroform and chloroform/ethyl cellosolve (1:1) mixture. Identification of the products was done by gel permeation chromatography (GPC) and thin layer chromatography (TLC).

Amino Acid Sequence↗

PubMed1990

[A polyvinyl alcohol (PVA) hydrogel as a soft contact lens material].

A transparent polyvinyl alcohol (PVA) hydrogel was prepared from a PVA solution in a mixed solvent consisting of water and a water miscible organic solvent by cooling. The physical properties were evaluated in comparison with commercially available soft contact lens materials, such as polyhydroxyethyl methacrylate (PHEMA) and copolymers of methyl methacrylate (MMA) and N-vinyl pyrrolidone (VP). The PVA hydrogel showed higher tensile strength and elongation at break than the other materials, while it had high water content and oxygen permeability the latter being comparable to those of PMMA/VP copolymers. The protein adsorption of the PVA hydrogel was much less than those of the other materials. The PVA hydrogel soft contact lenses were applied on rabbit eyes for 12 weeks. The influence on the cornea was studied by biomicroscopy, ultrasonic corneal pachymetry and histopathological examination. These examinations revealed no abnormal findings in the cornea. These results suggest that the PVA hydrogel may be promising as a new soft contact lens material.

Adsorption↗

PubMed1990

[Intravitreal drug delivery by microspheres of biodegradable polymers].

We evaluated the efficacy of microspheres of biodegradable polymers as a slow releasing drug delivery system in the vitreous body. Microspheres containing 5-FU were prepared with polymers of poly-(lactic acid) or copolymers of glycolic acid and lactic acid. The release of the drug was studied in vitro. Poly-(lactic acid) microspheres released 5-FU for 7 days. The intravitreal kinetics of the microspheres was studied in rabbits in vivo. The microspheres disappeared from the vitreous cavity of normal eyes by 48 +/- 5 days after injection. Disappearance was accelerated from the vitreous cavity of vitrectomized rabbits (14 +/- 2 days, p less than 10(-6)). No abnormality was found on electroretinographic or histological examinations after microspheres injection. These results suggested that microspheres of biodegradable polymers could be useful as a potential drug delivery system for sustained drug release in the vitreous body.

Animals↗

PubMed1990

Drug delivery systems for antitumor activation of macrophages.

Macrophages, one of the immunologically competent cells centrally contributing to host defense mechanisms, can be stimulated by a variety of immunomodulatory agents to exert antitumor activity. However, many problems, such as serious side effects attributed to the high-dosage regimens of the drugs, should be addressed for successful tumor immunotherapy using immunomodulatory agents. Thus, it is essential to develop carrier systems that use much lower doses of the drugs. This article reviews the carrier systems of drugs for effective immunopotentiation, especially macrophage activation of antitumor function. Since research in this field has just started, few investigations, including ours, have been reported.

Adjuvants, Immunologic↗

PubMed1990

Modification of synthesis and investigation of properties for 2-cyanoacrylates.

The conventional method for synthesis of 2-cyanoacrylate monomers was modified and the adhesive properties were studied for the cyanoacrylate monomers and the resultant polymers. Toluene was found to be better as reaction solvent than methyl alcohol or xylene. The higher the molecular weight of the condensation oligomer before pyrolysis and the narrower the molecular weight distribution, the higher the yield of cyanoacrylate monomer. Ethoxyethyl cyanoacrylate with an ether side chain was shown to be a soft and biodegradable adhesive. The softening and glass transition temperatures of ethoxyethyl cyanoacrylate polymer were much lower than those of cyanoacrylate polymers with methyl, ethyl or isobutyl side chains. Hydrolysis of poly(ethoxyethyl cyanoacrylate), evaluated from formaldehyde generation and mass loss, was faster than that of ethyl cyanoacrylate and isobutyl cyanoacrylate polymer. Hydrolysis of the ethoxyethyl cyanoacrylate polymers was greatly affected by the molecular weight of the polymers. The morphological change of the cyanoacrylate polymer films was studied by scanning electron microscopy.

Adhesiveness↗

PubMed1990

[Improvement in the mechanical properties of artificial blood vessel suitable for the extracranial cerebral artery].

Saphenous vein interposition grafts have been commonly used for the reconstruction of occlusive lesions in the extracranial cerebral vessels, such as carotid or vertebral arteries. In contrast, cerebral revascularization using an artificial blood vessel has not been so common. This is due to the fact that conventional artificial blood vessels have been too firm or too rigid for use in the neurosurgery. Another reason is that the long term patency rate of small caliber artificial blood vessels has usually been inferior to that found in autologous vein grafts. The purpose of this study was to develop a soft and compliant artificial blood vessel suitable for cerebrovascular surgery. This new artificial blood vessel is made of polyurethane, porous in structure (porous polyurethane). Thus, multiple small-sized pores exist both in the inner and outer surfaces, and in the wall of the porous polyurethane graft. To test its mechanical properties, we evaluated stress-strain curves and compliance. In comparison to expanded polytetrafluoroethylene graft (Goretex), which has been one of the most commonly used artificial blood vessels in the cardiovascular surgery, the mechanical properties of the porous polyurethane graft more closely resembled those of the common carotid artery in dogs. Thus, porous polyurethane graft was shown to be a soft and compliant new artificial blood vessel. This means not only that it can be maneuvered with technical ease for anastomosis but also that there is a reduction of compliance-mismatch between the host vessel and the artificial vessel. Compliance mismatch has been documented as a major factor in the inducement of intimal hyperplasia, which causes a delayed occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Bioabsorption of polylactides with different molecular properties.

In order to study the effects of factors governing the bioabsorption rate of polylactides, implantation tests were carried out in rabbits using various samples (20 x 10 x 2 mm3) differing in their chemical composition, residual monomer content, and molecular orientation. Copolymer samples with a higher lactic acid content showed a lower rate of absorption, whereas those with a higher unreacted monomer content were absorbed faster and showed a more drastic decrease in molecular weight. In contrast, degradation of the purified polymers was slow; the purified poly-L-lactide showed no weight change and a 50% reduction in molecular weight after 6 months of implantation. Scanning electron microscopy of the samples containing monomers showed a microporous structure extending from the surface to the inner region a few days after implantation, whereas the purified poly-L-lactide did not exhibit a microporous structural change even after 10 months of implantation.

Animals↗

PubMed1989

Protein precoating of polylactide microspheres containing a lipophilic immunopotentiator for enhancement of macrophage phagocytosis and activation.

Biodegradable microspheres containing a lipophilic muramyl dipeptide, MDP-B30, were prepared from a L-lactic acid-glycolic acid copolymer. The effect of precoating the microspheres with water-soluble polymers including proteins on the antitumor activity of mouse peritoneal macrophages (M phi) was investigated. Macrophages activated by phagocytosis of the microspheres exhibited growth inhibitory activity toward Meth-A tumor cells. The activity correlated with the extent of M phi phagocytosis of the microspheres. M phi phagocytosis was greatly augmented by gelatin precoating of the microspheres, resulting in a significant increase of in vitro antitumor activity of M phi by the microspheres. However, potentiation of M phi activity by gelatin precoating was minimal after intraperitoneal injection of the microspheres, but cross-linking of the coated gelatin with glutaraldehyde afforded potentiation of the antitumor activity in vivo.

Adjuvants, Immunologic↗

PubMed1989

Evaluation of polyvinyl alcohol hydrogel as a sustained-release vehicle for rectal administration of indomethacin.

In order to evaluate an indomethacin polyvinyl alcohol (PVA) hydrogel for rectal administration, the in vitro release characteristics of indomethacin from the hydrogel and indomethacin plasma concentrations after rectal administration were examined. The PVA hydrogel containing indomethacin was prepared by a low-temperature crystallization method. The release of indomethacin from the PVA hydrogel agreed with the Fickian diffusion model for 10 hr. Rectal administration of indomethacin hydrogels to rats yielded high indomethacin plasma concentrations, without producing a sharp peak, and a sustained-release effect. In dogs, the indomethacin hydrogel produced a similar sustained-release effect; however, the indomethacin plasma concentration was relatively low compared with that of an indomethacin suppository.

Administration, Rectal↗

PubMed1989

Synthesis of gelatin microspheres containing interferon.

Gelatin microspheres with a diameter less than 2 microns were synthesized by means of cross-linking with glutaraldehyde. When the microspheres were subjected to degradation in phosphate-buffered saline solution containing collagenase, the digestion of microspheres was found to decrease with increasing cross-linking. Interferon was incorporated in the microspheres at a high trapping efficiency, and the rate of interferon release from the microspheres was regulated by the extent of cross-linking with glutaraldehyde. Gelatin microspheres incorporating interferon-alpha were readily phagocytosed by macrophages, regardless of the extent of cross-linking, and the phagocytosed microspheres were observed to be degraded gradually in the interior of macrophages, resulting in the slow release of the incorporated interferon in the cells.

Chemistry, Pharmaceutical↗

PubMed1989

In vivo effects of recombinant interferon alpha A/D incorporated in gelatin microspheres on murine tumor cell growth.

Intraperitoneal (ip) injections of gelatin microspheres containing a very small amount of recombinant human interferon alpha A/D (A/D-IFN) (IFN-microspheres) plus free A/D-IFN improved the survival of mice bearing ascitic Meth A-R1 cells which we had isolated as IFN-resistant cells under in vitro conditions. The dose of free A/D-IFN in one injection was 10,000 IU, which was insufficient by itself for manifesting in vivo antitumor activity. In these mice, in vivo R1 cell growth was suppressed and macrophage recruitment was enhanced in comparison with mice receiving other control agents. Administration of IFN-microspheres alone was also effective but less than that of IFN-microspheres plus free A/D-IFN. Peritoneal macrophages obtained from normal or R1-bearing mice receiving ip injection of IFN-microspheres with or without free A/D-IFN were activated to inhibit the in vitro growth of R1 cells. The intratumoral injection of IFN-microspheres strongly inhibited the growth of solid R1 tumors. Intravenous injection of IFN-microspheres was effective in preventing the pulmonary metastasis of B16 melanoma cells. These results indicate that the IFN-microsphere is much more effective against tumors than free A/D-IFN.

Animals↗

PubMed1989

Design of polyvinyl alcohol hydrogel as a controlled-release vehicle for rectal administration of dl-propranolol-HCl and atenolol.

Preparations of beta-blockers, propranolol-HCl and atenolol, in poly(vinyl alcohol) (PVA) hydrogel were designed for the therapeutic treatment of hypertension by transrectal delivery. In vitro release characteristics and plasma drug concentration profiles after rectal administration in rats and dogs were examined. The PVA hydrogels containing beta-blockers were prepared by a low-temperature crystallization method. The release of beta-blockers from hydrogel preparations was consistent with Fickian diffusion (Higuchi model); the drug release versus the square root of release time profile gave a straight line over 60% of the total release process. The release of beta-blockers from hydrogel preparations increased at higher concentrations of PVA in the hydrogel preparations and was not affected by the pH of hydrogel preparations. Plasma concentrations of beta-blockers after rectal administration of hydrogels were higher than those after administration of suppositories (Witepsol H-15) in rats and dogs. The drug plasma concentrations increased at higher concentrations of PVA in hydrogel preparations. In the case of propranolol, which is a hepatic high-clearance drug, area under the blood concentration curve, 0-8 h after rectal administration of a hydrogel preparation (20% w/w PVA, pH 7.0) was 2.16 times and 5.26 times higher than those obtained with Witepsol H-15 suppository and oral administration, respectively. Rectal administration with PVA hydrogels is a favorable route for a hepatic high-clearance drug such as propranolol.

Animals↗