Search PubMed⌕ Search

Biomedical subjects

Y Ikada

Publications and source records attributed to Y Ikada.

At least 145 records · Page 8Linked to original sources
PubMed1996

Size effect on the antibody production induced by biodegradable microspheres containing antigen.

Poly(L-lactic acid) (PLLA) microspheres containing a model antigen, ovalbumin (OVA), were prepared by the evaporation method using double emulsion, and fractionated into different sizes by counterflow elutriation. Following the intraperitoneal (i.p.) and subcutaneous (s.c.) injection of the microspheres to mice, the titer of anti-OVA antibody in the serum was measured to assess the size effect on the profile of antibody production. OVA was released from the microspheres for 80 days, irrespective of the microsphere size. In both the s.c. and i.p. immunization, the serum level of anti-OVA IgG antibody in the mice induced by the microspheres containing OVA was higher than that of free OVA when compared at the same dose. The serum level of antibody in the mice i.p. injected with the microspheres tended to increase with the decreasing size. On the other hand, in the s.c. immunization, the microsphere size had little influence on the antibody production. It is possible that the injected microspheres tend to aggregate in the s.c. tissue, disappearing the size effect on the antibody production. Since the amount of microspheres injected increases with the decreasing size when their OVA loading is fixed, the increase in the amount will promote the interaction with immune cells, resulting in an enhanced antibody production. The cell interaction with the microspheres in the peritoneal cavity seems to be influenced by their size to a greater extent than in the s.c. tissue, probably because of their more frequent interaction with immune cells.

Animals↗
PubMed1996

Adjuvant effect of biodegradable poly(DL-lactic acid) granules capable for antigen release following intraperitoneal injection.

Ovalbumin (OVA)-containing poly(DL-lactic acid) (PDLLA) granules were prepared with different conditions. Following the intraperitoneal (i.p.) immunization of mice with the granules containing OVA, production of anti-OVA IgG antibody in the mouse serum was investigated. The i.p. injection of the granules induced a strong antibody production compared with that of free OVA, irrespective of the amount of OVA released for initial a few weeks and the period of OVA release. The serum level of IgG antibody induced by the granules was retained at a high level over 16 weeks although the period of OVA release and the amount of OVA released initially were different from each other. The initial OVA release for a few weeks was essential to induce the enhanced antibody production. Comparison of mice immunization by granules with different OVA loadings but at a similar dose revealed that antibody level was higher for the granules with lower loading than for those with the higher loading. However, when the granules were injected after encapsulation into a poly(vinyl alcohol) (PVA) hydrogel tube, the difference in their antibody level became insignificant. Because PVA encapsulation did not affect the OVA release profile, this finding indicates that the injection amount of the granules seems to have influenced the antibody production. We conclude that the release profile of OVA is not always a key factor to enhance the antibody production of OVA-containing granules so far as the initial OVA controlled release is achieved.

Adjuvants, Immunologic↗
PubMed1996

Size effect on systemic and mucosal immune responses induced by oral administration of biodegradable microspheres.

Induction of systemic and mucosal immune responses following oral administration of biodegradable poly(D,L-lactic acid) (PDLLA) microspheres containing a model antigen, ovalbunin (OVA) was studied using microspheres with different average diameters of 0.6, 1.0, 4.0, 7.0, 11.0, 15.0, 21.0, and 26.0 microns. They were prepared from double emulsion with the solvent evaporation method, followed by size fractionation on counterflow elutriation. OVA was released from the microspheres in vitro over 80 days, irrespective of their size. Production of the serum anti-OVA IgG antibody and secretory OVA-specific IgA antibody in the mice gut was assessed following the oral administration of PDLLA microspheres containing OVA. Microspheres with a diameter of 4.0 microns enhanced the serum antibody in contrast with that of free OVA, but were not effective in inducing the gut secretion of IgA antibody. On the other hand, OVA-containing microspheres with a diameter of 7.0 microns enhanced IgA secretion to a significant extent compared with free OVA, whereas those with 26.0 microns in diameter were ineffective. Body distribution study revealed that the amount of microspheres taken up into Peyer's patches (PP) increased with the increasing size up to 11.0 microns, thereafter decreased, and finally became zero when their diameters were 21.0 microns or larger. The microspheres taken up into PP were translocated to the spleen, but no microspheres were noticed in the spleen when the size was larger than 5 microns. After being taken up inot PP, microspheres < 5 microns in diameter seemed to be transported to the spleen, a systemic lymphoid tissue, where the released antigen stimulated a serum antibody response, but larger microspheres probably remained at PP without being translocated to the spleen over the course of their antigen release, leading to induction of IgA secretion. It was concluded that the body distribution pattern of microspheres following the PP uptake was a key factor to regulate the induction of systemic and mucosal immune responses.

Administration, Oral↗
PubMed1996

Liver targeting of interferon through pullulan conjugation.

PURPOSE: The purpose of this study was to actively target interferon (IFN) to the liver through its chemical conjugation with pullulan, a water-soluble polysaccharide with a high affinity for the liver. METHODS: Chemical conjugation of IFN with pullulan was achieved by a cyanuric chloride method. Following intravenous injection of the conjugates to mice, their body distribution and the activity of an IFN-induced enzyme, 2', 5'-oligoadenylate (2-5A) synthetase in the liver and other organs, were evaluated. RESULTS: The cyanuric chloride method enabled us to prepare an IFN-pullulan conjugate that retained approximately 7-9% of the biological activity of IFN. Pullulan conjugation enhanced the liver accumulation of IFN and the retention period with the results being reproducible. When injected intravenously to mice, the IFN-pullulan conjugate enhanced the activity of 2-5A synthetase in the liver. The activity could be induced at IFN doses much lower than those of free IFN injection. In addition, the liver 2-5A synthetase induced by conjugate injection was retained for 3 days, whereas it was lost within the first day for the free IFN-injected mice. CONCLUSIONS: IFN-pullulan conjugation was promising for IFN targeting to the liver with efficient exertion of its antiviral activity therein.

2',5'-Oligoadenylate Synthetase↗
PubMed1996

New formulation of 5-fluorouracil in microspheres reduces toxicity in mice.

A new dosage formulation of 5-fluorouracil incorporated in microspheres (5-FU-MS) was developed for the treatment of peritoneal carcinomatosis. We studied the acute toxicity and side effects of i.p. 5-FU-MS in mice. The 50% lethal dose value for 5-FU-MS was 535.4 mg/kg of 5-FU, which was 2.22 times that of the aqueous 5-FU solution. Deaths occurred 12-17 days after the administration of 5-FU-MS, but within 11 days after the administration of aqueous 5-FU. Thus, lethal toxicity appeared later with 5-FU-MS than with aqueous 5-FU. There were no differences in pathologic findings on autopsy between mice given the two dosage formulations.

Animals↗
PubMed1996

An immuno-isolative membrane capable of consuming cytolytic complement proteins.

In an earlier article we demonstrated that xenogeneic islets of Langerhans in an agarose/poly(styrenesulfonic acid) (PSSa) microcapsule were protected from the host's immune rejection and that diabetic animals maintained a normal glucose level for a long period of time after their transplantation. In this study, we attempted to make clear the immuno-isolative mechanisms of the agarose-PSSa microcapsule from the standpoint of permeability of antibodies and complement proteins through this microcapsule membrane. It was found that the microcapsule was unable to prevent the permeation of IgG for longer than a few days, but protect the encapsulated cells from cytolytic complement attack. This strongly suggests that the cytolytic complement activity was lost during permeation through the microcapsule, probably because of the strong interaction of PSSa in the membrane with complement proteins. Based on these findings we proposed the minimum requirement for the immuno-isolative membrane to be applicable to xenotransplantation.

Animals↗
PubMed1996

New biodegradable oligoesters for pharmaceutical application.

Tartaric acid, malic acid, and glyceric acid were copolycondensed with glycolic acid at various molar ratios in feed to quickly synthesize biodegradable oligoesters. They were likely to have a moderately cross-linked structure with relatively low molecular weights and hydrophilic groups on the chains. In addition to macroscopic gels which were insoluble in any solvents, we could obtain the oligoesters which were insoluble in water but soluble in N,N-dimethylformamide. The degradation rate of the oligoesters was higher than that of lactic acid (LA) oligomers having molecular weights of a few thousands. On the contrary, their glass transition and flow temperatures were much higher than those of LA oligomers, indicating that their handling during the preparation of drug delivery dosage forms was much improved. The formulation of microspheres containing drugs from the oligoesters revealed that they were useful as biodegradable matrices having high degradation rates.

Antineoplastic Agents↗
PubMed1996

An observation on subsurface defects of ultra high molecular weight polyethylene due to rolling contact.

Ultra high molecular weight polyethylene (UHMWPE) has been used in artificial joints for a few decades, and wear of UHMWPE has been one of the main problems. Though many other materials have been tested over the years, the best clinical results are still achieved with UHMWPE. This makes the study of UHMWPE, especially in relation to artificial joints, very important. Frequently, more severe wear can be observed in artificial knee joints than in artificial hip joints especially when the flaking-like wear occurs. This flaking-like wear can lead to significant destruction of the artificial knee joint. Macroscopically, artificial knee joints have combinational movements of rolling and sliding in order to simulate the motion of the normal knee joint. The components of motion are separated to make study easier. Fatigue tests of UHMWPE under the rolling contact condition were performed in this study. Three ceramic spheres were rolled over the UHMWPE specimen using 37 degrees C distilled water as a lubricant. The UHMWPE specimen was observed by the scanning acoustic tomography, microscopy, and SEM. Some subsurface defects could be observed by SAT even before experiments. Although the apparent wear is not observed on the surface, there was an increase in the number of observable subsurface cracks in the UHMWPE specimen. This shows that cracks occur under the surface after a 10(7) rolling contact loading, which is very close to the cyclic loading and unloading with very little friction compared to the sliding contact.

Ceramics↗
PubMed1995

In vitro evaluation of cytotoxicity of diepoxy compounds used for biomaterial modification.

The toxicity of various diepoxy compounds used for biomaterials crosslinking was investigated with a cell culture method and compared with an in vivo method. The neutral red uptake by cells was used to count the number of cells still alive after contact with the diepoxy compounds, because this method was more sensitive in cell counting than the other four methods studied in this work. The amount of neutral red taken up by cells depended strongly on the activity of cells in comparison with other methods; only small amounts of neutral red were taken up when cells were in a low activity state even if they were still alive. The in vitro toxicity of diepoxy compounds evaluated by the neutral red method revealed a good correlation with that found by the in vivo Draize test. The in vitro cytotoxicity to a cell line of L929 was closely related to that of primary culture cells of the normal rabbit cornea epidermal cell. The toxicity of diepoxy compounds was lower as their chain was longer, probably because of the lower chemical reactivity. All the diepoxy compounds investigated in this study exhibited lower cytotoxicity than formaldehyde, glutaraldehyde, and a water-soluble carbodiimide.

Animals↗
PubMed1995

Fate of water-soluble polymers administered via different routes.

The biological fate of synthetic water-soluble polymers administered to mice by injection at different sites is described. After intraperitoneal (ip), subcutaneous (sc), and intramuscular (im) injections of 125I-labeled poly(vinyl alcohol) (PVA) and poly(ethylene glycol) (PEG) with various molecular weights, the time-course of polymer concentration in the blood was measured and analyzed pharmacokinetically. The location of PVA in the body was similar to that of PEG; that is, the elimination from the injection sites and the translocation from the injection sites into the blood circulation were similar for both polymers. The elimination rate of both polymers from the injection sites increased in the order ip > sc > im. After sc and im injections of polymers, the elimination rate decreased with an increase in the molecular weight, whereas the elimination rate of polymers injected showed no molecular weight dependence over the range studied, regardless of the type of polymers used. The time-course of polymer concentration in the blood depended largely on the injection route of the polymers, and the polymer elimination from the blood circulation was enhanced with the decreasing molecular weight of polymers injected. It was concluded that the molecular weight and the injection site are the important factors that affect the concentration profile of polymers in the blood circulation.

Alcohols↗
PubMed1995

Further applications of "bilayer artificial skin".

A "bilayer artificial skin", composed of an inner layer of collagen sponge and an outer silicone layer, was developed by modifying the material reported by Yannas and Burke. Since our early results from experimental and clinical use of the original version of the "bilayer artificial skin" were reported, several improvements have been made in stages to eliminate some drawbacks related to disinfection and preservation and to reduce the primary cost of manufacture. The latest version of the material was successfully used in 27 sites on 23 patients. In this paper, the improvements in the material and the clinical results are described.

Adolescent↗
PubMed1995

Simple method for platelet counting.

A method is proposed for counting the number of adhered platelets based on the determination of lactate dehydrogenase activity in bulk after lysis of adhered platelets. This method was compared with the widely used radioisotope labelling technique. It was concluded that the present lactate dehydrogenase method is effective in counting the adhered platelets, as no significant difference was found between the readings of two methods when commercial polymers and glass were used as samples.

Biocompatible Materials↗
PubMed1995

Degradation of high molecular weight poly(L-lactide) in alkaline medium.

To study the effect of molecular weight and morphology on hydrolytic degradation, four poly(L-lactide)s (PLLAs) with average molecular weight of 3.0 x 10(5), 4.5 x 10(5), 6.5 x 10(5) and 3 x 10(6) were used. PLLA films with different morphologies were obtained by solution casting. Degradation of the films was performed at 37 degrees C in 0.01 N NaOH solution and this alkaline hydrolysis seemed to simulate well the real case while offering significant acceleration of the degradation process. Diverse microscopy techniques (light, polarizing and scanning electron) were used to study the surface change of morphology and erosion of the PLLA films. Swelling was visualized by scanning electron microscopy, particularly on the spherulites, which were eroded from the centre by hydrolysis. In the case of highly amorphous film, crystallization took place as degradation proceeded. The reduction in transparency of PLLA films, measured by a spectrophotometer at 570 nm, was ascribed to the increased density of spherulites. Differential scanning calorimetry revealed that the crystallinity of PLLA increased with degradation time, in accordance with accelerated spherulite formation.

Biocompatible Materials↗