Biomedical subjects

Y Ikada

Publications and source records attributed to Y Ikada.

At least 19 recordsLinked to original sources

PubMed1992

[The effect of nicardipine on angiogenesis in vitro].

We studied the effect of nicardipine, a calcium channel blocker, on the morphological change of endothelial cells in vitro. Cultured endothelial cells derived from bovine carotid artery make tubular structures between collagen gel layers. Tube formation of endothelial cells was suppressed by culture with 10(-9)-10(-5) M of nicardipine in a dose dependent manner. Migration of endothelial cells was also suppressed by the same dose of nicardipine. However, proliferation of endothelial cells was not enhanced. These findings suggest that nicardipine acts as an inhibitor of angiogenesis in vitro by inhibiting the migration of endothelial cells.

Animals↗

PubMed1992

Toxicity test of biodegradable polymers by implantation in rabbit cornea.

To evaluate whether or not the corneal micropocket implantation is effective for determining the toxicity of polymeric materials, currently used biodegradable polymers such as poly(lactic acid) (PLA), poly(glycolic acid) (PGA), LA-GA copolymers, and three kinds of poly(2-cyano-acrylate)s (PCA) were implanted in a rabbit corneal pouch and the tissue responses were observed macroscopically and microscopically. It was found that PLA induced no vascularization, whereas a residual solvent and ethylene oxide gas remaining in the PLA matrix invoked vascularization. Vascularization clearly took place when PGA was implanted in the cornea, which became opaque, probably because of cellular infiltration. In the case of PCA implantation, severe inflammation as well as vascular invasion occurred in the initial stage. It is likely that these tissue reactions were caused by the leachables from the implanted materials, the extent being dependent on the leaching rate and the toxicity. It was concluded that the corneal micropocket assay is a good means to detect trace amounts of leachables from implanted materials without sacrificing the animals with the implanted materials.

Animals↗

PubMed1992

In vitro and in vivo studies on bioabsorbable ultra-high-strength poly(L-lactide) rods.

Ultra-high-strength poly(L-lactide) (PLLA) rods were fabricated using a drawing technique. Rods with a diameter of 3.2 mm and a draw ratio of 2.5:1 showed initial bending strength and modulus values of 240 MPa and 13 GPa, respectively. The purpose of this study was to investigate the in vitro and in vivo degradation of PLLA rods with a draw ratio of 2.5:1. The greater the rod diameter, the longer the bending strength was maintained in phosphate buffered saline at 37 degrees C. The bending strength retention of rods (diam. 3.2 mm) implanted in the subcutis of rabbits was almost equal to that of rods in the in vitro study, while those rods implanted in the medullary cavity of rabbit femora showed a slightly lower bending strength retention. Molecular weight was reduced to the greatest extent in the medullary cavity, followed by in the subcutis and in vitro. The weight of PLLA rods in the medullary cavity was reduced by 22% at 52 weeks and by 70% at 78 weeks after implantation. Histologically, no inflammatory or foreign body reaction was observed in the medullary cavity for 52 weeks. The drawn PLLA rods maintained a bending strength exceeding that of human cortical bone in the medullary canal for a period of 8 weeks, suggesting that the drawn PLLA rods may be useful in the repair of fractured human bones.

Absorption↗

PubMed1992

In vitro and in vivo digestion of collagen covalently immobilized onto the silicone surface.

In order to study the in vivo digestion of immobilized collagen and gelatin, these proteins labeled with 125I or fluorescein isothiocyanate (FITC) were covalently immobilized onto silicone surfaces, which were grafted with acrylic acid to introduce carboxyl groups, and implanted subcutaneously in rats and mice. When the proteins were labeled with FITC, the amount of proteins immobilized decreased with the increase of the number of FITC molecules conjugated with the protein molecule. In the wet state, FITC conjugated with the proteins was less stable than 125I. Approximately half of the amount of the immobilized proteins was digested in vivo within the first week and until 5 weeks after implantation the proteins were gradually digested. At that time, the amount of the proteins remaining on the silicone surface ranged from 0.6 to 1.0 microgram/cm2, which was several times larger than the amount of an assumed monolayer adsorption of proteins. Even after 15 weeks, the amount of proteins remaining on the silicone was almost the same as after 5 weeks. No significant difference in digestion was observed between collagen and gelatin, regardless of the labeling agent. Because of less stability and easier handling of FITC and higher stability and more difficult handling of 125I, FITC seems more suitable for short-term and 125I for long-term studies.

Animals↗

PubMed1992

Tissue reactions induced by modified poly(vinyl alcohol) hydrogels in rabbit cornea.

The purpose of this study was to compare the tissue reactions induced by modified poly(vinyl alcohol) (PVA) hydrogels with other materials implanted in the rabbit cornea. PVA hydrogels with and without covalently bonded collagen were compared to ethylene-vinyl alcohol copolymer, and polysulfone discs. These materials were implanted in the rabbit corneal stroma. The resultant tissue reactions were histologically and clinically studied. The PVA hydrogels had high flux rates of glucose and L-lactic acid in vitro. Covalent immobilization of collagen onto their surface was found to render them more biocompatible. However, excessive ulceration and vascularization of the cornea still occurred in vivo, possibly because of extremely little blinking of the rabbits, which might cause desiccation of the cornea.

Animals↗

PubMed1992

Interactions of poly(ethylene glycol)-grafted cellulose membranes with proteins and platelets.

The interactions of proteins and platelets with cellulose membranes grafted with poly(ethylene glycol) were studied. The poly(ethylene glycol) grafting was carried out using poly(ethylene glycol)-monoacid and poly(ethylene glycol)-diacid, which have one and two terminal carboxyl groups, respectively. The grafting operates through esterification between the carboxyl groups of poly(ethylene glycol) and the hydroxyl groups on the membrane surface. Both of the poly(ethylene glycol) grafted membranes reduced the complement activation. Adsorption of bovine serum albumin and gamma-globulin increased when the membrane was grafted with poly(ethylene glycol)-diacid, but did not change when it was grafted with poly(ethylene glycol)-monoacid. When platelets were incubated with serum proteins, the platelet adhesion to the membranes slightly decreased by grafting both the poly(ethylene glycol)-diacid and poly(ethylene glycol)-monoacid. The poly(ethylene glycol)-diacid grafted surface showed more clotting than the poly(ethylene glycol)-monoacid grafted and original surfaces.

Animals↗

PubMed1992

Evaluation of a bilayer artificial skin capable of sustained release of an antibiotic.

A bilayer artificial skin, composed of an upper silicone sheet and a lower collagen sponge, has been developed by modifying a technique proposed by Yannas and Burke. We have applied it clinically with success, but infection sometimes occurred in the area where the artificial skin was placed. To use it safely in an infected wound, we developed a new type of artificial skin capable of sustained release of antibiotic. Microspheres of poly-L-lactic acid containing an antibiotic, were installed in the upper silicone sheet. The usefulness of the new type of artificial skin was suggested by in vitro studies.

Biocompatible Materials↗

PubMed1992

Solidifying liquid with novel initiation system for detachable balloon catheters.

In endovascular surgery, to permanently hinder blood inflow into an aneurysm for example, a catheter is percutaneously introduced into an artery and the balloon is positioned and inflated by a solidifying liquid and then released into the diseased part. A novel solidifying liquid for the inflated balloon curable under the continuous feeding of oxygen through the wall of the balloon is described here. Glucose oxidase which oxidizes glucose producing hydrogen peroxide was used for polymerization of the solidifying liquid. This solidifying liquid cured even in the presence of oxygen and water. It was radiopaque when mixed with the iodinated X-ray contrast chemical iopamidol. In addition, the solidified liquid had appropriate mechanical properties. The endovascular surgery could be carried out safely using it.

Catheterization↗

PubMed1992

Degradation of collagen suture in vitro and in vivo.

In vitro and in vivo degradation of collagen suture was investigated focussing on the change in the mechanical properties and weight. The in vitro hydrolysis was carried out for catguts using collagenase (pH 7.4) and pepsin (pH 1.6), simulating the in vivo environments. The kinetic study on the weight loss of the fibre at the collagenase hydrolysis suggested that the degradation proceeded gradually from the surface of the fibre into the core. The enzymatic hydrolysis was different from the non-enzymatic acidic hydrolysis which resulted in almost homogeneous degradation throughout the cross-section of the fibre from the beginning of the hydrolysis reaction. The rate of weight loss with enzymatic hydrolysis was in good agreement with that predicted under the assumption of continuous erosion from the surface. When the collagen sutures were implanted in the subdermal tissue of rabbits, severe infiltration of macrophages and neutrophils was observed at 4 wk post-implantation, probably because of the degradation products from the implanted sutures. Comparison of the tensile strength decrease with the weight loss observed at the in vivo degradation revealed that enzymatic and non-enzymatic hydrolysis occurred concurrently in the subcutaneous tissue.

Animals↗

PubMed1992

Controlled cisplatin delivery system using poly(D,L-lactic acid).

Cisplatin (CDDP)-containing poly(D,L-lactic acid) microspheres (CDDP-MS) and beads (CDDP-B) with an average molecular weight of the oligomer of 1.2 x 10(4) and 4% CDDP loading were prepared. In Tris buffer, 95% of CDDP disappeared from CDDP-MS within 3 d. In vitro and in vivo, CDDP-B released CDDP for 30-57 d, and for 21-42 d, respectively. The other CDDP-B with an average oligomer molecular weight of 9.6 x 10(3) with 5% lactic acid monomers, that contained 4% CDDP, showed a two-phase CDDP release pattern and CDDP disappeared within 41 d in vitro, and within 21 d in vivo. Histologically, tissue necrosis surrounding the CDDP-B was not severe.

Animals↗

PubMed1992

In vitro evaluation of biocompatibility of surface-modified poly(methyl methacrylate) plate with rabbit lens epithelial cells.

Collagen type I was immobilized onto a poly(methyl methacrylate) (PMMA) plate by covalent bonding following surface modification by two methods. One method introduced amino groups by aminolysis with N-lithioethylenediamine (PMMA-NH2) and the other introduced carboxyl groups by graft copolymerization of acrylic acid (AAc) and acrylamide (AAm) (PMMA-COOH). Lens epithelial rabbit cells were cultured on the PMMA plate which was immobilized with collagen. Polygonal cells with a mosaic appearance were observed on the PMMA-COOH plate immobilized with collagen type I, whereas pleomorphic cells were present on the virgin PMMA and on the PMMA-NH2 plate immobilized with collagen type I. We concluded the PMMA-COOH plate immobilized with collagen type I provided a more comfortable atmosphere for lens epithelial cells, causing no metaplasia, than the other plates used in this cell culture model experiment.

Animals↗

PubMed1992

Effects of nicardipine on tube formation of bovine vascular endothelial cells in vitro.

BACKGROUND AND PURPOSE: The purpose of this study was to assess the effect of nicardipine, a Ca2+ channel blocker, on angiogenesis in vitro. METHODS: Bovine carotid artery endothelial cells were cultured between type I collagen gel layers with 10(-9) to 10(-5) M nicardipine. The morphological changes were monitored by phase-contrast microscopy and photographed. The total length of tubular structures was measured with an image analyzer system. Endothelial proliferation and migration assays were also performed with the same doses of nicardipine. RESULTS: Cultured endothelial cells form tubular structures between collagen gel layers. Tube formation of endothelial cells was suppressed by culture with 10(-9) to 10(-5) M nicardipine in a dose-dependent manner. Migration of endothelial cells was also suppressed by the same doses of nicardipine. However, proliferation of endothelial cells was not enhanced. CONCLUSIONS: Nicardipine acts as an inhibitor of angiogenesis in vitro by inhibiting the migration of endothelial cells. This result suggests that nicardipine may have therapeutic potential in angiogenic disorders such as tumor growth, atherogenesis, and diabetic retinopathy.

Animals↗

PubMed1992

Rapid morphological changes in bovine brain microvascular endothelial cells on extracellular matrices.

The morphological changes in endothelial cells derived from bovine brain microvasculature, carotid artery, and aorta during growth on extracellular matrices were compared. All cells formed tubular structures on a basement membrane. Ultrastructural studies showed that the tubular structures had lumens surrounded by many endothelial cells. On type I collagen gel, brain microvascular endothelial cells still formed tubular structures, but the other two cell types formed confluent monolayers. However, when a second layer of collagen gel was laid over these cells, tubular structures developed within 2-3 days. Brain microvascular endothelial cells form tubular structures more readily than endothelial cells derived from large vessels on both basement membrane and type I collagen gel.

Animals↗

PubMed1992

[Rapid morphogenesis of brain microvascular endothelial cells in culture system].

Endothelial cells of bovine brain microvascular vessels (BBECs), carotid artery (BCECs) and aorta (BAECs) were cultured on type I collagen and Matrigel. BBECs make tubular structures and BCECs and BAECs grow and make confluent monolayer on type I collagen gel. But BCECs and BAECs make tubular structures when second layer was overlaid. BBECs, BCECs and BAECs make tubular structures on Matrigel. These morphological changes were not affected by basic fibroblast growth factor. These results suggest that BBECs have more potent angiogenic ability than BCECs and BAECs.

Animals↗

PubMed1992

Biodegradable microspheres containing adriamycin in the treatment of proliferative vitreoretinopathy.

The use of biodegradable polymer microspheres containing adriamycin for the treatment of proliferative vitreoretinopathy (PVR) in an experimental rabbit model was investigated. A single injection of microspheres containing 10 micrograms of adriamycin effectively decreased traction retinal detachment to 10% (n = 10), whereas 50% of eyes injected with blank microspheres (n = 10) developed retinal detachment (P < 0.05). A single injection of microspheres, containing 3 micrograms of adriamycin, did not suppress retinal detachment. Electroretinographic and histologic studies confirmed that the 10 micrograms injection of adriamycin in microspheres was not toxic to the retina, although the injection of the same amount of free adriamycin caused retinal necrosis and detachment. Thus, microspheres containing adriamycin hold promise as a new treatment modality for PVR.

Animals↗

PubMed1992

Injectable microspheres with controlled drug release for glaucoma filtering surgery.

The authors evaluated the effects of biodegradable poly (lactic acid) microspheres that provided the controlled release of the antimetabolic agent adriamycin (ADR) to prevent post surgical fibrosis after glaucoma filtering surgery. Fifty six eyes of 28 rabbits underwent posterior lip sclerotomy and received a 0.2 ml subconjunctival injection that contained microspheres 90 degrees from the filtering site immediately after surgery. Microspheres containing ADR (100 or 200 micrograms) were randomly administered to one eye. The fellow eyes served as controls and received microspheres without the drug. Intraocular pressure in the eyes treated with the microspheres that contained the drug was significantly lower than that in the control eyes from days 7-12 in the 100 micrograms group and from days 6-16 in the 200 micrograms group (P < .05). Eyes that received ADR had a significantly longer patent filtering bleb compared with the control eyes (P < .05). No corneal complications were observed in the eyes treated with 100 micrograms of ADR and the control eyes. Peripheral corneal opacities (25%) and epithelial erosion (17%) were observed in the eyes that received the 200 micrograms dose, but the cornea returned to normal after 4 wk. These results suggest that controlled-drug-release microspheres with an antimetabolic agent may be promising for preventing fibrosis after surgery.

Animals↗

PubMed1992

Clinical use of synthetic absorbable cuff material for peripheral vascular anastomosis.

End to end arteriovenous (AV) fistulas were created using the cuff technique for hemodialysis in 12 patients with end stage renal disease. The cuff used was made of a synthetic biodegradable material, a lactic glycolic acid co-polymer with the same composition as absorbable surgical suture. Cephalic vein radial artery fistulas in the forearm were created electively in six patients to convert a Scribner shunt to a fistula in three patients and because of malfunction of a fistula created previously in three patients. Eleven patients underwent hemodialysis, with pump speeds of more than 200 milliliters per minute, and were evaluated for 129 to 477 days. These subcutaneous AV fistulas were maintained as patent functional veins and continued to function without complication. After five weeks, one patient had conversion to a prosthetic AV fistula because of poor venous maturation. The overall patency rate was 92 percent. The diameter of the AV anastomosis increased gradually with time. At 20 weeks, however, it reached more than 70 percent of the diameter of the radial artery lumen. These observations led us to believe that the cuff material used is biodegraded until 20 weeks and gives sufficient flexibility. In the future, the cuff method is expected to be clinically developed as another approach for vascular anastomosis.

Adult↗

PubMed1992

Isolation of adult pig islet. In vitro assessment and xenotransplantation.

This study was conducted to develop an isolation method for adult pig islets and to investigate in vivo function after xenotransplantation as well as in vitro function of isolated islets. From the splenic portion of the glands (n = 20), 3277 +/- 645 islets per gram of pancreas were isolated and recovered by a five-step dextran discontinuous density gradient method. Purity of the final preparation obtained from 20 different consecutive pig pancreata was 80-90%. In vitro incubation study revealed a significant insulin release from isolated adult pig islets in response to glucose stimulation. In vitro perifusion study demonstrated a biphasic insulin response to glucose stimulation from isolated islets. Xenotransplantation of approx 2000 isolated adult pig islets into the portal vein of diabetic Wistar rats (n = 8) significantly reduced serum glucose levels from 431 +/- 24 mg/dL to 173 +/- 18 mg/dL 24 h after transplantation. This study provides a development of an isolation method for adult pig islets and demonstrates that isolated islets are viable and functioning both in vitro study and in vivo study of xenotransplantation.

Animals↗