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Biomedical subjects

Y Ikada

Publications and source records attributed to Y Ikada.

At least 271 records · Page 15Linked to original sources

Targeted and sustained delivery of aclarubicin to lymphatics by lactic acid-oligomer microsphere in rat.

We examined targeted delivery of an anticancer drug, aclarubicin (ACR), to the lymphatic system in rats by encapsulation of the drug in microsphere (MS) prepared from nontoxic and biodegradable L-lactic acid-oligomer with an average molecular weight (Mw) of 3600. ACR was released at an almost constant rate from two kinds of ACR-MSs having different size (1-5 microns and less than 1 micron) over 20 d in phosphate-buffered saline at 37 degrees C. The intraperitoneal administration of both ACR-MSs (dose of ACR; 5 mg/kg) to rats sustained an almost constant ACR level (300-400 and 400-600 ng/ml) in the lymph of the thoracic duct during over 10 d, and the ACR level in the blood was extremely low, although intraperitoneal injection of ACR alone gave lower level of ACR in the lymph than in the blood level within 12 h.

Aclarubicin↗

Traumatic sternal segment dislocation in a child.

We present an extremely rare case of traumatic dislocation of a sternal body segment in a child. We treated this sternal segment dislocation by means of open reduction using a newly developed pin made from poly-L-lactide containing 10 percent by weight hydroxyapatite. It is not necessary to remove this type of pin later because it is degradable and absorbed within the body within about one year after implantation. A two-year follow-up of this case revealed a good clinical result.

Biocompatible Materials↗

Macrophage phagocytosis of biodegradable microspheres composed of L-lactic acid/glycolic acid homo- and copolymers.

A variety of biodegradable microspheres were prepared from L-lactic acid, DL-lactic acid, or glycolic acid homopolymers and copolymers of different molecular weights and monomer compositions. Phagocytosis of the microspheres by mouse peritoneal macrophages was studied in cell culture system using scanning electron microscopy as well as light microscopy. The diameter of microspheres prepared was less than 2 microns, regardless of the starting polymers. No dependence of the chemical nature of starting polymers was observed on the extent of phagocytosis of the microspheres by macrophages. Precoating the microspheres with water-soluble macromolecules such as proteins had great influence on phagocytosis by macrophages. It was demonstrated that precoating with bovine serum albumin and non-proteinaceous macromolecules reduced the phagocytosis of microspheres, while bovine gamma-globulin, human fibronectin, bovine tuftsin, and gelatin precoating enhanced the phagocytosis. This trend was not influenced by the presence of serum. Only in the case of gelatin precoating, the phagocytosis was greatly enhanced by the presence of serum as compared to precoating with other proteins. Microscopic observation clearly indicated that the phagocytosed microspheres were gradually degraded in the macrophage interior with the incubation time, leading to release of a fluorescent dye encapsulated in the microspheres. The rate of microsphere degradation in cells could be controlled by changing the molecular weight and the monomer composition of the copolymers comprising the microspheres.

Animals↗

Effect of the size and surface charge of polymer microspheres on their phagocytosis by macrophage.

Polystyrene and phenylated polyacrolein microspheres of different diameters, as well as modified cellulose microspheres with different surface charges, were prepared in order to study the size and surface charge effect on their phagocytosis by mouse peritoneal macrophages. It was found that the maximal phagocytosis of polystyrene and phenylated polyacrolein microspheres took place when their size was in the range 1.0-2.0 microns. Microspheres with hydrophobic surfaces were more readily phagocytosed than those with hydrophilic surfaces. There was no significant difference in phagocytosis between cationic and the anionic surfaces when compared at a zeta potential of the same absolute value. The least phagocytosis was observed for cellulose microspheres with non-ionic hydrophilic surfaces. Addition of fetal calf serum to the culture medium resulted in decrease in phagocytosis for all microspheres.

Acrolein↗

Potentiation of antitumor activity of macrophages by recombinant interferon alpha A/D contained in gelatin microspheres.

Gelatin microspheres containing recombinant human interferon alpha A/D (A/D-IFN) (IFN-microspheres) potentiated the antitumor activity of mouse peritoneal macrophages (M phi) much more efficiently than free A/D-IFN. M phi acquired the inhibitory activity on tumor cell growth by the ingestion of IFN-microspheres without the aid of lipopolysaccharide (LPS), though LPS was required as a second signal for activating M phi primed with free IFN. The IFN-microspheres were much more efficient than free IFN plus LPS in respect of the IFN amount and the time required for M phi activation. Furthermore, M phi pretreated with the IFN-microspheres maintained their activated state for a much longer period than those pretreated with free A/D-IFN plus LPS. A monoclonal anti-IFN-alpha A antibody, which was capable of neutralizing A/D-IFN, did not interfere with the M phi activation by the IFN-microspheres. Even human IFN-alpha A was effective in activating murine M phi similarly to A/D-IFN, when given in the form of IFN-microspheres, though human IFN-alpha A in the free form was ineffective. These results argue that the mechanism of M phi activation by the IFN-microspheres is different from that by free IFN.

Animals↗

["One-knot" microvascular anastomosis using glutide as an external splint--experimental arterio-arterial anastomosis in rats].

Experimental microvascular anastomosis using a glutide copolymer (lactide: glycolide = 80: 20) as an external splint was undertaken in rats between the left and the right carotid arteries. Both arteries were dissected free over a 1-cm length, the left carotid artery was transected at the cranial end, and the right carotid artery was cut at the caudal end. The left carotid artery was then introduced into a glutide pipe-splint. The arterial wall was turned back 180 degrees over the edge of the splint. The reflected part of the artery and the glutide were covered with the freed-up right carotid artery. One stitch was made around the two arteries and the glutide in a manner similar to that of binding a barrel with steel wire. The "One-knot anastomosis" was then complete. We call this type of anastomosis "antegrade anastomosis". If, on the other hand, the right carotid artery is introduced into the pipe, turned back at the edge of the glutide, covered with the left carotid artery and secured with one stitch, the technique is known as "retrograde anastomosis". The patency rates of the resulting vessels were as follows: antegrade anastomosis, 83% (15/18); and retrograde anastomosis, 92% (23/25); so that the average patency rate was 88% (38/43). We measured the anastomosing time that is the time between the transection of one of the two arteries and the completion of the anastomosis. The average anastomosing time was 21 minutes for antegrade anastomosis and 14 minutes for retrograde anastomosis. But the 'pure anastomosing time' (the time taken to connect the two already prepared arteries) was 2-3 minutes. We believe that one-knot anastomosis technique for future clinical application is promising.

Anastomosis, Surgical↗

Macrophage activation through phagocytosis of muramyl dipeptide encapsulated in gelatin microspheres.

Gelatin microspheres containing muramyl dipeptide (MDP) were prepared by crosslinking with glutaraldehyde. They were added to mouse peritoneal macrophages (PMs) to potentiate the tumour growth inhibitory activity. The PMs which had internalized the microspheres exhibited growth inhibitory activity to syngeneic, allogeneic, and xenogeneic tumour cells. A similar effect was observed for PMs incubated with free MDP, but the MDP encapsulated in the microspheres was more efficient in enhancing the PM activity than the free MDP. In addition, PMs were activated in much shorter periods upon incubation with the microsphere-encapsulated MDP. The duration of activity could be controlled for up to 7 days by changing the extent of crosslinking of microspheres. Dose-response experiments established that microsphere-encapsulated MDP is able to activate PMs to inhibit growth of tumour cells at concentrations approximately 2000 times lower than the free MDP present in media. The activity of PMs was also acquired on intraperitoneal injection of the microspheres, in contrast to PMs with the free MDP.

Acetylmuramyl-Alanyl-Isoglutamine↗

One-knot microvascular anastomosis. An experimental study in rats.

Experimental microvascular anastomosis using a glutide copolymer (lactide:glycolide, 80:20) as an external splint was undertaken in 33 rats between the carotid artery and the jugular vein. Both vessels were dissected free over a 1-cm length and cut at the cranial end of the dissected part. The carotid artery was then introduced into a glutide pipe-splint. The arterial wall was turned 180 degrees over the edge of the splint. This reflected artery wall and the glutide were covered by the freed-up jugular vein. One stitch was made around the vein, the artery, and the glutide in a manner similar to binding steel wire over a barrel. Thus, the "one-knot anastomosis" was completed. The patency rate at the anastomosed site was 100%, confirmed by angiography in 30 rats and by direct surgery in three. The time required to produce the anastomosis was between 5 and 7 minutes. Light microscopic observation showed that there was no obstruction by thrombus formation at 1 and 5 weeks after the anastomotic surgery. This technique may be clinically applicable for extracranial-intracranial bypass surgery, reconstruction of venous sinuses, and other vascular procedures.

Animals↗

[Sutureless method of micro-vascular anastomosis using low-energy Nd-YAG laser].

Sutureless end-to-end anastomosis of rat common carotid artery was carried out, low energy Nd-YAG laser being used thereby. An intraluminal-intervascular splint, made of water-soluble poval, was used for precise adaptation of the intimas. Neither stay suture nor glue was required. The patency rate of the anastomosed vessels, 24 hours after operation, was as high as 91%. The vessels were confirmed to be likewise patent on the 7th and 30th postoperative day. Complications such as pseudoaneurysm formation or stenotic change, were negligible. The fusion of the anastomosis with Nd-YAG laser was histologically proved to be satisfactory and the result of tensile strength test was excellent. Temperature at the anastomotic site during laser irradiation was measured, optimal energy for anastomosis determined and possible mechanism of vascular fusion by laser beam postulated. The major advantages of the laser technique combined with poval splint, such as rapidity, consistency and no residual foreign body (thread or adhesive), are discussed.

Anastomosis, Surgical↗

Polymer-hydroxyapatite composites for biodegradable bone fillers.

A number of composites made from biodegradable polymers and hydroxyapatite were studied in vivo and in vitro in an attempt to develop biodegradable artificial bone fillers. Histological observation in rats revealed that polylactic acid, of low molecular weight (PLAoligomer), was rapidly resorbed and replaced by newly formed bone tissue when incorporated with hydroxyapatite and this suggested that the incorporated hydroxyapatite seemed to play an active role in the new bone formation. In vitro testing revealed that the solubility of hydroxyapatite was markedly enhanced when mixed with PLAoligomer.

Animals↗

Immobilization of collagen onto polymer surfaces having hydroxyl groups.

The cyanogen bromide (CNBr) activation method was adopted to link collagen molecules onto the surface of cellulose and poly(vinyl alcohol) (PVA) films via covalent bonding. The amount of bound protein was determined by the ninhydrin method and found to be 1.0 microgram/cm2 for the native collagen and 0.6 microgram/cm2 for the denatured collagen. The amount of bound protein was larger for cellulose than PVA. When p-toluene-sulphonyl chloride was used to activate the cellulose film, this activation method was found to be effective in grafting the collagen as well. The cellulose film was found to become brittle and weak after activation with CNBr, but the PVA films was not. This might be due to the difference in the extent of crosslinking between cellulose and PVA films, as demonstrated by the change in degree of swelling and solubility of both the activated films.

Biocompatible Materials↗

An experimental study on prevention of postlaminectomy scar formation by the use of new materials.

An experimental study was performed to investigate the prevention of scar formation after lumbar laminectomy, using Elastase and the new polylactic acid (PLA) membrane containing Elastase. The experimental animals consisted of four groups: control group, E group (using intravenous administration of Elastase), P group (covering the laminectomy defect with PLA membrane), and P-E group (covering the laminectomy defect with "PLA" + Elastase" membrane). The animals were killed at varying intervals (2-12 weeks) and changes in the lumbar spines were evaluated histologically. Scar formation was suppressed most significantly in the P-E group, followed in order by the E group, the P group, and the controls.

Animals↗

New small-caliber antithrombotic vascular prosthesis: experimental study.

Vascular prostheses with the inner diameter smaller than 1 mm were implanted to the common carotid artery of rats, and their patency was examined. Four types of tubes were prepared for this purpose in Experiment 1: polyethylene (PE), poly-(acrylic acid)-grafted polyethylene (PE-AA), polyacrylamide-grafted polyethylene (PE-AAm), and poly(vinyl alcohol) (PVA) tubes. Comparative studies made using nonsuture anastomosis revealed that the PE-AAm and PVA tubes were antithrombotic, although disconnection was noted at the anastomotic sites within 1 week and 1 month, respectively. Thereafter in Experiment 2, the PVA tubes were implanted to the common carotid artery of 20 rats using conventional anastomosis. Neither anticoagulants nor fibrinolytic agents were used in both series of experiments. Patency of the PVA tubes was 80% after 1 week and 70% after 1 month. In patent cases after 1 month, the luminal surfaces of the prostheses and the host arteries were examined using scanning electron microscopy. The lumen of the arteries and anastomotic sites was covered with endothelial cells, while the lumen of the PVA tubes was free from thrombi and there was no neointima formation. So far, there has been reported no manmade material that has completely antithrombotic property in vivo. However, our studies disclosed that PVA is antithrombotic and one of the most promising materials for the inner surface of small vascular prostheses.

Acrylic Resins↗