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Biomedical subjects

T Yotsuyanagi

Publications and source records attributed to T Yotsuyanagi.

At least 55 records · Page 3Linked to original sources
PubMed1997

[Chemotherapy targeting regional lymph nodes by gastric submucosal injection of liposomal adriamycin in patients with gastric cancer].

We investigated the delivery of adriamycin (ADR) to the regional lymph nodes of the stomach following the gastric submucosal injection of liposomal adriamycin (Lipo-ADR) in 34 gastric carcinoma patients, as well as following intravenous administration of free ADR (F-ADR) in 18 patients, then followed these patients for a minimum of 5 years or until death. Prior to radical gastrectomy. Lipo-ADR was endoscopically injected into the gastric submucosa adjacent to the primary tumor via a needle-tipped catheter. After Lipo-ADR injection, the ADR concentration in the primary and secondary drainage lymph nodes was higher than in the other regional lymph nodes. Thus, the regional nodes more susceptible to the involvement of metastasis showed higher levels of ADR. In contrast, the intravenous administration of F-ADR produced a similar and far lower ADR concentration in all the nodes. Delivery of ADR to the primary drainage lymph nodes following injection of 5 mg of Lipo-ADR (n = 19) was compared with delivery to the left gastric artery lymph nodes after intravenous administration of an equal dose of Lipo-ADR. The ADR levels (microgram/g) after gastric submucosal injection were 15.1 +/- 8.30 on day 1 (n = 4) and 11.9 +/- 4.80 on day 4 (n = 6), whereas, the ADR levels after intravenous administration were 0.29 +/- 0.10 on day 1 (n = 4) and 0.36 +/- 0.0 on day 4 (n = 2). The differences between the two groups were significant (p < 0.05). The ADR levels after the gastric submucosal injection were far higher than those after intravenous administration. These findings indicate that the gastric submucosal injection of Lipo-ADR can specifically deliver ADR to the regional lymph nodes at high concentrations. Disease-free survival of the stage III a-b patients (n = 7) with this regional lymph nodes-targeted chemotherapy was 71.4% in 5 years, while that with intravenous F-ADR administration (n = 5) was 60.0%. This preoperative adjuvant chemotherapy targeting the regional lymph nodes may be effective in preventing the recurrence of gastric carcinoma.

Antibiotics, Antineoplastic↗
PubMed1997

[Possibility of alpha-tricalcium phosphate (alpha-TCP) particles as a drug carrier for treatment of abdominal carcinomatosis].

It is reported that cancer foci are unevenly distributed in abdominal carcinomatosis after intraperitoneal inoculation of cancer cells in rats. The organs may be briefly classified into two groups in terms of the deposit of cancer cells: one that shows an affinity to the cells includes the greater omentum, mesenterium, and gonadal fat and etc., and the other having lesser affinity the stomach, intestine, and spleen and etc. Such uneven distributions are likely to occur in clinical cases of abdominal carcinomatosis resulting from progressive digestive cancers. We have explored the possibility of alpha-Tricalcium Phosphate (alpha-TCP) particles as a drug carrier in which carboplatin (CBDCA) was incorporated. alpha-TCP, which has chemically similar properties to hydroxyapatite, is known to have an excellent biocompatibility with human tissues and is biodegradable. The present study focused on the localization and the forms of alpha-TCP particles, and the morphological changes of the surrounding tissues after intraperitoneal administration using normal and cancer-bearing rats. The following results were obtained: (1) alpha-TCP particles were taken up to a large extent in the "milky spot" of the greater omentum, followed by the "stomata" of the mesenterium, gonadal fat, diaphragm, peritoneum, and liver in normal rats. No alpha-TCP particles were caught up in the tissues of the stomach, small intestine, colon, and spleen. The margination and emigration of lymphocytes were slightly observed around those organs. (2) alpha-TCP particles were predominantly detected on the cancer mass of the greater omentum in abdominal carcinomatosis-bearing rats. It should be noted that the particles collected in the same place where cancer cells were caught, suggesting that the localization of the drug-containing particles result in higher drug concentrations in the cells possibly for extended times. The alpha-TCP particles system is expected to be a good candidate for targeting chemotherapy and specially for abdominal carcinomatosis.

Abdominal Neoplasms↗
PubMed1996

Facial injury by mercury from a broken thermometer.

The case of a 2-year-old girl with a facial soft-tissue injury from an accident with a mercury thermometer is presented. All tissues containing droplets of metallic mercury should be removed immediately and careful examination for signs of mercury poisoning should be conducted over the long term.

Child, Preschool↗
PubMed1996

Relationship between uptake of p-hydroxybenzoic acid esters by Escherichia coli and antibacterial activity.

The relationship between the uptake and antimicrobial activity of p-hydroxybenzoic acid esters (parabens) was studied using Escherichia coli. The uptake into bacterial cells and the antibacterial activity of parabens were logarithmically proportional to the carbon number of the alkyl group from methyl to butyl paraben. The free energy change for the transfer of the methylene group of parabens from the aqueous to the cell phase was less than that obtained from the n-hexane and n-octanol-water partition systems. This demonstrates that the hydrophilicity of the cells is larger than n-hexane and n-octanol. The uptake of hydrophobic ethyl benzoate was less than that of the more hydrophilic butyl paraben possessing a phenolic hydroxyl group. Parabens may thus be incorporated into cells by both hydrophobic and hydrophilic interactions. The apparent concentration of parabens in the bacterial cells required to produce the same antibacterial activity decreased logarithmically with an increasing carbon number of the alkyl group. The dependence of the antibacterial activity of parabens on the alkyl chain length may thus be concluded to be due to the alkyl group, not only for uptake into bacterial cells but also for accumulation or concentration on biological receptors after incorporation into the cells.

Cell Wall↗
PubMed1996

Application of alginate gel as a vehicle for liposomes. I. Factors affecting the loading of drug-containing liposomes and drug release.

To explore the feasibility of alginate gel as a vehicle for liposomes, we investigated the effects of various factors associated with the loading of drug-containing liposomes into the gel beads. The loading process includes (I) mixing of liposomes and alginate solution, (2) calcium induced gelation of alginates, (3) the time-dependent contraction of a gel body squeezing out interior water, and (4) possible leakage or release of a drug entrapped in liposomes in a series of each of theses processes. These effects were examined in terms of the leakage of a marker 5(6)-carboxyfluorescein (CF) from liposomes of egg phosphatidylcholine (EPC) and EPC/cholesterol (EPC/Cho) and liposome (phosphorus) release from curing and fully-cured gel beads whose initial polymer concentrations were 4 and 2%. Major findings were: (1) Alginate induced the leakage of a water-soluble drug incorporated in the liposomes as a function of the polymer concentration and the mixing time. (2) Calcium ions also stimulated the leakage of the drug. EPC/Cho liposomes were several times more resistant to the leakage of CF than were EPC liposomes. (3) The liposomes were well loaded without any loss in the gel bead despite the squeezing outflow of water and the bead contraction during gel curing. (4) Such curing caused leakage of the drug from the EPC liposomes in the very early stage while no effect was observed in the EPC/Cho liposomes. (5) In the gel-eroding medium (pH 7.4 Tris-HCl, 37 degrees C), the total drug release was controlled by the erosion rate of the bead body. Immediately after the bead erosion, EPC liposomes retained about 60% of the drug in the 2% bead and only about 20% in the 4% bead, whereas EPC/Cho liposomes retained more than 85% regardless of the initial alginate concentration. The results provide valuable information for the design and applicability of the gel-loaded liposome delivery system.

Alginates↗
PubMed1996

Effects of the structures of polyoxyethylene alkyl ethers on uptake of butyl p-hydroxybenzoate by Escherichia coli and its antibacterial activity.

The effects of the structures of non-ionic surfactants on the uptake of butyl p-hydroxybenzoate (BP) into Escherichia coli cells and its antibacterial activity were systematically studied using polyoxyethylene alkyl ethers (PAEs) possessing various oxyethylene and hydrocarbon chain lengths. The uptake of BP into bacterial cells in an aqueous PAE solution was proportional to free BP in an aqueous phase, depending on the structures of PAEs. The antibacterial activity of BP decreased in the presence of PAEs, whereas it was greater than that anticipated from free BP. However, only PAE with 12 carbons in the hydrophobic group caused unusual increases in the uptake and antibacterial activity of BP, and the surfactant was more extensively incorporated into bacterial cells, differing from other PAEs, which were much less incorporated. The PAEs were thus concluded to increase the susceptibility of bacteria against BP due to direct interactions with the cells. Particularly, the PAE with 12 carbons in the hydrophobic group, which penetrated abundantly into the cells, might result in an increase in the fluidity of the cellular lipid matrix and a decrease in the resistance of drug permeation.

Escherichia coli↗
PubMed1996

[Intraperitoneal administration of carboplatin loaded alpha-tricalcium phosphate (alpha-TCP) particles in rats bearing abdominal carcinomatosis].

It is difficult to treat abdominal carcinomatosis with conventional chemotherapy, and many kinds of localized chemotherapy have been attempted. We used alpha-tricalcium phosphate (alpha-TCP) particles as a drug carrier in this study. alpha-TCP, which has chemically similar properties to human bone, has an excellent biocompatibility with human tissues and is biodegradable. The particles measured 50 to 100 microns in diameter, were round in shape and very porous. These particles have many open micro-pores of about 1 to 3 microns, which are beneficial for containing drugs. The compatibility and biodegradation of alpha-TCP particles were studied following intraperitoneal (ip) administration in normal rats. The following results were obtained: (1) alpha-TCP particles were intaken in the great omentum, and dissolved gradually. (2) The efficacy of ip administration of carboplatin-loaded alpha-TCP (alpha-TCP-CBDCA) was examined using a Donryu rat model with AH130 abdominal carcinomatosis. The alpha-TCP-CBDCA contained 200 mg alpha-TCP and 4 mg CBDCA. The pharmacokinetics of CBDCA following ip administration of alpha-TCP-CBDCA were studied. Pt levels in ascites and great omentum were higher in the alpha-TCP-CBDCA ip from 0.5 to 168 hours than those in the free-CBDCA ip and iv groups. These results suggest that the efficacy of CBDCA may be enhanced by utilizing alpha-TCP particles as a drug delivery carrier.

Animals↗
PubMed1996

Studies of succinate dehydrogenase inhibition (SDI) test with cisplatin encapsulated liposome against cancer cells.

In the present study, by means of encapsulating into liposome, cisplatin was made a soluble capsule, and augmentation of the antitumor effect through the cell affinity of liposome was investigated by chemosensitivity test for cancer cells. Augmentation of the antitumor effect by collaboration of the cell affinity of liposome with the diffusion by concentration gradient was expected. However, although a difference in absorbancy was in fact observed, no statistically significant difference of effect superior to cisplatin alone was observed.

Animals↗
PubMed1995

Sustained release of basic fibroblast growth factor from the synthetic vascular prosthesis using hydroxypropylchitosan acetate.

We designed a model vascular prosthesis consisting of expanded polytetrafluoroethylene (Gore Tex) loaded with basic fibroblast growth factor (bFGF), and studied its in vivo bFGF release behavior. To control the release rate of bFGF, biodegradable hydroxypropylchitosan acetate (HPCHA) was also incorporated into the Gore Tex disks with bFGF. HPCHA was dissolved in bFGF solution (180 micrograms/ml) at a concentration of 4% (wt/vol). A Gore Tex tube was cut into a length of about 5 cm and one end was sealed with a vascular clamp. The tube was then filled with resulting solution under appropriate pressure until the solvents seeped through the pores. The tube loaded with bFGF solution was freeze-dried and was cut into disks (0.75 cm in diameter). bFGF content in a HPCHA-free Gore disk was 2.05 +/- 0.32 micrograms (SE, n = 5). bFGF content in a HPCHA Gore disk was 2.71 +/- 0.41 micrograms (SE, n = 5). In an in vivo study in which the bFGF loaded Gore Tex disk was implanted in rabbit skin pockets, almost 100% of bFGF from HPCHA-free disks was released within 24 h, whereas some 60% remained after 24 h in the HPCHA-loaded disks. HPCHA is a useful biodegradable carrier for controlling the release rate of the drug from the synthetic vascular prosthesis.

Animals↗
PubMed1995

Prevention of bone loss by percutaneous estradiol implants in ovariectomized rats.

This study was conducted to investigate whether hydroxyapatite (HAP) is appropriate as a percutaneous drug carrier for estradiol (E2) for the suppression of bone loss. Ten-week-old female Sprague-Dawley rats were subjected either to bilateral ovariectomy (OVX) or to sham surgery (control). Ovariectomized rats were implanted percutaneously with E2-HAP disks containing low, medium or high doses of estradiol (50, 250, or 500 micrograms E2/rat, respectively). Ovariectomized rats without implant and OVX rats implanted only with HAP served as additional controls. All rats were sacrificed 90 days after surgery. At the end of the experiment, bone mineral density of the lumbar spine was measured by dual energy X-ray absorption, and serum E2 was assayed by radioimmunoassay. The bone mineral density of OVX and HAP-treated OVX rats decreased by 18% compared to sham surgery rats, but decreased by only 13, 7, and 3% in rats treated with 50, 250, and 500 micrograms E2/rat, respectively. The in vitro release of E2 from E2-HAP devices was determined by an HPLC method. Estradiol release from the HAP devices followed almost a zero-order kinetics. Estradiol remained intact in E2-HAP implants for up to six months when stored at 5, 25, and 40 degrees C. This study indicates that E2-HAP implants are effective in suppressing bone loss in the spine of OVX rats in a dose-dependent manner.

Animals↗
PubMed1994

A simple and compressive splint for palmar skin grafting in young children with burns.

A simple, compressive, and easily applied splint which is suitable even for fearful and uncooperative patients after skin grafting for paediatric deep palmar burns is described. The hand, including the wrist and the forearm, is inserted between the palmar and dorsal plates of the splint and thus compression and immobilization act to decrease flexion contracture and dysfunction of the digits. Compression can be easily controlled by the use of leather bands.

Burns↗
PubMed1994

Earlobe reconstruction using a chondrocutaneous flap.

A postauricular chondrocutaneous flap including a postauricular artery was used in reconstructing congenital dysplasia of the earlobe. This flap had a safe and sufficient blood supply and had an excellent texture match. To reconstruct congenitally absent earlobes of two patients, a skin flap of the mastoid region and a chondrocutaneous flap that has a subcutaneous pedicle were used. To reconstruct congenital hypoplastic earlobe clefts of three patients, hinge flaps of two small earlobes and a transpositioned chondrocutaneous flap were used. The reconstructed earlobes had a thin, natural form, and deformity by contracture had not developed. The donor scar left by the flap was inconspicuous.

Child↗
PubMed1994

Chemotherapy targeting regional lymph nodes by gastric submucosal injection of liposomal adriamycin in patients with gastric carcinoma.

We investigated the delivery of adriamycin (ADR) to the regional lymph nodes of the stomach following the gastric submucosal injection of liposomal adriamycin (Lipo-ADR) in 34 gastric carcinoma patients, as well as following intravenous administration of free ADR (F-ADR) in another 18 patients. Prior to radical gastrectomy, Lipo-ADR was endoscopically injected into the gastric submucosa adjacent to the primary tumor via a needle-tipped catheter. After Lipo-ADR injection, the ADR concentration in the primary and secondary drainage lymph nodes was higher than in the other regional lymph nodes. Thus, the regional nodes more susceptible to metastasis showed higher levels of ADR. In contrast, the intravenous administration of F-ADR produced a similar and far lower ADR concentration in all the nodes. Delivery of ADR to the primary drainage lymph nodes following injection of 5 ml of Lipo-ADR was compared with delivery to the left gastric artery lymph nodes after intravenous administration of an equal dose of F-ADR. The ADR levels (micrograms/g) after gastric submucosal injection were 15.1 +/- 8.30 on day 1 (n = 4); and 11.9 +/- 4.80 on day 4 (n = 6). Those after intravenous administration were 0.29 +/- 0.10 on day 1 (n = 4); and 0.36 +/- 0.0 on day 4 (n = 2). The differences between the two groups were significant (P < 0.05). The ADR levels after the gastric submucosal injection were far higher than those after intravenous administration. These findings indicate that the gastric submucosal injection of Lipo-ADR can specifically deliver ADR to the regional lymph nodes at high concentrations. Such preoperative adjuvant chemotherapy targeting the regional lymph nodes may be useful for preventing the lymph node recurrence of gastric carcinoma.

Adult↗
PubMed1994

Binding and aggregation of human gamma-globulin by cis-diamminedichloroplatinum(II) through disulfide bond.

The incubation of gamma-globulin with cis-diamminedichloroplatinum (II) (cis-DDP) resulted in gradual formation of insoluble aggregates. Since the precipitates, composed of polymerized gamma-globulin and cis-DDP, were completely solubilized with urea, the reaction mixture containing precipitate was examined in terms of the binding of cis-DDP and the effect on disulfide (S-S) bonds in the gamma-globulin. When gamma-globulin was incubated with 30 molar excess cis-DDP at pH 7.4 and 37 degrees C, cis-DDP gradually bound to as much as 12 mol per mol of gamma-globulin in 14 d. Concurrently, about four disulfide bonds were cleaved without reaching a certain plateau. An sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of the aggregated gamma-globulin induced by cis-DDP was significantly different from that of the heat-denaturated aggregate form or the reduced form by sulfitolysis. The aquated complexes of cis-DDP also produced an insoluble precipitate and affected the S-S bond to a greater extent than the parent drug.

Cisplatin↗
PubMed1994

Anticancer effects of adriamycin-loaded hydroxyapatite implants determined in a Swarm rat chondrosarcoma model.

We investigated the antitumor effects of adriamycin (ADR)-loaded hydroxyapatite (HAP) beads in a Swarm rat chondrosarcoma model. When one ADR-loaded HAP bead (ADR: 0.8 mg/bead) was implanted into the central portion of a rat bearing tumor, the ADR-loaded HAP beads showed good therapeutic effects, increasing the life span (ILS) by 90%. Significantly, leukopenia and diarrhea were not observed. These results suggest that HAP delivery offers an interesting and a potentially effective method.

Animals↗
PubMed1994

Antitumor effects and distribution of adriamycin incorporated into hydroxyapatite implants in a cancer rat model bearing swarm rat chondrosarcoma.

We investigated the antitumor effects and tissue distribution of adriamycin (ADR) incorporated into a hydroxyapatite (HAP) bead in a cancer rat model bearing Swarm rat chondrosarcoma. The Porous HAP bead (8.48 mm in diameter, 531 +/- 0.7 mg in weight) was used as a model bone graft. One ADR-HAP bead (ADR 0.4 mg-6.0 mg/bead) was implanted s.c. into a Sprague-Dawley rat at 6 days postinoculation of Swarm rat chondrosarcoma. ADR-HAP beads showed strong antitumor activities in a dose dependent manner. The dose of 6.0 mg/bead showed the highest efficacy with no toxic death: It caused a 98% growth inhibition on Day 31 postinoculation and a survival advantage of a 339% increase in life span. After the implantation of the ADR-HAP bead (0.4 mg/bead/body) and the i.v. administration of an equal dose of free adriamycin, we determined the tissue distribution of ADR for up to 90 days. ADR-HAP bead implanted in the tumors released ADR over a 12-week period in the target area. The diffusion of the drug to other organs such as the heart and liver was very low compared with the tumors. The area under the ADR concentration-time curve (AUC) of the tumors was 181.6 micrograms.day/g and 5.22 micrograms.day/g after the implantation of the ADR-HAP bead and the i.v. administration of free ADR, respectively. The targeting index of the tumors, defined as the ratio of the AUC after the implantation of the ADR-HAP bead to that after administration of free ADR, was 34.8.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Compressive plastic splint for postoperative management of the ear.

A new splint for use after ear reconstruction is described. This splint adjusts suitably to the complicated contours of the ear without requiring any impressions before fabrication. The splint controls expansion and contractile forces and consequently prevents some of the complications following ear surgery.

Adult↗