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Biomedical subjects

T Yotsuyanagi

Publications and source records attributed to T Yotsuyanagi.

At least 73 records · Page 4Linked to original sources

Expanding oral plastic splint for burn patients.

An expanding oral plastic splint for preventing microstomia from deep facial burns is described. This splint adjusts to suit the affected oral angles without the need for taking any impression before fabrication. It is especially suitable for severely injured patients starting from the early period shortly after injury, even if the patient has been intubated. Furthermore the expansion forces can be controlled easily according to the degree of contracture.

Adult↗

Delivery of lymph node-targeted adriamycin by gastric submucosal liposomal injection in rabbits.

We investigated the feasibility of specifically delivering adriamycin (ADR) to the regional lymph nodes via gastric submucosal injection of liposomal adriamycin (Lipo-ADR) in a rabbit model. We determined the tissue distribution of ADR for up to 7 days after the gastric submucosal injection of Lipo-ADR (0.4 mg/kg of ADR potency) and i.v. administration of an equal dose of free adriamycin (F-ADR). The area under the ADR concentration-time curve (AUC) of the regional lymph nodes was 85.4 micrograms.day/g after gastric submucosal injection of Lipo-ADR and 8.44 micrograms.day/g after i.v. administration of F-ADR. The targeting index of the regional lymph nodes, defined as the ratio of the AUC after gastric submucosal injection of Lipo-ADR to the AUC after i.v. administration of F-ADR, was 10.1. Gastric submucosal injection of Lipo-ADR enhanced lymph node-specific delivery of ADR compared with i.v. administration of F-ADR. The targeting index was 0.47 for the heart, 0.25 for the bone marrow, and 0.41 for the spleen, indicating that gastric submucosal injection of Lipo-ADR reduced delivery of ADR to these organs, as compared with i.v. administration of F-ADR. These data demonstrate that gastric submucosal injection of Lipo-ADR is well suited for specific delivery of ADR to the regional lymph nodes, suggesting that this method of administration may be useful in delivering preoperative adjuvant chemotherapy for preventing gastric cancer recurrence.

Animals↗

Alteration of fibrinogen secondary structure by cis-diamminedichloroplatinum(II) and calcium protection.

The structural alteration of human fibrinogen (Fbg) by cis-diamminedichloroplatinum(II) (cis-DDP) was investigated using intrinsic fluorescence and circular dichroism (CD) spectra. In a preceding report, incubation of Fbg with cis-DDP under physiological conditions resulted in the cleavage of disulfide (S-S) bonds (N. Ohta, T. Yotsuyanagi and K. Ikeda, J. Pharmacobio-Dyn., 15, 611 (1992)). The intensity of fluorescence for cis-DDP-treated Fbg, in which 6.7 S-S bonds per mol of protein were cleaved, was reduced to 42% relative to native Fbg. CD studies suggested that the alpha-helix content decreased from 42% in its natural state to 29% in the cis-DDP-treated form. The extent of the fluorescence quenching and the decrease in helix correlated with the number of cleaved S-S bonds. The results indicate that cis-DDP leads to a secondary conformational alteration of Fbg involving a structural perturbation of nearby tryptophan residue(s) through S-S bond cleavage. In a buffer containing calcium, however, the smaller fluorescence quenching and the smaller helix decline were observed in cis-DDP-treated-Fbg, even though the same level of S-S cleavage occurred. Calcium binding would protect Fbg in terms of structural alteration as well as S-S cleavage by both dithiothreitol (DTT) and cis-DDP.

Binding Sites↗

Synthesis of antibiotic-loaded hydroxyapatite beads and in vitro drug release testing.

Various forms of hydroxyapatite (HAP) materials have been developed for use as bone grafts. Since the risk of local infection is associated with surgery, it seems reasonable to incorporate drugs such as antibiotics into implant materials. We therefore investigated the characteristics of drug incorporation into a spherical porous HAP bead (diameter = 8.48 mm, bulk porosity = 0.439) and its in vitro release behavior. Cefotiam (CTM) was used as a model antibiotic. Because of nonuniform pore distribution in the bead, distribution of CTM was estimated from the amounts of CTM experimentally determined at three different sites: the surface, halfway to the center, and the center of the beads. The results indicated that 90% of the drug was incorporated in the concentric outer 0.387 (radius = 1) section of the bead. CTM was released with a short lag time when the dry HAP bead was placed in water. Incorporation of CTM with egg phosphatidylcholine eliminated initial lag time and decreased the release rate of the drug from the bead. The lipid load was useful in controlling the release of CTM from the beads. In addition, to protect relatively unstable drugs from humidity and avoid contamination of drug-incorporated HAP beads an apparatus was designed with which the beads could be enclosed in vials in vacuo and under aseptic conditions on a bench-scale basis.

Bacterial Infections↗

A technique of haemostasis of the extremities after debridement of burn wounds.

A technique used to achieve prompt haemostasis in burned wounds of the extremities is described. After tangential debridement using a tourniquet, thrombin solution (1000 units in 1 ml of saline solution) is applied on the entire wound. Immediately after removing the tourniquet; the wound is tightly wrapped with a thin plastic film and a pressure bandage over the entire wound. The pressure bandage is kept on for approximately 10 min after removing the tourniquet. With this procedure, haemostasis of the capillary oozing can be promptly and completely achieved. Furthermore, arterial and venous haemostasis can also be achieved, with clots present at the arterial and venous haemorrhagic points. As these clots can be removed easily, ligation or electrocoagulation is necessary. This technique is especially useful for haemostasis in a wound of the extremity after tangential excision leading to decreasing blood loss.

Adolescent↗

Prevention of dressing slippage under an elastic bandage.

A technique is described to prevent the shift in position of dressing materials by applying a double-sided adhesive tape between the skin and the elastic bandage. This technique also prevents a shift in position of a pressure garment, especially when applied around joints on the extremities.

Adhesives↗

Disulfide bond cleavage of human fibrinogen by cis-diamminedichloroplatinum(II).

Disulfide bridges in fibrinogen (Fbg) were cleaved by cis-diamminedichloroplatinum(II) (cis-DDP). Incubation with 120 molar excess of cis-DDP at pH 7.4 and 37 degrees C in the presence of EDTA resulted in cleavage of seven disulfide bridges out of 29. In the presence of calcium, however, the number of cleavages were reduced to four. The result indicates that calcium, which has three high affinity sites on Fbg, protects disulfide bridges from the rupture. Thrombin clottability was examined by turbidity measurement. The cis-DDP treated Fbg was shown to give a decreased fiber thickness. As the cleavage proceeded, the clotting ability of Fbg decreased.

Cisplatin↗

Effect of glycyrrhizinate on dissolution behavior and rectal absorption of amphotericin B in rabbits.

The effects of dipotassium glycyrrhizinate (GLYK) on the dissolution behavior and bioavailability of amphotericin B (AMB) were investigated. The mixtures of AMB and GLYK were prepared at different molar ratios by lyophilization. Lyophilization resulted in amorphous AMB either alone or in the mixture. Dissolution rates of AMB of the mixtures were markedly faster than that of lyophilized AMB alone, which was followed by a decrease of dissolution. The initially-enhanced dissolution rate was likely to be due to the improvement of surface wettability of drug particles with GLYK rather than the amorphous state of AMB. A phase solubility study of AMB with GLYK indicated that the increasing solubility was caused by micellar solubilization. The in vitro release rate of AMB from suppositories containing the lyophilized mixtures was significantly accelerated by increasing the amount of GLYK. The rectal absorption of AMB from suppositories containing either the drug alone, a physical mixture or a lyophilized mixture was studied using rabbits. The absorption of the mixture (AMB/GLYK = 1/9) was about 35 times greater in the area under the serum concentration-time curve (0-24 h) than that of lyophilized AMB alone. These results suggest that GLYK is useful for improving the dissolution property of AMB and the bioavailability of the drug incorporated in suppositories.

Amphotericin B↗

Determination of aluminum in the human serum of a dialysis patient by ion-pair reversed-phase partition high-performance liquid chromatography.

An ion-pair reversed-phase partition high-performance liquid chromatography-spectrophotometric method is described for the determination of aluminum in human serum, based on its complexation with 2,2'-dihydroxyazobenzene. The chelate is separated on C18-bonded silica packing by using an aqueous methanol mobile phase containing tetrabutylammonium bromide and is detected with 0.005 AU full-scale at 510 nm. The proposed system offers a simple, sensitive, and selective method. The detection limits defined as twice the standard deviation of the blank signal, are 0.2 micrograms L-1 in pure solution and 6 micrograms L-1 in serum. The sample solution is prepared from 0.4 mL of serum after protein precipitation with hydrochloric acid and methanol. There was good agreement between the values obtained by this method and graphite furnace atomic absorption spectrophotometry. The aluminum concentrations in 121 patients on hemodialysis were 6-201 micrograms L-1.

Aluminum↗

A thrombin ointment that achieves rapid haemostasis of split thickness donor wounds, particularly on the scalp.

A procedure is described to achieve rapid haemostasis of split thickness donor wounds by using an ointment containing thrombin (10,000 units mixed in 10 g of petroleum jelly-based gentamicin ointment). The ointment, prepared just before the removal of the skin graft, is immediately spread over the wound after the graft has been taken. With this technique, a steady haemostasis is promptly and simply achieved without the recurrence of bleeding compared to the technique using only a thrombin solution (bleeding time: a mean of 11.5 s for the thrombin ointment and 25.5 s for the thrombin solution, P less than 0.01). Thus, particularly when many skin grafts are needed, further skin grafts from adjacent areas can be readily taken without interference by bleeding. This procedure has proved to be extremely useful in achieving rapid haemostasis of split thickness skin donor wounds, especially when taking skin grafts from the scalp.

Administration, Topical↗

Multiple and irreversible binding of cis-diamminedichloroplatinum(II) to human serum albumin and its effect on warfarin binding.

Irreversible bindings of cis-diamminedichloroplatinum(II) (cis-DDP) to human serum albumin (HSA) were investigated in a pH 7.4 buffer containing 0.1 M NaCl at various molar ratios (cis-DDP/HSA) up to 60 over a 14 d period (37 degrees C). The metal binding seemed to reach a plateau when incubated at less than 10 times excess of cis-DDP. As the molar ratio increased, the reaction rate was relatively fast within the first day, followed by a moderate increase in the metal binding. When incubated at 60 times excess of cis-DDP, the metal bound as much as 20 mol per mol of HSA in 14 d. Fluorescence quenching of the metal-bound protein suggested that the tryptophan residue was gradually exposed to a hydrophilic environment as the metal binding increased. Furthermore, cis-DDP cleaved disulfide bonds at the ratio of 1 mol of disulfide bond per 5.3 mol of the metal binding. It was therefore suggested that the metal binding also occurred at several sites other than the disulfide bond. Warfarin binding to the metal-bound protein, examined by fluorescence changes, also decreased with increasing metal binding or cleavage of the disulfide bonds. Thus, cis-DDP bound to multiple sites in addition to the lone sulfhydryl group (Cys-34), suggesting that massive conformational changes of the protein took place.

Cisplatin↗

[Clinical application of chemotherapy via the portal vein with liposome-encapsulated adriamycin in inoperable metastatic liver cancer].

We studied the effects of liposome-entrapped adriamycin (L-ADM) administered via the portal vein and the clinical application of this treatment in the therapy and inhibition of liver metastasis, experimentally and clinically. Liposomes composed of egg phosphatidylcholine (cholesterol 50 mol%) were used as drug carriers. We examined the distribution in tissues and antitumor effect of freeze-dried L-ADM administered via the portal vein to rabbits bearing VX2 tumors. The liver concentration of ADM increased after delivery and cardiac uptake decreased compared with free drug treatment. The life span was prolonged by L-ADM treatment compared with the control group and the free ADM group. This L-ADM administration was confirmed to be safe and revealed a decrease in the heart toxicities compared with free adriamycin. Nineteen cases were studied from Jan. 1986 to May 1991 via the portal vein and the clinical effects were evaluated. From Mar. 1988 to date, 10 cases were treated with L-ADM (20-30 mg every 2 weeks/body) in patients with inoperable cases using subcutaneously implanted reservoir. The median survival was 450 days; 275 days for colon cancer, 492 days for gastric cancer, and 1,052 days for uterine cancer (range: 136-1,152 days), compared with 141 days (range: 52-253 days) in 9 cases of historical control treated with free-ADM via the portal vein. These results suggest that chemotherapy via the portal vein with L-ADM for metastatic liver cancer may increase survival time.

Aged↗

A new system of treating wounds by a continuous topical application of medication.

A new procedure using a silicone gel sheet that enables the continuous topical application of a drug to a wound, and the effect of this therapeutic procedure on experimental skin flaps of rats, are described. Although a silicone gel sheet without a drug did not augment the flap survival length, silicone gel sheets containing Prostaglandin E1 (PGE1) and Ofloxacin showed significant elongation of the survival length of the flaps without signs of infection. Similarly, silicone gel sheets containing PGE1 inserted under the flap, like a drain, also showed statistically significant augmentation of the flap survival length. These facts showed a therapeutic potential of this new silicone gel sheet containing a drug.

Administration, Topical↗

A silicone gel sheet dressing containing an antimicrobial agent for split thickness donor site wounds.

Treatment of a split thickness donor site wound in 20 patients by means of a silicone gel sheet containing Ofloxacin, an antimicrobial agent, has been tested. For a comparison, each wound was divided into two parts, one for the silicone gel treatment and the other with a collagen sheet (10 cases) or an ointment-impregnated gauze (10 cases). Although Staphylococcus aureus was detected in three wounds treated with the collagen sheet, no wound treated with the silicone gel developed an infection even though the infected wound was adjacent. Results have shown that prompt epithelialisation occurred in the silicone gel-covered wounds, with little exudate and pain compared to wounds treated with either of the dressings. Although some wounds treated with the silicone gel tended to exhibit a slightly prolonged redness compared to wounds treated with an ointment-impregnated gauze, no subsequent cosmetic problem resulted.

Adolescent↗

Treatment of dermal depth burn wounds with an antimicrobial agent-releasing silicone gel sheet.

Silicone gel sheets containing 0.02 per cent Ofloxacin were used in the treatment of 24 patients with a total of 27 dermal depth burn wounds. The gel provided a continuing drug delivery system from the dressing to the wound. Clinically the silicone gel sheets did not adhere to the wound and could be removed easily without pain. No infection developed in any of the dermal depth burn wounds treated with the gel sheets. The silicone gel sheets were found to promote prompt epithelialization in 16 burn wounds of superficial dermal depth (mean 8.4 days) compared with ointment-impregnated gauze dressings (mean 14 days, P less than 0.01). There was less pain and discharge by macroscopic observation of the absorbent materials from both dressings. In nine wounds of mixed superficial and deep dermal burn, the silicone gel also provided prompt epithelialization (mean 12 days) compared to the control wounds (mean 22 days, P less than 0.01).

Adolescent↗

Experiences using silicone gel tie-over dressings following skin grafting.

Twenty-six patients with 27 skin grafts treated with tie-over dressings using silicone gel sheets containing 0.02 per cent Ofloxacin are described. This method ensured direct in-progress inspection of healing of the grafted skin. Although the silicone gel tie-over procedure without any additional pressure resulted in haematoma and congestion in four out of 12 grafts (33.3 per cent), in the group with additional pressure (approximately 20-30 mmHg) limited to the early period after surgery there was no haematoma and congestion of the grafts in 15 grafts (P less than 0.05, Chi-square test). It is surmised that adequate pressure applied to the graft for a few days after surgery would be beneficial in preventing haematoma formation.

Adolescent↗

Expanding oral angle plasty using a subcutaneous pedicle flap to correct severe microstomia after extensive facial burns.

Expanding oral angle plasty using a subcutaneous pedicle flap to correct severe microstomia due to extensive facial scar contractures is described. This technique is especially suited for the elderly, who are unable to tolerate large skin grafting of the face, and for patients with insufficient normal donor skin to undertake extensive correction of scar contractures.

Age Factors↗

Antitumor effect of liposome-entrapped adriamycin administered via the portal vein.

We examined the distribution in tissues and antitumor effect of freeze-dried liposome-entrapped adriamycin (Lipo-ADM) administered via the portal vein to rabbits bearing VX2 tumors. Liposomes composed of egg phosphatidylcholine (cholesterol 50 mol%) were used as drug carriers. The liver concentration of ADM increased after delivery and cardiac uptake decreased compared with free drug treatment. The in vivo antitumor effect of Lipo-ADM was determined in rabbits inoculated with VX2 tumor. Repeated injections of free ADM via the portal vein prolonged the life span of tumor-bearing rabbits. The life span was further prolonged by Lipo-ADM treatment compared with the control group and the free ADM group. Histological examination revealed that the damage to the liver caused by Lipo-ADM administered via the portal vein did not differ from that observed in animals treated with free ADM. These results indicate that portal vein administration of Lipo-ADM may be more effective in dealing with liver metastases than treatment with free ADM and may be therapeutically useful without toxic side effects.

Alanine Transaminase↗