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Biomedical subjects

H Takeuchi

Publications and source records attributed to H Takeuchi.

At least 145 records · Page 8Linked to original sources
PubMed2000

A comparison of prednisolone and methylprednisolone for renal transplantation.

A large difference in immunosuppressive potency between methylprednisolone and prednisolone has been suggested in vitro. However, the selection of the best glucocorticoid for renal transplantation has been seldom considered so far. Thus, the present study was undertaken to compare therapeutic efficacy between prednisolone and methylprednisolone in renal transplantation. We studied 42 renal transplant recipients who were operated on between 1990 and 1994. The patients were divided into two treatment groups: a methylprednisolone/ cyclosporine group (n = 19) and a prednisolone/cyclosporine group (n = 23). Clinical outcome and drug side effects were compared retrospectively between the treatment groups 24-84 months after transplantation. The overall graft survival time in patients treated with methylprednisolone/cyclosporine was superior to that in patients treated with prednisolone/cyclosporine (p < 0.05). Among the recipients from cadaver donors, 5/16 (31.3%) treated with prednisolone required nephrectomy, whereas none of the 10 patients treated with methylprednisolone received nephrectomy (p < 0.01). An examination of the recipients from living related donors revealed that serum creatinine levels 24-36 months after operation were significantly lower in the methylprednisolone group (p < 0.05). Cyclosporine trough levels and glucocorticoid side effects were similar between the treatment groups. The results raised the possibility that methylprednisolone is superior to prednisolone when combined with cyclosporine for maintenance immunosuppressive therapy in renal transplantation.

Adult↗
PubMed2000

Identification of the urease operon in Helicobacter pylori and its control by mRNA decay in response to pH.

We investigated the transcription of the urease gene cluster ureABIEFGH in Helicobacter pylori to determine the regulation of gene expression of the highly produced enzyme urease. Northern blot hybridization analysis demonstrated that cells of the wild-type strain grown in an ordinary broth had transcripts of ureAB, ureABI, ureI, ureIE' and ure'FGH, but cells of a ureI-disrupted mutant had only the ureAB transcript. When the wild-type cells were exposed to pH 8 for 30 min, very little mRNA was detected. However, when exposed to pH 6, a large amount of the ureIE" transcript, which was longer than the ureIE' transcript, together with the additional transcripts ureABIEFGH and ure'EFGH were detected. Rifampicin addition experiments demonstrated that urease mRNAs, and the ureIE' transcripts in particular, are more stable at pH 5.5 than at pH 7. In accord with these results, urease activity in the crude cell extract of the pH 5.5 culture was twice as much as that of the pH 7 culture, although the amounts of UreA and UreB detected by immunoblot analysis were similar. The transcription start point of ureI was identified by primer extension using a ureA promoter-deleted mutant, and a consensus sequence of RpoD-RNA polymerase was found in the ureI promoter. The 3' end of the ureIE" mRNA, determined using S1 nuclease mapping, revealed that the transcript is able to cover the majority of the ureE open reading frame (ORF) that might be sufficient for UreE activity. Based on the above results, we conclude that the urease gene cluster of H. pylori consists of two operons, ureAB and ureIEFGH, and that primary transcripts of the latter as well as the read-through transcript, ureABIEFGH, are cleaved to produce several species of mRNA. It has been suggested that the ureIEFGH operon is regulated post-transcriptionally by mRNA decay in response to environmental pH. We are tempted to speculate that the ureE" transcript present in acidic pH may contribute to produce an active product that can proceed the nickel incorporation to the active centre, the final step of urease biosynthesis.

Amino Acid Sequence↗
PubMed2000

Domain organization of p130, PLC-related catalytically inactive protein, and structural basis for the lack of enzyme activity.

The 130-kDa protein (p130) was isolated as a novel inositol 1,4, 5-trisphosphate [Ins(1,4,5)P3]-binding protein similar to phospholipase C-delta1 (PLC-delta1), but lacking catalytic activity [Kanematsu, T., Takeya, H., Watanabe, Y., Ozaki, S., Yoshida, M., Koga, T., Iwanaga, S. & Hirata, M. (1992) J. Biol. Chem. 267, 6518-6525; Kanematsu, T., Misumi, Y., Watanabe, Y., Ozaki, S., Koga, T., Iwanaga, S., Ikehara, Y. & Hirata, M. (1996) Biochem. J. 313, 319-325]. To test experimentally the domain organization of p130 and structural basis for lack of PLC activity, we subjected p130 to limited proteolysis and also constructed a number of chimeras with PLC-delta1. Trypsin treatment of p130 produced four major polypeptides with molecular masses of 86 kDa, 55 kDa, 33 kDa and 25 kDa. Two polypeptides of 86 kDa and 55 kDa started at Lys93 and were calculated to end at Arg851 and Arg568, respectively. Using the same approach, it has been found that the polypeptides of 33 kDa and 25 kDa are likely to correspond to regions between Val569 and Arg851 and Lys869 and Leu1096, respectively. All the proteolytic sites were in interconnecting regions between the predicted domains, therefore supporting domain organization based on sequence similarity to PLC-delta1 and demonstrating that all domains of p130, including the unique region at the C-terminus, are stable, tightly folded structures. p130 truncated at either or both the N-terminus (94 amino acids) and C-terminus (851-1096 amino acids) expressed in COS-1 cells showed no catalytic activity, indicating that p130 has intrinsically no PLC activity. A number of chimeric molecules between p130 and PLC-delta1 were constructed and assayed for PLC activity. It was shown that structural differences in interdomain interactions exist between the two proteins, as only some domains of p130 could replace the corresponding structures in PLC-delta1 to form a functional enzyme. These results suggest that p130 and the related proteins could represent a new protein family that may play some distinct role in cells due to the capability of binding Ins(1,4,5)P3 but the lack of catalytic activity.

Animals↗
PubMed2000

Clinical significance of negative esophageal pressure in sleep apnea syndrome.

The authors investigated the relationship between esophageal pressure fluctuation (DPes) during sleep and the following parameters: respiratory disorder variables and daytime sleepiness manifested as the Epworth sleepiness scale (ESS). In the younger patient group under 60 years of age (n=33), DPes was correlative to both the apnea-hypopnea index and ESS. However, in the elderly group of 60 years and over (n = 16), the variables showed smaller values than did those in the younger group. These results suggest that DPes may be associated with the aggravating process of sleep apnea syndrome (SAS) in the younger patient.

Adult↗
PubMed2000

Vascular invasion and potential for tumor angiogenesis and metastasis in gastric carcinoma.

BACKGROUND: Hematogenous metastasis occurs when cancer cells released from the primary site enter blood vessels and are transported to distant organs, where they attach and proliferate. Angiogenesis is essential for tumor growth and metastasis and depends on the production of angiogenic factors by tumor cells. METHODS: We analyzed data on 1184 Japanese adult men and women with gastric cancer with respect to the relation between vascular invasion and the potential for tumor angiogenesis and metastasis. All these patients were treated from 1976 to 1995 in the Department of Surgery II, Kyushu University. In 300 patients, the expression of vascular endothelial growth factor (VEGF) and p53 protein in tumor tissues was examined by using an immunohistochemical staining method or Northern blotting or both. Intratumoral microvessels were stained with anti-CD31 monoclonal antibody. RESULTS: Vascular invasion was evident in 254 patients (21.5%), and in these patients lymphatic invasion was more frequent and the rate of lymph node metastasis was higher in relation to the extent of vascular invasion. The positive findings were directly related to the depth of invasion and the presence of lymph node and liver metastasis. Tumor invasive and metastatic rates increased in relation to the extent of vascular invasion. Expressions of VEGF and p53 protein were higher and microvessel density was more prominent in tumor tissues in relation to the extent of vascular invasion. A close relation between VEGF and p53 protein expressions was also noted in tumors that showed vascular invasion. The expression of VEGF is one of the independent risk factors for vascular invasion. The postoperative outcome was poorer in patients with vascular invasion in relation to the extent of vascular invasion. CONCLUSIONS: Our findings show that gastric cancers with characteristics of vascular invasion have greater intratumoral angiogenesis and that VEGF and p53 overexpression is associated with intratumoral angiogenesis and metastases to distant organs.

Adult↗
PubMed2000

Analysis of the proliferative potential of tumor cells after stereotactic radiosurgery for recurrent astrocytic tumors.

We analyzed the effectiveness of stereotactic radiosurgery (SRS) for recurrent astrocytic tumors histologically. Five patients were followed by pathological examination after radiosurgery treatment of recurrent astrocytic tumors. Histological diagnoses at the time of the last operation before SRS were Daumas-Duport grade II in two patients and grade IV (glioblastoma) in three patients. No histological diagnoses at the time of SRS were identified in any patients. Contrast enhanced lesions enlarged gradually on magnetic resonance (MR) images after SRS, and local control by SRS was judged as progressive disease radiologically in all patients. Four of five patients received re-operation after SRS, and the other patient died without re-operation and underwent post-mortem examination. After SRS, Ki-67 labeling indices (LIs) of recurrent astrocytomas initially diagnosed as grade II were 2.6% and 1.1%. These LIs were relatively lower than those of the control group of patients with recurrent grade II astrocytomas that were not treated by SRS. Ki-67 LIs of three glioblastomas after SRS were 23.5%, 18.6%, and 17.8%. These LIs were significantly lower than those before SRS (2.3%, 4.5%, and 0.9%). In the autopsy case, there was a significant difference between the LI of tumor cells in the radiosurgically treated region (0.9%) and that in the untreated region (29.2%). These results suggest that the proliferative potential of malignant astrocytic tumors in the radiosurgically treated area is reduced after SRS, and that radiological enlargement of enhanced lesions on MR images is due to propagation of the residual tumor cells that were not covered by radiosurgical target volume or to radiation necrosis. SRS may be a useful therapeutic tool in multidisciplinary treatment of malignant gliomas.

Adult↗
PubMed2000

Ultrasonographic detection of very thin percutaneous central venous catheter in neonates.

To assess the ability of ultrasonography to detect the tip of a very thin (0.4 mm outer diameter) percutaneous central venous catheter (PCVC) in neonates, the PCVC tip location was assessed by ultrasonography (US) and compared to the location estimated by standard radiography for 57 PCVCs in 44 neonates. Of 57 occasions, the examiner could not find the PCVC tip in three cases (5%). In the remaining 54 instances, in 87% of cases, the PCVC tip position was consistent with the location implied by skeletal landmarks on standard radiographs. On 24 occasions we also assessed catheter tip dislodgement according to flexion and extension of the infant's arm. US could detect 78% of cases of catheter tip dislodgement. The PCVC tip was sometimes visualized as a dot and parallel lines as well as mere parallel lines. In a large population of cases, US is a reliable method for detection of a thin PCVC tip. US provides precise information about the PCVC tip position in relation to vascular structure and contributes to safer positioning of the PCVC than traditional radiography alone.

Age Factors↗
PubMed2000

Mucoadhesive DL-lactide/glycolide copolymer nanospheres coated with chitosan to improve oral delivery of elcatonin.

The purpose of this work was to develop a novel mucoadhesive DL-lactide/glycolide copolymer (PLGA) nanosphere system to improve peptide absorption and prolong the physiological activity following oral administration. The desired PLGA nanospheres with elcatonin were prepared by the emulsion solvent diffusion method to coat the surface of the resultant nanospheres with a mucoadhesive polymer such as chitosan, poly(acrylic acid), and sodium alginate. Their mucoadhesive properties were evaluated by measuring the nanospheres adsorbed to a rat everted intestinal sac (in vitro). The chitosan-coated nanospheres showed higher mucoadhesion to the everted intestinal tract in saline than the other polymer-coated nanospheres. There was no mucoadhesion site-specificity of the chitosan-coated nanospheres between duodenal, jejunal, and ileal sacs. The payload of drug in the chitosan-coated nanospheres was successfully increased by using the solvent diffusion method in oil. The pattern of drug release of the resultant nanospheres did not differ markedly from that of uncoated nanospheres. The chitosan-coated nanospheres with elcatonin were administered intragastrically to fasted Wistar rats. The chitosan-coated nanosphere reduced significantly the blood calcium level compared with elcatonin solution and uncoated nanospheres, and the reduced calcium level was sustained for a period of 48 hr. Even under nonfasting conditions, the mucoadhesion of chitosan-coated nanospheres was unaltered and the reduction in blood Ca levels was maintained satisfactorily.

Acrylic Resins↗
PubMed2000

Temperature- and moisture-induced crystallization of amorphous lactose in composite particles with sodium alginate prepared by spray-drying.

The purpose of this study was to investigate the temperature- and moisture-induced crystallization of amorphous lactose in the composite particles prepared by spray-drying an aqueous solution of crystalline lactose and sodium alginate. The temperature-induced crystallization of amorphous lactose in the composite particles was suppressed by increasing the amount of sodium alginate in the particles. The stabilizing effect of sodium alginate on amorphous lactose in the composite particles was greater than that in physical mixtures having the same formulating ratios. The improved stability of amorphous lactose in the composite particles was attributed to an increase in the glass transition temperature (Tg) of the mixture. Moisture-induced crystallization of amorphous lactose was also retarded by increasing the amount of sodium alginate in composite particles. Although the Tg of the mixture was reduced by increasing the water content of the particles, the values were higher than that of 100% amorphous lactose when particles of the same water content were compared. The change in the Tg of the composite particles with increasing water content was interpreted as involving three components of the Gordon-Taylor equation. In the amorphous lactose-sodium alginate systems, the Tg values of the composite particles containing sodium alginate were higher than the theoretical line predicted by two components of the Gordon-Taylor equation. These results suggested that there was a specific interaction between the sodium alginate and lactose molecules. This specific interaction was suggested by the fact that only very little amorphous lactose was measured in the spray-dried composite particles stored under humid conditions using differential scanning calorimetry. This molecular interaction may also be partly responsible for the suppression of both the temperature- and moisture-induced crystallization of amorphous lactose in the composite particles.

Alginates↗
PubMed2000

Comparison of outer membrane protein genes omp and pmp in the whole genome sequences of Chlamydia pneumoniae isolates from Japan and the United States.

Chlamydia pneumoniae is a widespread pathogen of the respiratory tract that is also associated with atherosclerosis. The whole genome sequence was determined for a Japanese isolate, C. pneumoniae strain J138. The sequence predicted a variety of genes encoding outer membrane proteins (OMPs) including ompA and porB, another 10 predicted omp genes, and 27 pmp genes. All were detected in the whole genome sequence of strain CWL029, a strain isolated and sequenced in the United States. A comparative study of the OMPs of the two strains revealed a nucleotide sequence identity of 89.6%-100% (deduced amino acid sequence identity, 71.1%-100%). The overall genomic organization and location of genes are identical in both strains. Thus, a few unique sequences of the OMPs may be essential for specific attributes that define the differential biology of two C. pneumoniae strains.

Bacterial Outer Membrane Proteins↗
PubMed2000

Effective suppression of HIV-1 gene expression by a mammalian tRNA 3' processing endoribonuclease and external guide sequence oligozymes.

We examined the suppression of virus expression by cleavage of the HIV-1 RNA gene using a mammalian tRNA 3' processing endoribonuclease and an External Guide Sequence Oligozyme (EGS) in vivo. We constructed an EGS expression vector that used the tRNA(met) promoter as an expression cassette for EGS. The EGS expression vector was targeted to the upstream region of gag, region. The EGS expression vector was co-transfected into COS cells with the HIV-1 gene plasmid vector. As compared with the EGS non-expressing cells and the EGS expressing cells, the EGS expressing cells with the targeted gag start codon had a clearly decreased amount of the HIV-1 gag p24 protein. The EGS expressing cells with the targeted gag start codon showed effective suppression of HIV-1 gene expression. Thus, these studies describe novel gene targeting agents for the inhibition of gene expression and antiviral activity.

Animals↗
PubMed2000

Serum immunosuppressive acidic protein and natural killer cell activity in patients with metastatic renal cell carcinoma before and after nephrectomy.

PURPOSE: To our knowledge the impact of nephrectomy on stage M1 renal cell carcinoma remains to be determined. We previously reported that nephrectomy is beneficial in patients with elevated serum C-reactive protein before treatment, and those in whom nadir C-reactive protein decreases postoperatively to within the normal range may expect longer survival when surgery is combined with postoperative immunotherapy. In this study we determine the effect of nephrectomy on the immune response in patients with metastatic renal cell carcinoma. MATERIALS AND METHODS: We retrospectively reviewed the records of 40 patients with metastatic renal cell carcinoma diagnosed at our institution between 1986 and 1999. These patients underwent nephrectomy before cytokine therapy with interferon. Before and after nephrectomy we measured serum C-reactive protein, serum immunosuppressive acidic protein and peripheral blood natural killer cell activity. RESULTS: In 15 patients with pretreatment serum C-reactive protein within the normal range (less than 1 ng./ml.) there was no significant difference before and after nephrectomy in the serum immunosuppressive acidic protein level or natural killer cell activity (p = 0.4587 and 0.3892, respectively). On the other hand, in 25 patients with serum C-reactive protein elevated before treatment to 1 ng./ml. or greater serum immunosuppressive acidic protein decreased significantly and natural killer cell activity increased significantly after cytoreductive surgery (p = 0.0002 and 0.0286, respectively). CONCLUSIONS: Our study implies that nephrectomy may be beneficial in patients with elevated serum C-reactive protein before treatment. Further evaluation by a prospective study is needed to make a definitive conclusion.

Adult↗
PubMed2000

Chemopreventive effect of curcumin on N-nitrosomethylbenzylamine-induced esophageal carcinogenesis in rats.

Modifying effects of curcumin (derived from the rhizome of Curcuma longa L.) during the initiation or post-initiation phase of N-nitrosomethylbenzylamine (NMBA)-induced esophageal carcinogenesis were investigated in male F344 rats. Five-week-old rats were divided into 5 groups, and groups 1, 2 and 3 were given intraperitoneal injections of NMBA (0.5 mg / kg body weight / injection 15 times) for 5 weeks from 7 weeks old to induce esophageal neoplasms. Groups 2 and 3 were fed the diet containing 500 ppm curcumin during the initiation and post-initiation phases, respectively. Group 4 was given the diet containing curcumin throughout the experiment, and group 5 was kept on the basal diet alone and served as an untreated control. Incidence and multiplicity of esophageal neoplasms of group 1 (NMBA alone) were 66.7% and 0.83 +/- 0.70, respectively. Those of groups 2 and 3 were significantly less than those of group 1 (39.3%, 0.46 +/- 0.64, P < 0.05; 33.3%, 0.36 +/- 0.56, P < 0.05, respectively). Furthermore, the incidence and multiplicity of esophageal preneoplastic lesions (moderate or severe epithelial dysplasia) of group 2 (57.1%, 0.61 +/- 0.57; 40%, 0.29 +/- 0.46) or 3 (56.7%, 0.67 +/- 0.66; 23.3%, 0.23 +/- 0.43) were less than those of group 1 (100%, 1.67 +/- 0.70; 70.8%, 0.92 +/- 0.72) (P < 0.05). In this experiment, feeding of curcumin significantly decreased the expression of cell proliferation biomarkers (5-bromo-2'-deoxyuridine labeling index) in the non-lesional esophageal epithelium (P < 0.01). These findings indicate that curcumin inhibits NMBA-induced esophageal carcinogenesis when given during the post initiation as well as initiation phase. This inhibition may be related to suppression of the increased cell proliferation induced by NMBA in the esophageal epithelium.

Animals↗
PubMed2000

A prospective randomized study comparing endocrinological and clinical effects of two types of GnRH agonists in cases of uterine leiomyomas or endometriosis.

OBJECTIVE: In order to assess the endocrinological changes associated with 2 types of low-dose GnRH agonists depot as well as their clinical efficacy, we performed a randomized prospective comparison study of patients having uterine leiomyomas or endometriosis. METHODS: A prospective randomized study involving 67 patients with uterine leiomyomas or endometriosis was carried out. These patients were randomly administered either buserelin MP 1.8 mg (Group B, n = 34) or leuprolide 1.88 mg (Group L, n = 33). In each group we evaluated the symptoms of genital bleeding and hot flashes during GnRHa treatment, as well as the levels of serum LH, FSH, and estradiol 8 weeks after the start of treatment. In addition, the endometrial thickness was measured by transvaginal ultrasonography, and changes in the volume of the uterine leiomyoma or endometrial cyst at the end of treatment. The GnRHa depot was administered from 3 to 8 times, 28 days apart, in both groups. RESULTS: The incidence of menstruation-like genital bleeding 8 weeks after treatment was significantly (p < 0.01) higher in Group B. However this difference disappeared by 12 weeks after treatment. The climacteric symptom of hot flashes was found to be significantly (p < 0.01) more severe in Group L, and this tendency continued until 20 weeks after treatment. The 2 groups did not differ significantly with regard to the levels of the serum LH, FSH, and estradiol at 8 weeks after treatment or in the endometrial thickness at the end of the GnRHa treatment. In both groups, the volumes of the uterine leiomyomas were significantly (p < 0.01) lower after the treatment. In contrast, the volumes of the endometrial cysts did not decrease after administration of GnRHa in both groups. CONCLUSION: Leuprolide 1.88 induced pituitary down regulation more rapidly than buserelin MP. However the hypoestrogenic symptoms such as hot flashes were more severe in cases treated with leuprolide 1.88 than in those treated with buserelin MP. Our data confirm that the therapeutic efficacy of buserelin MP and leuprolide 1.88 are similar, with both being sufficient to treat uterine leiomyomas and endometriosis.

Adult↗
PubMed2000

Prostate-specific antigen levels and clinical response to flutamide as the second hormone therapy for hormone-refractory prostate carcinoma.

BACKGROUND: Some authors have recently reported that maximum androgen block (MAB), in which the nonsteroidal anti-androgen, flutamide, is used together with conventional hormone therapy such as castration or luteinizing hormone-releasing hormone analogue, is more effective for prostate cancer than conventional methods. However, others have reported that the effect of MAB on survival is minimal, and definite conclusions concerning MAB remain unclear. Conversely, using flutamide as a second-line hormone therapy after recurrence is also considered, but few authors have reported whether this therapeutic option is effective or for which patients it is effective. MATERIALS AND METHODS: 124 patients with prostate cancer were diagnosed and followed at Kobe City General Hospital between 1995 and 1997. Twenty-two of these cases developed recurrence during first-line hormone therapy, and flutamide was prescribed in these cases. The prognostic value and effectiveness of flutamide were evaluated by measurement of serum prostate-specific antigen (PSA) at diagnosis, posttreatment nadir PSA level, PSA at the time of flutamide use, histological grade, recurrence-free time after firstline hormone therapy and age at the time of diagnosis. RESULTS: Six of 9 cases whose post-treatment nadir PSA levels after initial hormone therapy were within the normal limit (<4 ng/ml) achieved complete remission (CR) with flutamide use, but no patient whose post-treatment nadir PSA level remained elevated achieved CR. PSA at diagnosis and PSA at the start of flutamide use were significantly lower for patients with CR. However, the results of multivariate logistic regression analysis demonstrated that only the post-treatment nadir PSA level was significantly correlated with prognosis of flutamide use. CONCLUSIONS: Flutamide use as second-line hormone therapy should be limited to cases in which first-line hormone therapy has been highly effective and for whom the post-treatment nadir PSA level was within normal limits, and other patients should undergo other therapies. By limiting flutamide use to patients in whom the effect of flutamide is considered to be maximal, the incidence of complications and medication costs can be decreased.

Aged↗
PubMed2000

Temperature-induced crystallization and compactibility of spray dried composite particles composed of amorphous lactose and various types of water-soluble polymer.

The purpose of this study was to investigate the temperature-induced crystallization and the compactibility of the composite particles containing amorphous lactose and various types of polymers. The composite particles were prepared by spray-drying an aqueous solution of lactose and various types of gel forming water-soluble polymers at various formulating ratios. The stabilizing effect of hydroxypropylcellulose (HPC) and polyvinyl pyrrolidone (PVP) on amorphous lactose in the composite particles was smaller than that of sodium alginate in comparing at the same formulating ratios. The difference in the stability of amorphous lactose in the composite particles was attributed to the difference in the glass transition temperature (Tg) of the composite particles caused by the polymers formulated. The tensile strength of compacted spray-dried composite particles containing the polymers was higher than commercial lactose for direct tabletting (DCL21). The tensile strength of the composite particles was increased with an increase in water content in the particles. The difference in compactibility of the composite particles containing the different amount of polymer and water could be explained by the difference in Tg of the particles.

Alginates↗
PubMed2000

Modification of the physicochemical properties of minocycline hydrochloride ointment with cyclodextrines for optimum treatment of bedsore.

Modification to find the best physicochemical properties of minocycline hydrochloride ointment for optimum treatment of bedsore was investigated by coformulating various types of cyclodextrins (CyD) in the ointment base. It was found that the drug release rate from the ointment base was modified according to the preparation method of ointment base and the type of CyD admixed. The physicochemical properties, such as viscosity, elution volume, water absorption of ointment base were also modified by those factors. The mechanism of physicochemical modification with CyD was explained by the structural change of ointment base and the change of surface tension of emulsifying agent solution with the CyD. The stability of ointment was investigated by confirming the reproducibility of drug release rate after storage at ambient and cooled temperature conditions. In conclusion, a fused mixed ointment with beta-CyD was found to be preferable for treatment of bedsore, because of the improved drug release rate, lowered viscosity and increased elution volume of the resultant ointment.

Absorption↗