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Biomedical subjects

M Ueda

Publications and source records attributed to M Ueda.

At least 1,657 records · Page 92Linked to original sources
PubMedDate not supplied

Preparation of microcapsules masking the bitter taste of enoxacin by using one continuous process technique of agglomeration and microencapsulation.

In order to mask the bitter taste of drugs, a novel microencapsulation process combined with the wet spherical agglomeration (WSA) technique was developed by using a modified phase separation method. The spherical agglomerates of enoxacin (ENX) with various additives including disintegrants were successfully produced in the system of acetone-n-hexane-ammonia water or acetone-n-hexane-distilled water by the WSA, using flocculation phenomena of particles in liquid. Resultant agglomerates could be microencapsulated continuously with Eudragit RS utilizing the phase separation method in the same system as agglomeration under stirring. 'Explosible' microcapsules which were free from the bitter taste could be produced in formulating finer particle size of ENX and 50 per cent of Primojel in core agglomerates, using distilled water as a bridging liquid, and treating with 20 per cent polymer coating level. These microcapsules were bioequivalent to the commercial ENX 100 mg tablets in beagle dogs. One continuous process technique of agglomeration and microencapsulation was useful for the design of ENX powders which masked the bitter taste and controlled the drug release rate.

Animals↗
PubMedDate not supplied

Preparation and characteristics of microcapsules containing enoxacin by one continuous process of agglomeration and microencapsulation.

A novel microencapsulation technique was carried out with the phase separation of Eudragit RS from the wet spherical agglomeration (WSA) system by non-solvent addition. To elucidate the characteristics of microcapsules the spherical agglomerates containing enoxacin (ENX), lactose or Avicel which are different in their affinity to water (i.e. insoluble, soluble or absorbable properties, respectively), were prepared as core particles in an acetone/n-hexane mixture (volume ratio 3/7) by a WSA technique. The size of all kinds of spherical agglomerates was controlled by the amount of bridging liquid (ammonia water or distilled water) used. In the microencapsulation process encapsulation was performed efficiently at 400-600 rpm. Avicel agglomerates could be coated up to 30 per cent with Eudragit RS with less aggregation. Various additives were compared as additions into the system to avoid the aggregation of encapsulated particles. Addition of more than 3 per cent magnesium stearate based on the core weight in the system, before or at the same time as phase separation of Eudragit RS occurred, resulted in low aggregation of microcapsules for spherical agglomerates containing ENX or lactose. In formulating a water-absorbable excipient such as Avicel in the agglomerates of ENX, adding some 10 per cent Eudragit RS-dichloromethane solution into the WSA system, and using magnesium stearate as a protective agent, the resultant microcapsules could be obtained efficiently without aggregation, showing sustained release of ENX depending on coating level.

Acrylic Resins↗
PubMedDate not supplied

Optimization of the preparation of loperamide-loaded poly (L-lactide) nanoparticles by high pressure emulsification-solvent evaporation.

The entrapment of loperamide hydrochloride (LPM) in biodegradable polymeric drug carriers such as nanoparticles might enable its passage across the blood-brain barrier. The optimization of the preparation of the LPM-loaded PLA nanoparticles was performed employing high pressure emulsification-solvent evaporation. The resulting nanoparticles were characterized by particle size, distribution, thermal analysis, and drug release profiles. The partition of LPM into the organic phase increased with an increase in pH of the aqueous phase and with addition of lipophilic surfactants such as sorbitan fatty acid esters, resulting in an increase in the drug entrapment in the nanoparticles. Evaporation of the organic phase under reduced pressure and the addition of ethanol in the organic phase yielded a high drug entrapment due to the rapid polymer precipitation. The addition of the sorbitan fatty acid esters further increased the drug entrapment even at higher LPM concentrations. The results of thermal analysis suggest that LPM was homogeneously dispersed in the amorphous polymer matrix. The in vitro release of the drug from nanoparticles was biphasic, with a fast initial phase, followed by a second slower phase. Different drug release profiles from nanoparticles can be achieved by addition of sorbitan fatty acid esters, or the employment of different solvents as the organic phase.

Antidiarrheals↗
PubMedDate not supplied

Influence of the preparation methods on the drug release behaviour of loperamide-loaded nanoparticles.

Polylactide (PLA) or poly(lactide-coglycolide) (PLGA) nanoparticles containing loperamide (LPM) were prepared by an incorporation or adsorption method with the objective of developing nanoparticles with a rapid drug release. The use of polymers such as PLA with lower molecular weights and the addition of sorbitan fatty acid esters (SFAE) for the incorporation led to an almost complete entrapment of LPM in nanoparticles. Preparation of PLA nanoparticles by adsorption was performed by addition of LPM methanol solution before, during and after evaporation of dichloromethane from the system. The adsorption of LPM onto the nanoparticles with low molecular weight PLA (m.w. 2000) showed an isotherm with a good correlation to the Langmuir equation. A high amount of LPM can be entrapped or adsorbed in nanoparticles only with low molecular weights of PLA or PLGA. In the incorporation method, the addition of SFAEs increased drug entrapment. However, in the adsorption method they had no effect on nanoparticle drug adsorption. The drug-release profiles from both nanoparticles, prepared by the adsorption and incorporation methods, were biphasic with an initial rapid release and a second slower release phase, although their initial extents of release were different. The release rates were almost the same for both the adsorption and incorporation method without SFAEs. The addition of SFAEs to the adsorption system increased the extent of drug release from nanoparticles. In conclusion, a rapid loperamide release from nanoparticles can be achieved by use of PLA or PLGA with low molecular weights and in the adsorption method by the addition of SFAEs.

Adsorption↗
PubMedDate not supplied

Preoperative thermochemotherapy of oral cancer using magnetic induction hyperthermia (Implant Heating System: IHS).

Eight patients with primary cancer of the oral cavity were preoperatively treated by combined treatment with hyperthermia and chemotherapy. They received two courses of chemotherapy, which included intra-arterial infusion of 100 mg of cisplatin (CDDP) and 25 mg of peplomycin (PEP) via the superficial temporal artery. The patients also received interstitial hyperthermia for 45 min once a week using the Implant Heating System (IHS) with chemotherapy. IHS consists of ferromagnetic implant, induction coil and generator to produce high frequency magnetic field. The ferromagnetic implant is made of Fe-Pt alloy (Fe: 73%, Pt: 27%), and has a Curie temperature of 68 degrees C. As a result, clinical complete response (CR) was observed in seven patients and partial response (PR) in one, and postoperative pathological examination showed no residual tumour cells in any specimen. Combined interstitial hyperthermia by IHS and chemotherapy is thus found to be an effective therapeutic method for treating oral cancers.

Adult↗
PubMedDate not supplied

Hsp40, a possible indicator for thermotolerance of murine tumour in vivo.

The relationship between Hsp40/Hsp70 synthesis and the development of thermotolerance was investigated using mouse squamous cell carcinoma in vivo. To examine the thermotolerance, tumours were heated at 44 degrees C for 30 min as conditioning heating. After various intervals they were heated again at 44 degrees C for 90 min as challenge heating. The tumour response to heat was evaluated by the growth delay. Thermotolerance rapidly developed with increasing interval and reached a maximum at 12 h interval. Subsequently, thermotolerance gradually decayed and almost disappeared at 120 h interval. Under this condition, synthesis of Hsp40/Hsp70 increased after conditioning heating, reached a maximum at 12 h interval, then gradually decreased thereafter within 120 h. The kinetics of accumulation and decay of both Hsp40 and Hsp70 were very similar. The extent of thermotolerance was well correlated with the relative amount of Hsp40/Hsp70. These results obtained in vivo were very similar to those in vitro (Kaneko et al. 1995). Our findings suggest that Hsp40 could be a useful indicator of the degree of thermotolerance in addition to Hsp70 in vivo as in vitro.

Animals↗
PubMedDate not supplied

Selective cytotoxicity of adriamycin immunoconjugate of monoclonal antibody MSN-1 to endometrial adenocarcinoma in vitro and in vivo.

Missile therapy, which destroys cancer cells specifically, has been regarded as an effective treatment modality for carcinoma. The monoclonal antibody MSN-1 (IgM), which reacts strongly with endometrial adenocarcinomas, was combined with adriamycin (ADM) by a disulfide bond using N-succinimidyl-3-(2-pyridyldithio) propionate (SPDP) and 2-iminothiolane. Its selective cytotoxicity against SNG-II was examined in a colony formation in vitro, and on athymic mice in vivo. The results of our study suggest that the or IC50, of the MSN-1-ADM immunoconjugate against SNG-II to be 57 times that of ADM alone in vitro. The reductions in resected weights of target tumor cells, at the local site of the MSN-1-ADM immunoconjugate treatment, were 25% with caudal vein administration, and 38% with local administration, as compared with the untreated group, in vivo. There was no weight loss in treated mice. Our results suggest that this MSN-1-ADM immunoconjugate has potential clinical application in the treatment of endometrial adenocarcinomas.

Adenocarcinoma↗
PubMedDate not supplied

Further evidence that altered p16/CDKN2 gene expression is associated with lymph node metastasis in squamous cell carcinoma of the esophagus.

Esophageal squamous cell carcinoma (ESCC) has high malignant potential with a poor outcome. Lymph node metastasis is the most useful indicator for predicting the outcome of ESCC. The p16/MTS1/CDKN2 gene and the cyclin D1/PRAD-1 gene cooperatively regulate CDK4-mediated phosphorylation of RB protein in the cell cycle. We immunohistochemically detected p16, cyclin D1, and RB expressions in both primary lesions and metastatic lymph nodes in ESCC. Among the 50 ESCC primary lesions, 24 (48%) were positive for p16, while 26 (52%) were negative for p16. Sixteen (32%) were p16-positive, 34 (68%) were p16-negative among the 50 ESCC metastatic lymph nodes. Eight cases (16%) were p16-positive in primary lesion and p16-negative in lymph node, however, no cases that was p16-negative in the primary tumor exhibited p16-positivity in metastatic lymph nodes (p < 0.0001). Seventeen (34%) of the 50 ESCC primary lesions were cyclin D1-positive, while 33 (66%) were cyclin D1-negative. Twenty-four (48%) were cyclin D1-positive, 26 (52%) were cyclin D1-negative among the 50 metastatic lymph nodes. Five cases (10%) were cyclin D1-positive in primary lesion and cyclin D1-negative in lymph node, and 12 cases (24%) were cyclin D1-negative in primary lesion and cyclin D1-positive in lymph nodes. Nine cases (18%) were RB-negative in 50 primary lesions, and the rate of loss of RB expression in metastatic lymph nodes was not markedly higher than in primary lesions. Thirty-nine (78%) of 50 primary lesions and 46 (92%) of 50 metastatic lymph nodes had altered expression of at least one of the three G1 control genes. Tumor cell with disruption of these cell cycle regulators can get a growth advantage and metastatic potential during tumor progression, especially p16/CDKN2 alterations may be associated with lymph node metastasis in ESCC. These results also suggest that tumor cells in metastatic lymph nodes may have more aggressive proliferation and higher malignant potential than tumor cells in primary lesions.

Adult↗
PubMedDate not supplied

Correlation between EGF receptor expression and peplomycin cytotoxicity in squamous cell carcinoma cell lines.

The relationship between sensitivity to anti-cancer agents and EGF receptor expression on squamous cell carcinoma (SCC) cells was investigated. The cytotoxicity of peplomycin (PEP) was correlated with the number of the EGF receptors expressed on the cancer cells, but no correlations were found between the cytotoxicity of adriamycin and cisplatin and EGF receptors. Addition of TNFalpha increased the number of EGF receptors in the SCC cell lines 1.5- to 2-fold. The cytotoxic effect of combined administration of PEP and TNFalpha was correlated with the number of EGF receptors, and produced a 2- to 5-fold increase in IC50 compared with administration of PEP alone. These observations suggest that EGF receptor expression is closely associated with the cytotoxic effect of PEP on SCC cells.

Antibiotics, Antineoplastic↗
PubMedDate not supplied

Histologic evaluation of clinically successful osseointegrated implants retrieved from irradiated bone: a report of 2 patients.

The present study described the histologic findings of 2 implants and surrounding tissues retrieved from human irradiated bone. For the treatment of a malignant tumor, 50 Gy of irradiation after implant placement and 60 Gy of irradiation before implant placement were provided for patients 1 and 2, respectively. In patient 1, the implant and surrounding tissues were removed from the frontal bone 24 months after implant placement because of the patient's death from a tumor recurrence. In patient 2, the implant and surrounding tissue were removed from a maxillectomy site 26 months after implant placement because of tumor recurrence. In each patient, new bone formation surrounding the implants was observed. The ratio of direct bone-implant contact along the threaded implant surface was 61.3% in patient 1 and 69.0% in patient 2. The ratio of the area occupied by mineralized bone in each thread was 75.8% in patient 1 and 81.2% in patient 2. These results indicate the potential of irradiated bone to achieve osseointegration of titanium implants.

Adenocarcinoma↗
PubMedDate not supplied

The inhibitory effect of DL-alpha-tocopheryl ferulate in lecithin on melanogenesis.

Oral vitamin E (alpha-tocopherol) supplementation has been reported to improve facial hyperpigmentation. The compound of alpha-tocopherol and ferulic acid, also an antioxidant connected with an ester bond, alpha-tocopheryl ferulate (alpha-TF) can absorb ultraviolet (UV) radiation and thus maintain tocopherol in a stable state. Our aim was to determine whether alpha-TF can be applied to improve and prevent facial hyperpigmentation induced by UV as a whitening agent as well as an antioxidant. In this study, the effects of alpha-TF on melanogenesis were examined using cultured human melanoma cells and normal human melanocytes in vitro. alpha-TF solubilized in 0.5% lecithin inhibited melanization significantly at the concentration of 30 micrograms/ml compared with arbutin (100 micrograms/ml), kojic acid (100 micrograms/ml), ascorbic acid (600 micrograms/ml), and tranexamic acid (600 micrograms/ml). alpha-TF had no effect on the protein amounts of tyrosinase, TRP (tyrosinase related protein)-1, and TRP-2 of human melanoma cells exposed to UV radiation, but inhibited tyrosine hydroxylase activity. alpha-TF neither directly inhibited tyrosinase activity of the large granule fraction extracted from melanoma cells, nor modulated glycosylation of tyrosinase. These results suggest that alpha-TF may be a candidate for whitening agent which suppresses melanogenesis, possibly by inhibiting tyrosine hydroxylase activity in an indirect manner. Further, alpha-TF decreased the amount of 8-hydroxydeoxyguanosine produced indirectly through active oxygen species (AOS) in guinea pig skin exposed to 2 times the minimal erythema dose of UVB radiation, but did not suppress the direct formation of cyclobutane pyrimidine dimers and (6-4) photoproducts. Thus alpha-TF may reduce AOS-induced DNA damage and thereby contribute at least in part to suppressing or retarding skin cancer development.

8-Hydroxy-2'-Deoxyguanosine↗
PubMedDate not supplied

Epidermal growth factor receptor-dependent cytotoxic effect of anti-EGFR antibody-ribonuclease conjugate on human cancer cells.

We have conjugated the murine monoclonal antibody (528) against the human epidermal growth factor receptor (EGFR) to mammalian pancreatic ribonuclease (RNase) via N-succinimidyl-3-(2-pyridyldithio) propionate (SPDP) and 2-iminothiolene (2-IT). The conjugate showed dose-dependent cytotoxicity against EGFR-producing squamous cancer cells (A431, TE8, TE5, Ca9-22) and no detectable cytotoxicity against EGFR-deficient small-cell lung cancer cells (H69). The cytotoxicity of the conjugate was positively correlated with the EGFR numbers of each cell line. The addition of excess 528 antibody to the medium protected A431 cells from the conjugate cytotoxicity. This immunoconjugate might be useful for targeted treatment of squamous cell carcinomas hyperexpressing EGFR.

Animals↗
PubMedDate not supplied

Experimental alveolar ridge augmentation by distraction osteogenesis using a simple device that permits secondary implant placement.

The purpose of this study was to develop an improved technique of alveolar ridge augmentation by distraction osteogenesis using distraction screws, and to investigate tissue reactions to titanium implants at the distraction site. The left mandibular premolars were extracted from 6 adult dogs. After 12 weeks, a box-shaped osteotomy of the alveolar bone was carried out, and distraction devices were placed on the transport and base segments. After a 7-day latency period, the alveolar bone was augmented by 7 mm vertically at a rate of 1.0 mm/day. Just after distraction, these devices were replaced with dental implants for fixation of the transport segment and bone formation of the distraction site. Histologic and radiographic evaluations were made at 8 and 12 weeks after distraction. Vertical augmentation averaged 6.1 mm after 12 weeks of consolidation. It was possible to lengthen the alveolar bone without great difficulty, and good bone formation was recognized in the distraction site. Greater integration between the implant and the distracted bone was observed at 12 weeks after distraction than at 8 weeks. Distraction osteogenesis was successfully applied to alveolar ridge augmentation by this improved technique, and the implants osseointegrated in the augmented ridge.

Alveolar Ridge Augmentation↗
PubMedDate not supplied

Osseous proliferation of the mandible after placement of endosseous implants.

Spontaneous alveolar ridge growth in the posterior region of the mandible following placement of endosseous implants is reported. The study included 27 patients with totally edentulous mandibles and fixed prostheses supported by osseointegrated implants placed between the mental foramina. In 5 patients, an increase in the height of the alveolar crest was observed in the molar region; the increase ranged from 3.3% to 8.6%. This osseous proliferation may be a physiologic response to stress distribution in the molar region.

Adult↗
PubMedDate not supplied

Anti-influenza virus activity of a lignin fraction from cone of Pinus parviflora Sieb. et Zucc.

When mice were inoculated intranasally or intracerebrally with lethal doses of influenza virus A/WSN/33, most died within 12 days. However, the infectivity of virus that had been preincubated with a lignin prepared from cones of Pinus parviflora Sieb. et Zucc. (PC-Fr. VI) was significantly reduced. Intraperitoneal or oral administration of PC-Fr. VI, prior to virus inoculation, slightly increased the survival ratio of the infected mice. Experiments using radiolabeled PC-Fr. VI revealed that this fraction effectively binds to virions as well as to cultured cells. These data suggest that PC-Fr. VI either inactivates the virus or induces the anti-viral state in cells by binding to virions or cells.

Administration, Oral↗
PubMedDate not supplied

Cytologic study of the tissue repair cells of the uterine cervix. With special reference to their origin.

In order to characterize tissue repair cells (TR) of the uterine cervix and clarify their origin, exfoliated cells obtained after laser conization for early cervical lesions were examined. One specimen was first examined by Papanicolaou staining and then examined for epithelial membrane antigen (EMA) and vimentin by immunocytochemical staining, using a restaining method. The other specimen was observed by phosphotungstic acid-hematoxylin (PTAH) staining. Morphologic findings on TR were investigated together with the histologic findings on the wound healing process. TR were classified morphologically into three groups: stromal (STR), epithelial (ETR) and of unknown origin (UTR). Validity of this classification was confirmed by the findings of immunocytochemical staining with EMA and vimentin. These cells appeared one to eight weeks after laser conization. TR with relatively large nuclei, or atypical TR (ATR), appeared when each type of TR was most plentiful, at two to five weeks. Regarding the origins of each TR, cytologic and histologic findings could be considered to offer evidence that ETR originated with hyperplasia of immature cells of the squamous epithelium or reserve cells below the columnar epithelium. The presence of myofibrils in cytoplasm, demonstrated by PTAH staining for STR and some UTR, strongly suggested the possibility that these cells were myofibroblasts in granulation tissue.

Carcinoma in Situ↗
PubMedDate not supplied

Targeted killing of squamous carcinoma cells by a monoclonal antibody-peplomycin conjugate which recognizes the EGF receptor.

We determined in vitro the antitumor activity of a conjugate prepared by binding a monoclonal antibody (B4G7), which recognizes the human epidermal growth factor (EGF) receptor, with peplomycin (PEP), which is an antitumor agent effective against squamous cell carcinoma. This B4G7-PEP conjugate was prepared by coupling of B4G7 and carboxymethylpeplomycin active ester. The conjugate killed A431 cells of squamous cell carcinoma which overexpress EGF receptors at lower concentrations than PEP alone. On the basis of its IC50, the conjugate was six times more potent than PEP alone. A simple mixture of B4G7 and PEP was as effective as PEP alone in cytotoxicity. The addition of ten times the amounts of B4G7 to this conjugate decreased its cytotoxicity. When other squamous cell carcinoma cell lines with different levels of EGF receptors (NA, Ca9-22, TE-1, TE-8) were treated with the conjugate, cells were killed dose-dependently and the cytotoxicity was dependent on the number of EGF receptors. When each squamous cell carcinoma cell line was treated with a control conjugate prepared by combining PEP with mouse IgG instead of B4G7, no cytotoxicity was observed. These results indicate that B4G7-PEP will be a useful weapon in multidisciplinary treatment which utilizes the EGF receptor, as these receptors are detected in a higher incidence in squamous cell carcinoma.

Antibiotics, Antineoplastic↗