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排序方式: 共有5934条查询结果,搜索用时 15 毫秒
1.
Alf Lamprecht Hiromitsu Yamamoto Hirofumi Takeuchi Yoshiaki Kawashima 《European journal of pharmaceutics and biopharmaceutics》2005,59(2):367-371
5-Fluorouracil (5-FU) in combination with leucovorin (LV) is nowadays the standard treatment in colon cancer and would be a candidate to be delivered orally to the colon. Eudragit P-4135F or Eudragit RS100 were used separately to prepare microspheres by an oil/oil emulsification process trapping 5-FU and LV simultaneously. Scanning electron microscopy permitted a structural analysis, process parameters were analyzed and drug loading and release profiles were recorded. Particle size varied between 123 (RS100) and 146 microm (P-4135F). Generally, higher encapsulation rates were found with RS100 (5-FU, 60.3+/-9.7%; LV, 81.4+/-8.6%) compared to P-4135F (5-FU, 48.3+/-2.0%; LV, 55.4+/-2.7%). Microparticles made from Eudragit RS100 released the incorporated drug combination within 8 h not exhibiting general differences between the kinetics of both drugs. P-4135F was found to maintain the undesired 5-FU release at pH 6.8 lower than 25% within 4 h while at pH 7.4, a nearly immediate release (within 15 min) was observed. Although the release was similar at pH 7.4, at pH 6.8 LV showed a distinct initial drug loss of about 60% and a complete release within 2 h. SEM analyses revealed a substantial presence of LV crystals on the particle surface provoking a distinct burst effect of LV. These observations were concluded to be related to the high lipophilicity of P-4135F provoking a separation between P-4135F and LV during the preparation process. 相似文献
2.
Hirofumi Tomiyama Jiko Yamada Yutaka Koji Minoru Yambe Kohki Motobe Kazuki Shiina Yoshio Yamamoto Akira Yamashina 《Hypertension research》2007,30(5):417-426
This observational study of Japanese men without metabolic syndrome (MetS) (age: 41+/-8 years) was conducted to clarify whether or not heart rate elevation precedes the development of full-blown MetS. MetS was defined based on two modifications of the criteria of the Japanese Expert Committee on the Diagnosis and Classification of Metabolic Syndrome. Premetabolic syndrome subjects were defined as those having one component of MetS with increased body mass index (BMI). Among the subjects without MetS (n=1,859 when the BMI criterion was >or=25 and n=2,020 when the BMI criterion was >or=27.5), the incidence of progression to full-blown MetS by the time of the second examination at the end of the 3-year study period was higher in the subjects with premetabolic syndrome than in those without it. The receiver-operator characteristic curve analysis and binary logistic regression analysis revealed that the odds ratio (OR) of a heart rate >or=69 beats/min at the first examination for progression to full-blown MetS by the time of the second examination was significant in subjects with premetabolic syndrome (BMI>or=25: OR=3.64 [1.22-10.88]; BMI>or=27.5: OR=3.67 [1.28-10.55]; p<0.05). Thus, heart rate elevation appears to precede the development of full-blown MetS in subjects with premetabolic syndrome. Heart rate seems to be a simple and useful marker for predicting the progression to full-blown MetS of middle-aged Japanese men with premetabolic syndrome. 相似文献
3.
Hirofumi Nakanishi Akira Myoui Takahiro Ochi Katsuyuki Aozasa 《Journal of cancer research and clinical oncology》1997,123(6):352-356
Multidrug resistance (MDR) is an important problem in chemotheraphy for neoplastic disease. In humans, MDR is mainly mediated by P-glycoprotein (P-gp), a product of theMDR1 gene, which acts as a transmembrane protein pump and eliminates chemotherapeutic agents from the cells. Expression of P-gp was immunohistochemically studied by using two monoclonal antibodies, JSB-1 and C-219, on paraffin-embedded sections from 55 patients with soft-tissue sarcoma. The histological diagnosis of tumors was malignant fibrous histiocytoma in 24 cases, liposarcoma in 9, synovial sarcoma in 7, malignant neurogenic tumors in 6, leiomyosarcoma in 5, others in 4. The histological grade was determined on the basis of criteria previously proposed by us. Out of 55 cases, 34 (62%) were positive for P-gp expression. There was a significant difference in P-gp expression between high-grade (90%) and intermediate and low-grade tumors (46%) (P<0.005). Tumors expressing P-gp had a less favorable prognosis than P-gp-negative tumors in the high- and intermediate-grade tumors. The current study demonstrated that the estimation of P-gp expression could be used to select appropriate therapeutic modalities.Abbreviations
MDR
multidrug resistance
-
P-gp
P-glyco-protein 相似文献
4.
A pH-sensitive microsphere system for the colon delivery of tacrolimus containing nanoparticles. 总被引:2,自引:0,他引:2
Alf Lamprecht Hiromitsu Yamamoto Hirofumi Takeuchi Yoshiaki Kawashima 《Journal of controlled release》2005,104(2):337-346
Nanoparticles (NP) are known to accumulate at the site of inflammation in inflammatory bowel disease. In order to avoid premature uptake or degradation of NP during their passage through the small intestine, it appeared necessary to devise a form of local delivery system for NP. Tacrolimus (FK506) loaded poly(lactic-co-glycolic acid) NP entrapped into pH-sensitive microspheres (NPMS) were designed to achieve greater selectivity to their site of action when administered orally. The therapeutic efficacy of this drug delivery system was tested in an experimental colitis in rats. The in vitro characterization showed a successful incorporation of FK506-NP and strongly pH-sensitive release kinetics of both NP and drug. During the in vivo studies, clinical activity, colon/body weight index, and myeloperoxidase activity were determined to assess the severity of inflammation. Systemic availability of a fluorescent dye entrapped in the microspheres was measured in order to determine possible adverse effects. The NPMS as well as the controls of NP and MS formulations exhibited significant mitigating effects in the clinical activity index after 3 days of treatment with similar levels for the various therapies. When observing colon/body weight index and myeloperoxidase activity, only the NPMS group reached statistically significant differences (P<0.05) compared to the colitis control group while other groups did not (colitis control: 21.94+/-4.97; FK506 solution: 15.81+/-3.42; FK506-NP: 17.03+/-5.52; FK506-MS: 15.17+/-7.81; and FK-NPMS: 10.26+/-7.76 U/mg tissue). Moreover, the NPMS system reduced the systemic absorption of the entrapped dye compared to the dye solution or simple NP formulation (relative biovailability-solution: 100+/-14.9%; NP: 46.8+/-8.6%; and NPMS: 29.4+/-3.3%). The results suggest that the NPMS system can provide selective delivery of NP in the colon and develop a significant mitigating effect, while the control group treatments appeared to be insufficient. 相似文献
5.
Eichi Itadera Yoshimasa Miyake Yoichi Nakatsuka Hirofumi Akazawa Shigeru Mitani Kiyoshi Aoki 《Journal of orthopaedic science》1996,1(4):252-258
We report satisfactory results with a new operative treatment, conducted via an extensive anterolateral approach, involving
360 degree circumferential capsulotomy, for residual subluxation in congenital dislocation of the hip (CDH). Long-term radiographic
results of this procedure (group A) were compared retrospectively with the results of partial capsulotomy (group B), which
preserved the posteroinferior joint capsule. The mean center edge angle in group A (22.5°) was greater than that in group
B (16.0°). Satisfactory results were achieved in 11 of 15 hips (73%) (Severin class I or II) in group A, and in 5 of 12 hips
(42%) in group B. These results suggest that whole circumferential capsulotomy can remove obstacles to complete reduction,
and that acetabular development can be expected in hips reduced by the procedure, without the performance of innominate osteotomy.
We believe that our technique is a useful alternative for the treatment of residual subluxation in CDH. 相似文献
6.
Masanori Hisaoka Takatoshi Aoki Hiromi Kouho Hirofumi Chosa Hiroshi Hashimoto 《Skeletal radiology》1997,26(3):191-194
The case of a 49-year-old man with Maffucci’s syndrome, who developed multiple spindle cell hemangioendotheliomas, is presented.
The case provides support for recent reports suggesting an association between this peculiar vascular lesion and skeletal
enchondromatosis. 相似文献
7.
Takashi Ishimori Satoru Nakano Masahiro Kagawa Koiku Yokoe Tarou Togami Hirofumi Asakura Toshiaki Kusuhara Motoomi Ohkawa Syeigo Nagao Yuichi Yamashita Satoshi Sugiura 《Magnetic resonance in medical sciences》2003,2(3):145-149
Three-dimensional fast asymmetric spin echo (3D FASE) cisternography provides high spatial resolution and excellent contrast as a water image acquisition technique. It is also useful for the evaluation of various anatomical regions. This study investigated the usefulness and limitations of virtual endoscopic images obtained by 3D FASE MR cisternography in the preoperative evaluation of patients with neurovascular compression. The study included 12 patients with neurovascular compression: 10 with hemifacial spasm and two with trigeminal neuralgia. The diagnosis was surgically confirmed in all patients. The virtual endoscopic images obtained were judged to be of acceptable quality for interpretation in all cases. The areas of compression identified in preoperative diagnosis with virtual endoscopic images showed good agreement with those observed from surgery, except in one case in which the common trunk of the anterior inferior cerebellar artery and posterior inferior cerebellar artery (AICA-PICA) bifurcated near the root exit zone of the facial nerve. The veins are displayed in some cases but not in others. The main advantage of generating virtual endoscopic images is that such images can be used for surgical simulation, allowing the neurosurgeon to perform surgical procedures with greater confidence. 相似文献
8.
Kei-ichi Katayama Masaki Ueno Hirofumi Yamauchi Hiroyuki Nakayama Kunio Doi 《Experimental and toxicologic pathology》2002,54(3):193-196
Ethylnitrosourea (ENU) is a simple alkylating agent. It induces gene mutations in fetal primordial germ cells (PGCs), and a high incidence of congenital malformations is also found in the offspring of male mice treated with ENU at the embryonic stage. It is also reported that decreases in the fertility rate and weights of the testis and ovary were found in the offspring from dams treated with ENU. In this study, we analyzed the occurrence of apoptotic cell death and the expression of p53 protein which is thought to play an important role in the DNA damage-induced apoptosis after administration of ENU to pregnant rats on day 13 of gestation to obtain a clue for clarifying the toxic effect of ENU on PGCs. Apoptotic cells increased in PGCs in fetal gonads from 3 h after treatment. The number of apoptotic PGCs peaked at 6 h and gradually decreased towards 24 h after treatment. On the other hand, p53-positive PGCs increased from I h after treatment, prior to the induction of apoptosis. The number of p53-positive PGCs peaked at 3 h and returned to the control level at 24 h after treatment. These results suggest that ENU induces apoptosis in rat fetal PGCs immediately after its administration to dams and excess cell death by apoptosis may have a close relation to the later occurrence of decreases in the fertility rate and gonadal weight. Moreover, a possible involvement of p53 is suggested in the ENU-induced apoptosis in PGCs. 相似文献
9.
Four cases with hysterical amblyopia in youngsters under 15-year-old showed the poor reproducibility of visual field, that is, when the same target was moved from the periphery toward the fixation ten times along the same meridian during the same examination, the position of the plotted points were rather variable. The range of variation was measured from the innermost point to the outermost one, after the two first points were omitted because points first detected were usually far from the others. The variation of cases measured by this method was compared with that of normal persons. Results were as follows; 1. in normal person, the mean value of its range was 5.5° in first decade and 4.2° in second to seventh decade; 2. patients with psychogenic visual disturbances showed a variability of 14.2°, and this was significantly different from normal (p < 0.01). These results suggest that this convenient method was helpful for diagnosis of hysteria. It should also be remembered that when we evaluate the visual field, changes under 4° are probably not significant. 相似文献