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排序方式: 共有526条查询结果,搜索用时 15 毫秒
41.
Kosuke Kusamori Hidemasa Katsumi Mari Abe Asuka Ueda Ryota Sakai Rie Hayashi Yuka Hirai Ying‐shu Quan Fumio Kamiyama Toshiyasu Sakane Akira Yamamoto 《Journal of bone and mineral research》2010,25(12):2582-2591
Bisphosphonates are widely used for the treatment and prevention of bone diseases, including Paget disease, hypercalcemia of malignancy, and postmenopausal osteoporosis. In this study, we developed a novel transdermal patch of alendronate, a nitrogen‐containing bisphosphonate, for the treatment of bone diseases. The maximum permeation fluxes of alendronate through rat and human skin after application of this patch were 1.9 and 0.3 µg/cm2 per hour, respectively. The bioavailability (BA) of alendronate in rats was approximately 8.3% after the application of alendronate patch and approximately 1.7% after oral administration. These results indicated that the transdermal permeation of alendronate using this patch system was sufficient for the treatment of bone diseases. The plasma calcium level was effectively reduced after application of the alendronate patch in 1α‐hydroxyvitamin D3–induced hypercalcemia model rats. The alendronate patch also effectively suppressed the decrease in bone mass in model rats with osteoporosis. Modest alendronate‐induced erythema of rat skin was observed after application of the alendronate patch. Incorporation of butylhydroxytoluene in the alendronate patch almost completely suppressed this alendronate‐induced skin damage while maintaining the transdermal permeation and pharmacologic effects of alendronate. These findings indicate that our novel transdermal delivery system for alendronate is a promising approach to improve compliance and quality of life of patients in the treatment of bone diseases. © 2010 American Society for Bone and Mineral Research. 相似文献
42.
Kataoka M Iwai K Masaoka Y Sakane T Sakuma S Yamashita S 《International journal of pharmaceutics》2011,414(1-2):69-76
The aim of this study is to establish a theoretical method for the prediction of human intestinal permeability from in vitro permeation assay. Pore radius and porosity/length and ion selectivity of the paracellular pathway were calculated using the Renkin function using permeabilities of mannitol and urea and potential difference study to evaluate paracellular permeability in Caco-2 cell monolayer; they were calculated to be 5.91 ?, 7.51 cm(-1) and 2.75, respectively. These values in the human epithelium were calculated from the reported intestinal permeability. The area factor, which can correct the difference in the transcellular permeability between Caco-2 cell monolayer and human epithelium, was obtained using the ratio of permeability of high lipophilicity compounds (human/Caco-2) and was calculated to be 13.3. Paracellular and transcellular permeabilities of 9 compounds in human epithelium were estimated on the basis of the characteristics of the paracellular pathway using physicochemical properties of compounds and the area factor, respectively. Human intestinal permeabilities were predicted by the sum of estimated transcellular and paracellular permeabilities. A linear correlation whose slope and intercept were nearly 1 and 0, respectively, was observed between predicted and reported human intestinal permeabilities. We successfully predicted human intestinal permeability from in vitro data. 相似文献
43.
44.
Yasuno T Okamoto H Nagai M Kimura S Yamamoto T Nagano K Furubayashi T Yoshikawa Y Yasui H Katsumi H Sakane T Yamamoto A 《Biological & pharmaceutical bulletin》2012,35(4):588-593
The variety of physiologic and biologic functions of zinc is fascinating and could be applicable to medicine. Our previous studies demonstrated that the absorption of zinc after oral administration to rats is dose-dependent. In order to clarify the detailed mechanism of the dose-dependent in vivo absorption, the transport of zinc across intestinal epithelial cells was investigated using Caco-2 monolayers and isolated rat intestinal membranes. The permeation of zinc across Caco-2 monolayers is concentration-dependent, and both saturable and nonsaturable components are involved. The Michaelis constant and maximum transport rate for saturable transport are 11.7 μM and 31.8 pmol min(-1) cm(-2), respectively; the permeability coefficient for nonsaturable trasnport is 2.37×10(-6) cm s(-1). These parameters for permeation across membranes isolated from duodenum, ileum, and jejunum of rats are similar with those of Caco-2 cells. The comparison of the parameters for permeation across isolated intestinal membrane suggests that the major site of intestinal zinc absorption in rats is the duodenum. The maximum rate of zinc transport across the isolated intestinal membrane (V(max)) shows no correlation with mRNA expression of ZIP4, ZIP5 or ZnT1 in rats, but shows an inverse correlation with that of metallothioneins (MTs). This finding may be partly explained by the buffering role of metallothionein in intestinal absorption. The saturable transport of zinc is not simply determined only by the influx transporter, ZIP4, since three influx and efflux transporters are involved in the transport of zinc. 相似文献
45.
Makoto Iwahashi Mikihito Nakamori Masaki Nakamura Teiji Naka Toshiyasu Ojima Takeshi Iida Masahiro Katsuda Kentaro Ueda Hiroki Yamaue 《World journal of surgery》2009,33(9):1882-1888
Background The double tract (DT) method was compared with the Roux-en-Y (R-Y) method to identify the optimal reconstruction procedure
after total gastrectomy for patients with gastric cancer. The DT reconstruction is as simple as the R-Y, and it can be safely
performed even after total gastrectomy. However, these have been no studies evaluating the usefulness of DT reconstruction
in comparison to R-Y reconstruction.
Methods A group of 44 patients with gastric cancer were intraoperatively randomized for R-Y (n = 23) or DT reconstruction (n = 21) after total gastrectomy (TG). Body weight, food intake, nutritional conditions, and quality of life (QOL) were determined
at 3 and 12 months after the operation. This study is registered with ClinicalTrials.gov, no. NCT00746161.
Results Food intake significantly decreased soon after the operation. No differences were observed between the DT and R-Y groups.
The body weight decreased throughout the ensuing period (P < 0.05) and thereafter gradually recovered. However, no differences were observed between the two groups. Among the nutritional
laboratory parameters, serum prealbumin, retinol-binding protein, total cholesterol, and triglyceride were decreased soon
after the operation. The changes of those parameters were not substantially different between the two groups. The postoperative
QOL was evaluated, and no differences were observed between those groups.
Conclusions There were no particular advantages in the DT method after TG in comparison to the simple R-Y method in terms of body weight,
QOL, and nutritional conditions, suggesting that the DT method might not be recommended after TG for patients with gastric
cancer. 相似文献
46.
47.
It is said that airway management is an important part of lifesaving at the prehospital care for a seriously ill emergency patient. We performed the training of endotracheal intubation for an emergency medical technician, and in this report we discussed the results of trainings and examined 3 cases of endotracheal intubation in the emergency situation after training. Various kinds of problem arose through this training, for example, difficulty to get the consent from patients, overlap of a case for clinical resident and emergency medical technician, large responsibility of the anesthesiologist as a teaching staff. In addition, there may be no useful case for lifesaving at the emergency situation in 3 cases of endotracheal intubation. We consider that it may be difficult, but possibility cannot deny if endotracheal intubation by emergency medical technicians contribute to lifesaving rate improvement from viewpoint of prehospital care. 相似文献
48.
Shin-ichiro Hayashi Akitsugu Yamamoto Fukka You Kentaro Yamashita Yuka Ikegame Masahiro Tawada Tamotsu Yoshimori Shigeomi Shimizu Shigeru Nakashima 《The American journal of pathology》2009,175(5):2226-2234
Clinical studies have indicated that the stent-eluting drugs sirolimus and paclitaxel impact restenosis; however, it is still elusive how these drugs affect the vascular endothelium at the molecular and cellular levels. The purpose of this study was to determine whether sirolimus and paclitaxel induce molecular and cellular alterations in the vascular endothelium. Endothelial regrowth was assessed in human aortic endothelial cells and rat aortic endothelium. Molecular and cellular alterations were analyzed in human aortic endothelial cells by Western blot analysis, transmission electron microscopy, and immunofluorescence staining. Green fluorescent protein-LC3 mice were used to analyze autophagic endothelium. Here, we show that sirolimus and paclitaxel differentially induce self-digesting autophagy in vascular endothelial cells with changes in expression of LC3B, p53, and Bcl-2, considerably suppressing re-endothelialization and revascularization. These results suggest that phenotypic alteration in the endothelium by sirolimus or paclitaxel might affect the rates of late stent thrombosis, myocardial infarction, and mortality.Sirolimus and paclitaxel, which were originally used for immunosuppression or cancer treatment, have been shown to have a new therapeutic application in preventing restenosis after angioplasty.1,2 Angioplasty induces target vascular injury that often accelerates mitogen-mediated vascular smooth muscle proliferation and formation of neointimal hyperplasia. In this situation, both sirolimus and paclitaxel have been shown to inhibit cell cycle proliferation and migration of vascular smooth muscle cells.3 On the basis of these findings, drug-eluting stents (DES), including a sirolimus-eluting stent, and a paclitaxel-eluting stent, have been implanted in millions of patients with coronary artery disease undergoing percutaneous coronary intervention, and their efficacy and safety relative to bare-metal stents have been investigated in randomized clinical trials worldwide.4While enthusiasm for DES use with this technology has been increasing, recent reports have sounded an alarm that patients with DES may encounter life threatening complications such as late stent thrombosis, in-stent thrombosis, and myocardial infarction.5,6 These clinical data, together with the effects of sirolimus and paclitaxel on cell cycle inhibition,3 indicate that endothelial dysfunction may exist. However, presently, little information is available regarding the direct effects of sirolimus and paclitaxel on the vascular endothelium. Here, we hypothesized that sirolimus and paclitaxel would have undefined effects on the vascular endothelium, which correlate with unfavorable outcomes after DES use. 相似文献
49.
50.
Asai H Shinozaki E Nozaki A Watanabe T Suenaga M Matuzaka S Chin K Mizunuma N Yasukawa M Hatake K 《Gan to kagaku ryoho. Cancer & chemotherapy》2011,38(8):1285-1291
Mutation of the KRAS gene in patients with metastatic colorectal cancer(mCRC)has been established as a predictive marker of poor response to anti-EGFR cetuximab. The Japanese Society of Medical Oncology recommends that the KRAS mutation status at codon 12 and codon 13 should be genotyped by direct-sequencing or allele-specific PCR. In this study, we tested the point mutation of codon 12 and 13 in the KRAS gene by Luminex(xMAP)flow cytometry with sequence-specific oligonucleotide probes for 39 out of 64 unresectable mCRC patients enrolled from Sep 2008 to Oct 2009, who were administered cetuximab in combination with irinotecan(CPT-11)as third-line therapy. We retrospectively analyzed the relationship between KRAS mutation status and responses to combination therapy. Mutations in the KRAS gene were detected in 38. 5% of cases(codon12: 73%, codon 13: 27%), and the median follow-up time was 8. 2 months(range, 1. 4-15. 2 months). The response rates for patients with KRAS wild-type and patients with KRAS mutations were 33. 3%(95%CI 14. 5-52. 2%)and 0%(p=0. 015); the disease control rates were 75%(95%CI 57. 7-92. 3%)and 40%(95%CI, 15. 2-64. 8%; p=0. 044); the median TTF was 7 months(95%CI 4. 6-9. 3)and 2. 3 months(95%CI 1. 3-3. 2; p=0. 0007), and the median OS was 12. 9 months(95%CI 6. 7-19. 1)and 10. 8 months(95%CI 5. 0-16. 7; p=0. 15), respectively. Therefore, we concluded that the KRAS mutation in mCRC is a predictive factor for the lack of response to combination therapy with cetuximab plus CPT- 11, as reported in previous clinical studies. 相似文献