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61.
Kinoshita M Baba K Nagayasu A Yamabe K Shimooka T Takeichi Y Azuma M Houchi H Minakuchi K 《Journal of pharmaceutical sciences》2002,91(2):362-370
The aim of the present study was to improve the solubility and oral bioavailability of a poorly water-soluble drug, 3-bis(4-methoxyphenyl) methylene-2-indolinone (TAS-301), by its melt-adsorption on a porous calcium silicate, Florite RE (FLR), without any solvents. The melt-adsorbed products were prepared by two methods: the small-scale batch method and the twin screw extruder method. The drug was melted and adsorbed on FLR (i.e., "melt-adsorption"), above its melting point. Crystallinity of the drug in the melt-adsorbed product was estimated by differential scanning calorimetry (DSC) and powder X-ray diffraction analysis. The dissolution test was conducted by the JP XIII paddle method. Oral absorption of the melt-adsorbed product was studied in fasted and fed dogs. The melt-adsorbed products prepared by the two methods were in powder forms. The drug existed in an amorphous state in the product and hardly recrystallized even after storing at a stressed condition (60 degrees C/80% RH for 3 days). The TAS-301 dissolution rate from the melt-adsorbed product was markedly enhanced compared with drug crystals. The area under the plasma concentration-time curve (AUC) and peak concentration (C(max)) values of the drug after dosing the melt-adsorbed product were significantly greater than those after dosing the drug crystals. The solubility and bioavailability of TAS-301 were improved by its melt-adsorption on FLR. The present findings suggest melt-adsorption is a useful technique for improving solubility and bioavailability of poorly water-soluble drugs. 相似文献
62.
Sakuta R Tazoe M Narita N Murakami N Nagai T 《No to hattatsu. Brain and development》2003,35(5):394-400
Using State-Trait Anxiety Inventory (STAI) we examined 13 junior high school students with school refusal and indefinite complaints. Significant increase of the anxiety levels was higher in these children than in the control group. Serotonin reuptake inhibitors (SSRIs) were administered to 19 elementary and junior high school students with school refusal and indefinite complaints. The indefinite symptoms improved markedly in 2 children, moderately in 11, and mildly in 6. We conclude that high anxiety may cause indefinite symptoms in children with school refusal and that the treatment of indefinite symptoms with SSRI is an effective supportive therapy. 相似文献
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Masuda T Oyama Y Yonemori S Takeda Y Yamazaki Y Mizuguchi S Nakata M Tanaka T Chikahisa L Inaba Y Okada Y 《Phytotherapy research : PTR》2002,16(4):353-358
The cytotoxic activity of methanol extracts of leaves collected from 39 seashore plants in Iriomote Island, subtropical Japan was examined on human leukaemia cells (K562 cells) using a flow cytometer with two fluorescent probes, ethidium bromide and annexin V-FITC. Five extracts (10 microg/mL) from Hernandia nymphaeaefolia, Cerbera manghas, Pongamia pinnata, Morus australis var. glabra and Thespesia populnea greatly inhibited the growth of K562 cells. When the concentration was decreased to 1 microg/mL, only one extract from H. nymphaeaefolia still inhibited the cell growth. A cytotoxic compound was isolated from the leaves by bioassay-guided fractionation and was identified as (-)-deoxypodophyllotoxin (DPT). The fresh leaves of H. nymphaeaefolia contained a remarkably high amount of DPT (0.21 +/- 0.07% of fresh leaf weight), being clarified by a quantitative HPLC analysis. DPT at 70-80 pM started to inhibit the growth of K562 cells in an all-or-none fashion and at 100 pM or more it produced complete inhibition in all cases. Therefore, the slope of the dose-response curve was very steep. DPT at 100 pM or more decreased the cell viability to 50%-60% and increased the number of cells undergoing apoptosis (annexin V-positive cells). The results indicate that DPT contributes to the cytotoxic action of the extract from the leaves of H. nymphaeaefolia on K562 cells. 相似文献
66.
This article attempts to clarify the psychopathological features of "primary social withdrawal". Since the concept of "social withdrawal" in general may include various diseases, we isolated and defined "primary social withdrawal" by excluding cases that could be diagnosed by established classifications of mental disorders. First, we examined two cases of "primary social withdrawal" which could not be classified using DSM-IV. We then compared these patients' psychopathological features to those seen in apathy syndrome, taijin kyofu sho and personality disorders. Based on this comparison, we identified five pathological features of "primary social withdrawal": (1) episodes of defeat without a struggle, (2) protecting the ideal image of the expected self, (3) parents' investment in that ideal self, (4) holding an ideal self image shaped more by the desires of others than those of themselves, and (5) avoidance behavior to maintain the positive opinion of others. Finally, we discuss the socio-cultural background of social withdrawal and possible therapies. 相似文献
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68.
Benign or malignant stricture of extrahepatic bile ducts may result when small intrahepatic bile ducts are anastomosed to the jejunal loop after resection of extrahepatic bile ducts, hepatic parenchyma, and intrahepatic bile ducts. We applied a parachute technique, which has been used for fine vascular anastomosis, to hepaticojejunostomy in eight patients with either extrahepatic bile duct carcinoma or intrahepatic cholangiocellular carcinoma. One to four small bile ducts were anastomosed to the jejunal loop. No patient experienced a complication due to this anastomosis. Postoperative elevation of the serum bilirubin was transient, and all patients were discharged within 36 days after surgery. Although the follow-up period in this series is not yet long enough to evaluate the long-term outcome of this technique, the ease of the hepaticojejunostomy and good short-term results warrant farther clinical investigation of this technique. 相似文献
69.
Michihiro Mutoh Kouji Watanabe Tomohiro Kitamura Yutaka Shoji Mami Takahashi Toshihiko Kawamori Kousuke Tani Michiyoshi Kobayashi Takayuki Maruyama Kaoru Kobayashi Shuichi Ohuchida Yukihiko Sugimoto Shuh Narumiya Takashi Sugimura Keiji Wakabayashi 《Cancer research》2002,62(1):28-32
Accumulating evidence indicates that overproduction of prostanoids attributable to overexpression of cyclooxygenase-2 (COX-2) plays an important role in colon carcinogenesis. We have shown recently that the prostaglandin (PG) E receptor, EP(1), but not EP(3), is involved in mouse colon carcinogenesis. In line with our previous study, here we examined the role of prostanoid receptors in colon carcinogenesis using six additional lines of knockout mice deficient in prostanoid receptors EP(2), EP(4), DP, FP, IP, or TP. The animals were treated with the colon carcinogen, azoxymethane (AOM), and examined for the development of aberrant crypt foci (ACFs), putative preneoplastic lesions in the colon. Formation of ACFs was decreased only in the EP(4)-knockout mice, to 56% of the wild-type level. To confirm these results, we also examined the inhibitory effects of an EP(4)-selective antagonist, ONO-AE2-227, in the diet on the formation of AOM-induced colon ACFs in C57BL/6Cr mice and on the development of intestinal polyps in Min mice. ONO-AE2-227 at a dose of 400 ppm reduced the formation of ACFs to 67% of the control level, and intestinal polyp numbers in Min mice receiving 300 ppm were decreased to 69% of the control level. Plating efficiency assays showed that addition of 1.0 microM ONO-AE1-329, an EP(4)-selective agonist, resulted in a 1.8-fold increase in the colony number of the human colon cancer cell line, HCA-7, similar to the effect of PGE(2). Moreover, EP(4) mRNA expression was clearly observed in normal colon mucosa and colon tumors in mice. Our previous and present results indicate that PGE(2) contributes to colon carcinogenesis through its actions mediated through EP(1) and EP(4) receptors; therefore, antagonists for these two receptors may be good candidates as chemopreventive agents against colon cancer. 相似文献
70.
Tsunoda Y Shimizu Y Tsunoda A Shibusawa M Kamiya K Kusano M Fukuchi K 《European surgical research. Europ?ische chirurgische Forschung. Recherches chirurgicales européennes》2001,33(3):232-236
The effects of the aromatase inhibitor, CGS16949A, and the fluoropyrimidine, 5-fluorouracil (5-FU), on cell cycle distribution and growth were studied using FACS analysis and MTT assay in the human breast cancer cell line, SK-BR-3. CGS16949A induced an increase in the G0-G1 fraction on SK-BR-3 cells, and the growth inhibition rate of the combination of both (65.7 +/- 3.0%) was significantly higher than 10 nM CGS16949A (37.9 +/- 6.9%) or 100 microg/ml 5-FU (45.6 +/- 4.5%); p < 0.01). Administering 5-FU after preincubation with CGS16949A significantly increased the combined cytotoxic efficacy, suggesting that clinical therapy using this combined therapy may be more efficient. 相似文献