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991.
Nakamura Y Nagao J Saida Y Nakamura Y Enomoto T Katagiri M Nagao S Watanabe M Kusachi S Sumiyama Y 《Gan to kagaku ryoho. Cancer & chemotherapy》2006,33(10):1461-1463
A 65-year-old man underwent distal gastrectomy for advanced gastric cancer. Histological examination revealed that a lymph node metastasis extended to the para-aortic nodes. After operation, he was treated with TS-1 as first-line chemotherapy. After 10 months of the first-line chemotherapy, the lymph node swelling increased in size, and new lesions were detected. Then, the patient was treated by combination therapy of doxifluridine and weekly paclitaxel. Weekly paclitaxel administration (PTX 80 mg/m(2), 2 consecutive weeks, 1 week break) and oral administration of doxifluridine (600 mg/m(2), 14 consecutive days) were performed as the second-line chemotherapy. After 2 courses, abdominal CT scan showed a remarkable reduction of the para-aortic lymph nodes. The second-line chemotherapy was continued until the 7th course, then stopped without progression of the disease, and the patient maintained good quality of life. PTX/5'-DFUR combination therapy was thought to be an effective chemotherapy for advanced gastric cancer. 相似文献
992.
Fukuda T Nakashima Y Harada M Toyoshima S Koshitani O Kawaguchi Y Nakayama M 《The Journal of toxicological sciences》2006,31(3):229-234
Although the toxic effects of citrate including hemodynamic and cardiovascular changes result from a decrease in ionized calcium levels in serum due to chelating action, these effects of citrate on blood coagulation have not yet been fully clarified. The present study examines whether serum citrate and ionized calcium levels affect whole blood clotting time in rats using the test tube method in which citrate is administered by rapid intravenous infusion. Citrate was infused via the tail vein into 10 rats at 3, 4 or 5 mmol/kg/hr for 1 hr, and then whole blood clotting time, serum citrate and ionized calcium levels were determined. Whole blood clotting time did not significantly change at citrate infusion rates of 3 and 4 mmol/kg/hr. However, at 5 mmol/kg/hr, whole blood clotting time was significantly prolonged by a factor of 2.1 relative to the untreated group, when the serum citrate level was 10.03 +/- 1.39 mmol/l (59.0-fold higher than that in the untreated group) and the serum-ionized calcium level was 0.29 +/- 0.02 mmol/l (0.2-fold lower than that in the untreated group). These results suggest that whole blood clotting time is significantly prolonged in rats with severe ionized hypocalcemia. 相似文献
993.
Kobayashi T Takahashi M Nagatsuka Y Hirabayashi Y 《Biological & pharmaceutical bulletin》2006,29(8):1526-1531
Lipid rafts are liquid ordered membrane domains enriched with sphingolipids and cholesterol. After 20 years since the proposal of the original concept, the structure and function of lipid rafts are still obscure. Recently new tools to study lipid rafts have been developed. Lysenin is a sphingomyelin binding protein that specifically recognizes the lipid clusters. Poly(ethyleneglycol)-derivatized cholesterol ether (PEG-Chol) is a non-toxic cholesterol probe. These probes have revealed the heterogeneity of lipid rafts. The heterogeneity of lipid rafts is further supported by the discovery of a new lipid component, phosphatidylglucoside. Metabolic inhibitors are another useful tool. Sulfamisterin is a new addition to the serine palmitoyltransferase inhibitors. Recent findings have uncovered a previously unrecognized activity of a glycosphingolipid synthesis inhibitor, D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (D-PDMP). 相似文献
994.
Uesugi M Masuda S Katsura T Oike F Takada Y Inui K 《Pharmacogenetics and genomics》2006,16(2):119-127
It has been reported that hepatic and intestinal cytochrome P450 (CYP) 3A4, CYP3A5 and P-glycoprotein affect the pharmacokinetics of tacrolimus, and that these proteins are associated with the large inter-individual variation in the pharmacokinetics of this drug. We previously showed that the concentration/dose ratio of tacrolimus tended to be lower in recipients of living-donor liver transplantation (LDLT) with a CYP3A5*1/*1-carrying graft. However, the effect of intestinal CYP3A5 remains to be elucidated. In the present study, we examined the CYP3A5 genotype in both recipients and donors, and the effect of the recipients' polymorphism on the concentration/dose ratio of tacrolimus in patients after LDLT. The CYP3A5*3 allele frequency was 80% in recipients and 77% in donors. The intestinal CYP3A5 mRNA expression level was significantly associated with genotype. The tacrolimus concentration/dose ratio was lower in recipients with the CYP3A5*1/*1 and *1/*3 genotype (CYP3A5 expressors) compared to the CYP3A5*3/*3 genotype (non-expressors). Amongst the combination of CYP3A5 genotypes between the graft liver and the native intestine, CYP3A5 expressors in both the graft liver and the native intestine had the lowest concentration/dose ratio of tacrolimus during 35 days after LDLT. Patients with the intestinal CYP3A5*1 genotype tended to require a higher dose of tacrolimus compared to the other group with the same hepatic CYP3A5 genotype. These results indicate that intestinal CYP3A5, as well as hepatic CYP3A5, plays an important role in the first-pass effect of orally administered tacrolimus. 相似文献
995.
Bioactive secolignans from Peperomia dindygulensis 总被引:2,自引:0,他引:2
Wu JL Li N Hasegawa T Sakai J Mitsui T Ogura H Kataoka T Oka S Kiuchi M Tomida A Turuo T Li M Tang W Ando M 《Journal of natural products》2006,69(5):790-794
Thirteen secolignans, including eight new ones (1-8), were isolated from the EtOAc extract of Peperomia dindygulensis. The structures were mainly elucidated by 1D and 2D NMR and MS experiments, the relative configurations were determined by NOE correlations, and the absolute configurations were established by the optical rotations and CD spectra. Cytotoxicity and MDR (multidrug resistance) reversal activity of the isolated compounds were examined. Compounds 6 and 7, peperomins B (10) and E (12), showed moderate to strong growth inhibitory activity against a malignant lung tumor cell (VA-13) with IC(50) values of 15.2, 13.5, 13.9, and 1.93 microM, respectively, and also inhibited the growth of a normal lung fibroblast cell (WI-38) at the same levels. Compound 7 and peperomin E (12) exhibited inhibitory activity against a liver tumor cell (HepG2) with IC(50) values of 22.3 and 12.1 microM. Compounds 5 and 7 and peperomins A, B, C, and E (9-12) enhanced calcein accumulation in MDR 2780 cells at 25 microg/mL. Compounds 2, 3, 7, and peperomin E (12) showed inhibitory activity on induction of the intercellular adhesion molecule-1 (ICAM-1). 相似文献
996.
Three new rearranged vibsane-type diterpenes, neovibsanin F (1), 14-epi-neovibsanin F (2), and 14-epi-18-oxoneovibsanin F (3), have been isolated from the leaves of Viburnum suspensum, and their structures were elucidated on the basis of spectroscopic data and comparison with those of previously reported vibsane-type diterpenes. 相似文献
997.
Hirose K Kanemitsu H Kanemitsu N Kameyama T Miwa S Nishina T Ikeda T Nishimura K Komeda M 《Kyobu geka. The Japanese journal of thoracic surgery》2004,57(9):827-32; discussion 832-5
We evaluate the outcomes of isolated coronary artery bypass grafting (CABG) in high-risk octogenarians. There are 20 cases in 5 years, which contain 1 re-operation case, and 10 emergency cases. Nineteen cases were performed off-pump CABG (OPCAB), and conventional CABG was performed for only 1 case because of unstable hemodynamics with intraaortic balloon pumping (IABP). We generally performed CABG with aorta no-touch technique. There is no death case, and no serious complication like stroke. We used 23 artery and 11 vein grafts for CABG, and mean number of grafts per patient was 1.8+/-0.7. And "hybrid therapy" with percutaneous transluminal coronary angioplasty (PTCA) was done for 5 cases. Octogenarians are at increased risk for perioperative morbidity and mortality after CABG, but we have performed OPCAB for them and have had good results. And we think that aorta no-touch technique, proper selection and use of graft are important. 相似文献
998.
Hirose T Uwahodo Y Yamada S Miwa T Kikuchi T Kitagawa H Burris KD Altar CA Nabeshima T 《Journal of psychopharmacology (Oxford, England)》2004,18(3):375-383
The antipsychotic efficacy of aripiprazole is not generally associated with extrapyramidal symptoms, cardiovascular effects, sedation or elevations in serum prolactin that characterize typical or atypical antipsychotics. The aim of this study was to clarify the mechanism of action of aripiprazole that underlies its favourable clinical profiles. The preclinical efficacy and side-effect profiles of aripiprazole were evaluated using several pharmaco-behavioural test systems in mice and rats, both in vivo and ex vivo, and compared with those of other conventional and atypical antipsychotics. Each of the antipsychotics induced catalepsy and inhibited apomorphine-induced stereotypy. The catalepsy liability ratios for these drugs were 6.5 for aripiprazole, 4.7 for both olanzapine and risperidone. The ptosis liability ratios for aripiprazole, olanzapine and risperidone were 14, 7.2 and 3.3, respectively. Aripiprazole slightly increased DOPA accumulation in the forebrain of reserpinised mice, reduced 5-HTP accumulation at the highest dose and exhibited a weaker inhibition of 5-methoxy-N,N-dimethyl-tryptamine-induced head twitches. Aripiprazole did not inhibit physostigmine- or norepinephrine-induced lethality in rats. In conclusion, aripiprazole shows a favourable preclinical efficacy and side-effect profile compared to a typical antipsychotics. This profile may result from its high affinity partial agonist activity at D2 and 5-HT1A receptors and its antagonism of 5-HT2A receptors. 相似文献
999.
1000.