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排序方式: 共有415条查询结果,搜索用时 15 毫秒
81.
Mori T Nomura M Yoshizawa K Nagase H Sawaguchi T Narita M Suzuki T 《Journal of pharmacological sciences》2006,100(2):157-161
Generalizations of NMDA-receptor antagonists to the discriminative stimulus effects of kappa-opioid receptor agonists in rats were examined. Phencyclidine, MK-801, and ketamine, non-competitive NMDA-receptor antagonists, generalized to the discriminative stimulus effects of U-50,488H, but not those of TRK-820, whereas (+/-)-3-(2-carbaxypiperazine-4-yl) propyl-1-phosphonic acid (CPP), a competitive NMDA-receptor antagonist, and ifenprodil, an NR1/NR2B NMDA-receptor antagonist, did not, suggesting that non-competitive NMDA-receptor antagonists possess U-50,488H-like discriminative stimulus effects in rats. Since U-50,488H and phencyclidine both induce aversive effects, our findings indicate that the cue of the discriminative stimulus effects of U-50,488H and non-competitive NMDA-receptor antagonists may be associated with their aversive effects. 相似文献
82.
Takehisa H Naoko E Masahiko S Katsuhide T Moriyuki O Keizoh S Mutsuko T Kenji K Shin'ichiro N Toshio O 《International journal of pharmaceutics》2005,297(1-2):30-37
The release behavior of diethylhexyl phthalate (DEHP) from polyvinyl-chloride (PVC) tubing, which composes materials in an intravenous administration set, was investigated using polysorbate 80 (Tween 80) aqueous solutions. When Tween 80 solution was circulated in PVC tubing, the amount of DEHP released increased with increasing circulation velocity and temperature. In order to clarify the effect of temperature on the release behavior of DEHP, PVC films containing varying amounts of DEHP were mounted on a cylindrical shaft and rotated at 5 and 40 degrees C. The cumulative amount of DEHP released increased with an increase in temperature, the diffusion coefficients [Dx10(-10) cm2 min-1] at 5 and 40 degrees C were 9.1 and 156.0, respectively. The glass transition temperature (Tg) of PVC films decreased with an increase in DEHP in the PVC film, as measured by differential scanning calorimeter (DSC) and release of DEHP occurred at temperatures above Tg. These results indicate that the release of DEHP from PVC tubing is closely associated with the state of the PVC and is related to diffusion of DEHP throughout the PVC. 相似文献
83.
Hirata-Koizumi M Kusuoka O Nishimura N Wada H Ogata H Fukuda N Ito Y Kamata E Ema M Hasegawa R 《The Journal of toxicological sciences》2005,30(1):29-42
Newborn rat studies were conducted with oral administration of 1,3-dibromopropane (DBP) and 1,1,2,2-tetrabromoethane (TBE) from postnatal Days 4 to 21 to allow comparison of NOAELs and unequivocally toxic levels with those from 28-day young rat studies starting at 5-6 weeks of age. The unequivocally toxic level was estimated by our specified criteria, requiring simultaneous change of organ weights, histopathology, some biochemical parameters and body weights, because in this study only hypertrophy of hepatocytes was observed as a major histopathological change. DBP caused centrilobular hypertrophy of hepatocytes with alteration in biochemical parameters, as well as lowering of body weights, regardless of sex, in both newborn and young rats. NOAELs and unequivocally toxic levels were considered to be 50 and 150 mg/kg/day in newborn rats and 10 and 250 mg/kg/day in young rats, respectively. In the newborn rat study of TBE, some hepatic effects observed at the top dose of 50 mg/kg were not considered adverse because of the lack of histopathological changes. Significant lowering of body weight was noted at 200 mg/kg in the dose-finding study but histopathological data were not available. In the young rat study, there was no definite toxicity at 6 mg/kg and hypertrophic changes in liver and thyroids without body weight change occurred at 200 mg/kg. There were no clear sex differences in both the newborn and young rat studies. NOAELs were considered to be 50 and 6 mg/kg/day in newborn and young rats, respectively, but unequivocally toxic levels for both rats could not be estimated. Abnormalities of external and sexual development and reflex ontogeny in the newborn were not observed with either chemical. Based on these results, it can be concluded that the target organ of DBP and TBE is the liver in both newborn and young rats, and that while the doses at which toxic signs began to appear are higher in newborn rats, those causing clear toxicity may be paradoxically lower in the newborn case. 相似文献
84.
Effect of CYP2D6*10 on the pharmacokinetics of R- and S-carvedilol in healthy Japanese volunteers 总被引:3,自引:0,他引:3
Honda M Nozawa T Igarashi N Inoue H Arakawa R Ogura Y Okabe H Taguchi M Hashimoto Y 《Biological & pharmaceutical bulletin》2005,28(8):1476-1479
This study was performed to investigate the effect of CYP2D6*10 on the pharmacokinetics of R- and S-carvedilol in healthy Japanese volunteers. Five or 10 mg of carvedilol was orally administered to 23 subjects (22-44 years old), and blood samples were taken at 2 and 6 h after dosing. We determined the polymorphic alleles of CYP2D6 in each subject. The whole blood concentration of R- and S-carvedilol was measured by an HPLC method. The pharmacokinetic parameters in individual subjects were estimated by the Bayesian method using the nonlinear mixed effects model (NONMEM) program. The mean values of oral clearance for R- and S-carvedilol were estimated to be 1.01 and 2.15 l/h/kg, respectively. The oral clearance was highly correlated with the apparent volume of distribution among the subjects, suggesting that the interindividual difference in bioavailability was largely responsible for the pharmacokinetic variability of carvedilol. The oral clearance and also volume of distribution of both enantiomers were significantly lower in the subjects with the CYP2D6*10 allele than with the CYP2D6*1/*1 or *1/*2 genotype. These results suggested that the systemic and/or pre-systemic metabolism of R- and S-carvedilol in the liver is significantly decreased in Japanese with the CYP2D6*10 allele. 相似文献
85.
Shimoeda S Ohta S Kobayashi H Saitou H Kubota A Yamato S Shimada K Sasaki M Kawano K 《Biological & pharmaceutical bulletin》2005,28(3):477-480
In 29 patients (40 samples) with hematological diseases who had been treated with a candin antifungal agent, micafungin (MCFG), we measured the blood level of MCFG by high-performance liquid chromatography (HPLC). There was a correlation between the dose and the blood level of MCFG (r = 0.729, p < 0.001). In addition, there was a correlation between the total bilirubin level and the C/D value (r = 0.458, p < 0.01), which was calculated by dividing the blood level of MCFG by the dose, although there was no correlation between creatinine clearance and the C/D value. These findings suggest that the dose of MCFG must be regulated in patients with biliary stasis-type liver hypofunction. In addition, there was no significant difference in the blood level of MCFG between the group in which tacrolimus (FK506) was combined with MCFG and the group in which MCFG alone was administered. These results suggest that there are no changes in the blood level of MCFG even when MCFG is combined with FK506. 相似文献
86.
Tsusaki H Yonamine H Tamai A Shimomoto M Iwao H Nagata R Kito G 《Journal of pharmacological and toxicological methods》2005,52(1):182-187
INTRODUCTION: A timed non-invasive determination of cardiac function is potentially important for safety pharmacology and toxicity studies. The objectives of this study were to evaluate the accuracy of real-time three-dimensional (RT3D) echocardiography measurements of the left ventricular (LV) volume and LV function and to investigate the effects of some drugs on LV function in cynomolgus monkeys. METHODS: RT3D echocardiography was performed (SONOS 7500, Philips Med Sys) under isoflurane inhalation. RT3D echocardiography measurements and reconstructions were obtained using Tom-Tec (4DLV analysis). We determined end-diastolic volume (EDV), end-systolic volume (ESV), ejection fraction (EF), stroke volume (SV), cardiac output (CO) and heart rate as assessments of LV function. EDV, calculated from two-dimensional (2D) echocardiography and RT3D echocardiography, and the actual LV volume were evaluated and compared. Furthermore, each parameter was determined before and after intravenous infusion (5 or 10 min) of propranolol, verapamil and dobutamine. RESULTS: A strong correlation was found between the actual LV volume and that calculated from RT3D echocardiography (r=0.96, p<0.001). Propranolol (0.1 mg/kg/10 min, n=5) caused an increase in ESV, but not EDV, resulting in a decrease in EF and SV, while verapamil produced increases in both EDV and ESV. Dobutamine (0.01 mg/kg/5 min, n=5) produced decreases in both EDV and ESV and thereby the increased CO resulted from the increased SV. DISCUSSION: These results demonstrate that RT3D echocardiography provides a feasible and accurate estimation of LV volume and EF for safety pharmacology and toxicity studies. 相似文献
87.
Sakai S Hirayama K Iwasaki S Yamadori A Sato N Ito A Kato M Sudo M Tsuburaya K 《Journal of child neurology》2002,17(10):731-737
We attempt to evaluate the residual visual capacities of nine patients (seven males and two females; age range 4 to 35 years, mean 13.8 +/- 9.98) with cerebral visual impairment coupled with severe motor and intellectual disabilities by their contrast sensitivities to sine-wave gratings. Two methods were used for detecting the occurrence of ocular responses to stimuli: (1) detection of optokinetic nystagmus to drifting sinusoidal gratings by naked-eye observation and electronystagmography and (2) detection of ocular pursuit for a drifting Gabor patch by naked-eye observation. We succeeded in measuring the sensitivities of eight cases. For the remaining one case, only the Gabor method could be applied. Most cases showed low contrast sensitivity in both higher (2 and 4 cycles/degree) and lower (0.125 and 0.25 cycles/degree) spatial frequencies and relatively high contrast sensitivity in the middle (0.5 and 1 cycle/degree) range of spatial frequencies. We conclude that the residual visual capacities of patients with severe motor and intellectual disabilities and cerebral visual impairment can be measured fairly accurately by these behavioral methods. 相似文献
88.
Goto S Takebayashi K Shiotani M Fujiwara M Hirose M Noda Y 《The Journal of reproductive medicine》2003,48(5):370-374
OBJECTIVE: To evaluate the effectiveness of 2-step (consecutive) embryo transfer (ET), in which two cleaved embryos are transferred on day 2 (first step of ET) and a single blastocyst is transferred on day 5 (second step of ET) in comparison with conventional day 2 ET. STUDY DESIGN: Observational comparative study at different time periods. Subjects were those who had > or = 4 embryos on day 2 after oocyte retrieval. Those in the conventional group (n = 60) received conventional day 2 ET, in which 3 cleaved embryos were transferred on day 2 between January 1999 and June 2000. Those in the 2-step group (n = 124) received 2-step embryo transfer, in which 2 cleaved embryos were transferred on day 2 and a blastocyst was transferred on day 5 between September 2000 and February 2002. Patients who planned to receive 2-step ET but could not proceed to the second step of ET because of failure to produce blastocysts were included in the 2-step group. RESULTS: The ongoing pregnancy rate with 2-step ET (51.6%) was significantly higher than with conventional ET (26.7%) (P < .01). The clinical pregnancy rate and implantation rate in conventional and 2-step ET were 30.0% vs. 59.7% and 11.1% vs. 27.8%, respectively (P < .001). CONCLUSION: Two-step ET may benefit patients who can obtain a sufficient number of embryos. 相似文献
89.
Cyclic phosphatidic acid inhibits RhoA-mediated autophosphorylation of FAK at Tyr-397 and subsequent tumor-cell invasion 总被引:2,自引:0,他引:2
Mukai M Iwasaki T Tatsuta M Togawa A Nakamura H Murakami-Murofushi K Kobayashi S Imamura F Inoue M 《International journal of oncology》2003,22(6):1247-1256
We demonstrated previously that rat ascites hepatoma MM1 cells require both lysophosphatidic acid (LPA) and fibronectin (FN) for phagokinetic motility and transcellular migration and that these events are regulated through the RhoA-ROCK pathway and tyrosine phosphorylation of proteins including focal adhesion kinase (FAK). Moreover, we reported that palmitoyl-cyclic phosphatidic acid (Pal-cPA), a structural analogue of LPA, inhibits LPA-induced migration of MM1 cells and experimental metastasis of B16 murine melanoma cells. However, the molecular mechanisms of action of Pal-cPA remains to be clarified. To examine this, total cellular lysates after stimulation with LPA or FN were subjected to time-course immunoblot analysis with anti-phophotyrosine and anti-pY397-FAK antibodies. Tyrosine-phosphorylation of FAK especially at Tyr-397 was obviously persistent after stimulation with LPA + FN compared to after stimulation with LPA alone. This persistent phosphorylation was necessary for MM1 cell migration and inhibited by Pal-cPA as by C3 exoenzyme Rho inhibitor. RhoA activity (GTP-bound RhoA) was also measured by the pull down assay using the Rho binding domain of Rhotekin. LPA-induced RhoA-activation of MM1 cells was completely inhibited by Pal-cPA. Moreover, we demonstrated that autophosphorylation of FAK at Tyr-397, downstream of RhoA, contributed to formation of focal adhesions and was critical in LPA-induced MM1 cell migration by developing autophosphorylation-deficient (Y397F) FAK-transfectants. Collectively, Pal-cPA hampered LPA-induced morphological changes and transcellular migration of MM1 cells through downregulating active RhoA and inhibiting its downstream events including autophosphorylation of FAK. Pal-cPA also inhibited endogenous (LPA-independent) activation of RhoA in human fibrosarcoma HT-1080 cells. Pal-cPA may potentially provide a new therapy for the treatment of cancer invasion and metastasis. 相似文献
90.
Limited efficacy of lamivudine against hepatitis B virus infection in allogeneic hematopoietic stem cell transplant recipients 总被引:3,自引:0,他引:3
Ohnishi M Kanda Y Takeuchi T Won Kim S Hori A Niiya H Chizuka A Nakai K Saito T Makimoto A Tanosaki R Watanabe T Kobayashi Y Tobinai K Takaue Y Mineishi S 《Transplantation》2002,73(5):812-815
BACKGROUND: Reactivation of chronic hepatitis B virus (HBV) infection is a major complication when HBV carriers receive immunosuppressive therapy. Recipients of allogeneic hematopoietic stem cell transplantation (HSCT) carry the highest risk of fatal HBV disease (up to 12%). METHODS: In an attempt to identify a suitable procedure for the prevention and management of HBV reactivation, the administration of lamivudine over the course was tested in two patients. RESULTS: Generally, the patients transplant courses were successfully managed despite their difficult clinical situations: a high HBV load before transplant in one patient and intense steroid therapy for complicated acute graft-versus-host disease (GVHD) in the other patient. However, one patient showed a reactivation of HBV after discontinuing lamivudine and the other showed persistently high DNA polymerase activity despite prolonged administration of lamivudine. CONCLUSIONS: We concluded that lamivudine could have a place in the management of patients who suffer from chronic HBV infection and who are undergoing allogeneic HSCT. However, the efficacy of lamivudine seemed to be limited compared with other settings, including solid organ transplantation and autologous HSCT. 相似文献