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排序方式: 共有435条查询结果,搜索用时 15 毫秒
1.
2.
Aoyama Takao Yamamoto Koujirou Kotaki Hajime Sawada Yasufumi Iga Tatsuji 《Pharmaceutical research》1997,14(11):1601-1606
Purpose. The locomotive activity changes after intravenous (i.v.) administration of methylphenidate (MPD) in rats were pharmacodynamically analyzed.
Methods. MPD concentration in plasma, MPD concentration and dopamine (DA) level in striatal dialysate collected by microdialysis method, and the locomotor activity after i.v. administration of MPD (2, 5 and 10 mg/kg doses) were used for the analysis.
Results. The transport of MPD from plasma to the interstitial fluid in the brain could be expressed by the linear two-compartment model. The clockwise hysteresis between the MPD concentration and the DA level in the dialysate could be explained by the pharmacodynamic model considering Michaelis-Menten type reuptake process of the extracellular DA into the terminal of the dopaminergic nerve and its competitive inhibition by the extracellular MPD. The inhibition constant (Ki) of MPD for DA reuptake was estimated to be 41.3 ± 73.8 nM (mean ± SE), which was closely consistent with the in vitro value after correction with dialysis recovery. The relationship between DA level in dialysate and locomotor activity was expressed by the Emax model considering two contrary effects, hyperkinesia and stereotypy. The bi-phasic locomotor activity-time profiles after high dose of MPD could be represented by this model.
Conclusions. The developed model made it possible to explain the tolerance in DA increase and the complicated locomotive change induced by MPD, and may be useful for other DA reuptake inhibitors, such as amphetamine and methamphetamine. 相似文献
3.
Seiji Miyauchi Yuichi Sugiyama Yasufumi Sawada Kaname Morita Tatsuji Iga Manabu Hanano 《Journal of pharmacokinetics and pharmacodynamics》1987,15(1):25-38
Hepatic elimination of 4-methylumbelliferone (4MU), which has been used as a model compound for conjugative metabolism, was studied by means of a multiple indicator dilution (MID) method in the isolated perfused rat liver. Using this method, three intrinsic hepatic clearances, CL
int,inf
, CL
int,eff, and CL
int,seq, which represent the influx, efflux, and sequestration processes, respectively, were obtained. When the dose was increased from a low dose (50 g/rat liver) to a high dose (3000 g/rat liver), the hepatic availability of 4MU increased from 0.11 to 0.73. With increasing dose, the CL
int,eff value increased approximately two times, while the CL
int,seq value decreased to approximately one-third. The remarkable dose dependence of hepatic availability was due to nonlinearity in both CL
int,eff and CL
int,seq values. However, the CLint,inf
value was almost independent of dose. The dose-dependent change in CLint,seq
might be explained by the saturation of conjugative metabolism of 4-MU, while the increase in the CL
int,eff value with increasing dose might be partly explained by the nonlinear tissue binding of 4-MU, since the tissue unbound fraction determined by an ultrafiltration method using liver homogenate increased approximately 1.5 times at higher concentration of 4-MU compared to that at lower concentrations. In addition, based on a comparison of the individual intrinsic clearances, i.e., CL
int,inf
, CL
int,eff, and CL
int,seq, the major determining process of the apparent hepatic intrinsic clearance of 4MU is thought to be the sequestration process at the high dose. However, at the low dose, the membrane transport process (influx and efflux processes) as well as the sequestration process also determine the apparent hepatic intrinsic clearance. 相似文献
4.
5.
Okudaira Kazuho Yamazaki Masayo Sawada Yasufumi Sugiyama Yuichi Iga Tatsuji Hanano Manabu 《Pharmaceutical research》1992,9(9):1152-1156
The role of the multispecific bile acid transporter for cardiac glycoside uptake is still controversial. This study was designed to examine the inhibitory effects of basic drugs (verapamil, dipyridamole, nifedipine, chlorpromazine, disopyramide, quinidine, propranolol, and lidocaine) on taurocholate uptake by isolated rat hepatocytes and to compare these effects with inhibition of ouabain uptake. Sodium-dependent taurocholate uptake was significantly reduced, to 50-70% of the control value, by 50 µM verapamil, dipyridamole, and nifedipine. Sodium-independent taurocholate uptake was more extensively inhibited, to 20-40%, by these basic drugs. The inhibition of ouabain uptake correlated better with sodium-independent taurocholate uptake ( = 0.918) than with sodium-dependent taurocholate uptake ( = 0.714). Taurocholate competitively inhibited ouabain uptake in the absence of sodium. These results indicate that the cardiac glycoside transport system is similar to the sodium-independent taurocholate transport system. 相似文献
6.
Andrea Choe Tatsuji Chuman Stephan H. von Reuss Aaron T. Dossey Joshua J. Yim Ramadan Ajredini Adam A. Kolawa Fatma Kaplan Hans T. Alborn Peter E. A. Teal Frank C. Schroeder Paul W. Sternberg Arthur S. Edison 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(51):20949-20954
Nematodes use an extensive chemical language based on glycosides of the dideoxysugar ascarylose for developmental regulation (dauer formation), male sex attraction, aggregation, and dispersal. However, no examples of a female- or hermaphrodite-specific sex attractant have been identified to date. In this study, we investigated the pheromone system of the gonochoristic sour paste nematode Panagrellus redivivus, which produces sex-specific attractants of the opposite sex. Activity-guided fractionation of the P. redivivus exometabolome revealed that males are strongly attracted to ascr#1 (also known as daumone), an ascaroside previously identified from Caenorhabditis elegans hermaphrodites. Female P. redivivus are repelled by high concentrations of ascr#1 but are specifically attracted to a previously unknown ascaroside that we named dhas#18, a dihydroxy derivative of the known ascr#18 and an ascaroside that features extensive functionalization of the lipid-derived side chain. Targeted profiling of the P. redivivus exometabolome revealed several additional ascarosides that did not induce strong chemotaxis. We show that P. redivivus females, but not males, produce the male-attracting ascr#1, whereas males, but not females, produce the female-attracting dhas#18. These results show that ascaroside biosynthesis in P. redivivus is highly sex-specific. Furthermore, the extensive side chain functionalization in dhas#18, which is reminiscent of polyketide-derived natural products, indicates unanticipated biosynthetic capabilities in nematodes. 相似文献
7.
Hiroshi Miyakawa Eriko Kitazawa Kazuhiro Abe Naomi Kawaguchi Hirotoshi Fuzikawa Kentaro Kikuchi Makoto Kako Tatsuji Komatsu Naoaki Hayashi Kendo Kiyosawa 《Journal of gastroenterology》1997,32(6):769-776
To determine whether “autoimmune hepatitis type IIb” should be categorized as a subgroup of autoimmune hepatitis, we conducted a clinicopathological study of 25 adult Japanese patients who were positive for anti-liver/kidney microsome-1 (anti-LKM-1) antibody and infected with the hepatitis C virus (HCV). Anti-LKM-1 was determined by indirect immunofluo-rescence and by the double immunodiffusion assays we have developed. Twenty-two patients did not present any unusual symptoms or any associated diseases during the course of their chronic HCV infection. The spectrum of HCV genotypes of these patients did not significantly differ from that of anti-LKM-1-negative Japanese patients with chronic hepatitis C. Histological examination of liver biopsy specimens showed the usual characteristics of chronic hepatitis C and lack of characteristics of autoimmune hepatitis type I. No disease-specific HLA haplotypes were noted, and HLA-DR4, which is detectable in 88.7% of Japanese patients with autoimmune hepatitis type I, was detected in only 50.0% of our group, the same rate as the background frequency. Prednisolone was effective in none of the six patients treated, but interferon was effective in six of ten treated patients (60%). From these results, we conclude that “autoimmune hepatitis type IIb” should not be categorized as autoimmune hepatitis, and that this subgroup is essentially chronic hepatitis C in which an autoantibody has been produced during the course of chronic HCV infection. 相似文献
8.
Sakamoto Kazumasa Ito Kiyoaki Yotsuyanagi Hiroshi Yatsuhashi Hiroshi Tanaka Yasuhito Hige Shuhei Takikawa Yasuhiro Ueno Yoshiyuki Yamamoto Kazuhide Imazeki Fumio Inoue Jun Kurosaki Masayuki Umemura Takeji Toyoda Hidenori Mita Eiji Michitaka Kojiro Maeshiro Tatsuji Yamada Norie Suetsugu Atsushi Kawanaka Miwa Seko Yuya Matsuura Kentaro Okumura Akinori Fukuzawa Yoshitaka Sugiyama Masaya Mizokami Masashi Yoneda Masashi 《Journal of gastroenterology》2022,57(12):971-980
Journal of Gastroenterology - Hepatitis B virus (HBV) is one of the most prevalent chronic viral infections that causes chronic hepatitis B (CHB). In Japan, genotypes B and C account for most of... 相似文献
9.
Clinical usefulness of biochemical markers of liver fibrosis in patients with nonalcoholic fatty liver disease 总被引:5,自引:0,他引:5
Sakugawa H Nakayoshi T Kobashigawa K Yamashiro T Maeshiro T Miyagi S Shiroma J Toyama A Nakayoshi T Kinjo F Saito A 《World journal of gastroenterology : WJG》2005,11(2):255-259
AIM: Nonalcoholic steatohepatitis (NASH) is a severe form of nonalcoholic fatty liver disease (NAFLD), and progresses to the end stage of liver disease. Biochemical markers of liver fibrosis are strongly associated with the degree of histological liver fibrosis in patients with chronic liver disease. However, data are few on the usefulness of markers in NAFLD patients. The aim of this study was to identify better noninvasive predictors of hepatic fibrosis, with special focus on markers of liver fibrosis, type VI collagen 7S domain and hyaluronic acid. METHODS: One hundred and twelve patients with histologically proven NAFLD were studied. RESULTS: The histological stage of NAFLD correlated with several clinical and biochemical variables, the extent of hepatic fibrosis and the markers of liver fibrosis were relatively strong associated. The best cutoff values to detect NASH were assessed by using receiver operating characteristic analysis: type VI collagen 75 domain ≥5.0 ng/mL, hyaluronic acid ≥43 ng/mL. Both markers had a high positive predictive value: type VI collagen 7S domain, 86% and hyaluronic acid, 92%. Diagnostic accuracies of these markers were evaluated to detect severe fibrosis. Both markers showed high negative predictive values: type VI collagen 7S domain (≥5.0 ng/mL), 84% and hyaluronic acid (≥50 ng/mL), 78%, and were significantly and independently associated with the presence of NASH or severe fibrosis by logistic regression analysis. CONCLUSION: Both markers of liver fibrosis are useful in discriminating NASH from fatty liver alone or patients with severe fibrosis from patients with non-severe fibrosis. 相似文献
10.
Yamauchi K Yamaguchi N Furukawa T Takatsu K Nakanishi T Ishida K Komatsu T Tokushige K Nagahara H Hashimoto E Shiratori K 《Hepatology (Baltimore, Md.)》2005,42(1):149-155
We have previously reported an immunoglobulin (Ig) M autoantibody to hepatocyte-related 190-kd molecules in patients with type 1 autoimmune hepatitis (AIH). This molecule was first isolated by hepatocyte-specific human monoclonal antibody (MoAb). To elucidate the role of this IgM autoantibody in hepatocyte injury, we examined the reactivity of this MoAb to murine hepatocytes and then questioned whether acute hepatic injury could be induced in mice via injection of this MoAb. The reactivity of MoAb was examined via both FACS analysis using murine hepatocytes and immunostaining of liver tissues. We then identified the murine hepatocyte membrane molecule recognized by this MoAb. The role of this MoAb in the immunopathogenesis of AIH was assessed by testing whether its injection into mice could increase serum aminotransferase levels as well as cause changes in liver histology. The present results demonstrate that this MoAb cross-reacted with murine hepatocytes and recognized a 190-kd molecule on the murine hepatocyte membrane just as in human hepatocytes. One hour after the injection of MoAb, the deposition of both IgM and complement component 3 was found in liver tissues. At 8 hours after the injection, serum aminotransferase levels were significantly increased in MoAb-injected mice compared with controls. Histological study revealed massive hepatocyte necrosis in MoAb-injected mice. In conclusion, human MoAb recognized a 190-kd molecule of both human and murine hepatocytes, and the injection of this MoAb to mice resulted in acute liver injury, indicating that this type of autoantibody may play an important role in the immunopathogenesis of AIH. 相似文献