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排序方式: 共有843条查询结果,搜索用时 109 毫秒
1.
An attempt was made to explore the quantitative relationship between the intestinal absorption data obtained from in vivo studies and in situ perfusion studies. The time course of the fraction remaining to be absorbed of L-glucose, erythritol, and urea in the small intestine following the intrajejunal administration to rats was described by a one-compartment model. Thus derived first-order intestinal absorption rate constants (ka) obtained from the in vivo studies in rats were compared with the membrane permeability clearances (CLa,m) estimated in a single-pass perfusion system. Not only were ka and CLa,m in the same increasing order of L-glucose less than erythritol less than urea, but also the operational luminal volumes given as CLa,m/ka were in agreement with the in vivo luminal volume of jejunum estimated by an inulin dilution method. This result suggests that the in vivo intestinal absorption rate (or ka) can be correlated with the intestinal membrane permeability (or CLa,m) by taking the in vivo luminal volume into account. 相似文献
2.
3.
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
4.
Murali Pagala N. V. Nandakumar S. A. T. Venkatachari Kadirimangalam Ravindran Bellamakonda Amaladevi Tatsuji Namba David Grob 《Muscle & nerve》1993,16(9):911-921
Fatigue mechanisms in normal intercostal muscle and muscle from patients with myasthenia gravis (MG) were evaluated by monitoring the compound muscle action potential (CMAP) and tetanic tension responses to repetitive nerve or muscle stimulation in vitro. When fatigue was induced by nerve stimulation at 30 Hz for 0.5 s every 2.5 s, about half of the original tension decreased after 30 min in normal muscle and 5 min in MG muscle. Analysis of the changes in area of CMAPs and tension indicated that impairment of neuromuscular transmission, muscle membrane excitation, and excitation-contraction (E-C) coupling and contractility accounted for 40%, 29%, and 31% of fatigue in normal muscle, and 83%, 0%, and 17% of fatigue in MG muscle. When fatigue was induced by muscle stimulation at 30 Hz, tension declined by a quarter after 30 min in normal muscle, but by a half after 17 min in MG muscle. Impairment of muscle membrane excitation and E-C coupling and contractility accounted for 58% and 42% of fatigue in normal muscle, and 22% and 78% of fatigue in MG muscle. Thus, fatigue of normal muscle is caused by impairment of at least four processes, and enhanced fatigue of MG muscle is caused by greater impairment of neuromuscular transmission, E-C coupling, and contractility. © 1993 John Wiley & Sons, Inc. 相似文献
5.
Toshiya Inada M.D. Fumiko Minagawa B.A. Satoru Iwashita M.D. Tatsuji Tokui M.D. 《Psychiatry and clinical neurosciences》1994,48(4):729-735
Abstract: In order to examine the characteristics of potential difficult-to-manage psychiatric cases, seven potential subgroups were extracted from the criminal offenders who were sent to the division of psychiatric diagnosis, Tokyo District Public Prosecutors Office for Pre-Prosecution Psychiatric Justice (PPPJ). The following criteria were used to select the potential subgroups: offenders who had experienced compulsory discharge from a mental hospital, those who had experienced Involuntary Admission to the mental hospital by the Prefectural Governor at least twice, those who had experienced admission to mental hospitals on more than 5 occasions, those who had been put on PPPJ previously for other criminal matters at least 3 times, those who had previously attempted suicide, and those who had committed homicide or arson. From the results of this study, it could be concluded that at least two types of "difficult-to-manage" psychiatric cases exist in the criminal offenders. 相似文献
6.
Membrane-limited hepatic transport of the conjugative metabolites of 4-methylumbelliferone in rats 总被引:1,自引:0,他引:1
The hepatic transports of 4-methylumbelliferone (4-MU) and its conjugative metabolites, the glucuronide (4-MUG) and sulfate (4-MUS), were investigated in rats with various methods. The extraction ratio (E) was estimated with the multiple indicator dilution (MID) method using isolated perfused rat liver. The values of E for 4-MUG and 4-MUS were much lower (less than 0.2) than that for the parent compound, 4-MU (0.89). In addition, we examined the simulation of the outflow curves of conjugates based on the "distributed" model in which we varied the permeability between the blood and hepatocytes. When the permeability was much smaller relative to the hepatic blood flow, the simulated curve was superimposed on the dilution curve. These results suggest that the influx permeabilities of these conjugates are so low that little extraction occurs during the passage through the liver. Measuring the unidirectional uptake of these conjugates into the liver with the in vitro centrifugal filtration method using isolated hepatocytes, we determined the influx permeabilities (PSinf(total] for the total ligands. The value of PSinf(total) determined with the in vitro method was extrapolated to that per gram of liver, assuming 1 g of liver has 1.3 X 10(8) cells. The values of PSinf(total) for 4-MU, 4-MUG, and 4-MUS were 4.8, 0.06, and 0.11 mL/min/g liver, respectively. Thus, the influx permeabilities for 4-MUG and 4-MUS were much smaller than the hepatic blood flow (1.6 mL/min/g liver), confirming the results of MID method. 相似文献
7.
8.
T Hosaka K Shirakura T Iga H Ohsuga K Noji S Nezu 《The Tokai journal of experimental and clinical medicine》1987,12(5-6):319-324
This article demonstrates one clinical application of biofeedback treatment with a microvibration (MV) transducer to relieve functional tremors. A MV transducer, a kind of accelerometer, was originally developed to detect invisible tremors from the body surface but this equipment is also utilized to detect visible tremors to convert them to auditory signals. Our method uses almost the same procedure as electromyographic biofeedback treatment. The threshold level for production of auditory signals should be determined as high as possible between the superimposed amplitudes of essential MV and tremor components. As the sessions progress, the predeterminate threshold level should be gradually lowered to almost the same amplitude as MV itself. In determining the threshold, it is more appropriate to utilize records of the frequency band in which the tremor components are described more clearly, in order to remove noises or MV waves of different frequency ranges. Because of the high sensitivity of this accelerometer, such "tremor feedback" treatment can be recommended only if the tremor is present while the patient is resting or remains still. 相似文献
9.
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
10.
H Sato Y Sugiyama S Miyauchi Y Sawada T Iga M Hanano 《Journal of pharmaceutical sciences》1986,75(1):3-8
The effect of a uniform diffusional barrier on hepatic extraction of the parent drug by evenly or unevenly distributed uni-enzyme was quantitatively determined by the present simulation study. Five models of enzymic distribution were defined with regard to the hepatic blood flow path, and the extraction ratios were calculated or simulated under the various conditions of average intrinsic clearances and diffusion clearances across hepatocytes. Differences in the extraction ratios among the five models were evaluated by the "relative extraction ratios," which are the extraction ratios in each model divided by that in the model where the enzymatic activity is evenly distributed. It was found that when a diffusion clearance was high compared to the intrinsic clearance, enzymic distribution was not an important determinant of the extent of hepatic extraction. By contrast, when a diffusional barrier across hepatocytes exists, i.e., the diffusion clearance is low or intermediate compared to the intrinsic clearance, extraction ratios differed widely among the models of enzymic distribution, especially at intermediate average intrinsic clearances. In the presence of a diffusional barrier, the more skewed the distribution of the enzymatic activity is, the lesser the amount of drug eliminated at steady state. The most efficient metabolism occurred when the enzymatic activity was evenly distributed. 相似文献