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71.
Liver Targeting of Interferon Through Pullulan Conjugation 总被引:1,自引:0,他引:1
Xi Keli Tabata Yasuhiko Uno Kazuko Yoshimoto Miwa Kishida Tsunataro Sokawa Yoshihiro Ikada Yoshito 《Pharmaceutical research》1996,13(12):1846-1850
Purpose. The purpose of this study was to actively target interferon (IFN) to the liver through its chemical conjugation with pullulan, a water-soluble polysaccharide with a high affinity for the liver.
Methods. Chemical conjugation of IFN with pullulan was achieved by a cyanuric chloride method. Following intravenous injection of the conjugates to mice, their body distribution and the activity of an IFN-induced enzyme, 2,5-oligoadenylate (2-5A) synthetase in the liver and other organs, were evaluated.
Results. The cyanuric chloride method enabled us to prepare an IFN-pullulan conjugate that retained approximately 7–9 % of the biological activity of IFN. Pullulan conjugation enhanced the liver accumulation of IFN and the retention period with the results being reproducible. When injected intravenously to mice, the IFN-pullulan conjugate enhanced the activity of 2-5A synthetase in the liver. The activity could be induced at IFN doses much lower than those of free IFN injection. In addition, the liver 2-5A synthetase induced by conjugate injection was retained for 3 days, whereas it was lost within the first day for the free IFN-injected mice.
Conclusions. IFN-pullulan conjugation was promising for IFN targeting to the liver with efficient exertion of its antiviral activity therein. 相似文献
72.
Terashima Keisuke Takai Satomi Usami Yoshiko Adachi Tetsuo Sugiyama Tadashi Katagiri Yoshihiro Hirano Kazuyuki 《Pharmaceutical research》1996,13(9):1327-1330
Purpose. Indomethacin is well known to be metabolized via O-demethylation and N-deacylation. In this paper we found an enzyme involved in the hydrolysis of amide-linkage of indomethacin and partially characterized it as well as its substrate specificity.
Methods. An indomethacin hydrolyzing enzyme was purified to homogeneity from pig liver microsomes using columns of Q-Sepharose, Red-Sepharose and Blue-Sepharose. The enzyme activity was assayed by measuring of -chlorobenzoic acid liberated from indomethacin by HPLC.
Results. The purified enzyme effectively hydrolyzed the amide linkage in indomethacin but not those in -naphthylacetate and -nitrophenylacetate, which are typical substrates for carboxylesterase. The subunit molecular mass of the enzyme was 65 kDa according SDS-polyacrylamide gel electrophoresis. The Michaelis constant (Km) and maximum velocity (Vmax) values for indomethacin were 67.8 µM and 9.02 nmol/min/mg protein, respectively. The amino acid sequence analysis of the enzyme after cyanogen bromide cleavage showed high homology with a mouse carboxylesterase isozyme designated as ES-male. The activity of indomethacin hydrolysis was relatively high in the pig, rabbit and human liver homogenate, but not in those from rat and mouse. On the other hand, purified human liver carboxylesterases pl 5.3 and 4.5, and pig liver carboxylesterases have no catalytic activity for indomethacin.
Conclusions. These results indicate that the hydrolysis of amide-linkage of indomethacin in humans would be associated with an enzyme similar to the indomethacin hydrolyzing enzyme from pig liver microsomes described here. 相似文献
73.
Delayed image of iodine-123 iomazenil as a relative map of benzodiazepine receptor binding: The optimal scan time 总被引:2,自引:0,他引:2
Yoshihiro Onishi Yoshiharu Yonekura Fumiko Tanaka Sadahiko Nishizawa Hidehiko Okazawa Koichi Ishizu Toru Fujita Junji Konishi Takao Mukai 《European journal of nuclear medicine and molecular imaging》1996,23(11):1491-1497
Delayed single-photon emission tomograpic (SPET) images after an intravenous bolus injection of iodine-123 iomazenil have been used as a relative map of benzodiazepine receptor binding. We determined the optimal scan time for obtaining such a map and assessed the errors of the map. SPET and blood data from six healthy volunteers and five patients were used. A three-compartment kinetic model was employed in simulation studies and analyses of actual data. The simulation studies suggested that, in the normal brain, the scan time at which a single SPET image best represented the relative receptor binding was 3.0–3.5 h post-injection. This finding was supported by actual data from the volunteers. The simulation studies also suggested that the optimal scan time was not greatly changed by the variability of the input functions, and that the error in the SPET image contrast in the vicinity of the optimal scan time was not increased by changes in the tracer kinetics in the entire brain. The SPET image contrast in the patients at 3.0 h post-injection agreed well with the reference receptor binding estimated by kinetic analysis, with a mean error of 3.6%. These findings support the use of a single SPET image after bolus injection of [123I]iomazenil as a relative map of benzodiazepine receptor binding. For this purpose, a SPET scan time of 3.0-3.5 h post-injection is recommended. 相似文献
74.
Yuji Yamamori Yoji Saito Megumi Kaneko Yumiko Kirihara Shinichi Sakura Yoshihiro Kosaka 《Journal canadien d'anesthésie》1996,43(11):1175-1179
Purpose
The present study was designed to examine the antinociceptive effects of orally administered ONO-9902, an enkephalinase inhibitor, on both somatic and visceral pain after visceral stress conditions.Methods
Twenty six male rats were examined. Tail-flick (TF) and colorectal distension (CD) tests were used to determine somatic and visceral antinociceptive effects, respectively. Measurements were performed in rats under immediate post-stress conditions (group ST; n = 14) and in rats nor under stress conditions (group NST; n = 12). In the stressed group, the same device, CD, for visceral antinociceptive effects was used for visceral stress and was applied with an intracolonic pressure of 60 mmHg for 20 min after drug administration. The TF latency and CD threshold were measured before and at 30, 40, 50, 60 and 90 min after administration of ONO-9902 300 mg · kg?1 or distilled water.Results
Orally administered ONO-9902 did not produce any changes in the % maximum possible effect (%MPE) in either TF or CD tests in the unstressed group. In the stressed group, %MPE in the CD test increased 18% and 31% at 30 and 40 min, respectively, after oral administration of ONO-9902 compared with the control group (P < 0.05). However, %MPE to TF test did not alter even after the CD-induced stress condition.Conclusion
These results suggest that ONO-9902 may have analgesic effects on visceral pain but not on somatic pain under immediate post-stress conditions. 相似文献75.
The change of the cerebrospinal pressure wave from during the continuous monitoring of intracranial pressure is often experienced. We supposed that this phenomenon would be the result of the change of transmission of spinal fluid pulse through the cerebrospinal fluid (CSF) system. Our study was performed to determine the change of auto power spectrum of CSF pulse when CSF pressure was increased by the slow infusion of lactate linger solution. The spectrum of CSF pulse was found to be composed of four main waves; wave derived from the respiratory movement, fundamental wave of cardiac origin and its 2nd and 3rd harmonic waves. The power of waves derived from the cardiac beats were increased when CSF pressure was elevated by the slow infusion, but the degree of increment was larger in the fundamental wave than harmonic waves. Elevation of CSF pressure caused relative attenuation of the harmonic waves included in CSF pulse. From the result of this study we found that CSF system would have the function of "high-cut filter" and its cut-off frequency was lowered by the slow infusion of lactate linger solution. 相似文献
76.
Multiple primary left ventricular myxomas with multiple intraventricular recurrences. 总被引:3,自引:0,他引:3
Y Soma S Ogawa S Iwanaga R Yozu M Kudo S Handa S Kawada H Sugiura 《The Journal of cardiovascular surgery》1992,33(6):765-767
A 23-year-old male was operated on for two primary left ventricular myxomas of the "complex" type. Ten months later, abnormal echo reappeared and reoperation was carried out to excise 2 recurrent myxomas in the left ventricle. Multiple foci were most likely responsible for the recurrence. No recurrence has been detected for 20 months postoperatively. This may be the first reported case of multiple primary left ventricular myxoma with multiple recurrences in the left ventricular cavity. 相似文献
77.
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80.
The effect of exogenous nitric oxide on endothelial dysfunction in two-kidney, one-clip renovascular hypertensive rats 总被引:2,自引:0,他引:2
Otsuka Y Harasawa S Sugiura H Koike M Akimoto H Ishii T Abeta H Okabe T Kushiro T Kanmatsuse K 《Nihon Jinzo Gakkai shi》2000,42(8):619-624
Previous studies have shown that hypertension causes endothelial dysfunction. To study the influence of exogenous nitric oxide(NO) on endothelial dysfunction produced by hypertension, we administered a non-depressor dose of nipradilol to two-kidney, one-clip renovascular hypertensive rats(2K1C). Sprague-Dawley rats underwent either sham surgery(G-1) or clipping of the left renal artery. From day seven, 2K1C were randomized into 3 groups, placebo treatment(G-2), nipradilol treatment(G-3,) and propranolol treatment(G-4). Urinary NO2- + NO3-(NOx) excretion (UNOx V) was measured 4 weeks after clipping, and then, acetylcholine(Ach), A23187, or sodium nitroprusside(SNP)-induced relaxation were measured in the aorta. Blood pressure was increased in G-2, G-3, and G-4 compared to G-1. UNOx V was lower in G-2, G-3, and G-4 compared to G-1, but UNOx V was higher in G-3 compared to G-2 and G-4. Although Ach or A23187-induced relaxation was significantly decreased in isolated artery from G-2, G-3, and G-4 compared with those from G-1. Ach- or A23187-induced relaxation was improved in G-3. SNP-induced relaxation did not differ among the 4 groups. These results suggest that exogenous NO from nipradilol reduces the endothelial dysfunction caused by hypertension without changing the blood pressure. 相似文献