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1.
S Kato T Morie K Hino T Kon S Naruto N Yoshida T Karasawa J Matsumoto 《Journal of medicinal chemistry》1990,33(5):1406-1413
With the purpose of obtaining more potent and selective gastric prokinetic than metoclopramide (1), a new series of N-[(2-morpholinyl)alkyl]benzamides (17-52) were synthesized and their gastric prokinetic activity was evaluated by determining effects on the gastric emptying of phenol red semisolid meal and of resin pellets solid meal in rats and mice. The morpholinyl moiety was newly designed after consideration of the side-chain structure of cisapride (2) and produced the desired activity when coupled with the 4-amino-5-chloro-2-methoxybenzoyl group of both metoclopramide and cisapride. Modification of the substituents of the benzoyl group markedly influenced the activity. In particular, 4-amino-N-[(4-benzyl-2-morpholinyl)methyl]-5-chloro-2-methoxybenzamide (17) and the 4-(dimethylamino) and 2-ethoxy analogues (25 and 29) of 17 showed potent and selective gastric prokinetic activity along with a weak dopamine D2 receptor antagonistic activity. 相似文献
2.
K. Hamano Hiroshi Ito Andrew Bushell Kathryn J. Wood Kensuke Esato 《Transplant international》1997,10(4):293-298
In this study, the effect of combining anti-CD4 monoclonal antibody (mAb) and cyclosporin (CyA) therapy at the time of transplantation
was examined. A mouse cardiac allograft model was used. Anti-CD4 mAb administered perioperatively induces long-term survival.
The addition of a short course of CyA given subcutaneously in a regimen of either a high-dose treatment or a standard dose
treatment to the anti-CD4 mAb treatment protocol did not have a detrimental effect on graft survival. Despite having no significant
effect on graft survival, the addition of CyA to the treatment protocol did result in a significant decrease in the level
of IL-2 present in the hearts 7 days after transplantation. The decrease in IL-2 production was directly related to the presence
of CyA in vivo. When CyA treatment was continued throughout the period during which unresponsiveness to the graft is induced
by anti-CD4 mAb therapy, 50 % of the grafted hearts were rejected once the CyA was discontinued. In conclusion, the combined
use of anti-CD4 mAb therapy and CyA did not have a negative effect on graft survival in this model when the two agents were
used concurrently at the time of transplantation.
Received: 2 October 1996 Received after revision: 31 January 1997 Accepted: 5 February 1997 相似文献
3.
Masato Miwa Mayumi Matsunaga Noriyuki Nakajima Shintaro Yamaguchi Kensuke Watanabe 《Otolaryngology--head and neck surgery》2007,136(1):62-66
OBJECTIVE: The effect of tonicity changes in nebulizer solutions and irrigations on nasal mucosa is not well known. The present study aims to determine the basic mechanism of hypertonic solution on airway epithelial barrier. STUDY DESIGN AND SETTING: We investigated the electrical potential difference (PD) that is influenced by both active transport and the transepithelial electrical resistance of the epithelial mucosa in the human nose in vivo. The short circuit current (SCC) revealed net ion transport across the epithelium in the guinea pig trachea in vitro. Finally, the size dependency of macromolecules across the tracheal mucosa was determined in vitro using FITC-labeled dextrans of different sizes. RESULTS: PD was significantly decreased after topical application of hypertonic solution both in human and in guinea pig nose. SCC was significantly decreased after application of hypertonic solution. The transport of these dextrans from the basolateral to the apical side was not increased significantly after apical application of hypertonic saline. CONCLUSIONS: Hypertonic saline enhances the electrical permeability of the airway epithelial mucosa but not transport of macromolecule in the short term. 相似文献
4.
Conditioned medium wherein bovine retinal pigment epithelial cells have been cultured (RPE-CM) inhibited proliferation of the capillary endothelial cells (CEC) of the bovine adrenal gland. The RPE-CM was fractionated into three fractions; molecular weight of more than 30 kilo Daltons (kDa) (30 kDa fraction), between 10 and 30 kDa (10 kDa-30 kDa fraction), and less than 10 kDa (10 kDa fraction). Each fraction was tested for its effect on the proliferation, morphology and movement of the CEC. The proliferation of CEC was inhibited in the more than 30 kDa fraction and less than 10 kDa fraction, but not in the 10 kDa-30 kDa fraction. The RPE-CM changed morphology of the CEC into slender shape. This morphological change was observed only in the more than 30 kDa fraction, and the CEC in the other fractions maintained normal morphology. When the CEC proliferation was arrested by hydroxyurea, RPE-CM and the more than 30 kDa fraction did not change morphology. Unfractionated RPE-CM and the more than 30 kDa fraction which changed the morphology of the CEC also inhibited movement of the CEC, such as the migration of cells from a confluent cell layer and single cell movement. These findings suggested that the RPE in culture secrete soluble anti-angiogenic factors into the medium. 相似文献
5.
Protective effects of benidipine on arachidonic acid-induced acute cerebral ischemia in rats. 总被引:1,自引:0,他引:1
Acute cerebral ischemia was produced in rats by injection of arachidonic acid (AA) into the internal carotid artery. Evans blue (EB) was intravenously injected and its extravasation into the brain was determined as an indicator of disturbances in the blood-brain barrier and endothelial cells. Control animals showed severe cerebral edema and marked blue staining of the brain. Benidipine (30 micrograms/kg, i.p.) suppressed the increase in cerebral water content and the extravasation of EB. Similarly nicardipine (100 micrograms/kg, i.p.) suppressed the elevation of water content and the extravasation of EB. Furthermore, both benidipine (30 micrograms/kg, i.p.) and nicardipine (100 micrograms/kg, i.p.) improved the neuronal injuries following AA-injection. An antiplatelet agent, ticlopidine (100 mg/kg, i.p.), and a thromboxane A2 synthetase inhibitor, OKY-1581 (3 mg/kg, i.p.), also suppressed the elevation of cerebral water content. A lipoxygenase inhibitor, AA-561 (200 mg/kg, p.o.), and a cyclooxygenase inhibitor, indomethacin (10 mg/kg, i.p.), did not prevent the increase in cerebral water content. Neither benidipine (3-30 micrograms/kg, i.v.) nor nicardipine (100 micrograms/kg, i.v.) inhibited the AgNO3-induced thrombus formation of the abdominal aorta, whereas ticlopidine (100 mg/kg, p.o.) and OKY-1581 (3 mg/kg, i.v.) prevented the thrombus formation. From the present results, it is suggested that benidipine, as well as nicardipine, may protect against AA-induced acute cerebral infarction via a mechanism independent of antithrombotic action. 相似文献
6.
Yasuyuki Kato Satoru Miyamoto Hirokazu Minamimura Takumi Ishikawa Kensuke Ohue Yoshihiro Shimizu 《The Japanese Journal of Thoracic and Cardiovascular Surgery》2005,53(1):46-48
In embryology, a persistent connection of the left superior vena cava to the left atrium rarely coexists with a coronary sinus.
We herein report an unusual case of persistent left superior vena cava terminating in a left atrium with normal coronary sinus,
which was revealed at the time of permanent pacemaker implantation after a second operation for recurrent left atrioventricular
valve regurgitation. Because this anomaly had gone undiagnosed at the first operation, we were unable to diagnose it prior
to the second operation, because the preoperative coronary angiogram clearly demonstrated a coronary sinus that was not dilated.
We would have repaired the anomaly using a patch or other procedure had it been diagnosed before the second operation in order
to prevent cyanosis or brain complications secondary to right-to-left shunting. One should always be on guard for this rare
condition. 相似文献
7.
Toshihiro Kawamura Hiroshi Motoyama Atsushi Yanaihara Takeshi Yorimitsu Akane Arichi Yasuhiro Karasawa Kahori Suga Kaoru Miya Seika Ishikawa Shiho Mizushima Makiko Kawamura 《Reproductive Medicine and Biology》2007,6(1):53-57
Aim: To compare the clinical outcomes of cryopreserved-thawed embryo transfer among patients with a normal menstrual cycle who had natural or hormone-replacement cycles.
Methods: From January 2004 to June 2006, cryopreserved embryos following conventional in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) were thawed and transferred in a total of 720 natural cycles and 136 hormone-replacement cycles.
Results: Cryopreserved-thawed embryo transfer in patients who had a natural or hormone-replacement cycle resulted in clinical pregnancy in 43.1% and 40.4%, respectively; a rate of miscarriage of 14.5% and 23.6%, respectively; and a rate of ongoing pregnancy and delivery of 36.5% and 30.9%, respectively. None of these differences were statistically significant.
Conclusions: Patients with a normal menstrual cycle who have natural or hormone-replacement cycles can be expected to have comparable clinical outcomes with cryopreserved-thawed embryo transfer. (Reprod Med Biol 2007; 6 : 53–57) 相似文献
Methods: From January 2004 to June 2006, cryopreserved embryos following conventional in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) were thawed and transferred in a total of 720 natural cycles and 136 hormone-replacement cycles.
Results: Cryopreserved-thawed embryo transfer in patients who had a natural or hormone-replacement cycle resulted in clinical pregnancy in 43.1% and 40.4%, respectively; a rate of miscarriage of 14.5% and 23.6%, respectively; and a rate of ongoing pregnancy and delivery of 36.5% and 30.9%, respectively. None of these differences were statistically significant.
Conclusions: Patients with a normal menstrual cycle who have natural or hormone-replacement cycles can be expected to have comparable clinical outcomes with cryopreserved-thawed embryo transfer. (Reprod Med Biol 2007; 6 : 53–57) 相似文献
8.
E Ohshima H Takami H Sato S Mohri H Obase I Miki A Ishii S Shirakura A Karasawa K Kubo 《Journal of medicinal chemistry》1992,35(18):3402-3413
A series of 11-[2-(1-benzimidazolyl)ethylidene]-6,11-dihydrodibenz[b,e]oxep in-2- carboxylic acid derivatives and related compounds were synthesized and found to be potent TXA2/PGH2 receptor antagonists. Each compound synthesized was tested for its ability to displace [3H]U-46619 binding from guinea pig platelet TXA2/PGH2 receptors. Structure-activity relationship studies revealed that the following key elements were required for enhanced activities: (1) an (E)-2-(1-benzimidazolyl)ethylidene side chain in the 11-position of the dibenzoxepin ring system and (2) a carboxyl group in the 2-position of the dibenzoxepin ring system. The studies also indicated that the TXA2/PGH2 receptor binding affinities of this series of compounds in guinea pig platelet were poorly correlated with those in human platelet. Introduction of substituent(s) to the benzimidazole moiety was effective and sodium (E)-11-[2-(5,6-dimethyl-1-benzimidazolyl)ethylidene]- 6,11-dihydrodibenz[b,e]oxepin-2-carboxylate monohydrate (57) recorded the highest affinity for human platelet TXA2/PGH2 receptor with a K(i) value of 1.2 +/- 0.14 nM. It demonstrated potent inhibitory effects on U-46619-induced guinea pig platelet aggregation (in vitro and ex vivo) and human platelet aggregation (in vitro). Compound 57, now designated as KW-3635, is a novel, orally active, and specific TXA2/PGH2 receptor antagonist with neither TXA2/PGH2 receptor agonistic nor TXA2 synthase inhibitory effects. It is now under clinical evaluation. 相似文献
9.
Masahiko Kawaguchi Masakazu Kuro Hisatoshi Ohsumi Toshito Nakajima Yoshihiro Kuriyama Jun Karasawa 《Journal of anesthesia》1994,8(1):60-63
We assessed the local cerebral blood flow (LCBF) in 40 patients under fentanyl-diazepam anesthesia. The measurement of LCBF
was made using 50%–70% stable xenon with 20 min of inhalation interval and a shuttle method for computed tomography imaging.
All patients were anesthetized with 5.95±1.76 μg·kg−1 fentanyl and 0.22±0.07 mg·kg−1 diazepam under mechanical ventilation during CBF measurement. The values and distribution of LCBF on non-affected hemisphere
appeared to be unaltered by fentanyldiazepam anesthesia. We also assessed the cerebral carbon dioxide reactivity in 6 patients.
The cerebral carbon dioxide reactivity, expressed as percentage change in LCBF per unit change in arterial carbon dioxide
partial pressure, was 5.39±1.07, and there were no significant differences of reactivity among regions studied. In conclusion,
we showed reference values of LCBF and carbon dioxide reactivity, measured by stable xenon-enhanced computed tomography, in
patients under fentanyl-diazepam anesthesia. Carbon dioxide reactivity was preserved in all regions including gray matter,
white matter, and basal ganglia. 相似文献
10.
Takahiro Narishige Kensuke Egashira M.D. Yutaka Akatsuka Teisuke Takahashi Akira Takeshita 《Cardiovascular and interventional radiology》1993,16(6):343-347
The effects of an intracoronary administration of iomeprol, a new nonionic tri-iodinated water-soluble contrast medium, on
coronary circulation were compared to those of iopamidol and those of nitroglycerin in 6 chronically instrumented conscious
dogs. A pair of 10 MHz piezoelectric crystals and an electromagnetic flow probe were placed on the left circumflex coronary
artery (LCCA) to measure the epicardial coronary diameter (CD) and coronary blood flow (CBF). Polyethylene tubing for drug
administration was inserted into the LCCA proximal to the sonomicrometers. Iomeprol at the dose of 1 ml and 3 ml/min for 1
min significantly increased CD by 0.6±0.1% and 1.4±0.3%, respectively and CBF by 44.5±9% and 70±10%, respectively. Iopamidol
at the same rates also significantly increased CD by 0.8±0.1% and 1.5±0.3% and CBF by 50±11% and 82±14%, respectively. There
was no statistically significant difference between iomeprol-and iopamidol-induced increases in CD and CBF. However, the duration
of the increase in CD was significantly shorter (p<0.05) after iomeprol than after iopamidol. Nitroglycerin (10 μg/kg) significantly increased CD by 4.5±1% and CBF by 105±10%.
The increases in CD and CBF in response to iopamidol and iomeprol were significantly smaller (p<0.01) than to nitroglycerin. We conclude that vasodilating effects of iomeprol and iopamidol on the large epicardial coronary
artery and coronary blood flow are comparable in conscious dogs and significantly lower than after nitroglycerin in the doses
used by us.
This study was supported by a grant from the EI-ZA1 Pharmaceutical Co., Tokyo, Japan. 相似文献