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Y Takeshige

Publications and source records attributed to Y Takeshige.

10 recordsLinked to original sources

Pharmacokinetics and pharmacodynamics of intravenous OPC-18790 in humans: a novel nonglycosidic inotropic agent.

OPC-18790, a nonglycosidic intropic agent, is now under clinical development for treatment of congestive heart failure. Two separate studies (one placebo-controlled) were conducted to evaluate its pharmacokinetics and pharmacodynamics after intravenous administration to a total of 36 healthy male subjects. The drug was administered both rapidly as a .05-, .1-, .2-, or .4-mg/kg intravenous dose, and as a 1-hour infusion of .5, 1.0, 2.5, 5.0, 10.0, or 15.0 micrograms/kg/minute. Echocardiograms (ECHO) were evaluated before and immediately and 4 hours after the rapid administrations. Blood pressure (BP), heart rate (HR), and QTc in the electrocardiogram also were monitored in the rapid administration study. OPC-18790 was generally well tolerated by all subjects. Maximum peak plasma concentration and area under the curve increased linearly with dose in both studies. The t1/2, total body clearance of drug from plasma (CL), and the dose fraction excreted unchanged in the urine (fe) were comparable and dose-independent at the doses tested in both studies. The overall mean values of t1/2 alpha, t1/2 beta, CL, and fe were .08 +/- .01 hours, 3.64 +/- .22 hours, .46 +/- .01 L/kg, and 43.5 +/- 1.0%, respectively. Echocardiograms showed that, immediately after rapid administration of up to .4 mg/kg, OPC-18790 increased left cardiac function dose-proportionally (P < .05 to .01): the ejection fraction by 21.1% and fractional shortening by 26.5% compared with the predose values, blood pressure, heart rate, and QTc did not differ between subjects given OPC-18790 and these receiving placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The wall structure of the arteries in the corpora cavernosa penis of rabbits; light and electron microscopy.

Wall structures of the arteries in the corpora cavernosa penis were observed in rabbits. The deep (central) arteries in the proximal part of the penis have five or more independent ridges of the wall which are formed by the internal layer of the media consisting of almost longitudinal muscle cell layers. Electron microscopy of these regions revealed that the endothelial cells are connected to each other by many maculae and zonulae adherentes, and that smooth muscle cells of the media are separated from one another by a wide intercellular space embedding abundant collagenous fibers. The epithelioid cells constituting the media of the helicine branches of the deep artery vary in their fine structure from close resemblance to muscle cells, to cells with easily identified special features. Frankly epithelioid cells have few scattered cytoplasmic filaments of a single type, 60-90A in diameter, abundant ribosomes, active Golgi, and other features different from the typical smooth muscle cells. There is no suggestion that these epithelioid cells are either degenerative or undifferentiated forms of smooth muscle cells, as postulated by light microscopists. Transitions from muscle to epithelioid cells are consistent with, but not proved by, our data.

Animals↗

Electron microscopy of endothelial microvilli of large arteries.

Scanning electron microscopic investigations by others have revealed "hair-like" projections from the endothelial surface of the rabbit aorta. We have confirmed by transmission electron microscopy that endothelial microvilli are found, in a limited number of areas in the aortic arch, particularly at the presumed site of fetal origin of the ductus arterious and near the origin of the subclavian artery. The microvilli are almost uniform in diameter (about 0.1 mum) and are as long as 3 mum in length. The outer leaflet of the limiting membrane shows a fuzzy appearance, and thin filaments are recognized in their interiors. A profuse array of endothelial microvilli was also found over the entire surface of the large arteries of human fetuses. The possible hemodynamic significance of these processes is discussed.

Animals↗