Search PubMed⌕ Search

Biomedical subjects

M Yoshimura

Publications and source records attributed to M Yoshimura.

At least 721 records · Page 40Linked to original sources
PubMed1985

Pharmacokinetics of nipradilol (K-351), a new antihypertensive agent. II. Influence of the route of administration on bioavailability in dogs.

The pharmacokinetic parameters of nipradilol (NIP), a new potent antihypertensive and antianginal agent, and propranolol were determined after oral, intravenous and intraportal administration to the beagle dog implanted with cannula in portal vein at a dose of 1 mg/kg. Orally administered NIP underwent extensive first-pass metabolism leading to low bioavailability (11%), despite of complete gastrointestinal absorption. On the constant infusion for 30 min into the portal vein, hepatic extraction ratio was 0.71. The reduction in the systemic availability of orally administered NIP could partly be attributed to the fact that denitration and glucuronidation of NIP occur primarily in the intestinal tract and liver, respectively. Following oral administration of NIP, smaller amount of unchanged drug (1.9%) was excreted into the urine than that of intravenous administration (5.8%). However, in the qualitative and the quantitative aspects on urinary metabolic patterns, there was no appreciable influence of the route of administration. On the other hand, the systemic availability and the hepatic extraction ratio of propranolol were 11% and 0.86, respectively, suggesting that the first-pass metabolism through the liver actually contributes to the reduced availability.

Administration, Oral↗
PubMed1985

Pharmacokinetics of nipradilol (K-351), a new antihypertensive agent. I. Studies on interspecies variation in laboratory animals.

The pharmacokinetics, plasma protein binding and metabolism of nipradilol (K-351: NIP), a new potent antihypertensive and antianginal agent, were compared in dogs, monkeys, rabbits and rats. In all species studied, NIP did not appreciably bind plasma protein (less than 30%) and was extensively distributed in tissues. There was a good correlation between the volume of distribution at steady state (Vss, 1) and body weight (B, kg) of the animal species as follows: Vss = 4.42 B0.805. In addition, Vss increased as a function of the plasma free fraction. Intrinsic clearance of unbound drug (CLuint, 1/h) also correlated with body weight as follows: CLuint = 4.78 B0.722, but blood clearance in rabbits exceeded hepatic blood flow, suggesting extrahepatic metabolism. Following oral administration, the systemic availability for all species increased with the oral dose, while the half-life was about 2 h, and was independent of dose. The apparent threshold dose (ATD, mg/kg) was observed to vary inversely with body weight of the animal species as follows: ATD = 4.33 B-0.472. Less than 2% of the dose was excreted into the urine as unchanged NIP in all species. The metabolic profile for all species was similar, but pronounced quantitative differences among species was observed for aliphatic and aromatic hydroxylation of the 3,4-dihydro-2 H-1-benzopyran ring.

Administration, Oral↗
PubMed1985

Centrally induced vasodepressor and sympathetic nerve responses to taurine.

The effects of taurine on central cardiovascular regulation were investigated by intracerebroventricular (ICV) injection of taurine in urethane-anesthetized rats. Blood pressure fell gradually to attain the maximum level at 10 to 15 min after the injection of 50 micrograms taurine and returned to the basal level 20 min later. After injecting 200 micrograms of taurine, blood pressure began to fall within 30 seconds and attained the maximum level at 2 to 5 min and did not return to the basal level by 20 min. Both heart rate and abdominal sympathetic nerve activity decreased as the blood pressure fell, However, the similar amount of taurine injected intravenously did not affect the blood pressure, the heart rate or the abdominal sympathetic nerve activity. These results suggest that taurine causes the central nervous system to lower the blood pressure by decreasing the sympathetic nerve outflow.

Animals↗
PubMed1985

Centrally inhibitory effect of adrenaline on cardiovascular and sympathetic nerve system in urethane anesthetized rat.

The present study was undertaken to determine the central effect of adrenaline. Adrenaline was administered to the cisterna magna in urethane anesthetized rats. Following the intracisternal injections, the blood pressure dropped and reached a plateau after 15 min, the hypotensive effect continuing for at least 30 min. The heart rate also slowed concomitantly with the depressor effect. The vehicle treated rats did not show any cardiovascular responses. The cardiovascular responses in the experimental rats were accompanied by an inhibition of the sympathetic nerve activity. Pressor responses to electrical stimulation of the posterior hypothalamus were partly inhibited, while pressor responses to intravenous injections of noradrenaline remained unchanged. In DOCA hypertensive rats, the depressor responses to intracisternal injections of adrenaline were augmented. These findings suggest that adrenaline in the brain could contribute to the inhibitory mechanism of the cardiovascular system accompanied by inhibition of the sympathetic nerve system, and that this mechanism may be attenuated in DOCA hypertensive rats.

Anesthesia↗
PubMed1985

Renal denervation inhibits hypothalamo-sympathetic nerve system in normotensive and hypertensive rats.

The role of the renal nerve in influencing the hypothalamo-sympathetic nerve system to regulate the cardiovascular system was studied in normotensive Wistar and spontaneously hypertensive rats (SHR). Renal denervation attenuated pressor and sympathetic nerve responses to electrical stimulation of the hypothalamus without lowering the basal blood pressure at 48 hours after denervated operation. These findings suggest that renal denervation could inhibit the hypothalamo-sympathetic nerve system in normotensive rats. The development of hypertension in SHR was completely inhibited by renal denervation during 2 weeks of observation (from 7 to 9 weeks of age) without increasing water intake and urine volume. Pressor responses to intravenous injection of norepinephrine were not affected by renal denervation. The results show that the antihypertensive effect of renal denervation was not due to the changing of vascular reactivity. Pressor and sympathetic nerve responses to hypothalamic stimulation were strongly diminished in renal denervated rats. These results suggest that renal denervation strongly inhibited they hypothalamo-sympathetic nerve system. It is also suggested that the renal afferent nerve may facilitate the hypothalamo-sympathetic nerve system in regulating blood pressure and that this facilitation may contribute to the development of hypertension in SHR.

Animals↗
PubMed1985

Peroneal island flap for skin defects in the lower extremity.

Two types of peroneal island-flap transfer were used in fourteen patients with a large defect in the soft tissues of the lower extremity. The peroneal artery and vein and their cutaneous branches form the pedicle, and an extensive transfer of skin is possible either from above the knee or from the lateral side of the leg to as far distal as the foot. Two methods were used: in the first we severed the peroneal artery and vein distally, with an island of skin attached, and elevated them proximally, and in the second we severed the proximal portions of the peroneal vessels, with an island of skin attached, and elevated them distally. The largest flap that we used in this series measured fourteen by 16.5 centimeters and the smallest, 2.5 by five centimeters. All fourteen transfers healed, with no necrosis of the flap.

Adult↗
PubMed1985

Peculiar glomerular lesions in Takayasu's arteritis.

Seventeen kidney specimens (6 biopsies and 11 autopsies) of Takayasu's arteritis disclosed two types of glomerular lesions. One was a mild axial mesangial proliferation associated with intramembranous and mesangial electron dense deposits consisting of IgG, IgM and C3 (axial type). The other was a centrolobular mesangial thickening associated with a hyaline deposition showing a mosaic pattern ("centrolobular mesangiopathy": centrolobular type). Mesangiolytic lesions, nodulous lesions, microaneurysms in glomeruli and extensive deposition of hyaline materials both in afferent and efferent arterioles were also observed. The former lesion was found in 4 patients with an active arteritis; and the latter was mainly observed in autopsy cases having a long-term clinical course. In the genesis of the axial type, immune complex deposition caused by the active aortitis may be involved, while the glomerular ischemia caused by the vascular lesions may be implicated in the development of the centrolobular type.

Adolescent↗
PubMed1985

A new method for monitoring circulation of grafted bone by use of electrochemically generated hydrogen.

The patency of the anastomosed blood vessels in a free vascularized bone graft is difficult to ascertain during the early postoperative stage. For this purpose, the local blood flow was measured by means of electrochemically generated hydrogen. Although only three cases have been tested thus far, the method proves to be a simple and useful monitor of the blood flow in a free vascularized bone graft.

Aged↗
PubMed1985

Purification and characterization of an antitumor principle from Streptococcus hemolyticus, Su strain.

An antitumor principle (SAGP) has been purified from cell-free crude extract (CE) of group A Streptococcus hemolyticus, Su strain. The antitumor activity of each fraction was evaluated by measuring the in vitro growth inhibitory effect on transformed hamster embryonic lung cells (THEL). CE was subjected to thermal treatment, streptomycin precipitation, ammonium sulfate precipitation, and chromatography on octyl-Sepharose CL-4B, DEAE-cellulose, and Sephadex G-200 in that order. The active fraction from the last chromatography was dialyzed against distilled water. The resulting precipitate was removed and the supernatant was lyophilized (SAGP). SAGP is a homogeneous glycoprotein as judged by polyacrylamide gel electrophoresis, gel filtration, immunodiffusion, and PAS-staining. The molecular weight of SAGP was determined to be 140,000 to 150,000 by the gel filtration technique. SAGP is composed of subunits, each of which has a molecular weight of about 50,000. The isoelectric point of SAGP is 4.3. Amino acid analysis revealed an abundance of aspartic and glutamic acid residues in SAGP. The 50% growth inhibitory dose of SAGP on THEL was 0.062 micrograms/ml. Intraperitoneal administration of SAGP (20 mg/kg/day X 4) to ICR mice bearing Ehrlich ascites carcinoma cells increased their life span to 254% of the control.

Amino Acids↗