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Biomedical subjects

Y Morimoto

Publications and source records attributed to Y Morimoto.

At least 415 records · Page 23Linked to original sources
PubMed1989

Skin permeability of water-soluble drugs.

The permeabilities of several water-soluble drugs through excised hairless rat skin from their aqueous suspensions were investigated by using newly designed two-chamber diffusion cells. Disodium cromoglycate, diclofenac sodium, dopamine hydrochloride, isoproterenol hydrochloride, diltiazem hydrochloride and papaverine hydrochloride were selected as water-soluble drugs. Indomethacin, a lipophilic drug, and deuterium oxide (D2O) were used for comparison. The skin permeability coefficients of these water-soluble drugs were 100--1000 times lower than that of indomethacin. Since these drugs have high solubility in the donor solution (distilled water or lactate buffer), however, the skin permeation rates, which are in general proportional to the product of skin permeability coefficient and solubility of drugs in the drug-donor compartment, were comparable to or higher than that of indomethacin (1.7 micrograms/cm2/h): the skin permeation rate of dopamine hydrochloride (458 micrograms/cm2/h) was about 300 times higher than that of indomethacin. The water-soluble drugs with lower molecular weight and higher solubility in water showed higher skin permeation rates. These results suggest that some water-soluble drugs with low molecular weight and high solubility in water might be good candidates for transdermal drug delivery.

Animals↗
PubMed1989

[Neuroleptic properties of Y-20024, a new benzofurancarboxamide derivative].

N-[(1-butyl-2-pyrrolidinyl)methyl]-2-methyl-5-sulfamoyl-2,3- dihydrobenzofuran-7-carboxamide hydrochloride (Y-20024) was synthesized in our laboratories in anticipation of developing a new psychotropic drug. In the present study, the pharmacological properties of Y-20024 were compared with those of sulpiride (SPR) and haloperidol (HPD). Administered orally, Y-20024 was 10 times stronger than SPR in inhibiting apomorphine (0.5 mg/kg, s.c.)-induced hyperactivity in mice; administered intravenously or intracerebroventricularly, it was 2 times or one third as strong, respectively. Y-20024 was almost equipotent to SPR in antagonizing apomorphine (0.1 mg/kg, s.c.)-induced vomiting in dogs. Combined with methamphetamine (5 mg/kg, i.p.), Y-20024 and SPR induced mortality dose-dependently in rats, but HPD did not. The mammotropic activity of Y-20024 administered orally once a day for 5 days was almost equipotent to that of SPR. From these results, Y-20024, pharmacologically similar to SPR, but superior in bioavailability and penetration through the blood brain barrier, may have potential usefulness as an antipsychotic drug.

Animals↗
PubMed1989

[Study on transdermal absorption of borneol-salicylic acid eutectic mixture].

Borneol is an organic drug having property to form eutectic mixture with salicylic acid. We compared the transdermal absorption rate of borneol alone with that of borneol-salicylic acid eutectic mixture in hairless rats. The results showed that the borneol-salicylic acid eutectic mixture can evidently increase the absorption rate of borneol and provided a method for manufacturing borneol preparation which can easily be absorbed transdermally.

Animals↗
PubMed1989

Percutaneous absorption enhancer applied to membrane permeation-controlled transdermal delivery of nicardipine hydrochloride.

In the design of nicardipine hydrochloride-transdermal delivery systems (NC-TDS), the enhancing and regulating effects of penetration-enhancers and permeation controlling membranes were evaluated. Laurocapram (Azone) was selected as a model enhancer. Since its enhancing effect is considered to occur in the stratum corneum, its release from ethylene-vinyl acetate copolymers (EVAc), ethylene-vinyl alcohol copolymers (EVAl) or poly(2-hydroxyethylmethacrylate) (pHEMA) membranes was used as a criterion for membrane selection. The release rate was highest from pHEMA. Accordingly, a TDS consisting of a NC reservoir containing 1 w/v% Azone and a pHEMA membrane was prepared, and the effect of skin stripping on the plasma concentration of NC after NC-TDS administration was evaluated in rats. The increased ratio in drug plasma concentration caused by skin stripping was lower when the NC-TDS treatment was compared with a non-regulating NC-gel treatment. Our results suggest that the membrane permeation-controlled TDS of NC may be useful for long-term constant drug delivery with minimum dependence on skin conditions.

Administration, Cutaneous↗
PubMed1989

[Acute and chronic effects of a new oral inotropic agent, ibopamine hydrochloride, on hemodynamic and metabolic responses to ergometer exercise in patients with severe congestive heart failure].

The hemodynamic and metabolic effects of ibopamine, an orally active 3,4-diisobutylic ester of N-methyl-dopamine, at rest and during exercise, were evaluated in 8 patients with severe congestive heart failure, initially at 2 hrs after oral 100 mg and after 4 weeks of maintenance therapy (100 mg, 3 times a day). At rest, a single dose of ibopamine increased CI, SVI and SWI, and reduced PCWP, PAm, RA and PVR. These beneficial hemodynamic effects were maintained during supine bicycle exercise: CI and SVI increased markedly (p less than 0.05) and PCWP, PAm, RA and SVR increased at a lower extent (p less than 0.05) after ibopamine than on control conditions. After chronic therapy with the drug, LVDd and CTR decreased (p less than 0.05) and exercise tolerance time increased (p less than 0.01). HR, BPm, double product, norepinephrine, epinephrine, renin activity, aldosterone and lactate/pyruvate did not change significantly after administration of ibopamine. Clinical responses after 4 weeks of maintenance therapy were good in 4 cases and fair in 1 case. No adverse effects were observed. Therefore, ibopamine seems to have not only a positive inotropic action, but also a potent vasodilating action, leading to both afterload and preload reduction and so to be useful for the treatment of severe congestive heart failure at rest and during exercise after acute and chronic therapy with the drug.

Administration, Oral↗
PubMed1989

Characterization of very low density lipoprotein from Watanabe heritable hyperlipidemic rabbits.

We investigated the properties of very low density lipoprotein (VLDL) from two types of Watanabe heritable hyperlipidemic (WHHL) rabbits: one with a high incidence of coronary atherosclerosis (type 1), and the other with a low incidence (type 2). When incubated with mouse peritoneal macrophages, VLDL from type 1 WHHL rabbit (type 1-VLDL) stimulated cholesteryl ester synthesis 10.5-fold more than VLDL from the type 2 WHHL rabbit (type 2-VLDL) did. Moreover, a similar difference was seen in the stimulation of cholesteryl ester synthesis in peritoneal macrophages isolated from the WHHL rabbits. The mass ratios of cholesterol to protein in type 1- and type 2-VLDL were 5.69 and 2.05, respectively. Agarose gel electrophoresis of type 1-VLDL showed beta mobility, and that of type 2-VLDL showed pre-beta mobility. No difference was seen between the sizes of VLDL particles of the two types. The amount of apolipoprotein E in type 1-VLDL was greater than that in type 2-VLDL. In conclusion, the difference between type 1 and type 2 WHHL rabbits is at least partly due to the presence in type 1 animals of VLDL particles rich in cholesteryl esters and apolipoprotein E, particles which are very similar to beta-VLDL in conformation.

Animals↗
PubMed1988

Molecular organization of a high molecular weight multi-protease complex from rat liver.

A latent multifunctional protease with a molecular weight of 722,000 to 760,000 purified from rat liver cytosol has been reported. This paper reports on the structure and subunit composition of the enzyme. Electron microscopy showed that the enzyme was a ring-shaped particle of 160(+/- 7) A diameter and 110(+/- 10) A height with a small hole of 10 to 30 A diameter (1 A = 0.1 nm). Small-angle X-ray scattering analysis indicated that the enzyme had a prolate ellipsoidal structure with an ellipsoid cavity in the center. The maximum dimension of the enzyme was estimated to be 210 A from a pair-distance distribution function. The radius of gyration obtained from a Guinier plot and the Stokes radius based on the ellipsoidal model were 66 A and 76 A, respectively. On two-dimensional gel electrophoresis, the purified enzyme separated into 13 to 15 characteristic components with molecular weights of 22,000 to 33,000 and isoelectric points of 4 to 9. These multiple components were not artifacts produced by limited proteolysis during purification of the enzyme, because the cell-free translation products in a reticulocyte lysate with poly(A)-mRNA of rat liver consisted of multiple components of similar sizes, and because peptide mapping analyses with lysylendopeptidase and V8 protease demonstrated clear differences in the primary structures of these components. The 13 main components were isolated from the purified enzyme by reverse-phase high performance liquid chromatography and shown to be non-identical. A model of the enzyme is proposed on the basis of these observations and previous physicochemical studies. Interestingly, the morphology of this protease is similar to that of the 16 to 22 S ring-shaped particles found in a variety of eukaryotic organisms. The structural similarity between this multi-protease complex and various reported subcellular particles is discussed.

Animals↗
PubMed1988

Complements in diabetes mellitus: activation of complement system evidenced by C3d elevation in IDDM.

To characterize insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM) in terms of the complement system, some components of the system as well as the related substances and indices were studied. CH50, C3, C4 and C3bINA significantly increased in both IDDM and NIDDM compared with non-diabetic healthy controls. ACH50 was also elevated in NIDDM, whereas it was similar in IDDM and controls. Besides, the serum concentration of C3d, a breakdown product of C3, was higher in IDDM than in NIDDM and healthy controls, but that in NIDDM did not differ significantly from the control. B1Hg1 was not different among IDDM, NIDDM and non-diabetic controls. These observations suggested that there is a high level of complements in both types of diabetes mellitus, but the complement activation seems to be much enhanced in IDDM compared with NIDDM.

Complement Activation↗
PubMed1988

Complements in non-insulin-dependent diabetes mellitus with complications.

A relation of the complement system to the development of complications in non-insulin-dependent diabetes mellitus (NIDDM) was evaluated by measuring some components of the complement system. CH50, C3, C4 and C3bINA were significantly elevated in subjects with NIDDM as compared with healthy non-diabetic controls. However, CH50 and C3 did not differ between diabetics with and without complications. C4 was higher in diabetics with retinopathy as well as with retinopathy and neuropathy than in diabetics without these complications. ACH50, beta 1Hg1 and C3d were similar in subjects with NIDDM and non-diabetics, and not associated with complications of NIDDM. C3d/C3 in NIDDM without complications was lower than in healthy subjects, but did not significantly differ between the types of complications. These results suggest that the high level of complements in NIDDM might be due to enhanced production of complements and the development of diabetic complications would be related to the elevated level of complements.

Complement System Proteins↗
PubMed1988

Dynamic relationship between urea and glutamine synthesis in the mechanism of ammonia detoxication: a tracer study using 15NH4Cl in fulminant hepatic failure rats.

Fulminant hepatic failure (FHF) was produced in rats with intraperitoneal injection of D-galactosamine. 15NH4Cl (50 mg/kg of body weight) was injected into the rats via the tail vein. Arterial blood was drawn before and 5, 15, 30, 60 min after the injection of 15NH4Cl. 15N-ammonia, -urea, and -glutamine (amide and amino) were determined by gas chromatography and mass spectrometry. The plasma 15N-ammonia level was higher but decreased more rapidly in the FHF rats than in the control rats. This suggests that in FHF rats, the systemic vascular pool of ammonia is enlarged and ammonia clearance from blood is increased. The incorporation of 15N into urea was significantly different between the two groups. In FHF rats, the plasma urea-15N level rose 5 min after the injection, decreased at 15 min and was elevated again up to 60 min after injection. This biphasic change suggests that in FHF rats the incorporation of 15N into the extrahepatic glutamine pool is accelerated up to 15 min and that after 30 min a larger volume of glutamine-amide-15N is transferred to the urea cycle.

Ammonia↗
PubMed1988

Crystallization and preliminary X-ray studies on human epidermal growth factor.

Single crystals of human epidermal growth factor have been prepared from a polyethylene glycol solution and characterized by X-ray diffraction. The crystals grow in a space group of P2(1) with unit cell dimensions of a = 32.7, b = 32.5, c = 22.3 A, and beta = 96.9 degrees. They contain a single molecule per asymmetric unit and show better diffraction than 2.5 A.

Crystallization↗
PubMed1988

Studies on metabolic pathways of cyanate in rats.

Metabolic pathways of cyanate in rats were studied by means of measurements of cyanate, carbamyl phosphate and S-carbamyl group. Approximately 30-50% of cyanate administered to rats (0.5 mmol/kg body weight) was found in buffered gastric contents, and was also detected as ammonia liberated by acid hydrolysis. However, the gastric excretion of cyanate was a temporary phenomenon just after cyanate administration. Biliary and urinary excretion of cyanate and acid-soluble S-carbamyl group are minor metabolic pathways.

Animals↗