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Biomedical subjects

Y Morimoto

Publications and source records attributed to Y Morimoto.

At least 397 records · Page 22Linked to original sources
PubMed1990

[Studies on the synthesis of condensed pyridazine derivatives. II. Synthesis and anxiolytic activities of 2-aryl-4,4a,5,6-tetrahydropyridazino[4,3-c]quinolin-3(2H)-ones, 2-aryl-4a,5-dihydro-2H-(1)benzothiopyrano[4,3-c]pyridazin-3(4H)-ones, and related compounds].

A series of 2-aryl-4,4a,5,6-tetrahydropyridazino[4,3-c]quinolin-3(2H)- ones, 2-aryl-4a,5-dihydro-2H-(1)benzothiopyrano[4,3-c]pyridazin-3( 4H)-ones, and related compounds were synthesized and tested for their ability to displace [3H]diazepam from rat brain membranes in vitro, and to prevent bicuculline-induced convulsions in mice in vivo. Among them, 2-(4-chlorophenyl)-4a,5-dihydro-2H-(1)benzothiopyrano[4,3-c]pyr idazin-3(4H)- one (16b) showed remarkable activities both in vitro (Ki 48 nM) and in vivo (ED50 12.4 mg/kg, p.o.). The trans sulfoxide (19a) of 16b exhibited anxioselective pharmacological activities. Compound 19a was equipotent with diazepam in the anticonflict assay (Vogel type, rat, MED 10 mg/kg, p.o.) while exhibiting reduced muscle relaxation (rotarod test) and narcotic potentiation. The structure-activity relationships are discussed.

Animals↗
PubMed1990

[Effect of Y-516 on the hyperactivity induced by dopamine injected bilaterally into the nucleus accumbens].

The effect of Y-516 on the hyperactivity induced by dopamine injected bilaterally into the nucleus accumbens was compared with those of clocapramine (CCP), haloperidol (HPD) and chlorpromazine (CPZ). Dopamine (5-50 micrograms) injected into the nucleus accumbens induced a dose-dependent hyperactivity following pretreatment with nialamide (100 mg/kg, i.p., 2 hr). The hyperactivity induced by 10 micrograms of dopamine was antagonized by the i.p. administration of Y-516 (0.5-1.0 mg/kg), CCP (5-25 mg/kg), HPD (0.05-0.5 mg/kg) and CPZ (1-5 mg/kg) in a dose-dependent manner. The ED50 values of Y-516, CCP, HPD and CPZ were 0.85, 16.5, 0.098 and 2.53 mg/kg, respectively. These results suggest that Y-516 has a potential inhibitory effect on the mesolimbic dopaminergic system and may be a beneficial neuroleptic drugs.

Animals↗
PubMed1990

Effect of monoglycerides on the percutaneous absorption of papaverine hydrochloride.

The skin permeation enhancement of papaverine hydrochloride by free fatty acids (C3-C12), monoglycerides (side chains C5-C12) and caprylic acid (C8) esters was evaluated using the excised hairless rat skin. Enhancement was marked in the case of glyceryl monocaprylate; the cumulative amount of papaverine that permeated through skin over 28 hours from an aqueous suspension was 29.7 mg/cm2 with, and 26.9 micrograms/cm2 without glyceryl monocaprylate. The mechanism of enhancement was studied by measuring the effect the enhancers had on the diffusion and partition parameters of papaverine. Free fatty acids mainly affected the drug's diffusion, and monoglycerides mainly affected the drug's partition. For monoglyceride enhancers, a good linear relationship between the flux of papaverine and the amount of enhancer in skin was established. n-Octanol-water partition coefficients (log Pcal) of the enhancers were selected as indicators of their physicochemical properties, and related to their penetration-enhancing abilities. A parabolic relationship was found between the log of the flux of papaverine and log Pcal, for all types of enhancers. The relationship may be a good indicator in predicting enhancing effects.

1-Octanol↗
PubMed1990

[A successful surgical repair of ventricular septal perforation following acute myocardial infarction in a 83-year-old man].

A 83-year-old man, who experienced a sudden severe malacia 13 days before, was admitted, complaining of dyspnea since 8 hours before. A loud systolic murmur of Levine IV/VI was audible on the left sternal border of the 4th intercostal space. The chest X-ray film demonstrated severe pulmonary congestion. The ECG showed abnormal Q waves in II, III, a VF and V1-5. The right heart catheterization revealed an intraventricular shunt from left to right and thus ventricular septal perforation (VSP) 13 days after acute anteroseptal-inferior myocardial infarction was diagnosed. Continuing an aggressive medical treatment with the intraaortic balloon pumping, an emergency operation for VSP was performed 2 days after the onset. A single Teflon patch was sutured on the left side of the septum around VSP (2.5 x 2.5 cm) and the ventricular free wall was closed including the patch with two felt strips. The patient survived through the operation and is doing well at the 11 months of follow-up. Twenty patients above 70 years old have been surgically treated with success for VSP after acute myocardial infarction in Japan. Our patient was the oldest.

Aged↗
PubMed1990

[A case report of traumatic transection of the aortic arch].

A 16-year-old male, who sustained a blunt chest trauma in a traffic accident, was brought into the emergency room in an unconscious state, with an initial systolic blood pressure of 80 mmHg. He was found to have multiple fractures and a flail chest. The initial roentgenogram of the chest showed widening of the mediastinum. An emergency aortogram demonstrated intimal flap and aneurysmal dilatation of the aortic arch. Because of a coexisting severe contusion of the lung, operation was postponed until 15 days after admission. He was successfully treated by direct repair under profound hypothermia and circulatory arrest, which was induced by surface cooling in combination with ECC. Postoperatively he did well and 23 days after the operation, surgical repair of femoral and humeral fractures was performed by orthopedists.

Adolescent↗
PubMed1990

[Effects of lidocaine and its metabolite, monoethylglycine xylidide (MEGX), on transmembrane action potentials in guinea-pig papillary muscles].

Effects of lidocaine 5, 10, 20 micrograms.ml-1 and its metabolite, MEGX 5, 10, 20 micrograms.ml-1, on transmembrane action potentials were studied in isolated guinea-pig papillary muscles, perfused with modified Tyrode's solution. The basic driving rate was 1 Hz and the rate was changed from 1 Hz to 0.25, 0.5, 2, 3 and 4 Hz in a stepwise manner. Both lidocaine and MEGX produced dose- and rate-dependent depression of maximum rate of rise of action potential (Vmax) without significant changes in resting membrane potentials. The recovery kinetics of Vmax was studied by either applying premature stimuli at basic driving rate of 0.25 Hz or by stopping the basic driving of 1 Hz for 1s to 60s. A slow component (time constant: 176-206 ms for lidocaine, 300-340 ms for MEGX) was observed in premature response. And a slower component (time constant: 3-4s for MEGX) was observed in the first response after stopping stimulation. Both drugs shortened the action potential duration. These results suggest that MEGX has a lidocaine-like class I antiarrhythmic actions and that it might modify the actions of lidocaine especially in patients with elevated plasma MEGX concentration.

Action Potentials↗
PubMed1989

Target antigen of islet cell antibody in Japanese insulin-dependent diabetes mellitus.

The target antigens of islet cell antibody (ICA) have not been clarified. We tried to modify the antigen in human pancreatic tissues and characterize the ICA with immunohistochemical methods. Human pancreatic tissues were treated with periodate (A), borohydride (B), neuraminidase (C), methanol (D), chloroform-methanol (E), or protease (F) to modify the antigens, and stained by an immunofluorescent method using ICA-positive sera from five Japanese insulin-dependent diabetes mellitus (IDDM) patients. In all sera the fluorescence of islets disappeared or waned after A, C, D, and E, and did not change after F. The disappearance or loss of fluorescence induced by A was recovered after B. It is, therefore, suggested that one of the antigens of ICA in Japanese IDDM patients is the sialic acid residue of glycolipid.

Adolescent↗
PubMed1989

Effect of dimethylthiourea on syngeneic rodent islet transplantation.

We studied the effects of a hydroxyl radical scavenger, dimethylthiourea (DMTU), on syngeneic islet grafts. Six hundred fresh islets taken from two Wistar rats were transplanted intraportally into other Wistar rats made diabetic with streptozotocin. DMTU was given to five recipients intraperitoneally for a month while nine controls received only intraperitoneal saline. The DMTU-treated group had significantly lower fasting plasma glucose levels at 1.5, 4.5, 5, 5.5, 6, 7, 9 and 11 weeks and had higher mean fasting body weights between the 2.5th week and their eventual sacrifice. Their islets also survived significantly longer than did those of the controls (73.6 +/- 3.4 vs. 21.6 +/- 9.4 days). This suggests that oxygen free radical production endangers graft survival and that the hydroxyl radical scavenger DMTU protects syngeneic islet grafts.

Animals↗
PubMed1989

A case of giant cell interstitial pneumonia.

This report is of a case of giant cell interstitial pneumonia (GIP) diagnosed by transbronchial lung biopsy (TBLB) and treated effectively with corticosteroid. The patient was a 61-year-old man with cough, dyspnea and findings of diffuse reticular opacities on chest X-ray. In the microscopic section of a biopsied specimen, varied forms of giant cells were observed, some with a cannibalistic appearance. Numerous giant cells and some lymphocytes were also observed in the bronchoalveolar lavage fluid. The possibility of measles pneumonia was ruled out by a negative serum antibody test and the absence of inclusion bodies in the giant cells. The patient had neither a past history of exposure to heavy metals nor to organic dusts. A distinct improvement was obtained with 30 mg of prednisolone administered daily for two weeks and then tapered off gradually.

Biopsy↗
PubMed1989

The presence of islet cell antibodies in malnutrition-related diabetes mellitus.

The etiology of malnutrition-related diabetes mellitus (MRDM), mostly seen in the developing countries, is still unknown, though an excessive consumption of cassava and a low intake of protein are considered to be its causative factors. Previous immunological studies, though rarely performed, have so far, to our knowledge, shown no case of MRDM with iselt cell antibodies (ICA). We found a 16-year-old MRDM boy with ICA and report on this in the present communication.

Adolescent↗
PubMed1989

Stabilizing effects of some amino acids on membranes of rabbit erythrocytes perturbed by chlorpromazine.

Hemolysis experiments indicated that glycine (20 mM) remarkably suppressed the chlorpromazine (CPZ)-induced osmotic permeability enhancing effect in rabbit erythrocytes. Lysine and aspartic acid also showed a similar protecting effect at the same concentration. Thus, the acid-base properties of amino acids were not a determining factor in stabilizing the cell membranes perturbed by CPZ. These results suggest that amino acids stabilize the membranes of the erythrocytes by inhibiting the osmotic water transfer from the outside to the inside of the cells. The kinetic studies in isotonic suspensions of erythrocytes indicated that glycine decreased the hemolytic activity of CPZ, and it was suggested that glycine molecules possibly inhibited penetration of CPZ into the cell membranes. The data also showed that the membrane stabilizing action of glycine was not affected by the dissociation of CPZ molecules. The degree of dissociation of glycine molecules was not found to be related to the degree of the protection. The FT-IR spectroscopy data indicated that glycine made the acyl chains of the liposome perturbed by CPZ more orderly.

Amino Acids↗
PubMed1989

Type-specific antigen of Streptococcus rattus strains (KAY1 and FA1). I. Characterization.

A serotype-specific antigen was extracted from Streptococcus rattus KAY1 strain isolated first in Japan from human dental plaque and purified on an ion exchange column to compare it chemically and immunologically with that of FA1 strain which had been examined extensively by previous workers. Antigens of both strains reacted in a double diffusion test specifically with anti-FA1 serum which had previously been demonstrated specific for the strains in the same test, agglutination reactions and/or radioimmunoassay using whole cells. After separation on a DEAE-Sephadex A-25 ion exchange column the antigen was found to be resistant to various enzymatic treatments with pronases, lipase and nucleases and produce a single precipitin band against absorbed anti-FA1 serum in immunoelectrophoresis. Chemical analysis of this antigen revealed that it composed of carbohydrate, protein and a few percentages of glycerol and phosphorus. Hapten inhibition tests between antigen and antibody showed that galactose as well as glucose were the most potent inhibitors, suggesting their involvement in the antigenic determinant. Involvement of the sugars was also supported by gas chromatographic analysis and abolishment of reactivity with antiserum after the treatment of antigens with NaIO4. Moreover, protein does not seem to be involved since after SDS-PAGE analysis an enzyme immunoassay gave a negative reaction with immunoblotted antigens.

Antigens, Bacterial↗
PubMed1989

Utility of topical formulations of morphine hydrochloride containing azone and N-methyl-2-pyrrolidone.

In order to develop the transdermal formulations of morphine hydrochloride with high skin permeation rate and prolonged action, several gels and patches containing potent penetration enhancer, laurocapram (Azone), were prepared. Since there was a long lag time period for morphine permeation through the excised hairless rat skin in Azone treatment, N-methyl-2-pyrrolidone was added to the Azone gel or patch as a co-enhancer to increase the skin permeation of morphine hydrochloride, especially in the early phase. The mixed solvent of N-methyl-2-pyrrolidone and water showed cosolvency of morphine hydrochloride, and the co-enhancer could shorten the lag time period of skin permeation of morphine hydrochloride. However, the co-enhancer alone had little effect on the skin permeation of morphine hydrochloride. It was effective only when using with Azone. Coadministration of Azone with the co-enhancer showed high in vitro skin permeation and in vivo blood level of the drug. A marked analgesic effect was found after application of morphine hydrochloride patch containing Azone and N-methyl-2-pyrrolidone. The pharmacological effect was much more prolonged than that after the conventional s.c. injection. From these results, it was predicted that the topical formulations of morphine hydrochloride containing Azone and N-methyl-2-pyrrolidone might be useful for the relief of severe chronic pain in patients.

Administration, Topical↗
PubMed1989

Prediction of the in-vitro human skin permeability of nicorandil from animal data.

A method for estimating the in-vitro permeability of human skin to drugs, based on in-vitro permeation studies using animal skins, has been developed. The skins from hairless rats, guinea-pigs, dogs and pigs were used, with nicorandil and deionized water as model drug and solvent in a drug-donor compartment. Diffusion coefficients through the skin barrier, D, and partition coefficients from the drug-donor compartment to skin, K, of the drug, in each species, were calculated by curve-fitting the in-vitro permeation data to a diffusion equation describing the drug permeation through a homogeneous membrane, using a non-linear least squares method. Each barrier thickness, L, was measured microscopically from microtomed skin sections. A positive relationship was found between the skin permeability, Kp, and K value among the four species, but species differences in the D and L values were small in spite of the Kp values being different among the four species. A positive correlation was also observed between the calculated and experimental K values among the four species, and hence it was suggested that the main factor for the species difference in the skin permeability of nicorandil would be the difference in partitioning of the drug from vehicle to stratum corneum. As a result, it has become feasible to predict and estimate skin permeability of nicorandil in humans by substituting each parameter, extrapolated from the animal skin permeation data and partition experiments, in the diffusion equation.

Animals↗
PubMed1989

Effect of several enhancers on the skin permeation of water-soluble drugs.

Since the percutaneous absorption rates of water-soluble drugs are low in general, an enhancing system is needed when using the skin as an administration site for the drugs. We have investigated the effect of various penetration enhancers on the in vitro and in vivo percutaneous absorptions of catecholamine analogs, i.e. levodopa (LD), dopamine hydrochloride (DPH) and isoproterenol hydrochloride (IPH), as model water-soluble drugs. It was found that medium-chain glycerides (Sefsol 318) markedly enhanced the in vitro permeation of the drugs through excised hairless rat skin among the enhancers tested in the present experiments; the permeation rates with 5% Sefsol 318 in water were about 65, 34 and 53 times higher than the corresponding control (without enhancer) for LD, DPH and IPH, respectively. In addition, the in vivo percutaneous absorption experiments showed that the blood levels of these drugs after application of aqueous gels containing 5% Sefsol 318 on rat skin were higher than those in the absence of enhancer. Drug levels in the liver and kidney were also higher than without Sefsol 318. Percutaneous administration of DPH with Sefsol 318 to hairless rats resulted in lower diastolic blood pressure and a slightly higher heart rate with as compared to administration without the enhancer. These results suggest that Sefsol 318 is a potential candidate to enhance the transdermal absorption of water-soluble drugs.

Animals↗