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S Yasuda

Publications and source records attributed to S Yasuda.

At least 181 records · Page 10Linked to original sources
PubMed1997

Severe diastolic dysfunction with preserved energy conversion efficiency after countershock.

The left ventricular (LV) mechanical performance and the LV myocardial oxygen consumption (VO2)-to-pressure-volume area (PVA; LV total mechanical energy index) relationship were measured in isovolumic contraction of isolated blood-perfused dog hearts before and after direct current (DC) countershocks. At a constant LV volume, DC shocks increased LV end-diastolic pressure progressively and strikingly with the progression of myocardial edema and a marked prolongation of the time constant of LV pressure decay. In contrast, DC shocks changed neither the slope of the LV end-systolic pressure-volume relationship nor the contractile efficiency (the slope of the Vo2-PVA relationship). The oxygen cost of contractility (the slope of the relationship between PVA-independent VO2 and LV contractility) increased 27% after DC shocks. However, the magnitude of this change was considerably smaller than that previously reported in postischemic stunned myocardium (123%), suggesting that the adverse effect of DC shocks on the energy cost of excitation-contraction coupling is relatively minor. Thus, despite the severe diastolic dysfunction, DC shocks do not substantially impair either the efficiency of cross-bridge cycling or calcium cycling. Myocardial interstitial edema is more likely a potential mechanism of diastolic dysfunction after DC shocks.

Animals↗
PubMed1997

Endothelin-1 ameliorates contractile depression by lipopolysaccharide in cardiac myocytes.

Lipopolysaccharide (LPS) induces cardiac depression by activating nitric oxide pathways to increase guanosine 3',5'-cyclic monophosphate (cGMP), a second messenger of nitric oxide. Endothelin-1 (ET-1) may interact with nitric oxide pathways. We hypothesized that ET-1 modulates LPS-induced contractile depression in cardiac myocytes. Adult rabbit cardiac myocytes exposed to LPS (10 ng/ml) developed decreased cell shortening after 6 h, with an increase in cardiac cGMP levels [606 +/- 36 (SE) fmol/mg protein] compared with control myocytes (360 +/- 26 fmol/mg protein, P < 0.05). LPS effects were completely blocked by coincubation with the nitric oxide synthase inhibitor NG-monomethyl-L-arginine (1 mM). Coincubation with ET-1 (10 nM) attenuated the contractile depression and increase in cGMP with LPS (482 +/- 28 fmol/mg protein, P < 0.05 vs. LPS alone). ET-1 alone did not alter cGMP levels (350 +/- 30 fmol/mg protein). ET-1 effects on contractile function were blocked by BQ-123 (10 microM), a selective ET-1 type A receptor antagonist. We conclude that ET-1 ameliorates LPS-induced contractile depression in cardiac myocytes by attenuating LPS effects on nitric oxide-cGMP pathways.

Animals↗
PubMed1997

Lipopolysaccharide depresses cardiac contractility and beta-adrenergic contractile response by decreasing myofilament response to Ca2+ in cardiac myocytes.

Lipopolysaccharide (LPS) plays a key role in the pathogenesis of sepsis. Cardiac function and the inotropic response to beta-adrenergic stimulation are impaired in sepsis. We hypothesized that LPS, in clinically relevant levels (1 ng/mL), directly depresses contractility and beta-adrenergic responses in cardiac myocytes. Cardiac myocytes were isolated from the left ventricle of adult rabbits using digestive enzymes (collagenase and protease). We depyrogenated the enzymes (LPS contamination lowered from 100 to 300 ng/mL to < 0.7 ng/mL) to minimize development of LPS tolerance during cell isolation. After 6 hours of incubation with 1 ng/mL LPS, there was a decrease in the extent of active cell shortening with no change in Ca2+ transients (measured with indo 1 fluorescence), indicating decreased myofilament responsiveness to Ca2+. This was related to NO pathways, since cGMP (a second messenger of NO) increased in cardiac myocytes and LPS effects were completely reversed with a 1 mmol/L NG-monomethyl-L-arginine (L-NMMA, a NO synthase inhibitor). LPS did not alter the intracellular Ca2+ response to beta-adrenergic stimulation with isoproterenol but attenuated the contractile response (maximal cell shortening, 15.5 +/- 1.0% versus 23.3 +/- 1.1% in control myocytes; P < .001). LPS attenuation of the contractile response to isoproterenol was restored completely by L-NMMA and almost completely restored (to 86% of the control response) by an inhibitor of cGMP-dependent protein kinase. We conclude that LPS depresses cardiac contractility and the contractile response to beta-adrenergic stimulation by a NO-cGMP-mediated decrease in myofilament responsiveness to Ca2+. The direct effects of low levels of LPS on cardiac myocytes may contribute to cardiac depression and hemodynamic decompensation during sepsis.

Actin Cytoskeleton↗
PubMed1997

Synthesis and dual antagonistic activity against thromboxane A2 and leukotriene D4 of [4-[1-(benzenesulfonamido)alkyl]phenyl]alkanoic acid derivatives.

In order to find new antiasthmatic agents with dual antagonistic activity against thromboxane A2 (TXA2) and leukotriene D4 (LTD4) receptors, synthesis and pharmacological evaluation of various [4-[1-(benzenesulfonamido)-alkyl]phenyl]alkanoic acid derivatives were undertaken. TXA2 and LTD4 antagonistic activities in vitro were evaluated by measuring the inhibitory effects on L-46619-induced contraction of guinea-pig trachea and LTD4-induced contraction of guinea-pig ileum and trachea. Several compounds showed satisfactory dual antagonistic activities, and their effect (after oral administration) on LTD4-induced bronchoconstriction in guinea-pig in vivo was examined. The results demonstrated that both 4-[4-[1-(4-chlorobenzenesulfonamido)hexyl]phenyl]butyric acid (12e) and 4-[4-[1-(4-chlorobenzenesulfonamido)-5-methylhexyl]phenyl]bu tyric acid (12m) possessed good anti-LTD4 activities. Compounds 12e and 12m were then evaluated for other related pharmacological effects involving the arachidonic acid cascade. These compounds appear to be hybrid eicosanoids antagonists having antagonistic activity against contraction of guinea-pig trachea induced by prostaglandin D2 (PGD2) and PGF2 sigma, as well as TXA2 and LTD4 antagonistic activities.

Animals↗
PubMed1997

[Synthesis and dual antagonistic activity against thromboxane A2 and leukotriene D4 of benzenesulfonamide derivatives].

In order to find dual antagonists against both thromboxane A2 (TXA2) and leukotriene D4 (LTD4) receptors for a new antiasthmatic agent, various benzenesulfonamide derivatives were synthesized and evaluated for those pharmacological effects. TXA2 and LTD4 antagonistic activities in vitro were evaluated by the inhibitory effects on LTD4-induced and U-46619-induced contraction of guinea-pig trachea. Furthermore, TXA2 and LTD4 antagonistic activities in vivo were evaluated by the inhibitory effects on LTD4-induced and U-46619-induced bronchoconstriction of guinea-pig after oral administration of test compounds. It was found that 4-[5-[1-(4-chlorobenzenesulfonamido)-5-methylhexyl]-2-thi eny l]butyric acid and 4-[5-[1-(4-fluorobenzenesulfonamido)-5-methyl-hexyl]-2-thienyl]but yric acid possess good anti-LTD4 and anti-TXA2 activities by oral administration.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1997

Spectroscopic analysis of the cytoagglutinating activity of abrin-b isolated from Abrus precatorius seeds against leukemic cells.

The cytoagglutinating activity of abrin-b, a toxic lectin isolated from Abrus precatorius seeds, against cultured cell strains derived from acute lymphoblast leukemia (ALL) was investigated by visible (VIS) spectroscopy. Upon addition of abrin-b, the turbidity at 600 nm of cell suspension decreased and this change could be recorded as the cytoagglutination curve. From this curve, the cytoagglutination velocity (CV) and cytoagglutination intensity (CI) of each cell strain was measured. Each cell strain showed the respective CV and CI values and the cell strains derived from the T cell line were strongly agglutinated by abrin-b compared with those derived from the B cell line. Further, it has become apparent that the cytoagglutinating activity increased with an increase in the order of the differentiation of cell strains.

Abrin↗
PubMed1997

Mn-metalloporphyrin conjugated with Gd-DTPA (Gd-ATN10): tumor enhancement agent for magnetic resonance imaging.

A conjugate of manganese-metalloporphyrin and gadolinium (Gd)-diethylenetriaminepenta-acetic acid (Gd-ATN10) was developed as a tumor-specific enhancement agent for magnetic resonance (MR) imaging. Gd-ATN10 was evaluated in an experimental 9L gliosarcoma rat tumor model. T1-weighted MR imaging showed enhancement of the tumor which persisted for up to 24 hours. Gd concentration measurement by inductively coupled plasma atomic emission spectroscopy revealed the peak Gd concentration was reached after 30 minutes and Gd was retained in the blood and tumor up to 24 hours. There was no uptake of Gd in the normal brain and little in the skin. Gd-porphyrin derivatives are potentially useful agents for tumor diagnosis on MR imaging and for neutron capture therapy.

Animals↗
PubMed1997

[Acute subdural hemorrhage of arterial origin: report of three cases].

Three cases of acute subdural hematoma without head injury, but associated with bleeding from cortical artery are described. Case 1: a 74-year-old male had sudden headache during a bronchial asthma attack followed by deterioration of consciousness. He was deeply comatose on admission, and CT scans revealed a huge subdural hematoma. Evacuation of the large hematoma revealed a spurting cortical branch of the middle cerebral artery beneath it. Case 2: Four days before admission, a 69-year-old male developed headache during a fit of coughing. His CT scans on admission showed a thin subdural hematoma. Because it was increasing in volume, the hematoma was removed surgically. A spurting cortical branch of the middle cerebral artery was seen on the surface of the temporal lobe. Case 3: a 80-year-old male, who had had an operation for inguinal hernia under spinal anesthesia ten days before, suffered a sudden headache just after he stood up. CT scans revealed a thick subdural hematoma. As the clot was being removed a spurting artery was seen in the Sylvian region. In a review of 116 surgical cases of acute subdural hematoma at our institute, the incidence of acute spontaneous subdural hemorrhage was 2.6%. The etiology of nontraumatic hematoma is a matter of controversy. Our three cases suggested that the etiology might be the rupture of a cortical artery at the site of adhesion with the dura mater. This would predispose the artery to tearing with minor trauma. Hematoma evacuation by craniotomy and treatment of the ruptured cortical artery were necessary for favorable outcome.

Acute Disease↗
PubMed1997

[A case of liver metastasis of gastric leiomyosarcoma successfully treated by transarterial hepatic chemo-embolization and intra hepato-arterial chemotherapy repeated with infusion-a-port].

The patient was a 68-year-old male, who underwent total gastrectomy for giant leiomyosarcoma of the stomach and then had multiple hepatic metastases one year and six months later. Thus, transarterial hepatic chemo-embolization therapy with Lipiodol, adriamycin and gelfoam was given. Moreover, using a reservoir catheter and infusion arterial port, intermittent arterial infusion therapy with adriamycin, cyclophosphamide, and vincristine was attempted. In the metastasis lesion where there were rich blood vessels, Lipiodol was accumulated and the tumor was reduced on abdominal CT. The result indicated the efficacy of this treatment.

Aged↗
PubMed1996

The effects of pH on N-methacryloyl glycine primer on bond strength to acid-etched dentin.

To develop a more effective adhesive primer, it is imperative to understand the adhesion mechanisms of the resin to the demineralized dentin through a dentin primer. When the bonding agent was directly applied to the dentin etched by 40 wt % phosphoric acid without a primer pretreatment, the bond strength of the resin to the dentin was 5 MPa. Conversely, when the demineralized dentin was pretreated with the N-methacryloyl glycine (NM alpha A) primer solution with a pH value of 1.5, the bond strength increased considerably to 15 MPa. However, the bond strength dropped dramatically from 15 to 3 MPa when the sodium salt of NM alpha A was added, thereby increasing the pH value of the NM alpha A primer solution from 3.2 to 5.0. When the pH value was increased above 3.5 (pKa value), the number of ionized NM alpha A species increased in the solution. As a result, the bond strength of the resin fell to approximately 3 MPa. This result was obtained despite the 5-micron-thick hybrid layer that was created in the subsurface of the intertubular dentin. The number of unionized NM alpha A species increased by lowering the pH value below 3.5. As a result, the NM alpha A primer provided a higher bond strength of the resin to the demineralized dentin. In contrast, when 10 wt % citric acid containing 3 wt % ferric chloride was applied to the dentin, maximum bond strength was obtained when the pH value of the NM alpha A primer solution was 3.5. The pH dependency of the bond strength obtained following 10 wt % citric acid containing 3 wt % ferric chloride etching is different from the results obtained from 40 wt % phosphoric acid etching. This can be attributed to the difference in the characteristics of the demineralized collageous layer.

Acid Etching, Dental↗
PubMed1996

Endotoxin-induced cardiac depression is associated with decreased cardiac dihydropyridine receptors in rabbits.

Endotoxin depresses left ventricular (LV) contractility independently of alterations in loading conditions, acidosis, or hypoxia (Hung and Lew, 1993a). We evaluated if endotoxin-induced LV depression is associated with a decrease in functional L-type calcium channels, as reflected by the number of dihydropyridine receptors measured by [3H]-PN200-110 binding. New Zealand white rabbits were instrumented with sonomicrometers to measure the end-systolic pressure-volume relationship after i.v. saline (group 1, n = 6), 5 micrograms/kg endotoxin (group II, n = 6), or 10 micrograms/kg endotoxin (group III, n = 6). The end-systolic volume (ESV) measured at a matched end-systolic pressure did not change significantly over 6 h in group I (ESV changed by < 5 +/- 2% S.E.) and group II (ESV changed by < 3 +/- 2%), but increased markedly in group III (ESV increased 70 +/- 24%, P < 0.05), indicating LV systolic depression. We measured [3H]-PN200-110 binding in crude membrane homogenates from the left ventricle. There was a dose-dependent decrease in Bmax: 75 +/- 5 fmol/mg protein in group I, 62 +/- 3 fmol/mg in group II, and 56 +/- 5 fmol/mg in group III (P = 0.02 by ANOVA). Since the majority of dihydropyridine receptors are functional L-type calcium channels in rabbits (Lew et al., 1991), we conclude that a decreased number of dihydropyridine receptors contributes to endotoxin-induced LV depression.

Animals↗
PubMed1996

Coronary angioplasty ameliorates hypoperfusion-induced endothelial dysfunction in patients with stable angina pectoris.

OBJECTIVES: This study sought to investigate the effect of coronary angioplasty on chronic hypoperfusion-induced endothelial dysfunction in patients with coronary heart disease. BACKGROUND: The endothelium is an important component for organ flow regulation. Ischemia with or without reperfusion is known to cause endothelial dysfunction. We tested the hypothesis that chronic hypoperfusion impairs endothelial function in the angiographically normal coronary artery segment distal to stenosis and that the impairment by chronic hypoperfusion is reduced by coronary angioplasty. METHODS: In 13 patients with stable angina pectoris, substance P (10, 30 and 100 pmol) and nitroglycerin (200 micrograms) were sequentially infused into the coronary artery in a cumulative manner on the day after coronary angioplasty. In 10 of these patients, vascular responses to these agents were again investigated 3 months after angioplasty. Changes in vascular diameter were evaluated in vessels located proximal and distal to the target lesion, both of which were angiographically normal, by performing computer-assisted quantitative coronary angiography. In five patients, the transstenotic pressure gradient was also measured with a pressure sensor-mounted guide wire before angioplasty. RESULTS: On the day after angioplasty, the magnitude of dilation by substance P in distal segments was significantly less than that in proximal segments and inversely correlated with the transstenotic pressure gradient (p < 0.05) and lesion stenosis (p < 0.05). There was no difference in nitroglycerin-induced vasodilation between the two vessel segment groups. Three months later, the impaired response to substance P in the distal segment was restored to normal. CONCLUSIONS: We conclude that chronic hypoperfusion impairs endothelium-dependent dilation of coronary artery distal to critical stenosis in patients with ischemic heart disease and that coronary angioplasty ameliorates the endothelial dysfunction within 3 months.

Aged↗
PubMed1996

Protective effects of ME3221 on hypertensive complications and lifespan in salt-loaded stroke-prone spontaneously hypertensive rats.

1. A comparison was made on the protective effects of the following: ME3221, a competitive angiotensin AT1 receptor antagonist; losartan, in which a major active metabolite is a non-competitive angiotensin AT1 receptor antagonist; and enalapril, an angiotensin-converting enzyme inhibitor, using the salt-loaded stroke-prone spontaneously hypertensive rats (SHRSP). 2. SHRSP received orally ME3221 (3 and 10 mg/kg per day), losartan (10 mg/kg per day) and enalapril (10 mg/kg per day) from the 6th to the 20th week of age. All the control rats showed rapid elevation of systolic blood pressure (SBP), accompanied by hypertensive complications, and died by 15 weeks of age. 3. ME3221, losartan and enalapril suppressed the elevation of SBP in the salt-loaded SHRSP to a comparable degree. ME3221 and losartan increased the survival rate to > 90%, and diminished hypertensive complications such as cerebral apoplexy (stroke), renal injury (increased proteinuria, and total N-acetyl-beta-D-glucosaminidase activity) and heart failure (cardiac hypertrophy and pleural effusion). 4. Competitive (ME3221) and non-competitive (losartan) angiotensin AT1 receptor antagonists showed comparable efficacy against the complications and mortality of the salt-loaded SHRSP; both were more potent than enalapril in the protective effect.

Angiotensin Receptor Antagonists↗
PubMed1996

Studies on quinolone antibacterials. IV. Structure-activity relationships of antibacterial activity and side effects for 5- or 8-substituted and 5,8-disubstituted-7-(3-amino-1-pyrrolidinyl)-1-cyclopropyl-1, 4-dihydro-4-oxoquinoline-3-carboxylic acids.

A series of 7-(3-amino-1-pyrrolidinyl)-1-cyclopropyl-1,4-dihydro-4- oxoquinoline-3-carboxylic acids bearing various substituents (H, F, C1, Me, OH, OMe, OEt, OCH2F, OCHF2, OCF3, SMe) at the C-8 position was prepared and evaluated for in vitro antibacterial activity against both standard laboratory strains and bacteria resistant to quinolones such as ciprofloxacin (CPFX, 1) and ofloxacin (OFLX, 2) from clinical isolates. The 8-methyl (8a), 8-fluoro (9a), 8-chloro (10a) and 8-methoxy (12a) compounds were 4 times more potent than CPFX (1) against both gram-positive and gram-negative bacteria. But these four compounds caused injury to the chromosomes of mammalian cells at a concentration of 100 micrograms/ml. Next, a series of quinolones having various substituents (H, C1, Me, NH2, NHMe, NMe2) at the C-5 position was prepared and evaluated for antibacterial activity and injurious effect on the chromosome. We found that the 5-amino-8-methyl compound (8d) showed strong antibacterial activity (in vitro antibacterial activity of 8d is 4 times more potent than that of CPFX (1) against both gram-positive and gram-negative bacteria), reduced injury to the chromosome, and reduced quinolone-type toxicity (free from both phototoxicity at a dosage of 30 mg/kg in guinea pigs (i.v.) and convulsion-inducing activity when coadministered with fenbufen at dosage of 100 mg/kg in mice (i.p.)).

4-Quinolones↗
PubMed1996

Studies on quinolone antibacterials. V. Synthesis and antibacterial activity of chiral 5-amino-7-(4-substituted-3-amino-1-pyrrolidinyl)-6- fluoro-1,4-dihydro-8-methyl-4-oxoquinoline-3-carboxylic acids and derivatives.

We previously demonstrated that 5-amino-7-(3-amino-1-pyrrolidinyl) -1-cyclopropyl-1,4-dihydro-8-methyl-4-oxoquinoline-3-carboxylic acid (7) has strong in vitro antibacterial activity even against quinolone-resistant bacteria. We examined optimization of the 3-aminopyrrolidine moiety of 7 by introduction of C-alkyl (Me, Et, Pr, di-Me, cyclopropyl) and N-alkyl groups (Me, di-Me). C-Alkylation at the 4-position of the 3-aminopyrrolidine moiety enhanced in vitro and in vivo antibacterial activity. (S)-5-Amino-7-(7-amino-5-azaspiro[2.4]hept-5-yl)-1-cyclopropyl-pyr rolidinyl) -1-cyclopropyl-6-fluoro-1,4-dihydro-8-methyl-4-oxoquinoline-3-carboxylic acid (15b) showed strong antibacterial activity (in vitro antibacterial activity including quinolone-resistant bacteria is 4 times more potent than that of ciprofloxacin (CPFX) (1); in vivo antibacterial activity is 1.5 to 20 times more potent than that of CPFX (1)) and reduced quinolone toxicity (free from both phototoxicity at a dosage of 30 mg/kg in guinea pigs (i.v.) and convulsion when coadministered with 4-biphenylacetic acid at a dosage of 20 micrograms in rats (i.c.v.)). Their selectivity between DNA topoisomerase II (derived from eukaryotic cells) and DNA gyrase (derived from bacterial cells) was about 3000-fold.

Animals↗