Biomedical subjects

K Ishikawa

Publications and source records attributed to K Ishikawa.

At least 145 records · Page 8Linked to original sources

PubMed2001

Platelet-dependent thrombin generation in patients with unstable angina pectoris.

Platelet-dependent thrombin generation was assessed during both unstable and stable periods in 59 patients with unstable angina and at rest in 31 healthy controls. Thrombin generation during the unstable period was significantly greater than that at rest in the healthy control group (p < 0.0001) and that during the stable period (p < 0.0001). Changes in thrombin generation were related to the time after onset of unstable angina, not to degree of improvement in the severity of coronary stenosis.

Adult↗

PubMed2001

tPA via infusion catheters followed by continuous IV infusion for 3 days prevents intimal hyperplasia after balloon injury.

A rabbit model was used to examine the effects of tissue plasminogen activator (tPA) on development of intimal hyperplasia following balloon injury. Thirty-two hereditary hypercholesterolemic (KHC) rabbits underwent percutaneous transluminal coronary artery balloon catheterization and injury to the common iliac artery, after which they were divided into four groups: untreated (control); Dispatch catheterized-30 minutes local saline delivery [D(+)-tPA(-)]; D(+)-30 minutes local tPA delivery (0.6 mg/kg) [D(+)-tPA(30 min)]; and D(+)-30 minutes local tPA + 3 days intravenous infusion (0.6 mg/kg/24 h) [(D(+)-tPA(30 min + 3 d)]. Twenty-eight days later, the intimal cross-sectional areas of all three Dispatch catheterized groups were significantly smaller than those of control groups, as were the intimal/medial area ratios. Moreover, the intima/media ratios of the D(+)-tPA(30 min + 3 d) group were significantly smaller than those of the D(+)-tPA(-) group. Thus, local delivery of tPA via Dispatch catheters followed by continuous intravenous infusion of tPA for 3 days prevented intimal hyperplasia after angioplasty.

Angioplasty, Balloon, Coronary↗

PubMed2001

Rate and equilibrium constants for the epimerization of the endothelin receptor antagonist J-104,132 in aqueous solution.

The degradation of [5S-[5alpha,6beta,7alpha(R*)]]-2-butyl-5-(1,3-benzodioxol-5-yl)-7-[(2-carboxypropyl)-4-methoxyphenyl]-6-dihydro-5H-cyclopenta[b]pyridine-6-carboxylic acid (J-104,132) was studied in aqueous solution as a function of temperature and pH. The degradation reaction does not proceed to completion; rather, a stable equilibrium is attained in which approximately 2% of the degradate is produced. Kinetic data for the formation of the degradate are analyzed using an integrated form of the rate law for a reversible first-order reaction, and the forward and reverse rate constants and overall equilibrium constants are presented. Isolation and spectroscopic structural determination indicate that the degradate is the C7 beta-epimer of the drug. A mechanism for the epimerization reaction involving a novel enamine-like intermediate is proposed and shown to be consistent with the kinetic data. The rate and equilibrium constants are used to predict the room temperature stability of an injectable formulation of J-104,132, and these predictions are compared to actual data from long-term stability studies. It is concluded that the preformulation kinetic studies provide essential data needed for optimum drug product development.

Endothelin Receptor Antagonists↗

PubMed2001

Stress-induced ST-segment elevation following myocardial infarction and its role in wall motion abnormality, myocardial ischemia and viability: comparison of response to exercise, dobutamine and dipyridamole.

Stress-induced ST-segment elevation following myocardial infarction (MI) has been correlated with myocardial ischemia, viability and wall motion abnormality, but its mechanism is still unclear, so the present study compared ST-segment elevation and wall motion response during exercise, dobutamine and dipyridamole stresses. Twenty-five patients with their first anterior MI underwent exercise, dobutamine and dipyridamole echocardiography on different days 4-6 weeks after MI. Left ventricular wall motion was analyzed using 5-grade/16-segment model and myocardial ischemia was considered as a worsening of the wall motion score index (WMSI) during the stress test; myocardial viability was defined as a reduction of WMSI during low dose dobutamine. Dyskinesis formation was defined by visual analysis as akinesis that became dyskinetic or if the dyskinesis worsened. Both exercise and dobutamine induced ST-segment elevation, but dipyridamole did not. There was no significant difference in the degree of ST-segment elevation between the patients with and without myocardial ischemia or dyskinesis formation. Exercise induced a higher ST-segment elevation in patients with myocardial viability than those without (0.17+/-0.09 mV vs 0.09+/-0.07 mV, p<0.05). Exercise-induced ST-segment elevations correlated with dobutamine-induced ST-segment elevations (p<0.01), changes in heart rate (p<0.05) and systolic blood pressure (p<0.05). In conclusions, stress-induced ST-segment elevation does not correlate with either myocardial ischemia or stress-induced dyskinesis, but may be associated with myocardial viability.

Cardiotonic Agents↗

PubMed2001

Role of cardiac ATP-sensitive K+ channels induced by angiotensin II type 1 receptor antagonist on metabolism, contraction and relaxation in ischemia-reperfused rabbit heart.

The role of cardiac adenosine triphosphate-sensitive K+ (K(ATP)) channels induced by angiotensin II type 1 (AT1) receptor antagonist, CV-11974, on myocardial metabolism and contraction during ischemia, and reperfusion by the phosphorus 31-nuclear magnetic resonance in Langendorff-perfused rabbit hearts was investigated. After 20 min of continuous normothermic global ischemia, 30 min of postischemic reperfusion was carried out. CV-11974 with or without the K(ATP) channel blocker, glibenclamide, or the bradykinin B2 receptor antagonist, D-Arg-[Hyp3,D-Phe7]bradykinin, was administered 40 min prior to the global ischemia. Adenosine triphosphate (ATP), creatine phosphate (PCr), inorganic phosphate (Pi), intracellular pH (pHi), left ventricular systolic developed pressure, left ventricular end-diastolic pressure (LVEDP), and coronary flow were measured. Twenty-eight hearts were divided into 4 experimental groups consisting of 7 hearts each. Group I consisted of controls, Group II perfused with CV-11974 (10(-6) mol/L), Group III perfused with CV-11974 (10(-6) mol/L) in combination with glibenclamide (10(-6) mol/L), and Group IV perfused with CV-11974 (10(-6) mol/L) in combination with D-Arg-[Hyp3,D-Phe7]bradykinin (10(-6) mol/L). Group II showed a significant inhibition of the decrease in ATP during ischemia and reperfusion compared with Group I (p<0.01), being 42+/-3% and 19+/-4% at ischemia, 69+/-3% and 47+/-4% at reperfusion in Group II and Group I, respectively. Group II also showed a significant inhibition of the increase in LVEDP during ischemia and reperfusion compared with Group I (p<0.01), being 13+/-4 mmHg and 52+/-8 mmHg at ischemia, 8+/-2 mmHg and 26+/-5 mmHg at reperfusion in Group II and Group I, respectively. However, Group II did not inhibit the decrease in ATP and the increase in LVEDP during ischemia and reperfusion. Group IV also showed no inhibition of the aforementioned parameters during the same period. These results suggest that CV-11974 has a significant beneficial effect for improving myocardial energy metabolism and relaxation during both myocardial ischemia and reperfusion, which is provided by K(ATP) channels and bradykinin B2 receptor. The cardioprotective quality of the AT1 receptor antagonist is caused by the K(ATP) channels that are mediated by the bradykinin B2 receptor.

Angiotensin Receptor Antagonists↗

PubMed2001

Relationship between blood pressure and cardiac events in patients with a healed myocardial infarction.

This study investigated the association between blood pressure (diastolic [DBP] and systolic [SBP]) and cardiac events in a total of 6,602 patients with a healed myocardial infarction (MI) (5,320 men, 1,282 women; mean age, 58.9+/-10.4 years), including in-patients and out-patients, from January 1986 to January 1999. The primary endpoints (cardiac events) were recurrent MI (fatal and non-fatal), death from congestive heart failure, or sudden death. The total number of cardiac events was 195 (3.0%) and the incidences of the 3 cardiac events were compared among the 3 DBP groups (DBP low group, <70 mmHg; DBP middle group, 70-89 mmHg; DBP high group, > or =90 mmHg). There were some significant differences in the characteristics of patients among the 3 groups, but no significant difference in cardiac death and total mortality was found among the 3 groups. Cardiac events occurred in 59 of 1,780 patients (3.3%, 33.9/1,000 person years) in the DBP low group, tended to be reduced in number in the DBP middle group (87 of 3,549 patients 2.5%, 21.4/1,000 person years) and were slightly increased in number in the DBP high group (24 of 642 patients 3.7%, 35.2/1,000 person years). Although this correlation between BP and cardiac events appears to be J-shaped, because there is no statistically significant difference in the rate of cardiac events among the 3 groups, we conclude that DBP does not influence the occurrence of cardiac events. The prevalence of cardiac events tended to be greater with a SBP less than 120 mmHg.

Aged↗

PubMed2001

Thallium-201 single photon emission computed tomography (SPECT) in patients with duchenne's progressive muscular dystrophy: a histopathologic correlation study.

The pathomorphologic mechanism responsible for abnormal perfusion imaging during thallium-201 myocardial single photon emission computed tomography (201Tl-SPECT) in patients with Duchenne's progressive muscular dystrophy (DMD) was investigated. Hearts from 7 patients with DMD were evaluated histopathologically at autopsy and the results correlated with findings on initial and delayed resting 201Tl-SPECT images. The location of segments with perfusion defects correlated with the histopathologically abnormal segments in the hearts. Both the extent and degree of myocardial fibrosis were severe, especially in the posterolateral segment of the left ventricle. Severe transmural fibrosis and severe fatty infiltration were common in segments with perfusion defects. In areas of redistribution, the degree of fibrosis appeared to be greater than in areas of normal perfusion; and intermuscular edema was prominent. Thus, the degree and extent of perfusion defects detected by 201Tl-SPECT were compatible with the histopathology. The presence of the redistribution phenomenon may indicate ongoing fibrosis. Initial and delayed resting 201Tl-SPECT images can predict the site and progress of myocardial degeneration in patients with DMD.

Adolescent↗

PubMed2001

[New strategy on medical research after completion of genome sequencing].

Real advances in biotechnology made it possible to complete human whole genome sequencing within a short duration. Although the genome includes a huge amount of information about biological functions and the interest is now directed to the study using genomic information, the genomic strategy is not clearly understood. The following 4 studies were therefore presented and discussed about the strategy after the completion of the genomic sequence in the 74th Annual Meeting of Japanese Pharmacological Society: 1) Asthma and atopic dermatitis: models for genetic and genomic investigations of complex genetic diseases, by W.C.O. Cookson (University of Oxford, Asthma Genetics Group, Wellcome Trust Centre for Human Genetics); 2) Molecular classification by global gene expression profiling: application on oncogenomic research, by H. Aburatani (Genome Science Division, Research Center for Advanced Science and Technology, University of Tokyo); 3) Functional genomic search of disease-related genes using microarrays with normalized rat cDNA library, by G. Tsujimoto, et al. (Department of Molecular, Cell Pharmacology, National Children's Medical Research Center: and 4) Acute ischemic change of mRNA expression in the hippocampus by GeneChip array analysis: a starting point for post-genome strategy, by S. Asai, et al.

Animals↗

PubMed2001

Cardioprotection with angiotensin converting enzyme inhibitor and angiotensin II type 1 receptor antagonist is not abolished by nitric oxide synthase inhibitor in ischemia-reperfused rabbit hearts.

Although angiotensin converting enzyme (ACE) inhibitor and/or angiotensin II type 1 (AT1) receptor antagonist can protect the myocardium against ischemia-reperfusion injury, the mechanisms of the effect have not yet been characterized at the cellular level. We here examined the effect of the combination of an ACE inhibitor, temocaprilat, an AT1 receptor antagonist, CV-11974 and/or a nitric oxide synthase inhibitor, L-NAME, on the myocardial metabolism and contraction during ischemia and reperfusion by using phosphorus 31-nuclear magnetic resonance (31P-NMR) in Langendorff rabbit hearts. After normothermic 20 min global ischemia, postischemic reperfusion of 30 min was carried out. Twenty-one hearts were divided into three experimental groups consisting of 7 hearts each: a Tem+CV group perfused with a combination of temocaprilat and CV-11974; a Tem+CV+L-NAME group perfused with a combination of temocaprilat and CV-11974 plus L-NAME, and a control group. During ischemia, both the Tem+CV group and Tem+CV+L-NAME group showed a significant inhibition of the decrease in adenosine triphosphate (ATP) compared with the control group (p<0.01); the increase in ATP was 50+/-3%, 42+/-4%, and 19+/-4% in the Tem+CV group, Tem+CV+L-NAME group, and control group, respectively. Both experimental groups also showed a significant inhibition of the increase in left ventricular end-diastolic pressure (LVEDP) compared with the control group (p<0.01). After postischemic reperfusion, the Tem+CV group and Tem+CV+L-NAME group again showed a significant improvement of ATP as compared with the control group (p<0.01); the increase in ATP was 73+/-3%, 64+/-3%, and 47+/-4% in the Tem+CV group, Tem+CV+L-NAME group, and control group, respectively, and a significant decrease of LVEDP as compared with the control group (p<0.01). There were no differences in ATP, or LVEDP during ischemia and reperfusion between the Tem+CV group and Tem+CV+ L-NAME group. In conclusion, the combination of temocaprilat and CV-11974 showed significant potential for improving myocardial energy metabolism and relaxation during both myocardial ischemia and reperfusion. This beneficial effect was not dependent on NO synthase.

Angiotensin Receptor Antagonists↗

PubMed2001

Role of cardiac ATP-sensitive K+ channels induced by HMG CoA reductase inhibitor in ischemic rabbit hearts.

Although 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors can protect the myocardium against ischemic injury, the mechanisms of their effect have not yet been characterized at the cellular level. Therefore, we investigated the role of cardiac ATP-sensitive K+ (K(ATP)) channels induced by the HMG-CoA reductase inhibitor known as pravastatin on the myocardial metabolism during ischemia by phosphorus 31-nuclear magnetic resonance (31P-NMR) in isolated rabbit hearts. Forty-five min of continuous normothermic global ischemia was carried out. Pravastatin with or without the K(ATP) channel blocker glibenclamide or the nitric oxide synthase inhibitor L-NAME was administered beginning 60 min prior to the global ischemia. Twenty-eight hearts were divided into 4 experimental groups consisting of 7 hearts each: the control group, the P group consisting of pravastatin treatment, the P+G group consisting of pravastatin treatment with glibenclamide, and the P+L group consisting of pravastatin treatment with L-NAME. During ischemia, the decreases in adenosine triphosphate (ATP) and intracellular pH (pHi) were significantly inhibited in the P group in comparison with Control group (at end of ischemia, respectively; both p<0.01), as was the increase in inorganic phosphate (Pi) (at end of ischemia, p<0.01). However, the decreases in ATP and pHi and the increase in Pi were not inhibited in the P+G group during ischemia. The P+L group also showed no inhibition of the aforementioned parameters during the same period. These results suggest that pravastatin has a significant beneficial effect for improving the myocardial energy metabolism, which is provided by K(ATP) channels and nitric oxide (NO), during myocardial ischemia. The cardioprotection of HMG-CoA reductase inhibitor may be caused by the K(ATP) channels that are mediated by the NO.

Adenosine Triphosphate↗

PubMed2001

Characterization of classical swine fever virus associated with defective interfering particles containing a cytopathogenic subgenomic RNA isolated from wild boar.

Classical swine fever virus (CSFV) strain WB82, isolated from a wild boar in 1982, induced a distinct cytopathic effect (CPE) in primary swine testicle cell culture and in most of the porcine cell lines. This strain of CSFV was found to be composed of two biotypes. cytopathogenic (cp) CSFV, as a minor population, and noncytopathogenic (noncp) CSFV, as a major population. The noncp CSFV (designated strain WB82/E+) was obtained by biological cloning, and it showed the exaltation of Newcastle disease virus phenomenon. In Northern blot analysis and RT-PCR assay, CSFV RNA with a subgenomic (sg) length was detected in addition to full-length viral RNA only in the cells in which a CPE had been revealed. These RNAs represent the genomes of typical defective interfering (DI) particles because of the strict dependence on a complementing helper virus and interference with replication of the helper virus. The sg RNA, which exhibits the genomes of the DI particles, lacked the nucleotides of the viral genomic region from Npro to NS2 (4764 bases). When extracted sg RNA was transfected to the cells infected with the WB82/E+ strain, a distinct CPE was observed. Interestingly, the CPE was observed in cells infected with other heterologous noncp CSFV ALD and GPE- strains by sg RNA transfection. The results suggested that these noncp CSFVs act as helper viruses for the replication of sg RNA (DI particles). It was also shown that the cytopathogenicity of strain WB82 is caused by apoptosis.

Animals↗

PubMed2001

Eradication of foot and mouth disease in Japan.

An outbreak of foot and mouth disease (FMD) was recorded in Japan in the spring of 2000, the first for ninety-two years. Between 25 March and 11 May, four farms were infected. However, the disease was eradicated without resorting to vaccination, through a campaign of culling, movement control of cloven-hoofed animals in areas surrounding infected premises, and intensive clinical and serological surveillance. Japan regained FMD-free status by the end of September 2000. The authors describe the nature of the outbreaks, the eradication measures implemented, and the clinical and serological surveillance methods used. The possible sources of infection are also examined. Finally, the direct and indirect economic losses are presented.

Animals↗

PubMed2001

Protective effect of PEG-SOD against early coronary reperfusion injury assessed in reperfused and non-reperfused ischaemic areas of the same heart.

OBJECTIVE: In order to investigate the salvage of ischaemic myocardium by polyethylene glycol-conjugated superoxide dismutase (PEG-SOD), we compared reperfused and non-reperfused regions in the same canine heart and measured regional myocardial blood flow (RMBF) and myocardial CPK during coronary occlusion and reperfusion using non-radioactive, coloured microspheres. METHODS AND RESULTS: The chests of 17 mongrel dogs were opened under anaesthesia, and the left circumflex coronary artery was occluded for 90 min and then reperfused for 5 min. During this procedure, polystyrene microspheres of different colours were infused at four different times: prior to occlusion (orange), 10 min (red) and 90 min (blue) after occlusion, and 5 min after reperfusion (yellow). Thereafter, the heart was excised, cut in slices along the left circumflex coronary artery, and flow rates at the various times were assessed as a function of microsphere counts. In the control group (n=9), there are significant differences in the myocardial CPK level between reperfused and non-reperfused areas. The myocardial CPK level in reperfused area was significantly reduced compared to non-reperfused area in the outer layers (54 +/- 8 IU/g vs. 74 +/- 9 IU/g, P < 0.05), and also reduced in the inner layers (59 +/- 9 IU/g vs. 74 +/- 13 IU/g), however, it was not significantly different. In the PEG-SOD group (n=8), there was no significant difference in the myocardial CPK level between reperfused and non-reperfused areas in both inner and outer layers (inner layers; 68 +/- 11 IU/g vs. 68 +/- 6 IU/g, outer layer; 69 +/- 17 IU/g vs. 67 +/- 18 IU/g), indicating a significant protective effect of PEG-SOD. In the control group, transmural necrosis of the reperfused areas was 22.4 +/- 10.0%, which showed no significant difference compared with non-reperfused areas (23.1 +/- 9.9%). In the PEG-SOD group, transmural necrosis of the reperfused areas by TTC staining was 8.1 +/- 8.1%, which showed no significant difference compared with non-reperfused areas (8.5 +/- 7.1%). CONCLUSIONS: PEG-SOD prevents infarct extension during early coronary reperfusion.

Analysis of Variance↗

PubMed2001

Successful treatment of a case of relapsed acute promyelocytic leukemia with arsenic trioxide.

We report a patient with an initial relapse of acute promyelocytic leukemia (APL) who achieved a second complete remission (CR) after treatment with arsenic trioxide. The patient, a 66-year-old woman diagnosed as having relapsed APL, received arsenic trioxide intravenously at a dose of 10 mg/day. At day 36, the patient achieved a second CR. The side effects were slight neuralgia and mild skin erythematous changes, which improved following cessation of the drug. Although arsenic trioxide may be effective for relapsed APL, it should be used with caution because of various complications.

Aged↗

PubMed2001

Effects of polysiloxane coating of NaF on the release profile of fluoride ion from Bis-GMA/TEGDMA resin containing NaF.

The aim of this study was to regulate fluoride release from restorative resin containing NaF using N-(beta-aminoethyl)-gamma-aminopropylmethyldimethoxysilane (AMMS) and evaluate factors that regulate fluoride release from the resin. ESCA analysis, FT-IR measurements along with SEM observations demonstrated that a polysiloxane layer was formed on the surface of NaF treated with AMMS. Bis-GMA/TEGDMA resin containing NaF powder treated with AMMS released lower concentrations of fluoride for longer periods when compared with that containing untreated NaF. However, AMMS treatment of NaF was less effective for the regulation of fluoride released from the resin than gamma-methacryloxypropyltrimethoxysilane (gamma-MPTS) treatment, despite its higher hydrophobic polysiloxane layer formation. These findings may have been caused by the higher density of polysiloxane prepared with gamma-MPTS than that prepared with AMMS. The present findings suggested, therefore, that alkoxysilane should be chosen based not only on hydrophobicity but also the density of polysiloxane to effectively regulate fluoride release from the restorative resin containing NaF.

Bisphenol A-Glycidyl Methacrylate↗

PubMed2001

Heme oxygenase as an intrinsic defense system in vascular wall: implication against atherogenesis.

Recent developments in our understanding of the atherosclerotic process and factors that trigger ischemic cardiovascular disease have led to the consideration of antioxidative responses or exogenous antioxidants, which are proposed to inhibit multiple proatherogenic and prothrombotic events in arterial wall. Heme oxygenases (HO), an enzyme essential for heme degradation, have been shown to have such antioxidative properties via the production of bile pigments, carbon monoxide and ferritin induction. We have demonstrated that mildly oxidized LDL markedly induces HO-1, an inducible form of HO, in human aortic endothelial and smooth muscle cell cocultures and that its induction results in the attenuation of monocyte chemotaxis induced by mildly oxidized LDL. We also confirmed abundant expression of HO-1 in human, murine and rabbit atherosclerotic lesions. By modulating HO activities in LDL-receptor knockout mice and Watanabe heritable hyperlipidemic rabbits during their atherosclerotic lesion developments, anti-atherogenic properties of HO have demonstrated as judged by the quantitative analyses of atherosclerotic lesion formation. HO expression was inversely correlated with the levels of plasma and tissue lipid peroxides. HO also influenced on nitric oxide pathway. These observations may suggest that HO, induced during atherosclerotic process, functions as an intrinsic protective pathway in vascular wall.

Animals↗

PubMed2001

Synthesis and antibacterial activity of novel 1beta-methyl carbapenems with cycloalkylamine moiety at the C-2 position.

Novel 1beta-methyl carbapenems with a cycloalkylamine moiety as a side chain were synthesized and their structure-activity relationships were studied. These carbapenems showed potent antibacterial activities against a wide range of Gram-positive and Gram-negative bacteria, and moderate urinary recovery when administered intraperitoneally in mice.

Anti-Bacterial Agents↗

PubMed2001

[A case of ventricular tachycardia immediately after electroconvulsive therapy in a schinzophrenic patient].

A 33 year-old man weighting, 93 kg with schizophrenia underwent repeated electroconvulsive therapy (ECT) under general anesthesia with thiamylal 200 mg and suxamethonium 80 mg. On his fourth ECT, he developed ventricular tachycardia (VT) immediately after the treatment under general anesthesia with the same agents. The duration of VT was approximately 30 s. The VT returned to sinus rhythm without any special treatment. We speculate that light anesthesia with a small amount of thiopental associated with release of serum potassium caused by suxamethonium induced increased release of catecholamine by ECT to cause VT. After that incident, the patient underwent ECT six times under general anesthesia with thiamylal 250 mg and vecuronium 8 mg, in combination with preventive injection of magnesium sulfate 20 g without any cardiovascular complications. We conclude that the anesthetic management of patients undergoing ECT under general anesthesia should be paid a careful attention for cardiovascular instability, even if they do not have any heart diseases.

Adult↗