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Biomedical subjects

K Ichihara

Publications and source records attributed to K Ichihara.

At least 145 records · Page 8Linked to original sources
PubMed1993

Calcium entry blocking activities of MPC-1304 and of its enantiomers and metabolites.

The Ca2+ entry blocking effects of MPC-1304, a new Ca2+ entry blocker of the 1,4-dihydropyridine type, and of its (S) and (R) enantiomers and metabolites were examined on Ca(2+)-induced contractions in isolated rabbit arteries. The Ca2+ entry blocking activity of the (S) enantiomer of MPC-1304 was approximately 150 times greater than that of its (R) enantiomer. Likewise, the antihypertensive effect of the (S) enantiomer was twice as great as that of MPC-1304 (racemate) in conscious spontaneously hypertensive rats, while the (R) enantiomer was ineffective. Thus, most of the pharmacological activity of MPC-1304 resides in its (S) configuration. The main metabolic products of MPC-1304 also inhibited the Ca(2+)-induced contraction in the isolated vascular smooth muscles. These active metabolites showed a stereoselectivity similar to that of MPC-1304 for Ca2+ entry blocking activity, and may contribute to the potent antihypertensive action of MPC-1304.

Animals↗
PubMed1993

Mediation of dopamine D1 and D2 receptors in the effects of GBR 12909 on latent learning and locomotor activity in mice.

We investigated the involvement of dopamine D1 and D2 receptor subtypes in the effects of GBR 12909, a selective dopamine uptake inhibitor, on latent learning in the performance of a water-finding task and on locomotor activity in mice. GBR 12909 (10 and 20 mg/kg) impaired latent learning, and this effect was counteracted by the dopamine D2 receptor antagonist, (-)-sulpiride (20 and 40 mg/kg), but not by the dopamine D1 receptor antagonist, SCH 23390 (0.025 and 0.05 mg/kg). The dopamine D2 receptor agonist, quinpirole (0.5 and 1 mg/kg) and the dopamine D1 receptor agonist, SKF 38393 (20 mg/kg) impaired latent learning, but both effects were less than that of GBR-12909. The effect of quinpirole, but not of GBR 12909, on latent learning was potentiated by combination with SKF 38393. In contrast to its effect on learning, SCH 23390 (0.025 and 0.05 mg/kg) was more effective to suppress the stimulant effect of GBR 12909 on locomotor activity than was (-)-sulpiride (40 and 80 mg/kg). These findings suggest that both dopamine D1 and D2 receptors play an important role in the action of endogenously released dopamine in latent learning and locomotor activity, and that while the dopamine D2 receptor is involved predominantly in latent learning, both dopamine D1 and D2 receptors play a critical role in locomotor activity.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1993

Effects of iloprost, a PGI2 derivative, on ischemic myocardial energy and carbohydrate metabolism in dogs.

Effects of iloprost, which is a stable prostacyclin analogue, on the ischemic myocardium were examined in the open-chest dog heart in terms of biochemical parameters. Ischemia was initiated by ligating the left anterior descending coronary artery. When the coronary artery was ligated for 3 min, the levels or glycogen, fructose-1,6-diphosphate (FDP), adenosine triphosphate and creatine phosphate decreased, and the levels of glucose-6-phosphate (G6P), fructose-6-phosphate (F6P), lactate, adenosine diphosphate and adenosine monophosphate increased. During ischemia, therefore, energy charge potential was significantly decreased from 0.89 +/- 0.01 to 0.82 +/- 0.01, and ([G6P] + [F6P])/[FDP] and [lactate]/[pyruvate] ratios were significantly increased from 1.75 +/- 0.30 to 29.05 +/- 5.70 and 13 +/- 3 to 393 +/- 112, respectively. Iloprost (0.1, 0.3, or 1 microgram.kg-1) was injected intravenously 5 min before the onset of ischemia. Iloprost (0.1, 0.3, and 1 micrograms.kg-1) reduced the ischemia-induced decrease in energy charge potential to 94, 74, and 86%, respectively, the increase in ([G6P] + [F6P])/[FDP] to 38, 29, 32%, respectively, and the increase in [lactate]/[pyruvate] to 67, 45, 65%, respectively. These results suggest that iloprost lessens the myocardial metabolic derangements produced by ischemia, and the most potent effect was obtained at the dose of 0.3 microgram.kg-1.

Adenosine Diphosphate↗
PubMed1993

Effects of amosulalol, a combined alpha 1- and beta-adrenoceptor-blocking agent, on ischemic myocardial energy metabolism in dogs.

The effect of amosulalol, a combined alpha 1- and beta-adrenoceptor-blocking agent, on changes in myocardial energy and carbohydrate metabolism during ischemia was studied. Ischemia was induced by ligating the left anterior descending coronary artery for 3 or 30 min during open-chest surgery in anesthetized dogs. The myocardial energy stores were depleted, and the levels of glycolytic intermediates were altered by 3 and 30 min of ischemia, indicating that anaerobic myocardial metabolism had occurred. Amosulalol (0.3 or 1 mg.kg-1) was injected intravenously 5 min before ischemia. Pretreatment with amosulalol, particularly at a dose of 0.3 mg.kg-1, reduced the myocardial energy depletion and the alteration of carbohydrate metabolism induced by ischemia. This result indicates that amosulalol can reduce ischemic influences on the myocardium.

Adenosine Diphosphate↗
PubMed1993

Effects of bunitrolol on ischemic myocardial energy metabolism in dogs.

The effect of bunitrolol, a beta-adrenergic blocking agent having intrinsic sympathomimetic activity, on ischemic myocardial metabolism was examined in anesthetized dog hearts. Ischemia was induced by ligating the left anterior descending coronary artery for 3 or 30 min. Bunitrolol (0.3 or 1.0 mg/kg of body weight) was injected intravenously 5 min before the onset of ischemia. Ischemia reduced myocardial high-energy phosphate levels and changed the levels of glycolytic intermediates. Bunitrolol at a dose of 0.3 mg/kg significantly decreased heart rate, whereas the drug at a dose of 1.0 mg/kg did not. This result suggests that intrinsic sympathomimetic activity is observed only at a high dose of bunitrolol. Pretreatment with bunitrolol at 0.3 but not 1.0 mg/kg attenuated the myocardial metabolic changes caused by 3 min of ischemia. After 30 min of ischemia, a beneficial effect of bunitrolol on the ischemic myocardium was not observed. These results suggest that bunitrolol may lessen the ischemic influence on the myocardium in the early stage of ischemia and that intrinsic sympathomimetic action may not have a beneficial effect on the ischemic myocardium.

Animals↗
PubMed1993

Phospholipid requirement of epididymal testosterone 5 alpha-reductase and phospholipid composition of epididymal microsomes.

We have investigated phospholipid requirement for testosterone 5 alpha-reductase solubilized from microsomal and nuclear fractions of rat epididymis. The 5 alpha-reductase from microsomal fraction was stimulated by phosphatidylcholine (PC) with long acyl-chain lengths, but inhibited by short chain PC. The nuclear enzyme activity was weakly activated by PC with various acyl-chain lengths tested. Synthetic phosphatidylserine (PS), such as dioleoylPS, most strongly stimulated the microsomal enzyme activity, but did not exhibit any activation of the nuclear enzyme activity. Endogenous phospholipids, such as PC, PS, and phosphatidylethanolamine (PE) separated from bovine epididymal microsomes were tested for their stimulatory effects on microsomal and nuclear enzymes. Among these endogenous phospholipids, PS most greatly stimulated the microsomal 5 alpha-reductase activity, whereas both PC and PE weakly activated the enzyme activity. On the other hand, endogenous PC and PS had no ability to support the nuclear enzyme activity. The fatty acid compositions of PC and PS from bovine epididymal microsomes were determined, in order to elucidate the relationship between 5 alpha-reductase activation by these phospholipids and the structure of their acyl chains. The relative content of fatty acids in PC, in a decreasing order, was palmitate > linoleate > oleate; that in PS was stearate > oleate > palmitate. Based on these observations, the roles of microsomal PS and PC in epididymal 5 alpha-reductase reaction will be discussed.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1993

Cardiovascular profile of MPC-1304, a novel dihydropyridine calcium antagonist: comparison with other calcium antagonists.

The cardiovascular profile of a novel calcium antagonist, MPC-1304 and its active metabolites were investigated in experimental animals in vitro and in vivo, and were compared with those of other calcium antagonists or nitroglycerin (NTG). The ratio of negative chronotropic/negative inotropic effect of MPC-1304 was 23 times higher than that of nifedipine in paced left and spontaneously beating right atria of guinea pigs. MPC-1304 and nifedipine did not change atrial-His (AH) conduction time or His-ventricular (HV) conduction time at hypotensive doses in open-chest dogs, whereas diltiazem prolonged AH time. MPC-1304 increased coronary blood flow, and strongly decreased myocardial oxygen consumption (MVO2) by decreasing blood pressure (BP) and heart rate (HR) in open-chest dogs. Left ventricular pressure (LVP) was not changed. Contractile force (dp/dt) was slightly increased by its action on afterload. MPC-1304 and nifedipine did not dilate the large coronary artery, but NTG did. MPC-1304 increased blood flow of the peripheral arteries, especially vertebral and CBF in anesthetized dogs. Cerebral blood flow (CBF) also increased. MPC-1304 decreased serum cholesterol levels and the plaque area of the aorta in cholesterol-fed rabbits. Because of this cardiovascular profile, MPC-1304 should be useful in treatment of hypertension as well as angina pectoris.

Animals↗
PubMed1993

Influences of pravastatin and simvastatin, HMG-CoA reductase inhibitors, on myocardial stunning in dogs.

We examined the effects of pravastatin and simvastatin, HMG-CoA reductase inhibitors, on stunned myocardium in vivo. Pravastatin and simvastatin were given orally 2 mg/kg for 3 weeks. After 3 weeks of administration, pentobarbital-anesthetized dogs were subjected to 15-min left anterior descending (LAD) coronary artery occlusion followed by 2-h reperfusion. Myocardial segment function was determined by sonomicrometry. The tissue energy and carbohydrate metabolites were determined in the 2-h-reperfused hearts. Administration of pravastatin and simvastatin for 3 weeks decreased serum cholesterol level and blood pressure (BP). Simvastatin resulted in a worsening of segment shortening in the reperfused myocardium as compared with control and pravastatin groups. The level of ATP in the simvastatin group was significantly lower as compared with that in the control group. The other metabolite levels were not significantly altered by either pravastatin or simvastatin. These results suggest that simvastatin enhances stunning of the myocardium in association with ATP reduction after reperfusion subsequent to ischemia.

Adenosine Triphosphate↗
PubMed1993

Limitation of stunning in dog myocardium by nucleoside and nucleotide mixture, OG-VI.

BACKGROUND: OG-VI is a nucleoside-nucleotide solution composed of 30 mM inosine, 30 mM cytidine, 30 mM sodium 5'-guanylate, 22.5 mM uridine, and 7.4 mM thymidine. It is expected to enhance the efficacy of intravenous hyperalimentation in surgically stressed patients. One of the main causes of ischemic myocardial damage is loss of adenine nucleotides from heart cells. The aim of the present study, therefore, was to examine the effect of OG-VI on myocardial mechanical function and energy metabolism in stunned myocardium. METHODS: Pentobarbital-anesthetized dogs were subjected to 20 min ligation of the left anterior descending (LAD) coronary artery, followed by reperfusion for 30 min. OG-VI at 0.1 or 0.2 ml/kg/min or saline was infused from the left femoral vein throughout the experiment. The tissue levels of high-energy phosphates in the hearts were determined after 30 min reperfusion. RESULTS: LAD flow, first derivative of left ventricular pressure (LVdp/dt), and segment function were increased by OG-VI in a dose-dependent manner. OG-VI infusion resulted in a significant improvement in LVdP/dt and segment shortening in the ischemic/reperfused myocardium compared with saline infusion. The levels of segment shortening with saline, 0.1, and 0.2 ml/kg/min OG-VI after reperfusion for 30 min were -0.3, 75, and 82% of the preligation levels, respectively. The tissue level of adenosine triphosphate (ATP) after reperfusion in OG-VI-infused animals was significantly higher than that in saline-infused animals. CONCLUSION: OG-VI has a positive inotropic action, and its infusion results in a marked cardioprotective effect in stunned myocardium associated with the restoration of tissue ATP level.

Animals↗
PubMed1993

Effects of LP-805, a newly developed vasodilator, on myocardial metabolism in ischaemic dog hearts.

The effects of LP-805, a newly developed vasodilator, on changes in the myocardial energy and carbohydrate metabolism induced by ischaemia were studied in open-chest anaesthetized dogs. Ischaemia was induced by ligating the left anterior descending coronary artery for 3 min. The myocardial energy stores were depleted, and the levels of glycolytic intermediates were altered 3 min after the onset of ischaemia. Energy change potential was decreased, and ([G6P] + [F6P])/[FDP] and [lactate]/[pyruvate] ratios were increased by ischaemia. These findings indicated that the myocardial metabolism was converted from an aerobic to an anaerobic type by ischaemia. LP-805 (10, 30, or 100 micrograms kg-1) was injected intravenously 5 min before the onset of ischaemia. LP-805 prevented the myocardial energy depletion and alterations of myocardial carbohydrate metabolism due to ischaemia, indicating that it appeared to convert the anaerobic metabolism back to aerobic metabolism in the ischaemic myocardium. In conclusion, LP-805 may reduce the ischaemic influence on the myocardium.

Adenine Nucleotides↗
PubMed1993

Analysis of discordant test results among five second-generation assays for anti-hepatitis C virus antibodies also tested by polymerase chain reaction-RNA assay and other laboratory and clinical tests for hepatitis.

The diagnostic performances of five commercially available second-generation assays for anti-hepatitis C virus antibody, two enzyme-linked immunosorbent assays, one enzyme immunoassay, and two particle agglutination assays (passive hemagglutination assay and particle agglutination assay), were evaluated. Among 104 samples from healthy subjects and 300 consecutive samples from patient ordered for routine determinations of anti-hepatitis C virus antibody in serum, assay results showed variable degrees of discordance for 17 samples (4.2%). These 17 samples were further tested by an immunoblot assay, the polymerase chain reaction-RNA assay, and the hemagglutination inhibition assay. Four of the 17 samples were regarded as true positive, since all supplementary assays and clinical data indicated active hepatitis C virus infection. Another five samples were considered false positive because no confirmatory evidence was obtained from the laboratory analysis or clinical data. The remaining eight samples were negative for hepatitis C virus RNA, but the results of the other supplementary tests were indeterminate. Some of these samples with indeterminate results may have been from patients with subclinical cases of disease who spontaneously recovered from hepatitis with persistent anti-hepatitis C virus antibody in their sera.

Adult↗
PubMed1993

Dopaminergic agonists impair latent learning in mice: possible modulation by noradrenergic function.

The effects of the dopamine agonists apomorphine, GBR-12909, nomifensine and methamphetamine on latent learning were investigated using a one-trial, water-finding task in mice. Mice without water deprivation were given these agonists or their vehicle before a training trial which consisted of exposure to a novel open-field environment containing a water tube. Twenty-four hours later and after 20 hr of water deprivation, animals were placed in the same apparatus and tested for the time required to find the water tube. Vehicle control animals exposed to the training trial demonstrated latent learning as measured by a significantly shorter time taken to find the water tube during the test trial as compared with naive controls that had not been exposed to the training trial. All of the dopamine agonists impaired the development of latent learning. The effects of nomifensine and methamphetamine were relatively weaker than those of apomorphine and GBR-12909. (-)-Sulpiride, a dopamine D2 antagonist, counteracted the disruptive effect of apomorphine on latent learning, whereas SCH 23390, a dopamine D1 antagonist, did not. The noradrenaline uptake inhibitor desipramine had no significant effect on latent learning. The disruptive effect of GBR-12909 on latent learning was significantly reduced when desipramine was given concurrently. Moreover, noradrenaline depletion with the neurotoxin, DSP4, impeded latent learning. These results suggest that activation of dopaminergic systems by dopamine agonists suppresses acquisition of latent learning. The qualitative and quantitative differences in the effects produced by the various agonists may be associated with their effects on noradrenergic transmission.

Animals↗
PubMed1993

[Immunoassay].

Since the advent of radioimmunoassay in 1959, the immunoassay technology has developed enormously as a very sensitive assay system suitable for wide range of analytes of clinical interest. Current popularity of the noncompetitive principle is attributable to its higher sensitivity, wide dynamic range and shorter incubation time. Recent innovation includes time-resolved fluorescent immunoassay designed to eliminate non-specific fluorescence, amplified enzyme-linked immunoassay and enhanced chemiluminescent immunoassay for ultra-sensitivity, particle counting immunoassay with a high resolution power, simultaneous measurement of multiple analytes, and easy-to-perform multilayer film immunoassays. Despite these advances in the technology, there remain various assay problems such as lack of standardization in reagents, a large interlaboratory variations despite the use of same assay kits, non-linear results in diluted samples and so-called prozone phenomenon.

Immunoassay↗
PubMed1992

Effects of imidazoline-related compounds on the mechanical response to nicorandil in the rat portal vein.

The purpose of this study was to investigate the interactions of compounds structurally related to imidazoline at K+ channels located in the rat portal vein. Nicorandil, a K+ channel activator, dose dependently inhibited spontaneous contractions of the isolated rat portal vein. Glibenclamide (0.1-1 microM), an ATP-sensitive K+ channel blocker, competitively antagonized the response to nicorandil, whereas methylene blue (10 microM), a guanylate cyclase inhibitor, did not. Phentolamine, antazoline, tolazoline, and midaglizole also shifted the dose-response curve for nicorandil to the right in the dose range of 1-100 microM. The rank order of potency was glibenclamide much greater than phentolamine = antazoline = midaglizole greater than tolazoline. In contrast, clonidine, idazoxan, imidazole, 1-benzylimidazole, and yohimbine were ineffective. In addition, cromakalim (1-100 nM), a selective K+ channel activator, also inhibited spontaneous contractions of the rat portal vein, and this effect was antagonized by phentolamine in a similar way to that found with nicorandil. These results suggest that some 2-substituted imidazolines, including phentolamine, possibly act as K+ channel blockers, like glibenclamide, in vascular smooth muscle.

Animals↗
PubMed1992

Cardioprotective effect of pindolol in ischemic-reperfused isolated rat hearts.

The effects of pindolol and timolol on ischemia reperfusion damage were studied in isolated working rat hearts. Ischemia (15 min) decreased the mechanical function and the energy state, and increased the tissue levels of free fatty acids (FFA). During reperfusion (20 min), the mechanical function did not recover, but the energy state recovered incompletely, whereas FFA increased further. Pindolol (50 microM) accelerated recovery of the mechanical function and the energy state that had been decreased by ischemia during reperfusion, and inhibited the accumulation of FFA during ischemia and reperfusion, especially when it was applied during the whole period of reperfusion. Timolol (50 microM), however, did not accelerate recovery of the mechanical function and the energy state during reperfusion, although it attenuated FFA accumulation during reperfusion. The pindolol-induced recovery of the mechanical function during reperfusion was reduced by timolol. The results suggest that the intrinsic sympathomimetic activity of pindolol may play an important role, at least in part, in producing the cardioprotective effect, especially during reperfusion.

Adenine Nucleotides↗
PubMed1992

Effects of dopamine receptor agonists on passive avoidance learning in mice: interaction of dopamine D1 and D2 receptors.

The present study examined the effects of dopamine D1 and D2 receptor agonists on the acquisition stage of passive avoidance learning and on locomotor activity in mice. The D2 agonist, RU 24213 (1-10 mg/kg s.c.), and the non-selective agonist, apomorphine (0.3-3 mg/kg s.c.), but not the D1 agonist, SKF 38393 (1-10 mg/kg s.c.), impaired learning and activated locomotion. RU 24213 (1 mg/kg s.c.) was more effective in impairing learning than in activating locomotion. The concurrent administration of SKF 38393 (10 mg/kg i.p.) and RU 24213 (1 and 3 mg/kg s.c.) produced a synergistic effect in both behavioral situations. The D1 antagonist, SCH 23390 (0.025 mg/kg i.p.), slightly inhibited the effects of apomorphine and of the combination of SKF 38393 and RU 24213 on learning but not on locomotion. The D2 antagonist, (-)-sulpiride (40 mg/kg i.p.), completely blocked these effects in both situations. These results suggest that dopamine receptor agonists impair passive avoidance learning through the D2 receptor, and that D1 and D2 receptors act synergistically in this impairment, as they do in their effects on locomotion. The involvement of D1 and D2 receptors is qualitatively similar in each of these behaviors, although some small differences may exist.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1992

Decreases in alpha beta T cell receptor negative T cells and CD8 cells, and an increase in CD4+ CD8+ cells in active Hashimoto's disease and subacute thyroiditis.

We examined peripheral lymphocyte subsets in patients with autoimmune thyroid disease, or subacute thyroiditis, in the active stage when possible. During destructive thyrotoxicosis arising from alpha beta T cell receptor (TCR) negative T (WT31-CD3+) cells and CD8 (CD4-CD8+) cells decreased and those of CD4+CD8+ cells increased slightly, resulting in proportional increases in CD4 (CD4+CD8-) cells, non-T, non-B (CD5-CD19-) cells, and the CD4/CD8 cell ratio. Changes were similar in active subacute thyroiditis. During stimulative thyrotoxicosis in active Graves' disease, the numbers of such T lymphocyte subsets were not changed, but only the number of CD5+ B (CD5+CD19+) cells increased markedly, resulting in proportional decreases in total T (CD3+) cells, alpha beta+ TCR T (WT31+CD3+) cells, CD8 cells, and non-T, non-B cells. A serial study of some of the patients showed opposite changes in alpha beta TCR- T cells, the CD4/CD8 cell ratio, and CD5+ B cells between the active stages of Graves' and Hashimoto's diseases. alpha beta TCR- T cells were mostly gamma delta TCR+ T (IIF2+ CD3+) cells in these patients. These data suggest that alpha beta TCR-T (gamma delta TCR+ T), CD8, and CD4+ CD8+ cells are important in thyroid destruction in Hashimoto's disease and subacute thyroiditis, and that CD5+ B cells are important in thyroid stimulation in Graves' disease.

Adult↗