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Biomedical subjects

S Takeo

Publications and source records attributed to S Takeo.

At least 91 records · Page 5Linked to original sources
PubMed1995

Biliary secretion of antibody to dextran following oral immunization with dextran B512.

Anti-dextran in bile was induced to high levels by oral immunization with dextran B512. IgM anti-dextran were dominant in serum, whereas IgG anti-dextran was dominant in bile. The binding properties of these IgM and IgG antibodies were different, as determined by ELISA with several dextrans. Splenocytes produced equal amounts of IgG and IgM antidextran but cells from mesenteric lymph nodes (MLN) and Peyer's patches produced mainly IgG anti-dextran. Differences were observed among different strains of mice in their ability to produce anti-dextran in serum and bile upon immunization with dextran. BALB/c mice, which are intermediate responders in terms of their serum antibody levels, produced high levels of anti-dextran in bile. C3H/He and C57BL/6, which are high responders in terms of serum antibody levels, had intermediate responses in bile. DBA/2, which are low responders in terms of serum antibody levels, showed low responses in bile. The results provide further evidence of the existence of anti-dextran producing cells. These results indicate that B cells in systemic and mucosal-associated lymphoid tissues from BALB/c, C3H/He, C57BL/6 and DBA/2 mice respond differently to oral immunization with dextran B512.

Administration, Oral↗
PubMed1995

Effects of long-term therapy with ACE inhibitors, captopril, enalapril and trandolapril, on myocardial energy metabolism in rats with heart failure following myocardial infarction.

Although pharmacological therapy with angiotensin converting enzyme (ACE) inhibitors has proved to be effective in patients with heart failure (HF), the experimental basis of this effect has not yet been addressed. In the present study, animals with HF were treated with an oral administration of 10 mg/kg/day captopril, 10 mg/kg/day enalapril and 3 mg/kg/day trandolapril from the 2nd to 12th week after the operation. HF was induced by permanent occlusion of the left coronary artery of the rat at 2 mm from its origin. Treatment of the HF rats with the ACE inhibitors enhanced the decrease in mean arterial blood pressure, attenuated the rise in left ventricular end-diastolic pressure, an indirect marker of preload, and diminished the reduction in cardiac output and stroke volume indices of the HF animal. Treatment also reversed the reduction in ATP, creatine phosphate, creatine and the mitochondrial oxygen consumption rate of the viable left and right ventricles of the HF animal. The improvement of the cardiac output index and high-energy phosphate levels of the HF rat by the ACE inhibitors was associated with the recovery of the mitochondrial oxygen consumption rate. In sham-operated animals, treatment with the ACE inhibitors reduced mean arterial pressure and left ventricular systolic pressure, but not metabolic variables concerning myocardial energy metabolism. The present results provide evidence that ACE inhibitor therapy improves cardiac function and myocardial energy metabolism of experimental animals with chronic heart failure. The mechanism underlying the benefit of long-term treatment with ACE inhibitors is probably attributable to recovery or preservation of the mitochondrial function and reduction in preload.

Adenine Nucleotides↗
PubMed1995

Reperfusion at reduced flow rates enhances postischemic contractile recovery of perfused heart.

The effects of reperfusion at reduced flow rates on postischemic cardiac contractile function were examined in perfused rat hearts. Isolated hearts were subjected to 35-min ischemia followed by reperfusion at the preischemic flow rate (9.0 ml.g-1.min-1; ordinary flow rate) or at reduced flow rates (0.9-8.1 ml.g-1.min-1). Reperfusion at ordinary flow rate did not generate any left ventricular developed pressure (LVDP), whereas reperfusion at reduced flow rates (0.9-7.2 ml.g-1.min-1) elicited 13-57% of initial contractile force at reperfusion's end; optimal recovery occurred at 3.6 ml.g-1.min-1 (reduced flow rate). Reduced flow rate reperfusion attenuated ischemia-reperfusion-induced increase in left ventricular end-diastolic pressure (LVEDP) and perfusion pressure (PP), alteration in tissue Na+, K+, Ca2+, and Mg2+, release of creatine kinase and ATP metabolites, and development of triphenyltetrazolium chloride-unstained areas. Enhanced postischemic LVDP recovery was inversely related to higher coronary PP at the initial stage (4 min) of reperfusion (r = -0.763). The benefit of reduced flow rate reperfusion could not be attributed to rate of calcium delivery to the heart, formation of oxygen free radicals in myocardium, endothelium-dependent coronary artery dilation, or LVDEP reduction. Enhancement of postischemic LVDP recovery was associated with attenuation of ischemia-reperfusion-induced increases in myocardial sodium and calcium; failure of postischemic LVDP recovery was accompanied by an increase. Reduction in sodium and calcium overload may underlie the beneficial effects of reduced flow rate reperfusion in ischemic-reperfused heart.

Adenosine Triphosphate↗
PubMed1995

Changes in striatal dopamine metabolism after microsphere embolism in rats.

BACKGROUND AND PURPOSE: Dopamine plays an important role in striatal function. The present study was undertaken to elucidate the pathophysiological changes in striatal dopamine metabolism after microsphere embolism. METHODS: Microspheres (48 microns) were injected into the right internal carotid artery of rats. Extracellular levels of dopamine and its metabolites were measured by in vivo microdialysis with the aid of high-performance liquid chromatography. In vivo striatal tyrosine hydroxylation and turnover (catabolism) rate of dopamine were estimated on the first and third days after the embolism. These were estimated by measuring tissue dopa or dopamine content in the presence of either an aromatic L-amino acid decarboxylase inhibitor or a tyrosine hydroxylase inhibitor, respectively. RESULTS: In the microdialysis study, a 190-fold increase in the release of dopamine from the right striatum was observed 40 minutes after microsphere embolism, whereas the striatal dopamine metabolites decreased during the first 180 minutes after the embolism. Microsphere embolism decreased the striatal dopamine content throughout the experiment (28 days), whereas it increased tissue dopamine metabolites on the first day, followed by a decline in the metabolites on the third day or later. The in vivo turnover rate of dopamine decreased both on the first and third days, whereas the in vivo tyrosine hydroxylation decreased only on the third day after the embolism. CONCLUSIONS: The results suggest that microsphere embolism induces severe damage to striatal dopaminergic metabolism 3 to 28 days after the embolism. Dopamine synthesis may be more resistant to the embolism-induced ischemic insults than its catabolism.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1995

Diminished responsiveness to cardiac beta 1-adrenoceptor agonists in rats with chronic heart failure following myocardial infarction.

The present study was undertaken to determine whether cardiac response to beta 1-adrenergic agonists is altered in rats with chronic heart failure (CHF), and whether this alteration is related to beta-adrenergic receptor down-regulation in the viable tissue of the left ventricle of these rats. For this purpose, the cardiac response to denopamine, a selective beta 1-adrenergic agonist, and the change in cardiac beta-adrenoceptor density were examined in rats with CHF. A non-selective beta-adrenergic agonist, isoprenaline, was also examined as a comparison. Cardiac output and stroke volume indices were reduced 12 weeks after left coronary artery ligation, suggesting that CHF had developed at this time. Denopamine (2, 4 and 8 micrograms/kg i.v.), and isoprenaline (0.01 microgram/kg i.v.) increased the cardiac output and stroke volume indices in sham-operated rats, whereas such increases were attenuated in the CHF rat. The cardiac beta-adrenergic receptor density, measured by [3H]CGP-12177 binding assay, was reduced in homogenates and microsomal membranes in the viable tissue of the left ventricle of the CHF rat (homogenates: 29% reduction, microsomal membrane: 23% reduction). These results suggest that the cardiac responsiveness to denopamine is diminished in the CHF rat and this alteration is accounted for, in part, by a decrease in cardiac beta-adrenoceptor density.

Adrenergic beta-1 Receptor Agonists↗
PubMed1995

Effects of trandolapril on cardiac angiotensin I converting enzyme activity in rats with chronic heart failure following myocardial infarction.

The effects of long-term treatment with a novel angiotensin I converting enzyme (ACE) inhibitor, trandolapril, on ACE activity and cardiac function in rats with chronic heart failure (CHF) were examined and compared with those of captopril and enalapril. Left coronary artery ligation of rats resulted in decreases in mean arterial pressure, left ventricular systolic pressure, dP/dt, cardiac output and stroke volume indices, and increases in left ventricular end-diastolic pressure and systemic vascular resistance 12 weeks after the operation. A significant increase in ACE activity of the myocardium, but not that of serum or other tissues, was detected in the CHF rat 12 weeks after the operation. Oral treatment with ACE inhibitors (10 mg/kg/day captopril, 10 mg/kg/day enalapril or 3 mg/kg/day trandolapril) from the 2nd to 12th week, attenuated the changes in cardiac output and stroke volume indices, left ventricular end-diastolic pressure and systemic vascular resistance of the CHF rat. Treatment also attenuated the increase in the cardiac. ACE activity of CHF rats. A close relationship between the decrease in cardiac output index and the increase in cardiac ACE activity was detected. The results suggest that trandolapril, like other ACE inhibitors, exerts a beneficial effect on cardiac function in the CHF rat and that one of the mechanisms for this effect is attenuation of elevated cardiac ACE activity.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1995

Effects of NKH477, a water-soluble forskolin derivative, on cardiac function in rats with chronic heart failure after myocardial infarction.

Our study was designed to determine whether NKH477, a novel, potent and water-soluble forskolin derivative, may exert a positive inotropic effect in rats with chronic heart failure (CHF) after myocardial infarction. Cardiac output and stroke volume indices were decreased and systemic vascular resistance was increased 12 wk after left coronary artery ligation, suggesting that CHF has developed at this time. Dobutamine (4 micrograms/kg i.v.) increased the cardiac output and stroke volume indices in sham-operated rats (22.7 +/- 1.9 and 15.1 +/- 2.0% increase, respectively), whereas such increases were attenuated in rats 12 wk after the induction of myocardial infarction (cardiac output index: 4.0 +/- 1.4% increase and stroke volume index: 2.2 +/- 1.8% increase, respectively). In contrast to beta-adrenoceptor agonist, NKH477 (3, 10 and 30 micrograms/kg i.v.) increased cardiac output and stroke volume indices in the rats with CHF. The beta-adrenergic receptor density, measured by [3H] CGP-12177 binding assay, was reduced in homogenates of the failing heart. These results suggest that the decrease in cardiac beta-adrenergic receptor density may account, in part, for the reduction in the responsiveness to beta-adrenoceptor agonists. The primary defects in the signal transduction from beta-adrenergic receptor to adenylate cyclase, such as the receptor down-regulation and the failure in signaling from adenylate cyclase, may be present in the CHF heart. It may be possible to reverse the cardiac dysfunction associated with CHF with NKH477.

Animals↗
PubMed1995

A possible involvement of sodium channel blockade of class-I-type antiarrhythmic agents in postischemic contractile recovery of isolated, perfused hearts.

The present study was undertaken to test the hypothesis that the degree of sodium channel blockade by class-I-type antiarrhythmic agents accounts for enhancement of postischemic contractile recovery of ischemic/reperfused hearts. Electrophysiological studies showed that the class-I-type antiarrhythmic agents quinidine, disopyramide, procainamide, lidocaine, mexiletine, flecainide and pilsicainide suppressed the Vmax value of the rat left ventricular muscle cell, a marker of sodium channel blockade, in a concentration-dependent manner. Isolated rat hearts were subjected to 35 min of ischemia and 60 min of reperfusion. Postischemic contractile recovery, which was never detected in untreated hearts, was enhanced in hearts pretreated with these antiarrhythmic agents during the last 3 min before ischemia at concentrations ranging from 3 to 300 microM. Tissue Na, but not Ca, accumulation was also detected in the ischemic heart, and tissue Na and Ca accumulation was observed in the reperfused heart, which suggests that sodium overload occurs during ischemia, followed by sodium and calcium overload during reperfusion. The degree of postischemic contractile recovery seen in the presence of these antiarrhythmic agents was inversely related to tissue Na or Ca accumulation after reperfusion, which suggests that class-I-type antiarrhythmic agents inhibit sodium overload occurring in ischemic/reperfused myocardial cells. A close relationship between postischemic contractile recovery of the perfused heart and depression in the Vmax value of the ventricular muscle was also observed. These results suggest that the ability class-I-type antiarrhythmic agents to inhibit myocardial sodium channels plays a significant role in the enhancement of postischemic contractile recovery of the ischemic/reperfused heart.

Animals↗
PubMed1994

Effects of naftidrofuryl oxalate on microsphere-induced changes in acetylcholine and amino acid content of rat brain regions.

Effects of naftidrofuryl oxalate (naftidrofuryl) on neurotransmitter, acetylcholine, and amino acid content of brain regions following microsphere-induced cerebral embolism were examined to elucidate its possible therapeutic effects on ischemic brain. Rats received 900 microspheres (48 microns in diameter) via the right internal carotid artery, followed by ligation of the right common carotid artery; and histological and biochemical alterations were examined on the 3rd, 5th, and 28th days after embolism. The embolism induced increases in triphenyltetrazolium chloride- (TTC)-unstained areas and decreases in acetylcholine, glutamate, aspartate, and gamma-aminobutyric acid (GABA) contents in the cerebral cortex, striatum, and hippocampus of the right hemisphere, suggesting that microsphere embolism causes severe damage to these brain regions. Hematoxylin-eosin staining of the right cortical sections after embolism showed degeneration and necrosis of nerve cells with chromatolytic nuclei and eosinophilic cytoplasm. Changes in neurotransmitters of the left hemisphere were relatively small. Treatment with naftidrofuryl of the embolized rats with stroke-like symptoms took place from postoperative day 1 to 28. Treatment resulted in a reduction in TTC-unstained areas, less morphological damage to cerebral cortex on the 3rd and 5th days, and an appreciable restoration of acetylcholine content of three brain regions of the right hemisphere throughout the experiment, but restoration of neurotransmitter amino acids was observed to a smaller degree. The results suggest that naftidrofuryl is capable of preventing the development of ischemia-induced, sustained damage to brain regions vulnerable to oxygen deficiency, particularly by improving impaired acetylcholine metabolism.

Acetylcholine↗
PubMed1994

Analysis of effector T cells against the murine syngeneic tumor MethA in mice orally administered antitumor polysaccharide SPR-901.

The growth of MethA tumor was significantly inhibited by oral administration of the alpha-glucan SPR-901 in BALB/c (+/+) mice but not in nude mice. Mice treated orally with SPR-901 exhibited an augmentation of antigen-specific resistance against rechallenge with the tumor cells. The tumor-neutralizing activity of regional lymph node cells from MethA-bearing mice against the tumor was augmented by oral administration of SPR-901. The tumor-neutralizing activity of lymph node cells from SPR-901-treated mice mainly appeared in Lyt2+ cells. Furthermore, lymphokine-activated killer activity of these cells was enhanced by administration of SPR-901. The antitumor effect of SPR-901 was abrogated in mice depleted of either L3T4+ or Lyt2+ cells, and in cyclosporin-A-treated mice. These results suggest that Lyt2+ cells are important effector cells in MethA-bearing mice orally administered SPR-901 and that functional exertion of both Lyt2+ and L3T4+ T cells is necessary for the antitumor effect of orally administered SPR-901 in vivo.

Adjuvants, Immunologic↗
PubMed1994

Effect of antitumor polysaccharide SPR-901 on antitumor activity in combination with 5-FU.

We have examined the effects of the antitumor polysaccharide SPR-901 in combination with 5-fluorouracil (5-FU) on the antitumor activities against mouse syngeneic tumors. SPR-901 was administered p.o. from day 1 to day 10 at the dose rate of 30 mg/kg, and 5-FU was injected i.p. from day 1 to day 5 at the dose rate of 20 mg/kg after BALB/c mice were injected s.c. with 6 x 10(4) cells/mouse of Meth A on day 0. Tumor sizes of mice treated with both SPR-901 and 5-FU were significantly smaller than those from the untreated control group on days 10, 15 and 20. LAK activity of spleen cells from mice treated with both SPR-901 and 5-FU was higher than that from the untreated control group and either the SPR-901 or 5-FU treated group. Flow cytometrical analysis revealed that spleen cells from mice treated with both SPR-901 and 5-FU were much more abundant in both T-cell receptor alpha/beta+ and IL-2 receptor alpha+ T-cells. Furthermore, spleen cells from both the SPR-901- and 5-FU-treated groups exhibited higher growth responses to IL-2 than that from the untreated control group and either of the SPR-901- or 5-FU-treated groups. Therefore, the effects of the antitumor polysaccharide SPR-901 used in combination with 5-FU were augmented as compared with single drug use.

Animals↗
PubMed1994

Effects of tanshinone VI derivatives on post-hypoxic contractile dysfunction of perfused rat hearts.

The present study was undertaken to elucidate the effects of sodium tanshinone VI 1-phenolate (1), 1'-O-hydrogen succinyltanshinone VI 1-O-hydrogen succinate (2), and disodium 1'-O-succinyltanshinone VI 1-O-succinate (3), water-soluble derivatives of tanshinone VI, on post-hypoxic contractile recovery of isolated perfused rat hearts. The effects were compared with those of tanshinone VI as tested previously. The hearts were perfused for 20 min under hypoxic conditions, followed by 45 min reoxygenation, and their cardiac performance was determined. Changes in tissue sodium, potassium, calcium, and magnesium contents after reoxygenation, and release of creatine kinase and purines and bases (ATP metabolites) during hypoxia/reoxygenation were also examined. The derivatives were dissolved in a Krebs-Henseleit buffer and administered at concentrations of 42 nM into the buffer. Hypoxia/reoxygenation resulted in slight recovery of cardiac contractile force, significant alterations in tissue ion concentrations, and pronounced release of creatine kinase and ATP metabolites, suggesting hypoxia/reoxygenation-induced functional and morphological damage. The tanshinone VI derivatives improved post-hypoxic contractile recovery, which was associated with restoration of tissue ionic concentrations, and diminishment of the release of creatine kinase and ATP metabolites from the hypoxic/reoxygenated hearts. The efficacy of these compounds was similar to that of tanshinone VI. The results suggest that water-soluble tanshinone VI derivatives, like tanshinone VI itself, are beneficial for hypoxia/reoxygenation injury.

Adenosine Triphosphate↗
PubMed1994

Effects of naftidrofuryl oxalate on microsphere embolism-induced decrease in regional blood flow of rat brain.

1. The purpose of the present study was to determine whether naftidrofuryl oxalate (naftidrofuryl), a vasodilator, is capable of improving brain regional blood flow of animals in sustained ischaemia. 2. Cerebral ischaemia was induced by injecting 900 microspheres (48 microns in diameter) into the right internal carotid artery of rats. Cerebral blood flow of brain regions was measured by a hydrogen clearance method on the 3rd, 7th and 28th days after the onset of ischaemia. Ischaemic animals were treated with naftidrofuryl, 15 mg kg-1 day-1 i.p., from the first to 28th day. 3. Microsphere-embolism caused a sustained decrease in cortical and striatal blood flow over a period of 28 days, whereas hippocampal blood flow was decreased on the 3rd day but not on the 7th or 28th day. On the 3rd day, the striatal and hippocampal but not cortical blood flow of naftidrofuryl-treated, microsphere-embolized rats was higher than untreated rats. On the 7th and 28th days, the cortical and striatal blood flow of the treated and untreated animals did not differ. 4. Brain slices from microsphere-embolized rats contained areas, which were not stained with triphenyltetrazolium chloride (TTC), to a similar degree on the 3rd, 7th and 28th days, indicating the genesis of cerebral infarction. TTC-unstained areas of microsphere-embolized rats that had received naftidrofuryl treatment were smaller than those of untreated rats on the 3rd and 7th days, but not on the 28th day. 5. The results suggest that naftidrofuryl improves cerebral circulation impaired by microsphere-induced ischaemia and this higher level of cerebral blood flow of the treated animal may account for the delayed development of cerebral infarction.

Animals↗
PubMed1994

Hyperresponsiveness of cardiac muscles to histamine in reserpine-treated guinea pigs.

The hyperresponsiveness of cardiac tissue to histamine following treatment with reserpine was pharmacologically characterized. Guinea pig hearts were isolated 24 hours after intraperitoneal administration of 5 mg/kg reserpine. This treatment resulted in a complete depletion of tissue norepinephrine. Reserpine treatment potentiated the positive inotropic response of isolated perfused hearts to histamine at doses ranging from 0.3 to 3 micrograms (23 to 57% increase for reserpine-treated animals vs. 14 to 32% increase for control animals). Isolated left ventricular papillary muscle of reserpine-treated guinea pig hearts also showed hyperresponsiveness to histamine at concentrations of 0.1 microM or greater. The hyperresponsiveness of the papillary muscle contraction of the reserpine-treated animals to histamine was abolished in the presence of 1 microM cimetidine, but not attenuated in the presence of 1 microM diphenhydramine. This hyperresponsiveness was not modified by 1 microM bunazosin or 1 microM propranolol. The results suggest that H2-receptor mediated action plays a role in the hyperresponsiveness of cardiac muscles to histamine.

Animals↗
PubMed1994

Improvement of cardiac function and myocardial energy metabolism of rats with chronic heart failure by long-term coenzyme Q10 treatment.

The effects of long-term treatment with coenzyme Q10 (CoQ10) on myocardial energy metabolism of rats with chronic heart failure (CHF) were examined. Left coronary artery ligation resulted in decreases in blood pressure, left ventricular developed pressure, the first derivative of left ventricular developed pressure, cardiac output and stroke volume indices and caused an increase in left ventricular end-diastolic pressure 12 weeks after the operation. Significant decreases in adenosine-5'-triphosphate, creatine phosphate, creatine and inorganic phosphate contents and the mitochondrial oxygen consumption rate of the viable left and right ventricles were detected in the CHF rat. Oral administration of 5 mg/kg/day CoQ10 for 12 weeks attenuated the changes in the first derivative of left ventricular developed pressure, cardiac output and stroke volume indices of the CHF rat but did not significantly improve the survival of CHF animals. The developed infarct area was approximately 40% of the whole left ventricle, irrespective of treatment with or without CoQ10. There was no reversal in the decreased myocardial CoQ9 and CoQ10 contents of the CHF rat after treatment with exogenous CoQ10. In the right ventricle of CoQ10-treated animals, a significant recovery of creatine, inorganic phosphate and mitochondrial oxygen consumption rate, and a small restoration of creatine phosphate but not of adenosine-5'-triphosphate, were observed, which suggests an appreciable recovery of energy-producing ability in the right ventricle. In contrast, a significant restoration of tissue creatine and inorganic phosphate, but not of other variables, was detected in the left ventricle.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

[A case of nonresectable gastric cancer treated by sequential methotrexate and 5-fluorouracil].

An advanced gastric cancer patient with multiple retroperitoneal lymph node metastases and bone metastases was treated with sequential MTX and 5-FU. Complete response was obtained against both gastric primary lesion and retroperitoneal lymph nodes observed endoscopically and by computed tomography. Partial response was obtained against bone metastases observed by bone scintigraphy. Side effects of the chemotherapy were not observed.

Adenocarcinoma, Scirrhous↗
PubMed1993

Propafenone and disopyramide enhance post-ischemic contractile and metabolic recovery of perfused hearts.

The effects of sodium channel blockers, propafenone and disopyramide, on post-ischemic contractile dysfunction of perfused rat hearts were examined. Isolated hearts were subjected to 35 min ischemia, followed by 60 min reperfusion with and without administration of either drug during 3 min of pre-ischemia. Ischemia/reperfusion induced complete cardiac dysfunction, rise in left ventricular end-diastolic pressure, increase in perfusion pressure, accumulation of Na+ and Ca2+ and loss of K+ and Mg2+, and release of creatine kinase and purine nucleosides and bases from the heart. These observations suggest that ischemia/reperfusion in the current study induces cardiac cell necrosis or an increase in cell membrane permeability to ions, substrates and macromolecules. Treatment of perfused hearts with either propafenone at concentrations ranging from 5 to 70 microM, or disopyramide at concentrations of 100 microM or higher resulted in a pronounced contractile recovery of the heart, associated with suppression of reperfusion-induced tissue ion alteration and inhibition of reperfusion-induced release of creatine kinase and purine nucleosides and bases. Ischemic insult itself caused tissue Na+ accumulation and K+ loss without any change in tissue Ca2+ and Mg2+. The alterations in the electrolytes were attenuated by treatment with either agent. The results suggest that prevention of ischemia- and reperfusion-induced ionic disturbance of cardiac cells by propafenone and disopyramide plays a role in the improvement of post-ischemic contractile dysfunction.

Adenosine Triphosphate↗