Biomedical subjects

S Takeo

Publications and source records attributed to S Takeo.

At least 109 records · Page 6Linked to original sources

PubMed1993

Detection of serum cytokine levels in experimental cancer cachexia of colon 26 adenocarcinoma-bearing mice.

The aim of this study was to evaluate the correlations between tumor size and cachexia parameters including cytokine levels in serum. In transplantable colon 26 adenocarcinoma-bearing mice, parameters having negative correlations with tumor size were host weight changes, epididymal adipose tissue weight, glucose and interleukin 3 (IL-3) concentration in serum. Parameters having a positive correlation with tumor size were the number of circulating white blood cells and immunosuppressive acidic protein (IAP), interleukin 6 (IL-6) and transforming growth factor beta (TGF-beta) concentration in serum.

Adenocarcinoma↗

PubMed1993

Effects of naftidrofuryl oxalate on microsphere embolism-induced changes in tricarboxylic acid cycle intermediates of rats.

The present study was undertaken to determine whether naftidrofuryl oxalate, a cerebral vasodilator, may improve or attenuate microsphere embolism-induced damage to the mitochondrial tricarboxylic acid cycle. For this purpose, the intermediates in the tricarboxylic acid cycle were determined using cerebral cortex isolated from microsphere-injected rats with and without naftidrofuryl oxalate treatment. Seven-hundred microspheres, with a diameter of 48 microns were injected into the right hemisphere through the right common carotid artery. The presence of cerebral infarction on the 3rd day after the operation was confirmed by the development of triphenyltetrazolium chloride-unstained areas in brain sections. Succinate, fumarate, malate, citrate and alpha-ketoglutarate, but not oxaloacetate, contents were significantly decreased in the right hemisphere of rats on the 3rd day following microsphere embolism. In the left hemisphere, a similar but smaller decrease in these intermediates was seen. The rats, which showed typical stroke-like symptoms, were treated with 15 mg/kg naftidrofuryl oxalate i.p., twice daily for 2.5 days, resulting in a significant reversal of the intermediate content of both hemispheres toward the control and an increased in the triphenyltetrazolium-stained area of a coronal section of the right hemisphere relative to the untreated animals. The results suggest that naftidrofuryl oxalate attenuates the development of microsphere embolism-induced cerebral infarction and improves microsphere-induced impairment of the mitochondrial tricarboxylic acid cycle. The observed effects provided evidence for a possible site of action of the agent on ischemic brain energy metabolism.

Animals↗

PubMed1993

Serum antibody production by oral immunization with dextran B512.

Serum antibodies to dextran were detected when dextran B512 was orally administered to C3H/He mice. The amounts of serum antibodies were increased along with the dose of orally administered dextran B512. For serum antibody production, differences were observed among the strains of mice. C3H/He, C57BL/6 and CBA mice produced high levels of serum antibodies to dextran, while BALB/c and DBA/2 mice produced low levels of serum antibodies. The serum antibodies had groove-type combining sites, as determined by ELISA inhibitory assay.

Administration, Oral↗

PubMed1993

A role of prostaglandin in the secretion of inhibin and oestradiol-17 beta in equine chorionic gonadotrophin-primed rats.

The role of prostaglandins in the secretion of inhibin and oestradiol-17 beta was examined in immature female rats treated with equine chorionic gonadotrophin. Administration of prostaglandin (PG) F2 alpha to animals whose serum and ovarian levels of inhibin and oestradiol-17 beta had been suppressed by indomethacin given 24 h after equine chorionic gonadotrophin prevented the inhibition or restored the levels to normal. Initiation of PGF2 alpha replacement immediately after treatment with indomethacin was more effective. The results are consistent with the hypothesis that PGs play a regulatory role in the synthesis and secretion of inhibin and oestradiol-17 beta by the rat ovary.

Animals↗

PubMed1993

Application of 13C-labeling and nuclear magnetic resonance spectroscopy to pharmacokinetic research: measurement of metabolic rate of benzoic acid to hippuric acid in the rat.

The use of 13C-labeling and nuclear magnetic resonance (NMR) spectroscopy to trace the biotransformation of benzoic acid (BA) to hippuric acid (HA) in the rat has been described. Novel [2,4,6,7-13C4]BA, which was labeled in the specific protonated carbons, was used in order to enhance the sensitivity of 13C NMR detection on the basis of the nuclear Overhauser enhancement and short spin-lattice relaxation time. The urinary excretion of [2,4,6,7-13C4]HA formed from intravenously administered [2,4,6,7-13C4]BA was followed by proton-decoupled 13C NMR spectroscopy (only 10 min accumulation time) without any separation procedures such as extraction and chromatography, using [2-13C]sodium acetate as an internal standard for quantitation. The heights of resonances for C2,6 of [2,4,6,7-13C4]HA and C2 of the internal standard were used to calculate [2,4,6,7-13C4]HA concentration. The lower limit of measurable amounts (ca. 40 nmol) was found to be improved about one order of magnitude over that of the method using commercially available [7-13C]BA. In general, this tracer technique has the potential for wide application to pharmacokinetic research since xenobiotic and endogenous metabolism can be followed by very simple and convenient procedures.

Animals↗

PubMed1993

Regional energy metabolism of failing hearts following myocardial infarction.

To elucidate the relationship between functional alterations and disturbances in myocardial energy metabolism of rats with heart failure following coronary artery ligation, the left coronary artery of the rat was ligated and the time course of changes in cardiac function and myocardial energy state of the animal were examined for 12 weeks after the ligation. Coronary artery ligation resulted in approximately 40% infarction of the left ventricle, an increase in the right ventricular weight, a decrease in left ventricular developed pressure, an increase in left ventricular end-diastolic pressure throughout the experiment, suggesting the development of cardiac failure after the operation. Cardiac output and stroke volume indices were not altered during the first 4 weeks, but were significantly decreased on the 8th and 12th weeks, suggesting that cardiac function had further aggravated by 8 weeks after the operation. Myocardial energy profiles of the scar tissue, the remaining left ventricle and interseptum, and the right ventricle were determined. Tissue ATP (27.54 +/- 0.82 to 26.38 +/- 1.58 mumol/g dry tissue; n = 8-10) and creatine phosphate (26.73 +/- 1.63 to 24.38 +/- 1.83 mumol/g dry tissue; n = 8-10) of the remaining viable left ventricle were lower than control (33.17 +/- 0.73 and 40.04 +/- 1.07 mumol/g dry tissue; n = 8) throughout the experiment. A marked decrease in tissue ATP and CP was seen in the scar tissue throughout the experiment. Increases in tissue lactate of the remaining left ventricle and the right ventricle were detected from 1 to 2 weeks after the operation, but returned to the control levels thereafter. Mitochondrial oxygen consumption rates of isolated myocardial bundles from the 8th and 12th weeks (21.03 +/- 2.22 and 17.79 +/- 3.24 ng oxygen/min/mg dry tissue; n = 8) were lower than control (33.15 +/- 1.95 ng oxygen/min/mg dry tissue; n = 5), and those of the interseptum (23.71 +/- 1.33 ng oxygen/min/mg dry tissue; n = 8) and the right ventricle (22.44 +/- 2.73 ng oxygen/min/mg dry tissue; n = 8) on the 12th week after the operation were lower than control (33.58 +/- 2.80 and 34.83 +/- 2.64 ng oxygen/min/mg dry tissue; n = 5). The results provide evidence for a decline in myocardial energy store and energy producing ability associated with the development of cardiac failure.

Acute Disease↗

PubMed1993

Beneficial effects of quinidine on post-ischemic contractile failure of isolated rat hearts.

The present study was undertaken to determine whether quinidine may improve ischemia/reperfusion-induced functional and metabolic injury of isolated rat hearts. Thirty-five-min ischemia and the subsequent 60-min reperfusion resulted in no post-ischemic force generation, an increase in left ventricular end-diastolic pressure (about 1500%) and a sustained rise in perfusion pressure (136 +/- 15% of initial). This was associated with an increase in the release of creatine kinase and ATP metabolites from the reperfused heart, a decrease in tissue high-energy phosphates, changes in tissue sodium, calcium, potassium and magnesium contents, and a reduction in the triphenyltetrazolium chloride (TTC)-stained area, an indicator of infarction. Hearts were treated with 3-100 microM quinidine 3 min before ischemia. Quinidine at concentrations of 10 microM or greater resulted in post-ischemic contractile recovery in a concentration-dependent manner (61 +/- 8 to 95 +/- 8% of initial). Ischemia/reperfusion-induced metabolic and histologic alterations were also suppressed by treatment with quinidine in a concentration-dependent manner. The results suggest that quinidine has a cardioprotective effect in ischemic/reperfused hearts. Because transmembrane fluxes of ions, substrates, and enzymes were suppressed by treatment with quinidine, protection of cardiac cell membrane function and/or integrity against ischemia/reperfusion-induced ionic imbalance, presumably sodium imbalance, across the sarcolemma is a possible mechanism by which quinidine may act. Slightly higher levels of ATP were detected in the treated hearts at 10 and 15 min, but not at 35 min of ischemia. Such preservation of high-energy phosphates might also be beneficial for protecting myocardial cells against ischemic damage.

Adenosine Triphosphate↗

PubMed1993

Sustained decrease in brain regional blood flow after microsphere embolism in rats.

BACKGROUND AND PURPOSE: An experimental model that induces sustained ischemia and infarction may provide useful information relevant to prevention of the development of ischemic brain disease. The purpose of the present study was to elucidate the pathophysiological consequences of cerebral blood flow under sustained cerebral ischemia or oligemia and infarction in rats after microsphere embolism. METHODS: We injected 900 microspheres (48 microns in diameter) into the right internal carotid artery of 146 rats and determined the time course of changes in blood flow of the cerebral cortex, striatum, and hippocampus of both hemispheres by the hydrogen clearance method for a period of 28 days after the operation. Infarct area was determined by triphenyltetrazolium chloride staining and hematoxylin and eosin staining methods. RESULTS: Cortical and striatal blood flow of the right hemisphere of microsphere-injected rats was significantly decreased after the embolism, and this was sustained throughout the experiment. Hippocampal blood flow of the microsphere-injected hemisphere was also decreased on days 1 and 3 but tended to return toward control levels thereafter. In the left hemisphere, reduction in regional blood flow was detected in the cortex and hippocampus on day 1 and the striatum on day 3. A triphenyltetrazolium chloride-unstained area had developed by day 3 after the embolism. The extent of the area was similar to that on days 7 and 28. Microscopic examination revealed degenerative areas scattered mainly in the parietotemporal cortex, corpus callosum, hippocampus, thalamus, and lenticular nucleus of the embolized hemisphere, demonstrating the induction of widespread necrosis after embolism. CONCLUSIONS: Microsphere embolism resulted in a sustained decrease in regional blood flow and production of cerebral infarction in the brain regions of the microsphere-injected hemisphere.

Animals↗

PubMed1993

Inhibition by indomethacin of the already accelerated secretion of inhibin and estradiol in equine chorionic gonadotropin-primed immature female rats.

In immature female rats, the secretion of ovarian inhibin and estradiol is greatly accelerated by equine chorionic gonadotropin (eCG) treatment. The present study has been carried out to determine whether or not the levels of the two hormones are inhibited by a single s.c.-injection of indomethacin (INDO) 24 h after eCG administration. The levels of ovarian hormones and gonadotropins were measured by double-antibody radioimmunoassay using 125I-labeled radioligands. The serum levels of inhibin and estradiol were considerably inhibited within 24 and 12 h, respectively, after INDO injection. In addition, the serum levels of follicle-stimulating hormone (FSH) after INDO injection remained lower than the basal levels before eCG treatment. The luteinizing hormone (LH) levels were significantly reduced within 12 h after INDO treatment. The results demonstrate that the levels of inhibin and estradiol, even in the situation where the production of both hormones is already accelerated by eCG pretreatment, are suppressed by an inhibitor of prostaglandin (PG) synthesis, suggesting that locally produced PGs may play a role in the regulation of the production of both hormones in the ovary.

Animals↗

PubMed1993

A comparison of the effects of estradiol and 2- and 4-hydroxyestradiol on uterine ornithine decarboxylase activity in immature rats.

Effects of estradiol (E2) and catechol-estrogens (CEs: 2-OHE2 and 4-OHE2) on uterine ornithine decarboxylase (ODC) activity have been compared in immature rats. The intensity of their actions by s.c. (1 microgram) and intrauterine right-horn (i.u., 25 ng) injection was in the order of: 4-OHE2 > or = E2 > 2-OHE2. Although i.u. -injection of E2 caused an increase in ODC activity in the left (intact)-horn, which was about 60% that of the right-horn, the effects by CEs were limited only to the right-horn. The results are consistent with the previous view about the order of the potency of 4-OHE2 and 2-OHE2 and also suggest that locally produced CEs may play a role in the physiological functions of the production site.

Animals↗

PubMed1993

Sustained changes in acetylcholine and amino acid contents of brain regions following microsphere embolism in rats.

The present study was undertaken to explore changes in neurotransmitters and neuromodulators of brain regions impaired by microsphere embolism-induced, sustained ischemia. Nine hundred microspheres (48 microns) were injected into the right internal carotid artery of rats, and the time course of changes in the triphenyltetrazolium chloride (TTC)-stained areas of their brain slices and acetylcholine and amino acid contents in the cerebral cortex, striatum and hippocampus of both hemispheres were determined. The TTC-unstained area, a measure of infarction, was developed in the right hemisphere by the 3rd day after the embolism, which was similar to that on the 28th day. A marked decline in acetylcholine content of these three regions of the right hemisphere was detected throughout the experiment (28 days). The glutamate, aspartate, GABA, and taurine levels were markedly decreased following microsphere-embolism. Most of these decreases were significantly attenuated during the first 5 days following the embolism, and they then partially recovered with time after the operation. Minor metabolic changes were observed in the left hemisphere. The results suggest that microsphere-embolism induces cerebral infarction and/or sustained damage to acetylcholine and neurotransmitter amino acid synthesis and/or catabolism of the brain regions. This model may provide information concerning the pathophysiological alterations in long-term cerebral ischemia and infarction.

Acetylcholine↗

PubMed1993

In vivo profile of myocardial energy metabolism of pressure-overloaded rat.

Cardiac energy metabolism of pressure-overloaded rat hearts was examined under in vivo and in vitro conditions. Two, 4 and 6 weeks after constriction of the abdominal artery, the hemodynamic and metabolic profiles of hearts in vivo and of perfused hearts were determined. Significant increases in left ventricular weight/body weight (30 to 45% increase relative to the sham group), systolic and diastolic blood pressure (22 to 33% increase) and pressure-rate product (31 to 33% increase) were observed 2, 4 and 6 weeks after the operation, and a slight but significant decrease in heart rate was observed at 2 weeks after the operation. Tissue hydroxyproline content increased (17 to 93%) with time after pressure-overload. These findings are indicators of pressure-overloaded cardiac hypertrophy. The total high-energy phosphates of the in vivo rat myocardium under artificial respiration were lower than those of sham-operated rat myocardium 2 (23%) and 4 weeks (21%), but not 6 weeks after aortic constriction. The maximal oxygen consumption rates of mitochondria, when determined in the skinned cardiac fibers, also decreased 2 (47%) and 4 weeks (36%), but reversed 6 weeks after pressure-overload. However, the myocardial ATP, a utilizing form of high-energy phosphate, of pressure-overloaded rat myocardium remained normal at all times after cardiac hypertrophy. This suggests that alterations in hemodynamic variables of in vivo pressure-overloaded rats may not be attributable to a reduction in the myocardial energy production. In the perfused hearts isolated from pressure-overloaded rats, tissue ATP levels were similar to those of sham-operated rats, although the tissue creatine phosphate tended to be reduced in the pressure-overloaded animals at all stages of cardiac hypertrophy examined. Only a marginal decrease in the tissue high-energy phosphate (13%) was observed 4 weeks after the operation relative to that of sham-operated rats. In contrast, the developed tension of the perfused pressure-overloaded rat hearts was consistently lower (27 to 36%) than that of the sham-operated rat hearts. The results suggest that the high-energy phosphate levels of pressure-overloaded rat myocardium in vitro are unlikely to account for the observed decline in cardiac contractile function. The reduction of myocardial high-energy phosphates of pressure overloaded rats may be due to an adaptative change rather than a causal events.

Adenosine Triphosphate↗

PubMed1993

Novel cytocidal compounds, oxopropalines from Streptomyces sp. G324 producing lavendamycin. I. Taxonomy of the producing organism, fermentation, isolation and biological activities.

In the course of our investigation aimed at the discovery of novel antitumor antibiotics from microorganisms, Streptomyces sp. G324 was found to produce the antitumor antibiotic, lavendamycin, and also, to yield the novel beta-carboline compounds, oxopropalines. We isolated five compounds as oxopropalines A, B, D, E and G. Oxopropalines B, D and G showed cytocidal activities against human or murine tumor cell lines in vitro.

Animals↗

PubMed1993

Improvement of ischemia/reperfusion-induced contractile dysfunction of perfused hearts by class Ic antiarrhythmic agents.

The present study was undertaken to determine whether class Ic antiarrhythmic agents, flecainide and pilsicainide, improve ischemia/reperfusion-induced cardiac contractile dysfunction. Isolated rat hearts were subjected to a 35-min global ischemia, followed by a 60-min reperfusion, and the functional and metabolic consequences were examined. Ischemia/reperfusion resulted in no recovery of contractile function and a sustained rise in left ventricular and diastolic pressure of the perfused heart during reperfusion. The ischemia/reperfusion also induced increases in tissue sodium and calcium levels, decreases in potassium and magnesium ion contents and the release of creatine kinase and purine nucleosides and bases (ATP metabolites) from the heart, suggesting a pronounced change in cardiac transmembrane flux of ions, substrates and macromolecules. Treatment of the perfused heart with either 5 to 50 microM flecainide or 10 to 100 microM pilsicainide during preischemia resulted in diminishing the postischemic contractile dysfunction; suppressing the changes in tissue sodium, potassium, calcium and magnesium contents; and attenuating the release of creatine kinase and ATP metabolites in a concentration-dependent manner. Tissue sodium accumulation and potassium loss were also observed at the end of ischemia, which was attenuated by pretreatment with these agents. These results provided evidence that class Ic antiarrhythmic agents are capable of diminishing ischemia/reperfusion-induced contractile dysfunction and tissue ionic disturbance.

Adenosine Triphosphate↗

PubMed1993

[A case of solitary plasmacytoma that originated in a rib].

A 52-year-old woman was admitted to our hospital with the chief complaint of left anterior chest pain. A chest X-ray showed a tumor shadow in the left 4th rib. No abnormalities were detected in peripheral blood and aspirated bone marrow samples. The tumor was surgically resected with the involved bone, the intercostal muscle and the parietal pleura. The resected specimen contained a 3 x 6 x 3 cm lesion, and histological investigation of the tumor revealed a plasmacytoma of the rib. It relapsed as a multiple myeloma within two months after surgery. Chemotherapy was administered and the bone lesions were observed to disappear. We believe that the best way to treat solitary plasmacytoma is to first resect the solitary tumor, and then to add cobalt irradiation and chemotherapy after surgery.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1992

Indomethacin inhibits the secretion of inhibin and oestradiol-17 beta stimulated by pregnant mare serum gonadotrophin in the immature female rat.

The involvement of prostaglandins (PGs) in the regulation of inhibin and oestradiol-17 beta secretion from the ovary was studied by determining the effects of indomethacin and/or pregnant mare serum gonadotrophin (PMSG) on the levels of ovarian hormones in immature female rats. An increase in serum and ovarian levels of inhibin and oestradiol-17 beta was observed with a reciprocal reduction in serum follicle-stimulating hormone (FSH) levels from within 26 to 50 h after a single injection of 5 IU PMSG (s.c.) when the rats were 26 days of age. Administration of indomethacin to suppress PGs synthesis, simultaneously with PMSG, resulted in a substantial reduction in the levels of ovarian PGF2 alpha and serum inhibin and oestradiol-17 beta, which were both enhanced by PMSG treatment, 24 h after treatment with drugs. Indomethacin also reduced the basal serum level of inhibin. In the indomethacin-treated animals, the serum level of FSH was significantly increased regardless of the treatment with PMSG, indicating that the negative feedback regulation between FSH and inhibin is operating in these animals. These results demonstrate the inhibitory effects of indomethacin on PMSG-enhanced inhibin and oestradiol-17 beta production, suggesting that PGs play a regulatory role in the secretion of inhibin and oestradiol-17 beta from the gonadotrophin-stimulated ovary.

Animals↗

PubMed1992

Inhibitory and stimulatory actions of danazol in rat ovarian and uterine tissues.

We examined whether danazol has a direct action on ovarian steroid secretion and/or uterine prostaglandin (PG) F2 alpha catabolic activity in immature rats in which the first ovulation was induced and in adult ovariectomized rats. The preovulatory surge of estradiol and progesterone was markedly suppressed together with that of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) by danazol administration under conditions that blocked the first ovulation. Uterine weight and PGF2 alpha catabolic activity enhanced by endogenous estrogen were greatly decreased by danazol treatment at a dose that did not block the first ovulation in immature rats. When danazol (30 mg) was given s.c. once daily for 2 days to ovariectomized rats, the uterine weight and PGF2 alpha catabolic activity per uterus were clearly increased, and the compensatory increase in FSH levels as a result of castration was not influenced, although the compensatory increase in LH levels was inhibited. These results demonstrate that danazol has a direct action on the ovary and uterus, and give further support to the view put forward in our previous paper that these actions of danazol may contribute to its therapeutic effects.

Administration, Oral↗

PubMed1992

Protective effect of SPR-901 (RBS) on the decrease of peripheral leukocyte number in 5-fluorouracil-treated mice.

5-Fluorouracil (5-FU) induces a decrease in the number of peripheral leukocytes (leukopenia), which is one of the major obstacles in the chemotherapy of cancer. The number of peripheral leukocytes decreased by day 4 in mice injected i.p. with 130 mg/kg of 5-FU and recovered to the normal level by day 8. Such a decrease by 5-FU was prevented to some extent by the oral administration of 30 mg/kg/day of SPR-901. Proliferative responses of bone marrow cells to granulocyte/macrophage colony stimulating factor (GM-CSF) or granulocyte colony stimulating factor (G-CSF) were suppressed by 5-FU treatment and their recoveries were enhanced by SPR-901. The serum level of IL-6 in 5-FU-treated mice was increased by SPR-901. All of the mice treated with 300 mg/kg of 5-FU in combination with SPR-901 survived over 15 days, however, only 4 of 10 mice treated only with 300 mg/kg of 5-FU survived. These results suggest that SPR-901 acts on macrophages directly or indirectly, giving rise to the enhanced production of IL-1, IL-6, and other factors. Some of the factors derived from SPR-901 activated macrophages, perhaps mainly IL-6, act on the early stage of development of multipotent bone marrow progenitors synergistically with GM-CSF.

Animals↗