An application of HPLC for identification of abietane-type pigments from Salvia miltiorrhiza and their effects on post-hypoxic cardiac contractile force in rats.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to S Takeo.
Explore the source record for details and available documents.
BACKGROUND AND PURPOSE: Information on sustained damage to cerebral function and metabolism after cerebral ischemia is useful for prophylaxis and therapeutics of cerebral infarction. The purpose of the present study was to induce sustained damage to brain regions after cerebral ischemia in experimental animals. For this purpose, we examined animal behavior and cerebral energy metabolism following microsphere embolism in rats. METHODS: We injected 900 microspheres (48 microns in diameter) into the right internal carotid artery of 110 rats and determined the time course of changes in the rats' behavior and the energy metabolism of the cortex, striatum, and hippocampus of both hemispheres. We injected the same volume of vehicle, without microspheres, into 28 sham-operated rats; there were 14 nonoperated control rats. RESULTS: Peak increase in lactate content and decrease in adenosine triphosphate and creatine phosphate of these brain regions of the right hemisphere were seen on the first day after microsphere embolism, whereas peak increases in glucose and glycogen contents of these regions were observed on the third day. Most of the metabolic alterations in all these regions continued for up to 28 days after operation, although they recovered toward control levels with time after the operation. The extent and trend of metabolite changes of the right hemisphere after microsphere embolism were similar in the three brain regions. In the left hemisphere, similar metabolic changes were observed, but to a lesser degree. The time course of changes in behavioral scores following microsphere embolism revealed marked stroke-like symptoms on the first day and relatively rapid disappearance of the symptoms with time after embolism. CONCLUSIONS: Microsphere embolism is capable of inducing widespread, sustained damage to energy metabolism of brain regions.
The effects of oral administration of antitumor polysaccharide SPR-901 (RBS), an alpha-1,3 branched alpha-1,6 glucan, on concanavalin A (Con A)-induced interleukin 2 (IL-2) production of splenocytes were studied. The augmentation effect on Con A-induced IL-2 production was evident when more than 30 mg/kg of SPR-901 was administered orally to mice. On the other hand, oral administration of B512 dextran, an analogous alpha-1,6 glucan, did not show any augmentation effects on IL-2 production. The augmentation effect of SPR-901 on IL-2 production seemed to be mediated mainly by macrophages stimulated with SPR-901.
The present study was undertaken to determine whether befunolol (BFE 60, CAS 39543-79-8) a beta-adrenoceptor blocking agent, improves post-hypoxic contractile and metabolic recovery of perfused hearts. Isolated rat hearts were perfused for 20 min under hypoxic conditions, followed by 45-min reoxygenation. Hypoxia/reoxygenation induced less than 5% post-hypoxic recovery of cardiac contractile force, incomplete return of resting tension of hearts, accumulation of tissue calcium, and release of purine nucleosides and bases, and creatine kinase from the heart. When hypoxic hearts were treated with 500 mumol/l befunolol from 0 to 10 min of hypoxic perfusion, marked recovery of contractile force (more than 50% of the pre-hypoxic value), complete suppression of the tissue calcium accumulation and significant suppression of the increase in creatine kinase activity of the perfusate were seen after reoxygenation. This treatment also significantly prevented the release of purine nucleosides and bases during hypoxia. These results suggest that treatment with befunolol during hypoxic perfusion is beneficial for post-hypoxic recovery of cardiac function and myocardial metabolism, probably through a mechanism of suppression of transmembrane flux of substrates, ions and enzymes. Cardiac contractile force upon the onset of hypoxia declined more rapidly and myocardial high-energy phosphate content after 10 min of hypoxia was significantly higher in befunolol-treated hearts than in hearts without treatment. Thus, energy-sparing effects may also contribute to the beneficial post-hypoxic recovery of cardiac function and metabolism.
We measured pre- and postoperative CEA level in 330 patients who underwent resection for lung cancer at Kyushu Cancer Center Hospital between 1983 and 1986 using RIA method. There were 93 patients with high preoperative serum CEA level above 5 ng/ml. The interrelationships among preoperative serum CEA level, prognostic factors, outcome, and postoperative change of CEA level were investigated in the 93 patients. Five-year survival rate of patients with preoperative serum CEA level ranging from 5.0 to 10.0 ng/ml (N = 53) was 60.0%, while that of patients with preoperative CEA level over 10.1 ng/ml (N = 40) was 24.6% (P less than 0.05). Recurrent rate was higher in patients with preoperative CEA level over 10.1 ng/ml, especially in those with lung cancer at stages I or II. However, patients with preoperative CEA level about 50 ng/ml, showed good outcome after curative resection. All 12 patients in whom postoperative serum CEA level did not return to normal died within 4 years, indicating that normalization of CEA level is an important factor in prognosis. This study indicates that among lung cancer patients with high serum CEA level, the preoperative CEA level and postoperative change of CEA level are apparently prognostic factors.
The present study was undertaken to elucidate the possible therapeutic effects of naftidrofuryl on energy metabolism of brain regions impaired for extended periods by microsphere embolism. Nine hundred microspheres (48 microns in diameter) were injected into the right internal carotid artery of rats, and changes in their behavior and energy metabolism of the cortex, striatum and hippocampus of both hemispheres were determined with and without naftidrofuryl treatment. Microsphere embolism induced increases in lactate, glucose and glycogen contents and decreases in ATP and creatine phosphate of these brain regions of the right hemisphere for up to 28 days after the operation, suggesting long-lasting cerebral ischemia or sustained damage to energy metabolism. These changes were gradually reversed with time after the operation. Microsphere-injected rats were treated twice a day with 15 mg/kg naftidrofuryl, and their behavioral and metabolic protection were determined on the 3rd, 5th and 28th days after the operation. Treatment of embolized animals with naftidrofuryl improved these variables appreciably on the 3rd and 28th days, but little on the 5th day. The improvement on the 3rd day was more evident in all brain regions monitored than that on the 28th day. The results suggest that naftidrofuryl exerts beneficial effects on the energy metabolism of brains damaged by microsphere embolism, the mechanism of which may be due to protection against the development of embolism-induced derangement.
The present study was designed to induce massive accumulation of calcium in the myocardium and to evaluate the effect of calcium overload on myocardial contractile function and biochemical activity of cardiac subcellular membranes. Rats were treated with an oral administration of 500,000 units/kg of vitamin D3 for 3 consecutive days, and their hearts were sampled on the 5th day for biochemical analysis. On the 4th and 5th days, heart rate, mean aortic pressure, left ventricular systolic pressure and left ventricular dP/dt were significantly lowered in vitamin D3-treated rats, demonstrating the existence of appreciable myocardial contractile dysfunction. Marked increases in the myocardial calcium (67-fold increase) and mitochondrial calcium contents (24-fold increase) were observed by hypervitaminosis D3. Mitochondrial oxidative phosphorylation and ATPase activity were significantly reduced by this treatment. A decline in sarcolemmal Na+, K(+)-ATPase activity was also observed, while relatively minor or insignificant changes in calcium uptake and ATPase activities of sarcoplasmic reticulum were detectable. Electron microscopic examination revealed calcium deposits in the mitochondria after vitamin D3 treatment. The results suggest that hypervitaminosis D3 produces massive accumulation of calcium in the myocardium, particularly in the cardiac mitochondrial membrane, which may induce an impairment in the mitochondrial function and eventually may lead to a failure in the cardiac contractile function.
The present study was conducted to investigate the mode of action of danazol by monitoring the first ovulation, serum luteinizing hormone (LH) levels and ovarian prostaglandin (PG) F2 alpha metabolism in pregnant mare serum gonadotropin (PMSG)-primed immature female rats. When danazol (750 mg/kg) was given p.o. once a day for 5 days (day 24-28), the occurrence of the first ovulation, the increase in capacity to form 13,14-dihydro-PGF2 alpha and PGF2 alpha levels induced by PMSG (5 IU) injected on day 26 were clearly inhibited on day 29. Danazol also markedly suppressed the LH surge occurring on day 28. Although the danazol-induced blockage of ovulation was restored by injection of human chorionic gonadotropin, the number of oocytes was significantly decreased as compared with that of controls. The present data indicate that the inhibitory actions of danazol on ovulation and ovarian PGF2 alpha metabolism may occur via some direct effects on the ovary in addition to the suppression of gonadotropin release from the pituitary gland.
The present study was undertaken to elucidate the possible actions of yohimbine on cardiac function and metabolism in the hypoxic and subsequently reoxygenated myocardium. For this purpose, rabbit hearts were perfused for 20 min under hypoxic conditions, followed by 45 min reoxygenated perfusion, and their functional and metabolic alterations with and without yohimbine treatment were examined. Hypoxia induced cessation of cardiac contractile force, rise in resting tension and depletion of tissue high-energy phosphates, which were poorly recovered by subsequent reoxygenation. Hypoxia also induced release of creatine kinase and ATP metabolites from perfused hearts and increases in tissue calcium and sodium contents, which were further enhanced upon subsequent reoxygenation. When hypoxic hearts were treated with 3 to 30 microM yohimbine, several beneficial effects were observed in a concentration-dependent manner. This included enhancement of posthypoxic recovery of contractile function and suppression of the hypoxia- and reoxygenation-induced rise in resting tension. Hypoxia/reoxygenation-induced release of ATP metabolites was inhibited and restoration of myocardial high-energy phosphates enhanced. Inhibition of reoxygenation-induced rise in tissue calcium and sodium and creatine kinase release were also noted. The findings suggest that suppression of transmembrane flux of ions, substrates and enzymes during hypoxia/reoxygenation plays a role in the posthypoxic functional and metabolic recovery. Yohimbine (3-30 microM) significantly depressed the maximal stimulus frequency the left atria could follow. These results suggest a close relationship between depression in the maximal driving frequency of atria and enhancement of the posthypoxic contractile and metabolic recovery of perfused hearts.(ABSTRACT TRUNCATED AT 250 WORDS)
A rare case of an extrathoracic giant hematoma developing after a thoracoplasty in a 67 year old man is presented herein. The patient underwent a right thoracoplasty without removal of plombage and a left thoracoplasty with removal of plombage for tuberculosis of the bilateral upper lobes 27 and 24 years prior to presentation, respectively. He presented to us in May, 1987, with a subscapular tumor which had been growing over the last 5 years. A giant tumor, measuring 23 x 17 x 12 cm and weighing 2585 g was successfully removed and the patient has since been well without any evidence of recurrence.
The present study was undertaken to elucidate a possible role of non-beta-receptor mediated effects in dl-propranolol-induced enhancement of post-hypoxic contractile and metabolic recovery in perfused rat hearts. The rat hearts were perfused for 30 min under reoxygenated conditions following 15 min-substrate free-hypoxic perfusion, and the cardiac performance and myocardial metabolism were examined. Hypoxia induced complete cessation of cardiac contractile force, depletion of myocardial high-energy phosphates, release of ATP metabolites and creatine kinase from the heart. Subsequent reoxygenation produced little recovery of cardiac contractile activity and tissue high-energy phosphates, further enhancement of the release of creatine kinase and the accumulation of tissue calcium. Treatment of the hypoxic hearts with dl-propranolol, d-propranolol and atenolol was performed during 5 to 15 min of hypoxic perfusion. dl-Propranolol and d-propranolol at the concentration of 45 microM elicited a significant recovery of cardiac contractile activity and restoration of myocardial high-energy phosphates. This treatment also resulted in a suppression of the release of creatine kinase and ATP metabolites and the tissue calcium accumulation observed during hypoxia and/or reoxygenation. However, such beneficial effects were not seen in hearts treated with 45 microM atenolol. dl-Propranolol and atenolol, but not d-propranolol, in a concentration of 45 microM have been shown to reveal beta-adrenoceptor blocking action. Thus, the results suggest the involvement of non-beta-receptor mediated effects of propranolol in the enhanced post-hypoxic contractile and metabolic recovery of the perfused rat heart. The non-beta-receptor mediated activity of these drugs appears to be related to their ability to suppress the maximal driving frequency of left atrial preparations.
Rats with delayed implantation, induced by ovariectomy or hypophysectomy, as well as those with normal pregnancy were used to examine the changes in uterine prostaglandin F2 alpha (PGF2 alpha) associated with implantation. In normal pregnant rats, while maximal uterine production of PGF2 alpha was found at 09:00, maximal catabolic enzyme activity (CEA) was seen at 17:00 of day 4. Uterine content of PGF2 alpha was high at 17:00 of day 4, but decreased by 80% within the next 24 h. There was no change in PGF2 alpha production during the first 6 h after injection of estradiol to hypophysectomized animals. There was, however, a dramatic decrease in production within the next 6 h. In contrast, CEA was not different in animals treated with estrogen than in those receiving only progesterone. In ovariectomized animals, uterine PGF2 alpha production also was lowered by estrogen but in these animals CEA was significantly elevated 18 h after injection of estradiol. Estrogen caused a greater increase in PGF2 alpha content in the hypophysectomized, compared to the ovariectomized, rats. The results are consistent with the view that ovarian steroids play an important role in controlling the changes in uterine PGF2 alpha around the time of implantation in rat.
Explore the source record for details and available documents.
1. The present study was undertaken to determine whether beraprost, a stable prostacyclin-mimetic agent, may exert a beneficial effect on post-hypoxic recovery of cardiac function and metabolism. Isolated rabbit hearts were perfused by the Langendorff method for 20 min under glucose-free hypoxic conditions, followed by 45 min reoxygenation in the presence of glucose, and their functional and metabolic changes with or without beraprost-treatment were examined. 2. Hypoxic insult induced cessation of cardiac contractile force, depletion of myocardial high-energy phosphates, accumulation of tissue calcium, and release of creatine kinase and ATP metabolites. Subsequent reoxygenation resulted in a poor recovery of cardiac contractile force (less than 10% of the pre-hypoxic value), a poor restoration of high-energy phosphates, and increase in calcium content. A further release of creatine kinase and ATP metabolites from the heart was observed during reoxygenation. 3. Treatment with 0.45 microM beraprost during the whole hypoxic period resulted in a significant suppression of the increase in tissue calcium, and the release of creatine kinase and ATP metabolites during hypoxic perfusion. This treatment also elicited a significant post-hypoxic recovery of the cardiac contractile force and the tissue high-energy phosphates. Reoxygenation-induced release of creatine kinase and ATP metabolites was also prevented by treatment with beraprost. 4. When hearts were treated with prostacyclin sodium (0.50 microM) in the same manner for the purpose of comparison, similar improvement of post-hypoxic contractile and metabolic recovery were observed. 5. These results demonstrate that treatment with either beraprost or prostacyclin is beneficial for post-hypoxic recovery of cardiac function and metabolism. Since the observed effects on post-hypoxic contractile recovery were exerted at a concentration of approximately 0.50 microM of these agents (a concentration far from the physiological range) the underlying mechanism appears to be different from the physiological action of prostacyclin.
An antitumor polysaccharide SPR-901 was found in a fermented broth of a kind of lactic acid bacteria isolated from rice bran. SPR-901 is a high molecular alpha-glucan and its linkages are almost linear alpha-1,6 glucosidic ones with a small amount (ca. 5%) of branches at C-3 positions. It is a highly purified alpha-glucan and it contains no protein and no inorganic salts. SPR-901 showed significant antitumor activities against murine allogeneic and syngeneic tumors by both intraperitoneal and oral administration, and enhanced carbon clearance ability in mice, while it showed no direct cytotoxicities in vitro. The mechanism of antitumor activities of SPR-901 is supposed to be a host-mediated one, and this substance is classified as one of the biological response modifiers. These properties of SPR-901 were identical to those of RON, which was obtained from rice bran, therefore we concluded that these two polysaccharides were the same substance.
The present study was designed to elucidate pathophysiological changes in the brain energy metabolism after cerebral ischemia. Cerebral ischemia was induced in rats by administering microspheres into the right carotid canal, and the time course of changes in cerebral energy metabolism was examined up to the 7th day after the operation. Approximately 50% of the operated rats revealed typical symptoms of stroke. In the right hemisphere, cerebral ATP and creatine phosphate of the rat on the 1st to 7th day were greatly reduced by the microsphere-induced cerebral embolism (maximally 52 and 61%, respectively), whereas the tissue lactate level was increased on the 1st, 3rd and 5th day after the embolism (maximally 125%), suggesting an induction of microsphere-induced cerebral ischemia. These changes in the tissue metabolites were accompanied by a decrease in the mitochondrial oxidative phosphorylation measured in the presence of succinate. A similar trend in the changes of biochemical markers was observed in the left hemisphere, but to a lesser degree or to an insignificant degree. The pathophysiological alterations in behavior and cerebral metabolism of microsphere-injected rats tended to return toward the normal levels on the 7th day after the operation. The results provided information on a useful model for therapeutic studies of anti-ischemic agents in the brain.
The present study was undertaken to elucidate beta-adrenoceptor blocking effects of befunolol (BFE 60, CAS 39543-79-8) on changes in the myocardial metabolites induced by hypoxic respiration. When rats were subjected to hypoxic respiration, a significant increase in heart rate (about 13% increase) and a slight decline in mean aortic blood pressure (about 12% decrease) were observed at 1 min and 6 min after the onset of hypoxic respiration. The hypoxic respiration also elicited decreases in the myocardial ATP and creatine phosphate levels (each 18% decrease) and increases in the myocardial lactate (13% increase) and cyclic-AMP (20% increase) levels. In contrast, these changes were never observed throughout hypoxic respiration when rats had been treated with both reserpine and alpha-methyl-p-tyrosine methylester 20 to 22 h before experiment, suggesting that these metabolic alterations are mediated through beta-adrenoceptor stimulation. These hypoxic respiration-induced hemodynamic and metabolic changes were found to be suppressed by treatment with 1 and 10 micrograms/kg befunolol or 10 micrograms/kg propranolol to an appreciable degree. The results demonstrate protective action of befunolol, like propranolol, on hypoxia-induced changes in the myocardial energy metabolism.
A 13-year-old girl had a history of wide resection of the left fibula under the diagnosis of osteosarcoma three years before. Postoperatively, a thin walled cystic lesion in the right upper lung field, which enlarged gradually with thickening of the wall was found on the chest roentgenogram. The right upper lobectomy was performed after clinical evaluation. The pathologic examination confirmed that the tumor was the metastatic osteosarcoma of the lung. Although metastatic osteosarcoma is common in the lung, very rare cases demonstrate thin walled cavity formation in chest roentgenogram. We reported herein a case of a solitary metastatic osteosarcoma of the lung with thin walled cavity considering with pathogenesis of the lung.