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Biomedical subjects

S Takeda

Publications and source records attributed to S Takeda.

At least 307 records · Page 17Linked to original sources

Alternations in beta-Adrenoceptor Mechanisms in Hearts Perfused With Xanthine Plus Xanthine Oxidase.

BACKGROUND: Although beta-adrenoceptors and adenylyl cyclase are known to be affected upon exposing cardiac membranes to some oxyradical generating systems, the results are conflicting. Furthermore, functional significance of alterations in the beta-adrenoceptor-adenylyl cyclase systems in terms of changes in the inotropic responses to catecholamines is not clear. METHODS AND RESULTS: The positive inotropic effect of isoproterenol was augmented on perfusing the isolated rat hearts with xanthine (X) plus xanthine oxidase (XO) for 5 minutes but was attenuated by perfusion for 15 minutes. The isoproterenol-stimulated adenylyl cyclase activity in cardiac membranes showed an increase at 10 minutes and a decrease at 30 minutes perfusion of hearts with X plus XO. The density of beta-adrenoceptors in cardiac membraners was reduced after 10 minutes and 30 minutes of perfusion with X plus XO, whereas the affinity of beta-adrenoceptors was increased after 10 minutes and reduced after 30 minutes. Although beta-adrenoceptors was increased after 10 minutes and reduced after 30 minutes. Although beta-adrenoceptors were unaltered by 10 minutes of perfusion with X plus XO, their affinity was increased and density was decreased by 30 minutes of perfusion. The agonist competition curves using isoproterenol indicated an increase in the number of coupled receptors in the high affinity state on 10 minutes of perfusion and an increase in the low affinity state of coupled receptor due to 30 minutes of perfusion with X plus XO. The basal as well as forskolin-, NaF- and Gpp(NH)p-stimulated adenylyl cyclase activities in cardiac membranes exhibited an increase after 10 minutes and decrease after 30 minutes of perfusion with X plus XO. Although the presence of superoxide dismutase plus catalase in the perfusion medium prevented most of the alterations due to X plus XO, it did not alter the increased affinity of the beta-adrenoceptor upon perfusing hearts for 10 minutes with X plus XO. CONCLUSIONS: The results in this study suggest the biphasic nature of the oxyradical-induced alterations in both the inotropic responses to catecholamines and the beta-adrenoceptor-mediated signal transduction mechanism in the heart.

Journal Article↗

Pharmacokinetic study of paeonimetabolin I, a major metabolite of paeoniflorin from paeony roots.

Plasma concentrations of paeoniflorin (PF) and its major metabolite, paeonimetabolin I (PM-I), were estimated after oral administration of PF to rats at doses of 0.5 and 5 mg/kg. The maximal plasma concentrations (Cmax) of PF were 9.9 and 20.3, and those of PM-I were 16.5 and 101.7 ng/ml at each dose, respectively. The times to Cmax (tmax) of PF were 11.6 and 13.3, and those of PM-I were 60 and 80 min, respectively. The AUC(0-180) of PM-I were 1873 and 12358, and those of PF were 300 and 1174 ng min/ml, respectively. On the other hand, after intravenous administration of PM-I to rats at doses of 0.2 and 2 mg/kg (equal in molar ratio to 0.5 and 5 mg/kg PF), the plasma concentration of PM-I decreased rapidly and the plasma concentration-time curve profile of it fitted well with the two-compartment model at each dose, with terminal half lives (t1/2) of 90.9 and 90.6 min. The Vdss values were 0.91 and 3.79 l/kg, the CLtot values were 8.7 and 39.9 ml/min kg, and the AUC(0-180) values were 5614.1 and 13176.0 ng min/ml, at each dose, respectively. The significant increase in Vdss and CLtot with increasing doses suggested dose-dependent pharmacokinetics. When PM-I was given orally at the same doses, the following parameters were shown: Cmax of 102.2 and 285 ng/ml at tmax 6.2 and 7.5 min and AUCs of 4145.6 and 14182.1 ng min/ml, at each dose. The bioavailability (F) values were 0.8 and 1.07, respectively. These findings indicated that the high percentage of PM-I transformed by intestinal bacteria was rapidly absorbed from the gastrointestinal tract, and a significantly high concentration of PM-I, rather than PF, was present in the plasma after oral administration of PF.

Administration, Oral↗

Synthetic studies of vitamin D analogs. XXIV. Synthesis of active vitamin D3 analogs substituted at the 2 beta-position and their preventive effects on bone mineral loss in ovariectomized rats.

Analogs related to 1 alpha,25-dihydroxy-2 beta-(3-hydroxypropoxy)vitamin D3 (ED-71) (4), oxa-type and carba-type analogs of vitamin D3 bearing substituents at the 2 beta-position of 1 alpha,25-dihydroxyvitamin D3 (1), were synthesized from the alpha-epoxides (6 and 13). Three analogs, ED-71 (4) and two carba-type analogs (16 and 26), showed potent preventive effects on bone mineral loss in pre-osteoporosis model rats. ED-71 (4) was concluded to be an optimized analog and a promising candidate for the treatment of osteoporosis.

Absorptiometry, Photon↗

External high-frequency oscillation for hypercapnia after upper abdominal surgery.

The purpose of this study was to evaluate the efficacy of external high-frequency oscillation (EHFO) in patients with hypercapnia following upper abdominal surgery. Seven patients were ventilated with EHFO for 2 hr at 60 oscillations/min, with cuirass pressures of 36 cm H2O (-26 to +10), and an inspiratory to expiratory ratio of 1:1. Blood gases and cardiac functional parameters were examined during the 2 hr on EHFO. Pulmonary functional parameters were analyzed prior to the institution and after the termination of EHFO. PaCO2 significantly decreased from 61 +/- 8 mmHg to 48 +/- 7 mmHg after 10 min on EHFO (p < 0.01). PaO2 significantly increased from 74 +/- 10 mmHg 95 +/- 26 mmHg after 1 hr on EHFO (p < 0.01). The heart rate decreased significantly from 108 +/- 27 beats/min to 101 +/- 24 beats/min after 30 min on EHFO (p < 0.05). The FEV1 and FVC significantly increased from 1.09 +/- 0.54 L to 1.50 +/- 0.46 L (p < 0.01) and from 1.90 +/- 0.74 L to 2.18 +/- 0.60 L (p < 0.05), respectively. The other parameters of lung function also significantly improved after the termination of EHFO. The significant changes in all of the pulmonary functional parameters continued for 1 hr after the termination of EHFO. EHFO is an effective method of gas exchange which is associated with earlier return to preoperative lung function.

Aged↗

Efficacy of doramectin against intestinal nematodes and sarcoptic manage mites in naturally infected swine.

Endectocidal efficacy of doramectin administered intramuscularly at a dosage of 300 micrograms/kg was evaluated in 464 pigs naturally infected with intestinal nematodes or mange mites on 14 commercial farms in Japan. By doramectin treatment, fecal egg counts were reduced > 99% for Ascaris suum, Strongyloides ransomi, Oesophagostomum dentatum, and Trichuris suis; worm counts of T. suis and mite counts of Sarcoptes scabiei reduced 90.1% on Day 21 and 99.5% on Day 28 following treatment, respectively.

Animals↗

Vomiting induction by ipecac syrup in dogs and ferrets.

The dog has been used as an experimental animal in emesis research. In this study, we analyzed the emetic effects of ipecac syrup using a smaller animal, the ferret, and compared its response to that of the dog. Dogs and ferrets were divided into 4 groups (n = 4, each). Each group was given either 0.1, 0.25, 0.5, or 1.0 ml/kg of ipecac syrup, and the latency and numbers of retching and vomiting were recorded. Animals given an equal volume of saline served as controls. The numbers of vomiting and retching increased dose-dependently in both dogs and ferrets, and there was no difference in latency and numbers of vomiting between them. The numbers of retching were greater in ferrets than in dogs at > or = 0.25 ml/kg. Taking these results into consideration, the ferret seems to be as useful as the dog in studies on emetic effects of ipecac syrup.

Animals↗

[Tokyo Centenarian Study. 5. Nutritional status of Japanese centenarians].

To establish the guideline for nutrition in the very old, we analyzed biochemical and hematological data from 45 Japanese centenarians living in Tokyo metropolitan area during 1994 and 1995. Levels of cholesterol, HDL-cholesterol, apolipoprotein A1 and B, albumin, prealbumin in serum were lower than in a control group or lower than the reference range, which indicates that these centenarians were undernourished. RBC counts, hemoglobin, and hematocrit were also low in the centenarians. The concentration of albumin correlated positively with those of HDL-cholesterol and apolipoprotein A1, and negatively with concentration of Lp(a). The value for transferrin correlated positively with energy intake and with the concentration of apolipoprotein A1. The concentration of prealbumin correlated positively with the concentration of hemoglobin, hematocrit and the total cholesterol concentration. According to their nutritional status, the centenarians were divided into 2 groups: well-nourished and undernourished. Those who were well-nourished had higher levels of cholesterol, HDL, Hb, and apolipoprotein A1, their levels of ADL and cognitive function were also high. The findings of blood-chemical data in the centenarians may be partly due to undernutrition. Centenarians who were well-nourished were considered to be aging successfully. These results and others previously published indicate that the concentrations of albumin, prealbumin, transferrin and either CRI or IL-6 are useful for nutritional assessment in the very old.

Aged↗

Intratemporal facial nerve blood flow in guinea pigs.

HYPOTHESIS: To investigate the effect of interruption of the stylomastoid artery and the petrosal artery on the facial nerve blood flow with the use of a laser Doppler flowmeter. BACKGROUND: Ischemia of the facial nerve is thought to be one of the most possible causes in idiopathic facial palsy. The blood supply in the facial nerve has been studied morphologically in considerable detail; however, we have little information on its hemodynamics. METHODS: The animals used were 20 guinea pigs. The blood flow in the facial nerve at the geniculate ganglion was measured using a laser Doppler flowmeter, and the change in the facial nerve blood flow between before and after interruption of the stylomastoid artery and the petrosal artery was investigated. The interruption of both arteries was carried out by electrical cauterization with a bipolar coagulator. RESULTS: Interruption of the petrosal artery resulted in almost complete ischemia of the facial nerve at the geniculate ganglion. This decrease in the facial nerve blood flow was significant statistically (p < 0.001). But, interruption of the stylomastoid artery caused no change. CONCLUSIONS: The blood flow in the geniculate ganglion of the facial nerve is thought to come not from the stylomastoid artery but mainly from the petrosal artery. Peripheral facial palsy following ligation of the middle meningeal artery or embolization of the maxillary artery or intra-arterial infusion of anticancer drug into the maxillary artery is likely to be attributed to facial nerve ischemia at the level of the geniculate ganglion.

Animals↗

[Reconsideration of evaluation criteria for physical fitness tests of a working population--comparing conventional and new evaluation criteria].

We set up new evaluation criteria values for grip strength, sit ups, trunk flexion, standing on one leg with eyes closed, whole body reaction and maximum oxygen uptake by age and by sex, by analysing data for about 50,000 people collected by the Japan Industrial Safety & Health Association. We thought that the conventional evaluation criteria values used in the physical fitness tests for a working population did not appropriately reflect the present conditions, and so we compared the new evaluation criteria values with the conventional evaluation criteria values. As a result, a very significant difference was noted in each test item. Then, by examining the quality of the data, change of the times, number of persons tested, and characteristics of the groups studied, all of which could have caused such differences, it was concluded that the proposed new criteria values would be appropriate for evaluation of the physical fitness of the current working population.

Adult↗

Altered transcriptional regulation of the insulin-like growth factor 2 gene in human hepatocellular carcinoma.

The insulin-like growth factor 2 (IGF2) gene is regulated in a complex manner, involving developmentally regulated use of four different promoters as well as transcriptional repression of the maternal allele due to genomic imprinting. It has been well documented that liver is an exceptional organ in which overall transcription from the four IGF2 promoters is markedly imbalanced towards preferential paternal expression only in fetal life, this being relaxed during the postnatal period, resulting in biallelic expression thereafter. We previously reported a marked allelic-expression imbalance in the overall transcription of IGF2 in hepatocellular carcinoma (HCC), leading to preferential expression nonrandomly from the paternal allele. The study presented here, using 18 HCC specimens taken directly from patients, showed that this molecular change often reflects promoters switching from the adult P1 promoter to the fetal P2, P3, and P4 promoters. Interestingly, however, we found that restoration of allele-specific expression of the P1 promoter nonrandomly from the paternal allele was also frequent in HCC suggesting retention of an imprint for paternal expression from the P1 promoter of IGF2 in adult normal liver and altered availability of its modifying factor or factors in HCC. Further studies of the molecular mechanisms involved in the fluctuation of promoter usage and genomic imprinting of IGF2 are warranted to gain an insight into the biology of the liver in terms of development and oncogenesis.

Adult↗

[GRH test].

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Biomarkers↗

[Arginine test].

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Arginine↗