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Volume 64, Issue 11
Displaying 1-8 of 8 articles from this issue
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Mareo NAITOH, Takehiko TOMINAGA, Hiromichi SUZUKI, Takao SARUTA, Nobuh ...1988 Volume 64 Issue 11 Pages 1115-1123
Published: November 20, 1988
Released on J-STAGE: September 24, 2012
JOURNAL FREE ACCESSA 70-year-old man with a 5-year history of hemodialysis was admitted to Keio University Hospital due to severe constipation on March 27, 1986. He recognized constipation and abdominal distention one month before admission, and his general condition became gradually worse. After the admission, a barium enema revealed obstruction at the upper portion of the ascending colon. A right colectomy was successfully performed on April 8. Before the operation he showed frequent premature ventricular beats on his ECGs, but after the operation atrial fibrillation with rapid ventricular responses appeared. The arrhythmia was normalized with the intravenous administration of verapamil and disopyramide and oral administration of those drugs was continued. A few weeks later he was found to be drowsy occasionally. His fasting plasma glucose was revealed to be 29 mg/di. After the discontinuation of the antiarrhythmic agents his plasma glucose level returned to normal. To see what role disopyramide might play in this hypoglycemic phenomenon, oral glucose tolerance tests were done before and during the administration of disopyramide. The examination revealed stimulation of insulin secretion by disopyramide.View full abstractDownload PDF (1073K) -
Toru TAKEUCHI1988 Volume 64 Issue 11 Pages 1124-1139
Published: November 20, 1988
Released on J-STAGE: September 24, 2012
JOURNAL FREE ACCESSIt is known that amenorrhea, oligomenorrhea, irregular menstrual cycles, luteal insufficiency and infertility are frequently associated with hyperandrogenism. It has been reported in previous studies that the traditional herbal medicine, Shakuyaku-Kanzo-To (SKT) can lower high serum testosterone levels in oligomenorrheic or amenorrheic women, and that some of these sterile women conceive. SKT contains Shakuyaku (S) and Kanzo (K) in equal amounts. The main component of S and K is paeoniflorin and glycyrrhizin, respectively. This study was designed to investigate the mechanism in lowering serum testosterone (T) levels by SKT.
Experiment I : Female Wistar rats were injected subcutaneously with 500 μg of testosterone propionate at the age of 2 days, becoming androgen-sterilized rats (ASR). Fifty-six-day-old ASR were given orally SKT (22.5, 45, 90 and 180 mg/kg body weight), S or K (11.25, 22.5, 45 and 90 mg/kg b.w.) in water through a tube every day for 2 weeks. Control ASR were given only water. Each group consisted of 10 rats. Serum total and free T levels in SKT and S groups were significantly lower than those in the controls, and these decreases were dose-dependent.
Experiment II : Female Wistar rats were oophorectomized at the age of 60 days. From one week later they were given orally SKT (90 and 180 mg/kg b.w.), S or K (45 and 90 mg/kg b.w.) every day for 2 weeks. Control rats were given only water. Each group consisted of 11 rats. There was no change in serum T, LH and FSH levels in either groups. The results from experiment I and II suggest that SKT influences the T production by ovaries but not by adrenal glands.
Experiment III : The minced tissues of one ovary obtained from proestrous Wistar rats were incubated with media containing Paeoniflorin (P), Glycyrrhetinic acid (GA) or Glycyrrhizin (GL) (1, 50 and 100 μg/ml, respectively, n = 5 in each group) for 270 minutes at 37°C under an atmosphere of 95%O2 and 5%CO2. The T production by ovaries was significantly decreased in each treated group in comparison with the control, and this decrease was dosedependent. However, the Δ4-androstenedione (Δ4-A) production by ovaries was increased in each treated group. The ratio of T to Δ4-A was significantly lower in each treated group than in the control. The estradiol (E2) production by ovaries in each treated group was not changed in comparison with the control. The ratio of E2 to T was significantly higher in the GA group than in the control, and this increase was dose-dependent.
These results suggest that P, GA and GL probably suppress the conversion of Δ4 -A to T (17β-hydroxysteroid dehydrogenase activity) and stimulate aromatase activity to decrease T production by the ovaries. The effect of SKT in lowering serum T levels may be due to 13, GA and GL contained in it.View full abstractDownload PDF (1453K) -
Biochemical Characteristics of an Initial Degradation Product of Insulin by Insulin-Degrading EnzymeKazuyoshi YONEZAWA1988 Volume 64 Issue 11 Pages 1140-1156
Published: November 20, 1988
Released on J-STAGE: September 24, 2012
JOURNAL FREE ACCESSWe previously reported on the detection and HPLC separation of the initial degradation product (peak VI) of native insulin from the reaction of monocomponent porcine insulin with affinity-purified pig skeletal muscle insulin-degrading enzyme (IDE).
In the present study, we investigated the biological characteristics of the initial degradation product. Structural analysis of peak VI by amino acid composition and performate oxidation revealed that peak VI was composed of intact B-chain and a fragment of A-chain. In vivo, peak VI exhibited a hypoglycemic effect on rats. In vitro, this peptide had the binding capacity to insulin receptor of rat adipocytes and the ability to stimulate the glucose oxidation on rat adipocytes and the activity of insulin receptor kinase. However, the biological potencies of peak VI were 1/40 to 1/160 of those of insulin proper. Its reduced biological potencies were probably due to a decrease of affinity for insulin receptor, because both biological potencies of peak VI to bind to insulin receptor and to stimulate the glucose oxidation were 2.5% of insulin. Moreover peak VI showed the same full agonistic effect as insulin on the glucose oxidation at higher concentration. On the other hand, a cross-linking study suggested that peak VI preserves almost the same affinity to IDE as insulin.
These finidings may indicate the possibility that pig skeletal muscle IDE cleaves peptide bonds within A-chain at an early step of degradation of native porcine insulin and generates peak VI, which is the next substrate to insulin for IDE and keeps reduced insulinlike biological potencies, and then peak VI is converted into serveral relatively low molecular weight products.View full abstractDownload PDF (2138K) -
Masaki TAKAHASHI, Yukio MIURA, Naoki SANO, Takashi OHZEKI, Takashi SUG ...1988 Volume 64 Issue 11 Pages 1157-1168
Published: November 20, 1988
Released on J-STAGE: September 24, 2012
JOURNAL FREE ACCESSTo investigate the effects of dietary sodium on the peripheral dopaminergic mechanism, changes of unconjugated plasma dopamine (DA) and its related humoral factors were studied in 8 patients with essential hypertension (EH) and 8 age-matched normal controls (N) while they were receiving ordinary meals (Na, 130-180 mEq daily) followed by higher sodium (250-300 mEq daily) diets for a week. Plasma and urinary DA, norepinephrine (NE) and epinephrine (E) were measured by the highly sensitive COMT-mediated radioenzymatic procedure, which permits an accurate estimation of plasma DA as low as 5-6 pg/ml.
Under high sodium diets, blood pressure and heart rate were not changed significantly in N and EH subjects. Urinary NE and E tended to decrease, while urinary DA increased significantly in both groups of subjects (p<0.05). There was a significant correlation between urinary sodium and DA (r=0.590, p<0.001), but plasma DA failed to correlate significantly to urinary sodium or DA in all subjects. Plasma NE and E tended to decrease in both N and EH subjects, while plasma DA increased significantly (p<0.05) in EH from 7.2±0.8 pg/ml [mean±SEM] to 9.3±1.0 and slightly in N from 9.1±1.8 to 11.2± 13. Plasma renin activity (PRA) and plasma aldosterone (PAC) were invariably decreased in all subjects, while plasma prolactin (PRL) remained unchanged.
A significant correlation was observed between plasma DA and NE under ordinary meals (r=0.733, p<0.01), but this correlation disappeared under high sodium diets. Plasma DA showed an inverse correlation to PAC (r=-0.351, p<0.05) under both dietary conditions.
Upright posture induced a significant rise (p<0.05) in NE, E, DA, PRA and PAC with ordinary meals, but the responses of NE and PAC were apparently attenuated with high sodium diets.
An intravenous injection of metoclopramide (MCP, 10 mg), a DA receptor antagonist, provoked a slight rise in plasma NE and DA with ordinary meals, of which responses were further enhanced with high sodium diets. MCP induced a definite rise in PAC and PRL in all subjects under both dietary conditions (p<0.01), while plasma E and PRA remained unchanged after MCP challenge.
The results lend support to the view that unconjugated plasma DA could be a useful marker of peripheral dopaminergic activity, which might be a physiological regulator responsible for the suppression of aldosterone secretion and sympathetic nerve activity observed during high sodium intake.View full abstractDownload PDF (1169K) -
Hisanori MINAKAMI, Naohide ABE, Naoko OKA, Taro TAMADA1988 Volume 64 Issue 11 Pages 1169-1174
Published: November 20, 1988
Released on J-STAGE: September 24, 2012
JOURNAL FREE ACCESSStudies of normal human subjects have shown that prolactin (PRL) as well as thyrotropin (TSH) are secreted in pulsatile fashion. This study was designed to investigate whether or not these two hormones are secreted synchronously. Ten postmenopausal women who had had amenorrhea for at least 3 years and 2 women who had been ovariectomized 3 and 5 years before and were between 35-60 yr of age were studied. Blood samples were obtained between 1500-2000 h at 15 min intervals. Distinct pulsatile fluctuation of plasma TSH concentration was present in all subjects. However, only 31% of these pulses were observed to coincide with PRL pulses. The mean (±SD) increment of TSH (nadir to peak) was 1.2±0.5 μu/ml. The mean interval between pulses of TSH was 73 min. In contrast, regular episodic fluctuation of plasma PRL concentration were present in only 5 out of 12 women, and 48% of these pulses were observed to coincide with TSH pulses. These results indicate that pulses of TSH and PRL are generated independently. Since thyrotropinreleasing hormone (TRH) may be a direct generator of TSH pulse and a potent stimulator of PRL secretion, our results may suggest that physiological concentration of TRH in portal blood which is sufficient to elicite TSH pulse may be too low to elicite PRL pulse.View full abstractDownload PDF (540K) -
Kyosuke TAKEUCHI, Hajime MORIKAWA, Yasuo UEDA, Matsuto MOCHIZUKI1988 Volume 64 Issue 11 Pages 1175-1186
Published: November 20, 1988
Released on J-STAGE: September 24, 2012
JOURNAL FREE ACCESSIn order to clarify the dynamics in maternal calcium metabolism during pregnancy, serum concentrations of ionized calcium, calcium regulating hormones and intestinal calcium absorption were measured in pregnant and hypophysectomized (HX) rats. Serum concentrations of ionized calcium decreased significantly late in pregnancy. Serum levels of 1α, 25- (OH) 2 vitamin D3 (D3) increased late in pregnancy, however, those of parathyroid hormone (PTH) increased not significantly throughout pregnancy. Serum levels of calcitonin (CT) and intestinal calcium absorption increased as pregnancy progressed.
Administration of human placental lactogen (hPL), bovine growth hormone (bGH) and ovine prolactin (oPRL) to the HX-rats remarkably enhanced intestinal calcium absorption. Serum concentrations of 1α, 25- (OH) 2 D3 significantly increased by administration of bGH and hPL to the HX-rats, but they did not increase significantly by oPRL administration.
These data suggest that 1) maternal intestinal calcium absorption might be increased by the action of increased serum 1α, 25- (OH) 2 D3 and the maternal bone might be kept at the same density throughout pregnancy because serum CT protects the maternal skelton by resisting the bone-resorption activities of 1α, 25- (OH) 2 D3 ; and 2) placental lactogen may play an important role on the increase of intestinal calcium absorption by stimulating the production of 1α, 25- (OH) 2 D3 during pregnancy.
From these results, it is considered that these alternations of calcium metabolism in the maternal side are the rational responses to supply Ca to the fetus and newborn for keeping their calcium homeostasis.View full abstractDownload PDF (1199K) -
Masafumi YAJIMA1988 Volume 64 Issue 11 Pages 1187-1198
Published: November 20, 1988
Released on J-STAGE: September 24, 2012
JOURNAL FREE ACCESSCloned MC3T3-E1 cells which have retained several osteoblast-like characteristics were derived from newborn mouse calvaria. In order to elucidate the function of osteoblasts, the effects of 1, 25 (OH) 2D3, interleukin (IL) -1β, IL-3, interferon (INF) -γ and epidermal growth factor (EGF) on the activity of alkaline phosphatase (Al-P'ase), DNA synthesis and the production of prostaglandin E2 (PGE2) in MC3T3-E1 cells were studied. The influence of cyclosporin A (CSA), a potent immunosuppressive agent, was also studied.
The following results were obtained :
1 1, 25 (OH) 2D3 increased the incorporation of [45Ca] Cl2 into matrix and accelerated the calcification of MC3T3-E1 cells.
2 Al-P'ase activity and the incorporation of [3H] -thymidine into MC3T3-E1 cells were increased by 1, 25 (OH) 2 D3 but decreased by IL-1β, INF-γ, IL-3 and EGF.
3 IL-1β increased and INF-γ decreased PG-E2 production by MC3T3-E1 cells.
4 CSA decreased either Al-P'ase activity or incorporation of [3H] -thymidine, and increased PG-E2 production in MC3T3-E1 cells. CSA which was simultaneously incubated with these various cell growth factors, showed a similar effect to that of CSA alone.
These results suggest that cytokines produced from immune cells, could affect osteoblasts besides that of calcium regulating hormones like parathyroid hormone and 1, 25 (OH) 2D3, implying a probability for the participation of immunocompetent cells in the regulation of bone metabolism.View full abstractDownload PDF (1296K) -
Hideo KOSHIDA, Isamu MIYAMORI, Masatoshi IKEDA, Zenzo SAITO, Ryoyu TAK ...1988 Volume 64 Issue 11 Pages 1199-1208
Published: November 20, 1988
Released on J-STAGE: September 24, 2012
JOURNAL FREE ACCESSSeveral aldosterone metabolites are now known to possess some mineralocorticoid activities. In order to test the hypothesis that these metabolites could contribute to the pathogenesis of hypertension, we studied the aldosterone metabolism in SHR in vitro and in vivo.
In vitro experiment, male SHR and WKY rats of 4 and 15 weeks of age were used. The microsome, cytosol and heavy mitochondria fractions from liver and kidney were isolated by ultracentrifuge. 10mg protein/ml of each subcellular fraction was incubated with 3 H-aldosterone in Tris-HCl buffer at pH 7.4 containing NADPH, glucose-6-phosphate (G-6-P) and G-6-P dehydrogenase as described by Morris, D.J. et al. (Hypertension, 5 (suppl. I] : I-35-I-40, 1983.). Aldosterone and its metabolites synthesized were extracted with Sep-pak C18cartridges and separated by HPLC on a reverse phase column.
In vivo experiment, the urine of male SHR and WKY rats of 15 weeks old injected 10μCi 3 H-aldosterone intraperitoneally was collected for 48 hours, extracted and analyzed by HPLC. Peaks of steroids from SHR were compared with those from WKY.
Incubation of aldosterone with liver microsomes yielded at least 10 polar and 3 less polar metabolites (A-ring reduced metabolites). SHR liver microsomes synthesized larger amounts of 3 polar metabolites than WKY liver microsomes. Liver cytosol, liver heavy mitochondria and kidney subcellular fractions mainly synthesized less polar metabolites, but failed to synthesize as much polar metabolites as liver microsomes. Kidney microsomes and cytosol from 4 weeks old SHR synthesized larger amounts of less polar metabolites compared to those from WKY. In vivo experiment, SHR of 15 weeks of age excreted larger amounts of 2 polar metabolites than WKY.
The present study suggests that the difference of metabolism of aldosterone between SHR and WKY observed from an early stage in the liver and the target organ, kidney, may be associated with hypertension or its causative factors, and confirms that aldosterone will be metabolized to several polar and less polar forms by rat liver and kidney subcellular fractions.View full abstractDownload PDF (847K)
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