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Biomedical subjects

F Umeda

Publications and source records attributed to F Umeda.

157 records · Page 9Linked to original sources
PubMed1982

Effect of vitamin E on function of pituitary-gonadal axis in male rats and human subjects.

The role of vitamin E in the endocrine system, in particular the pituitary-gonadal axis, was studied in humans and male rats by examining the hormonal differences between vitamin E deficient and supplemented conditions. In vitamin E deficient rats, pituitary content and basal plasma level of FSH and LH were significantly lower than those of the control rats, but testicular content and basal plasma level of testosterone were not significantly changed. On the other hand, in vitamin E supplemented rats, FSH and LH content in pituitary tissue was significantly higher than that of the controls, but there was no significant rise in basal FSH and LH level in plasma. The testosterone level was significantly elevated in both testicular tissue and plasma. It was also demonstrated that basal plasma testosterone and F.T.I. were increased in normal male subjects following oral vitamin E administration and the responsiveness of plasma testosterone levels to HCG was significantly higher during vitamin E administration than before administration. These results suggest that vitamin E may play an important and potent role in hormone production in the pituitary-gonadal axis in humans and rats.

Animals↗
PubMed1982

Inhibitory effect of vitamin E on lipoperoxide formation in rat adrenal gland.

The tissue uptake of vitamin E administered to the rats was strikingly high in the adrenal glands, and microradioautographic studies showed that the vitamin was localized morphologically in the cells of fascicular and reticular zones of the adrenal cortex, where lipofuscin pigment appears with aging. On the other hand, it was confirmed that the TBA content in rat plasma and adrenal gland was elevated following whole-body 60Co irradiation as an aging model. It was also demonstrated that the TBA content in rat adrenal markedly increased in conditions of vitamin E deficiency with and without irradiation.

Adrenal Glands↗
PubMedDate not supplied

Reduction of urinary albumin excretion by thromboxane synthetase inhibitor, OKY-046, through modulating renal prostaglandins in patients with diabetic nephropathy.

We evaluated the effects of thromboxane synthetase inhibitor, OKY-046, on urinary albumin and prostaglandin (PG) excretion in 14 patients with non-insulin-dependent diabetes mellitus (NIDDM). Urinary excretion of 6-keto-PGF1 alpha (a stable metabolite of PGI2), TXB2 (a stable metabolite of TXA2) and PGE2 in NIDDM patients was comparable with that in control subjects. However, the urinary 6-keto-PGF1 alpha/TXB2 ratio in NIDDM patients with both micro- and macroalbuminuria was significantly (P less than 0.001) lower than that in the controls. By a single administration of OKY-046 (40 mg, i.v.) to the diabetic patients, urinary TXB2 excretion significantly (P less than 0.05) decreased from 169.7 +/- 23.9 to 140.2 +/- 17.9 ng/gCr, but urinary 6-keto-PGF1 alpha and PGE2 excretion did not change significantly. The urinary 6-keto-PGF1 alpha/TXB2 ratio thus significantly (P less than 0.01) increased from 1.02 +/- 0.13 to 1.73 +/- 0.41 as associated with significant increments in urine volume (P less than 0.05), urinary sodium excretion (P less than 0.01) and creatinine clearance (P less than 0.05). Of 14 diabetic patients, 7 with macroalbuminuria (albumin index exceeding 100 mg/gCr) were orally given OKY-046 (600 mg/day) for 8 weeks. After this period, the urinary albumin index significantly (P less than 0.05) decreased from 524.9 +/- 149.6 to 317.6 +/- 90.6 mg/gCr.(ABSTRACT TRUNCATED AT 250 WORDS)

Albuminuria↗
PubMedDate not supplied

Effects of cilostazol, a phosphodiesterase inhibitor, on urinary excretion of albumin and prostaglandins in non-insulin-dependent diabetic patients.

Microalbuminuria is characteristic in diabetic nephropathy and is thought to be influenced by renal hemodynamics, especially by the metabolism of prostaglandins (PGs) in glomruli. To reduce urinary albumin excretion in patients with non-insulin-dependent diabetes mellitus (NIDDM), we administered 100 mg of cilostazol, a phosphodiesterase inhibitor, daily for 3 months. The urinary albumin index (UAI: microgram albumin/mg creatinine) decreased significantly after 3 months of administering cilostazol. Urinary excretions of thromboxane B2 (TXB2), a stable metabolite of thromboxane A2, decreased significantly after treatment. However, it had no effects on urinary excretions of PGE2 and 6-keto PGF1 alpha (6KF), a stable metabolite of prostacyclin. The ratio 6KF/TXB2 has been known to reflect the renal metabolism of PGs. In this study, urinary 6KF/TXB2 ratio increased significantly in parallel with a significant reduction of UAI. Cilostazol had no adverse effects on the control of blood glucose and lipids. In conclusion, cilostazol has a beneficial effect on UAI in patients with NIDDM by reducing renal production of TXB2., which increases 6KF/TXB2 ratio.

6-Ketoprostaglandin F1 alpha↗
PubMedDate not supplied

Effects of thromboxane synthetase inhibitor (OKY-046) on urinary prostaglandin excretion and renal function in streptozotocin-induced diabetic rat.

The present study was undertaken to evaluate the effects of a selective thromboxane synthetase inhibitor (OKY-046) on urinary prostaglandins (PGs) excretion and renal parameters such as endogenous creatinine clearance rate (Ccr) and urinary protein excretion in streptozotocin (STZ)-induced diabetic rats. STZ-diabetic rats were divided into two groups; one fed standard chow (DM1) and the other, standard chow mixed with 0.1% OKY-046 (DM2) for 24 weeks. Male Wistar rats were fed standard chow for 24 weeks as control (C). Urinary thromboxane B2 (TXB2) and 6-keto-PGF1 alpha excretions significantly increased in STZ-induced diabetic rats (DM1 and DM2) compared with C after 24 weeks. The increased urinary TXB2 excretion in DM2 was significantly reduced (p < 0.05) compared with that in DM1 (261.1 +/- 18.6 ng/gCr versus 380.0 +/- 48.4 ng/gCr, mean +/- SEM). No significant difference could be found in urinary protein excretion between DM1 and DM2, which was significantly higher in both diabetic groups than C after 12 and 24 weeks. Ccr in both DM1 and DM2 significantly increased (p < 0.05) compared with C after 12 weeks. In contrast, after 24 weeks, Ccr in DM1 fell down to 0.18 +/- 0.02 mL/min 100 g body weight (BW), thus being significantly lower (p < 0.05) than that in C (0.27 +/- 0.03 mL/min 100 g BW) and DM2 (0.25 +/- 0.02 mL/min 100 g BW). Electron microscopic findings in diabetic rats after 24 weeks were the typical change of early diabetic nephropathy, whereas there were no obvious differences between DM1 and DM2.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Prostaglandins and diabetic nephropathy.

Abnormalities of renal prostaglandins (PGs) contribute to the pathogenesis of diabetic nephropathy through changes in renal hemodynamics. Our recent studies have demonstrated that urinary excretion ratio of 6-keto-PGF1 alpha (6KF) to TXB2 is decreased in patients with non-insulin-dependent diabetes mellitus (NIDDM). In the present study, we evaluated the clinical effects of some drugs on renal PG metabolism and diabetic nephropathy. Ozagrel, a specific thromboxane synthetase inhibitor, reduced urinary TXB2 excretion, resulting in the improvement of the decreased urinary 6KF/TXB2 ratio in NIDDM patients. Urinary albumin excretion was decreased and creatinine clearance (Ccr) was increased during ozagrel administration. The similar beneficial effect was also found in the administration of cilostazol, a phosphodiesteraase inhibitor, whereas a stable analogue of PGI2, berprost sodium, reduced urinary albumin excretion in relation to the reduction of platelet aggregation rate. In conclusion, the drugs modulating renal and platelet PGs metabolism with direction to an increase in 6KF/TXB2 ratio and an inhibition against platelet function might be beneficial for the treatment of diabetic nephropathy.

6-Ketoprostaglandin F1 alpha↗
PubMedDate not supplied

Stimulatory activity on prostacyclin production decreases in sera from streptozotocin-induced diabetic rats.

We recently reported that serum stimulatory activity on prostacyclin (PGI2) production by cultured bovine aortic endothelial cells decreased in noninsulin-dependent diabetic patients. In the present study, this activity was compared in streptozotocin-induced (STZ) diabetic rats and controls. Platelet-poor plasma-derived serum (PDS) from Wistar male rats stimulated 6-keto-PGF1 alpha production (a stable metabolite of PGI2) by cultured bovine aortic endothelial cells, rat lung fibroblasts, and rat aortic rings in a time- and dose-dependent manner. Namely, PDS from rats has a stimulatory activity on PGI2 production (PGI2 stimulatory activity; PSA). Furthermore, PSA in PDS from STZ diabetic rats (n = 12) significantly decreased as compared with that from control rats (n = 10) using three types of in vitro systems. The reduction in PDS-stimulated PGI2 production by the vascular wall may lead to platelet hyperaggregation and thrombus formation in diabetics, which is considered to be involved in the pathogenesis of diabetic macro- or microangiopathy.

6-Ketoprostaglandin F1 alpha↗
PubMedDate not supplied

Reduced expression of a novel peptide, prostacyclin-stimulating factor, in the kidneys of streptozotocin-induced diabetic rats.

Prostacyclin (PGI2) produced by vascular endothelial cells (ECs) is a potent vasoactive prostanoid involved in maintenance of vessel wall homeostasis. Reduced PGI2 synthesis by vascular ECs could be a mechanism of pathogenesis in the development of vascular lesions such as diabetic angiopathy. Recently, we purified and cloned a novel bioactive peptide, PGI2-stimulating factor (PSF), which stimulates PGI2 production by vascular ECs. PSF may act on vascular ECs in a paracrine and/or autocrine fashion to regulate PGI2 synthesis. Decreased PSF production in the vessel wall may result in an imbalance of prostanoid synthesis, leading to the development of vascular lesions such as diabetic angiopathy. Our immunohistochemical study demonstrated that PSF is located in vascular resident cells such as vascular smooth muscle cells (SMCs) and ECs, as well as in bronchial SMCs. Moreover, PSF mRNA was found to be expressed in various tissues in Wistar rats, particularly in the kidneys and lungs. The present study demonstrated that streptozotocin (STZ)-induced diabetic rats showed less PSF mRNA expression in the kidneys (PSF mRNA/28S rRNA ratio; STZ versus control; 1.7+/-0.2 versus 2.5+/-0.2, p < 0.05) and reduced immunohistochemical staining for PSF in arteries in the kidney. However, in the lungs, there were no changes in tissue PSF mRNA expression (STZ versus control; 10.9+/-0.9 versus 11.5+/-1.0, NS) or in the extent of PSF staining in bronchial SMCs of STZ-induced diabetic rats. These findings suggest that decreased expression of PSF in renal vessels of STZ-induced diabetic rats may cause an imbalance of prostanoid synthesis, leading to the development and progression of vascular damage in the kidney.

Animals↗
PubMedDate not supplied

Effects of a new oral hypoglycaemic agent (CS-045) on metabolic abnormalities and insulin resistance in type 2 diabetes.

The effects of a thiazolidinedione antidiabetic agent (CS-045) on diabetic metabolic abnormalities were studied in a double-blind clinical trial. Fourteen patients with Type 2 diabetes were selected according to study criteria. Eight were treated with oral CS-045 at 400 mg daily, and six were given placebo. A multi-step, hyperinsulinaemic, euglycaemic clamp study, with simultaneous plasma free fatty acid study, and glucagon tolerance test were performed before and after administration of drug. Following 3 months of treatment with CS-045, there were significant decreases in the mean levels of fasting plasma glucose (from 9.18 +/- 0.95 to 7.78 +/- 0.44 mmol l-1), postprandial plasma glucose (from 11.8 +/- 1.23 to 10.36 +/- 1.06 mmol l-1), and haemoglobin A1c (from 9.3 +/- 0.4 to 6.8 +/- 0.4%). Insulin sensitivity also improved (1st step: from 3.12 +/- 0.33 to 4.70 +/- 0.47 mg kg-1 min-1 (p < 0.01); 2nd step: from 5.61 +/- 0.63 to 7.54 +/- 0.58 mg kg-1 min-1 (p < 0.01); 3rd step: from 9.21 +/- 0.67 to 11.10 +/- 0.87 mg kg-1 min-1). The fasting free fatty acid level decreased significantly from 0.28 +/- 0.04 to 0.22 +/- 0.02 g l-1. The residual free fatty acid level (%) under insulin infusion clamp conditions decreased significantly from 63.7 +/- 9.7 to 45.0 +/- 9.2%. CS-045 treatment was associated with decrease in total cholesterol, total triglycerides, and increase in HDL cholesterol. Basal C-peptide immunoreactivity level decreased, but there was no change in the peak C-peptide immunoreactivity value.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗