Hyperglycemia in diabetic rats reduces the glutathione content in the aortic tissue.

The glutathione redox cycle plays a major role in scavenging hydrogen peroxide (H2O2) under physiological conditions. Recently, we demonstrated that a high glucose concentration in the culture medium reduced the level of H2O2 scavenging activity of human vascular smooth muscle cells (hVSMCs). We also showed that a high glucose concentration reduced the intracellular glutathione (GSH) content and the rate of uptake of cystine, which itself is a rate-limiting factor that maintains the GSH level (FEBS Lett.

Decreased Na,K-ATPase activity by glycation at the catalytic center.

The in vitro activity of Na,K-ATPase isolated from outer medulla of dog kidney was decreased in a dose- and time-dependent manner by interaction with 100 mM glucose 6-phosphate (G6P) during the first 8 h. In the subsequent 16 h no change in activity was observed. On the other hand, Amadori-products of the enzyme increased in a dose- and time-dependent manner by glycation up to 100 mM G6P during 24 h.

High concentration of glucose causes impairment of the function of the glutathione redox cycle in human vascular smooth muscle cells.

We demonstrated that high glucose reduced H2O2 scavenge activity in human vascular smooth muscle cells. In the cells exposed to high glucose, the intracellular glutathione content decreased, although the NADPH content was unchanged. The rate of uptake of cystine, which is a rate-limiting precursor of the glutathione synthesis, decreased in the high glucose group compared with the control group.

Restoration of nitric oxide production by aldose reductase inhibitor in human endothelial cells cultured in high-glucose medium.

The effects of elevated glucose and aldose reductase inhibitor (ARI:ONO-2235) on nitric oxide (NO) production in cultured human umbilical endothelial cells (HUVEC) were evaluated. Aldose reductase and nitric oxide synthase(NOS) share NADPH as an obligate cofactor, therefore it is suggested that the enhanced of glucose flux (27.5 mM) by aldose reductase inhibited NO production by blunting NOS activity.

The effect of nilvadipine on bloodflow in the dorsal pedis artery in type 2 diabetic patients--a study using duplex Doppler ultrasonography.

The effects of nilvadipine on the peripheral circulation in the lower extremities using a duplex system of two-dimensional colour and pulse Doppler ultrasonography were studied in 32 patients with type 2 diabetes mellitus and mild essential hypertension. The patients (19 men and 13 women) were randomly divided into treatment and control groups. The anatomical cross-sectional area and blood flow index of the dorsal pedis artery were determined by colour and pulse Doppler ultrasonography before and 60 min after administration of 4 mg nilvadipine or placebo.

Efficacy of Ibudilast on lower limb circulation of diabetic patients with minimally impaired baseline flow: a study using color Doppler ultrasonography and laser Doppler flowmetry.

Ibudilast is a prostacyclin-mediated vasodilator and antiplatelet agent. The hemodynamic effects of ibudilast were evaluated in 41 patients with non-insulin-dependent diabetes mellitus by means of two-dimensional Doppler ultrasonography and laser Doppler blood flowmetry. Before and one hour after oral administration of ibudilast (10 mg), or elastase (1800 U) as a control, the cross-sectional area (CSA) of the dorsal pedis artery, its blood flow index (BFI), and dermal microcirculatory blood volume (MBV) were measured.

The effect of non-enzymatic glycation on recombinant human aldose reductase.

It has been demonstrated that activation of aldose reductase (AR; EC 1.1.1.

Transient nephrogenic diabetes insipidus accompanied by possible psychogenic polydipsia.

A 50-year-old Japanese man had been suffering from polydipsia and polyuria for 2 months without any other specific symptoms. His daily urinary output reached 5 liters. On admission, no abnormalities of the kidneys, heart, thyroid, adrenals, pituitary or hypothalamus were detected by laboratory tests and MRI of the head.

Syndrome of inappropriate secretion of antidiuretic hormone (SIADH) and Gerhardt syndrome associated with Shy-Drager syndrome.

This is the first report on a case of syndrome of inappropriate secretion of antidiuretic hormone (SIADH) associated with Gerhardt syndrome (paralysis of bilateral vocal cords). A 67-year-old Japanese man suffering from progressive autonomic failure was diagnosed as having Shy-Drager syndrome (SDS) with hyponatremia due to SIADH and severe sleep apnea caused by a bilateral recurrent nerve palsy. Water load test showed alteration in diuresis which was corrected by phenytoin.

Eicosapentaenoic acid enhances intracellular free calcium in cultured human endothelial cells.

Eicosapentaenoic acid (EPA) caused elevations of intracellular free Ca2+ concentration ([Ca2+]i) measured by fura-2 fluorescence in cultured human endothelial cells. The EPA-induced increase in [Ca2+]i could still be observed when either cyclooxygenase or lipoxygenase inhibitors were added. These results suggest that EPA itself rather than its metabolites has direct effects on intracellular Ca2+ mobilization, causing the elevation of [Ca2+]i.

[A case of Shy-Drager syndrome complicated with syndrome of inappropriate secretion of antidiuretic hormone (SIADH) and incomplete paralysis of bilateral vocal cords].

A 67-year-old man with SIADH complicated by slowly progressing autonomic failure was described. The patient noticed constipation at the age of 57. In the following years, he suffered from urinary incontinence, depletion of sweating, impotence, sleeplessness with snore, and dizziness while walking.

Inactivation of Cu,Zn-superoxide dismutase by in vitro glycosylation and in erythrocytes of diabetic patients.

Purified bovine Cu,Zn-superoxide dismutase was nonenzymatically glycosylated in vitro at a rate proportional to incubation time (2 to 120 hrs) and glucose concentration (10 to 100 mM). Inverse correlation between glycosylation and the enzyme activity showed that increased glycosylation was accompanied with inactivation of the enzyme. Specific activities of glycosylated and non-glycosylated enzymes incubated with 100 mM glucose for 120 hrs were 1150 and 2860 units/mg protein, respectively.

Effect of insulin on the proline transport activity in cultured fibroblasts from patients with Werner syndrome.

The effect of insulin on the transport of proline has been studied in cultured fibroblasts from normal individuals, non-insulin-dependent diabetic patients, and patients with Werner syndrome. In fibroblasts from normal individuals and those with diabetes mellitus, incubation with 10(-7) M insulin resulted in more than a twofold increase in the transport rate after about 14 h incubation. In contrast, fibroblasts from patients with Werner syndrome had a markedly attenuated response to insulin, suggesting a defect in insulin action on the transport of this amino acid in Werner syndrome.

High glucose and hyperosmolarity increase platelet-derived growth factor mRNA levels in cultured human vascular endothelial cells.

We investigated the effects of high glucose and hyperosmolality on platelet-derived growth factor (PDGF) production and PDGF-B chain mRNA levels in cultured human umbilical vein endothelial cells. Under an excess of ambient glucose (13.8 and 27.

Amelioration of dermal lesions in streptozotocin-induced diabetic rats by aminoguanidine.

As aminoguanidine (AG) is known to prevent non-enzymatic glycosylation in various tissues, we have histologically and biochemically evaluated AG effects on the skin in control, SZ-diabetic and AG-treated (25 mg/kgbw/day, 10w) diabetic rats. HbA1c and plasma glucose levels in diabetic and AG-treated diabetic rats were maintained about two times higher than those in control rats during the 10 weeks of the experiment. Histological findings revealed that the dermis in diabetic rats was thin and edematous, associated with swelling and degeneration of collagen fibers.

Ascorbic acid prevents the inhibition of DNA synthesis induced by high glucose concentration in cultured human endothelial cells.

Effects of glucose and ascorbic acid on in vitro collagen and DNA synthesis were evaluated in human umbilical vein endothelial cells. Ascorbic acid significantly potentiated collagen synthesis. Incubation of cells with elevated glucose concentration for 24h significantly reduced [3H]-thymidine uptake (2h).

Effect of glucose and an aldose reductase inhibitor on myo-inositol uptake by cultured human endothelial cells.

The effects of an aldose reductase (AR) inhibitor, elevated glucose and other compounds were evaluated on in vitro 2-[3H] myo-inositol (MI) uptake in cultured human endothelial cells (ECs). Significant AR activity was present in ECs (1,373 +/- 170 mumol/mg.min: incubated with 28 mM glucose for 48 hr).

Aminoguanidine decreases urinary albumin and high-molecular-weight proteins in diabetic rats.

The effect of aminoguanidine (AG) on diabetic proteinuria was studied in control rats ([C]), streptozotocin (SZ)-induced diabetic rats ([DM]), control rats treated with AG [( C + AG]), or diabetic rats treated with AG [( DM + AG]). Increased glycation of hemoglobin (HbA1C), and glomerular basement membrane (GBM) type IV collagen (IV-C) at 10 wk of stable diabetes were associated with the appearance of high-molecular-weight (HMW) cross-linked type I collagen and HMW proteinuria of 62 kD, 69 kD albumin and 77 kD proteins to the levels of 362, 381, and 408%, while 9.9, 13.

Assessment of the relationship between serum thyroid hormone levels and peripheral metabolism in patients with anorexia nervosa.

It has been observed that basal and/or TRH-stimulated serum TSH levels occasionally conflict with the actual values of circulating thyroid hormones in patients with anorexia nervosa. In the present study sixteen female patients with anorexia nervosa during self-induced starvation displayed clinical findings suggesting hypothyroidism, e.g.

Reduced sensitivity to catecholamine in Werner's syndrome fibroblasts.

The beta-adrenergic receptor-coupled adenylate cyclase system has been investigated in normal and Werner's syndrome fibroblasts. The basal levels of cAMP in Werner and normal control cells were similar, whereas the isoproterenol-induced increase in cAMP levels was far less for Werner cells than for control cells. In the broken cell preparations isoproterenol stimulated the adenylate cyclase of only control cells, not of Werner cells, although NaF or prostaglandin E1 stimulated the enzyme of both cells to the same extent.

Relationship between serum free thyroxine, total thyroxine and thyroxine-binding globulin concentrations in patients with Graves' disease.

Statistical analysis of relationship between free thyroxine (FT4) and thyroxine (T4) in patients with Graves' disease has revealed that serum FT4 values correlated well with serum T4 values at variable thyroid states before and during treatment with anti-thyroid drugs. However, the ratio of FT4 concentration to T4 concentration at hyperthyroid state was more than twice as large as the ratio at euthyroid and hypothyroid states. These findings are considered to denote the elevation of per cent of FT4 to T4 (% FT4) in thyrotoxicosis.