Induction of renal metallothionein in rats with ischemic renal failure.

Metallothionein (MT) is induced by various types of oxidative stress. However, whether or not MT is induced in renal ischemia/reperfusion injury, in which oxidative stress is believed to play a major role, remains unknown. The present study investigated MT expression in the kidneys of rats with ischmic acute renal failure (IARF). Rats were subjected to 60 min of bilateral renal ischemia followed by reperfusion. Renal MT mRNA expression was then analyzed by Northern blotting. MT expression in ischemic kidney was also localized by in situ hybridization and immunohistochemistry. Renal MT mRNA expression, which was barely detectable in the sham-operated control kidney, increased significantly at 3 h afer reperfsion, continued to increase to a maximal level at 24 h that was maintained for 48 h. The level of MT mRNA expression returned to that of the control by day 4. A morphological study revealed that MT was expressed exclusively in the renal tubular epithelial cells, which are the targets of ischemia/reperfusion injury, and that MT predominated in the outer medulla in the IARF rat kidney at transcriptional and translational levels. These results suggest that MT induced in the IARF rat kidney plays an important role in protecting renal cells against oxidative stress induced by ischemia/reperfusion.

[Insulin resistance and hyperlipidemia in the elderly].

To elucidate the relationship between hyperlipidemias and insulin resistance in the elderly, we conducted three studies: 1) determination of the prevalence of hyperlipidemias in elderly subjects with impaired glucose tolerance or non-insulin dependent diabetes mellitus, 2) measurement of plasma glucose and insulin levels in patients with phyerlipidemias and atherosclerotic vascular disease, and 3) computation of correlation between levels of substances involved in coagulation and fibrinolysis (F-VII, F-X, and PAI-1) and levels of triglycerides and insulin in serum in hyperlipidemic patients with atherosclerotic vascular disease. The prevalence of hypertriglyceridemia was 4% in non-diabetic control subjects, 38% in subjects with impaired glucose tolerance, 22% in those with diabetes, and 29% in those with both conditions. Levels of glucose and insulin in plasma were measured after oral intake of 75 g of glucose. The insulin response was greater in the group with hypertriglyceridemia than in the group with normal triglyceride levels, although the glucose responses did not differ between the groups. The activities and levels of F-VII, F-X, and PAI-1 correlated with triglycerides in serum and also with fasting insulin levels in hyperlipidemic patients with atherosclerotic vascular disease. We conclude that hypertriglyceridemia plays an important role in the development of atherothrombotic vascular disease; it accompanies elevation of coagulation and antifibrinolytic activities in elderly patients with insulin resistance.

Complete atrioventricular block associated with regional myocardial scarring in a patient with Coxsackie B2 myocarditis.

Transient atrioventricular (A-V) conduction abnormalities are often experienced in patients with evolving acute viral myocarditis, but persistent complete A-V block requiring permanent cardiac pacing is rare. We describe a case who developed irreversible complete A-V block during the long-term course of Coxsackie B2 myocarditis. The endomyocardial biopsy revealed inflammatory cellular infiltrates and myocyte necrosis. A left ventriculogram and echocardiogram consistently demonstrated an aneurysm in the basal portion of the interventricular septum. It was speculated that the extensive myocardial scar caused by acute myocarditis resulted in the ventricular aneurysm of this particular myocardial region involving the A-V conduction system.

Metallothionein and zinc metabolism in endotoxin shock rats.

Zinc metabolism in endotoxicosis was investigated in rats. The zinc concentration in the serum decreased, while zinc contents increased in the lung, kidney and liver. Marked increase in zinc level was observed in the liver. In the liver cells, zinc concentrations of mitochondria and cytosol increased, but not in microsome. Metallothioneins (MTs), which probably participate in zinc metabolism, were induced by endotoxin administration. Although the same level of MT-2 as that of MT-1 was induced by zinc, the level of MT-2 was 3 to 4 fold higher than that of MT-1 by administrations of endotoxin or glucocorticoid hormone. Since no metallothionein was induced directly by addition of endotoxin to the media of cultured cells, the endotoxin was found not to induce MTs directly. The effect of zinc on superoxide generation of polymorphonuclear leukocytes was also studied. Zinc was found to inhibit superoxide generation dose-dependently.