In the present study, we have measured protein kinase C (PKC) specific activities and total diacylglycerol (DAG) level in the aorta and heart of rats, which showed that after 2 weeks of streptozotocin (STZ)-induced diabetes, membranous PKC specific activity and total DAG content were increased significantly by 88% and 40% in the aorta and by 21% and 72% in the heart, respectively. Hyperglycemia was identified as being a causal factor since elevated glucose levels increased DAG levels in cultured aortic endothelial and smooth muscle cells. Analysis by immunoblotting revealed that only a and 1II PKC isoenzymes are detected in these two tissues and vascular cells among those studied. In STZ-induced diabetic rats, PII isoenzyme is preferentially increased in both aorta and heart, whereas PKC a did not change significantly. The increases in membranous PKC specific activity and DAG level are observed in both spontaneous diabetes-prone diabetic BB rats as well as in STZ-induced diabetic BB and SpragueDawley rats, which persisted for up to 5 weeks. After 2 weeks of diabetes without treatment, the normalization of blood glucose levels for up to 3 weeks with islet cell transplants in STZ-induced diabetic BB rats reversed the biochemical changes only in the heart, but not in the aorta. These results suggest that PKC activity and DAG level may be persistently activated in the macrovascular tissues from diabetic animals and indicate a possible role for these biochemical parameters in the development of diabetic chronic vascular complications.Cardiovascular disease is the leading cause of mortality and morbidity in diabetic patients (1, 2). Pathological studies have shown an increased rate of atherosclerotic lesions (1, 2); cardiac muscle cell dysfunction has also been reported (3). Hyperglycemia appears to be one of the many possible risk factors in diabetic patients (4, 5). Several hypotheses have been proposed to explain the adverse effects of hyperglycemia (6-8). We have reported that protein kinase C (PKC) was activated in the retina of diabetic rats as well as in cultured vascular cells exposed to elevated levels of glucose (9). The mechanism of PKC activation may be due to increased production of diacylglycerol (DAG) in retinal microvessels due to high glucose levels (9). Other investigators have reported that hyperglycemia and glucose can activate PKC in the microvessels of renal glomeruli (10) and granulation tissues (11) due to an increase in production of DAG.The alteration of PKC by diabetes and glucose is interesting since PKC activity has been shown to modulate smooth muscle growth (12) and contraction (13,14), endothelial cell permeability (15), expression of signal transduction of hormones and growth factors (16, 17), and cardiomyocyte contractility (18). All of these functions have been reported to be abnormal in diabetic animals or patients. In the present study, we have determined the changes of PKC specific activities and its isoforms as well as DAG levels in the aorta and heart of diabetic rats. I...
A 49-yr-old homosexual man with acquired immunodeficiency syndrome presented with a left-sided neck mass. He was found to have a firm goiter. He was clinically euthyroid, but had laboratory evidence of primary hypothyroidism. Radioactive iodine scan of the thyroid showed homogeneous uptake over an enlarged right lobe and absence of uptake over the left lobe. Two fine needle aspiration biopsies of the thyroid revealed the presence of Pneumocystis carinii (P. carinii) organisms on the Gomori's methenamine silver strain. After courses of iv and oral therapy with trimethoprim-sulfamethoxazole, a third fine needle aspiration biopsy failed to reveal any organisms. A repeated radioactive iodine scan of the thyroid showed return of uptake over the left lobe. Thyroid function tests normalized with levothyroxine, and the goiter decreased in size. To our knowledge, this is the first report of hypothyroidism associated with P. carinii infection of the thyroid. P. carinii infection should be considered in the differential diagnosis of human immunodeficiency virus infected individuals presenting with cold thyroid nodules. Fine needle aspiration biopsy is a valuable tool in assessing these patients.
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