Sulfonylureas induce cholesterol accumulation in cultured human intimal cells and macrophages.

Using primary cultures of human smooth muscle intimal cells and mouse peritoneal macrophages it was demonstrated that oral hypoglycemic agents, sulfonylurea derivatives, at concentrations 10(-5)-10(-4) mol/l caused significant (by 25%-60%) intracellular total cholesterol accumulation. This in vitro atherogenic effect was confirmed in an ex vivo model. Sera from Type 2 diabetic patients, taken after sulfonylurea administration, acquired the ability to induce cholesterol accumulation in cultured cells. This enhanced atherogenic effect of patients' sera was observed for the next 2-4 h following the treatment and corresponded well to the pharmacokinetic characteristics of the tested drugs. The results suggest that sulfonylureas may exert a direct atherogenic action at the level of arterial cells, by increasing intracellular cholesterol content.

Modified low density lipoprotein from diabetic patients causes cholesterol accumulation in human intimal aortic cells.

Fifty-five serum samples from 99 Type 1 and 71 serum samples from 81 Type 2 diabetic patients (56% and 88%, respectively) brought about a 1.5-3.5-fold increase in total cholesterol content of cultured human intimal aortic cells. This atherogenic effect did not correlate with patient's age, diabetes duration or plasma lipid levels, and was mainly due to low density lipoprotein (LDL). Cholesterol accumulation in cells incubated with LDL highly correlated with that in cells exposed to corresponding patient's serum (r = 0.872 and r = 0.811, P < 0.0001, in Type 1 and Type 2 diabetic patients, respectively). In LDL from diabetic patients the sialic acid content was decreased by an average of 30% (P < 0.05), as compared with healthy subjects, and the fructosyl lysine content was increased by an average of 25% (P < 0.05). Atherogenic effect of patients' LDL significantly correlated with their fructosyl lysine content (P < 0.0001) and negatively correlated with sialic acid content (P < 0.0001). Two LDL fractions were further separated from the total LDL preparation by affinity chromatography on Ricinus communis agglutinin-agarose. The bound (desialylated) LDL fraction was characterized by an increased fructosyl lysine content and the altered neutral lipid and phospholipid composition, while non-bound (sialylated) LDL fraction did not differ from normal LDL. Desialylated, but not sialylated, LDL fraction induced massive cholesterol accumulation in cultured cells. In conclusion, the cholesterol accumulating effect of diabetic patients' blood sera is mainly related to atherogenic low density lipoprotein fraction, which is modified in various ways--by increased non-enzymatic glycosylation, desialylation and alterations in lipid composition. This multiple-modified LDL may contribute to the premature atherosclerosis development in diabetes mellitus.

[Atherogenic properties of sera and low-density lipoproteins in patients with diabetes mellitus]. / Aterogennye svoistva syvorotok krovi i lipoproteidov nizkoi plotnosti u bol'nykh sakharnym diabetom.

The effects of sera and low density lipoproteins (LDL) on cholesterol levels were evaluated in cultured aortic intimal cells from patients with Types 1 and 2 diabetes mellitus. About 80% Type 1 diabetic patients' sera and 90% of Type 2 diabetic patients' sera caused a 1.5-4-fold increase in intracellular cholesterol levels. LDL isolated from atherogenic sera induced intracellular cholesterol accumulation. There was a close correlation between the atherogenic effect of the sera and LDL. The atherogenic properties of the sera and LDL from patients with diabetes mellitus were unassociated with the examinees' age. There was a relationship between the atherogenic serum effect and the compensation of carbohydrate metabolism in male patients with Type 1 diabetes mellitus. The atherogenic effect of the sera and LDL failed to increase in patients with Types 1 and 2 diabetes mellitus concurrent with coronary heart disease. The property of the sera to accumulate intracellular cholesterol is likely to be typical of diabetes mellitus and mainly due to disturbed LDL metabolism.

[Dynamics of EKG changes in patients with Itsenko-Cushing disease before surgery, and following the 1st and 2d stages of adrenalectomy]. / Dinamika izmenenii EKG u bol'nykh bolezn'iu Itsenko--Kushinga do operatsii, posle pervogo i vtorogo étapov adrenaléktomii.

The results of examination of ECG in 44 patients suffering from Itsenko-Cushing's disease at different stages of surgical treatment are presented. The data obtained were compared with the blood potassium and sodium levels, 17-KS, and 17-OCS levels in the urine, arterial pressure and cholesterol content. Various ECG changes before the operation were revealed in 39 patients. Signs of enlargement of the left ventricle and deformity of the end part of the ventricular complex (negative T wave and or reduction of S-T segment in I, II, avL V5-6 leads) were found in 8 patients, and deformity of the end part of the ventricular complex without any signs of enlargement of the left ventricle--in 18 patients. There proved to be a significant dependence of the changes in the end port of the ventricular complex on increased urinary excretion of 17-OCS, hypokaliemia and hypernatriemia. Negative ECG changes after bilateral total adrenalectomy was significantly connected with postoperative hypocorticism.