Effects of dextro-thyroxine, a preparation almost free of levo-thyroxine, on thyroid function, serum lipids and apolipoprotein A-I in "double pre-beta lipoproteinemia".

Eight subjects, belonging to a large family kindred repeatedly showing the electrophoretic pattern of the "double pre-beta lipoproteinemia", were studied. In seven of them thyroid function, serum lipids and apolipoprotein A-I were determined before and after treatment with dextro-thyroxine, preparation almost free of levo-thyroxine. In most of the patients, total-T4 levels and free-T4 Index were in the lower normal range, but basal TSH levels and the TSH response to TRH were normal. Dextro-thyroxine was effective in reducing both serum total cholesterol and triglycerides, but the percentage decrease in serum triglycerides was definitely greater than that of serum total cholesterol. This marked, unexpected hypotriglyceridemic effect is similar to that observed in a group of obese, hypertriglyceridemic hypothyroid patients treated with levo-thyroxine. Besides serum total cholesterol and triglycerides, the VLDL cholesterol/triglycerides ratio and the electrophoretic "slow moving" pre-beta component were also significantly reduced after treatment, suggesting that dextro-thyroxine can remove efficiently "remnant" VLDL particles from the plasma. Following dextro-thyroxine therapy, the relatively low pretreatment values of apolipoprotein A-I were significantly increased, being restored to normal.

Evidence for a major role of plasma lipoproteins as hematoporphyrin carriers in vivo.

Hematoporphyrin (5 mg/ml), administered intravenously to tumor-bearing patients, becomes associated with different serum proteins, including lipoproteins (mainly HDL), globulin and albumin. No residual porphyrin is bound to the two latter classes of proteins after 48 h, whereas the complexation with the lipoproteins appears to be particularly stable probably owing to the hydrophobic nature of hematoporphyrin. The late persistence of hematoporphyrin in serum is due to the binding to the VLDL fraction with special regard to its cholesterol moiety. The importance of hematoporphyrin transport by lipoproteins for the photodynamic therapy of tumors is briefly discussed.

Relationship between 'sinking pre-beta-lipoprotein' (Lp(a) lipoprotein) and age in a family kindred.

Serum Lp(a) levels have been measured in a family kindred of three generations by Laurell electrophoresis. It was found that individuals with Lp(a) levels exceeding 30 mg/dl exhibited an extra pre-beta-band in agarose gel electrophoresis (sinking pre-beta positive), and a significant positive correlation existed between serum Lp(a) levels and age. A positive correlation between Lp(a) and total serum cholesterol was observed only in sinking pre-beta-positive individuals, but not in sinking pre-beta-negative individuals with Lp(a) levels of less than 30 mg/dl. These findings are not contradictory to the assumption that Lp(a) might be an independent rise factor for atherosclerosis.

Double pre-beta lipoprotein. Isolation and characterization of the two population of very low density lipoproteins by zonal ultracentrifugation.

Two electrophoretic populations of very low density lipoprotein are frequently observed in both normal and hyperlipidemic human sera. This gives the appearance of two pre-beta bands, called the "double pre-beta lipoprotein phenomenon." The slow and fast bands forming the double pre-beta lipoprotein were isolated by ultracentrifugation in the zonal rotor under rate flotation conditions. On the basis of the effluent position, the slow band showed a lower flotation coefficient than the fast one. The lipid and apoprotein composition of the two very low density lipoprotein populations isolated by zonal ultracentrifugation was in close agreement with those obtained by preparative agarose gel electrophoresis. The slow and fast pre-beta fractions had the same triglyceride fatty acid composition. Both fractions contained only higher molecular weight apo B-100, while the slow fraction was relatively enriched in apo E and apo C-III. Since the slow pre-beta fraction showed the typical properties of the remnant particle, studying this fraction could clarify the possible relationship between remnant lipoproteins and atherogenesis. Zonal rotor ultracentrifugation may be useful to characterize remnant particles in normal and hyperlipidemic subjects.

Further definition of lipid-lipoprotein abnormalities in children with various degrees of chronic renal insufficiency.

We characterized the lipid-lipoprotein abnormalities encountered in a series of 45 nonnephrotic uremic children with various degrees of chronic renal insufficiency. A mild hypertriglyceridemia associated with decreased serum high-density lipoprotein cholesterol levels was confirmed. The correlation between high-density lipoprotein cholesterol and creatinine clearance showed a power behavior with a marked decrease in high-density lipoprotein cholesterol below a creatinine clearance value of 40 ml/min/1.73 m2. A number of uremic children accumulate an abnormal population of very low-density lipoprotein particles in their plasma. On agarose gel electrophoresis these particles migrate as a slow moving pre-beta band and are clearly distinguished from the regular fast moving pre-beta very low-density lipoprotein band. This electrophoretic phenomenon has been called double pre-beta lipoproteinemia. The prevalence of double pre-beta lipoproteinemia increased significantly with the degree of impairment of renal function, reaching highest figures in patients on hemodialysis. Accordingly, the very low-density lipoprotein cholesterol/triglyceride ratio also was significantly increased. The double pre-beta lipoproteinemia phenomenon was not detected in any of the control, nonuremic subjects. The clinical importance of double pre-beta lipoproteinemia in uremic plasma is related to its possible atherogenic role.

The double pre-beta very low density lipoprotein lipoproteinemia (DPBL): a new dyslipoproteinemic state.

A new dyslipoproteinemic state, characterized by two populations of very low density lipoprotein particles giving the electrophoretic appearance of two pre-beta bands, the double pre-beta lipoproteinemia, is described. Based upon the lipid and apoprotein composition, it can be inferred that the slow moving pre-beta component is probably made up of remnant very low density lipoprotein particles; the absence of apo B 48 in the very low density lipoprotein fraction in these subjects rules out the intestinal origin of this remnant. Clinical interest in the double pre-beta lipoproteinemia relates to its potential atherogenicity; in fact it seems to be causally associated with such pathological conditions as hypothyroidism, uremia and dialysis, which are frequently accompanied by clinical complications of atherosclerosis. Double pre-beta lipoproteinemia also shows familial aggregation. Six years follow-up in a large family kindred has demonstrated that the family members carrying the double pre-beta lipoproteinemia, develop an incidence of coronary and cerebrovascular events higher than that of family members without the double pre-beta lipoproteinemia.