The increases in fetal serum concentrations of thyroid-stimulating hormone, thyroxine-binding globulin, and total and free T4 and T3 during gestation reflect increasing maturation of the pituitary, thyroid, and liver. The finding of increasing fetal serum concentrations of thyroid-stimulating hormone in the presence of increasing thyroid hormone concentrations suggests that the sensitivity of the fetal pituitary gland to negative feedback is limited or is counterbalanced by increasing stimulation by thyrotropin-releasing hormone from the hypothalamus.
The propensity of atherosclerotic plaques to disrupt may be influenced by their lipid content and the distribution of these lipids within the plaque. To investigate this, we analyzed the morphological and lipid profiles of 668 human aortic plaques from 30 males who had died of ischemic heart disease. Plaques were classified as disrupted or as intact types A or B, the latter distinction being based on the absence or presence, respectively, of disrupted plaques within the same aorta. Disrupted plaques have a greater content of lipid (P < .001) and macrophages (P < .001) as well as a thinner cap (P < .001) than intact plaques. Lipid concentrations are positively associated with macrophage accumulation in all plaque types and are negatively associated with minimum cap thickness at the edge of disrupted plaques (P < .05). Free cholesterol concentration is inversely associated with minimum cap thickness at the center of type B plaques only (P < .05). At the center of intact type A and B and disrupted plaques, the free-to-esterified cholesterol ratios were 0.9 (range, 0.0 to 2.7), 0.8 (0.0 to 3.9), and 1.6 (0.2 to 4.0), respectively. Esterified cholesterol concentrations were higher at the center of type B plaques, and those of free cholesterol were higher at the center of disrupted plaques. At the edge of disrupted plaques, the free-to-esterified cholesterol ratio was 0.5 (0.0 to 2.7) because of the accumulation of esterified cholesterol. Concentrations of all fatty acids were increased at the edge of disrupted plaques compared with the center, but as a proportion of total fatty acids, omega 6-polyunsaturated fatty acids (PUFAs) were lower (44% versus 46%, P < .01), possibly reflecting oxidation of PUFAs. These data demonstrate differences in lipid composition and intraplaque lipid distribution between intact and disrupted plaques. At the edge of advanced plaques, increased esterified lipid concentrations, inversely associated with cap thickness, may reflect macrophage activity and a predisposition to rupture.
The appropriate dose and type of progestin may reduce the adverse effects of oral contraceptives on many metabolic markers of risk for coronary heart disease. Progestin-only formulations or combinations containing desogestrel or low-dose norethindrone were associated wtih the most favorable profiles.
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