Abstract-We investigated the effects of atorvastatin, a new 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, on the biogenesis of apolipoprotein B (apoB) in intact and permeabilized HepG2 cells. Intact cells were pretreated either with single or multiple doses of atorvastatin (0.1 to 20 mol/L) for periods of 6 to 20 hours and pulsed with [ 35 S]methionine. In some cases the cells were permeabilized with digitonin. Experiments were performed to investigate the effects of atorvastatin on (1) the rates of lipid synthesis and secretion, (2) the synthesis and accumulation of apoB, (3) the intracellular stability of apoB, (4) the amount of apoB-containing lipoprotein particles assembled in HepG2 microsomes, and (5) 35 S]methionine by the cells nor did it influence the synthesis of apoB or a control protein, albumin. However, atorvastatin reduced the secretion of apoB into the culture medium, apparently by enhancing the degradation of apoB in the cell under basal and induced conditions with oleate. The stability of apoB associated with the lipoprotein particles was also significantly lowered by atorvastatin. The stimulated degradation of apoB in atorvastatin-treated cells was sensitive to MG132, a proteasome inhibitor. The net effect of atorvastatin was a reduction in the number of apoB-containing lipoprotein particles of different sizes isolated from microsomes and a reduction in apoB secretion into the culture medium. The data suggest that atorvastatin may impair the translocation of apoB into the lumen of the endoplasmic reticulum, thus increasing the amount of apoB degraded intracellularly. It is hypothesized that atorvastatin alters these parameters primarily as a result of inhibiting cholesterol synthesis and limiting the availability of cholesterol and/or cholesterol ester for the normal assembly of apoB-containing lipoprotein particles. (Arterioscler Thromb Vasc Biol. 1998;18:783-793.)

These results suggest that autophagy is altered in skeletal and cardiac muscle during hypertension.

Mitral annular calcification (MAC) has been considered a risk factor for thrombo-embolic disease. Superimposed thrombus formation on MAC has not been well described as a possible underlying mechanism for this association. We report three patients with mobile left ventricular (LV) thrombus arising from the LV aspect of severe calcified mitral annulus in the setting of normal LV function, mitral valve function, and sinus rhythm.

No abstract

OBJECTIVE -To identify hormonal, psychological, and demographic predictors of symptom detection and accuracy of blood glucose estimation during mild hypoglycemia in adolescents and young adults with type 1 diabetes. RESEARCH DESIGN AND METHODS-During an insulin-glucose clamp study, 53 adolescents and 19 young adults estimated blood glucose levels and reported symptoms at euglycemia and after 30 min of mild hypoglycemia (3.3 mmol/l). Epinephrine and pancreatic polypeptide were measured, and both change in anxiety level during hypoglycemia and baseline level of anxiety were measured with the Spielberger Anxiety Inventory. Elevated levels of anxiety during euglycemia were used as an indicator of the psychological trait "negative affectivity." Previous studies have suggested that individuals with higher negative affectivity are more internally focused and, therefore, more likely to report somatic and visceral changes.RESULTS -During mild hypoglycemia, 42% of the sample subjects reported an increase in autonomic symptoms; 29% reported an increase in neuroglycopenic symptoms, and 28% estimated blood glucose levels accurately (within 10% of actual). Hormonal excursions did not predict any outcome, but higher anxiety levels during the euglycemic baseline were associated with better detection of hypoglycemic symptoms and more accurate estimation of blood glucose values after controlling for change in anxiety level during hypoglycemia.CONCLUSIONS -Psychological factors such as elevated anxiety levels ("negative affectivity") can influence blood glucose estimation and symptom detection in adolescents and young adults and may explain why some individuals are more adept than others at reducing their risk of severe hypoglycemia after participation in a formal blood glucose awareness training program. Diabetes Care 25:852-858, 2002