Efficacy of a Therapeutic Lifestyle Change/Step 2 diet in moderately hypercholesterolemic middle-aged and elderly female and male subjects.

Lifestyle modification to decrease cardiovascular disease (CVD) risk has recently been reaffirmed by both the National Cholesterol Education Program and American Heart Association (AHA). Using a randomized crossover design, the Therapeutic Lifestyle Change (TLC)/Step 2 diet relative to a typical Western diet was assessed in 36 moderately hypercholesterolemic subjects in a clinical setting under isoweight conditions. Mean lipoprotein and apolipoprotein levels (fasting and non-fasting), fatty acid profiles, parameters of HDL metabolism, and glucose homeostasis were determined. Relative to the Western diet, the TLC/Step 2 diet resulted in 11% and 7% lower LDL cholesterol (LDL-C) and HDL cholesterol (HDL-C), respectively, with no significant change in TG levels or total cholesterol-HDL-C ratio. Similar responses were observed in the non-fasting state. Linoleic (18:2n-6c) and alpha-linolenic (18:3n-3) acids increased at the expense of oleic acid (18:1n-9c) in the cholesteryl ester, TG, and phospholipid subfractions. The dietary changes had no significant effect on fractional esterification rate of HDL, phospholipid transfer protein (PLTP), or cholesterol ester transfer protein activities, or glucose and insulin levels. Female and male subjects responded similarly. The TLC/Step 2 diet resulted in a decrease in some CVD risk factors and no apparent adverse effects in others.

Sequential involvement of Cdk1, mTOR and p53 in apoptosis induced by the HIV-1 envelope.

Syncytia arising from the fusion of cells expressing the HIV-1-encoded Env gene with cells expressing the CD4/CXCR4 complex undergo apoptosis following the nuclear translocation of mammalian target of rapamycin (mTOR), mTOR-mediated phosphorylation of p53 on Ser15 (p53(S15)), p53-dependent upregulation of Bax and activation of the mitochondrial death pathway. p53(S15) phosphorylation is only detected in syncytia in which nuclear fusion (karyogamy) has occurred. Karyogamy is secondary to a transient upregulation of cyclin B and a mitotic prophase-like dismantling of the nuclear envelope. Inhibition of cyclin-dependent kinase-1 (Cdk1) prevents karyogamy, mTOR activation, p53(S15) phosphorylation and apoptosis. Neutralization of p53 fails to prevent karyogamy, yet suppresses apoptosis. Peripheral blood mononuclear cells from HIV-1-infected patients exhibit an increase in cyclin B and mTOR expression, correlating with p53(S15) phosphorylation and viral load. Cdk1 inhibition prevents the death of syncytia elicited by HIV-1 infection of primary CD4 lymphoblasts. Thus, HIV-1 elicits a pro-apoptotic signal transduction pathway relying on the sequential action of cyclin B-Cdk1, mTOR and p53.