Elevation of serum cholesterol levels in mice by the antioxidant butylated hydroxyanisole

The food antioxidants butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) are structurally related to the hypocholesterolemic drug probucol. The purpose of this study was to determine if BHA can lower serum cholesterol levels as is observed with probucol. Treatment of mice with 0.75% BHA in their feed for 10 days resulted in a significant (P < or = 0.01) elevation of serum cholesterol levels. This effect contrasts with the cholesterol-lowering effect of probucol. Further, the degree of cholesterol elevation was comparable to that observed in mice administered 3% cholesterol in their feed for 7 days. The enzyme acyl CoA:cholesterol acyltransferase (ACAT) was decreased significantly (P < or = 0.01) in liver microsomes from BHA-treated mice. In contrast, hepatic microsomal ACAT activity was increased significantly (P < or = 0.01) in cholesterol-fed mice. These results suggested that the increased serum cholesterol observed in BHA-treated mice was not accompanied by an increase in hepatic cholesterol levels. Indeed, hepatic microsomal cholesterol levels were reduced in BHA-treated mice, but were increased significantly (P < or = 0.01) in cholesterol-fed mice. These results demonstrate that the common food additive BHA elevates serum cholesterol levels by a mechanism that apparently involves the decreased uptake of cholesterol by the liver.     

Predictors of individual differences in mail-coding skills and their variation with ability level.

Personality and cognitive predictors of mail coding were investigated in 2 samples, 1 of high coding ability (N?=?56) and 1 of mixed ability (N?=?158). Two approaches to predicting correlates of skill within groups of differing ability were compared: P. L. Ackerman's (1988) ability theory and D. A. Norman and T. Shallice's (1985) account of levels of action control. The predictors of mail-coding skill varied with ability: Personality variables were more predictive among higher ability Ss, and cognitive measures were more predictive among lower ability Ss. Implications of the findings for theories of individual differences in skill are discussed. There were 2 main practical conclusions. First, the measures used were more predictive than a standard psychometric selection test. Second, correlates of skill may be different among unselected job applicants and among the subset of applicants hired for subsequent operational training. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The positive-acting sulfur regulatory protein CYS3 of Neurospora crassa: nuclear localization, autogenous control, and regions required for transcriptional activation

The positive-acting global sulfur regulatory protein, CYS3, of Neurospora crassa turns on the expression of a family of unlinked structural genes that encode enzymes of sulfur catabolism. CYS3 contains a leucine zipper and an adjacent basic region (b-zip), which together constitute a bipartite sequence-specific DNA-binding domain. Specific anti-CYS3 antibodies detected a protein of the expected size in nuclear extracts of wild-type Neurospora under conditions in which the sulfur circuit is activated. The CYS3 protein was not observed in cys-3 mutants. Nuclear extracts of wild type, but not cys-3 mutants, also showed specific DNA-binding activity identical to that obtained with a CYS3 protein expressed in Escherichia coli. A truncated CYS3 protein that contains primarily the b-zip domain binds to DNA with high specificity and affinity in vitro, yet fails to activate gene expression in vivo, and instead inhibits the function of the wild-type CYS3 protein. Amino-terminal, carboxyterminal, and internal deletions as well as alanine scanning mutagenesis were employed to identify regions of the CYS3 protein that are required for its trans-activation function. Regions of CYS3 carboxy terminal to the b-zip motif are not completely essential for function although loss of an alanine-rich region results in decreased activity. All deletions amino terminal to the b-zip motif led to a complete loss of CYS3 function. Alanine scanning mutagenesis demonstrated that an unusual prolinerich domain of CYS3 appears to be very important for function and is presumed to constitute an activation domain. It is concluded that CYS3 displays nuclear localization and positive autogenous control in Neurospora and functions as a trans-acting DNA-binding protein.     

Role of imidazoline receptors in the cardiovascular actions of moxonidine, rilmenidine and clonidine in conscious rabbits

The present study in conscious rabbits with intracisternal (i.c.) catheters sought to determine the relative contribution of the I1 subtype of imidazoline receptors (IR) and alpha 2 adrenoceptors to the hypotensive effects of rilmenidine, clonidine and moxonidine with an I1-IR/alpha 2 adrenoceptor antagonist efaroxan and a specific alpha 2 adrenoceptor antagonist 2-methoxyidazoxan (2-MI). The alpha 2 adrenoceptor antagonist effect of efaroxan was compared with 2-MI by performing cumulative dose-response curves in the presence of alpha-methyldopa (400 micrograms/kg i.c.). 2-MI was 5.6 times more potent than efaroxan at reversing 75% of the hypotension elicited by alpha-methyldopa (P < .025). This dose ratio was used to match doses of efaroxan and 2-MI for similar alpha 2 adrenoceptor blockade. The effects of efaroxan (4.1, 13, 41 micrograms/kg i.c.) and 2-MI (0.74, 2.3, 7.4 micrograms/kg i.c.) were investigated on a single i.c. dose of rilmenidine (12 micrograms/kg), clonidine (0.75 microgram/kg) and moxonidine (0.51 microgram/kg). These doses of the antihypertensive agents, which were determined from cumulative dose-response curves, produce 90% of the maximum hypotension. Efaroxan was more effective at reversing the hypotension induced by moxonidine and rilmenidine than was 2-MI (P < .01). These findings suggest that rilmenidine and moxonidine act predominantly via IR. By contrast, 2-MI was more effective at reversing the clonidine-induced hypotension than was efaroxan (P < .001), suggesting that clonidine acts mainly via alpha 2 adrenoceptors in conscious normotensive rabbits. Thus, a higher selectivity of the second generation agents moxonidine and rilmenidine for I1-IR over alpha 2 adrenoceptors, compared with the first generation agent clonidine, appears to be necessary for this effect to be manifested in their hypotensive actions.