Chemical suppression of steroidogenesis.

A large number of chemicals are known to interfere with steroidogenesis in the adrenal cortex and other tissues. Many xenobiotics inhibit steroid hormone production as a result of interactions with cytochrome P-450-containing hydroxylases in adrenal mitochondria or microsomes. For example, metyrapone, a compound used clinically in the evaluation of pituitary-adrenocortical function, binds to various cytochromes P-450 in the adrenal, preventing the interactions of steroid substrates with the enzymes and inhibiting steroidogenesis. The mineralocorticoid antagonist, spironolactone, and its major circulating metabolite, canrenone, also competitively interact with adrenal steroid hydroxylases. In addition, spironolactone is converted by adrenal microsomes to an unknown metabolite which promotes the destruction of cytochromes P-450, decreasing the activities of steroid hydroxylases. Carbon tetrachloride is similarly "activated" by adrenal microsomal mixed function oxidases resulting in a decline in steroidogenic enzyme activity. Carbon tetrachloride (in the presence of NADPH) initiates lipid peroxidation in adrenal microsomes but its toxic effects on steroid hydroxylases are fully demonstrable when lipid peroxidation is inhibited by EDTA. A number of heavy metals, including cadmium, also inhibit adrenal steroid hydroxylases. When incubated with adrenal microsomes, cadmium does not affect cytochrome P-450 levels but decreases basal and substrate stimulated NADPH-cytochrome P-450 reductase activity. Although inhibitory effects of many chemicals on steroidogenesis have been described, the toxicological significance as well as definitive mechanisms of action have in most cases yet to be determined

A new paradigm for credibly administering placebo alcohol to underage drinkers

Background: The primary goal of this study was to establish a paradigm for credibly administering placebo alcohol to underage drinkers. We also sought to create a new, valid procedure for establishing placebo alcohol believability. Method: Participants were 138 American college students (66.7% female) predominantly (90.0%) under the legal drinking age. Groups of 2–3 participants and one same-sex confederate consumed mixed drinks, purportedly containing alcohol, ad-lib in a naturalistic bar-laboratory for 20 min. All beverages, however, were non-alcoholic but we used visual, olfactory, and taste cues to maximize placebo credibility. Also, the confederate made two scripted statements designed to increase the perception of drinking real alcohol. After the drinking portion, participants responded to survey items related to alcohol consumption and intoxication. Next, they were individually debriefed, with open-ended responses used to make a determination of whether the participant was deceived with respect to placebo alcohol. Results: All participants estimated consuming some amount of alcohol. However, using a more conservative criteria for estimating alcohol believability based on the debrief, 89.1% of participants were classified as deceived. Deceived participants were much more likely to estimate having a positive blood alcohol content and to say that their current level of intoxication was typical given the amount of alcohol consumed than non-deceived participants. Discussion: Credibly administering placebo alcohol to underage drinkers is possible. This approach carries great potential for future laboratory work. In addition, the methodology used here to classify participants as deceived or not deceived appears valid based on self-reported BAC estimation and intoxication levels

Ulceroglandular Tularemia: A Typical Case of Relapse

Tularemia is an infectious disease that continues to occur sporadically and in epidemics in the United States. It is characterized as an acute febrile illness with constitutional symptoms associated with skin, glandular, respiratory, or gastrointestinal involvement. Tularemia usually can be treated effectively with streptomycin. Relapse most often occurs when patients are treated with bacteriostatic agents such as chloramphenicol or tetracycline. We present a case of ulceroglandular tularemia distinguished by its relapse after initial streptomycin/doxycycline therapy and subsequent slow response to additional streptomycin

Constraint Release mechanisms for H-Polymers moving in Linear Matrices of varying molar masses

We investigate the influence of the environment on the relaxation dynamics of well-defined H-polymers diluted in a matrix of linear chains. The molar mass of the linear chain matrix is systematically varied and the relaxation dynamics of the H-polymer is probed by means of linear viscoelastic measurements, with the aim to understand its altered motion in different blends, compared to its pure melt state. Our results indicate that short unentangled linear chains accelerate the relaxation of both the branches and the backbone of the H-polymers by acting as an effective solvent. On the other hand, the relaxation of the H-polymer in an entangled matrix is slowed-down, with the degree of retardation depending on the entanglement number of the linear chains. We show that this retardation can be quantified by considering that the H-polymers are moving in a dilated tube at the rhythm of the motion of the linear matrix

Elasticity of smectic liquid crystals with focal conic domains

We study the elastic properties of thermotropic smectic liquid crystals with focal conic domains (FCDs). After the application of the controlled preshear at different temperatures, we independently measured the shear modulus G' and the FCD size L. We find out that these quantities are related by the scaling relation G' ~ \gamma_{eff}/L where \gamma_{eff} is the effective surface tension of the FCDs. The experimentally obtained value of \gamma_{\rm eff} shows the same scaling as the effective surface tension of the layered systems \sqrt{KB} where K and B are the bending modulus and the layer compression modulus, respectively. The similarity of this scaling relation to that of the surfactant onion phase suggests an universal rheological behavior of the layered systems with defects.Comment: 14 pages, 7 figures, accepted for publication in JPC