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Although chronic and excessive alcohol consumption is associated with liver disease, the mechanism of alcoholic liver injury is still not clear. Whether reduced hepatic production of nitric oxide, which is evident in models of liver injury, is associated with alcohol-induced liver injury has not been investigated. We measured nitric oxide synthase (NOS) activity in the liver of pair-fed rats receiving liquid diet with or without alcohol [3% (vol/vol)] for 12 wk. Compared with control rats, hepatic NOS activity was significantly reduced in alcohol-treated rats along with the evidence of liver injury. Interestingly, there was no difference in the hepatic expression of endothelial NOS (eNOS) between ethanol-fed and pair-fed rats. We then tested the hypothesis that an imbalance between the binding of eNOS with inhibitory and stimulatory proteins may underlie the reduced activity of eNOS because eNOS catalytic activity is regulated partly through dynamic interactions with the inhibitory protein caveolin-1 and the stimulatory protein calmodulin. We found that hepatic caveolin-1 was markedly increased in alcohol-treated rats compared with control rats, whereas calmodulin remained unaltered. The binding of caveolin-1 and calmodulin with eNOS was increased and decreased, respectively, in alcohol-treated rats. Our results suggest that chronic alcohol intake attenuates hepatic eNOS activity by increasing the expression of the inhibitory protein caveolin-1 and enhancing its binding with eNOS.

Abstract Lipid and carbohydrate retaining procedures were utilized to retain these components of surfactant in thin section. The origin of tubular myelin surfactant from multilamellar bodies was postulated on morphological evidence to be : an expansion of lamellae in pairs caused by the absorption of a homogeneous, probably carbohydratebased, material of undetermined origin; immediately after the pairs expanded to 438 A, the lamella (lipid bilayer) that was most peripheral in the multilamellar body underwent a molecular rearrangement to form the two cross lipid bilayers; the four lipid bilayers formed a square tubule 413 A of side and 0.16–1.8 μ long. The homogeneous material included within each tubule (the surfactant matrix) did not completely fill the intratubular space, but a centrally located, spherical, 57 A diameter, electron transparent, area was observed. The 413 A square tubules were separated on all sides by a 25 A fatty acid tail area. The phospholipid head areas were 46 A and the surfactant matrix was 132 A between the electron transparent, center area and the phospholipid heads layer. Extraction with several organic solvents was also studied: slight ethanol extraction—alteration of surfactant matrix and loss of transparent, central area. Moderate ethanol extraction—alteration of surfactant matrix to form artifactual tubules and filaments, disruption of lipid bilayers. Severe extraction—ethanol produced loss of integrity of both matrix and lipid bilayers; vinylcyclohexane dioxide or methacrylate produced complete loss of all lipid bilayers, but surfactant matrix retained tubular configuration ; DMP-30 produced complete loss of lipid bilayers, and although most of the matrix material was retained, all areas appeared fractured and randomly oriented.

We document the species richness and volatile oil diversity in Sonoran Desert plants found in the Arizona Uplands subdivision of this binational USA/Mexico region. Using floristics, we determined that more than 60 species of 178 native plants in the ancient ironwood-giant cactus forests emit fragrant biogenic volatile organic compounds (BVOCs), especially with the onset of summer monsoons. From these desert species, more than 115 volatile oils have been identified from one biogeographic region. For the 5 BVOCs most commonly associated with “forest bathing” practices in Asian temperate forests, at least 15 Sonoran Desert plant species emit them in Arizona Uplands vegetation. We document the potential health benefits attributed to each of 13 BVOCs in isolation, but we also hypothesize that the entire “suite” of BVOCs emitted from a diversity of desert plants during the monsoons may function synergistically to generate additional health benefits. Regular exposure to these BVOC health benefits may become more important to prevent or mitigate diseases of oxidative stress and other climate maladies in a hotter, drier world.

TorsinA, a novel protein in which a mutation causes dominant, early onset torsion dystonia, may serve as a chaperone for misfolded proteins that require refolding or degradation. It has been hypothesized that misfolded alpha-synuclein, a protein in which two mutations cause autosomal dominantly inherited Parkinson's disease, serves as a nidus for the development of a Lewy body. We hypothesized that torsinA plays a role in the cellular processing of alpha-synuclein. We demonstrate that anti-torsin antibodies stain Lewy bodies and Lewy neurites in the substantia nigra and cortex. Using sensitive fluorescent resonance energy transfer (FRET) techniques, we find evidence of a close association between torsinA and alpha-synuclein in Lewy bodies.

Background:  A low level of response (i.e., a low LR) to alcohol is a genetically influenced phenotype that predicts later alcoholism. While the low LR reflects, at least in part, a low brain response to alcohol, the physiological underpinnings of the low LR have only recently been addressed. Methods:  Forty‐nine drinking but not yet alcoholic matched pairs of 18‐ to 25‐year‐old subjects (N = 98; 53% women) with low and high LRs as established in separate alcohol challenges were evaluated in 2 event‐related functional magnetic resonance imaging (fMRI) sessions (placebo and approximately 0.7 ml/kg of alcohol) while performing a validated stop signal task. The high and low LR groups had identical blood alcohol levels during the alcohol session. Results:  Significant high versus low LR group and LR group × condition effects were observed in blood oxygen level–dependent (BOLD) signal during error and inhibitory processing, despite similar LR group performance on the task. In most clusters with significant (corrected p < 0.05, clusters > 1,344 μl) LR group × alcohol/placebo condition interactions, the low LR group demonstrated relatively less, whereas the high LR group demonstrated more, error and inhibition‐related activation after alcohol compared with placebo. Conclusions:  This is one of the first fMRI studies to demonstrate significant differences between healthy groups with different risks of a future life‐threatening disorder. The results may suggest a brain mechanism that contributes to how a low LR might enhance the risk of future heavy drinking and alcohol dependence.

Abstract As the part of a study to develop buparvaquone (BPQ) formulations for the treatment of cutaneous leishmaniasis, the topical delivery of BPQ and one of its prodrugs from a range of formulations was evaluated. In previous studies, BPQ and its prodrugs were shown to be potent antileishmanials in-vitro, with ED50 values in the nanomolar range. 3-Phosphono-oxymethyl-buparvaquone (3-POM-BPQ) was the most potent antileishmanial and was chosen, together with the parent drug, for further investigation. The ability of the parent and prodrug formulations to cross human and murine skin was tested in-vitro using the Franz diffusion cells. Formulations intended for topical application containing either BPQ or 3-POM-BPQ were developed using excipients that were either acceptable for topical use (GRAS or FDA inactive ingredients) or currently going through the regulatory process. BPQ was shown to penetrate both human epidermal membranes and full thickness BALB/c skin from a range of formulations (gels, emulsions). Similarly, 3-POM-BPQ penetrated full-thickness BALB/c skin from several gel formulations. In-vitro binding studies showed that BPQ bound melanin in a dose-dependent manner and preferably bound to delipidized skin over untreated BALB/c skin (on a weight to weight basis). The results confirm that BPQ and its prodrug 3-POM-BPQ can penetrate the skin from several formulations, making them potentially interesting candidates for further investigation of topical formulations using in-vivo models of cutaneous leishmaniasis.

The complete pathway of thiosulfate assimilation in baker's yeast is determined. The finding reveals the extensive overlap between sulfate and thiosulfate assimilation. Rhodanese is the only additional enzyme for thiosulfate utilization. The common presence of rhodanese in most organisms, including Bacteria , Archaea , and Eukarya , suggests that most organisms with the sulfate assimilation system also use thiosulfate. Since it takes less energy to reduce thiosulfate than sulfate for assimilation, thiosulfate has the potential to become a choice of sulfur in optimized media for industrial fermentation.

A multivariate analysis of dimensions of problem drinking and their stability across time is conducted through a series of confirmatory factor analyses (as opposed to exploratory factor analyses used in previous studies), using self-report data from a longitudinal sample of adolescents and youth. Analyses are performed separately by age and gender. Results indicate that traditional measures of problem drinking represent at least two distinct dimensions--intensity of use and use-related problems--rather than a unitary construct for adolescent males and females. The results also suggest that dimensions of problem drinking remain relatively stable from 15 to 21 years of age, except that alcohol-related problems are unstable for males from 15 to 18 years of age.