The Accumulation of Tissue Cholesterol and Its Relationship to Bile Acid and Sterol Turnover

Normal and hypophysectomized rats were divided into equal homogeneous groups to determine the effect of cholestyramine, corn oil and cholesterol on the excretion of fecal bile acids and sterols. Bile acid turnover rates, pool sizes, and spectrums were studied and compared

The Effect of Psyllium Hydrocolloid and Cholestyramine on Hepatic Bile Lipid Composition in Man

The effects of a mucoid - psyllium hydrocolloid - and an anion exchange polymercholestryamine - on the total cholesterol, total phospholipid, total bile salt, cholate, chenodeoxycholate, and deoxycholate concentrations of hepatic bile were determined in six post-cholecystectomy patients. Bile was obtained by drainage through an indwelling T-tube, which was clamped except during bile collection. Psyllium hydrocolloid treatment (12 gm/day) for 6 to 29 days had little or no effect on the cholesterol or phospholipid concentration of hepatic bile, but increased the total bile salt pool by gradually increasing the concentration of deoxycholate. Cholestyramine treatment (12 gm/day) for 8 to 12 days had no significant effect on cholesterol, phospholipid or total bile salt concentrations. There was a significant increase in the tri- to di-hydroxy bile salt ratio due to decreases in chenodeoxycholate and deoxycholate concentrations. The ratio of taurine to glycine conjugates decreased because of reductions in concentrations of taurine conjugates and compensating increases in glycine conjugates. The influence of these changes on bile micelle stability and cholesterol solubility is discussed. It is concluded that the changes effected by psyllium hydrocolloid may result in more stable bile micelles and greater cholesterol solubility. No definite conclusions can be reached with respect to cholestyramine\u27s effects

Pharmacological screening using an FXN-EGFP cellular genomic reporter assay for the therapy of Friedreich ataxia

Copyright @ 2013 Li et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Friedreich ataxia (FRDA) is an autosomal recessive disorder characterized by neurodegeneration and cardiomyopathy. The presence of a GAA trinucleotide repeat expansion in the first intron of the FXN gene results in the inhibition of gene expression and an insufficiency of the mitochondrial protein frataxin. There is a correlation between expansion length, the amount of residual frataxin and the severity of disease. As the coding sequence is unaltered, pharmacological up-regulation of FXN expression may restore frataxin to therapeutic levels. To facilitate screening of compounds that modulate FXN expression in a physiologically relevant manner, we established a cellular genomic reporter assay consisting of a stable human cell line containing an FXN-EGFP fusion construct, in which the EGFP gene is fused in-frame with the entire normal human FXN gene present on a BAC clone. The cell line was used to establish a fluorometric cellular assay for use in high throughput screening (HTS) procedures. A small chemical library containing FDA-approved compounds and natural extracts was screened and analyzed. Compound hits identified by HTS were further evaluated by flow cytometry in the cellular genomic reporter assay. The effects on FXN mRNA and frataxin protein levels were measured in lymphoblast and fibroblast cell lines derived from individuals with FRDA and in a humanized GAA repeat expansion mouse model of FRDA. Compounds that were established to increase FXN gene expression and frataxin levels included several anti-cancer agents, the iron-chelator deferiprone and the phytoalexin resveratrol.Muscular Dystrophy Association (USA), the National Health and Medical Research Council (Australia), the Friedreich’s Ataxia Research Alliance (USA), the Brockhoff Foundation (Australia), the Friedreich Ataxia Research Association (Australasia), Seek A Miracle (USA) and the Victorian Government’s Operational Infrastructure Support Program

Simple rules can guide whether land or ocean based conservation will best benefit marine ecosystems

Coastal marine ecosystems can be managed by actions undertaken both on the land and in the ocean. Quantifying and comparing the costs and benefits of actions in both realms is therefore necessary for efficient management. Here, we quantify the link between terrestrial sediment run-off and a downstream coastal marine ecosystem, and contrast the cost-effectiveness of marine and land-based conservation actions. We use a dynamic land- and sea-scape model to determine whether limited funds should be directed to one of four alternative conservation actions – protection on land, protection in the ocean, restoration on land, or restoration in the ocean – to maximise the extent of light-dependent marine benthic habitats, across decadal time-scales. We apply the model to a case study seagrass meadow in Australia. We find that marine restoration is the most cost-effective action over decadal time-scales in this system, based on a conservative estimate of the rate at which seagrass can expand into new habitat. The optimal decision will vary in different social-ecological contexts, but some basic information can guide optimal investments to counteract land and ocean based stressors: (1) marine restoration should be prioritised if the rates of marine ecosystem decline and expansion are similar and low; (2) marine protection should take precedence if the rate of marine ecosystem decline is high, or if the adjacent catchment is relatively intact and has a low rate of vegetation decline; (3) land-based actions are optimal when the ratio of marine ecosystem expansion to decline is >1.4, with terrestrial restoration typically the most cost effective; and (4) land protection should be prioritised if the catchment is relatively intact, but the rate of vegetation decline is high. These rules-of-thumb illustrate how cost-effective conservation outcomes for connected land-ocean systems can proceed without complex modelling

A research perspective towards a more complete biodiversity footprint: a report from the World Biodiversity Forum

ISSN:0948-3349ISSN:1614-750

Advances of the FRIB project

The Facility for Rare Isotope Beams (FRIB) Project has entered the phase of beam commissioning starting from the room-temperature front end and the superconducting linac segment of first 15 cryomodules. With the newly commissioned helium refrigeration system supplying 4.5K liquid helium to the quarter-wave resonators and solenoids, the FRIB accelerator team achieved the sectional key performance parameters as designed ahead of schedule accelerating heavy ion beams above 20MeV/u energy. Thus, FRIB accelerator becomes world's highest-energy heavy ion linear accelerator. We also validated machine protection and personnel protection systems that will be crucial to the next phase of commissioning. FRIB is on track towards a national user facility at the power frontier with a beam power two orders of magnitude higher than operating heavy-ion facilities. This paper summarizes the status of accelerator design, technology development, construction, commissioning as well as path to operations and upgrades