Does dietary tocopherol level affect fatty acid metabolism in fish?

Fish are a rich source of the n-3 polyunsaturated fatty acids (PUFA), particularly the highly unsaturated fatty acids (HUFA), eicosapentaenoic (EPA; 20:5n-3) and docosahexaenoic (DHA; 22:6n-3) acids, which are vital constituents for cell membrane structure and function, but which are also highly susceptible to attack by oxygen and other organic radicals. Resultant damage to PUFA in membrane phospholipids can have serious consequences for cell membrane structure and function, with potential pathological effects on cells and tissues. Physiological antioxidant protection involves both endogenous components, such as free radical scavenging enzymes, and exogenous dietary micronutrients including tocopherols and tocotrienols, the vitamin E-type compounds, widely regarded as the primary lipid soluble antioxidants. The antioxidant activities of tocopherols are imparted by their ability to donate their phenolic hydrogen atoms to lipid (fatty acid) free radicals resulting in the stabilisation of the latter and the termination of the lipid peroxidation chain reaction. However, tocopherols can also prevent PUFA peroxidation by acting as quenchers of singlet oxygen. Recent studies on marine fish have shown correlations between dietary and tissue PUFA/tocopherol ratios and incidence of lipid peroxidation as indicated by the levels of TBARS and isoprostanes. These studies also showed that feeding diets containing oxidised oil significantly affected the activities of liver antioxidant defence enzymes and that dietary tocopherol partially attenuated these effects. However, there is evidence that dietary tocopherols can affect fatty acid metabolism in other ways. An increase in membrane PUFA was observed in rats deficient in vitamin E. This was suggested to be due to over production of PUFA arising from increased activity of the desaturation/elongation mechanisms responsible for the synthesis of PUFA. Consistent with this, increased desaturation of 18:3n-3 and 20:5n-3 in hepatocytes from salmon fed diets deficient in tocopherol and/or astaxanthin has been observed. Although the mechanism is unclear, tocopherols may influence biosynthesis of n-3PUFA through alteration of cellular oxidation potential or “peroxide tone”

Candida glabrata : a review of its features and resistance

Candida species belong to the normal microbiota of the oral cavity and gastrointestinal and vaginal tracts, and are responsible for several clinical manifestations, from mucocutaneous overgrowth to bloodstream infections. Once believed to be non-pathogenic, Candida glabrata was rapidly blamable for many human diseases. Year after year, these pathological circumstances are more recurrent and problematic to treat, especially when patients reveal any level of immunosuppression. These difficulties arise from the capacity of C. glabrata to form biofilms and also from its high resistance to traditional antifungal therapies. Thus, this review intends to present an excerpt of the biology, epidemiology, and pathology of C. glabrata, and detail an approach to its resistance mechanisms based on studies carried out up to the present.The authors are grateful to strategic project PTDC/SAU-MIC/119069/2010 for the financial support to the research center and for Celia F. Rodrigues' grant

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Screening out irrelevant cell-based models of disease

The common and persistent failures to translate promising preclinical drug candidates into clinical success highlight the limited effectiveness of disease models currently used in drug discovery. An apparent reluctance to explore and adopt alternative cell-and tissue-based model systems, coupled with a detachment from clinical practice during assay validation, contributes to ineffective translational research. To help address these issues and stimulate debate, here we propose a set of principles to facilitate the definition and development of disease-relevant assays, and we discuss new opportunities for exploiting the latest advances in cell-based assay technologies in drug discovery, including induced pluripotent stem cells, three-dimensional (3D) co-culture and organ-on-a-chip systems, complemented by advances in single-cell imaging and gene editing technologies. Funding to support precompetitive, multidisciplinary collaborations to develop novel preclinical models and cell-based screening technologies could have a key role in improving their clinical relevance, and ultimately increase clinical success rates

Impact of GODAE products on nested HYCOM simulations of the West Florida Shelf

Nested non-assimilative simulations of the West Florida Shelf for 2004-2005 are used to quantify the impact of initial and boundary conditions provided by Global Ocean Data Assimilation Experiment ocean products. Simulations are nested within an optimum interpolation hindcast of the Atlantic Ocean, the initial test of the US Navy Coupled Ocean Data Assimilation system for the Gulf of Mexico, and a global ocean hindcast that used the latter assimilation system. These simulations are compared to one that is nested in a non-assimilative Gulf of Mexico model to document the importance of assimilation in the outer model. Simulations are evaluated by comparing model results to moored Acoustic Doppler Current Profiler measurements and moored sea surface temperature time series. The choice of outer model has little influence on simulated velocity fluctuations over the inner and middle shelf where fluctuations are dominated by the deterministic wind-driven response. Improvement is documented in the representation of alongshore flow variability over the outer shelf, driven in part by the intrusion of the Loop Current and associated cyclones at the shelf edge near the Dry Tortugas. This improvement was realized in the simulation nested in the global ocean hindcast, the only outer model choice that contained a realistic representation of Loop Current transport associated with basin-scale wind-driven gyre circulation and the Atlantic Meridional Overturning Circulation. For temperature, the non-assimilative outer model had a cold bias in the upper ocean that was substantially corrected in the data-assimilative outer models, leading to improved temperature representation in the simulations nested in the assimilative outer models

Evaluation of Global Ocean Data Assimilation Experiment Products on South Florida Nested Simulations with the Hybrid Coordinate Ocean Model

The South Florida Hybrid Coordinate Ocean Model (SoFLA-HYCOM) encompasses a variety of coastal regions (the broad Southwest Florida shelf, the narrow Atlantic Keys shelf, the shallow Florida Bay, and Biscayne Bay) and deep regions (the Straits of Florida), including Marine Protected Areas (the Florida Keys Marine Sanctuary and the Dry Tortugas Ecological Reserve). The presence of the strong Loop Current/Florida Current system and associated eddies connects the local and basin-wide dynamics. A multi-nested approach has been developed to ensure resolution of coastal-scale processes and proper interaction with the large scale flows. The simulations are free running and effects of data assimilation are introduced through boundary conditions derived from Global Ocean Data Assimilation Experiment products. The study evaluates the effects of boundary conditions on the successful hindcasting of circulation patterns by a nested model, applied on a dynamically and topographically complex shelf area. Independent (not assimilated) observations are employed for a quantitative validation of the numerical results. The discussion of the prevailing dynamics that are revealed in both modeled and observed patterns suggests the importance of topography resolution and local forcing on the inner shelf to middle shelf areas, while large scale processes are found to dominate the outer shelf flows. The results indicate that the successful hindcasting of circulation patterns in a coastal area that is characterized by complex topography and proximity to a large scale current system requires a dynamical downscaling approach, with simulations that are nested in a hierarchy of data assimilative outer models