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Exogenous Substances (exogenous + substance)
Selected AbstractsSDS-PAGE of recombinant and endogenous erythropoietins: benefits and limitations of the method for application in doping controlDRUG TESTING AND ANALYSIS, Issue 1 2009Christian Reichel Abstract Doping of athletes with recombinant and genetically modified erythropoietins (EPO) is currently detected by isoelectric focusing (IEF). The application of these drugs leads to a significant change in the isoform profile of endogenous urinary erythropoietin (uhEPO). Dynepo, MIRCERA, biosimilars with variable IEF-profiles as well as active urines and effort urines have made additional testing strategies necessary. The new generation of small molecule EPO-receptor stimulating agents like Hematide will also challenge the analytical concept of detecting the abuse of erythropoiesis stimulating agents (ESA). By determining their apparent molecular masses with SDS-PAGE a clear differentiation between endogenous and exogenous substances also concerning new EPO modifications is possible. Due to the orthogonal character of IEF- and SDS-PAGE both methods complement each other. The additional benefits of SDS-PAGE especially in relation to active and effort urines as well as the detection of Dynepo were investigated. Due to significant differences between the apparent molecular masses of uhEPO/serum EPO (shEPO) and recombinant, genetically or chemically modified erythropoietins the presence of active or effort urines was easily revealed. The characteristic band shape and apparent molecular mass of Dynepo on SDS-PAGE additionally evidenced the presence of this substance in urine. A protocol for the detection of EPO-doping in serum and plasma by SDS-PAGE was developed. Blood appears to be the ideal matrix for detecting all forms ESA-doping in the future. Copyright © 2009 John Wiley & Sons, Ltd. [source] An assessment of endocrine disruption in mollusks and the potential for developing internationally standardized mollusk life cycle test guidelines,INTEGRATED ENVIRONMENTAL ASSESSMENT AND MANAGEMENT, Issue 3 2008Peter Matthiessen Abstract This paper summarizes what is known about the endocrine systems of mollusks and how they can be disrupted by exogenous substances. It then examines the various possibilities for using mollusk-based toxicity tests to detect and assess the environmental risks of endocrine-disrupting chemicals (EDCs). It is concluded that there are no internationally standardized tests with mollusks available at present that are suitable for assessing the risks of long-term exposure to EDCs but that several published methods show potential. At the present state of knowledge, the most promising mollusk species for use in partial life cycle testing is probably the fresh- and brackish-water mesogastropod, Potamopyrgus antipodarum, which is known to be responsive to both direct and indirect androgens and to estrogens (and their mimics). Less experience of full life cycle testing exists with mollusks, but the freshwater pulmonate gastropod Lymnaea stagnalis at present offers the best possibility for a practical procedure. In both cases, there is a need for substantial test optimization and validation before these procedures could form the basis of international guidelines. [source] New and active role of the interstitium in control of interstitial fluid pressure: potential therapeutic consequencesACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 2 2003H. Wiig Here we present recent data indicating that the present view of the interstitium as a passive fluid reservoir has to be revised. The connective tissue cells and extracellular matrix have a role in the control of Pif and a fundamental role in the rapid development of edema in burns and in the initial swelling in inflammation by generating a lowering of interstitial fluid pressure. In this process, the ,1 -integrin system seems to provide a common pathway by which the cells can lower as well as raise Pif. Inflammatory swelling can be reversed by endo- and exogenous substances, thereby suggesting that the connective tissue can serve as a novel target for pharmacological intervention. Furthermore, the new knowledge in interstitial physiology on means to reduce interstitial fluid pressure may be of importance for drug delivery into solid tumors, where a high Pif limits the uptake of therapeutic agents. [source] Biomedical applications of capillary electrophoresis with laser-induced fluorescence detectionBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 7-8 2001Ximena Páez Abstract Capillary electrophoresis (CE) is a high-efficiency analytical technique that has had a great impact as a tool in biomedical research, clinical and forensic practice in the last ten years. Only in one of the applications, the DNA analysis, it has had an explosive exponential growth in the last few years. This impact is expressed in an enormous amount of CE articles and many reviews. The CE advantages with respect to other analytical techniques: the required very small sample volume, rapid analysis, great resolution power and low costs, have made this technique ideal for the analysis of a numerous endogenous and exogenous substances present in biological fluids. The different modes of CE have been coupled to different detection techniques such as UV-absorbance, electrochemical, mass spectrometry and laser-induced fluorescence detection (LIFD) to detect different nature and molecular size separated analytes. This review focuses mostly on the applications of CE,LIFD, to measure drugs and endogenous neuroactive substances such as amino acids and monoamines, especially in microdialysis samples from experimental animals and humans. CE,LIFD trends are discussed: automated faster analysis with capillary array systems, resolution power improvement, higher detection sensitivity, and CE systems miniaturization for extremely small sample volume, in order to make CE easier and affordable to the lab bench or the clinical bed. Copyright © 2001 John Wiley & Sons, Ltd. [source] Zebrafish embryo extracts promote sphere-forming abilities of human melanoma cell lineCANCER SCIENCE, Issue 8 2009Yi-Rang Na Sphere-forming abilities in culture condition are considered a hallmark of cancer stem-like cells, which represents tumor cell invasiveness and stem-like characteristics. We aimed to show that the sphere-forming subpopulation of human malignant melanoma cell line WM-266-4 acts differently to zebrafish embryo extracts compared with their bulk counterpart. Spheres were maintained in neural stem cell culture conditions. The embryos of zebrafish at specific developmental stages were collected and the extracts were purified under 100 kDa. Spheres were treated with embyo extracts and proliferation assay and immunocytochemistry were conducted. Spheroid cells expressed nestin and epidermal growth factor receptor (EGFR) but not melanoma antigen recognized by T-cells (MART)1, indicating their stem-like character. Zebrafish embryo extracts at 50% epiboly stage inhibited melanoma bulk cell proliferation in a dose-dependent manner. However, sphere-forming abilities were significantly enhanced under 1 µg/mL concentration of 50% epiboly stage embryo extract treatment. Our findings implicate that we should consider cell subsets of a different character from the tumor origin that can respond differently to exogenous substances or tumor microenvironments. We suggest that cancer research should consider both minor stem-like subpopulations and the other major bulk tumor cells. (Cancer Sci 2009) [source] | ||||||||||