Investigation of fluorescent properties of plasma exosomes in diagnosis and prognosis of colorectal cancer

Exosomes of blood plasma were studied using multiphoton tomography (two-photon microscopy). Exosomes were isolated in patients with colorectal cancer and in healthy donors. Images of fluorescence of exosomes were obtained at a wavelength of 760 nm and second harmonic generation at a wavelength of 380 nm. As a result of the analysis of the obtained data, qualitative differences were found between samples from patients with colorectal cancer and healthy donors

Syntbesis and Properries of the Selective Antimuscarinic Agent Cyclohexylphenyl(3-piperidinopropyl)silanol

Die Synthese des selektiven Antimuskarinikums Cyclohexylpheny\{3-piperidinopropyl)sila· nol (1 b) wird beschrieben. 1 b wurde - ausgehend von (3·Chlorpropyl)trimethoxysilan - durch eine vierstufige Reaktionsfolge erhalten und als Hydrochlorid 2b mit einer Gesamtausbeute von etwa 45°/o isoliert. - 1 b ist aufgrund seiner großen pharmakologischen Se· lektivität zu einer Standardsubstanz in der experimentellen Pharmakologie bei der Differenzierung von Muskarinrezeptoren geworden.The synthesis of thc selective antimuscarinic agent cyclohexylphenyl(3-piperidinopropyl)silanol (1 b) is described. Starting with (3-chloropropyl)trimethoxysilane, I b was obtained by four reaction steps and isolated as hydrochloride 2b with a total yield of about 45°/o. - Because of its high pharmacological selectivity 1 b has become a reference drug in experimental pharmacology for the differentiation of muscarinic rcceptors

CD28 between tolerance and autoimmunity: The side effects of animal models [version 1; referees: 2 approved]

Regulation of immune responses is critical for ensuring pathogen clearance and for preventing reaction against self-antigens. Failure or breakdown of immunological tolerance results in autoimmunity. CD28 is an important co-stimulatory receptor expressed on T cells that, upon specific ligand binding, delivers signals essential for full T-cell activation and for the development and homeostasis of suppressive regulatory T cells. Many in vivo mouse models have been used for understanding the role of CD28 in the maintenance of immune homeostasis, thus leading to the development of CD28 signaling modulators that have been approved for the treatment of some autoimmune diseases. Despite all of this progress, a deeper understanding of the differences between the mouse and human receptor is required to allow a safe translation of pre-clinical studies in efficient therapies. In this review, we discuss the role of CD28 in tolerance and autoimmunity and the clinical efficacy of drugs that block or enhance CD28 signaling, by highlighting the success and failure of pre-clinical studies, when translated to humans

Risk of disordered eating among Division I female college athletes

International Journal of Exercise Science 8(3): 256-264, 2015. The purpose of this study was to assess the risk of disordered eating (DE) among female athletes in lean and non-lean sports using the ATHLETE survey. The ATHLETE survey is divided into six different constructs, and a high score indicates a high risk for DE. Eighty-three varsity female athletes from eight Campbell University sports teams completed the survey and a medical history form anonymously. The sports were divided into sports that traditionally have a high risk for DE (lean sports) and those with a low risk (non-lean sports). The lean sports included: cheerleading, cross country/track and field, swimming, and volleyball. The non-lean sports included: basketball, golf, soccer, and softball. The total mean score of the ATHLETE survey for the lean sports was 100.1 ± 17.4, compared to the non-lean sports scoring 90.1 ± 16.9, p = 0.011. The two constructs that showed significant difference between lean and non-lean sports were Social Pressure on Body Shape (lean: 12.2 ± 3.9, non-lean: 9.4 ± 4.6, p = 0.005) and Team Trust (lean: 7.4 ± 3.3, non-lean: 5.6 ± 2.2, p = 0.004). The results indicate that lean sports exhibited a higher risk for development of DE compared to athletes participating in non-lean sports. It appears that the primary influence of DE in these female athletes came from external social pressures that may therefore dictate their exercise and nutritional habits

Relationship between Friend virus and an associated lymphatic leukaemia virus.

virus into rats (Mirand and Grace, 1962; Dawson, Rose and Fieldsteel, 1966) an

Synergistic drug-cytokine induction of hepatocellular death as an in vitro approach for the study of inflammation-associated idiosyncratic drug hepatotoxicity

Idiosyncratic drug hepatotoxicity represents a major problem in drug development due to inadequacy of current preclinical screening assays, but recently established rodent models utilizing bacterial LPS co-administration to induce an inflammatory background have successfully reproduced idiosyncratic hepatotoxicity signatures for certain drugs. However, the low-throughput nature of these models renders them problematic for employment as preclinical screening assays. Here, we present an analogous, but high-throughput, in vitro approach in which drugs are administered to a variety of cell types (primary human and rat hepatocytes and the human HepG2 cell line) across a landscape of inflammatory contexts containing LPS and cytokines TNF, IFNγ, IL-1α, and IL-6. Using this assay, we observed drug–cytokine hepatotoxicity synergies for multiple idiosyncratic hepatotoxicants (ranitidine, trovafloxacin, nefazodone, nimesulide, clarithromycin, and telithromycin) but not for their corresponding non-toxic control compounds (famotidine, levofloxacin, buspirone, and aspirin). A larger compendium of drug–cytokine mix hepatotoxicity data demonstrated that hepatotoxicity synergies were largely potentiated by TNF, IL-1α, and LPS within the context of multi-cytokine mixes. Then, we screened 90 drugs for cytokine synergy in human hepatocytes and found that a significantly larger fraction of the idiosyncratic hepatotoxicants (19%) synergized with a single cytokine mix than did the non-hepatotoxic drugs (3%). Finally, we used an information theoretic approach to ascertain especially informative subsets of cytokine treatments for most highly effective construction of regression models for drug- and cytokine mix-induced hepatotoxicities across these cell systems. Our results suggest that this drug–cytokine co-treatment approach could provide a useful preclinical tool for investigating inflammation-associated idiosyncratic drug hepatotoxicity.Pfizer Inc.Institute for Collaborative BiotechnologiesMIT Center for Cell Decision ProcessesNational Institute of Mental Health (U.S.) (grant P50-GM68762)National Institute of Mental Health (U.S.) (grant T32-GM008334)Massachusetts Institute of Technology. Biotechnology Process Engineering CenterMassachusetts Institute of Technology. Center for Environmental Health SciencesNational Institute of Mental Health (U.S.) (grant U19ES011399)Whitaker Foundatio