Adv Exp Med Biol
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Historically, hemoglobin-based oxygen carriers (HBOCs) were being developed as "blood substitutes," despite their transient circulatory half-life (~ 24 h) vs. transfused red blood cells (RBCs). More recently, HBOC commercial development focused on "oxygen therapeutic" indications to provide a temporary oxygenation bridge until medical or surgical interventions (including RBC transfusion, if required) can be initiated. This included the early trauma trials with HemAssist ® (BAXTER), Hemopure ® (BIOPURE) and PolyHeme ® (NORTHFIELD) for resuscitating hypotensive shock. ⋯ This was key to the successful conduct of their Phase 2 program (ex-US, from 2009 to 2012) to evaluate MP4OX as an adjunct to standard fluid resuscitation and transfusion of RBCs. In 2013, SANGART shared their Phase 2b results with the FDA, and succeeded in getting the FDA to agree that a planned Phase 2c higher dose comparison study of MP4OX in trauma could include clinical sites in the US. Unfortunately, SANGART failed to secure new funding and was forced to terminate development and operations in Dec 2013, even though a regulatory path forward with FDA approval to proceed in trauma had been achieved.
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Review
The Mechanistic Role of the Calcium-Activated Chloride Channel ANO1 in Tumor Growth and Signaling.
Multiple studies have described the high expression and amplification of Anoctamin 1 (ANO1) in various cancers, including, but not limited to breast cancer, head and neck cancer, gastrointestinal stromal tumors and glioblastoma. ANO1 has been demonstrated to be critical for tumor growth in breast and head and neck cancers through its regulation of EGFR signaling and pathway modulators like MAPK and protein kinase B. However, the discovery of ANO1 as a calcium activated chloride channel came as a surprise to the field and has given rise to many questions. How does a chloride channel promote oncogenesis? Is the chloride channel function of ANO1 important for its role in cancer? Does ANO1 exhibits chloride-independent functions in cancer cells? This review summarizes the current understanding of ANO1's function in cancer, provides a synopsis of the findings addressing the open questions in the field and gives an outlook on the promising future of ANO1 as a potential therapeutic target for the treatment of various cancers.
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The effect of acute exposure to cigarette smoke (CS) on the respiratory system has been less extensively studied than the long term effects of smoking. The aim of the present study was to evaluate the acute response to CS in smokers suffering from chronic obstructive pulmonary disease (COPD) and in healthy smokers. Nineteen stable COPD patients and 19 young healthy smokers were enrolled. ⋯ Post-CS TNF-α correlated inversely with FEV1/FVC in healthy smokers. We conclude that CS does not acutely increase the EBC concentration of the inflammatory markers either in COPD patients or healthy smokers. The short term CS-induced oxidative stress is higher in young smokers than in COPD patients, which what may indicate a higher susceptibility to CS content of the former.
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The impulse oscillometry (IOS) is recognized as a complementary method to spirometry in the diagnostics of obstructive pulmonary disorders. The IOS enables to measure total respiratory resistance (R5) and proximal respiratory resistance (R20), with the R5-R20 difference reflecting small airway resistance. This study seeks to evaluate the usefulness of R5-R20, maximal mid-expiratory flow (MMEF), and forced expiratory volume in 3 s/forced vital capacity ratio (FEV3/FVC), in the assessment of small airway obstruction in chronic obstructive pulmonary disease (COPD). ⋯ We conclude that the R5-R20 difference is superior to spirometry in the assessment of small bronchi obstruction. A high sensitivity of R5-R20 in reflecting the MMEF makes the IOS method particularly useful for detection of mild lung injury, while a high specificity of the spirometric FEV3/FVC ratio makes it useful to exclude obstruction of small airways. Both methods are thus complimentary.
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Cardiac rehabilitation is a comprehensive and multidisciplinary program, and exercise training is extremely crucial in the whole program. In the past decades, many researches have shown the beneficial effects of exercise for cardiovascular disease (CVD) is indisputable Nevertheless, only a well-designed exercise prescription may achieve the ideal benefits. In this chapter, we will have a discussion of what is exercise prescription and how to establish a scientific and appropriate exercise prescription for CVD patients depending on the current scientific evidence and recommendations.