Adv Exp Med Biol
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Hypertension remains the most important risk factor for cardiovascular disease. If antihypertensive drugs choice is well guided today, blood pressure (BP) target still a subject of controversies. Residual risk is matter of debate and the lower- the better dogma is come back again regarding to data reported from recent trials. ⋯ In diabetic patients, SBP target should be less than 140 mmHg according to ACCORD trial. However, for patients with protein-creatinine ratio >500 mg/g (albumin-creatinine ratio > 300 mg/g), with or without diabetes, lower SBP target should be proposed for renal protection aiming SBP < 130 mmHg as recommended by KDIGO guidelines. In patients at low or intermediate risk, without cardiovascular disease, SBP should start to be treated when SBP is above 140 mmHg, and when treated, target BP should be less than 140 mmHg as reported by HOPE-3 trial.
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Huntington's disease (HD) is a genetic, fatal autosomal dominant neurodegenerative disorder typically occurring in midlife with symptoms ranging from chorea, to dementia, to personality disturbances (Philos Trans R Soc Lond Ser B Biol Sci 354:957-961, 1999). HD is inherited in a dominant fashion, and the underlying mutation in all cases is a CAG trinucleotide repeat expansion within exon 1 of the HD gene (Cell 72:971-983, 1993). ⋯ The rate-limiting mechanism(s) of neurodegeneration in HD still remains elusive: many different processes are commonly disrupted in HD cell lines and animal models, as well as in HD patient cells (Eur J Neurosci 27:2803-2820, 2008); however, epigenetic-chromatin deregulation, as determined by the analysis of DNA methylation, histone modifications, and noncoding RNAs, has now become a prevailing feature. Thus, the overarching goal of this chapter is to discuss the current status of the literature, reviewing how an aberrant epigenetic landscape can contribute to altered gene expression and neuronal dysfunction in HD.
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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.