Adv Exp Med Biol
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Mitochondria individually encapsulate their own genome, unlike other cellular organelles. Mitochondrial DNA (mtDNA) is a circular, double-stranded, 16,569-base paired DNA containing 37 genes: 13 proteins of the mitochondrial respiratory chain, two ribosomal RNAs (rRNAs; 12S and 16S), and 22 transfer RNAs (tRNAs). The mtDNA is more vulnerable to oxidative modifications compared to nuclear DNA because of its proximity to ROS-producing sites, limited presence of DNA damage repair systems, and continuous replication in the cell. mtDNA mutations can be inherited or sporadic. ⋯ In this chapter, we summarize our current understanding of mtDNA mutations and their role in cardiac involvement. In addition, epigenetic modifications of mtDNA are briefly discussed for future elucidation of their critical role in cardiac involvement. Finally, current strategies for dealing with mitochondrial mutations in cardiac disorders are briefly stated.
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Excessive dietary salt (sodium chloride) intake is associated with an increased risk for hypertension, which in turn is especially a major risk factor for stroke and other cardiovascular pathologies, but also kidney diseases. Besides, high salt intake or preference for salty food is discussed to be positive associated with stomach cancer, and according to recent studies probably also obesity risk. On the other hand a reduction of dietary salt intake leads to a considerable reduction in blood pressure, especially in hypertensive patients but to a lesser extent also in normotensives as several meta-analyses of interventional studies have shown. ⋯ Regarding dietary interventions for the reduction of blood pressure the Dietary Approaches to Stop Hypertension (DASH) diet can be recommended. In addition, body weight should be normalized in overweight and obese people (BMI less than 25 kg/m2), salt intake should not exceed 5 g/day according to WHO recommendations (<2 g sodium/day), no more than 1.5 g sodium/d in blacks, middle- and older-aged persons, and individuals with hypertension, diabetes, or chronic kidney disease, intake of potassium (~4.7 g/day) should be increased and alcohol consumption limited. In addition, regular physical activity (endurance, dynamic resistance, and isometric resistance training) is very important.
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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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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.