Journal of internal medicine
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The idiopathic inflammatory myopathies are characterized by muscle weakness, skin disease and internal organ involvement. Autoimmunity is known to have a role in myositis pathogenesis, and myositis-specific autoantibodies, targeting important intracellular proteins, are regarded as key biomarkers aiding in the diagnosis of patients. ⋯ In this review, we will describe the main myositis-specific and myositis-associated autoantibodies and their frequencies and clinical associations across different ages and ethnic groups. We will also discuss preliminary studies investigating correlations between specific myositis autoantibody titres and clinical markers of disease course, collectively demonstrating the utility of myositis autoantibodies as both diagnostic and prognostic markers of disease.
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Review
Therapeutic effects of inorganic nitrate and nitrite in cardiovascular and metabolic diseases.
Nitric oxide (NO) is generated endogenously by NO synthases to regulate a number of physiological processes including cardiovascular and metabolic functions. A decrease in the production and bioavailability of NO is a hallmark of many major chronic diseases including hypertension, ischaemia-reperfusion injury, atherosclerosis and diabetes. This NO deficiency is mainly caused by dysfunctional NO synthases and increased scavenging of NO by the formation of reactive oxygen species. ⋯ Administration of nitrate or nitrite in animal models of cardiovascular disease shows promising results, and clinical trials are currently ongoing to investigate the therapeutic potential of nitrate and nitrite in hypertension, pulmonary hypertension, peripheral artery disease and myocardial infarction. In addition, the nutritional aspects of the nitrate-nitrite-NO pathway are interesting as diets suggested to protect against cardiovascular disease, such as the Mediterranean diet, are especially high in nitrate. Here, we discuss the potential therapeutic opportunities for nitrate and nitrite in prevention and treatment of cardiovascular and metabolic diseases.
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Evidence from cross-sectional studies has suggested a positive association between moderate alcohol consumption and health-related quality of life but prospective data remain scarce. ⋯ Amongst young and middle-aged women, moderate alcohol intake was associated with a small improvement in physical health-related quality of life 2 years later and vice versa. Moderate alcohol consumption was not associated with mental health-related quality of life in either direction.
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Genetic variation in the cluster on chromosome 15, encoding the nicotinic acetylcholine receptor subunits (CHRNA5-CHRNA3-CHRNB4), has shown strong associations with tobacco consumption and an additional risk increase in smoking-related diseases such as chronic obstructive pulmonary disease (COPD), peripheral artery disease and lung cancer. ⋯ Our data suggest that gene variance in the CHRNA5-CHRNA3-CHRNB4 cluster is associated with an increased risk of death, incidence of COPD and tobacco-related cancer in smokers. These findings indicate an individual susceptibility to tobacco use and its complications; this may be important when targeting and designing smoking cessation therapies.
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Review
Asthma phenotyping: a necessity for improved therapeutic precision and new targeted therapies.
Asthma is a common heterogeneous disease with a complex pathophysiology that carries a significant mortality rate and high morbidity. Current therapies based on inhaled corticosteroids and long-acting β-agonists remain effective in a large proportion of patients with asthma, but ~10% (considered to have 'severe asthma') do not respond to these treatments even at high doses or with the use of oral corticosteroids. Analytical clustering methods have revealed phenotypes that include dependence on high-dose corticosteroid treatment, severe airflow obstruction and recurrent exacerbations associated with an allergic background and late onset of disease. ⋯ Research efforts are now focusing on elucidating the phenotypes underlying the non-Th2-high (or Th2-low) group, which constitutes ~50% of severe asthma cases. There is an increasing need to use biomarkers to indicate the group of patients who will respond to a specifically targeted treatment. The use of improved tools to measure activity of disease, a better definition of severe asthma and the delineation of inflammatory pathways with omics analyses using computational tools, will lead to better-defined phenotypes for specific therapies.