Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0016382 (flushing)
 6,387 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fumaric acid esters (FAEs) are increasingly used as a systemic treatment for psoriasis, but there are still uncertainties regarding their suitability. The objective of this systematic review was to assess the evidence for the efficacy and safety of FAEs in psoriasis treatment. A systematic literature search was performed in seven databases up to 17 August 2015. Inclusion criteria were studies that reported clinical effects of FAEs in patients with psoriasis without restrictions in study design, language or publication date. Methodological quality of randomized controlled trials (RCTs) and overall level of quality were assessed using the Cochrane risk of bias tool and the Grading of Recommendation, Assessment, Development and Evaluation approach, respectively. A total of 68 articles were included. There were seven RCTs (total 449 patients) that had an unclear risk of bias and were too clinically heterogeneous to allow a meta-analysis. Overall, mean Psoriasis Area and Severity Index decreased by 42-65% following 12-16 weeks of treatment. There were 37 observational studies (a total of 3457 patients) that supported the RCT findings, but most were uncontrolled with a high risk of bias. Commonly reported adverse events included gastrointestinal complaints and flushing, leading to treatment withdrawal in 6-40% of patients. Several case-reports described rare adverse events, such as renal Fanconi syndrome and progressive multifocal leukoencephalopathy. There was a lack of studies focusing on long-term use and comparisons with other treatments. This review concluded that there is low-quality evidence to recommend the use of oral FAEs to treat plaque psoriasis in adult patients. Studies focusing on long-term safety and comparison with systemic psoriasis treatments could lead to a better understanding of the role of FAEs as a treatment for psoriasis.
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PMID:Efficacy, effectiveness and safety of fumaric acid esters in the treatment of psoriasis: a systematic review of randomized and observational studies. 2691 24

Maintenance of the hematopoietic stem cell (HSC) compartment depends on the ability to metabolize exogenously and endogenously generated toxins, and to repair cellular damage caused by such toxins. Reactive aldehydes have been demonstrated to cause specific genotoxic injury, namely DNA interstrand cross-links. Aldehyde dehydrogenase 2 (ALDH2) is a member of a 19 isoenzyme ALDH family with different substrate specificities, subcellular localization, and patterns of expression. ALDH2 is localized in mitochondria and is essential for the metabolism of acetaldehyde, thereby placing it directly downstream of ethanol metabolism. Deficiency in ALDH2 expression and function are caused by a single nucleotide substitution and resulting amino acid change, called ALDH2*2. This genetic polymorphism affects 35-45% of East Asians (about ~560 million people), and causes the well-known Asian flushing syndrome, which results in disulfiram-like reactions after ethanol consumption. Recently, the ALDH2*2 genotype has been found to be associated with marrow failure, with both an increased risk of sporadic aplastic anemia and more rapid progression of Fanconi anemia. This review discusses the unexpected interrelationship between aldehydes, ALDH2 and hematopoietic stem cell biology, and in particular its relationship to Fanconi anemia.
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PMID:Aldehyde dehydrogenase 2 in aplastic anemia, Fanconi anemia and hematopoietic stem cells. 2765 66