Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.5.4.4 (adenosine deaminase)
 5,136 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ticagrelor, a recently approved platelet antagonist indicated for the reduction of thrombotic cardiovascular events in patients with acute coronary syndrome (ACS), has been reported to cause dyspnea in more than 13% of patients. Dyspnea is not a clinically relevant adverse event with other medications indicated for ACS. One suggested mechanism of ticagrelor-induced dyspnea involves an increase in systemic adenosine concentrations through adenosine deaminase inhibition. Dyspnea, a subjective finding resulting from physiologic and sensory mechanisms, may be a consequence of increased systemic adenosine concentrations, leading to amplified and prolonged receptor activity. Current literature suggests, however, that pulmonary status is not compromised, with no reduction of efficacy seen in patients with ticagrelor-induced dyspnea, thus allowing clinicians to continue therapy without reservation. Still, patients with a history of asthma and chronic obstructive pulmonary disease may be more susceptible to ticagrelor-induced dyspnea, potentially leading to nonadherence and exacerbations of morbidity. Therefore, it is paramount that health care providers continually monitor these patients with the aims of maintaining medication therapy adherence and providing relevant options if dyspnea becomes intolerable.
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PMID:Potential role of endogenous adenosine in ticagrelor-induced dyspnea. 2371 33

On a global scale, tuberculosis (TB) remains one of the most frequent causes of pleural effusions. Our understanding of the pathogenesis of the disease has evolved and what was once thought to be an effusion as a result of a pure delayed hypersensitivity reaction is now believed to be the consequence of direct infection of the pleural space with a cascade of events including an immunological response. Pulmonary involvement is more common than previously believed and induced sputum, which is grossly underutilised, can be diagnostic in approximately 50%. The gold standard for the diagnosis of tuberculous pleuritis remains the detection of Mycobacterium tuberculosis in pleural fluid, or pleural biopsy specimens, either by microscopy and/or culture, or the histological demonstration of caseating granulomas in the pleura along with acid fast bacilli (AFB). In high burden settings, however, the diagnosis is frequently inferred in patients who present with a lymphocytic predominant exudate and a high adenosine deaminase (ADA) level, which is a valuable adjunct in the diagnostic evaluation. ADA is generally readily accessible, and together with lymphocyte predominance justifies treatment initiation in patients with a high pre-test probability. Still, false-negative and false-positive results remain an issue. When adding closed pleural biopsy to ADA and lymphocyte count, diagnostic accuracy approaches that of thoracoscopy. The role of other biomarkers is less well described. Early pleural drainage may have a role in selected cases, but more research is required to validate its use and to define the subpopulation that may benefit from such interventions.
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PMID:Tuberculous pleural effusions: advances and controversies. 2615 Sep 11

Transfer RNAs acquire a variety of naturally occurring chemical modifications during their maturation; these fine-tune their structure and decoding properties in a manner critical for protein synthesis. We recently reported that in the eukaryotic parasite, Trypanosoma brucei, a methylation and deamination event are unexpectedly interconnected, whereby the tRNA adenosine deaminase (TbADAT2/3) and the 3-methylcytosine methyltransferase (TbTrm140) strictly rely on each other for activity, leading to formation of m3C and m3U at position 32 in several tRNAs. Still however, it is not clear why these two enzymes, which work independently in other systems, are strictly codependent in T. brucei Here, we show that these enzymes exhibit binding synergism, or a mutual increase in binding affinity, that is more than the sum of the parts, when added together in a reaction. Although these enzymes interact directly with each other, tRNA binding assays using enzyme variants mutated in critical binding and catalytic sites indicate that the observed binding synergy stems from contributions from tRNA-binding domains distal to their active sites. These results provide a rationale for the known interactions of these proteins, while also speaking to the modulation of substrate specificity between seemingly unrelated enzymes. This information should be of value in furthering our understanding of how tRNA modification enzymes act together to regulate gene expression at the post-transcriptional level and provide a basis for the interdependence of such activities.
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PMID:Binding synergy as an essential step for tRNA editing and modification enzyme codependence in Trypanosoma brucei. 2904 5