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  • KU55933 br Experimental section br Results and discussion br


    Experimental section
    Results and discussion
    Conclusions We present a simple, sensitive and selective assay of ADA activity and its inhibitor using the enzyme catalyzed reaction and the different interaction intensity of dye-labeled AD aptamer, aptamer/AD complex with GO. The as-proposed method which only needs one dye labeled DNA compared with the previous reports is not only simple, cost-effective, but also provides a low detection limit of 0.0129U/mL for ADA activity analysis in aqueous solution, owing to the exceptionally high fluorescence quenching efficiency of GO, which is more than one order of magnitude lower than that of previous reports (0.2U/mL). Meanwhile, a high specificity is also obtained in this design. Furthermore, the sensitive assays of ADA in human serum and its inhibitor, make it a promising tool for the diagnosis of ADA-relevant diseases and drug development.
    Introduction The magnitude of tuberculosis (TB) pertains to be one of the most indispensable global health dilemma apparently. According to the World Health Organization (WHO) report, in 2015, there was an estimate of 10.4 million new cases of TB world-wide, in which, 1.4 million died from it. Translucently, TB meningitis (TBM) is the most severe form of TB and accounts for approximately 1% of the entire forms of TB and up to 20% of extra-pulmonary form of TB. Limpidly, the outcomes for TBM are severe; in addition, more than 30% of TBM patients die despite anti-TB chemotherapy.3, 4 Therefore, rapid TBM diagnosis and treatment is quite crucial to reduce mortality and morbidity rate and the neurologic defects. Nevertheless, TBM diagnosis is often ambiguous due to the non-specific clinical presentation and insensitive prognostic methods.5, 6, 7 Eloquently, Ziehl-Neelsen staining the cerebrospinal fluid (CSF), is a fast and reliable technique to be used; however, the sensitivity is quite poor (approximately 10–20%). Furthermore, culturing mycobacteria is a slow process for clinical decision-making since the procedure ought to be done in a specialized TB laboratories.8, 9 Nucleic KU55933 amplification techniques, have long promised to overcome the inadequacies of conventional methods, but, they have lacked sensitivity compared to clinical diagnosis. Recently WHO endorsed use of an automated rapid molecular assay GeneXpert® MTB/RIF for the detection of Mycobacterium tuberculosis. However, GeneXpert lacks the sensitivity and negative predictive value to confidently rule out TBM. As a matter of fact, adenosine deaminase (ADA) is an enzyme which is widely distributed in tissues and body fluid; consequently, it has been used in TBM diagnosis. Conspicuously, the amenity and measurement of TB by the mentioned enzyme is a simple phenomenon and has been applied extensively in the clinical practice for decades. Although, this technique is widely used in many countries, there is no KU55933 consensus regarding its usefulness and sensitivity for TBM diagnosis. Therefore, there is a high need to prove the accuracy and precision of this test to make clinicians believe in the usage of ADA test for patients who get diagnosed with TBM. To the best of our knowledge, this is the first precise meta-analysis regarding the diagnostic test accuracy of ADA in TBM with comprehensive analysis. Indeed, the aim of the present review was to assess the usefulness of ADA measurement for the diagnosis of TBM by gathering a systematic review and meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement.
    Material and methods
    Discussion Categorically, TBM is a progressive and severe disease, which could continue to be a substantial cause of high mortality and severe neurological morbidity. Thereby, early diagnosis is indispensable for prevention and treatment of TBM. Conventional methods for detection of TBM are time consuming and hindered. As a matter of fact, CSF levels for ADA have been transparently recommended to be useful for the detection of TBM. Previously, two meta-analysis studies published regarding the accuracy for ADA test for diagnosis of TBM. According to Tuon et al., solely 13 studies from 1982 to 2002 were included in the analysis precisely. Furthermore, the other meta-analysis which was conducted by Xu et al., only 10 studies were included from 1986 to 2006 for analysis. Apparently, the two mentioned reports were published in 2010 with different results advocating the accuracy of ADA test for diagnosis of TBM. Considering the current evidence, we attained the phenomenon of the present meta-analysis to emphasize the practical usage of ADA measurement for the diagnosis of TBM. Consequently, we retrieved the most recent published studies (from January 1, 2000, to January 31, 2016) with fulfilling quality (analyzed with RevMan5 software and QUADS2 checklist). The number of included publications and wide vary analysis provides robust evidence to support the accuracy of ADA for detection of TBM. For demonstration of the ADA test accuracy for diagnosis of TBM, the row data for 20 studies were extracted and analyzed in the present analysis.