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1.
Am J Trop Med Hyg ; 98(1): 227-230, 2018 01.
Article in English | MEDLINE | ID: mdl-29141724

ABSTRACT

Prostatic involvement is common in men with melioidosis. Indeed, some clinicians recommend radiological screening of all male patients as an undrained prostatic abscess may result in relapse of this potentially fatal disease. However, sophisticated medical imaging is frequently unavailable in the remote and resource-poor locations where patients are managed. In this retrospective study from Queensland, Australia, 22/144 (15%) men with melioidosis had a radiologically confirmed prostatic abscess. The absence of urinary symptoms had a negative predictive value (NPV) (95% confidence interval [CI]) for prostatic abscess of 96% (90-99%), whereas a urinary leukocyte count of < 50 × 106/L had an NPV (95% CI) of 100% (94-100%). A simple clinical history and basic laboratory investigations appear to exclude significant prostatic involvement relatively reliably and might be used to identify patients in whom radiological evaluation of the prostate is unnecessary. This may be particularly helpful in locations where radiological support is limited.


Subject(s)
Abscess/diagnosis , Burkholderia pseudomallei , Melioidosis/diagnosis , Prostatic Diseases/diagnosis , Abscess/diagnostic imaging , Abscess/microbiology , Adult , Aged , Humans , Leukocyte Count , Male , Melioidosis/diagnostic imaging , Middle Aged , Prostate/diagnostic imaging , Prostate/microbiology , Prostatic Diseases/diagnostic imaging , Prostatic Diseases/microbiology , Radiography , Tomography, X-Ray Computed
2.
Br J Pharmacol ; 166(8): 2231-42, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22428706

ABSTRACT

BACKGROUND AND PURPOSE: So far, there is only limited information about the regulation of the endogenous synthesis of hydrogen sulfide (H(2) S), an important gaseous signalling molecule. This study was done to evaluate the redox-dependent signalling events that regulate the expression of the H(2) S synthesising enzyme cystathionine-γ-lyase (CSE) in rat mesangial cells. EXPERIMENTAL APPROACH: The effects of platelet-derived growth factor (PDGF)-BB and antioxidants on CSE expression and activity in cultured rat renal mesangial cells were assessed. Activity of nuclear factor erythroid-2-related factor-2 (Nrf2) was measured as the binding capacity to a radiolabelled consensus element by electrophoretic mobility shift assay (EMSA). Furthermore, CSE and Nrf2 expression was analysed in a rat model of anti-Thy-1-induced glomerulonephritis by immunohistochemistry. KEY RESULTS: Treatment of mesangial cells with PDGF-BB resulted in a marked time- and dose-dependent up-regulation of CSE mRNA and protein levels, as well as CSE activity accompanied with increased formation of reactive oxygen species. Remarkably, co-administration of antioxidants, such as N-acetylcysteine, ebselen or diphenylene iodonium chloride, drastically reduced PDGF-BB-induced CSE expression. PDGF-BB induced binding of Nrf2 to a corresponding consensus antioxidant element in a redox-dependent manner. Furthermore, PDGF-BB-induced CSE expression in mouse mesangial cells was completely abolished in Nrf2 knockout mice compared with wild-type mice. In a rat model of anti-Thy-1-induced proliferative glomerulonephritis, we observed a marked up-regulation of CSE protein paralleled by a stabilization of Nrf2 protein. CONCLUSIONS AND IMPLICATIONS: PDGF-BB regulated CSE via a redox-mediated activation of Nrf2. Such action would aid the resolution of glomerular inflammatory diseases. LINKED ARTICLE: This article is commented on by Gallyas, pp. 2228-2230 of this issue. To view this commentary visit http://dx.doi.org/10.1111/j.1476-5381.2012.01976.x.


Subject(s)
Cystathionine gamma-Lyase/metabolism , Gene Expression Regulation, Enzymologic/drug effects , Mesangial Cells/drug effects , Proto-Oncogene Proteins c-sis/pharmacology , Animals , Antioxidants/pharmacology , Becaplermin , Cells, Cultured , Cystathionine gamma-Lyase/genetics , Gene Expression Regulation, Enzymologic/physiology , Glomerulonephritis/chemically induced , Glomerulonephritis/metabolism , Isoantibodies/pharmacology , Macrophages , Mesangial Cells/enzymology , Mice , Mice, Knockout , NF-E2-Related Factor 2/genetics , NF-E2-Related Factor 2/metabolism , Oxidation-Reduction , Rats , Rats, Sprague-Dawley , Reactive Oxygen Species/metabolism , Spleen/cytology
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