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Objective: Adrenal vein sampling (AVS) and computed tomography (CT) often show confusingly discordant lateralisation results in primary aldosteronism (PA). We tested a biochemical algorithm using AVS data to detect cortisol cosecretion as a potential explanation for discordant cases. Design: Retrospective analysis from a large PA + AVS database. Patients: All patients with PA and AVS, 2005–2020. Measurements: An algorithm using biochemical data from paired AVS + CT images was devised from physiological first principles and informed by data from unilateral, AVS–CT concordant patients. The algorithm involved calculations based upon the expectation that low cortisol levels exist in adrenal vein effluent opposite an aldosterone‐and‐cortisol‐producing adrenal mass and may reverse lateralisation due to inflated aldosterone/cortisol ratios. Main Outcomes: The algorithm was applied to cases with discordant CT–AVS lateralisation to determine whether this might be a common or explanatory finding. Clinical and biochemical characteristics of identified cases were collected via chart review and compared to CT–AVS concordant cases to detect evidence of biological plausibility for cortisol cosecretion. Results: From a total of 588 AVS cases, 141 AVS + CT pairs were clear unilateral PA cases, used to develop the three‐step algorithm for AVS interpretation. Applied to 88 AVS + CT discordant pairs, the algorithm suggested possible cortisol cosecretion in 40%. Case review showed that the proposed cortisol cosecretors, as identified by the algorithm, had low/suppressed adrenocorticotropic hormone levels, larger average nodule size and lower plasma aldosterone. Conclusions: Pending external validation and outcome verification by surgery and tissue immunohistochemistry, cortisol cosecretion from aldosteronomas may be a common explanation for discordant CT–AVS results in PA. [ABSTRACT FROM AUTHOR]

Abstract Background Tuberculosis remains a major world-wide health threat which demands the discovery and characterisation of new drug targets in order to develop future antimycobacterials. The regeneration of methionine consumed during polyamine biosynthesis is an important pathway present in many microorganisms. The final step of this pathway, the conversion of ketomethiobutyrate to methionine, can be performed by aspartate, tyrosine, or branched-chain amino acid aminotransferases depending on the particular species examined. Results The gene encoding for branched-chain amino acid aminotransferase in Mycobacterium tuberculosis H37Rv has been cloned, expressed, and characterised. The enzyme was found to be a member of the aminotransferase IIIa subfamily, and closely related to the corresponding aminotransferase in Bacillus subtilis, but not to that found in B. anthracis or B. cereus. The amino donor preference for the formation of methionine from ketomethiobutyrate was for isoleucine, leucine, valine, glutamate, and phenylalanine. The enzyme catalysed branched-chain amino acid and ketomethiobutyrate transamination with a Km of 1.77 – 7.44 mM and a Vmax of 2.17 – 5.70 μmol/min/mg protein, and transamination of ketoglutarate with a Km of 5.79 – 6.95 mM and a Vmax of 11.82 – 14.35 μmol/min/mg protein. Aminooxy compounds were examined as potential enzyme inhibitors, with O-benzylhydroxylamine, O-t-butylhydroxylamine, carboxymethoxylamine, and O-allylhydroxylamine yielding mixed-type inhibition with Ki values of 8.20 – 21.61 μM. These same compounds were examined as antimycobacterial agents against M. tuberculosis and a lower biohazard M. marinum model system, and were found to completely prevent cell growth. O-Allylhydroxylamine was the most effective growth inhibitor with an MIC of 78 μM against M. marinum and one of 156 ��M against M. tuberculosis. Conclusion Methionine formation from ketomethiobutyrate is catalysed by a branched-chain amino acid aminotransferase in M. tuberculosis. This enzyme can be inhibited by selected aminooxy compounds, which also have effectiveness in preventing cell growth in culture. These compounds represent a starting point for the synthesis of branched-chain aminotransferase inhibitors with higher activity and lower toxicity.

The purpose of this review is to identify, summarize, and critically appraise studies on dietary salt and health outcomes that were published from April 2017 to March 2018. The search strategy was adapted from a previous systematic review on dietary salt and health. Identified studies were screened based on a priori defined criteria to identify publications eligible for detailed critical appraisals. Overall, 6747 citations were identified by the search strategy, and 42 health outcome studies were identified. Three of the 42 studies met the criteria for methodological quality and health outcomes and underwent detailed critical appraisals and commentary. In addition, a systematic review and meta-analysis was critically appraised, although it did not strictly meet our methodological criteria. All four of the studies critically appraised found that sodium reduction improved blood pressure, especially in individuals with hypertension. In addition, sodium reduction reduced albuminuria in patients with stage 1-3 chronic kidney disease. Examination of the time course of blood pressure responses to sodium reduction revealed lowering sodium in the context of an average American diet may not produce maximal blood pressure reductions within a 4-week intervention period. This review provides further evidence of the benefit of sodium reduction for blood pressure lowering and gives insights into the subgroups of the population that may derive the greatest benefit from sodium reduction and the time course required to see benefit. Only three high-quality studies were identified during this 12-month review period, highlighting the critical need for more well-conducted rigorous studies in this area. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis remains a major world-wide health threat which demands the discovery and characterisation of new drug targets in order to develop future antimycobacterials. The regeneration of methionine consumed during polyamine biosynthesis is an important pathway present in many microorganisms. The final step of this pathway, the conversion of ketomethiobutyrate to methionine, can be performed by aspartate, tyrosine, or branched-chain amino acid aminotransferases depending on the particular species examined. Results: The gene encoding for branched-chain amino acid aminotransferase in Mycobacterium tuberculosis H37Rv has been cloned, expressed, and characterised. The enzyme was found to be a member of the aminotransferase IIIa subfamily, and closely related to the corresponding aminotransferase in Bacillus subtilis, but not to that found in B. anthracis or B. cereus. The amino donor preference for the formation of methionine from ketomethiobutyrate was for isoleucine, leucine, valine, glutamate, and phenylalanine. The enzyme catalysed branched-chain amino acid and ketomethiobutyrate transamination with a Km of 1.77 - 7.44 mM and a Vmax of 2.17 - 5.70 µmol/ min/mg protein, and transamination of ketoglutarate with a Km of 5.79 - 6.95 mM and a Vmax of 11.82 - 14.35 µmol/min/mg protein. Aminooxy compounds were examined as potential enzyme inhibitors, with O-benzylhydroxylamine, O-t-butylhydroxylamine, carboxymethoxylamine, and Oallylhydroxylamine yielding mixed-type inhibition with Ki values of 8.20 - 21.61 µM. These same compounds were examined as antimycobacterial agents against M. tuberculosis and a lower biohazard M. marinum model system, and were found to completely prevent cell growth. OAllylhydroxylamine was the most effective growth inhibitor with an MIC of 78 µM against M. marinum and one of 156 µM against M. tuberculosis. Conclusion: Methionine formation from ketomethiobutyrate is catalysed by a branched-chain amino acid aminotransferase in M. tuberculosis. This enzyme can be inhibited by selected aminooxy compounds, which also have effectiveness in preventing cell growth in culture. These compounds represent a starting point for the synthesis of branched-chain aminotransferase inhibitors with higher activity and lower toxicity. [ABSTRACT FROM AUTHOR]

Plasmablastic lymphoma (PBL) is a variant of lymphoma originally described in the oral cavity of patients with advanced HIV. Our patient developed PBL despite well-controlled HIV and a CD4 count greater than 800 cells/µl. A drug interaction with an inhaled corticosteroid and ritonavir likely contributed to the development of this malignancy through increased immune suppression.