A quaternary anti-cholinesterase probe for determining the integrity of the blood--brain barrier

7-(Methylethoxyphosphinyloxy)-1-methyl quinolinium iodide (MEPQ), a new quaternary anti-cholinesterase (anti-ChE) compound was prepared and evaluated as a potential probe for assessing changes in the blood-brain barrier (B-BB) permeability. MEPQ was found to be 170 times more potent in its cholinesterase inhibitory activity than phospholine iodide, a previously reported anti-ChE probe in B-BB research. In rats and mice with impaired B-BB induced by osmotic opening, MEPQ readily penetrated through the damaged site as demonstrated by considerable reduction of ChE activity. In controls, brain ChE activity remained unaffected. It is suggested that MEPQ is a useful probe for both qualitative (histological staining) and quantitative (brain homogenated) assessment of permeability changes in the B-BB.     

Media matters! Alterations in the loading and release of Histoplasma capsulatum extracellular vesicles in response to different nutritional milieus

Histoplasma capsulatum is a dimorphic fungus that most frequently causes pneumonia, but can also disseminate and proliferate in diverse tissues. Histoplasma capsulatum has a complex secretion system that mediates the release of macromolecule‐degrading enzymes and virulence factors. The formation and release of extracellular vesicles (EVs) are an important mechanism for non‐conventional secretion in both ascomycetes and basidiomycetes. Histoplasma capsulatum EVs contain diverse proteins associated with virulence and are immunologically active. Despite the growing knowledge of EVs from H. capsulatum and other pathogenic fungi, the extent that changes in the environment impact the sorting of organic molecules in EVs has not been investigated. In this study, we cultivated H. capsulatum with distinct culture media to investigate the potential plasticity in EV loading in response to differences in nutrition. Our findings reveal that nutrition plays an important role in EV loading and formation, which may translate into differences in biological activities of these fungi in various fluids and tissues.