Инкреторная функция слюнных желёз и изменения слизистой полости рта при некоторых эндокринных заболеваниях

The review describes the up-to-date data of the native and foreign literature concerning the incretory function of salivary glands. The authors lay stress on the necessity: of taking into account the oral mucosa alterations under the most frequent endocrine diseases, despite of nonspecificity of observable alteration, because sometimes they are manifestation and frequently unique symptoms of the pathological process for a long time. The mentioned alterations of oral mucosa are very significant in diagnosis of endocrine diseases and should be taken into account for their treatment.В огляді наведені сучасні дані вітчизняної та зарубіжної літератури стосовно інкреторнгої функції слинних залоз, яка полягає у синтезі в складі слини ряду біологічно активних речовин, що мають системний вплив на організм. Підкреслена необхідність взяти до уваги зміни ротової порожнини при ендокринних захворюваннях, які.найчастіше зустрічаються, незважаючи на неспецифічність змін, що спостерігаються, тому що вони іноді є маніфестуючими і часто єдиними ознаками того чи іншого патологічного процесу упродовж тривалого часу. Зазначені зміни слизової порожнини рота допомагають при діагностиці ендокринних захворюваннях та повинні враховуватися при корекції останніх.Приведены современные данные отечественной и зарубежной литературы относительно инкреторной. функции слюнных желёз, состоящей в синтезе в составе слюны ряда биологически активных веществ, обладающих системным действием на организм. Подчёркивается необходимость принятия во внимания изменений слизистой полости рта при наиболее часто встречающихся эндокринных заболеваниях, несмотря на неспецифичность наблюдаемых изменений, так как они иногда являются манифестирующими и часто единственными признаками того или иного патологического процесса в точение длительного времени. Указанные изменения слизистой полости рта важны при диагностике эндокринных заболеваний и должны учитываться при их коррекции

Farnesol-Induced Apoptosis in Candida albicans Is Mediated by Cdr1-p Extrusion and Depletion of Intracellular Glutathione

Farnesol is a key derivative in the sterol biosynthesis pathway in eukaryotic cells previously identified as a quorum sensing molecule in the human fungal pathogen Candida albicans. Recently, we demonstrated that above threshold concentrations, farnesol is capable of triggering apoptosis in C. albicans. However, the exact mechanism of farnesol cytotoxicity is not fully elucidated. Lipophilic compounds such as farnesol are known to conjugate with glutathione, an antioxidant crucial for cellular detoxification against damaging compounds. Glutathione conjugates act as substrates for ATP-dependent ABC transporters and are extruded from the cell. To that end, this current study was undertaken to validate the hypothesis that farnesol conjugation with intracellular glutathione coupled with Cdr1p-mediated extrusion of glutathione conjugates, results in total glutathione depletion, oxidative stress and ultimately fungal cell death. The combined findings demonstrated a significant decrease in intracellular glutathione levels concomitant with up-regulation of CDR1 and decreased cell viability. However, addition of exogenous reduced glutathione maintained intracellular glutathione levels and enhanced viability. In contrast, farnesol toxicity was decreased in a mutant lacking CDR1, whereas it was increased in a CDR1-overexpressing strain. Further, gene expression studies demonstrated significant up-regulation of the SOD genes, primary enzymes responsible for defense against oxidative stress, with no changes in expression in CDR1. This is the first study describing the involvement of Cdr1p-mediated glutathione efflux as a mechanism preceding the farnesol-induced apoptotic process in C. albicans. Understanding of the mechanisms underlying farnesol-cytotoxicity in C. albicans may lead to the development of this redox-cycling agent as an alternative antifungal agent

A Phenotypic Profile of the Candida albicans Regulatory Network

Candida albicans is a normal resident of the gastrointestinal tract and also the most prevalent fungal pathogen of humans. It last shared a common ancestor with the model yeast Saccharomyces cerevisiae over 300 million years ago. We describe a collection of 143 genetically matched strains of C. albicans, each of which has been deleted for a specific transcriptional regulator. This collection represents a large fraction of the non-essential transcription circuitry. A phenotypic profile for each mutant was developed using a screen of 55 growth conditions. The results identify the biological roles of many individual transcriptional regulators; for many, this work represents the first description of their functions. For example, a quarter of the strains showed altered colony formation, a phenotype reflecting transitions among yeast, pseudohyphal, and hyphal cell forms. These transitions, which have been closely linked to pathogenesis, have been extensively studied, yet our work nearly doubles the number of transcriptional regulators known to influence them. As a second example, nearly a quarter of the knockout strains affected sensitivity to commonly used antifungal drugs; although a few transcriptional regulators have previously been implicated in susceptibility to these drugs, our work indicates many additional mechanisms of sensitivity and resistance. Finally, our results inform how transcriptional networks evolve. Comparison with the existing S. cerevisiae data (supplemented by additional S. cerevisiae experiments reported here) allows the first systematic analysis of phenotypic conservation by orthologous transcriptional regulators over a large evolutionary distance. We find that, despite the many specific wiring changes documented between these species, the general phenotypes of orthologous transcriptional regulator knockouts are largely conserved. These observations support the idea that many wiring changes affect the detailed architecture of the circuit, but not its overall output