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Vitamin D and Infectious Diseases: Simple Bystander or Contributing Factor?

ABSTRACT: Vitamin D (VD) is a fat-soluble steroid essential for life in higher animals. It is technically a pro-hormone present in few food types and produced endogenously in the skin by a photochemical reaction. In recent decades, several studies have suggested that VD contributes to diverse processes extending far beyond mineral homeostasis. The machinery for VD production and its receptor have been reported in multiple tissues, where they have a pivotal role in modulating the immune system. Similarly, vitamin D deficiency (VDD) has been in the spotlight as a major global public healthcare burden. VDD is highly prevalent throughout different regions of the world, including tropical and subtropical countries. Moreover, VDD may affect host immunity leading to an increased incidence and severity of several infectious diseases. In this review, we discuss new insights on VD physiology as well as the relationship between VD status and various infectious diseases such as tuberculosis, respiratory tract infections, human immunodeficiency virus, fungal infections and sepsis. Finally, we critically review the latest evidence on VD monitoring and supplementation in the setting of infectious diseases.

SUBMITTER: Gois PHF

PROVIDER: S-EPMC5537771 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Vitamin D and Infectious Diseases: Simple Bystander or Contributing Factor?

Gois Pedro Henrique França PHF Ferreira Daniela D Olenski Simon S Seguro Antonio Carlos AC

Nutrients 20170624 7

Vitamin D (VD) is a fat-soluble steroid essential for life in higher animals. It is technically a pro-hormone present in few food types and produced endogenously in the skin by a photochemical reaction. In recent decades, several studies have suggested that VD contributes to diverse processes extending far beyond mineral homeostasis. The machinery for VD production and its receptor have been reported in multiple tissues, where they have a pivotal role in modulating the immune system. Similarly, ...[more]

PMID: 28672783

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Project description:The Immucillins are chemically stable analogues that mimic the ribocation and leaving-group features of N-ribosyltransferase transition states. Infectious disease agents often rely on ribosyltransferase chemistry in pathways involving precursor synthesis for nucleic acids, salvage of nucleic acid precursors, or synthetic pathways with nucleoside intermediates. Here, we review three infectious agents and the use of the Immucillins to taget enzymes essential to the parasites. First, DADMe-Immucillin-G is a purine nucleoside phosphorylase (PNP) inhibitor that blocks purine salvage and shows clinical potential for treatment for the malaria parasite Plasmodium falciparum, a purine auxotroph requiring hypoxanthine for purine nucleotide synthesis. Inhibition of the PNPs in the host and in parasite cells leads to apurinic starvation and death. Second, Helicobacter pylori, a causative agent of human ulcers, synthesizes menaquinone, an essential electron transfer agent, in a pathway requiring aminofutalosine nucleoside hydrolysis. Inhibitors of the H. pylori methylthioadenosine nucleosidase (MTAN) are powerful antibiotics for this organism. Synthesis of menaquinone by the aminofutalosine pathway does not occur in most bacteria populating the human gut microbiome. Thus, MTAN inhibitors provide high-specificity antibiotics for H. pylori and are not expected to disrupt the normal gut bacterial flora. Third, Immucillin-A was designed as a transition state analogue of the atypical PNP from Trichomonas vaginalis. In antiviral screens, Immucillin-A was shown to act as a prodrug. It is active against filoviruses and flaviviruses. In virus-infected cells, Immucillin-A is converted to the triphosphate, is incorporated into the viral transcript, and functions as an atypical chain-terminator for RNA-dependent RNA polymerases. Immucillin-A has entered clinical trials for use as an antiviral. We also summarize other Immucillins that have been characterized in successful clinical trials for T-cell lymphoma and gout. The human trials support the potential development of the Immucillins in infectious diseases.

Project description:Abstract Background Gender inequities in academic advancement persist in many specialties, including Infectious Diseases (ID). Prior studies of advancement disparities have been predominantly quantitative, utilizing large physician databases or surveys. We used qualitative methods to explore ID physicians’ experiences and beliefs about causes and ways to mitigate gender inequities in advancement. Methods We conducted semistructured focus group discussions with academic ID physicians in the United States at IDWeek 2019 to explore perceived barriers and facilitators to academic advancement. Participants were assigned to focus groups based on their academic rank and gender. We analyzed focus group transcripts using content analysis to summarize emergent themes. Results We convened 3 women-only focus groups (1 for instructors/assistant professors, 1 for associate professors, and 1 for full professors) and 1 men-only focus group of full professors (total N = 50). Our analyses identified several major themes on barriers to equitable academic advancement, including (1) interpersonal and institutional gender bias, (2) difficulty balancing the demands of family life with work life, and (3) gender differences in negotiation strategies. Conclusions Barriers to gender equity in academic advancement are myriad and enduring and span the professional and personal lives of ID physicians. In addition to swift enactment of policy changes directed at critical issues such as ending workplace harassment and ensuring adequate parental leaves for birth and nonbirth parents, leaders in academic medicine must shine a bright light on biases within the system at large and within themselves to correct these disparities with the urgency required. Quantitative data repeatedly show a gender gap in academic advancement in ID. This qualitative exploration of barriers to advancement identifies key themes perpetuating disparities, including institutional and interpersonal gender bias, difficulty balancing work and family, and gender differences in negotiation. Graphical Abstract Graphical Abstract

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Vitamin D and Infectious Diseases: Simple Bystander or Contributing Factor?

Publications

Vitamin D and Infectious Diseases: Simple Bystander or Contributing Factor?

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