Dataset Information

Levels of 25-hydroxy Vitamin D3 and Vitamin D Receptor Polymorphism in Severe Dengue Cases from New Delhi.

ABSTRACT: Dengue is the "phoenix" that never went to ashes. First identified in 1943, in Japan, dengue virus has worldwide distribution and is a grave public health concern in developing countries like India; Methods: A cross sectional study was conducted among adults suspected of having dengue fever and attending Lok Nayak Hospital, New Delhi. Restriction Fragment Length Polymorphism was completed for the detection of vitamin D receptor (VDR) gene polymorphism; Results: Serum 25-hydroxy vitamin D3 (vitamin D) levels were found to be 1.6 times elevated in severe dengue cases as compared to healthy controls. Vitamin D levels were significantly higher in secondary infections compared to primary infections as well as secondary severe dengue cases as compared to secondary non-severe cases (p value < 0.05). A significant association of the T allele (rs2228570) was seen in severe dengue cases, while, when comparing the A/A with A/C and C/C genotypes (rs7975232) among dengue cases and healthy controls, the odds ratio was estimated to be 1.24 (0.55-2.75, p > 0.05) and 0.28 (0.08-0.96, p < 0.05) respectively; Conclusions: The present study is an attempt at decoding the role of vitamin D in dengue disease pathogenesis and exploring the role of genetic polymorphism in dengue disease pathogenesis.

SUBMITTER: Chakravarti A

PROVIDER: S-EPMC7344752 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Levels of 25-hydroxy Vitamin D3 and Vitamin D Receptor Polymorphism in Severe Dengue Cases from New Delhi.

Chakravarti Anita A Bharara Tanisha T Kapoor Neeru N Ashraf Anzar A

Tropical medicine and infectious disease 20200503 2

<h4>Background</h4>Dengue is the "phoenix" that never went to ashes. First identified in 1943, in Japan, dengue virus has worldwide distribution and is a grave public health concern in developing countries like India; Methods: A cross sectional study was conducted among adults suspected of having dengue fever and attending Lok Nayak Hospital, New Delhi. Restriction Fragment Length Polymorphism was completed for the detection of vitamin D receptor (VDR) gene polymorphism; Results: Serum 25-hydrox ...[more]

PMID: 32375246

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Project description:BackgroundOxysterols are promising biomarkers of neurodegenerative diseases that are linked with cholesterol and vitamin D metabolism. There is an unmet need for methods capable of sensitive, and simultaneous quantitation of multiple oxysterols, vitamin D and cholesterol pathway biomarkers.MethodsA method for simultaneous determination of 5 major oxysterols, 25-hydroxy vitamin D3 and cholesterol in human plasma was developed. Total oxysterols were prepared by room temperature saponification followed by solid phase extraction from plasma spiked with deuterated internal standards. Oxysterols were resolved by reverse phase HPLC using a methanol/water/0.1% formic acid gradient. Oxysterols and 25-hydroxy vitamin D3 were detected with atmospheric pressure chemical ionization mass spectrometry in positive ion mode; in-series photodiode array detection at 204nm was used for cholesterol. Method validation studies were performed. Oxysterol levels in 220 plasma samples from healthy control subjects, multiple sclerosis and other neurological disorders patients were quantitated.ResultsOur method quantitated 5 oxysterols, cholesterol and 25-hydroxy vitamin D3 from 200 μL plasma in 35 minutes. Recoveries were >85% for all analytes and internal standards. The limits of detection were 3-10 ng/mL for oxysterols and 25-hydroxy vitamin D3 and 1 μg/mL for simultaneous detection of cholesterol. Analytical imprecision was <10 %CV for 24(S)-, 25-, 27-, 7α-hydroxycholesterol (HC) and cholesterol and ≤15 % for 7-keto-cholesterol. Multiple Sclerosis and other neurological disorder patients had lower 27-hydroxycholesterol levels compared to controls whereas 7α-hydroxycholesterol was lower specifically in Multiple Sclerosis.ConclusionThe method is suitable for measuring plasma oxysterols levels in human health and disease. Analysis of human plasma indicates that the oxysterol, bile acid precursors 7α-hydroxycholesterol and 27-hydroxycholesterol are lower in Multiple Sclerosis and may serve as potential biomarkers of disease.

Project description:Adjunctive vitamin D treatment for pulmonary tuberculosis enhances resolution of inflammation but has modest effects on bacterial clearance. Sodium 4-phenylbutyrate (PBA) is in clinical use for a range of conditions and has been shown to synergise with vitamin D metabolites to upregulate cathelicidin antimicrobial peptide (CAMP) expression. We investigated whether clinically attainable plasma concentrations of PBA (0.4-4 mM) directly affect Mycobacterium tuberculosis (Mtb) growth and human macrophage and PBMC response to infection. We also tested the ability of PBA to enhance the immunomodulatory actions of the vitamin D metabolite 25(OH)D3 during infection and synergistically inhibit intracellular Mtb growth. PBA inhibited Mtb growth in broth with an MIC99 of 1 mM, which was reduced to 0.25 mM by lowering pH. During human macrophage infection, PBA treatment restricted Mtb uptake, phagocytic receptor expression and intracellular growth in a dose-dependent manner. PBA independently regulated CCL chemokine secretion and induced expression of the antimicrobial LTF (lactoferrin), the anti-inflammatory PROC (protein C) and multiple genes within the NLRP3 inflammasome pathway. PBA co-treatment with 25(OH)D3 synergistically modulated expression of numerous vitamin D-response genes, including CAMP, CYP24A1, CXCL10 and IL-37. This synergistic effect was dependent on MAPK signalling, while the effect of PBA on LTF, PROC and NLRP3 was MAPK-independent. During PBA and 25(OH)D3 co-treatment of human macrophages, in the absence of exogenous proteinase 3 (PR3) to activate cathelicidin, Mtb growth restriction was dominated by the effect of PBA, while the addition of PR3 enhanced growth restriction by 25(OH)D3 and PBA co-treatment. This suggests that PBA augments vitamin D-mediated cathelicidin-dependent Mtb growth restriction by human macrophages and independently induces antimicrobial and anti-inflammatory action. Therefore through both host-directed and bacterial-directed mechanisms PBA and vitamin D may prove an effective combinatorial adjunct therapy for tuberculosis to both resolve immunopathology and enhance bacterial clearance.

Dataset Information

Levels of 25-hydroxy Vitamin D3 and Vitamin D Receptor Polymorphism in Severe Dengue Cases from New Delhi.

Publications

Levels of 25-hydroxy Vitamin D3 and Vitamin D Receptor Polymorphism in Severe Dengue Cases from New Delhi.

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