Potential Role of Vitamins A, B, C, D and E in TB Treatment and Prevention: A Narrative Review

(1) Background: Tuberculosis (TB) is one of the world’s top infectious killers, in fact every year 10 million people fall ill with TB and 1.5 million people die from TB. Vitamins have an important role in vital functions, due to their anti-oxidant, pro-oxidant, anti-inflammatory effects and to metabolic functions. The aim of this review is to discuss and summarize the evidence and still open questions regarding vitamin supplementation as a prophylactic measure in those who are at high risk of Mycobacterium tuberculosis (MTB) infection and active TB; (2) Methods: We conducted a search on PubMed, Scopus, Google Scholar, EMBASE, Cochrane Library and WHO websites starting from March 1950 to September 2021, in order to identify articles discussing the role of Vitamins A, B, C, D and E and Tuberculosis; (3) Results: Supplementation with multiple micronutrients (including zinc) rather than vitamin A alone may be more beneficial in TB. The WHO recommend Pyridoxine (vitamin B6) when high-dose isoniazid is administered. High concentrations of vitamin C sterilize drug-susceptible, MDR and extensively drug-resistant MTB cultures and prevent the emergence of drug persisters; Vitamin D suppresses the replication of mycobacterium in vitro while VE showed a promising role in TB management as a result of its connection with oxidative balance; (4) Conclusions: Our review suggests and encourages the use of vitamins in TB patients. In fact, their use may improve outcomes by helping both nutritionally and by interacting directly and/or indirectly with MTB. Several and more comprehensive trials are needed to reinforce these suggestions.

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Dose dependence of efficacy but not of safety in sublingual immunotherapy

Monaldi Archives for Chest Disease ◽

10.4081/monaldi.2006.584 ◽

2016 ◽

Vol 65 (1) ◽

Author(s):

F. Frati ◽

C. Incorvaia ◽

F. Marcucci ◽

L. Sensi ◽

G. Di Cara ◽

...

Keyword(s):

Sublingual Immunotherapy ◽

Clinical Symptoms ◽

Meta Analysis ◽

Dose Dependence ◽

Subcutaneous Immunotherapy ◽

High Dose ◽

Systemic Reactions ◽

Significant Difference

Sublingual immunotherapy (SLIT) currently represents, as indicated by meta-analysis of its efficacy and safety, a valid option to the generally used traditional subcutaneous immunotherapy (SCIT) for treating respiratory allergy. Regarding efficacy, recent studies demonstrated that, similar to what has already been observed in SCIT as well as in experimental and clinical studies about the magnitudo of allergen exposure, the effectiveness on both clinical symptoms and immunologic changes depends on the amount of allergen administered during treatment. In addition, in vitro studies addressed with the role of dendritic cells, currently considered to be of pivotal importance in orienting toward tolerance the immune response to allergens, showed that the internalisation of allergen molecules, which is followed by tolerogenic presentation to T cells, depends on the amount of allergen. However, such dose dependence is not apparent concerning the safety. In fact, the comparison of studies respectively conducted with high and low allergen doses did not show differences in the rate of systemic reactions, which in any case never had the presentation of anaphylaxis, and instead a significant difference in the rate of local reactions, following the oral and gastrointestinal contact with the allergen extract, in favour of high dose studies.

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Colchicine-binding protein of the liver. Its characterization and relation to microtubules.

The Journal of Cell Biology ◽

10.1083/jcb.66.3.609 ◽

1975 ◽

Vol 66 (3) ◽

pp. 609-620 ◽

Cited By ~ 36

Author(s):

C Patzelt ◽

A Singh ◽

Y L Marchand ◽

L Orci ◽

B Jeanrenaud

Keyword(s):

High Speed ◽

Specific Binding ◽

Electrophoretic Analysis ◽

Binding Activity ◽

Low Concentrations ◽

Electrophoretic Behavior ◽

High Affinity Binding Site ◽

High Concentrations

Colchicine-binding activity of mouse liver high-speed supernate has been investigated. It has been found to be time and temperature dependent. Two binding activities with different affinities for colchicine seem to be present in this high-speed supernate, of which only the high-affinity binding site (half maximal binding at 5 x 10(-6) M colchicine) can be attributed to microtubular protein by comparison with purified tubulin. Vinblastine interacted with this binding activity by precipitating it when used at high concentrations (2 x 10(-3) M), and by stabilizing it at low concentrations (10(-5) M). Lumicolchicine was found not to compete with colchicine. The colchicine-binding activity was purified from liver and compared with that of microtubular protein from brain. The specific binding activity of the resulting preparation, its electrophoretic behavior, and the electron microscope appearance of the paracrystals obtained upon its precipitation with vinblastine permitted its identification as microtubular protein (tubulin). Electrophoretic analysis of the proteins from liver supernate that were precipitated by vinblastine indicated that this drug was not specific for liver tubulin. Preincubation of liver supernate with 5 mM EGTA resulted in a time-dependent decrease of colchicine-binding activity, which was partly reversed by the addition of Ca++. However, an in vitro formation of microtubules upon lowering the Ca++ concentration could not be detected. Finally, a method was developed enabling that portion of microtubular protein which was present as free tubulin to be measured and to be compared with the total amount of this protein in the tissue. This procedure permitted demonstration of the fact that, under normal conditions, only about 40% of the tubulin of the liver was assemled as microtubules. It is suggested that, in the liver, rapid polymerization and depolymerization of microtubules occur and may be an important facet of the functional role of the microtubular system.

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2'-Deoxycytidine protects normal human bone marrow progenitor cells in vitro against the cytotoxicity of 3'-azido-3'-deoxythymidine with preservation of antiretroviral activity

Blood ◽

10.1182/blood.v74.6.1923.1923 ◽

1989 ◽

Vol 74 (6) ◽

pp. 1923-1928 ◽

Cited By ~ 12

Author(s):

K Bhalla ◽

M Birkhofer ◽

GR Li ◽

S Grant ◽

W MacLaughlin ◽

...

Keyword(s):

Bone Marrow ◽

Progenitor Cells ◽

High Dose ◽

Normal Bone Marrow ◽

Normal Bone ◽

Bone Marrow Progenitor Cells ◽

Bone Marrow Progenitor ◽

High Concentrations ◽

Anti Hiv

Abstract Bone marrow cytotoxicity of 3′-azido-3′-deoxythymidine (AZT), an anti- human immunodeficiency virus (anti-HIV) drug, has been attributed to deoxyribonucleotide pool perturbations that might result in impaired DNA synthesis in normal bone marrow elements. We examined, in vitro, the effect of high, but clinically achievable and nontoxic, concentrations of 2′-deoxycytidine (dCyd) (greater than or equal to 100 mumol/L) on high-dose AZT mediated growth inhibition and intracellular biochemical perturbations in normal bone marrow progenitor cells. Colony formation by bone marrow progenitor cells in semisolid medium was significantly protected by dCyd against the inhibitory effects of co-administered, high concentrations of AZT (10 mumol/L). Also, dCyd significantly corrected AZT mediated depletion of intracellular thymidine triphosphate (dTTP) and dCyd triphosphate (dCTP) levels in normal bone marrow mononuclear cells (BMMC). Moreover, dCyd reduced the intracellular accumulation of AZT triphosphate (AZT-TP) and its DNA incorporation in BMMC. In contrast, co-administration of dCyd (100 mumol/L to 1 mmol/L) did not reverse AZT (10 mumol/L) mediated suppression of HIV infectivity in HUT-102 cells in culture, although a partial reduction in intracellular AZT-TP pools and its DNA incorporation as well as a correction of AZT mediated depletion of dTTP and dCTP pools was observed in these cells. These studies suggest that dCyd at high concentrations might ameliorate the bone marrow cytotoxicity of high-dose AZT without impairing its anti-HIV effect.

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High doses of immunoglobulin G attenuate immune aggregate-mediated complement activation by enhancing physiologic cleavage of C3b in C3bn- IgG complexes

Blood ◽

10.1182/blood.v88.1.184.184 ◽

1996 ◽

Vol 88 (1) ◽

pp. 184-193 ◽

Cited By ~ 98

Author(s):

HU Lutz ◽

P Stammler ◽

E Jelezarova ◽

M Nater ◽

PJ Spath

Keyword(s):

Inflammatory Diseases ◽

Factor H ◽

Human Igg ◽

Partial Protection ◽

Beneficial Effects ◽

High Concentrations ◽

High Doses ◽

Immune Aggregates

Abstract Intravenously applied human IgG has beneficial effects in treating inflammatory diseases, presumably because it has a complement attenuating role. This role of IgG was studied in vitro by following C3 activation and inactivation in sera that were supplemented with exogenous human IgG and incubated with immune aggregates. IgG added at 2 to 10 mg/mL stimulated the physiologic inactivation of C3b-containing complexes twofold to threefold in 20% sera. This, in turn, lowered the overall C3 activation by 28%, as new C3 convertases primarily assembled on C3b-containing complexes. Exogenous IgG (5 mg/mL) also stimulated inactivation of purified C3b2-IgG complexes, whereby their half-life dropped from 3–4 to 1.5 minutes in 20% serum. IgG appeared to act like a modulator of factor H and I because it did not stimulate inactivation of C3b-containing complexes in factor I-deficient serum. Thus, the known partial protection of C3bn-IgG complexes from inactivation by factor H and I was downregulated by high concentrations of IgG. The ability of high doses of IgG to stimulate complement inactivation is a novel regulatory role of IgG. This may be one of the molecular principles for its therapeutic efficacy in treating complement-mediated inflammations.

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A CRITICAL REVIEW ON HYPOTHESIS, PATHOPHYSIOLOGY OF SCHIZOPHRENIA, AND ROLE OF VITAMINS IN ITS MANAGEMENT

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2018.v11i8.23259 ◽

2018 ◽

Vol 11 (8) ◽

pp. 25

Author(s):

Rosmi Jose ◽

Venketeswaramurthy N ◽

Sambath Kumar R

Keyword(s):

Vitamin D ◽

Vitamin E ◽

Vitamin C ◽

Critical Review ◽

Methylenetetrahydrofolate Reductase ◽

Vitamin Supplementation ◽

Vitamin B ◽

High Dose ◽

Main Effects

This review describes about the literatures addressing the role of vitamin supplementation in schizophrenia. Evidence is suggesting that vitamin supplementation includes Vitamin A, Vitamin D, Vitamin E, Vitamin B complex, and Vitamin C may be important in treatment. In schizophrenia, patients may have increased level of homocysteine (Hcy), due to the polymorphism in methylenetetrahydrofolate reductase and hypofunction of N-methyl-D-aspartate receptors. The vitamins main effects are reduced the Hcy level and maintain dopamine and serotonin levels. Add-on treatment with high-dose B vitamins including B6, B9, and B12 and also Vitamin D can significantly reduce symptoms of schizophrenia more than standard treatments alone.

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Radiotherapy Planning and Molecular Imaging in Lung Cancer

Current Radiopharmaceuticals ◽

10.2174/1874471013666200318144154 ◽

2020 ◽

Vol 13 (3) ◽

pp. 204-217

Author(s):

Angelina Filice ◽

Massimiliano Casali ◽

Patrizia Ciammella ◽

Marco Galaverni ◽

Federica Fioroni ◽

...

Keyword(s):

Lung Cancer ◽

Case Reports ◽

Locally Advanced ◽

Inflammatory Cells ◽

High Rate ◽

Radiotherapy Planning ◽

High Dose ◽

18F Fdg

Introduction: In patients suitable for radical chemoradiotherapy for lung cancer, 18F-FDGPET/ CT is a proposed management to improve the accuracy of high dose radiotherapy. However, there is a high rate of locoregional failure in patients with locally advanced non-small cell lung cancer (NSCLC), probably due to the fact that standard dosing may not be effective in all patients. The aim of the present review was to address some criticisms associated with the radiotherapy image-guided in NSCLC. Materials and Methods: A systematic literature search was conducted. Only published articles that met the following criteria were included: articles, only original papers, radiopharmaceutical ([18F]FDG and any tracer other than [18F]FDG), target, only specific for lung cancer radiotherapy planning, and experimental design (eventually “in vitro” studies were excluded). Peer-reviewed indexed journals, regardless of publication status (published, ahead of print, in press, etc.) were included. Reviews, case reports, abstracts, editorials, poster presentations, and publications in languages other than English were excluded. The decision to include or exclude an article was made by consensus and any disagreement was resolved through discussion. Results: Hundred eligible full-text articles were assessed. Diverse information is now available in the literature about the role of FDG and new alternative radiopharmaceuticals for the planning of radiotherapy in NSCLC. In particular, the role of alternative technologies for the segmentation of FDG uptake is essential, although indeterminate for RT planning. The pros and cons of the available techniques have been extensively reported. : Conclusion: PET/CT has a central place in the planning of radiotherapy for lung cancer and, in particular, for NSCLC assuming a substantial role in the delineation of tumor volume. The development of new radiopharmaceuticals can help overcome the problems related to the disadvantage of FDG to accumulate also in activated inflammatory cells, thus improving tumor characterization and providing new prognostic biomarkers.

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In vivo and in vitro study on the role of 3,3'-diindolylmethane in treatment and prevention of nasopharyngeal carcinoma

Carcinogenesis ◽

10.1093/carcin/bgt122 ◽

2013 ◽

Vol 34 (8) ◽

pp. 1815-1821 ◽

Cited By ~ 11

Author(s):

C. Chen ◽

S.-M. Chen ◽

B. Xu ◽

Z. Chen ◽

F. Wang ◽

...

Keyword(s):

Nasopharyngeal Carcinoma ◽

In Vitro Study ◽

Vitro Study ◽

Treatment And Prevention

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In vitro inhibition of porcine cytochrome P450 by 17β-estradiol and 17α-estradiol

Interdisciplinary Toxicology ◽

10.2478/v10102-011-0014-x ◽

2011 ◽

Vol 4 (2) ◽

pp. 78-84 ◽

Cited By ~ 5

Author(s):

Galia Zamaratskaia ◽

Martin Rasmussen ◽

Isabelle Herbin ◽

Bo Ekstrand ◽

Vladimir Zlabek

Keyword(s):

Cytochrome P450 ◽

Inhibitory Effect ◽

17Β Estradiol ◽

Cyp2e1 Activity ◽

High Concentrations ◽

Testicular Steroids ◽

Sexually Mature

In vitro inhibition of porcine cytochrome P450 by 17β-estradiol and 17α-estradiol Sexually mature pigs are known to possess high concentrations of testicular steroids, which have been shown to change the activities of cytochrome P450 in vitro. The aim of the present study was to evaluate the regulation of CYP1A and CYP2E1 activity by the steroids dihydrotestosterone (DHT), 3β-androstenol, 17β-estradiol and 17α-estradiol. Catalytic activities of 7-ethoxyresorufin O-deethylase (EROD) and 7-methoxyresorufin O-demethylase (MROD) were used as markers of CYP1A activities, while p-nitrophenol hydroxylase (PNPH) was used as a marker of CYP2E1 activities. Of the steroids tested, only 17β-estradiol and 17α-estradiol inhibited EROD and MROD activities. This inhibition was observed when a steroid concentration of 100 μM was used, while lower concentrations showed no inhibitory effect. PNPH activities were inhibited only by 100 μM of 17β-estradiol. The significance of these results in vivo is unknown because inhibition was only found when concentrations of estrogens higher than physiological levels were used. Nevertheless, the results provided further evidence on the important role of estrogens in regulation of porcine cytochrome P450 activities.

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Effect of low doses of estradiol and tamoxifen on breast cancer cell karyotypes

Endocrine Related Cancer ◽

10.1530/erc-16-0078 ◽

2016 ◽

Vol 23 (8) ◽

pp. 635-650 ◽

Cited By ~ 6

Author(s):

Milena Rondón-Lagos ◽

Nelson Rangel ◽

Ludovica Verdun Di Cantogno ◽

Laura Annaratone ◽

Isabella Castellano ◽

...

Keyword(s):

Breast Cancer ◽

Cell Proliferation ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Chromosomal Abnormalities ◽

Chromosomal Rearrangements ◽

Low Doses ◽

Treatment And Prevention

Evidence supports a role of 17&-estradiol (E2) in carcinogenesis and the large majority of breast carcinomas are dependent on estrogen. The anti-estrogen tamoxifen (TAM) is widely used for both treatment and prevention of breast cancer; however, it is also carcinogenic in human uterus and rat liver, highlighting the profound complexity of its actions. The nature of E2- or TAM-induced chromosomal damage has been explored using relatively high concentrations of these agents, and only some numerical aberrations and chromosomal breaks have been analyzed. This study aimed to determine the effects of low doses of E2and TAM (10&8 mol L&1and 10&6 mol L&1respectively) on karyotypes of MCF7, T47D, BT474, and SKBR3 breast cancer cells by comparing the results of conventional karyotyping and multi-FISH painting with cell proliferation. Estrogen receptor (ER)-positive (+) cells showed an increase in cell proliferation after E2treatment (MCF7, T47D, and BT474) and a decrease after TAM treatment (MCF7 and T47D), whereas in ER& cells (SKBR3), no alterations in cell proliferation were observed, except for a small increase at 96 h. Karyotypes of both ER+ and ER& breast cancer cells increased in complexity after treatments with E2and TAM leading to specific chromosomal abnormalities, some of which were consistent throughout the treatment duration. This genotoxic effect was higher in HER2+ cells. The ER&/HER2+ SKBR3 cells were found to be sensitive to TAM, exhibiting an increase in chromosomal aberrations. Thesein vitroresults provide insights into the potential role of low doses of E2and TAM in inducing chromosomal rearrangements in breast cancer cells.

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Olanzapine inhibits hepatic apolipoprotein A5 secretion inducing hypertriglyceridemia in schizophrenia patients and mice

10.1101/2021.02.26.21252514 ◽

2021 ◽

Author(s):

Xiansheng Huang ◽

Yiqi Zhang ◽

Wenqiang Zhu ◽

Piaopiao Huang ◽

Jingmei Xiao ◽

...

Keyword(s):

Mrna Expression ◽

Plasma Triglyceride ◽

High Dose ◽

Mrna Levels ◽

Apolipoprotein A5 ◽

Protein Levels ◽

Olanzapine Treatment ◽

Primary Mouse

Olanzapine, an antipsychotic drug, was reported to induce hypertriglyceridemia, whereas the underlying mechanism remains incompletely understood. This study was to determine the role of apolipoprotein A5 (apoA5) in olanzapine-induced hypertriglyceridemia. In this study, 36 drug-naive and first-episode schizophrenic adult patients (aged 18-60 years) in a multi-center clinical trial (ClinicalTrials.gov NCT03451734) were enrolled. Before and after olanzapine treatment, plasma lipid and apoA5 levels were detected. Moreover, 21 female C57BL/6 J mice (8 weeks old) were divided into 3 groups (n = 7/each group): low-dose olanzapine (3 mg/kg/day), high-dose olanzapine (6 mg/kg/day) and control group. After 6 weeks, plasma glucose, lipids and apoA5 as well as hepatic apoA5 protein and mRNA expression in these animals were detected. In our study in vitro, primary mouse hepatocytes and HepG2 cells were treated with olanzapine of 25, 50, 100 μmol/L, respectively. After 24 hours, apoA5 protein and mRNA levels in hepatocytes were detected. Our study showed that olanzapine treatment significantly increased plasma triglyceride levels and decreased plasma apoA5 levels in these schizophrenic patients. A significant negative correlation was indicated between plasma triglyceride and apoA5 levels in these patients. Consistently, olanzapine dose-dependently increased plasma triglyceride levels and decreased plasma apoA5 levels in mice. Surprisingly, an elevation of hepatic apoA5 protein levels was detected in mice after olanzapine treatment, with no changes of APOA5 mRNA expression. Likewise, olanzapine increased apoA5 protein levels in hepatocytes in vitro, without changes of hepatocyte APOA5 mRNA. Therefore, our study provides the first evidence about the role of apoA5 in olanzapine-induced hypertriglyceridemia. Furthermore, plasma apoA5 reduction, resulting in hypertriglyceridemia, could be attributed to olanzapine-induced inhibition of hepatic apoA5 secretion.

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