The Need to Consider Context in the Evaluation of Anti-infectious and Immunomodulatory Effects of Vitamin A and its Derivatives

2019 ◽  
Vol 20 (8) ◽  
pp. 871-878 ◽  
Author(s):  
Pedro Xavier-Elsas ◽  
Bruno M. Vieira ◽  
Daniela Masid-de-Brito ◽  
Monica G. Barradas ◽  
Maria I.C. Gaspar-Elsas
Keyword(s):  
Vitamin A ◽  
Clinical Presentation ◽  
Infectious Agents ◽  
Hypervitaminosis A ◽  
General Role ◽  
Significant Toxicity ◽  
Vast Literature ◽  
Gut Mucosa ◽  
Anti Inflammatory ◽  
Pathogen Exposure

Vitamin A and its derivatives (retinoids) act as potent regulators in many aspects of mammalian reproduction, development, repair, and maintenance of differentiated tissue functioning. Unlike other vitamins, Vitamin A and retinoids, which have hormonal actions, present significant toxicity, which plays roles in clinically relevant situations, such as hypervitaminosis A and retinoic acid ("differentiation") syndrome. Although clinical presentation is conspicuous in states of insufficient or excessive Vitamin A and retinoid concentration, equally relevant effects on host resistance to specific infectious agents, and in the general maintenance of immune homeostasis, may go unnoticed, because their expression requires either pathogen exposure or the presence of inflammatory co-morbidities. There is a vast literature on the roles played by retinoids in the maintenance of a tolerogenic, noninflammatory environment in the gut mucosa, which is considered by many investigators representative of a general role played by retinoids as anti-inflammatory hormones elsewhere. However, in the gut mucosa itself, as well as in the bone marrow and inflammatory sites, context determines whether one observes an anti-inflammatory or proinflammatory action of retinoids. Both interactions between specialized cell populations, and interactions between retinoids and other classes of mediators/regulators, such as cytokines and glucocorticoid hormones, must be considered as important factors contributing to this overall context. We review evidence from recent studies on mucosal immunity, granulocyte biology and respiratory allergy models, highlighting the relevance of these variables as well as their possible contributions to the observed outcomes.

An in vitro model for investigation of vitamin A effects on wound healing

2021 ◽  
pp. 1-6
Author(s):  
Hoda Keshmiri Neghab ◽  
Mohammad Hasan Soheilifar ◽  
Gholamreza Esmaeeli Djavid
Keyword(s):  
Wound Healing ◽  
Endothelial Cell ◽  
Vitamin A ◽  
In Vitro Model ◽  
Cellular Proliferation ◽  
Endothelial Cell Migration ◽  
Normal Fibroblast ◽  
Anti Inflammatory ◽  
Vitro Model

Abstract. Wound healing consists of a series of highly orderly overlapping processes characterized by hemostasis, inflammation, proliferation, and remodeling. Prolongation or interruption in each phase can lead to delayed wound healing or a non-healing chronic wound. Vitamin A is a crucial nutrient that is most beneficial for the health of the skin. The present study was undertaken to determine the effect of vitamin A on regeneration, angiogenesis, and inflammation characteristics in an in vitro model system during wound healing. For this purpose, mouse skin normal fibroblast (L929), human umbilical vein endothelial cell (HUVEC), and monocyte/macrophage-like cell line (RAW 264.7) were considered to evaluate proliferation, angiogenesis, and anti-inflammatory responses, respectively. Vitamin A (0.1–5 μM) increased cellular proliferation of L929 and HUVEC (p < 0.05). Similarly, it stimulated angiogenesis by promoting endothelial cell migration up to approximately 4 fold and interestingly tube formation up to 8.5 fold (p < 0.01). Furthermore, vitamin A treatment was shown to decrease the level of nitric oxide production in a dose-dependent effect (p < 0.05), exhibiting the anti-inflammatory property of vitamin A in accelerating wound healing. These results may reveal the therapeutic potential of vitamin A in diabetic wound healing by stimulating regeneration, angiogenesis, and anti-inflammation responses.

scholarly journals Anti-Tumor and Anti-Inflammatory Activity In Vivo of Apodanthera congestiflora Cogn. (Cucurbitaceae)

Pharmaceutics ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 743
Author(s):  
Geovana F. G. Silvestre ◽  
Renally P. Lucena ◽  
Genil D. Oliveira ◽  
Helimarcos N. Pereira ◽  
Jhonatta A. B. Dias ◽  
...  
Keyword(s):  
Inflammatory Activity ◽  
Phytochemical Investigation ◽  
Significant Toxicity ◽  
Biological Tests ◽  
Ehrlich's Carcinoma ◽  
Anti Inflammatory ◽  
Pharmacological Potential ◽  
First Time ◽  
Anti Tumor Activity

This work aimed to carry out a study of Apodanthera congestiflora by investigating its chemical composition and pharmacological potential. From the dichloromethane phase (Dic-Ac) of the A. congestiflora stems, three compounds were identified: cayaponoside C5b (Ac-1), cabenoside C (Ac-2) and fevicordin C2 glucoside (Ac-3), being last identified for the first time as a natural product. These compounds were obtained by chromatographic methods and their structures were elucidated by means of spectroscopic analysis of IR, MS and NMR. In the quantification of Dic-Ac, it was possible to observe the presence of 7% of cayaponoside C5b. Dic-Ac showed significant toxicity for in vivo tests, with macroscopic and biochemical changes. The anti-inflammatory activity of Dic-Ac was investigated using the paw edema model. A decrease in inflammatory signs was observed in the first 5 h and the most effective dose in reducing edema with was 7.5 mg kg−1 (66.6%). Anti-tumor activity of Dic-Ac was evaluated by Ehrlich’s carcinoma model, which showed inhibition rate of 78.46% at 15 mg kg−1 dosage. The phytochemical investigation, together with the biological tests carried out in this study, demonstrated that A. congestiflora is a promising species in the search for therapeutics, since it contains substances with high pharmacological potential in its composition.

scholarly journals CFTR Modulator Therapy with Lumacaftor/Ivacaftor Alters Plasma Concentrations of Lipid-Soluble Vitamins A and E in Patients with Cystic Fibrosis

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 483
Author(s):  
Olaf Sommerburg ◽  
Susanne Hämmerling ◽  
S. Philipp Schneider ◽  
Jürgen Okun ◽  
Claus-Dieter Langhans ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Vitamin E ◽  
Vitamin A ◽  
Clinical Chemistry ◽  
Pancreatic Insufficiency ◽  
Plasma Concentrations ◽  
Plasma Vitamin ◽  
Hypervitaminosis A ◽  
Cholesterol Ratio ◽  
Fat Soluble Vitamins

Rationale: Cystic fibrosis (CF), caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, leads to impaired pancreatic function and therefore reduced intestinal absorption of lipids and fat-soluble vitamins especially in patients with CF developing pancreatic insufficiency (PI). Previous studies showed that CFTR modulator therapy with lumacaftor-ivacaftor (LUM/IVA) in Phe508del-homozygous patients with CF results in improvement of pulmonary disease and thriving. However, the effects of LUM/IVA on plasma concentration of the lipid soluble vitamins A and E remain unknown. Objectives: To investigate the course of plasma vitamin A and E in patients with CF under LUM/IVA therapy. Methods: Data from annual follow-up examinations of patients with CF were obtained to assess clinical outcomes including pulmonary function status, body mass index (BMI), and clinical chemistry as well as fat-soluble vitamins in Phe508del-homozygous CF patients before initiation and during LUM/IVA therapy. Results: Patients with CF receiving LUM/IVA improved substantially, including improvement in pulmonary inflammation, associated with a decrease in blood immunoglobulin G (IgG) from 9.4 to 8.2 g/L after two years (p < 0.001). During the same time, plasma vitamin A increased significantly from 1.2 to 1.6 µmol/L (p < 0.05), however, levels above the upper limit of normal were not detected in any of the patients. In contrast, plasma vitamin E as vitamin E/cholesterol ratio decreased moderately over the same time from 6.2 to 5.5 µmol/L (p < 0.01). Conclusions: CFTR modulator therapy with LUM/IVA alters concentrations of vitamins A and vitamin E in plasma. The increase of vitamin A must be monitored critically to avoid hypervitaminosis A in patients with CF.

scholarly journals South African preschool children habitually consuming sheep liver and exposed to vitamin A supplementation and fortification have hypervitaminotic A liver stores: a cohort study

2019 ◽  
Vol 110 (1) ◽  
pp. 91-101 ◽  
Author(s):  
Martha E van Stuijvenberg ◽  
Muhammad A Dhansay ◽  
Jana Nel ◽  
Devika Suri ◽  
Michael Grahn ◽  
...  
Keyword(s):  
South Africa ◽  
Preschool Children ◽  
Vitamin A ◽  
Total Serum ◽  
High Dose ◽  
Serum Retinol ◽  
Hypervitaminosis A ◽  
Total Liver ◽  
Before And After ◽  
Retinyl Esters

ABSTRACT Background In some regions, multiple vitamin A (VA) interventions occur in the same target groups, which may lead to excessive stores. Retinol isotope dilution (RID) is a more sensitive technique than serum retinol to measure VA status. Objective We evaluated VA status before and after a high-dose supplement in preschool children living in a region in South Africa with habitual liver consumption and exposed to VA supplementation and fortification. Methods After baseline blood samples, subjects (46.7 ± 8.4 mo; n = 94) were administered 1.0 μmol [14,15]-13C2-retinyl acetate to estimate total liver retinol reserves by RID with a follow-up 14-d blood sample. Liver intake was assessed with a frequency questionnaire. In line with current practice, a routine 200,000 IU VA capsule was administered after the RID test. RID was repeated 1 mo later. Serum retinyl esters were evaluated using ultra-performance liquid chromatography. Results At baseline, 63.6% of these children had hypervitaminosis A defined as total liver retinol reserves ≥1.0 μmol/g liver, which increased to 71.6% after supplementation (1.13 ± 0.43 to 1.29 ± 0.46 μmol/g; P < 0.001). Total serum VA as retinyl esters was elevated in 4.8% and 6.1% of children before and after supplementation. The odds of having hypervitaminosis A at baseline were higher in children consuming liver ≥1/mo (ratio 3.70 [95% CI: 1.08, 12.6]) and in children receiving 2 (4.28 [1.03, 17.9]) or 3 (6.45 [0.64, 65.41]) supplements in the past 12 mo. Total body stores decreased after the supplement in children in the highest quartile at baseline compared with children with lower stores, who showed an increase (P = 0.007). Conclusions In children, such as this cohort in South Africa, with adequate VA intake through diet, and overlapping VA fortification and supplementation, preschool VA capsule distribution should be re-evaluated. This trial was registered at https://clinicaltrials.gov/ct2/show/NCT02915731 as NCT02915731.

VITAMIN A POISONING

PEDIATRICS ◽  
1951 ◽  
Vol 7 (3) ◽  
pp. 372-385
Author(s):  
DONALD GRIBETZ ◽  
SAMUEL H. SILVERMAN ◽  
ALBERT E. SOBEL
Keyword(s):  
Vitamin A ◽  
Experimental Studies ◽  
Plasma Vitamin ◽  
Hypervitaminosis A ◽  
Total Vitamin ◽  
Toxic Factor ◽  
Vitamin Intake ◽  
First Case ◽  
Alcohol Fraction ◽  
Clinical Literature

Two cases of hypervitaminosis A have been presented together with a review of experimental and clinical literature. The first case presented the highest reported fasting plasma vitamin A level, the increase being chiefly due to a high vitamin A alcohol fraction. This elevated level of alcoholic vitamin A probably denotes large stores of vitamin A in the liver and data have been given to show that it is a better index of hypervitaminosis A than is the total vitamin A level. In addition, evidence has been presented that the toxic factor in hypervitaminosis A is the permanent elevated plasma vitamin A level. The similarity between the experimental studies in animals and the observations in the authors' first case has been shown. The important points necessary for making a diagnosis of hypervitaminosis A have been discussed and several similar conditions have been differentiated. It cannot be emphasized too strongly that excess vitamin intake may be as dangerous as a deficient intake.

Postscript: prescribing for acute diarrhea (30 December 1983, p 101–4)

1984 ◽  
Vol 22 (16) ◽  
pp. 64-64
Keyword(s):  
Acute Diarrhea ◽  
Clinical Presentation ◽  
Health Workers ◽  
Teaching Tool ◽  
London School ◽  
Infectious Agents ◽  
Basic Information ◽  
Professional Health ◽  
And Control ◽  
Made In

A CHART – Most of the points made in our article are also summarised in an information chart “Coping with Diarrhoea”, produced last year by the Ross Institute. It is intended as a teaching tool for professional health workers involved in the clinical management of diarrhoea, and gives basic information on clinical presentation, treatment, epidemiology and control of the most common agents of diarrhoea. A second chart summarises scientific knowledge of the major infectious agents of diarrhoea, and is intended for reference. The charts can be obtained from Miss S. O’Driscoll, Ross Institute, London School of Hygiene & Tropical Medicine, Keppel Street, London WC1E 7HT (cost £1 for the first and £2 for the second chart).

Vitamin A Acid and Hypervitaminosis A

Nature ◽  
1960 ◽  
Vol 188 (4751) ◽  
pp. 672-673 ◽  
Author(s):  
J. N. THOMPSON ◽  
G. A. J. PITT
Keyword(s):  
Vitamin A ◽  
Hypervitaminosis A ◽  
Vitamin A Acid

scholarly journals Multiple Vaccinations and the Enigma of Vaccine Injury

Vaccines ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 676
Author(s):  
Anthony R. Mawson ◽  
Ashley M. Croft
Keyword(s):  
Retinoic Acid ◽  
Vitamin A ◽  
Neurodevelopmental Disorders ◽  
Vaccine Safety ◽  
Mass Vaccination ◽  
Adverse Outcomes ◽  
Interactive Effects ◽  
Hypervitaminosis A ◽  
Ear Infections ◽  
The Impact

A growing number of vaccines are administered at the same time or in close succession, increasing the complexity of assessing vaccine safety. Individual vaccines are assumed to have no other effect than protection against the targeted pathogen, but vaccines also have nonspecific and interactive effects, the outcomes of which can be beneficial or harmful. To date, no controlled trials and very few observational studies have determined the impact of vaccination schedules on overall health. The balance of the risks and benefits from mass vaccination therefore remains uncertain. Recent studies worryingly suggest links between multiple vaccinations and increased risks of diverse multisystem health problems, including allergies, infections, and neuropsychiatric or neurodevelopmental disorders. Here, we propose that, in susceptible persons, multiple vaccinations activate the retinoid cascade and trigger apoptotic hepatitis, leading to cholestatic liver dysfunction, in which stored vitamin A compounds (retinyl esters and retinoic acid) enter the circulation in toxic concentrations; this induces endogenous forms of hypervitaminosis A, with the severity of adverse outcomes being directly proportional to the concentration of circulating retinoids. In very low concentrations, vitamin A and its major metabolite retinoic acid contribute to immune function and to the process of immunization, whereas excess vitamin A increases the risk of adverse events, including common “side-effects” as well as chronic adverse outcomes. The increasing rates of allergy, ear infections, and neurodevelopmental disorders (NDDs) in countries with high rates of vaccination could be related to mass vaccination and to its impact on liver function and vitamin A metabolism, collectively representing endogenous manifestations of hypervitaminosis A. Further studies of health outcomes in vaccinated and unvaccinated groups are urgently needed, to increase understanding of the pathophysiology and treatment of vaccine injury, to identify the risk factors and screen for vaccine injury, to inform public health policy on potential hazards related to vaccination schedules, and to optimize the safety and benefits of vaccines.

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