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Immunogenicity of an oral rotavirus vaccine administered with prenatal nutritional support in Niger: A cluster randomized clinical trial.
Isanaka, S, Garba, S, Plikaytis, B, Malone McNeal, M, Guindo, O, Langendorf, C, Adehossi, E, Ciglenecki, I, Grais, RF
PLoS medicine. 2021;(8):e1003720
Abstract
BACKGROUND Nutritional status may play a role in infant immune development. To identify potential boosters of immunogenicity in low-income countries where oral vaccine efficacy is low, we tested the effect of prenatal nutritional supplementation on immune response to 3 doses of a live oral rotavirus vaccine. METHODS AND FINDINGS We nested a cluster randomized trial within a double-blind, placebo-controlled randomized efficacy trial to assess the effect of 3 prenatal nutritional supplements (lipid-based nutrient supplement [LNS], multiple micronutrient supplement [MMS], or iron-folic acid [IFA]) on infant immune response (n = 53 villages and 1,525 infants with valid serology results: 794 in the vaccine group and 731 in the placebo group). From September 2015 to February 2017, participating women received prenatal nutrient supplement during pregnancy. Eligible infants were then randomized to receive 3 doses of an oral rotavirus vaccine or placebo at 6-8 weeks of age (mean age: 6.3 weeks, 50% female). Infant sera (pre-Dose 1 and 28 days post-Dose 3) were analyzed for anti-rotavirus immunoglobulin A (IgA) using enzyme-linked immunosorbent assay (ELISA). The primary immunogenicity end point, seroconversion defined as ≥3-fold increase in IgA, was compared in vaccinated infants among the 3 supplement groups and between vaccine/placebo groups using mixed model analysis of variance procedures. Seroconversion did not differ by supplementation group (41.1% (94/229) with LNS vs. 39.1% (102/261) with multiple micronutrients (MMN) vs. 38.8% (118/304) with IFA, p = 0.91). Overall, 39.6% (n = 314/794) of infants who received vaccine seroconverted, compared to 29.0% (n = 212/731) of infants who received placebo (relative risk [RR]: 1.36; 95% confidence interval [CI]: 1.18, 1.57, p < 0.001). This study was conducted in a high rotavirus transmission setting. Study limitations include the absence of an immune correlate of protection for rotavirus vaccines, with the implications of using serum anti-rotavirus IgA for the assessment of immunogenicity and efficacy in low-income countries unclear. CONCLUSIONS This study showed no effect of the type of prenatal nutrient supplementation on immune response in this setting. Immune response varied depending on previous exposure to rotavirus, suggesting that alternative delivery modalities and schedules may be considered to improve vaccine performance in high transmission settings. TRIAL REGISTRATION ClinicalTrials.gov NCT02145000.
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B Vitamins and One-Carbon Metabolism: Implications in Human Health and Disease.
Lyon, P, Strippoli, V, Fang, B, Cimmino, L
Nutrients. 2020;(9)
Abstract
Vitamins B9 (folate) and B12 are essential water-soluble vitamins that play a crucial role in the maintenance of one-carbon metabolism: a set of interconnected biochemical pathways driven by folate and methionine to generate methyl groups for use in DNA synthesis, amino acid homeostasis, antioxidant generation, and epigenetic regulation. Dietary deficiencies in B9 and B12, or genetic polymorphisms that influence the activity of enzymes involved in the folate or methionine cycles, are known to cause developmental defects, impair cognitive function, or block normal blood production. Nutritional deficiencies have historically been treated with dietary supplementation or high-dose parenteral administration that can reverse symptoms in the majority of cases. Elevated levels of these vitamins have more recently been shown to correlate with immune dysfunction, cancer, and increased mortality. Therapies that specifically target one-carbon metabolism are therefore currently being explored for the treatment of immune disorders and cancer. In this review, we will highlight recent studies aimed at elucidating the role of folate, B12, and methionine in one-carbon metabolism during normal cellular processes and in the context of disease progression.
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Cerebral folate deficiency: Analytical tests and differential diagnosis.
Pope, S, Artuch, R, Heales, S, Rahman, S
Journal of inherited metabolic disease. 2019;(4):655-672
Abstract
Cerebral folate deficiency is typically defined as a deficiency of the major folate species 5-methyltetrahydrofolate in the cerebrospinal fluid (CSF) in the presence of normal peripheral total folate levels. However, it should be noted that cerebral folate deficiency is also often used to describe conditions where CSF 5-MTHF is low, in the presence of low or undefined peripheral folate levels. Known defects of folate transport are deficiency of the proton coupled folate transporter, associated with systemic as well as cerebral folate deficiency, and deficiency of the folate receptor alpha, leading to an isolated cerebral folate deficiency associated with intractable seizures, developmental delay and/or regression, progressive ataxia and choreoathetoid movement disorders. Inborn errors of folate metabolism include deficiencies of the enzymes methylenetetrahydrofolate reductase, dihydrofolate reductase and 5,10-methenyltetrahydrofolate synthetase. Cerebral folate deficiency is potentially a treatable condition and so prompt recognition of these inborn errors and initiation of appropriate therapy is of paramount importance. Secondary cerebral folate deficiency may be observed in other inherited metabolic diseases, including disorders of the mitochondrial oxidative phosphorylation system, serine deficiency, and pyridoxine dependent epilepsy. Other secondary causes of cerebral folate deficiency include the effects of drugs, immune response activation, toxic insults and oxidative stress. This review describes the absorption, transport and metabolism of folate within the body; analytical methods to measure folate species in blood, plasma and CSF; inherited and acquired causes of cerebral folate deficiency; and possible treatment options in those patients found to have cerebral folate deficiency.
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Homocysteine, vitamin B12, and folate levels in patients with multiple sclerosis in Chinese population: A case-control study and meta-analysis.
Pan, L, Yin, Y, Chen, J, Ma, Z, Chen, Y, Deng, X, Zhang, HT, Leng, H, Wu, K
Multiple sclerosis and related disorders. 2019;:101395
Abstract
BACKGROUND Current studies suggested discrepancies on the correlations between multiple sclerosis (MS) and blood levels of homocysteine (Hcy), vitamin B12 (VB12), and folate. We performed a case-control study and meta-analysis to help resolve the controversy of these lab values in Chinese patients with MS. METHODS We recruited 80 Chinese MS patients, 86 age/sex matched neurological controls (patients with peripheral vertigo or sleep disorders), and 80 age- and sex-matched healthy controls. Serum Hcy levels were measured using flourimetric high-performance liquid chromatography, serum levels of VB12 and folate using immune assay. A literature search of PubMed, Embase, Web of Science, Chinese National Knowledge Infrastructure, Wanfang, and SinoMed was conducted for case-control studies with pure Chinese populations published up to March 16, 2019. The effective size was estimated by the pooled standardized mean difference (SMD) and associated 95% confidence interval (CI). RESULTS The case-control study results suggest higher Hcy levels (mean ± SD) and frequency of hyperhomocysteinemia in the Chinese MS cases than control groups (all p < 0.001), lower for VB12 levels (mean ± SD, p = 0.043 or 0.039). No significant difference was observed for levels of folate (mean ± SD, both p > 0.05), and for frequency of folate or VB12 deficiency (all p > 0.05). Analysis of pooled SMDs and 95% CIs suggested increased Hcy levels in Chinese MS patients (SMD: 2.31, 95% CI: 1.33-3.28, p < 0.001), and in relapsing or remitting cases relative to controls (SMD: 0.94 or 0.85, 95% CI: 0.49-1.39 or 0.35-1.34, both p < 0.001). The meta-analysis results also suggested reduced VB12 levels in Chinese MS patients (SMD: -0.30, 95% CI: -0.46-0.14, p < 0.001), and in relapsing MS patients compared to controls (SMD: -0.31, 95% CI: -0.47-0.15, p < 0.001), while no statistical difference for cases in remission. No significant difference was observed for levels folate in all comparisons. CONCLUSION Patients with MS tend to have increased blood Hcy levels compared to controls. MS patients of Chinese origin and those in relapse may have decreased levels of VB12. Hcy and VB12 may contribute to pathogenesis of the disease, and VB12 may correlate with MS relapse.
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Depression, isotretinoin, and folic acid: A practical review.
Abdelmaksoud, A, Vojvodic, A, Ayhan, E, Dönmezdil, S, Jovicevic, TV, Vojvodic, P, Lotti, T, Vestita, M
Dermatologic therapy. 2019;(6):e13104
Abstract
Isotretinoin (ISO) is a first-generation retinoid discovered in 1952 and approved by the FDA for the treatment of nodulocystic acne in 1982. The anti-inflammatory properties of ISO have found its use in disorders other than acne. ISO can create psychiatric problems, including depression and suicidal ideation. These neuropsychiatric problems are very similar to disorders secondary to hyperhomocysteinemia (HHcy), vitamin B12, and folic acid (vitamin B9) deficiencies. Given that previous literature suggested folate supplementation improved the efficacy of traditional antidepressant medications, clinicians may wish to consider folate supplementation for patients with depression or possible depressive symptoms, such as acne patients with genetic susceptibility. Brain-derived neurotrophic factor may be a cytokine-specific screening biomarker in immune-based antidepressive therapy.
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Folate-targeted nanoparticles for rheumatoid arthritis therapy.
Nogueira, E, Gomes, AC, Preto, A, Cavaco-Paulo, A
Nanomedicine : nanotechnology, biology, and medicine. 2016;(4):1113-1126
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Abstract
UNLABELLED Rheumatoid arthritis (RA) is the most common inflammatory rheumatic disease, affecting almost 1% of the world population. Although the cause of RA remains unknown, the complex interaction between immune mediators (cytokines and effector cells) is responsible for the joint damage that begins at the synovial membrane. Activated macrophages are critical in the pathogenesis of RA and showed specifically express a receptor for the vitamin folic acid (FA), folate receptor β (FRβ). This particular receptor allows internalization of FA-coupled cargo. In this review we will address the potential of nanoparticles as an effective drug delivery system for therapies that will directly target activated macrophages. Special attention will be given to stealth degree of the nanoparticles as a strategy to avoid clearance by macrophages of the mononuclear phagocytic system (MPS). This review summarizes the application of FA-target nanoparticles as drug delivery systems for RA and proposes prospective future directions. FROM THE CLINICAL EDITOR Rheumatoid arthritis is a debilitating autoimmune disease of the joints which affects many people worldwide. Up till now, there is a lack of optimal therapy against this disease. In this review article, the authors outlined in depth the current mechanism of disease for rheumatoid arthritis and described the latest research in using folic acid-targeted nanoparticles to target synovial macrophages in the fight against rheumatoid arthritis.