Vitamin D status, oxidative stress, and inflammation in children and adolescents: A systematic review.

Vitamin D deficiency is considered a global public health problem with high prevalence in children and adolescents. The majority of the studies in the literature have identified a relationship between vitamin D insufficiency/deficiency and obesity, as well as other traditional cardiometabolic risk factors in children and adolescents. Scarce studies address vitamin D status with oxidative stress and inflammation in the young population. The aim of this systematic review was to evaluate the evidence of the association of vitamin D status with oxidative stress and inflammation in children and adolescents. This is a systematic review based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) guideline on reporting systematic reviews. Eight studies were selected for this review. All included studies evaluated inflammatory biomarkers and two out of eight evaluated biomarkers of oxidative stress. The majority of the studies (five out of eight) found association of vitamin D status with biomarkers of oxidative stress and inflammation such as C-reactive protein (CRP), interleukin-6 (IL-6), cathepsin S, vascular cell adhesion molecule-1 (VCAM-1), malondialdehyde (MDA), myeloperoxidase, 3-nitrotyrosine, and superoxide dismutase (SOD). Vitamin D status is associated with oxidative stress and inflammation in the majority of the studies with children and adolescents. Thus, the assessment of vitamin D status is important because it is associated with nontraditional cardiometabolic markers in the pediatric population (review registration: PROSPERO CRD42018109307).

Adipokines, tumor necrosis factor and its receptors in female patients with systemic lupus erythematosus.

OBJECTIVES: To analyze the association of adipokines and tumor necrosis factor α (TNFα) and its receptors with characteristics of systemic lupus erythematosus (SLE) and to investigate the correlation between adipokines and the TNF system. METHODS: One hundred and thirty-six SLE women, aged ≥18 years old, were assessed. TNFα, soluble TNFα receptors 1 (sTNFR1) and 2 (sTNFR2) and adipokines were analyzed by ELISA kits. RESULTS: The median (IQR) of age was 41.5 (33.0-49.7) years old and of disease duration 11.3 (7.8-15.8) years. The median (IQR) of disease activity was 0 (0-4) and of damage index was 2 (1-3). Higher levels of sTNFR1 and sTNFR2 were associated with nephritis (p < 0.001 for both), and sTNFR1 (p = 0.025) and TNFα (p = 0.014) were positively associated with arthritis. Higher sTNFR1 levels were found in participants that were not using antimalarial drugs (p = 0.04). Independent correlation was found between sTNFR1 (ß = 0.253; p = 0.003) and sTNFR2 (ß = 0.297; p < 0.001) levels and disease activity and damage index (sTNFR1: ß = 0.367; p < 0.001; sTNFR2: ß = 0.335; p < 0.001). Higher adiponectin levels were independently associated with nephritis (p = 0.009) and antimalarial drugs use (p = 0.015). There was a positive correlation between leptin and sTNFR2 levels (p = 0.002) and between resistin levels and sTNFR1 (p < 0.001) and sTNFR2 (p < 0.001). CONCLUSION: The correlation between adipokines and TNF system allows a better understanding of the role of adipokines in the inflammatory response in SLE patients.

Increased serum levels of eotaxin/CCL11 in late-stage patients with bipolar disorder: An accelerated aging biomarker?

BACKGROUND: Bipolar disorder (BD) is commonly comorbid with many medical disorders including atopy, and appears characterized by progressive social, neurobiological, and functional impairment associated with increasing number of episodes and illness duration. Early and late stages of BD may present different biological features and may therefore require different treatment strategies. Consequently, the aim of this study was to evaluate serum levels of eotaxin/CCL11, eotaxin-2/CCL24, IL-2, IL-4, IL-6, IL-10, IL-17, TNF-α, IFNγ, BDNF, TBARS, carbonyl, and GPx in a sample of euthymic patients with BD at early and late stages compared to controls. METHODS: Early-stage BD patients, 12 late-stage patients, and 25 controls matched for sex and age were selected. 10mL of peripheral blood was drawn from all subjects by venipuncture. Serum levels of BDNF, TBARS, carbonyl content, glutathione-peroxidase activity (GPx), cytokines (IL-2, IL-4, IL-6, IL-10, IL-17, TNF-α and IFNγ), and chemokines (eotaxin/CCL11 and eotaxin-2/CCL24) were measured. RESULTS: There were no demographic differences between patients and controls. No significant differences were found for any of the biomarkers, except chemokine eotaxin/CCL11, whose serum levels were higher in late-stage patients with BD when compared to controls (p=0.022; Mann-Whitney U test). LIMITATIONS: Small number of subjects and use of medication may have influenced in our results. CONCLUSION: The present study suggests a link between biomarkers of atopy and eosinophil function and bipolar disorder. These findings are also in line with progressive biological changes partially mediated by inflammatory imbalance, a process referred to as neuroprogression.

Evidence for the contribution of adult neurogenesis and hippocampal cell death in experimental cerebral malaria cognitive outcome.

Cognitive dysfunction is a major sign of cerebral malaria (CM). However, the underlying mechanisms of CM cognitive outcome remain poorly understood. A body of evidence suggests that adult neurogenesis may play a role in learning and memory processes. It has also been reported that these phenomena can be regulated by the immune system. We hypothesized that memory dysfunction in CM results from hippocampal neurogenesis impairment mediated by the deregulated immune response during the acute phase of CM. C57Bl/6 mice were infected with Plasmodium berghei ANKA (PbA) strain, using a standardized inoculation of 10(6) parasitized erythrocytes. Long-term working memory was evaluated using the novel object recognition test. The mRNA expression of brain-derived neurotrophic factor (BDNF), tropomyosin-receptor-kinase (TRK-B) and nerve growth factor (NGF) in the frontal cortex and hippocampus was estimated by real-time polymerase chain reaction (PCR). The protein levels of cytokine interleukin-2 (IL-2), IL-4, IL-6, IL-10, interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and CCL11 and neurotrophins BDNF and NGF were determined using a cytometric bead array (CBA) kit or enzyme-linked immunosorbent assay. Cell viability in the hippocampus was analyzed by Confocal Microscopy. Neurogenesis in the dentate gyrus was determined through quantification of doublecortin (DCX) positive cells. PbA-infected mice presented working memory impairment on day 5 post-infection. At this same time point, CM mice exhibited a decrease in DCX-positive cells in the dentate gyrus in parallel with increased cell death and elevated inflammatory cytokines (IL-6, TNF-α, IFN-γ and CCL11) in the hippocampus and frontal cortex. A significant reduction of BDNF mRNA expression was also found. IL-6 and TNF-α correlated negatively with BDNF and NGF levels in the hippocampus of CM mice. In summary, we provide further evidence that neuroinflammation following PbA-infection influences neurotrophin expression, impairs adult hippocampal neurogenesis and increases hippocampal cell death in association with memory impairment following CM course. The current study identified potential mediators of memory impairment in CM.

Pharmacological and toxicological studies of Drimys angustifolia Miers. (Winteraceae).

Drimys angustifolia Miers. (Winteraceae) is a Brazilian medicinal plant used as analgesic, antiulcer and anti-inflammatory without studies to assure its efficacy and safety Leaf and stem bark extracts were evaluated to determine the antiulcer, analgesic, antiinflammatory and antioxidant activities. Preliminary toxic effects and qualitative phytochemical profile were also performed. The antiulcer activity was detected in both extracts. Administration of the leaf extract at 250 mg/kg inhibited total lesion area by 76.50% (p < 0.01 in ethanol/HCl method), while carbenoxolone at 250 mg/kg reduced lesions by 69.48%. Stem bark extract (250 mg/kg) inhibited lesion by 81.42%, while carbenoxolone by 74.10%. Similar effects were observed in the ethanol-induced ulcer method, but no activity was observed in piroxican model. The effects involve nitric oxide in gastric protection, since the L-NAME treatment reversed the protection given by the extracts. Antioxidant effects suggest an involvement against oxidative stress. In the pain (writhing, tail-flick and hot-plate tests) and inflammation (carrageenan-induced paw edema) models, the extracts did not present any effect. The phytochemical studies demonstrated that both extracts contain flavonoids, saponins, glycosilated triterpenoids, fixed acids, cyanogenic glycosides, quinones, tannins, xanthone and steroidal aglycones. Toxicological studies showed that the extracts are safe at the effective antiulcer doses.

Vitamin E stimulates endotoxin-inhibited monocyte migration and phagocytosis in vivo.

Intravenous administration of E. coli endotoxin (LPS, 30 micrograms/kg, iv) inhibited thioglycollate-stimulated accumulation of monocytes into the rat peritoneal cavity, measured 48 and 72 h later, by about 40%. Pretreatment of animals with vitamin E (50 mg/kg, im) restored thioglycollate-induced monocyte migration in LPS-challenged rats to control levels. Vitamin E also partially reversed LPS-induced inhibition of monocyte phagocytosis in vivo. The results suggest that vitamin E could be beneficial in restoring leukocyte function in septicemic states.

Vitamin E stimulates endotoxin-inhibited monocyte migration and phagocytosis in vivo

Intravenous administration of E. coli endotoxin (LPS, 30 microng/kg, iv) inhibited thioglycollatestimulated accumulation of monocytes into the rat peritoneal cavity, measured 48 and 72 h later, by about 40%. Pretreatment of animals with vitamin E (50 mg/kg, im) restored thioglycollate-induced monocyte migration in LPS-challenged rats to control levels. Vitamin E also partially reversed LPS-induced inhibition of monocyte phagocytosis in vivo. The results suggest that vitamin E could be beneficial in restoring leukocyte function in septicemic states

Restoration by levamisole of endotoxin-inhibited neutrophil migration, oedema and increased vascular permeability induced by carrageenin.

Intravenous administration of E. coli lipopolysaccharide (LPS) inhibited the migration of neutrophils into the pleural cavity that occurs following challenge with intrapleural carrageenin. Treatment of animals with levamisole (10 mg/kg i.p.) 30 min after the intravenous administration of LPS almost restored carrageenin-induced neutrophil migration to control levels without affecting the number of circulating neutrophils. Intravenous administration of LPS (30 micrograms/kg) blocked neutrophil migration in vivo and significantly reduced the oedema and the increased vascular permeability induced by intraplantar administration of carrageenin. These LPS effects were partly counteracted by levamisole (10 mg/kg) given 30 min after LPS. Intravenous LPS did neither affect oedema nor the increase in vascular permeability induced by intraplantar administration of dextran. It is suggested that (a) the exudation and oedema formation induced by carrageenin partially depend upon migrating neutrophils and (b) inhibition of cell migration by circulating LPS may constitute an important contributing factor in septicaemia. Levamisole restores both cell migration and vascular inflammatory events inhibited by circulating LPS.