Food-Grade Metal Oxide Nanoparticles Exposure Alters Intestinal Microbial Populations, Brush Border Membrane Functionality and Morphology, In Vivo (Gallus gallus).

Among food additive metal oxide nanoparticles (NP), titanium dioxide (TiO2) and silicon dioxide (SiO2) are commonly used as food coloring or anti-caking agents, while zinc oxide (ZnO) and iron oxide (Fe2O3) are added as antimicrobials and coloring agents, respectively, and can be used as micronutrient supplements. To elucidate potential perturbations associated with NP consumption on gastrointestinal health and development, this in vivo study utilized the Gallus gallus (broiler chicken) intraamniotic administration to assess the effects of physiologically relevant concentrations of food-grade metal oxide NP on brush border membrane (BBM) functionality, intestinal morphology and intestinal microbial populations in vivo. Six groups with 1 mL injection of the following treatments were utilized: non-injected, 18 MΩ DI H2O; 1.4 × 10-6 mg TiO2 NP/mL, 2.0 × 10-5 mg SiO2 NP/mL, 9.7 × 10-6 mg ZnO NP/mL, and 3.8 × 10-4 mg Fe2O3 NP/mL (n = 10 per group). Upon hatch, blood, cecum, and duodenum were collected to assess mineral (iron and zinc) metabolism, BBM functional, and pro-inflammatory-related protein gene expression, BBM morphometric analysis, and the relative abundance of intestinal microflora. Food additive NP altered mineral transporter, BBM functionality, and pro-inflammatory cytokine gene expression, affected intestinal BBM development and led to compositional shifts in intestinal bacterial populations. Our results suggest that food-grade TiO2 and SiO2 NP have the potential to negatively affect intestinal functionality; food-grade ZnO NP exposure effects were associated with supporting intestinal development or compensatory mechanisms due to intestinal damage, and food-grade Fe2O3 NP was found to be a possible option for iron fortification, though with potential alterations in intestinal functionality and health.

Treatment with biological therapy is associated with faster recovery and lower frequency of treatment switch among rheumatic patients with Chikungunya fever.

BACKGROUND/OBJECTIVE: The effects of Chikungunya virus (CHIKV) infection on patients with rheumatic diseases have not been extensively studied. Our aim was to compare the clinical course of patients with rheumatoid arthritis and spondyloarthritis, categorized according to the use or not of biologic disease modifying anti-rheumatic drugs (bDMARDs), during and after infection by CHIKV. METHODS: Patients from a northeastern Brazilian city that suffered an epidemic outbreak of Chikungunya fever (CHIK) between Oct 2015 and Jul 2016, on regular follow-up in a longitudinal registry of rheumatic patients (BiobadaBrasil), were invited to participate. Participants underwent a standardized clinical interview and collection of blood sample for serological tests (IgM/IgG) for CHIKV. A positive IgG was considered evidence of previous CHIKV infection. RESULTS: 105 patients (84 with rheumatoid arthritis, 17 with ankylosing spondylitis, and 4 with psoriatic arthritis) were evaluated. Most patients (58, 55.2%) were on therapy with bDMARDs. The overall prevalence of seropositivity for CHIKV was 47.6% (39.7% in patients on bDMARDs and 57.4% in those exclusively on conventional synthetic (cs-) DMARDs (p = 0.070). Among seropositive patients, asymptomatic disease had similar frequency in those treated and not treated with bDMARDs (39.1% versus 33.3%, respectively; p = 0.670). However, patients exclusively on csDMARDs presented significantly higher prevalence of articular symptoms beyond 3 months and switched treatment more often than patients on bDMARDs (p < 0.05 for both comparisons). CONCLUSIONS: Among rheumatic patients with CHIK, those on bDMARDs had shorter persistence of articular symptoms and switched treatment scheme less often than patients exclusively treated with csDMARDs.

Fisioterapia associada à terapia assistida por animais em criança com paralisia cerebral: estudo de caso / Physical therapy associated with animal assisted therapy in child with cerebral palsy:casestudy

Introdução: A terapia com cães, assim como outros animais utilizados para fins terapêuticos, torna a fisioterapia mais prazerosa e está associada a benefícios na postura e movimento, esquema corporal, coordenação motora e funcionalidade nas atividades da vida diária. Objetivo: Buscou-se investigar o efeito da Terapia Assistida por Animais (TAA) no equilíbrio, funcionalidade e simetria postural de uma criança com Paralisia Cerebral. Métodos: Uma criança de seis anos em intervenção fisioterapêutica baseada na TAA. Para o nível de motricidade fina e grossa, foi utilizado o Gross Motor Function Classification System (GMFCS), para as atividades de vida diária, o Pediatric Evaluation of Disability Inventory (PEDI), e para o equilíbrio postural, a Pediatric Balance Scale (PBS). O alinhamento postural foi avaliado por fotogrametria e a análise postural foi realizada por meio do software para avaliação postural (SAPO). Resultados: Houve melhora na funcionalidade, equilíbrio estático e dinâmico, alinhamento corporal no plano coronal, identificando alterações na simetria corporal dos segmentos corporais e plano sagital, com deslocamento dos eixos pescoço, tronco e quadril. Conclusão: A intervenção com o cão teve efeitos positivos nas habilidades funcionais de uma criança com paralisia cerebral, sendo a estratégia terapêutica eficaz no equilíbrio, seja na manutenção da postura e/ou movimento, com maior independência funcional e, portanto, menor necessidade de supervisão.

Brazilian Society of Rheumatology 2020 guidelines for psoriatic arthritis.

Psoriatic arthritis (PsA) is a chronic and systemic immune disease characterized by inflammation of peripheral and/or axial joints and entheses in patients with psoriasis (PsO). Extra-articular and extracutaneous manifestations and numerous comorbidities can also be present. These recommendations replace the previous version published in May 2013. A systematic review of the literature retrieved 191 articles that were used to formulate 12 recommendations in response to 12 clinical questions, divided into 4 sections: diagnosis, non-pharmacological treatment, conventional drug therapy and biologic therapy. These guidelines provide evidence-based information on the clinical management for PsA patients. For each recommendation, the level of evidence (highest available), degree of strength (Oxford) and degree of expert agreement (interrater reliability) are reported.

The Brazilian Society of Rheumatology guidelines for axial spondyloarthritis - 2019.

Spondyloarthritis is a group of chronic inflammatory systemic diseases characterized by axial and/or peripheral joints inflammation, as well as extra-articular manifestations. The classification axial spondyloarthritis is adopted when the spine and/or the sacroiliac joints are predominantly involved. This version of recommendations replaces the previous guidelines published in May 2013.A systematic literature review was performed, and two hundred thirty-seven studies were selected and used to formulate 29 recommendations answering 15 clinical questions, which were divided into four sections: diagnosis, non-pharmacological therapy, conventional drug therapy and biological therapy. For each recommendation the level of evidence supporting (highest available), the strength grade according to Oxford, and the degree of expert agreement (inter-rater reliability) is informed.These guidelines bring evidence-based information on clinical management of axial SpA patients, including, diagnosis, treatment, and prognosis.

Gut microbiota modulation accounts for the neuroprotective properties of anthocyanins.

High-fat (HF) diets are thought to disrupt the profile of the gut microbiota in a manner that may contribute to the neuroinflammation and neurobehavioral changes observed in obesity. Accordingly, we hypothesize that by preventing HF-diet induced dysbiosis it is possible to prevent neuroinflammation and the consequent neurological disorders. Anthocyanins are flavonoids found in berries that exhibit anti-neuroinflammatory properties in the context of obesity. Here, we demonstrate that the blackberry anthocyanin-rich extract (BE) can modulate gut microbiota composition and counteract some of the features of HF-diet induced dysbiosis. In addition, we show that the modifications in gut microbial environment are partially linked with the anti-neuroinflammatory properties of BE. Through fecal metabolome analysis, we unravel the mechanism by which BE participates in the bilateral communication between the gut and the brain. BE alters host tryptophan metabolism, increasing the production of the neuroprotective metabolite kynurenic acid. These findings strongly suggest that dietary manipulation of the gut microbiota with anthocyanins can attenuate the neurologic complications of obesity, thus expanding the classification of psychobiotics to anthocyanins.

Sex-specific effects of dehydroepiandrosterone (DHEA) on glucose metabolism in the CNS.

DHEA is a neuroactive steroid, due to its modulatory actions on the central nervous system (CNS). DHEA is able to regulate neurogenesis, neurotransmitter receptors and neuronal excitability, function, survival and metabolism. The levels of DHEA decrease gradually with advancing age, and this decline has been associated with age related neuronal dysfunction and degeneration, suggesting a neuroprotective effect of endogenous DHEA. There are significant sex differences in the pathophysiology, epidemiology and clinical manifestations of many neurological diseases. The aim of this study was to determine whether DHEA can alter glucose metabolism in different structures of the CNS from male and female rats, and if this effect is sex-specific. The results showed that DHEA decreased glucose uptake in some structures (cerebral cortex and olfactory bulb) in males, but did not affect glucose uptake in females. When compared, glucose uptake in males was higher than females. DHEA enhanced the glucose oxidation in both males (cerebral cortex, olfactory bulb, hippocampus and hypothalamus) and females (cerebral cortex and olfactory bulb), in a sex-dependent manner. In males, DHEA did not affect synthesis of glycogen, however, glycogen content was increased in the cerebral cortex and olfactory bulb. DHEA modulates glucose metabolism in a tissue-, dose- and sex-dependent manner to increase glucose oxidation, which could explain the previously described neuroprotective role of this hormone in some neurodegenerative diseases.

Effect of chronic consumption of blackberry extract on high-fat induced obesity in rats and its correlation with metabolic and brain outcomes.

Flavonoids have been presented as potential protectors against metabolic and cognitive dysfunction. However, mechanisms underlying these 'claims' have not been sufficiently explored. To analyse the effect of long-term supplementation with blackberry extract (BE) in the context of a high-fat or a standard diet, Wistar rats were divided into 4 groups (n = 6) fed with a standard or a high-fat diet, with or without BE supplementation at 25 mg per kg body weight per day. A high-fat diet significantly impaired glucose tolerance and increased body weight, caloric ingestion, very-low-density lipoprotein, triglycerides and cholesterol. Furthermore, it was observed that a high-fat diet increased dopamine content in the prefrontal cortex and decreased brain derived neurotrophic factor (BDNF) levels both in the prefrontal cortex and in plasma. BE supplementation only affected some of these aspects. BE slightly improved glucose metabolism and significantly decreased levels of lactate, independent of diet. BE decreased levels of BDNF and also interacted with the dopaminergic system, increasing dopamine turnover in the striatum, and reverting dopamine content induced by a high-fat diet in the prefrontal cortex. This study shows that, despite some particular benefits of anthocyanin supplementation, some long-term effects may not be desirable and further studies are needed to optimize ingestion conditions.

The impact of chronic blackberry intake on the neuroinflammatory status of rats fed a standard or high-fat diet.

Neuroinflammation has been suggested as a central mediator of central nervous system dysfunction, including in dementia and neurodegenerative disease. Flavonoids have emerged as promising candidates for the prevention of neurodegenerative diseases and are thought to be capable of antiinflammatory effects in the brain. In the present study, the impact of a chronic intake of an anthocyanin extract from blackberry (BE) on brain inflammatory status in the presence or absence of a high-fat diet was investigated. Following intake of the dietary regimes for 17 weeks neuroinflammatory status in Wistar rat cortex, hippocampus and plasma were assessed using cytokine antibody arrays. In the cortex, intake of the high-fat diet resulted in an increase of at least 4-fold, in expression of the cytokine-induced neutrophil chemoattractant CINC-3, the ciliary neurotrophic factor CNTF, the platelet-derived growth factor PDGF-AA, IL-10, the tissue inhibitor of metalloproteinase TIMP-1 and the receptor for advanced glycation end products RAGE. BE intake partially decreased the expression of these mediators in the high-fat challenged brain. In standard-fed animals, BE intake significantly increased cortical levels of fractalkine, PDGF-AA, activin, the vascular endothelial growth factor VEGF and agrin expression, suggesting effects as neuronal growth and synaptic connection modulators. In hippocampus, BE modulates fractalkine and the thymus chemokine TCK-1 expression independently of diet intake and, only in standard diet, increased PDGF-AA. Exploring effects of anthocyanins on fractalkine transcription using the neuronal cell line SH-SY5Y suggested that other cell types may be involved in this effect. This is the first evidence, in in vivo model, that blackberry extract intake may be capable of preventing the detrimental effects of neuroinflammation in a high-fat challenged brain. Also, fractalkine and TCK-1 expression may be specific targets of anthocyanins and their metabolites on neuroinflammation.

Superoxide dismutase enzymosomes: carrier capacity optimization, in vivo behaviour and therapeutic activity.

PURPOSE: A strategy not usually used to improve carrier-mediated delivery of therapeutic enzymes is the attachment of the enzymes to the outer surface of liposomes. The aim of our work was to design a new type of enzymosomes with a sufficient surface-exposed enzyme load while preserving the structural integrity of the liposomal particles and activity of the enzyme. METHODS: The therapeutic antioxidant enzyme superoxide dismutase (SOD) was covalently attached to the distal terminus of polyethylene glycol (PEG) polymer chains, located at the surface of lipid vesicles, to obtain SOD-enzymosomes. RESULTS: The in vivo fate of the optimized SOD-enzymosomes showed that SOD attachment at the end of the activated PEG slightly reduced the residence time of the liposome particles in the bloodstream after IV administration. The biodistribution studies showed that SOD-enzymosomes had a similar organ distribution profile to liposomes with SOD encapsulated in their aqueous interior (SOD-liposomes). SOD-enzymosomes showed earlier therapeutic activity than both SOD-liposomes and free SOD in rat adjuvant arthritis. SOD-enzymosomes, unlike SOD-liposomes, have a therapeutic effect, decreasing liver damage in a rat liver ischemia/reperfusion model. CONCLUSIONS: SOD-enzymosomes were shown to be a new and successful therapeutic approach to oxidative stress-associated inflammatory situations/diseases.