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1.
Pediatr Allergy Immunol ; 34(2): e13911, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36825745

RESUMO

The neonatal immune ontogeny begins during pregnancy to ensure that the neonate is well-suited for perinatal life. It prioritizes Th2/M2 and regulatory responses over Th/M1 activity to avoid excessive inflammatory responses and to ensure immune tolerance and homeostasis. Newborns also present increased Th17/Th22 responses providing effective anti-fungal immunity and mucosal protection. Intrauterine exposure to immune modulatory drugs with the placental transfer may influence the natural course of the fetal immune development. The vertical transfer of both biological therapy and small molecules begins during the first trimester through neonatal Fc receptor or placental diffusion, respectively, reaching its maximum transfer potential during the third trimester of pregnancy. Most of the biological therapy have a prolonged half-life in newborn's blood, being detectable in infants up to 12 months after birth (usually 6-9 months). The use of immunomodulators during pregnancy is gaining global interest. Current evidence mainly reports birth-related outcomes without exhaustive analysis of the on-target side effect on the perinatal immune system ontogeny, the infection risk, or the immune dysregulation. The present review will focus on: (1) the main characteristics of the perinatal immune system to understand its specific features and vulnerabilities to immune modulation; (2) the mechanisms of placental transfer of immunomodulators; and (3) the immune changes reported to date in newborns exposed to immunomodulators with emphasis on the current concerns and gaps in knowledge.


Assuntos
Agentes de Imunomodulação , Placenta , Lactente , Gravidez , Recém-Nascido , Humanos , Feminino , Parto
2.
Gastroenterology ; 157(1): 149-162, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30905652

RESUMO

BACKGROUND & AIMS: We investigated the effect of albumin treatment (20% solution) on hypoalbuminemia, cardiocirculatory dysfunction, portal hypertension, and systemic inflammation in patients with decompensated cirrhosis with and without bacterial infections. METHODS: We performed a prospective study to assess the effects of long-term (12 weeks) treatment with low doses (1 g/kg body weight every 2 weeks) and high doses (1.5 g/kg every week) of albumin on serum albumin, plasma renin, cardiocirculatory function, portal pressure, and plasma levels of cytokines, collecting data from 18 patients without bacterial infections (the Pilot-PRECIOSA study). We also assessed the effect of short-term (1 week) treatment with antibiotics alone vs the combination of albumin plus antibiotics (1.5 g/kg on day 1 and 1 g/kg on day 3) on plasma levels of cytokines in biobanked samples from 78 patients with bacterial infections included in a randomized controlled trial (INFECIR-2 study). RESULTS: Circulatory dysfunction and systemic inflammation were extremely unstable in many patients included in the Pilot-PRECIOSA study; these patients had intense and reversible peaks in plasma levels of renin and interleukin 6. Long-term high-dose albumin, but not low-dose albumin, was associated with normalization of serum level of albumin, improved stability of the circulation and left ventricular function, and reduced plasma levels of cytokines (interleukin 6, granulocyte colony-stimulating factor, interleukin 1 receptor antagonist, and vascular endothelial growth factor) without significant changes in portal pressure. The immune-modulatory effects of albumin observed in the Pilot-PRECIOSA study were confirmed in the INFECIR-2 study. In this study, patients given albumin had significant reductions in plasma levels of cytokines. CONCLUSIONS: In an analysis of data from 2 trials (Pilot-PRECIOSA study and INFECIR-2 study), we found that albumin treatment reduced systemic inflammation and cardiocirculatory dysfunction in patients with decompensated cirrhosis. These effects might be responsible for the beneficial effects of albumin therapy on outcomes of patients with decompensated cirrhosis. ClinicalTrials.gov, Numbers: NCT00968695 and NCT03451292.


Assuntos
Albuminas/administração & dosagem , Infecções Bacterianas/imunologia , Citocinas/imunologia , Hipertensão Portal/fisiopatologia , Hipoalbuminemia/tratamento farmacológico , Cirrose Hepática/tratamento farmacológico , Albumina Sérica/metabolismo , Infecções Bacterianas/complicações , Infecções Bacterianas/fisiopatologia , Estudos de Casos e Controles , Feminino , Hemodinâmica , Humanos , Hipertensão Portal/etiologia , Hipoalbuminemia/etiologia , Hipoalbuminemia/imunologia , Hipoalbuminemia/fisiopatologia , Inflamação , Circulação Hepática , Cirrose Hepática/complicações , Cirrose Hepática/imunologia , Cirrose Hepática/fisiopatologia , Masculino , Pessoa de Meia-Idade , Pressão na Veia Porta , Sistema Porta , Estudos Prospectivos , Renina/sangue
3.
Alzheimers Dement ; 16(10): 1412-1425, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32715623

RESUMO

INTRODUCTION: This phase 2b/3 trial examined the effects of plasma exchange (PE) in patients with mild-to-moderate Alzheimer's disease (AD). METHODS: Three hundred forty-seven patients (496 screened) were randomized (1:1:1:1) into three PE treatment arms with different doses of albumin and intravenous immunoglobulin replacement (6-week period of weekly conventional PE followed by a 12-month period of monthly low-volume PE), and placebo (sham). RESULTS: PE-treated patients performed significantly better than placebo for the co-primary endpoints: change from baseline of Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL; P = .03; 52% less decline) with a trend for Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog; P = .06; 66% less decline) scores at month 14. Moderate-AD patients (baseline Mini-Mental State Examination [MMSE] 18-21) scored better on ADCS-ADL (P = .002) and ADAS-Cog (P = .05), 61% less decline both. There were no changes in mild-AD patients (MMSE 22-26). PE-treated patients scored better on the Clinical Dementia Rating Sum of Boxes (CDR-sb) (P = .002; 71% less decline) and Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) (P < .0001; 100% less decline) scales. DISCUSSION: This trial suggests that PE with albumin replacement could slow cognitive and functional decline in AD, although further studies are warranted.


Assuntos
Doença de Alzheimer/terapia , Troca Plasmática/métodos , Idoso , Idoso de 80 Anos ou mais , Albuminas/administração & dosagem , Disfunção Cognitiva , Feminino , Humanos , Imunoglobulinas Intravenosas/administração & dosagem , Masculino , Pessoa de Meia-Idade
5.
Cir Esp ; 95(9): 536-541, 2017 Nov.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-29033071

RESUMO

INTRODUCTION: Currently, there is no agreement regarding if it would be necessary to perform an axillary lymph node dissection (ALND) in patients who have macrometastases in the sentinel lymph node (SLN). We studied the utility of the secondary node analysis (SN), defined as the following node after the SLN in an anatomical and lymphatic pathway, as a sign of malignant axillary involvement. METHODS: An observational, retrospective and multicentre study was designed to assess the utility of the SN as a sign of axillary involvement. Among 2273 patients with breast cancer, a valid sample of 283 was obtained representing those who had the SN studied. Main endpoints of our study were: the SLN, the SN and the ALND histological pattern. Sensitivity, specificity and precision of the test were also calculated. RESULTS: SN test, in cases with positive SLN, has a sensitivity of 61.1%, a specificity of 78.7%, a positive predictive value of 45.8% and a negative predictive value of 87.3% with a precision of 74.7%. CONCLUSION: The study of the SN together with the technique of the SLN allows a more precise staging of the axillary involvement, in patients with breast cancer, than just the SLN technique.


Assuntos
Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Excisão de Linfonodo , Biópsia de Linfonodo Sentinela , Axila , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos
6.
Rev Esp Enferm Dig ; 107(1): 39-40, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25603331

RESUMO

Systemic lupus erithematosus (SLE) is an autoimmune disease with multiorgan involvement caused principally by vasculitis of small vessels. The gastrointestinal tract is one of the most frequently affected by SLE, with abdominal pain as the most common symptom. An early diagnosis and treatment of lupus enteritis is essential to avoid complications like hemorrhage or perforation, with up to 50 % of mortality rate. However, differential diagnosis sometimes is difficult, especially with other types of gastrointestinal diseases as digestive involvement of antiphospholipid syndrome (APS), moreover when both entities may coexist. We describe the case of a patient with both diseases that was diagnosed with lupus enteritis and treated with steroid therapy; the patient had an excellent response.


Assuntos
Abdome Agudo/etiologia , Neoplasias Intestinais/complicações , Linfangioma/complicações , Humanos , Neoplasias Intestinais/patologia , Jejuno/patologia , Jejuno/cirurgia , Laparotomia , Linfonodos/patologia , Linfangioma/patologia , Masculino , Mesentério , Pessoa de Meia-Idade
7.
JHEP Rep ; 6(4): 101017, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38544553

RESUMO

Background & Aims: Effective treatments for acute-on-chronic liver failure (ACLF) are a major unmet need. This proof-of-concept pilot study was aimed at evaluating the effects of plasma exchange (PE) with albumin 5% (PE-A5%) on albumin functional capacity and organ dysfunction in patients with ACLF. Methods: Ten adult patients were enrolled in a single-center phase II, prospective, open-label, non-controlled study. Six PE-A5% sessions were performed in 10 days followed by a 1-month follow-up visit. Albumin functional capacity and circulatory function were assessed, as were renal, cerebral, and liver function, and systemic inflammation. The main safety variable was the percentage of PE sessions associated with at least one procedure-related adverse event (AE). Results: Patients with ACLF showed lower albumin binding capacity, lower antioxidant capacity, and lower levels of albumin with preserved structure compared to healthy donors (n = 19). From baseline to day 11, PE-A5% treatment increased albumin levels and improved albumin binding capacity to Sudlow site II (15.3±1.6 mg/ml to 18.9±1.7 mg/ml; p = 0.003), fatty acid-binding capacity (8.2±1.4 µM to 3.1±1.5 µM; p = 0.013) and antioxidant capacity (human mercaptalbumin 9.5±1.5 mg/ml to 14.6±1.6 mg/ml; p = 0.001). Native albumin levels were increased throughout day 1-11 PE-A5% sessions (6.5±1.0 mg/ml to 10.2±1.4 mg/ml; p = 0.035). PE-A5% improved systemic hemodynamics (mean arterial pressure, heart rate, cardiac index), renal function (creatinine level, blood urea nitrogen), cerebral function (hepatic encephalopathy grade), liver parameters (transaminases, bilirubin) and inflammatory parameters (C-reactive protein, leukocyte count). All patients had at least one of the 78 AEs reported, mostly mild (product/procedure-related: 36%). Sixteen serious AEs were reported in eight patients (procedure/product-related: none). Conclusions: PE-A5% was a safe procedure associated with positive effects on albumin functionality, and circulatory, renal, cerebral, and liver function in patients with ACLF. Impact and implications: Acute-on-chronic liver failure (ACLF) is a clinical condition characterized by severe systemic inflammation, organ failure, and high mortality. Plasma exchange removes patient's plasma containing pathogenic substances, replacing it with 5% albumin and fresh frozen plasma (PE-A5%). In this study, cirrhotic patients with ACLF were treated with PE-A5%, which was a safe procedure that increased binding and antioxidant capacity of patients' albumin, while improving circulatory, kidney, brain, and liver functions. These beneficial effects could impact survival in ACLF. ClinicalTrialsgov Identifier: NCT01201720. EudraCT number: 2010-021360-15.

8.
EClinicalMedicine ; 57: 101898, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36936402

RESUMO

Background: Anti-COVID-19 hyperimmune immunoglobulin (hIG) can provide standardized and controlled antibody content. Data from controlled clinical trials using hIG for the prevention or treatment of COVID-19 outpatients have not been reported. We assessed the safety and efficacy of subcutaneous anti-COVID-19 hyperimmune immunoglobulin 20% (C19-IG20%) compared to placebo in preventing development of symptomatic COVID-19 in asymptomatic individuals with SARS-CoV-2 infection. Methods: We did a multicentre, randomized, double-blind, placebo-controlled trial, in asymptomatic unvaccinated adults (≥18 years of age) with confirmed SARS-CoV-2 infection within 5 days between April 28 and December 27, 2021. Participants were randomly assigned (1:1:1) to receive a blinded subcutaneous infusion of 10 mL with 1 g or 2 g of C19-IG20%, or an equivalent volume of saline as placebo. The primary endpoint was the proportion of participants who remained asymptomatic through day 14 after infusion. Secondary endpoints included the proportion of individuals who required oxygen supplementation, any medically attended visit, hospitalisation, or ICU, and viral load reduction and viral clearance in nasopharyngeal swabs. Safety was assessed as the proportion of patients with adverse events. The trial was terminated early due to a lack of potential benefit in the target population in a planned interim analysis conducted in December 2021. ClinicalTrials.gov registry: NCT04847141. Findings: 461 individuals (mean age 39.6 years [SD 12.8]) were randomized and received the intervention within a mean of 3.1 (SD 1.27) days from a positive SARS-CoV-2 test. In the prespecified modified intention-to-treat analysis that included only participants who received a subcutaneous infusion, the primary outcome occurred in 59.9% (91/152) of participants receiving 1 g C19-IG20%, 64.7% (99/153) receiving 2 g, and 63.5% (99/156) receiving placebo (difference in proportions 1 g C19-IG20% vs. placebo, -3.6%; 95% CI -14.6% to 7.3%, p = 0.53; 2 g C19-IG20% vs placebo, 1.1%; -9.6% to 11.9%, p = 0.85). None of the secondary clinical efficacy endpoints or virological endpoints were significantly different between study groups. Adverse event rate was similar between groups, and no severe or life-threatening adverse events related to investigational product infusion were reported. Interpretation: Our findings suggested that administration of subcutaneous human hyperimmune immunoglobulin C19-IG20% to asymptomatic individuals with SARS-CoV-2 infection was safe but did not prevent development of symptomatic COVID-19. Funding: Grifols.

9.
Alzheimers Dement (N Y) ; 5: 61-69, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30859122

RESUMO

INTRODUCTION: Preliminary studies have shown that treatment with plasma exchange (PE) plus therapeutic albumin replacement in patients with Alzheimer's disease (AD) induced mobilization of plasma and cerebrospinal fluid amyloid ß protein, associated with an improvement in memory and language functions, as well as the stabilization of brain perfusion, which persisted after treatment discontinuation. METHODS: Alzheimer's Management By Albumin Replacement (AMBAR) is a multicenter, randomized, blinded and placebo-controlled, parallel-group, phase IIb/III trial enrolling patients with mild to moderate AD. The study evaluates PE with different replacement volumes of therapeutic albumin (5% and 20% Albutein®, Grifols), with or without intravenous immunoglobulin (Flebogamma® 5% DIF, Grifols). Patients are randomized to one of three active treatment groups or one control (sham PE) group (1:1:1:1). The intervention regime includes a first 6-week stage of intensive treatment, followed by a second 12-month stage of maintenance treatment. The change from the baseline to the end of treatment periods in the ADAS-Cog and ADCS-ADL scores are the coprimary efficacy variables. Secondary efficacy variables include change from the baseline in scores on cognitive, functional, behavioral, and overall progression tests; changes in plasma and cerebrospinal fluid levels of amyloid ß and tau protein; and assessment of structural and functional changes in brain areas of interest. Safety and tolerability are assessed. RESULTS: The study has enrolled 496 patients from 41 centers (19 in Spain and 22 in the USA); 347 of these patients were randomized and underwent close to 5000 PEs, of which approximately 25% were sham PEs. DISCUSSION: We present an innovative approach for treating AD. The study has been designed to demonstrate clinical efficacy, defined as slow decline of the patient's cognition and brain function. The sample size has adequate power to detect differences between any of the active treatment groups and the control group, as well as between the three active treatment groups combined and the control group.

10.
J Alzheimers Dis ; 61(1): 321-332, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29154283

RESUMO

BACKGROUND: Recently, modifications of Aß1-42 levels in CSF and plasma associated with improvement in memory and language functions have been observed in patients with mild-moderate Alzheimer's disease (AD) treated with plasma exchange (PE) with albumin replacement. OBJECTIVE: To detect structural and functional brain changes in PE-treated AD patients as part of a Phase II clinical trial. METHODS: Patients received between 3 and 18 PE with albumin (Albutein® 5%, Grifols) or sham-PE (controls) for 21 weeks (divided in one intensive and two maintenance periods) followed by 6-month follow-up. Brain perfusion assessed by SPECT scans using an automated software (NeuroGam®) and brain structural changes assessed by MRI were performed at weeks 0 (baseline), 21, and 44 (with additional SPECT at weeks 9 and 33). Statistical parametric mapping (voxel-based analysis, SPM) and Z-scores calculations were applied to investigate changes to baseline. RESULTS: 42 patients were recruited (39 evaluable; 37 analyzed: 18 PE-treated; 19 controls). There was a trend toward decreasing hippocampi and total intracranial volume for both patient groups during the study (p < 0.05). After six months, PE-treated patients had less cerebral perfusion loss than controls in frontal, temporal, and parietal areas, and perfusion stabilization in Brodmann area BA38-R during the PE-treatment period (p < 0.05). SPM analysis showed stabilization or absence of progression of perfusion loss in PE-treated patients until week 21, not observed in controls. CONCLUSIONS: Mild-moderate AD patients showed decreased brain volume and impairment of brain perfusion as expected for the progression of the disease. PE-treatment with albumin replacement favored the stabilization of perfusion.


Assuntos
Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/terapia , Neuroimagem/métodos , Troca Plasmática/métodos , Albumina Sérica Humana/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Tomografia Computadorizada de Emissão de Fóton Único , Resultado do Tratamento
11.
J Agric Food Chem ; 55(3): 779-86, 2007 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-17263474

RESUMO

In recent years, the wine industry has become increasingly interested in the influence of the terroir characteristics on the features of a wine and, in particular, the mechanisms by which a soil influences wine quality. Among published papers on this topic, most merely describe the effect of the soil; few explain it. In this study were conducted a sensory evaluation and phenolic composition and stilbene concentration tests in order to analyze the effects of soil on wine. Significant differences were found in the results of the tests conducted on two vineyards during two consecutive harvests in 2004 and 2005. The results, in line with previous reports, show that the more fertile of the two vineyards, which was also the one with the greatest water-holding capacity, produced wines that presented significantly lower color intensity and shade, as well as lower total phenolic composition and a smaller quantity of hydroxycinnamic compounds. In 2004, these wines presented significantly higher trans-resveratrol content, due to a fungal attack that was favored by the vineyard's soil characteristics. Extreme drought conditions in 2005 had a marked impact on the characteristics of the wines, increasing wavelength measurements significantly and reducing stilbene concentrations. Finally, sensory evaluations revealed significant differences between the wines produced on the two vineyards in both years for five of the seven attributes evaluated. No significant differences were found from one year to the next between the wines produced from the same vineyard, indicating that the attributes of these wines were maintained despite markedly different vintage conditions.


Assuntos
Frutas/química , Solo/análise , Vitis/química , Vitis/crescimento & desenvolvimento , Vinho/análise , Adulto , Humanos , Pessoa de Meia-Idade , Fenóis/análise , Estilbenos/análise , Paladar , Fatores de Tempo , Água
12.
J Alzheimers Dis ; 56(1): 129-143, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27911295

RESUMO

BACKGROUND: Studies conducted in animal models and humans suggest the presence of a dynamic equilibrium of amyloid-ß (Aß) peptide between cerebrospinal fluid (CSF) and plasma compartments. OBJECTIVE: To determine whether plasma exchange (PE) with albumin replacement was able to modify Aß concentrations in CSF and plasma as well as to improve cognition in patients with mild-moderate Alzheimer's disease (AD). METHODS: In a multicenter, randomized, patient- and rater-blind, controlled, parallel-group, phase II study, 42 AD patients were assigned (1 : 1) to PE treatment or control (sham) groups. Treated patients received a maximum of 18 PE with 5% albumin (Albutein®, Grifols) with three different schedules: two PE/weekly (three weeks), one PE/weekly (six weeks), and one PE/bi- weekly (12 weeks), plus a six-month follow-up period. Plasma and CSF Aß1-40 and Aß1-42 levels, as well as cognitive, functional, and behavioral measures were determined. RESULTS: CSF Aß1-42 levels after the last PE compared to baseline were marginally higher in PE-treated group versus controls (adjusted means of variation: 75.3 versus -45.5 pg/mL; 95% CI: -19.8, 170.5 versus 135.1, 44.2; p = 0.072). Plasma Aß1-42 levels were lower in the PE-treated group after each treatment period (p < 0.05). Plasma Aß1-40 levels showed a saw-tooth pattern variation associated with PE. PE-treated patients scored better in the Boston Naming Test and Semantic Verbal Fluency (p < 0.05) throughout the study. Neuropsychiatric Inventory scores were higher in controls during the PE phase (p < 0.05). CONCLUSION: PE with human albumin modified CSF and plasma Aß1-42 levels. Patients treated with PE showed improvement in memory and language functions, which persisted after PE was discontinued.


Assuntos
Albuminas/uso terapêutico , Peptídeos beta-Amiloides/sangue , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Transtornos Cognitivos/terapia , Troca Plasmática/métodos , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/complicações , Doença de Alzheimer/diagnóstico por imagem , Transtornos Cognitivos/diagnóstico por imagem , Feminino , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Escalas de Graduação Psiquiátrica , Tomógrafos Computadorizados
13.
Food Funct ; 6(4): 1288-98, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25761658

RESUMO

Grape-derived polyphenols are considered to be one of the most promising ingredients for functional foods due to their health-promoting activities. We applied a HPLC-MS-based untargeted metabolomic approach in order to evaluate the impact of a functional food based on grape skin polyphenols on the urinary metabolome of healthy subjects. Thirty-one volunteers participated in two dietary crossover randomized intervention studies: with a single-dose intake (187 mL) and with a 15-day sustained consumption (twice per day, 187 mL per day in total) of a functional beverage (FB). Postprandial (4-hour) and 24-hour urine samples collected after acute consumption and on the last day of sustained FB consumption, respectively, were analysed using an untargeted HPLC-qTOF-MS approach. Multivariate modelling with subsequent application of an S-plot revealed differential mass features related to acute and prolonged consumption of FB. More than half of the mass features were shared between the two types of samples, among which several phase II metabolites of grape-derived polyphenols were identified at confidence level II. Prolonged consumption of FB was specifically reflected in urine metabolome by the presence of first-stage microbial metabolites of flavanols: hydroxyvaleric acid and hydroxyvalerolactone derivatives. Overall, several epicatechin and phenolic acid metabolites both of tissular and microbiota origin were the most representative markers of FB consumption. To our knowledge, this is one of the first studies where an untargeted LC-MS metabolomic approach has been applied in nutrition research on a grape-derived FB.


Assuntos
Bebidas/análise , Alimento Funcional/análise , Metaboloma , Extratos Vegetais/análise , Vitis/química , Adulto , Biomarcadores/urina , Cromatografia Líquida de Alta Pressão , Estudos Cross-Over , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Voluntários Saudáveis , Humanos , Hidroxibenzoatos/análise , Hidroxibenzoatos/farmacologia , Masculino , Espectrometria de Massas , Metabolômica , Pessoa de Meia-Idade , Análise Multivariada , Extratos Vegetais/administração & dosagem , Polifenóis/administração & dosagem , Polifenóis/análise , Período Pós-Prandial , Análise de Componente Principal
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