RESUMO
Recent discoveries have shown that enteric glial cells play an important role in different neurodegenerative disorders, such as Parkinson's disease (PD), which is characterized by motor dysfunctions caused by the progressive loss of dopaminergic neurons in the substance nigra pars compacta and non-motor symptoms including gastrointestinal dysfunction. In this study, we investigated the modulatory effects of the flavonoid rutin on the behavior and myenteric plexuses in a PD animal model and the response of enteric glia. Adult male Wistar rats were submitted to stereotaxic injection with 6-hydroxydopamine or saline, and they were untreated or treated with rutin (10 mg/kg) for 14 days. The ileum was collected to analyze tissue reactivity and immunohistochemistry for neurons (HuC/HuD) and enteric glial cells (S100ß) in the myenteric plexuses. Behavioral tests demonstrated that treatment with rutin improved the motor capacity of parkinsonian animals and improved intestinal transit without interfering with the cell population; rutin treatment modulated the reactivity of the ileal musculature through muscarinic activation, reducing relaxation through the signaling pathway of nitric oxide donors, and increased the longitudinal contractility of the colon musculature in parkinsonian animals. Rutin revealed modulatory activities on the myenteric plexus, bringing relevant answers regarding the effect of the flavonoid in this system and the potential application of PD adjuvant treatment.
Assuntos
Plexo Mientérico , Doença de Parkinson , Masculino , Ratos , Animais , Ratos Wistar , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Rutina/farmacologia , Rutina/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Modelos Animais de Doenças , Neurônios DopaminérgicosRESUMO
BACKGROUND: Visceral leishmaniasis (VL) is a tropical neglected disease with high associated rates of mortality. Several studies have highlighted the importance of the intestinal tract (IT) and gut microbiota (GM) in the host immunological defense. Data in the literature on parasite life cycle and host immune defense against VL are scarce regarding the effects of infection on the IT and GM. OBJECTIVES: This study aimed to investigate changes observed in the colon of Leishmania infantum-infected hamsters, including alterations in the enteric nervous system (ENS) and GM (specifically, levels of bifidobacteria and lactobacilli). METHODS: Male hamsters were inoculated with L. infantum and euthanised at four or eight months post-infection. Intestines were processed for histological analysis and GM analysis. Quantitative polymerase chain reaction (qPCR) was performed to quantify each group of bacteria: Bifidobacterium spp. (Bf) and Lactobacillus spp (LacB). FINDINGS: Infected hamsters showed histoarchitectural loss in the colon wall, with increased thickness in the submucosa and the mucosa layer, as well as greater numbers of intraepithelial lymphocytes. Forms suggestive of amastigotes were seen inside mononuclear cells. L. infantum infection induced changes in ENS, as evidenced by increases in the area of colonic enteric ganglia. Despite the absence of changes in the levels of Bf and LacB during the course of infection, the relative abundance of these bacteria was associated with parasite load and histological alterations. MAIN CONCLUSIONS: Our results indicate that L. infantum infection leads to important changes in the colon and suggest that bacteria in the GM play a protective role.
Assuntos
Bifidobacterium , Microbioma Gastrointestinal , Lactobacillus , Leishmania infantum , Leishmaniose Visceral , Animais , Cricetinae , Intestinos/parasitologia , Carga ParasitáriaRESUMO
Chronic Obstructive Pulmonary Disease (COPD) is a disease of the lungs characterized by chronic airflow obstruction. Individuals with preserved ratio impaired spirometry (PRISm) may be at risk for developing COPD. This study aimed to characterize PRISm and COPD patients in terms of their immune response and endocrine profile to identify differences extending beyond lung function. The participants performed the clinical assessment, pulmonary function test, and blood collection to determine serum hormone levels and concentrations of cytokine. Differences were observed in the nutritional status, lung function, and comorbidity. There were no differences in IL-6, IL-8, IL-10, IL-12, and TNF levels between PRISm and COPD groups. Both PRISm and COPD patients have lower dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEA-S) levels than controls. Correlation analysis of PRISm and COPD patients revealed positive correlations between serum levels of DHEA-S and DHEA, with forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC), which negatively correlated with IL-8 levels. The results indicated that despite differences in lung function parameters, the PRISm and COPD groups exhibited similarities in endocrine profile alterations. This study represents the first attempt to link endocrine with immune markers and lung function in individuals with PRISm.
Assuntos
Biomarcadores , Doença Pulmonar Obstrutiva Crônica , Espirometria , Humanos , Doença Pulmonar Obstrutiva Crônica/sangue , Masculino , Feminino , Biomarcadores/sangue , Pessoa de Meia-Idade , Idoso , Citocinas/sangue , Desidroepiandrosterona/sangue , Inflamação/sangue , Sulfato de Desidroepiandrosterona/sangue , Capacidade Vital , Testes de Função Respiratória , Volume Expiratório ForçadoRESUMO
Background/Objectives: Chronic Obstructive Pulmonary Disease (COPD) is a disease of premature aging, characterized by airflow limitations in the lungs and systemic chronic inflammation. This systematic review aimed to provide a systematic overview of immunosenescence and inflammation in Chronic Obstructive Pulmonary Disease (COPD). Methods: The PubMed, Science Direct, Scopus, Cochrane Library, and Web of Science databases were searched for studies on markers of immunosenescence. Observational studies comparing patients with COPD to individuals without disease were evaluated, considering the following markers: inflammation and senescence in COPD, naïve, memory, and CD28null T cells, and telomere length in leukocytes. Results: A total of 15 studies were included, eight of which were rated as high quality. IL-6 production, telomere shortening, and the higher frequencies of CD28null T cells were more prominent findings in the COPD studies analyzed. Despite lung function severity being commonly investigated in the included studies, the importance of this clinical marker to immunosenescence remains inconclusive. Conclusions: The findings of this systematic review confirmed the presence of accelerated immunosenescence, in addition to systemic inflammation, in stable COPD patients. Further studies are necessary to more comprehensively evaluate the impact of immunosenescence on lung function in COPD.
RESUMO
The progression of chronic obstructive pulmonary disease (COPD) is characterized by functional changes in the airways. The lung-gut axis and gut microbiota (GM) have been linked to the pathophysiology of airway diseases. Regarding COPD, studies have shown that GM alterations could be related the stages of this disease. However, the relationship between GM and clinical, biochemical and immunological parameters in patients with COPD are not well understood. The aim of this study was to compare the relative abundance of specific groups of beneficial gut bacteria between COPD patients and healthy controls (CTLs) in order to evaluate relationships with metabolic and inflammatory markers in COPD. METHODS: We included 16 stable COPD patients and 16 healthy volunteer CTLs. The relative abundances of Bifidobacterium spp. (Bf) and Akkermansia muciniphila (Akk) bacteria and the Bacteroidetes and Firmicutes phyla were assessed by qPCR. Pulmonary function was evaluated by spirometry, biochemical parameters by colorimetric methods and plasma cytokine levels by cytometric bead array analysis. RESULTS: The Firmicutes/Bacteroides ratio was related to emergency hospital visits and six-minute walk test (6MWT) results. Furthermore, the relative abundance of Bf was associated with plasma concentrations of glucose, triglycerides, HDL-C and IL-10. In addition, Firmicutes levels and the Firmicutes/Bacteroidetes ratio were associated with the IL-12/IL-10 ratio, while Akk abundance was linked to IL-12 levels. CONCLUSIONS: The present findings suggest that the abundance of beneficial bacteria in the GM could influence clinical presentation and immunoregulation in COPD.
Assuntos
Microbioma Gastrointestinal , Doença Pulmonar Obstrutiva Crônica , Humanos , Doença Pulmonar Obstrutiva Crônica/imunologia , Doença Pulmonar Obstrutiva Crônica/microbiologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Akkermansia , Bifidobacterium , Estudos de Casos e Controles , Citocinas/sangueRESUMO
Leishmaniasis is a serious health problem in several parts of the world, and localized cutaneous leishmaniasis (LCL) is the most frequent presentation of the tegumentary form of this disease cluster. Clinical presentations of leishmaniasis are influenced by both parasite and host factors, with emphasis on the host immune response. Alterations in plasma hormone levels have been described in many infections, and changes in hormone levels could be related to an imbalanced cytokine profile. In the present work, we evaluated a group of patients with LCL to determine changes in plasma hormone levels (cortisol, DHEA-S, estradiol, prolactin and testosterone) and their association with clinical markers of disease (lesion size, dose used to reach cure and time to cure) and with cytokines produced by PBMC stimulated by SLA (IFN-γ, IL-10 and TNF-α). Individuals with LCL exhibited lower plasma levels of DHEA-S, prolactin and testosterone compared with sex-matched controls, whereas levels of cortisol and estradiol were similar between patients and controls. Plasma levels of cortisol, estradiol or prolactin positively correlated with at least one clinical parameter. Cortisol and prolactin levels exhibited a negative correlation with levels of IFN-γ, whereas no correlation was observed with IL-10 or TNF-α levels. A decrease in DHEA-S levels was observed in male LCL patients when compared to male healthy controls. No other differences between the sexes were observed. Our results indicate a role for neuroendocrine regulation that restricts Th1 responses in human LCL. It is possible that, although impairing parasite killing, such neuroimmunomodulation may contribute to limiting tissue damage.
Assuntos
Citocinas/sangue , Hormônios Esteroides Gonadais/sangue , Hidrocortisona/sangue , Leishmaniose Cutânea/sangue , Prolactina/sangue , Adulto , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND AND AIMS: Stress can alter many aspects of the immune response, and many studies have been conducted on the effects of stress on inflammatory processes, but little is known about its influence on the resolution of inflammation in tissue homeostasis, which includes the clearance of apoptotic cells by macrophages in a non-phlogistic way. In the present study, we investigated the effect of acute cold stress on the phagocytosis of apoptotic cells by macrophages. METHODS: Mice were submitted to acute cold stress (4 degrees C for 4 h) and the capacity of peritoneal macrophages to phagocyte apoptotic thymocytes and to secrete anti-inflammatory cytokines was evaluated. Plasma corticosterone and catecholamine levels were investigated to assess their effect on the phagocytic capacity of macrophages in vitro. RESULTS: We showed that acute cold stress decreases phagocytosis of apoptotic cells at the inflammatory site by lipopolysaccharide-activated macrophages but did not affect resting macrophages. The inhibitory effect on phagocytosis is accompanied by a reduced level of TGF-beta and higher IL-10 secretion. After stress, plasma concentrations of corticosterone increased 6-fold, epinephrine 2-fold and norepinephrine 1.7-fold compared to control mice. In vitro experiments showed that the decrease in phagocytosis after stress could be attributed, at least in part, to the effects of corticosterone; epinephrine and norepinephrine had no effect. CONCLUSIONS: The current study shows that acute cold stress decreases phagocytosis of apoptotic cells from an inflammatory environment by macrophages, and this inhibition is mediated by the intracellular glucocorticoid receptor.
Assuntos
Apoptose/imunologia , Corticosterona/metabolismo , Macrófagos/imunologia , Fagocitose/imunologia , Estresse Fisiológico/imunologia , Linfócitos T/imunologia , Doença Aguda , Animais , Apoptose/efeitos dos fármacos , Catecolaminas/metabolismo , Temperatura Baixa/efeitos adversos , Modelos Animais de Doenças , Epinefrina/metabolismo , Inflamação/imunologia , Inflamação/metabolismo , Inflamação/fisiopatologia , Mediadores da Inflamação/farmacologia , Interleucina-10/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Norepinefrina/metabolismo , Receptores de Glucocorticoides/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Regulação para Cima/imunologiaRESUMO
A shrimp extract (SME) obtained from the mild-acid demineralization treatment of shrimp shells to produce chitosan was collected. It was mainly composed of fat (≈73%), protein (≈19%), and ash (≈9%) and contained considerable amounts of calcium (≈1.9â¯g/100â¯g), astaxanthin (≈30â¯mg/100â¯g) and unsaturated fatty acids (≈27% MUFA, ≈39% PUFA). The SME was used in combination with chitosan for wrapping raw salmon to produce a ready-to-eat product enriched in calcium. No significant changes in hardness were found, as compared to the unwrapped salmon. Estimated intakes of bioaccessible calcium increased significantly by 3.6-fold, whereas intake of bioaccessible fat was reduced by 15%. SFA were the main fatty acid group reduced (≈80%), whereas MUFA and PUFA were only reduced by ≈20% each. Total viable counts, pseudomonads, enterobacteria, and specific fish spoilers were reduced by 2-4 log CFU/g in wrapped sample during the chilled storage period (19â¯days).
Assuntos
Quitosana/análise , Decápodes/química , Salmão , Alimentos Marinhos/análise , Animais , Anti-Infecciosos/farmacologia , Proteínas de Artrópodes/análise , Disponibilidade Biológica , Quitosana/farmacologia , Ácidos Graxos Insaturados/análiseRESUMO
OBJECTIVE: We aimed to assess whether 2-hydroxyoleic acid (2-OHOA) and n-3 polyunsaturated fatty acids (PUFA) could counteract changes on adipokine secretion and cardiometabolic risk biomarkers associated with high-fat diet-induced obesity in mice. METHODS: Female ICR/CD1 mice (8 weeks old) were divided into four groups receiving different diets (n=8/group): (1) standard chow (control) for 18 weeks; (2) 22% fat for 4 weeks + 60% fat for 14 weeks (obesogenic diet, OD); 3) OD + 2-OHOA (1500mgkg-1 diet) for the last 6 weeks (ODHO); and 4) OD+n-3 PUFA (eicosapentaenoic+docosahexaenoic acids, 1500+1500mgkg-1 diet) for the last 6 weeks (OD-N3). After 18 weeks, body weight, periovarian visceral fat, heart and liver weights were measured, as well as cardiometabolic parameters (systolic and diastolic blood pressure, blood glucose, insulin, HOMA index, triglycerides, total cholesterol, apolipoproteins A1 and E), plasma adipokines and inflammatory proteins (leptin, adiponectin, plasminogen activator inhibitor 1 [PAI1], soluble E-selectin [sE-selectin], matrix metalloproteinase-9 [MMP-9], fibrinogen, soluble intercellular adhesion molecule [sICAM] and soluble vascular adhesion molecule [sVCAM]), and secretion of pro-inflamatory cytokines and inflammatory biomarkers from periovarian adipocytes. RESULTS: OD mice had greater body and heart weights, and plasma leptin, and lower adiponectin and resistin secretion from adipocytes. Supplementation with 2-OHOA reduced body and heart weights, blood pressure, triglycerides and leptin, and restored adiponectin and resistin secretion, while n-3 PUFA only reduced triglyceride levels (all P<0.05). CONCLUSION: 2-OHOA supplementation was more effective in reducing adiposity, modulating adipokine secretion and ameliorating cardiometabolic risk than n-3 PUFA.
Assuntos
Adiposidade/efeitos dos fármacos , Doenças Cardiovasculares/sangue , Suplementos Nutricionais , Ácidos Graxos Ômega-3/farmacologia , Doenças Metabólicas/sangue , Obesidade/sangue , Ácidos Oleicos/farmacologia , Adiponectina/sangue , Animais , Pressão Sanguínea/efeitos dos fármacos , Doenças Cardiovasculares/prevenção & controle , Feminino , Leptina/sangue , Doenças Metabólicas/prevenção & controle , Camundongos , Camundongos Endogâmicos ICR , Camundongos Obesos , Resistina/sangue , Risco , Triglicerídeos/sangueRESUMO
Introduction: studies have highlighted the importance of gut microbiota (GM) to the host immune defenses, influencing the host development and physiology. Changes in the composition and diversity of GM have been detected in some disease and could be implicated in the pathophysiological mechanisms of them. Objective: the purpose of this study was to show an overview of the current knowledge about the GM of patients with airway diseases (AD). Methodology: the literature search was performed in four databases, using a combination of the descriptors: "Gastrointestinal Microbiome", "Gut Microbiome", "Gut Microbiota", "Cystic Fibrosis" (CF), "Asthma", "Pulmonary Hypertension" (HP) and/or "Chronic Obstructive Pulmonary Disease" (COPD). Results: fifteen studies were herein included: ten of CF and five of asthma. No study about other AD matched the inclusion criteria. In all studies about CF, changes were detected in GM, particularly quantitative and qualitative microbial changes. For asthma, data showed changes in GM also including a reduction of microbial richness, evenness and diversity and in the Bacteroidetes/Firmicutes ratio. Conclusions: the current data indicate the existence of GM changes in AD. However, due to the few studies for asthma and the lack of investigations on HP and COPD, it was not possible to confirm whether these GM changes are observed in other AD. Furthermore, this review shows the necessity of more studies in this area to characterize dysbiosis and which alterations are more frequent observed in AD patients.
Introdução: estudos têm destacado a importância da microbiota intestinal (GM) para as defesas imunológicas do hospedeiro, influenciando o desenvolvimento e a fisiologia do hospedeiro. Mudanças na composição e diversidade da GM foram detectadas em algumas doenças e podem estar implicadas nos mecanismos fisiopatológicos delas. Objetivo: o objetivo desta revisão foi avaliar estudos sobre a microbiota intestinal (MI) de pacientes com doenças das vias aéreas (DA). Metodologia: esta pesquisa bibliográfica foi realizada em quatro bases de dados, utilizando a combinação dos descritores: "Microbioma Gastrointestinal", "Microbioma Intestinal", "Microbiota Intestinal", "Fibrose Cística" (CF), "Asma", "Hipertensão Pulmonar" (HP), "Doença Pulmonar Obstrutiva Crônica" (DPOC). Resultados: quinze estudos foram incluídos: dez de FC e cinco de asma. Nenhum estudo sobre outra DA correspondeu aos critérios de inclusão. Em todos os estudos sobre FC, foram detectadas alterações na MI, particularmente alterações microbianas qualitativas e quantitativas. Para a asma, os dados mostraram mudanças na MI, incluindo também uma redução da quantidade, uniformidade e diversidade microbiana e na razão Bacteroidetes/Firmicutes. Conclusão: os dados atuais indicam a existência de alterações na MI nas DA. No entanto, devido aos poucos estudos para asma e à falta de investigações para HP e DPOC, não foi possível confirmar se essas alterações na MI são observadas em outras DA também. Além disso, esta revisão mostra a necessidade de mais estudos nessa área para caracterizar a disbiose e quais alterações são mais frequentes em pacientes com DA.
Assuntos
Humanos , Doenças Respiratórias , Asma , Fibrose Cística , Doença Pulmonar Obstrutiva Crônica , Microbioma Gastrointestinal , Hipertensão Pulmonar , Base de DadosRESUMO
O trabalho analisa uma amostra de 32 diabéticos, pareados em sexo e idade, acima de 30 anos, com 32 näo-diabéticos, ambos frequentadores da Unidade Básica de Saúde Bndeirantes. O objetivo é verificar o perfil do diabético, conhecimento sobre a doença e observar se a frequência da doença na família dos diabéticos é maior do que na família de näo-portadores. Constatou-se que a prevalência de diabéticos é maior no sexo feminino, casado, com 1§ grau incompleto, do lar, do lar, raça branca e o diabetes é do tipo II (näo-insulino-dependente). Em relaçäo ao tratamento, 63,3 por cento têm dificuldades em adquirir a medicaçäo para uso diário e 59,3 por cento dos diabéticos entrevistados näo seguem a dieta necessária. O diabético faz menos exercícios que a populaçäo geral, desconhecendo o fato de que a falta de exercício é agravante da doença, o mesmo ocorrendo com o alccolismo, tabagismo, estresse, peso acima do normal e dieta irregular. O diabético tem mais informaçöes sobre os sintomas e as complicaçöes da doença em relaçäo ao controle. Os consanguíneos em 1§ grau dos diabéticos têm maior frequência de diabetes do que os familiares em 1§ grau dos näo-diabéticos. Estes estudos foram estatisticamente significativos