RESUMEN
Obesity results from an energy imbalance and has been considered an epidemic due to its increasing rates worldwide. It is classified as a low-grade chronic inflammatory disease and has associated comorbidities. Different nutritional strategies are used for the purpose of weight loss, highlighting low-carbohydrate (LC) diets, ketogenic diets, and intermittent fasting (IF). These strategies can lead to metabolic and behavioral changes as they stimulate different biochemical pathways. Therefore, this study evaluated memory, energy metabolism, neuroinflammation, oxidative stress, and antioxidant defense parameters in mice subjected to an LC diet, ketogenic diet (KD), or IF. Eighty male Swiss mice, 60 days old, were divided into 4 groups: control, LC, KD, or IF. Body weight was measured weekly, and food intake every 48 h. After 15 days of nutritional interventions, the animals were subjected to the behavioral object recognition test and subsequently euthanized. Then, visceral fat was removed and weighed, and the brain was isolated for inflammatory and biochemical analysis. We concluded from this study that the LC and KD strategies could damage memory, IF improves the production of adenosine triphosphate (ATP), and the LC, KD, and IF strategies do not lead to neuroinflammatory damage but present damage at the level of oxidative stress.
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Dieta Cetogénica , Estrés Oxidativo , Animales , Masculino , Ratones , Estrés Oxidativo/fisiología , Trastornos de la Memoria/metabolismo , Trastornos de la Memoria/etiología , Enfermedades Neuroinflamatorias/metabolismo , Dieta Baja en Carbohidratos , Ayuno/metabolismo , Metabolismo Energético/fisiología , Encéfalo/metabolismoRESUMEN
OBJECTIVE: The microbiome plays an important role in a wide variety of skin disorders. Hence, dysbiosis in the skin and/or gut microbiome is associated with an altered immune response, promoting the development of skin diseases, such as atopic dermatitis, psoriasis, acne vulgaris and dandruff. Studies have shown that paraprobiotics may be promising for the treatment of skin disorders through microbiota modulation and immunomodulation. So, the objective is to develop an anti-dandruff formulation using a paraprobiotic (Neoimuno) as active ingredient. METHODS: Randomized, double-blind, placebo-controlled clinical trial was performed in patients who had any degree of dandruff. A total of 33 volunteers were recruited and randomly divided into two groups: placebo or treated. (1% Neoimuno). The ingredient used was Neoimuno (Bifidobacterium lactis strain CCT 7858). Combability analysis and perception questionnaire were applied before and after treatment. Statistical analyses were performed. RESULTS: No adverse effects were reported by patients throughout the study. Through the combability analysis, a significant decrease in the number of particles was verified after 28 days of shampoo use. Regarding perception, there was a significant difference for the cleaning variables and improvement of the general appearance 28 days after the intervention. There were no significant differences for the itching and scaling parameters, as well as the perception parameters at 14 days. DISCUSSION: Topical application of the paraprobiotic shampoo containing 1% Neoimuno was able to significantly improve the feeling of cleanliness and general aspects of dandruff, in addition to reducing scalp flakiness. Thus, with the results obtained through the clinical trial, Neoimuno presents itself as a natural, safe and effective ingredient in the treatment of dandruff. The efficacy of Neoimuno in dandruff was visible within 4 weeks.
OBJECTIF: Le microbiome joue un rôle important dans une grande variété de troubles cutanés. Ainsi, la dysbiose du microbiome cutané et/ou intestinal est associée à une réponse immunitaire altérée, favorisant le développement de maladies cutanées, telles que la dermatite atopique, le psoriasis, l'acné vulgaire et les pellicules. Des études ont montré que les paraprobiotiques peuvent être prometteurs pour le traitement des troubles cutanés par la modulation du microbiote et l'immunomodulation. Ainsi, l'objectif est de développer une formulation antipelliculaire utilisant un paraprobiotique (Neoimuno) comme principe actif. MÉTHODES: Un essai clinique randomisé, en double aveugle et contrôlé par placebo a été réalisé chez des patients présentant des pellicules de n'importe quel degré. Au total, 33 volontaires ont été recrutés et divisés au hasard en deux groupes: placebo ou traité. (1% Neoimuno). L'ingrédient utilisé était le Neoimuno (souche Bifidobacterium lactis CCT 7858). Une analyse de combabilité et un questionnaire de perception ont été appliqués avant et après le traitement. Des analyses statistiques ont été effectuées. RÉSULTATS: Aucun effet indésirable n'a été signalé par les patients tout au long de l'étude. Grâce à l'analyse de combabilité, une diminution significative du nombre de particules a été vérifiée après 28 jours d'utilization du shampooing. Concernant la perception, il y avait une différence significative pour les variables de nettoyage et d'amélioration de l'aspect général 28 jours après l'intervention. Il n'y avait pas de différences significatives pour les paramètres de démangeaison et de desquamation, ainsi que les paramètres de perception à 14 jours. DISCUSSION: L'application topique du shampooing paraprobiotique contenant 1% de Neoimuno a pu améliorer significativement la sensation de propreté et les aspects généraux des pellicules, en plus de réduire la desquamation du cuir chevelu. Ainsi, avec les résultats obtenus grâce à l'essai clinique, Neoimuno se présente comme un ingrédient naturel, sûr et efficace dans le traitement des pellicules. L'efficacité de Neoimuno sur les pellicules a été visible en 4 semaines.
Asunto(s)
Bifidobacterium animalis , Caspa , Preparaciones para el Cabello , Humanos , Caspa/tratamiento farmacológico , Cuero Cabelludo , Piel , Prurito , Preparaciones para el Cabello/uso terapéuticoRESUMEN
AIMS: The protective effects of Bacillus amyloliquefaciens(CCT7935), Bacillus subtilis(CCT7935), Bacillus licheniformis (CCT 7836), and Bacillus coagulans (CCT 0199) against lipopolysaccharide (LPS)-induced intestinal inflammation were investigated. METHODS AND RESULTS: Male Swiss mice were assigned into six groups: control group, LPS group, LPS + B. subtilis (CCT7935) group, LPS + B. licheniformis (CCT 7836) group, LPS + B. amyloliquefaciens (CCT7935) group, and LPS + B. coagulans (CCT 0199) group. Each mouse of the groups Bacillus received 1 × 109 colony-forming units of Bacillus once daily by oral gavage during 30 days. Twenty-four hours after the last dose of Bacillus, all groups, except the control group, were intraperitoneally injected with LPS in the single dose of 15 mg kg-1. The mice were euthanized 24 h after the LPS administration. Histological alterations, myeloperoxidase activity, and nitrite levels were analyzed in the gut of mice and the inflammatory cytokines were analyzed in the gut and in the blood. The results demonstrate that the mice challenged with LPS presented the villi shortened and damaged, which were significantly protected by B. coagulans and B. amyloliquefaciens. Furthermore, all Bacillus tested were effective in preventing against the increase of myeloperoxidase activity, while B. amyloliquefaciens and B. subtilis prevented the increase of nitrite and IL-1ß levels in the gut of mice induced with LPS was decreased only B. subtilis. LPS also elevated the IL-1 ß, IL-6, and IL-10 levels in the blood, and these alterations were significantly suppressed by Bacillus, especially by B. subtilis. CONCLUSIONS: The study suggests that the Bacillus investigated in this study might be effective therapeutic agents for preventing intestinal inflammation, because they decrease the inflammatory process an protect against tissue damage.
Asunto(s)
Bacillus , Probióticos , Animales , Ratones , Masculino , Lipopolisacáridos , Peroxidasa , Nitritos , Probióticos/farmacología , Inflamación/inducido químicamente , Inflamación/prevención & controlRESUMEN
Animal models of cerebral ischemia have improved our understanding of the pathophysiology and mechanisms involved in stroke, as well as the investigation of potential therapies. The potential of zebrafish to model human diseases has become increasingly evident. The availability of these models allows for an increased understanding of the role of chemical exposure in human conditions and provides essential tools for mechanistic studies of disease. To evaluate the potential neuroprotective properties of minocycline against ischemia and reperfusion injury in zebrafish and compare them with other standardized models. In vitro studies with BV-2 cells were performed, and mammalian transient middle cerebral artery occlusion (tMCAO) was used as a comparative standard with the zebrafish stroke model. Animals were subjected to ischemia and reperfusion injury protocols and treated with minocycline. Infarction size, cytokine levels, oxidative stress, glutamate toxicity, and immunofluorescence for microglial activation, and behavioral test results were determined and compared. Administration of minocycline provided significant protection in the three stroke models in different parameters analyzed. Both experimental models complement each other in their particularities. The proposal also strengthens the findings in the literature in rodent models and allows the validation of alternative models so that they can be used in further research involving diseases with ischemia and reperfusion injury.
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Isquemia Encefálica , Fármacos Neuroprotectores , Daño por Reperfusión , Accidente Cerebrovascular , Animales , Humanos , Pez Cebra , Minociclina/farmacología , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Accidente Cerebrovascular/tratamiento farmacológico , Isquemia Encefálica/tratamiento farmacológico , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Daño por Reperfusión/tratamiento farmacológico , Modelos Animales de Enfermedad , MamíferosRESUMEN
Sepsis is defined as a life-threatening organ dysfunction caused by an inappropriate host response to infection. The presence of oxidative stress and inflammatory mediators in sepsis leads to dysregulated gene expression, leading to a hyperinflammatory response. Environmental conditions play an important role in various pathologies depending on the stimulus it presents. A standard environment condition (SE) may offer reduced sensory and cognitive stimulation, but an enriched environment improves spatial learning, prevents cognitive deficits induced by disease stress, and is an important modulator of epigenetic enzymes. The study evaluated the epigenetic alterations and the effects of the environmental enrichment (EE) protocol in the brain of animals submitted to sepsis by cecal ligation and perforation (CLP). Male Wistar rats were divided into sham and CLP at 24 h, 72 h, 10 days and 30 days after sepsis. Other male Wistar rats were distributed in a SE or in EE for forty-five days. Behavioral tests, analysis of epigenetic enzymes:histone acetylase (HAT), histone deacetylase (HDAC) and DNA methyltransferase (DNMT), biochemical and synaptic plasticity analyzes were performed. An increase in HDAC and DNMT activities was observed at 72 h, 10 days and 30 days. There was a positive correlation between epigenetic enzymes DNMT and HDAC 24 h, 10 days and 30 days. After EE, HDAC and DNMT enzyme activity decreased, cognitive impairment was reversed, IL1-ß levels decreased and there was an increase in PSD-95 levels in the hippocampus. Interventions in environmental conditions can modulate the outcomes of long-term cognitive consequences associated with sepsis, supporting the idea of the potential benefits of EE.
Asunto(s)
Hipocampo , Sepsis , Animales , Cognición , Modelos Animales de Enfermedad , Epigénesis Genética , Hipocampo/metabolismo , Masculino , Ratas , Ratas Wistar , Sepsis/complicacionesRESUMEN
The study evaluated the effects of supplementation with three different probiotic strains Bifidobacterium lactis (LACT GB™), Lactobacillus rhamnosus (RHAM GB™) and Lactobacillus reuteri (REUT GB™) on brain-intestinal immunomodulation in an animal model of LPS-induced inflammation. Fifty mice Balb/C were distributed into five groups: control; lipopolysaccharide (LPS); LPS + B. lactis (LACT GB™); LPS + L. rhamnosus (RHAM GB™); and LPS + L. reuteri (REUT GB™). The animals were supplemented with their respective probiotic microorganisms daily, for 30 days, at a concentration of 1 × 109 CFU/animal/day. After 30 days of supplementation, animals received the inflammatory insult by LPS (15 mg/kg). Behavioral tests, oxidative stress and inflammation were performed, as well as gut and brain histology. In the behavioral test, LPS + B. lactis group was less anxious than the other groups. Serum interleukin IL-1ß and IL-6 levels increased in all groups that received the LPS insult, and there was a reduction in inflammation in the supplemented groups when compared to the LPS group in brain and gut. There is a reduction in myeloperoxidase activity and oxidative stress in groups supplemented with probiotics. In intestine histological analysis occurs damage to the tissue integrity in the LPS group, in the other hand, occurs preservation of integrity in the probiotic supplemented animals. In the brain, infiltrates of perivascular inflammatory cells can be seen in the LPS group. The three probiotic studies showed efficient immunomodulating activity and ensured integrity of the intestinal barrier function, even after the severe insult by LPS. These results show the important role of probiotics in the gut-brain axis. Graphical abstract illustratively represents the gut-brain axis and how different probiotic strains influence the immunomodulatory response releasing different pro- and anti-inflammatory cytokines, and their role in the balance of dysbiosis.
Asunto(s)
Limosilactobacillus reuteri , Probióticos , Animales , Encéfalo , Endotoxinas , Inmunomodulación , Inflamación , Lipopolisacáridos/farmacología , Ratones , Probióticos/farmacología , Probióticos/uso terapéuticoRESUMEN
INTRODUCTION: Necrotizing Enterocolitis (NEC) is a serious intestinal disease that affects premature neonates, causing high mortality, despite the technological development in neonatal intensive care, with antibiotics, parenteral nutrition, surgery, and advanced life support. The correction of dysbiosis with fecal microbiome transplantation (FMT) has shown beneficial effects in experimental models of the disease. The different forms of administration and conservation of FMT and mixed results depending on several factors lead to questions about the mechanism of action of FMT. This study aimed to compare the effectiveness of fresh, sterile FMT and probiotic treatment under parameters of inflammation, oxidative stress, and tissue damage in a neonatal model of NEC. METHODS: One-day-old Wistar rats were used to induce NEC model. Animals were divided in five groups: Control + saline; NEC + saline; NEC + fresh FMT; NEC + sterile FMT and NEC+ probiotics. Parameters of inflammatory response and oxidative damage were measured in the gut, brain, and serum. It was also determined gut histopathological alterations. RESULTS: Proinflammatory cytokines were increased in the NEC group, and IL-10 levels decreased in the gut, brain, and serum. Fresh and sterile FMT decreased inflammation when compared to the use of probiotics. Oxidative and histological damage to the intestine was apparent in the NEC group, and both FMT treatments had a protective effect. CONCLUSION: Fresh and sterile FMT effectively reduced the inflammatory response, oxidative damage, and histological alterations in the gut and brain compared to an experimental NEC model.
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Enterocolitis Necrotizante , Enfermedades Fetales , Microbioma Gastrointestinal , Enfermedades del Recién Nacido , Animales , Enterocolitis Necrotizante/terapia , Trasplante de Microbiota Fecal , Femenino , Humanos , Recién Nacido , Inflamación/patología , Modelos Animales , Ratas , Ratas WistarRESUMEN
Resumo Observa-se no Brasil uma crescente precarização dos serviços públicos e do trabalho médico. Na Paraíba, há uma forma peculiar de contratação, denominada "codificação". Trata-se de um vínculo inconstitucional, estabelecido sem assinatura de contrato, por meio do qual o médico recebe por produção e sem garantia de direitos. O objetivo do presente artigo é discutir a precarização do trabalho médico no estado da Paraíba por meio da codificação e suas implicações bioéticas. O texto traz resultados de análise de dados disponíveis no Portal da Transparência do Tribunal de Contas do Estado. Os dados revelam que, no momento da pesquisa, 1.474 médicos trabalhavam na rede estadual de saúde, sendo 716 (48,6%) concursados e 758 (51,4%) codificados. Dentre os codificados, 55,8% são homens (p=0,001), 67,1% trabalham na Zona da Mata Paraibana (p=0,021), e mais de um terço presta serviços para o estado como clínicos. Conclui-se que a codificação é uma forma ilegal de contratação, e que é preciso resgatar o valor social do médico e a dignidade humana, para que a estabilidade desses trabalhadores e a formação de vínculo com os usuários não sejam prejudicadas.
Abstract Brazil faces an increasing precariousness in public services, as well as in medical work. Paraíba has a peculiar contracting modality called "codification", an unconstitutional employment relationship established without a signed contract, in which the physicians is paid for service provision without guarantee of labor rights. This arcticle discusses the precariousness of medical work in the State of Paraíba by examining the codification system and its bioethical implications. This is a cross-sectional study with data from the transparency portal of the State Court of Accounts on codified physicians. Results show that 1,474 physicians work in the state health care system, 716 (48.6%) of whom were hired through public entrance examinations and 758 (51.4%) by codification. Significantly, 55.8% of codified physicians are men (p = 0.001) and 67.1% work in Paraíba's Zona da Mata region (p = 0.021). More than a third is registered as clinicians. Recognizing the social value of the physician is essential to prevent negative impacts on job stability and on the formation of bonds between workers and users. We must re-establish human dignity in this context.
Resumen En Brasil existe una precariedad creciente de los servicios públicos, así como del trabajo médico. En Paraíba hay una forma contractual peculiar llamada "codificación", un vínculo inconstitucional establecido sin un contrato firmado en el que el médico recibe para la producción sin garantía de derechos. Este artículo propone discutir la precariedad del trabajo del médico en el estado de Paraíba mediante la codificación y sus implicaciones bioéticas. Este es un estudio transversal con análisis de datos del portal de transparencia del Tribunal de Cuentas del Estado sobre detalles de médicos codificados. De los 1.474 médicos que trabajan en la red de salud del estado, 716 (48,6%) son reclutados públicamente y 758 (51,4%) están codificados. Fue significativo que el 55,8% son hombres (p=0,001>) y el 67,1% trabaja en la Zona da Mata Paraibana (p=0,021). Más de un tercio están codificados como clínicos. Se concluye que la codificación es una forma ilegal de contratación y que el rescate del valor social del médico y la dignidad humana es esencial para que no haya interferencia en la estabilidad de estos trabajadores y en la formación de vínculos con los usuarios.
Asunto(s)
Humanos , Masculino , Femenino , Médicos , Trabajo , Empleo , Servicios Públicos de SaludRESUMEN
The nervous system is one of the first systems to be affected during sepsis. Sepsis not only has a high risk of mortality, but could also lead to cerebral dysfunction and cognitive impairment in long-term survival patients. The receptor for advanced glycation end products (RAGE) can interact with several ligands, and its activation triggers a series of cell signaling events, resulting in the hyperinflammatory condition related to sepsis. Recent studies show that elevated levels of S100B (RAGE ligand) are associated with the pathophysiology of neurodegenerative disorders. They also participate in inflammatory brain diseases and may lead to an increased activation of microglia and astrocytes, leading to neuronal death. This study aimed to determine the effect of S100B inhibition on the neuroinflammatory response in sepsis. Sepsis was induced in Wistar rats by cecal ligation and perforation (CLP). There were three groups: Sham, CLP, and CLP +10 µg/kg of monoclonal antibody (Anti-S100B) administered intracerebroventricularly. The animals were killed 30 days after sepsis following behavioral evaluation by open field, novel object recognition, and splash test. The hippocampus, prefrontal cortex, and amydgala were used for the determination of S100B and RAGE proteins by western blotting and for the evaluation of cytokine levels and verification of the number of microglial cells by immunohistochemistry. On day 30, both the Sham and CLP + anti-S100B groups were capable of recovering the habitual memory in the open field task. Regarding novel object recognition, Sham and CLP + anti-S100B groups increased the recognition index during the test session in comparison to the training session. There was a significant increase in the time of grooming in CLP + anti-S100B in comparison to the CLP group. There was a modulation of cytokine levels and immunohistochemistry showed that the CLP + anti-S100B group had a decrease in the number of microglial cells only in the hippocampus. These results helped to understand the role of S100B protein in the pathophysiology of sepsis-associated encephalopathy and could be helpful to further experimental studies regarding this subject.
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Encéfalo/metabolismo , Disfunción Cognitiva/metabolismo , Mediadores de Inflamación/metabolismo , Subunidad beta de la Proteína de Unión al Calcio S100/metabolismo , Sepsis/metabolismo , Animales , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Encéfalo/efectos de los fármacos , Disfunción Cognitiva/tratamiento farmacológico , Disfunción Cognitiva/psicología , Modelos Animales de Enfermedad , Mediadores de Inflamación/antagonistas & inhibidores , Masculino , Estrés Oxidativo/fisiología , Ratas , Ratas Wistar , Subunidad beta de la Proteína de Unión al Calcio S100/antagonistas & inhibidores , Sepsis/tratamiento farmacológico , Sepsis/psicología , Factores de TiempoRESUMEN
OBJECTIVE: The aim of this study was to investigate the protective effects of probiotics and fecal transplantation on inflammatory and oxidative parameters in the intestines of two rat models of sepsis. METHODS: Rats were treated with prebiotics, probiotics, or symbiotics and exposed to lipopolysaccharide (LPS) or zymosan after 15 d to induce endotoxemia. Oxidative damage and inflammation were analyzed, and histologic examination of the intestinal tissue was performed. Fecal microbiota transplantation (FMT) was carried out in LPS- and zymosan-induced rat models of sepsis. RESULTS: Supplementation with symbiotics for 15 d effectively reduced the inflammatory parameters compared with supplementation for 7 d. Probiotics, prebiotics, and symbiotics exerted different effects on the evaluated parameters. In general, Lactobacillus rhamnosus and L. casei exerted better local protective effects. Evaluation of the role of the intestinal microbiota through FMT revealed its protective effects irrespective of the previous treatment with probiotics. CONCLUSION: Probiotic strains significantly differ among themselves and exert different effects on the host's health. Symbiotics and FMT could offer additional immunomodulatory benefits to drug therapy, thus serving as a new therapeutic alternative in pediatric patients with sepsis.
Asunto(s)
Microbioma Gastrointestinal , Probióticos , Sepsis , Animales , Niño , Trasplante de Microbiota Fecal , Humanos , Prebióticos , Ratas , Sepsis/terapiaRESUMEN
BACKGROUND: In order to modulate microglial phenotypes in vivo, M1 microglia were depleted by administration of gadolinium chloride and the expression of M2 microglia was induced by IL-4 administration in an animal model of sepsis to better characterize the role of microglial phenotypes in sepsis-induced brain dysfunction. METHODS: Wistar rats were submitted to sham or cecal ligation and perforation (CLP) and treated with IL-4 or GdCl3. Animals were submitted to behavioral tests 10 days after surgery. In a separated cohort of animals at 24 h, 3 and 10 days after surgery, hippocampus was removed and cytokine levels, M1/M2 markers and CKIP-1 levels were determined. RESULTS: Modulation of microglia by IL-4 and GdCl3 was associated with an improvement in long-term cognitive impairment. When treated with IL-4 and GdCl3, the reduction of pro-inflammatory cytokines was apparent in almost all analyzed time points. Additionally, CD11b and iNOS were increased after CLP at all time points, and both IL-4 and GdCl3 treatments were able to reverse this. There was a significant decrease in CD11b gene expression in the CLP+GdCl3 group. IL-4 treatment was able to decrease iNOS expression after sepsis. Furthermore, there was an increase of CKIP-1 in the hippocampus of GdCl3 and IL-4 treated animals 10 days after CLP induction. CONCLUSIONS: GdCl3 and IL-4 are able to manipulate microglial phenotype in an animal models of sepsis, by increasing the polarization toward an M2 phenotype IL-4 and GdCl3 treatment was associated with decreased brain inflammation and functional recovery.
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Antiinflamatorios/farmacología , Conducta Animal/efectos de los fármacos , Cognición/efectos de los fármacos , Disfunción Cognitiva/prevención & control , Encefalitis/prevención & control , Gadolinio/farmacología , Hipocampo/efectos de los fármacos , Interleucina-4/farmacología , Microglía/efectos de los fármacos , Sepsis/tratamiento farmacológico , Animales , Antígeno CD11b/metabolismo , Proteínas Portadoras/metabolismo , Disfunción Cognitiva/metabolismo , Disfunción Cognitiva/patología , Disfunción Cognitiva/psicología , Citocinas/metabolismo , Modelos Animales de Enfermedad , Encefalitis/metabolismo , Encefalitis/patología , Encefalitis/fisiopatología , Hipocampo/metabolismo , Hipocampo/patología , Hipocampo/fisiopatología , Mediadores de Inflamación/metabolismo , Microglía/metabolismo , Microglía/patología , Óxido Nítrico Sintasa de Tipo II/metabolismo , Fenotipo , Ratas Wistar , Sepsis/metabolismo , Sepsis/patología , Sepsis/fisiopatología , Factores de TiempoRESUMEN
Inflammatory cytokines are related to impaired learning and memory processes in the central nervous system, contributing to the cognitive dysfunction present in sepsis survivors. In sepsis, brain of survivors presented increased deposition of amyloid-beta (Aß) peptide and this was associated with cognitive impairment. However, it is not known if the upregulation of secretase pathway is involved the deposition of Aß peptide and consequent development of cognitive impairment in survivors. The aim of the study is to evaluate the effects of secretase inhibitors on behavioral, Aß accumulation, and neuroinflammatory parameters in rats submitted to sepsis. Sepsis was induced by cecal ligation and perforation in Wistar rats, and the activity of alpha-, beta-, and gamma-secretases was determined in the hippocampus and prefrontal at different times. Additionally, in a different cohort of animal's epigallocatechin gallate, a beta-secretase inhibitor or a gamma-secretase inhibitor was administrated once a day for three consecutive days. Fifteen or 30 days after sepsis induction, Aß content, TNF-α, IL-1ß, and IL-6 and cognitive performance were determined. There was no increase in alpha-secretase activity. Both beta- and gamma-secretase activities increased, mainly late after sepsis. The inhibition of beta- or gamma-secretases improved cognitive performance 10 days after sepsis induction, and beta-secretase inhibition improved cognitive performance up to 30 days after sepsis induction. Furthermore, beta-secretase inhibition decreased IL-1ß and Aß brain levels. It was demonstrated that during sepsis development there was an increase in the amyloidogenic route, and the inhibition of this pathway promoted attenuation of neuroinflammation, Aß peptide content, and improvement of cognitive impairment.
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Secretasas de la Proteína Precursora del Amiloide/metabolismo , Disfunción Cognitiva/metabolismo , Encefalitis/metabolismo , Sepsis/metabolismo , Péptidos beta-Amiloides/metabolismo , Animales , Encéfalo/metabolismo , Modelos Animales de Enfermedad , Masculino , Ratas Wistar , Sepsis/complicacionesRESUMEN
We aim to characterize the kinetics of early and late microglial phenotypes after systemic inflammation in an animal model of severe sepsis and the effects of minocycline on these phenotypes. Rats were subjected to CLP, and some animals were treated with minocycline (10 ug/kg) by i.c.v. administration. Animals were killed 24 hours, 5, 10 and 30 days after sepsis induction, and serum and hippocampus were collected for subsequent analyses. Real-time PCR was performed for M1 and M2 markers. TNF-α, IL-1ß, IL-6, IL-10, CCL-22 and nitrite/nitrate levels were measured. Immunofluorescence for IBA-1, CD11b and arginase was also performed. We demonstrated that early after sepsis, there was a preponderant up-regulation of M1 markers, and this was not switched to M2 phenotype markers later on. We found that up-regulation of both M1 and M2 markers co-existed up to 30 days after sepsis induction. In addition, minocycline induced a down-regulation, predominantly, of M1 markers. Our results suggest early activation of M1 microglia that is followed by an overlap of both M1 and M2 phenotypes and that the beneficial effects of minocycline on sepsis-associated brain dysfunction may be related to its effects predominantly on the M1 phenotype.
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Citocinas/metabolismo , Modelos Animales de Enfermedad , Hipocampo/patología , Inflamación/patología , Microglía/patología , Sepsis/patología , Animales , Hipocampo/metabolismo , Inflamación/metabolismo , Masculino , Microglía/metabolismo , Fenotipo , Ratas , Ratas Wistar , Sepsis/metabolismoRESUMEN
Sepsis-associated encephalopathy is highly prevalent and has impact both in early and late morbidity and mortality. The mechanisms by which sepsis induces brain dysfunction include neuroinflammation, disrupted blood-brain barrier, oxidative stress, and microglial activation, but the cellular and molecular mechanisms involved in these events are not completely understood. Our objective was to determine the effects of microglial depletion in the early systemic and brain inflammatory response and its impact in phenotypes expression in an animal model of sepsis. Animals were subjected to CLP, and depletion of microglial cells was accomplished by administration of (Lipo)-encapsulated clodronate and microglial repopulation by doxycycline. Clod-lip treatment was effective in decreasing microglia density in the hippocampus of animals. Pro-inflammatory cytokines were increased in the CLP+PBS, and liposomes administration increased even further these cytokines mainly 7 days, suggesting that microglial depletion exacerbates both local and systemic inflammation. In contrast, repopulation with doxycycline was able to revert the cytokine levels in both serum and cerebral structures on day 7 and 14 after repopulation. There were no differences in the correlation between M1 and M2 markers by real-time PCR, but immunohistochemistry showed significant increase in CD11b expression in CLP+PBS with greater expression in CLP + liposomes in the hippocampus. These results suggest that the depletion of microglia during severe sepsis development could be associated with early exacerbation of brain and systemic inflammation and repopulation is able to revert this condition, once a rapid neurological recovery is noticed until 7 days after sepsis.
Asunto(s)
Inflamación/patología , Microglía/patología , Sepsis/patología , Animales , Antígeno CD11b/metabolismo , Citocinas/metabolismo , Modelos Animales de Enfermedad , Hipocampo/patología , Inflamación/complicaciones , Fenotipo , Ratas , Sepsis/complicacionesRESUMEN
Lettuce is the main leafy vegetable grown in the world, being the crispy-leaf lettuce type predominant. With consecutive cultivation in the same area, several factors may impair yield, highlighting the damage caused by root-knot nematodes, Meloidogyne spp. This study aimed at evaluating the reaction of twenty crispy-leaf lettuce cultivars to Meloidogyne incognita race 3, M. javanica and M. enterolobii. Three experiments were conducted, one for each nematode species. The experiments were carried out in a greenhouse, in pots with sterilized substrate. The design was completely randomized with five replications. Seedlings were inoculated with 1.000 eggs and second-stage juveniles of nematode per pot, on the day of transplantation of seedlings. The tomato 'Rutgers' was used as inoculum viability control for each specie tested. The variables evaluated were: reproduction factor (FR), total number of eggs and second-stage juveniles (NTOJ) and number of eggs and second-stage juveniles per gram of root (NOJGR), 60 days after inoculation. The results showed that the cultivars Veronica, Grand Rapids and Crespa para Verão are resistant to the three nematode species. The cultivars Thaís, SRV 2005 and Marisa are resistant to M. incognita race 3 and M. javanica. The cultivar Black Seed Simpson is resistant to M. enterolobii. The cultivars Vanda and Mônica SF 31 are resistant to M. incognita race 3. The cultivars Crespa, Rubia, Cinderela and Veneranda are resistant to M. javanica.
A alface é a principal hortaliça folhosa cultivada no mundo, sendo o tipo crespa mais comercializada. Com o cultivo consecutivo na mesma área, vários fatores podem prejudicar a produtividade, se destacando os danos causados pelos nematoides de galha, Meloidogyne spp. Este trabalho teve como objetivo avaliar vinte cultivares de alface, do grupo crespa, quanto a reação à Meloidogyne incognita, Meloidogyne javanica e Meloidogyne enterolobii. Foram realizados três ensaios, um para cada espécie de nematoide. Os experimentos foram conduzidos em casa de vegetação, em vaso com substrato autoclavado. O delineamento experimental foi em blocos casualizados, com cinco repetições. As plantas foram inoculadas com 1.000 ovos e eventuais juvenis de segundo estágio do nematoide, no dia do transplantio das cultivares. O tomateiro 'Rutgers' foi utilizado como padrão de viabilidade do inóculo de cada espécie de nematoide. As variáveis avaliadas foram: número total de ovos e juvenis do segundo estádio (NTOJ), fator de reprodução (FR) e número de ovos e juvenis de segundo estádio por grama de raízes (NOJGR) avaliadas 60 dias após a inoculação. Os resultados obtidos mostraram que as cultivares Verônica, Grand Rapids e Crespa para Verão foram resistentes as espécies M. enterolobii, M. incognita, M. javanica. As cultivares Thaís, SRV 2005 e Marisa foram resistentes as espécies M. incognita e M. javanica. A cultivar Black Seed Simpson foi resistente à M. enterolobii. Vanda e Mônica SF 31 foram resistentes à M. incognita. As cultivares Crespa, Rubia, Cinderela e Veneranda foram resistentes à M. javanica.
Asunto(s)
Tumores de Planta , Plantas , Tylenchoidea , Lactuca , NematodosRESUMEN
Total concentrations of Ni, Cr, Cu, Pb and Zn were determined in surface sediments from 30 stations in Guanabara Bay in 1999 and 2008. An approach using various environmental indices was used to assess contamination status of metals. This approach allowed the comparison with different coastal areas. Background Enrichment Index, Contamination index and Ecological Risk index (Pollution Load Index; Sediment Quality Guideline Quotient and Ecological Risk Index) were calculated for the metals. Results revealed a great load of organic matter and significant increases in Cu and Pb levels between 1999 and 2008. The concentrations of Cr and Zn were of great concern, surpassing the values of Probable Effect Level reference values. In spite of the differences of each index, results effectively revealed the striking contamination in Guanabara Bay concerning trace metals, and also suggested potential risk to local biota. The contamination of the northwest area was notably higher than the rest of the bay. In comparison with some other coastal bays around the world, Guanabara Bay stood out as a remarkably contaminated environment.
Asunto(s)
Bahías/química , Monitoreo del Ambiente/métodos , Sedimentos Geológicos/química , Metales/química , Contaminantes Químicos del Agua/química , Brasil , Oligoelementos/análisisRESUMEN
PURPOSE: To investigate the association between sociobehavioural variables and the pattern and severity of early childhood caries in Brazilian infants and toddlers ages 0-3 years. MATERIALS AND METHODS: This was a cross-sectional study with 768 children who attended 58 public nursery schools. Five previously calibrated teams (Kappa = 0.842) performed oral examinations, using the decayed, missing, filled teeth (dmft) index according to the WHO methodology. A pretested, self-administered questionnaire was given to the subjects' parents or guardians to obtain sociobehavioural information. RESULTS: Caries was observed in 134 of the 768 (17%) children. Caries and rampant caries were significantly more prevalent in low-income families (p = 0.0121) and the incidence of caries was associated with access to dental services (p < 0.05). The percentages of children who were caries free in the age groups of 0-11 months, 12-23 months, 24-35 months and 36-47 months were 100%, 96%, 88% and 76%, respectively. CONCLUSION: Programmes for prevention and oral health education should be instituted, preferably during the first year of life, especially for those in the most socioeconomically deprived groups.
Asunto(s)
Caries Dental/epidemiología , Determinantes Sociales de la Salud/estadística & datos numéricos , Factores de Edad , Brasil/epidemiología , Preescolar , Estudios Transversales , Índice CPO , Atención Odontológica/estadística & datos numéricos , Escolaridad , Estudios Epidemiológicos , Femenino , Accesibilidad a los Servicios de Salud/estadística & datos numéricos , Humanos , Renta/estadística & datos numéricos , Lactante , Recién Nacido , Masculino , Padres/educación , Pobreza/estadística & datos numéricos , Diente Primario/patología , Cepillado Dental/estadística & datos numéricos , Poblaciones Vulnerables/estadística & datos numéricosRESUMEN
Objetivo: Verificar conhecimentos de mulheres e orientações recebidas por elas sobre aleitamento materno, durante a gestação e após o nascimento dos bebês, e as influências destes sobre a prática da amamentação. Métodos: Trata-se de um estudo longitudinal, com acompanhamento de 84 pares de mães e bebês, da gestação ao sexto mês de vida dos bebês. Na primeira fase da pesquisa foram realizadas entrevistas domiciliares e em Unidades Básicas de Saúde com as gestantes, para obtenção de suas intenções e conhecimentos sobre a prática do aleitamento materno. Na segunda fase foi realizado acompanhamento das mães e bebês, do primeiro ao sexto mês de idade, para registro das dificuldades na amamentação e motivos de desmame. Resultados: No primeiro mês de vida, 94,3% (82) dos bebês foram amamentados, destes, apenas 49,4% (43) receberam leite materno exclusivamente. Ao final do sexto mês, 43,7% (38) dos bebês já tinham sido desmamados. Nenhuma mãe amamentava exclusivamente seu bebê ao sexto mês de vida. Durante a gravidez, 60,7% (51) das mães não receberam orientações sobre o aleitamento, e 83,4% (70) das mães receberam orientações sobre aleitamento após o nascimento das crianças. A maioria das mães (76,2%) tinha conhecimento do período ideal de amamentação. Um total de 73 (86,9%) mães acreditava que o aleitamento era benéfico ao bebê, mas somente 41 (48,8%) destas amamentaram. Somente 11 (13,1%) mulheres do estudo foram acompanhadas pela equipe do sistema público de saúde durante a lactação. Conclusão: Apesar da maioria das gestantes terem sido orientadas e possuírem conhecimento sobre o aleitamento materno, houve desmame precoce. Orientar é importante, entretanto, o apoio e o acompanhamento das mães são fundamentais para que se tenha sucesso na prática da amamentação...
Objective: To assess the knowledge of women and the instructions received on breastfeeding during pregnancy and after childbirth, and their influence on breastfeeding practice.Method: This study was a longitudinal investigation following 84 pairs of mothers and babies from pregnancy through the sixth month of baby?s life. In the first phase of the research, interviews were made with the pregnant women at home and at Basic Health Units to collect information about their intentions and knowledge of breastfeeding. In the second phase of the research, mothers and babies were followed up from the first to sixth month of baby?s life to record the difficulties of breastfeeding and reasons for weaning.Results: In the first month, 94.3% (82) of the babies were breastfed, but only 49.4% (43) were breastfed exclusively. At the end of the sixth month of life, 43.7% (38) of the babies had already been weaned. No mother breastfed exclusively her baby within the sixth month. During pregnancy, 60.7% (51) of the mothers had no instructions about breastfeeding and 83.4% (70) of the mothers received instructions on breastfeeding after childbirth. Most mothers (76.2%) knew about the ideal breastfeeding period. Seventy-three (86.9%) mothers believed that breastfeeding was beneficial for the baby, but only 41 (48.8%) of them really breastfed. Only 11 (13.1%) mothers were followed up by the public health system team during lactation.Conclusion: Although most women had been instructed during pregnancy or after childbirth and had knowledge of breastfeeding, early weaning occurred. Advising is important, but the support and follow up of the mothers are of utmost importance for a successful breastfeeding practice...
Asunto(s)
Humanos , Femenino , Embarazo , Lactancia Materna/psicología , Destete , Educación en Salud , Estrategias de Salud Nacionales , Distribución de Chi-Cuadrado , Estudios ProspectivosRESUMEN
The aim of this study was to analyze the influence of socio-behavioral variables on the prevalence and severity of dental caries in 4- to 6-year-old children. A cross-sectional study was performed on a sample of 1993 children enrolled in 58 public preschools from Araçatuba City, São Paulo State, Brazil, during 2010. The exams were made using the decayed, missing, and filled teeth index (World Health Organization methodology) and detection criteria for non-cavitated lesions. A tested, self-administered questionnaire was sent to parents to obtain information about their socio-behavioral characteristics. Standardization was performed to verify concordance among examiners (kappa = 0.84). The prevalence of cavitated caries lesions was 41.2% (821), and the prevalence of both, cavitated and non-cavitated caries lesions, was 43.9% (875). The means ± standard deviations of the decayed, missing, and filled teeth index for children aged 4, 5, and 6 years were 1.18 ± 2.45, 1.65 ± 2.67, and 1.73 ± 2.77, respectively. Caries were significantly more prevalent in children from families with low incomes and low educational levels. The presence of dental caries was associated with access to dental services (p < 0.05). The associations between both, cavitated and non-cavitated dental caries lesions, and the frequency of oral hygiene were statistically significant. The prevalence of dental caries in preschoolers was strongly associated with factors related to the children's parents. Therefore, information about parents' socio-economic status, behaviors, and attitudes in relation to oral health should be considered when planning prevention and educational programs for the oral health of preschool children.