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BACKGROUND/OBJECTIVES: Proinflammatory cytokines are increased in obese adipose tissue, including inflammasome key masters. Conversely, IL-18 protects against obesity and metabolic dysfunction. We focused on the IL-18 effect in controlling adipose tissue remodeling and metabolism. MATERIALS/SUBJECTS AND METHODS: We used C57BL/6 wild-type (WT) and interleukine-18 deficient (IL-18-/-) male mice fed a chow diet and samples from bariatric surgery patients. RESULTS: IL-18-/- mice showed increased adiposity and proinflammatory cytokine levels in adipose tissue, leading to glucose intolerance. IL-18 was widely secreted by stromal vascular fraction but not adipocytes from mice's fatty tissue. Chimeric model experiments indicated that IL-18 controls adipose tissue expansion through its presence in tissues other than bone marrow. However, IL-18 maintains glucose homeostasis when present in bone marrow cells. In humans with obesity, IL-18 expression in omental tissue was not correlated with BMI or body fat mass but negatively correlated with IRS1, GLUT-4, adiponectin, and PPARy expression. Also, the IL-18RAP receptor was negatively correlated with IL-18 expression. CONCLUSIONS: IL-18 signaling may control adipose tissue expansion and glucose metabolism, as its absence leads to spontaneous obesity and glucose intolerance in mice. We suggest that resistance to IL-18 signaling may be linked with worse glucose metabolism in humans with obesity.
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Tejido Adiposo , Interleucina-18 , Ratones Endogámicos C57BL , Obesidad , Animales , Interleucina-18/metabolismo , Ratones , Masculino , Tejido Adiposo/metabolismo , Humanos , Obesidad/metabolismo , Intolerancia a la Glucosa/metabolismo , Modelos Animales de Enfermedad , Ratones NoqueadosRESUMEN
PURPOSE: Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders with important impact on global health. Prebiotic and probiotic strategies are thought to be useful in the context of experimental IBD. Here, we compared the effects of preventive versus therapeutic treatment with a high fiber diet (prebiotic) in combination or not with Bifidobacterium longum (probiotic) in a murine model of chronic colitis. METHODS: Colitis was induced by adding dextran sulfate sodium (DSS) to drinking water for 6 days (acute colitis) or for 5 cycles of DSS (chronic colitis). RESULTS: Administration of the high fiber diet protected from acute colitis. Protection was optimal when diet was started 20 days prior to DSS. A 5-day pretreatment with acetate, a short-chain fatty acid, provided partial protection against acute colitis. In chronic colitis, pretreatment with the high fiber diet attenuated clinical and inflammatory parameters of disease. However, when the treatment with the high fiber diet started after disease had been established, overall protection was minimal. Similarly, delayed treatment with acetate or B. longum did not provide any protection even when the probiotic was associated with the high fiber diet. CONCLUSION: Preventive use of a high fiber diet or acetate clearly protects mice against acute and chronic damage induced by DSS in mice. However, protection is lost when therapies are initiated after disease has been established. These results suggest that any therapy aimed at modifying the gut environment (e.g., prebiotic or probiotic strategies) should be given early in the course of disease.
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Biomarcadores/sangre , Colitis/dietoterapia , Dieta , Fibras de la Dieta/administración & dosificación , Acetatos/administración & dosificación , Enfermedad Aguda , Animales , Conducta Animal , Bifidobacterium/metabolismo , Enfermedad Crónica , Colitis/inducido químicamente , Colon/microbiología , Sulfato de Dextran/efectos adversos , Modelos Animales de Enfermedad , Ácidos Grasos Volátiles/administración & dosificación , Femenino , Ratones , Ratones Endogámicos BALB C , Prebióticos , Probióticos/administración & dosificaciónRESUMEN
OBJECTIVES: The aim of this study was to evaluate the effects of 8 wk of time-restricted eating (TRE) along with a caloric restriction on metabolic profile, metabolic rate, symptoms of mood, and eating disorders and weight loss in women with overweight or obesity. METHODS: Women age 18 to 59 y with a body mass index of ≥25 kg/m2 were enrolled in this parallel-arm, randomized, clinical trial. Participants were randomly allocated into two groups (8-h TRE or non-TRE group) using a 2:1 allocation strategy. Both groups received a diet plan with caloric restriction. Body weight, resting metabolic rate, metabolic profile, and symptoms of mood and eating disorders were evaluated at baseline and on follow up. RESULTS: Thirty-six subjects were included in this study, with 24 in the TRE group and 12 in the non-TRE group. Subject in the TRE group showed more pronounced loss of weight, body fat mass, and fat-free mass than those in the non-TRE group. These losses were not associated with changes in resting metabolic rate, metabolic profile, and eating or mood disorder symptoms. CONCLUSIONS: This study showed that 8 wk of TRE does not influence behavioral parameters in individuals with overweight or obesity, but could lead to weight loss.
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Dieta Reductora , Sobrepeso , Humanos , Femenino , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Obesidad/metabolismo , Restricción Calórica , Pérdida de Peso , Ayuno , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
OBJECTIVES: One of the leading causes of obesity is the consumption of excess nutrients. Obesity is characterized by adipose tissue expansion, chronic low-grade inflammation, and metabolic alterations. Although consumption of a high-fat diet has been demonstrated to be a diet-induced obesity model associated with gut disorders, the same effect is not well explored in a mild-obesity model induced by high-refined carbohydrate (HC) diet intake. The intestinal tract barrier comprises mucus, epithelial cells, tight junctions, immune cells, and gut microbiota. This system is susceptible to dysfunction by excess dietary components that could increase intestinal permeability and bacterial translocation. The aim of this study was to evaluate whether an HC diet and the alterations resulting from its intake are linked to small intestine changes. METHODS: Male BALB/c mice were fed a chow or an HC diet for 8 wk. RESULTS: Although differences in body weight gain were not observed between the groups, mice fed the HC diet showed increased adiposity associated with metabolic alterations. The interferon-γ expression and myeloperoxidase levels were increased in the small intestine in mice fed an HC diet. However, the intestinal villi length, the expression of tight junctions (zonula occludens-1 and claudin-4) and tumor necrosis factor-α cytokine, and the percentage of intraepithelial lymphocytes did not differ in the jejunum or ileum between the groups. We did not observe differences in intestinal permeability and bacterial translocation. CONCLUSION: Metabolic alterations caused by consumption of an HC diet lead to a mild obesity state that does not necessarily involve significant changes in intestinal integrity.
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Mucosa Intestinal , Obesidad , Masculino , Ratones , Animales , Obesidad/metabolismo , Mucosa Intestinal/metabolismo , Dieta Alta en Grasa/efectos adversos , Inflamación/etiología , Carbohidratos de la Dieta/efectos adversos , Carbohidratos de la Dieta/metabolismo , Ratones Endogámicos C57BLRESUMEN
OBJECTIVES: Acute physical exercise acts as a metabolic stressor, promoting activation of the immune system, and this response could be relevant in the adipose tissue remodeling process. In addition, some cytokines have important functions in lipolysis. Because chronic exercise improves obesity-related metabolic and inflammatory dysfunction, herein we investigated the effect of acute exercise on the inflammatory responses in the adipose tissues of lean and obese mice. METHODS: Lean mice were fed a standard chow diet, whereas obese mice were fed a high-refined carbohydrate diet for 8 wk. Both groups were subjected to 60 min of moderate-intensity exercise. RESULTS: In the epididymal adipose tissue of lean mice, exercise enhanced interleukin (IL)-6 and tumor necrosis factor-α levels, which correlated positively with increased serum free fatty acid concentrations. In vivo confocal imaging of epididymal adipose tissue vessels revealed higher recruitment of neutrophils after exercise. Also, the number of leukocytes expressing CD11b+F480- was elevated 6 h after exercise. Similarly, the chemokine (C-X-C motif) ligand 1 level increased at 6 h and remained high until 24 h after exercise. Myeloperoxidase activity was increased at 6, 12, and 24 h after exercise. Surprisingly, however, no changes were observed in epididymal adipose tissue from obese mice, considering proinflammatory cytokines (IL-6 and tumor necrosis factor-α). On the other hand, IL-13, IL-4, and IL-10 levels were higher in obese mice after exercise. CONCLUSIONS: These data suggest that acute exercise promotes an inflammatory response in the adipose tissue of lean mice that is observed as part of its role in adipose tissue remodeling. In contrast, acute exercise promotes an antiinflammatory response in adipose tissue from obese mice, likely as an important tool for restoring homeostasis.
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BACKGROUND: Eosinophils are generally related to helminth infections or allergies. Their association with metabolic alterations and adipose tissue (AT) remodeling has been demonstrated mainly in animal models of obesity. However, their physiological role in driving metabolic features has not yet been well described. Herein, we aimed to evaluate the participation of eosinophils in metabolic and adipose tissue homeostasis in mice and humans, focusing on a translational perspective. MATERIAL AND METHODS: Male BALB/c wild-type (WT) mice and GATA-1 knockout (Δdb/GATA-1-/-) mice were followed until 16-week-age in a regular diet or were fed with a high-refined-carbohydrate (HC) diet or high-fat (HF) diet for eight weeks. In subjects with obesity, clinical parameters and omental AT gene expression were evaluated. RESULTS: Eosinophils lack in mice fed a regular diet induced insulin resistance and increased adiposity. Their adipose tissue showed augmented cytokine levels, which could be attributed to increased leukocytes in the tissue, such as neutrophils and pro-inflammatory macrophages. Bone marrow transplant from WT mice to Δdb/GATA-1-/- mice showed some improvement in glucose metabolism with lower adipose tissue mass accretion. Upon an unhealthy diet challenge, Δdb/GATA-1-/- mice fed HC diet showed a mild degree of adiposity and glucose metabolic dysfunction severe in those mice fed HF diet. The expression of eosinophil markers in omental AT from humans with severe obesity was positively correlated to eosinophil cytokines and insulin sensitivity surrogate markers and negatively correlated to systemic insulin, HOMA-IR, and android fat mass. CONCLUSIONS: Eosinophils seem to have a physiological role by controlling systemic and adipose tissue metabolic homeostasis by modulating glucose metabolism, inflammation, and visceral fat expansion, even in lean mice. Indeed, eosinophils also seem to modulate glucose homeostasis in human obesity.
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Eosinófilos , Resistencia a la Insulina , Masculino , Humanos , Animales , Ratones , Lactante , Eosinófilos/metabolismo , Obesidad/genética , Obesidad/metabolismo , Tejido Adiposo/metabolismo , Citocinas/metabolismo , Resistencia a la Insulina/genética , Dieta Alta en Grasa , Glucosa/metabolismo , Ratones Noqueados , Ratones Endogámicos C57BLRESUMEN
INTRODUCTION: Periodontal diseases (PD) are inflammatory conditions that affect the teeth supporting tissues. Increased body fat tissues may contribute to activation of the systemic inflammatory response, leading to comorbidities. Some studies have shown that individuals with obesity present higher incidence of PD than eutrophics. OBJECTIVE: To investigate the impact of obesity on periodontal tissues and oral microbiota in mice. METHODOLOGY: Two obesity mice models were performed, one using 12 weeks of the dietary protocol with a high-fat (HF) diet in C57BL/6 mice and the other using leptin receptor-deficient mice (db/db-/-), which became spontaneously obese. After euthanasia, a DNA-DNA hybridization technique was employed to evaluate the microbiota composition and topical application of chlorhexidine (CHX), an antiseptic, was used to investigate the impact of the oral microbiota on the alveolar bone regarding obesity. RESULTS: Increased adipose tissue may induce alveolar bone loss, neutrophil recruitment, and changes in the oral biofilm, similar to that observed in an experimental model of PD. Topical application of CHX impaired bone changes. CONCLUSION: Obesity may induce changes in the oral microbiota and neutrophil recruitment, which are associated with alveolar bone loss.
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Pérdida de Hueso Alveolar , Microbiota , Enfermedades Periodontales , Ratones , Animales , Ratones Endogámicos C57BL , Obesidad/complicaciones , ADNRESUMEN
OBJECTIVES: Dietary fibers, such as fructooligosaccharide (FOS) and partially hydrolyzed guar gum (PHGG) have several gastrointestinal functions. The aims of this study were to evaluate the effect of acute ingestion of FOS and PHGG on the percentage of gastric emptying and small intestinal transit and to evaluate the effect of these dietary fibers on the levels of intestinal hormones-active glucagon-like peptide-1, pancreatic polypeptide, and gastric inhibitory peptide-and their effect on feelings of hunger and satiety and the desire to eat. METHODS: In this crossover, randomized controlled clinical trial, we compared the effects of these two fibers on gastrointestinal transit. The tests were performed using scintigraphy. On three different days, healthy participants consumed a test meal containing 20 g of digestible maltodextrin (placebo), 20 g of FOS, or 20 g of PHGG. RESULTS: The gastric emptying of the FOS-based diet (84.2 ± 9.4%) within 2 h was statistically increased compared with the placebo and PHGG-based diets (78 ± 10.2% and 74 ± 15.3%, respectively; P < 0.05). However, a reduction in small intestinal transit was observed after consumption of both FOS- and PHGG-based diets (28.5 ± 15.56% and 24.2 ± 13.7%, respectively) compared with the placebo diet (41.20 ± 15.4%; P < 0.05). There were no changes in the levels of intestinal hormones, feeling of hunger and satiety, or desire to eat after consuming the three diets (P > 0.05). CONCLUSION: The acute intake of FOS increased gastric emptying, whereas both FOS and PHGG reduced small intestine transit without altering the levels of intestinal hormones, hunger feelings and satiety, or the desire to eat.
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Hormonas Gastrointestinales , Tránsito Gastrointestinal , Fibras de la Dieta/farmacología , Galactanos , Hormonas Gastrointestinales/farmacología , Humanos , Mananos/farmacología , Oligosacáridos , Gomas de PlantasRESUMEN
The perivascular adipose tissue (PVAT) is an active endocrine organ responsible for release several substances that influence on vascular tone. Increasing evidence suggest that hyperactivation of the local renin-angiotensin system (RAS) in the PVAT plays a pivotal role in the pathogenesis of cardiometabolic diseases. However, the local RAS contribution to the PVAT control of vascular tone during obesity is still not clear. Since the consumption of a high-carbohydrate diet (HC diet) contributes to obesity inducing a rapid and sustained increase in adiposity, so that the functional activity of PVAT could be modulated, we aimed to evaluate the effect of HC diet on the PVAT control of vascular tone and verify the involvement of RAS in this effect. For that, male Balb/c mice were fed standard or HC diet for 4 weeks. Vascular reactivity, histology, fluorescence, and immunofluorescence analysis were performed in intact thoracic aorta in the presence or absence of PVAT. The results showed that HC diet caused an increase in visceral adiposity and also in the PVAT area. Phenylephrine-induced vasoconstriction was significantly reduced in the HC group only in the presence of PVAT. The anticontractile effect of PVAT induced by HC diet was lost when aortic rings were previously incubated with angiotensin-converting enzyme inhibitor, Mas, and AT2 receptors antagonists, PI3K, nNOS, and iNOS inhibitors, hydrogen peroxide (H2O2) decomposing enzyme or non-selective potassium channels blocker. Immunofluorescence assays showed that both Mas and AT2 receptors as well as nNOS and iNOS isoforms were markedly expressed in the PVAT of the HC group. Furthermore, the PVAT from HC group also exhibited higher nitric oxide (NO) and hydrogen peroxide bioavailability. Taken together, these findings suggest that the anticontractile effect of PVAT induced by HC diet involves the signaling cascade triggered by the renin-angiotensin system through the activation of Mas and AT2 receptors, PI3K, nNOS, and iNOS, leading to increased production of nitric oxide and hydrogen peroxide, and subsequently opening of potassium channels. The contribution of PVAT during HC diet-induced obesity could be a compensatory adaptive characteristic in order to preserve the vascular function.
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OBJECTIVES: Fasting has long been practiced for political and religious reasons and to lose weight. However, biological responses during fasting have yet to be fully understood. Previous studies have shown that cytokines may control fat pad expansion, at least in part, owing to the induction of lipolysis. Indeed, we have previously shown that mice with a lower inflammatory response, such as platelet-activating factor receptor knockout mice (PAFR-/-), are prone to gain weight and adiposity. The aims of this study were to determine whether adipose tissue becomes inflamed after fasting and to evaluate whether the PAF signaling is a factor in the fat loss induced by fasting. METHODS: Wild-type (WT) and PAFR-/- mice were fasted for 24 h. Adiposity, leukocyte recruitment, and cytokine levels were evaluated. Multiple comparisons were performed using two-way analysis of variance and post hoc Fisher exact test. RESULTS: After fasting, male WT mice showed lower adiposity (P < 0.001), higher recruitment of immune cells (P < 0.001), and increased cytokine levels (P < 0.05) in adipose tissue. Although WT mice lost ~79% of their adipose tissue mass, PAFR-/- mice lost only 36%. Additionally, PAFR-/- mice did not show enhanced cytokine and chemokine levels after fasting (P > 0.05). CONCLUSION: Despite low-grade inflammation being associated with metabolic syndrome, at least in part, the inflammatory milieu is also important to induce proper fat mobilization and remodeling of adipose tissue.
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Tejido Adiposo/metabolismo , Adiposidad/fisiología , Ayuno/metabolismo , Glicoproteínas de Membrana Plaquetaria/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Animales , Citocinas/metabolismo , Inflamación , Leucocitos/metabolismo , Masculino , Ratones , Ratones Noqueados , Transducción de SeñalRESUMEN
Inflammation induced by obesity contributes to insulin resistance and atherosclerosis. Indeed, high levels of proinflammatory cytokines trigger chronic low-grade inflammation and promote detrimental metabolic effects in the adipose tissue. On the other hand, inflammation seems to control fat pad expansion and to have important functions on lipolysis and glucose metabolism. Thus, it is possible that inflammation may also drive fat pad loss, as seen during long-fast periods. Herein, we have used fasting as a strategy to induce weight loss and evaluate the possible role of inflammation on adipose tissue remodeling. Male BALB-c mice were fed with chow diet (lean mice) or with high-carbohydrate refined diet (mildly obese mice) for 8 weeks. After that, animals were subjected to 24 h of fasting. There was a 63% reduction of adiposity in lean mice following fasting. Furthermore, the adipose tissue was enriched of immune cells and had a higher content of IL-6, TNF-alpha, IL-10, TGF-ß and CXCL-1. Interestingly, mildly obese mice, subjected to the same 24-h fasting period, lost only 33% of their adiposity. Following fasting, these mice did not show any increment in leukocyte recruitment and cytokine levels, as did lean mice. Our findings indicate that inflammation participates in fat mass loss induced by fasting. Although the chronic low-grade inflammation seen in obesity is associated with metabolic diseases, a lower inflammatory response triggered by fasting in mildly obese mice impairs fat pad mobilization.
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Tejido Adiposo , Adiposidad/fisiología , Ayuno/fisiología , Obesidad/fisiopatología , Paniculitis/fisiopatología , Animales , Peso Corporal , Quimiocina CXCL1/metabolismo , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Masculino , Ratones Endogámicos BALB C , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
The global rise in obesity rates is alarming since this condition is associated with chronic low-grade inflammation and secondary comorbidities as glucose intolerance, cardiovascular disease and liver damage. Therefore, a lot of dietary approaches are proposed to prevent and to treat obesity and its associated disorders. Virgin coconut oil (VCO) is well known as a functional food due to its significant amounts of medium-chain triglycerides. This study aimed to evaluate the effect of VCO on adiposity, metabolic and inflammatory dysfunctions induced by a high-refined carbohydrate-containing (HC) diet in mice. Male BALB/c mice were divided into two groups and fed with control (C) or HC diet to induce obesity for eight weeks. At the 9th week mice fed with HC diet were randomly regrouped into four groups, and were kept this way until the 12th week, as following: (i) HC diet alone or HC diet supplemented with three different VCO doses (ii) 1000 mg/kg, (iii) 3000 mg/kg and (iv) 9000 mg/kg. Regardless of the concentration used, VCO supplementation promoted lower adiposity and also improvement in glucose tolerance, lower serum glucose and lipid levels and decreased hepatic steatosis. Moreover, VCO intake induced a lower inflammatory response due to decreased number of leukocytes and TNF-α and IL-6 concentrations in adipose tissue, as well as reduced counts of total leukocytes, mononuclear and polymorphonuclear circulating cells. Our data showed that VCO can be considered as an interesting potential dietary approach to attenuate obesity and its metabolic and inflammatory alterations.
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Aceite de Coco/farmacología , Carbohidratos de la Dieta/efectos adversos , Obesidad/dietoterapia , Acetil-CoA Carboxilasa/metabolismo , Adipoquinas/sangre , Tejido Adiposo/efectos de los fármacos , Tejido Adiposo/metabolismo , Tejido Adiposo/patología , Animales , Dieta de Carga de Carbohidratos/efectos adversos , Suplementos Dietéticos , Metabolismo Energético/efectos de los fármacos , Glucosa/metabolismo , Lípidos/sangre , Masculino , Ratones Endogámicos BALB C , Obesidad/etiología , Consumo de Oxígeno/efectos de los fármacos , Paniculitis/dietoterapiaRESUMEN
OBJECTIVE: Acute inflammation is a normal response of tissue to an injury. During this process, inflammatory mediators are produced and metabolic alterations occur. Adipose tissue is metabolically activated, and upon food consumption, it disrupts the inflammatory response. However, little is known about the acute inflammatory response in joints that results from diet-induced adipose tissue remodeling. The objective of this study was to determine whether alterations in adipose tissue mass arising from food consumption modify the inflammatory response of antigen-induced joint inflammation in mice. METHODS: Male BALB/c mice were fed a chow diet, a highly refined carbohydrate-containing (HC) diet for 8 wk. They were then immunized and, after 2 wk, received a knee injection of methylated bovine serum albumin (mBSA). They were sacrificed at 6, 24, and 48 h after injection. The effect of the cafeteria diet for 8 wk, which also increases adipose tissue, or conjugated linoleic acid (CLA) supplementation for 4 wk, a model of lipodystrophy, was evaluated 24 h after knee challenge with mBSA. RESULTS: Cellular influx, predominantly neutrophils, in synovial fluid was attenuated in the HC diet group, as were levels of myeloperoxidase and IL-1ß in periarticular tissue and histopathological analysis. These responses were associated with reduced adiponectin and increased leptin in serum, which was pronounced in mice fed the HC diet. Cafeteria diet and CLA supplementation induced a profile similar to that seen with the HC diet in terms of inflammation, disease response, and metabolic alteration. Interestingly, after the injection of mBSA, the area of adipocytes in the infrapatellar fat pad increased in mice fed with chow diet similar to those fed the HC and cafeteria diet. CONCLUSIONS: We demonstrated that attenuation of joint response induced by diet was independent of adipose tissue remodeling but could be associated with metabolic alterations.
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Tejido Adiposo/metabolismo , Adiposidad , Artritis/metabolismo , Dieta , Inflamación/metabolismo , Lipodistrofia/metabolismo , Obesidad/metabolismo , Adipocitos , Adiponectina/sangre , Tejido Adiposo/patología , Animales , Artritis/inducido químicamente , Artritis/complicaciones , Artritis/patología , Carbohidratos de la Dieta/administración & dosificación , Carbohidratos de la Dieta/metabolismo , Grasas de la Dieta/administración & dosificación , Grasas de la Dieta/metabolismo , Suplementos Dietéticos , Inflamación/inducido químicamente , Interleucina-1beta/sangre , Articulación de la Rodilla/metabolismo , Articulación de la Rodilla/patología , Leptina/sangre , Ácidos Linoleicos Conjugados/farmacología , Metabolismo de los Lípidos , Lipodistrofia/complicaciones , Masculino , Metaboloma , Ratones Endogámicos BALB C , Neutrófilos/metabolismo , Obesidad/complicaciones , Peroxidasa/sangre , Albúmina Sérica BovinaRESUMEN
Abstract Periodontal diseases (PD) are inflammatory conditions that affect the teeth supporting tissues. Increased body fat tissues may contribute to activation of the systemic inflammatory response, leading to comorbidities. Some studies have shown that individuals with obesity present higher incidence of PD than eutrophics. Objective: To investigate the impact of obesity on periodontal tissues and oral microbiota in mice. Methodology: Two obesity mice models were performed, one using 12 weeks of the dietary protocol with a high-fat (HF) diet in C57BL/6 mice and the other using leptin receptor-deficient mice (db/db-/-), which became spontaneously obese. After euthanasia, a DNA-DNA hybridization technique was employed to evaluate the microbiota composition and topical application of chlorhexidine (CHX), an antiseptic, was used to investigate the impact of the oral microbiota on the alveolar bone regarding obesity. Results: Increased adipose tissue may induce alveolar bone loss, neutrophil recruitment, and changes in the oral biofilm, similar to that observed in an experimental model of PD. Topical application of CHX impaired bone changes. Conclusion: Obesity may induce changes in the oral microbiota and neutrophil recruitment, which are associated with alveolar bone loss.
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Cisplatin (CDDP) is a chemotherapeutic agent widely used in several anticancer protocols for instance head and neck, testicle, ovarian, lung and peritoneal carcinomatosis. According to the literature, the use of CDDP is associated with several side effects; among them, we highlighted the mucositis. CDDP, when administered by IP, promoted significant intestinal epithelium alterations in an experimental model. Our research group has proposed that the incorporation of CDDP into long-circulating and pH-sensitive liposomes (SpHL-CDDP) could help to overcome some side effects induced by this drug. Thus, we evaluated signs of intestinal toxicity 24h and 72h after the administration of a single i.p dose of free CDDP or SpHL-CDDP to healthy Swiss mice. Twenty-four hours after administration of free CDDP, the mice showed signs of intestinal toxicity, principally weight loss, increased intestinal permeability associated with a decrease in expression of tight junctions, and histological damage with the presence of inflammatory infiltrates and activation of ERK1/2 and NF-κB. These changes persisted after 72h. While signs of intestinal toxicity were also observed 24h after administration of SpHL-CDDP, after 72h body weight and intestinal permeability of mice in this group were similar to those of mice in the control group. In comparison with the free CDDP treatment group, 72h after treatment mice in the SpHL-CDDP group showed better histological parameters, lower levels of inflammatory infiltrate with increased IL-10 and IgA levels, and less activation of caspase-3, ERK1/2 and NF-κB. These differences could account for the recovery of the intestinal epithelium observed in mice treated with SpHL-CDDP but not in mice treated with free CDDP. In conclusion, here we show that encapsulation of CDDP in SpHL lessens intestinal damage and that, as such, SpHL-CDDP is a promising candidate for clinical use.
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Antineoplásicos/toxicidad , Cisplatino/toxicidad , Absorción Intestinal/fisiología , Liposomas/química , Animales , Antineoplásicos/administración & dosificación , Antineoplásicos/química , Antineoplásicos/farmacocinética , Caspasa 3/metabolismo , Cisplatino/administración & dosificación , Cisplatino/química , Cisplatino/farmacocinética , Preparaciones de Acción Retardada , Liberación de Fármacos , Humanos , Concentración de Iones de Hidrógeno , Interleucina-10/metabolismo , Masculino , Ratones , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , FN-kappa B/metabolismo , Permeabilidad , Distribución TisularRESUMEN
Stroke is one of the most frequent causes of death and disability worldwide causing a major clinical and socioeconomic impact. Although the pathophysiology of brain ischemia and reperfusion is complex, the inflammatory process plays an important role in pathogenesis, contributing to the expansion of brain injury. The 5-lipoxygenase (5-LOX) is a key enzyme in the biosynthesis of the leukotrienes and has been implicated and in the central nervous system (CNS) disorders such as Alzheimer's disease and acute ischemic stroke. Zileuton, a selective 5-LOX inhibitor, has antiinflammatory properties and exerts an inhibitory effect on inflammatory diseases. The objective of this study was to evaluate the effects of blocking 5-LOX activity in a murine model of transient and global brain ischemia. Zileuton improved neurological deficits and significantly decrease volume and density of lesion, compared to vehicle-ischemic animals measured by magnetic resonance imaging (MRI). In addition, the blockage of 5-LOX reduced infarct area and histopathological changes. Furthermore, by enzyme immunoassay (ELISA) increased brain levels of tumor necrosis factor-alpha (TNFalpha), interferon-gamma (IFN-gamma), interleukin-1beta (IL-1beta), interleukin-6 (IL-6), chemokine (C-X-C motif) ligand 1 (CXCL1), chemokine (C-C motif) ligand 3 (CCL3) and chemokine (C-C motif) ligand 5 (CCL5) were detected in the vehicle-ischemic group, whereas in Zileuton-ischemic group presented reduction of these mediators. The concentration of the antiinflammatory cytokine interleukin-10 (IL-10) was increased after 5-LOX inhibition. Our results suggest that Zileuton decreases brain damage and reduces inflammatory cytokines expression in the CNS which contributes, at least in part, to improve the neurological outcome of brain ischemia.
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Antiinflamatorios no Esteroideos/uso terapéutico , Infarto Encefálico/tratamiento farmacológico , Encefalitis/tratamiento farmacológico , Hidroxiurea/análogos & derivados , Enfermedades del Sistema Nervioso/complicaciones , Análisis de Varianza , Animales , Infarto Encefálico/etiología , Estenosis Carotídea/complicaciones , Citocinas/genética , Citocinas/metabolismo , Modelos Animales de Enfermedad , Regulación hacia Abajo/efectos de los fármacos , Encefalitis/etiología , Ensayo de Inmunoadsorción Enzimática , Hidroxiurea/uso terapéutico , Imagen por Resonancia Magnética , Masculino , Ratones , Ratones Endogámicos C57BL , Enfermedades del Sistema Nervioso/etiologíaRESUMEN
OBJETIVO: investigar a influência do risco nutricional, detectado ao início da internação, no desfecho terapêutico de pacientes.MÉTODOS: estudo de coorte prospectiva com 495 pacientes admitidos no pronto-atendimento de um hospital universitário, submetidos à triagem de risco nutricional com base no Nutritional Risk Screening, 2002. Ao final da internação, buscaram-se os prontuários para avaliação do desfecho, complicações e presença da terapia nutricional.RESULTADOS: do total de pacientes, 53,9% eram do sexo feminino, 71,3% tinham idade inferior a 60 anos e 11,7% evoluíram com cuidados paliativos/óbito. Segundo o índice de massa corporal, 15,5% dos pacientes foram classificados como desnutridos. O risco nutricional foi encontrado em 54,5% e associou-se fortemente ao desfecho terapêutico cuidados paliativos/óbito (HR: 5,92; IC 95%: 2,68-13,08), assim como seus componentes, estresse metabólico da doença (HR: 3,33; IC 95°%: 1,61-6,86) e estado nutricional prejudicado (moderado = HR: 3,24; IC 95°%: 1,31-8,00; grave = HR: 6,45; IC 95%: 2,36-17,63), após o ajuste por potenciais fatores de confusão.CONCLUSÃO: a prevalência de risco nutricional detectada foi alta e sua presença estava relacionada a pior desfecho terapêutico.
Objective: To investigate the influence of nutritional risk, detected upon being admitted to a hospital, on therapeutic outcomes in patients. Methods: This prospective cohort study was conducted with 495 patients admitted to the emergency clinic of a public hospital, where they were screened for nutritional risk based on the Nutritional Risk Screening 2002. At the end of hospitalization, the outcome, complications, and the presence of nutritional therapy were evaluated based on the medical records. Results: Of the total patients, 53.9% were female, 71.3% were less than 60 years of age, and 11.7% had the therapeutic outcome of palliative care / death. According to Body Mass Index (BMI), 15.5% of the patients were classified as malnourished. Nutritional risk was found in 54.5%, which correlated strongly with the therapeutic outcome of palliative care/death (HR: 5.92, 95% CI: 2.68 to 13.08) as well as their components of increased nutritional requirements (HR: 3.33, 95% CI: 1.61 to 6.86) and impaired nutritional status (HR = moderate: 3.24, 95% CI: 1.31 to 8.00, severe = HR: 6.45, 95% CI: 2.36 to 17.63) after adjustment for potential confounding factors. Conclusion: The prevalence of nutritional risk detected in the sample was high, and its presence was related to a poor therapeutic outcome.