RESUMO
Histoplasmosis usually presents primarily as lung infection. Occasionally, mainly in immunocompromised hosts, it can spread and cause systemic manifestations. Skin lesions have been reported in 10 to 15 percent of cases of disseminated histoplasmosis, and panniculitis has been described as an unusual form of presentation in affected patients. We present the case of a patient with systemic lupus erythematosus who presented cellulitis due to disseminated histoplasmosis.
Assuntos
Histoplasmose/patologia , Lúpus Eritematoso Sistêmico/complicações , Paniculite/patologia , Biópsia , Celulite/imunologia , Celulite/microbiologia , Celulite/patologia , Feminino , Histoplasma/isolamento & purificação , Histoplasmose/imunologia , Humanos , Imunocompetência , Pessoa de Meia-Idade , Paniculite/imunologia , Paniculite/microbiologiaRESUMO
Abstract: Histoplasmosis usually presents primarily as lung infection. Occasionally, mainly in immunocompromised hosts, it can spread and cause systemic manifestations. Skin lesions have been reported in 10 to 15 percent of cases of disseminated histoplasmosis, and panniculitis has been described as an unusual form of presentation in affected patients. We present the case of a patient with systemic lupus erythematosus who presented cellulitis due to disseminated histoplasmosis.
Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Paniculite/patologia , Histoplasmose/patologia , Lúpus Eritematoso Sistêmico/complicações , Biópsia , Paniculite/imunologia , Paniculite/microbiologia , Celulite/imunologia , Celulite/microbiologia , Celulite/patologia , Histoplasma/isolamento & purificação , Histoplasmose/imunologia , ImunocompetênciaRESUMO
Genetic- and diet-induced obesity and insulin resistance are associated with an increase in mechanistic target of rapamycin complex (mTORC) 1 activity in adipose tissue. We investigated herein the effects of pharmacological mTORC1 inhibition in the development of adipose tissue inflammation induced by high-fat diet (HFD) feeding, as well as in the polarization, metabolism and function of bone marrow-derived macrophages (BMDM). For this, C57BL/6J mice fed with a standard chow diet or a HFD (60% of calories from fat) and treated with either vehicle (0.1% Me2SO, 0.2% methylcellulose) or rapamycin (2mg/kg/ day, gavage) during 30days were evaluated for body weight, adiposity, glucose tolerance and adipose tissue inflammation. Although rapamycin did not affect the increase in body weight and adiposity, it exacerbated the glucose intolerance and adipose tissue inflammation induced by HFD feeding, as evidenced by the increased adipose tissue percentage of M1 macrophages, naive and activated cytotoxic T lymphocytes, and mRNA levels of proinflammatory molecules, such as TNF-α, IL-6 and MCP-1. In BMDM in vitro, pharmacological mTORC1 inhibition induced phosphorylation of NFκB p65 and spontaneous polarization of macrophages to a proinflammatory M1 profile, while it impaired M2 polarization induced by IL-4+IL-13, glycolysis and phagocytosis. Altogether, these findings indicate that mTORC1 activity is an important determinant of adipose tissue inflammatory profile and macrophage plasticity, metabolism and function.
Assuntos
Macrófagos/imunologia , Macrófagos/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/antagonistas & inibidores , Obesidade/imunologia , Obesidade/metabolismo , Paniculite/imunologia , Paniculite/metabolismo , Animais , Biomarcadores , Citocinas/metabolismo , Glucose/metabolismo , Imunofenotipagem , Mediadores da Inflamação/metabolismo , Leucócitos/imunologia , Leucócitos/metabolismo , Leucócitos/patologia , Macrófagos/efeitos dos fármacos , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/imunologia , Macrófagos Peritoneais/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/patologia , Paniculite/patologia , Fenótipo , Sirolimo/farmacologiaRESUMO
Overweight and obesity have become epidemic worldwide and are linked to sedentary lifestyle and the consumption of processed foods and drinks. Citrate is a metabolite that plays central roles in carbohydrate and lipid metabolism. In addition, citrate is the additive most commonly used by the food industry, and therefore is highly consumed. Extracellular citrate can freely enter the cells via the constitutively expressed plasma membrane citrate transporter. Within the cytosol, citrate is readily metabolised by ATP-citrate lyase into acetyl-CoA - the metabolic precursor of endogenously produced lipids and cholesterol. We therefore hypothesised that the citrate ingested from processed foods and drinks could contribute to increased postprandial fat production and weight gain. To test our hypothesis, we administered citrate to mice through their drinking water with or without sucrose and monitored their weight gain and other metabolic parameters. Our results showed that mice receiving citrate or citrate+sucrose did not show increased weight gain or an increase in the weight of the liver, skeletal muscles or adipose tissues (AT). Moreover, the plasma lipid profiles (TAG, total cholesterol, LDL and HDL) were similar across all groups. However, the group receiving citrate+sucrose showed augmented fasting glycaemia, glucose intolerance and the expression of pro-inflammatory cytokines (TNF-α, IL-1ß, IL-6 and IL-10) in their AT. Therefore, our results suggest that citrate consumption contributes to increased AT inflammation and altered glucose metabolism, which is indicative of initial insulin resistance. Thus, citrate consumption could be a previously unknown causative agent for the complications associated with obesity.
Assuntos
Ácido Cítrico/efeitos adversos , Sacarose Alimentar/efeitos adversos , Aditivos Alimentares/efeitos adversos , Intolerância à Glucose/etiologia , Resistência à Insulina , Gordura Intra-Abdominal/imunologia , Paniculite/etiologia , Animais , Citocinas/sangue , Dieta Ocidental/efeitos adversos , Intolerância à Glucose/imunologia , Intolerância à Glucose/metabolismo , Intolerância à Glucose/patologia , Gordura Intra-Abdominal/metabolismo , Gordura Intra-Abdominal/patologia , Lipídeos/sangue , Fígado/imunologia , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos , Músculo Esquelético/imunologia , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Tamanho do Órgão , Paniculite/imunologia , Paniculite/metabolismo , Paniculite/patologia , Distribuição AleatóriaRESUMO
BACKGROUND: Obesity is associated with a mild chronic inflammatory response, which has been suggested to be pivotal in the development of cardiometabolic alterations of obesity. However, little is known about the involvement of acute inflammation. OBJECTIVE: To evaluate whether circulating neutrophils, markers of acute inflammation, are associated (quantitatively and qualitatively) with adolescent obesity and whether leptin modulates these associations. SUBJECTS AND METHODS: We assessed 528 adolescents (16.8 yr old, 47% females), without chronic/acute illness. We measured anthropometry and dual energy X-ray absorptiometry and calculated fat mass percentage (FM%). Fasting serum glucose, high-density lipoprotein (HDL)-cholesterol, and triglycerides were used with blood pressure and waist circumference to compute a metabolic z-score. Leukocyte and neutrophil counts were obtained, together with levels of serum leptin. In a subsample of 23 males, flow cytometry was used to assess degranulation (CD66b expression) of neutrophils. RESULTS: Female sex and obesity were positively related to mean neutrophil counts (p < 0.05). When accounting for sex and weight status, leptin was associated with neutrophil counts (p < 0.05), partially explaining the association between obesity and neutrophil counts. Neutrophil counts were related to metabolic risk z-scores, controlling for fat mass. Participants with elevated FM% showed more neutrophil degranulation than controls (p < 0.05). CONCLUSIONS: Participants with increased adiposity had higher circulating neutrophil counts, suggesting acute inflammation. Furthermore, the neutrophils showed more degranulation, indicating inflammation. Obesity-induced alteration of the adipose secretory pattern (i.e., changes in leptin levels) could be involved in acute inflammation.