Manifestaciones pulmonares al diagnóstico de 170 pacientes con vasculitis asociadas a anticuerpos anticitoplasma de neutrófilos: cohorte retrospectiva de un centro universitario / Pulmonary manifestations at the diagnosis of 170 patients with vasculitis associated with anticytoplasmic neutrophil antibodies: retrospective cohort of a university center

INTRODUCCIÓN: Las Vasculitis Asociadas a Anticuerpos Anticitoplasma de Neutrófilos (VAA) son infrecuentes, pero de amplio espectro de presentación. Si bien el consenso de clasificación de Chapel Hill del año 2012, sigue vigente, la tendencia actual es clasificarlas de acuerdo al marcador inmunológico: anti-Proteinasa 3 (PR3) o anti-mieloperoxidasa (MPO). Las manifestaciones pulmonares clásicas son la hemorragia alveolar y los nódulos pulmonares. En los últimos 10 años se ha descrito la enfermedad pulmonar difusa (EPD). Los estudios epidemiológicos son escasos, y suelen representar en su mayoría poblaciones norteamericanas o europeas. El objetivo es describir las características del compromiso pulmonar al debut en VAA en un centro universitario. PACIENTES Y MÉTODO: De un total de 190 pacientes con diagnóstico de VAA se incluyeron 170 en seguimiento en nuestro centro. Se revisaron aspectos clínicos, demográficos, laboratorio e imagenológicos de los pacientes incluidos. RESULTADOS: De los 170 pacientes, 112 (65,88%) presentaron compromiso pulmonar. 106 (94,64%) de los pacientes fueron anticuerpos anti citoplasma de neutrófilos (ANCA) positivos; de estos, 56 (53,27%) MPO (+) y 39 (36,45%) PR-3 (+). Un tercio de los pacientes de ambos grupos presentó hemorragia alveolar. En los pacientes MPO (+) predomina la EPD (53,5%) y en PR-3 (+) los nódulos pulmonares (69,23%). Destaca la baja frecuencia de patología obstructiva asociada. CONCLUSIONES: El compromiso pulmonar en las VAA es prevalente y heterogéneo. En nuestra serie, destaca la frecuencia de EPD en VAA MPO (+), lo que releva la importancia del estudio con ANCA en paciente con diagnóstico y seguimiento por EPD.

INTRODUCTION: Antineutrophil Cytoplasmic Antibodies (ANCA) associated vasculitis (AAV) are uncommon, but of broad spectrum of presentation. Although the 2012 Chapel Hill classification consensus remains valid, the current trend is to classify them according to the immunological marker: anti-Proteinase 3 antibody (PR-3) or anti-Myeloperoxidase antibody (MPO). The classic pulmonary manifestations are alveolar hemorrhage and pulmonary nodules. Interstitial lung disease (ILD) has been described in the last 10 years. Epidemiological studies are scarce, and they usually represent mostly North American or European populations. The objective is to describe the characteristics of lung involvement upon debut in AAV in a university center. PATIENTS AND METHODS: Of a total of 190 patients diagnosed with AAV, 170 were included in follow-up at our center. Clinical, demographic, laboratory and imaging aspects of the included patients were reviewed. RESULTS: Of the 170 patients, 112 (65.88%) had lung involvement. 106 (94.64%) of the patients were ANCA (+); of these, 56 (53.27%) MPO (+) and 39 (36.45%) PR-3 (+). One third of the patients in both groups had alveolar hemorrhage. In MPO (+) patients, ILD predominates (53.5%) and in PR-3 (+) pulmonary nodules (69.23%). The low frequency of associated obstructive pathology stands out. CONCLUSIONS: Pulmonary manifestations in AAVs are frequent and heterogeneous. Locally, the association of ILD and AAV MPO (+) stands out, which highlights the importance of ANCA study in patients with diagnosis and follow-up by ILD.

Dynamic Changes in Perioperative Cellular Inflammation and Acute Kidney Injury after Coronary Artery Bypass Grafting

Abstract Introduction: This study investigated the role of the neutrophil-lymphocyte ratio (NLR), the perioperative changes in NLR (delta-NLR), the platelet-lymphocyte ratio (PLR), and the platelet count in predicting acute kidney injury (AKI) following coronary artery bypass grafting (CABG) during hospital stay. Methods: The records of 396 patients with preoperative creatinine < 1.5 mg/dl undergoing isolated CABG between October 2015 and October 2019 were reviewed retrospectively. Diagnosis of AKI was based on the Kidney Disease Improving Global Outcomes definition. Demographic data, operative data, in-hospital mortality, preoperative NLR, PLR, and platelet counts were compared between patients with (AKI group) and without (non-AKI group) postoperative AKI. Additionally, NLR, delta-NLR, and PLR values were calculated daily for the first four postoperative days. A "subsequent AKI group" was formed for the first four postoperative days by excluding patients diagnosed with AKI. The daily and overall predictivity of the markers for AKI are investigated. Results: AKI was present in 86 patients during the postoperative period, while 310 patients had normal postoperative renal functions. NLR, delta-NLR, and PLR on the first four postoperative days (P<0.001 for all) were significantly associated with the development of AKI in subsequent days. Multivariate analysis identified postoperative NLR (odds ratio 1.17, 95% confidence interval 1.11-1.23; P<0.001) as an independent predictor of AKI. PLR lost its significant association with AKI at the values measured at discharge from hospital (P>0.05). Conclusion: NLR values measured on the first four days postoperatively are a useful tool in predicting AKI during hospital stay following CABG.

Comparison between different tricuspid valve procedures through postoperative inflammation and myocardial enzymes

Abstract Introduction: The thoracoscopic procedure for tricuspid valve (TV) diseases is a minimally invasive method of treatment. This study focuses on comparing the changes in postoperative inflammatory reaction and myocardial injury markers after thoracoscopic and sternotomy/thoracotomy TV procedures. Methods: We retrospectively analyzed 88 patients (53 males, aged 50.9±16.2 years) with TV diseases (single-valve disease) (72 cases of TV plasty) between January 2018 and April 2019. A total of 56 patients underwent thoracoscopic procedure (50 cases of TV plasty). The leukocyte and C-reactive protein (CRP) levels were monitored as indicators of systemic inflammatory reaction. The lactate dehydrogenase, creatine kinase, creatine kinase myocardial band, aspartate aminotransferase, and troponin-T levels were recorded as markers of myocardial injury. Results: The CRP and white blood cells levels of patients in the sternotomy approach group were continuously higher than those in patients in the thoracoscopic approach group. And the levels of myocardial enzymes in patients in the thoracoscopic approach group were significantly lower than those in patients in the sternotomy approach group. Conclusion: Compared with sternotomy/thoracotomy procedures on TV, the thoracoscopic procedure can reduce postoperative myocardial injury significantly and systemic inflammatory reaction to a certain extent. It is technically feasible, safe, effective, and worthy of widespread adoption in clinical practice.

Treatment of pulmonary fibrosis in one convalescent patient with corona virus disease 2019 by oral traditional Chinese medicine decoction: A case report / 中西医结合学报

After one-month of oral treatment with traditional Chinese medicine decoction, without using other drugs, the lung inflammatory exudate, pulmonary fibrosis and quality of life of a 61-year-old female patient with corona virus disease 2019 (COVID-19) were significantly improved. No recurrence or deterioration of the patient's condition was found within seven weeks of treatment and follow-up, and no adverse events occurred, indicating that oral Chinese medicine decoction was able to improve the pulmonary inflammation and fibrosis in a patient recovering from COVID-19, but further research is still needed.

Prenatal mold exposure is associated with development of atopic dermatitis in infants through allergic inflammation / Exposição pré-natal a mofo está associada ao desenvolvimento de dermatite atópicaem neonatos por reação alérgica

Abstract Objective Mold exposure in early life may be associated with development of atopic dermatitis; however, studies of this link are inconclusive and evidence for the underlying mechanism(s) is lacking. This study identified the association between the time of mold exposure and development of atopic dermatitis and investigated the underlying mechanisms. Method The association between atopic dermatitis and mold exposure was examined in the Cohort for Childhood Origin of Asthma and Allergic Diseases birth cohort study (n = 1446). Atopic dermatitis was diagnosed at 1 year of age by pediatric allergists. Exposure to mold was assessed by questionnaire. The Illumina MiSeq platform was used to examine the environmental mycobiome in 20 randomly selected healthy infants and 20 infants with atopic dermatitis at 36 weeks of gestation. Results Prenatal, but not postnatal, mold exposure was significantly associated with atopic dermatitis (adjusted odds ratio, 1.36; 95% confidence interval, 1.01-1.83). Levels of total serum IgE at 1 year of age were higher in infants with atopic dermatitis exposed to mold during pregnancy than in healthy infants not exposed to mold during pregnancy (p = 0.021). The relative abundance of uncultured Ascomycota was higher in infants with atopic dermatitis than in healthy infants. The relative abundance of uncultured Ascomycota correlated with total serum IgE levels at 1 year of age (r = 0.613, p < 0.001). Conclusion Indoor mold exposure during the fetal period is associated with development of atopic dermatitis via IgE-mediated allergic inflammation. Avoidance of mold exposure during this critical period might prevent the development of atopic dermatitis.

Resumo Objetivo A exposição ao mofo no início da vida pode estar associada ao desenvolvimento de dermatite atópica; contudo, os estudos sobre esse vínculo são inconclusivos e faltam evidências dos mecanismos subjacentes. Identificamos a associação entre o momento da exposição ao mofo e o desenvolvimento de dermatite atópica e investigamos os mecanismos subjacentes. Método A associação entre dermatite atópica e exposição a mofo foi examinada em um estudo de coorte de nascimento da Origem da Asma e de Doenças Alérgicas em Crianças (COCOA) (n = 1446). A dermatite atópica foi diagnosticada em pacientes com um ano de vida por pediatras alergistas. A exposição ao mofo foi avaliada por um questionário. A plataforma Illumina MiSeq foi utilizada para examinar o microbioma ambiental em 20 neonatos saudáveis escolhidos aleatoriamente e 20 com dermatite atópica a 36 semanas de gestação. Resultados A exposição pré-natal, porém não pós-natal, ao mofo foi significativamente associada à dermatite atópica (razão de chances ajustada, 1,36; intervalo de confiança de 95%, 1,01-1,83). Os níveis séricos totais de Imunoglobulina E (IgE) no primeiro ano de vida foram maiores em neonatos com dermatite atópica expostos a mofo durante a gravidez do que em neonatos não expostos a mofo durante a gravidez (p = 0,021). A abundância relativa de Ascomycota não cultivado foi maior em neonatos com dermatite atópica do que em neonatos saudáveis. A abundância relativa de Ascomycota não cultivado correlacionou-se com os níveis séricos totais de IgE no primeiro ano de vida (r = 0,613, p < 0,001). Conclusão A exposição ao mofo no ambiente domiciliar durante a gravidez está associada ao desenvolvimento de dermatite atópica por meio de reação alérgica mediada por IgE. A prevenção à exposição ao mofo durante o período crítico da gravidez pode prevenir o desenvolvimento de dermatite atópica.

Adiposity, inflammation and fat-soluble vitamins in adolescents / Adiposidade, inflamação e vitaminas lipossolúveis em adolescentes

Abstract Objective: Evaluate the association between inflammatory process, adiposity, and vitamins A, D, and E in adolescents, according to gender. Methods: Cross-sectional study with adolescents aged 12-19 years old of both genders attending public schools in Recife. A questionnaire was used to collect data on socioeconomic level, lifestyle, and food intake of adolescents. Then, an anthropometric evaluation and a blood sampling were performed to analyze serum concentrations of α-1-acid glycoprotein, retinol, β-carotene, α-tocopherol, and 25-hydroxy-vitamin D. Results: The levels of α-1-acid glycoprotein were higher for abdominal obesity in both genders. Male adolescents with insufficient serum α-tocopherol levels had low levels of α-1-acid glycoprotein (p = 0.03) and an increased risk of 25-hydroxy-vitamin D and β-carotene deficiency in relation to total and abdominal fat; female adolescents had an increased risk of insufficient β-carotene with abdominal obesity (PR: 1.33; 95% CI: 1.2-1.5). Conclusion: Abdominal adiposity implies a higher risk of inflammation and causes different changes to the levels of fat-soluble vitamins according to gender.

Resumo: Objetivo: Avaliar a associação entre processo inflamatório, adiposidade e as vitaminas A, D e E em adolescentes, segundo o sexo. Métodos: Estudo transversal com adolescentes de 12 a 19 anos de ambos os sexos de escolas públicas de Recife. Foi utilizado um questionário para coleta de dados socioeconômicos, de estilo de vida e de consumo alimentar dos adolescentes. Em seguida, realizou-se a avalição antropométrica e coleta de sangue para análise das concentrações séricas de α-1-glicoproteína ácida, retinol, β-caroteno, α-tocoferol e 25-hidroxivitamina D. Resultados: Os níveis de α-1-glicoproteína ácida foram maiores na obesidade abdominal de ambos os sexos. Os meninos com níveis séricos insuficientes de α-tocoferol expressaram níveis reduzidos de α-1-glicoproteína ácida (p = 0,03) e apresentaram um maior risco de deficiência de 25-hidroxivitamina D e β-caroteno na adiposidade total e abdominal, enquanto as meninas mostraram maior risco de insuficiência de β-caroteno com a obesidade abdominal (RP 1,33; IC 95% 1,2-1,5). Conclusão: A adiposidade abdominal reflete maior risco de inflamação e causa alterações distintas nas concentrações das vitaminas lipossolúveis, de acordo com o sexo.

Kidney Disease in Diabetes Mellitus: Cross-Linking between Hyperglycemia, Redox Imbalance and Inflammation / Doença Renal do Diabetes: Cross-Linking entre Hiperglicemia, Desequilíbrio Redox e Inflamação

Abstract Chronic hyperglycemia is the key point of macro- and microvascular complications associated with diabetes mellitus. Excess glucose is responsible for inducing redox imbalance and both systemic and intrarenal inflammation, playing a critical role in the pathogenesis of diabetic kidney disease, which is currently the leading cause of dialysis in the world. The pathogenesis of the disease is complex, multifactorial and not fully elucidated; many factors and mechanisms are involved in the development, progression and clinical outcomes of the disease. Despite the disparate mechanisms involved in renal damage related to diabetes mellitus, the metabolic mechanisms involving oxidative/inflammatory pathways are widely accepted. The is clear evidence that a chronic hyperglycemic state triggers oxidative stress and inflammation mediated by altered metabolic pathways in a self-perpetuating cycle, promoting progression of cell injury and of end-stage renal disease. The present study presents an update on metabolic pathways that involve redox imbalance and inflammation induced by chronic exposure to hyperglycemia in the pathogenesis of diabetic kidney disease.

Resumo A hiperglicemia crônica é o ponto-chave das complicações macro e microvasculares associadas ao diabetes mellitus. O excesso de glicose é responsável por induzir desequilíbrio redox e inflamação sistêmica e intra-renal, desempenhando um papel crítico na patogênese da doença renal do diabetes, configurada atualmente como a principal causa de doença renal dialítica em todo o mundo. A patogênese da doença é complexa, multifatorial e, não totalmente elucidada, estando vários fatores e mecanismos associados ao seu desenvolvimento, progressão e desfechos clínicos. Apesar dos mecanismos díspares envolvidos nos danos renais durante o diabetes, os caminhos metabólicos pela via oxidativa/inflamatória são amplamente aceitos e discutidos. As evidências acentuam que o estado hiperglicêmico crônico desencadeia o estresse oxidativo e a inflamação mediada por diversas vias metabólicas alteradas em um ciclo-vicioso de autoperpetuação, promovendo aumento da injúria celular e progressão para a doença renal dialítica. O presente artigo traz, portanto, uma atualização sobre os caminhos metabólicos que envolvem o desequilíbrio redox e a inflamação induzidos pela exposição crônica à hiperglicemia na patogênese da doença renal do diabetes.

Influence of pregnancy on the inflammatory process following direct pulp capping: a preliminary study in rats

Abstract The purpose of this study was to evaluate the inflammatory process following direct pulp capping during pregnancy. This experimental study involved 48 maxillary first molars of female Wistar rats. The procedures were performed in pregnant and non-pregnant animals (n =20 each). Direct pulp capping with mineral trioxide aggregate (MTA) and restoration with a light-cured resin composite was performed in half of exposed pulp specimens. In the other half of specimens, light-cured composite was placed directly on the exposed pulp. In the control groups (n=4 each), no intervention was performed. Animals were euthanized at 3 and 7 days. All sections (three per slide) were viewed under an optical microscope. One previously calibrated pathologist performed descriptive analysis and assigned scores for inflammatory response and tissue organization adjacent to the pulp exposure. The Kappa value for intra-examiner variability was 0.91. At 3 days, in animals treated with MTA, inflammatory infiltrate was absent in non-pregnant animals while mild inflammatory infiltrate was observed in some pregnant animals. The inflammatory response ranged from mild to severe in both groups treated with composite alone. At 7 days, the inflammatory response was more intense in pregnant than in non-pregnant animals treated with MTA; while this difference were not evident in animals treated with composite alone. In conclusion, pregnancy may not influence the inflammatory process following direct pulp capping with light-cured resin composite, which was always harmful to the pulp; while the tissue response after the direct pulp with MTA were more favorable in non-pregnant animals.

Resumo O objetivo deste estudo foi avaliar o processo inflamatório do tecido pulpar após o capeamento pulpar direto, realizado durante a gestação. Este estudo experimental envolveu 48 primeiros molares superiores de ratos Wistar fêmeas. Os procedimentos foram realizados em animais prenhes e não prenhes (n=20). Após as exposições pulpares, o capeamento pulpar direto foi efetuado com agregado trióxido mineral (MTA) ou restauração direta com resina composta. Nos grupos controle (n=4), nenhuma intervenção foi realizada. Os animais foram submetidos à eutanásia após 3 e 7 dias. Todos os cortes foram avaliados através de um microscópio ótico. Um patologista previamente calibrado realizou analise histológica descritiva e estabeleceu escores para intensidade da resposta inflamatória e para o grau de organização tecidual na região adjacente à exposição pulpar. O valor de Kappa intra-examinador foi 0,91. No período experimental de 3 dias, nos animais tratados com MTA, o infiltrado inflamatório estava ausente nos não prenhes, enquanto infiltrado inflamatório moderado estava presente nos animais prenhes. A resposta inflamatória variou de moderada a severa em ambos os grupos tratados apenas com resina composta. Após o periodo experimental de 7 dias, a resposta inflamatória foi mais intensa nos animais prenhes que nos não prenhes do grupo do MTA, enquanto esta diferença não foi tão evidente nos animais que receberam capeamento pulpar direto com resina composta. Pode-se concluir, que a gestação pode não exercer influência no processo inflamatório do tecido pulpar após proteção pulpar direta com resina composta; a qual foi sempre danosa aos tecidos pulpares. No entanto, a resposta tecidual ao capeamento pulpar com MTA foi mais favorável nos animais não prenhes.

Association of malnutrition-inflammation-cardiovascular disease with cognitive deterioration in peritoneal dialysis patients / 北京大学学报(医学版)

OBJECTIVE@#To investigate the relationship between malnutrition-inflammation-atherosclerosis (MIA) syndrome and deterioration of global and specific domains of cognitive function in peritoneal dialysis (PD) patients.@*METHODS@#This was a multi-center prospective cohort study. The PD patients who met the inclusion criteria were examined with general and specific cognitive function between March 2013 and November 2013. The patients were divided into MIA0, MIA1 and MIA2 groups, according to items of "Yes" for whether or not having cardiovascular disease, serum albumin≤35 g/L or high-sensitive C-reactive protein (hs-CRP) ≥3 mg/L. After 2 years, the patients maintained on PD would be repeatedly measured with cognitive function. The Chi-square test, One-way ANOVA, Kruskal-wallis H rank sum test were used to compare the differences of clinical characteristics, biochemical data, and global and specific cognitive function parameters among the three groups at baseline, and two years later, respectively. The Bonferroni method was applied to adjust the significance level for further comparison between each two different groups. The change of score in each cognitive parameter of global and specific domains was used as dependent variable. Age, gender, education level, depression index, body-mass index, diabetes mellitus, serum sodium levels and MIA (MIA0 was control, MIA1 and MIA2 as dummy variables) were all included in the multivariable linear regression models to analyze the risk factors of the deterioration of cognitive function. The analysis for each cognitive domain was adjusted for the baseline score of the corresponding cognitive parameter. All the analyses were performed using SPSS for Windows, software version 25.0 (SPSS Inc., Chicago, IL).@*RESULTS@#Over two-year follow up, the prevalence of cognitive impairment increased from 20.0% to 24.7%, absolute decrease of 3MS scores were more significantly decreased in MIA2 (-3.9±12.0 vs. 1.1±6.7, P<0.01) and MIA1 group (-2.3±11.8 vs. 1.1±6.7, P<0.05) than those in MIA0 group respectively. Specific cognitive functions, included executive function (trail-making tests A and B, P=0.401, P=0.176), immediate memory (P=0.437), delayed memory (P=0.104), visuospatial skill (P=0.496), and language ability (P=0.171) remained unchanged. Advanced age, lower education, diabetes mellitus and depression were all correlated with the deterioration of one or more cognitive domains, and the patients having one item of MIA syndrome were prone to develop the deterioration of 3MS (P=0.022). Furthermore, the patients having two or more items of MIA syndrome were more likely to develop the deterioration of not only 3MS (P <0.001), but also delayed memory, visuospatial skill, and language ability (P=0.002, P=0.007, P=0.004, respectively).@*CONCLUSION@#Patients with one item or above of MIA syndrome were at high-risk for the deterioration of global cognitive function. The more MIA syndrome items there were, the more specific cognitive domains deteriorated.

Mesenteric lymph drainage alleviates hemorrhagic shock-induced spleen injury and inflammation

Abstract Purpose: To investigate the effect of mesenteric lymph drainage on the spleen injury and the expressions of inflammatory cytokines in splenic tissue in mice following hemorrhagic shock. Methods: Male C57 mice were randomly divided into the sham shock, shock and shock+drainage groups. The mice in both shock and shock+drainage groups suffered femoral artery bleeding, maintained mean arterial pressure (MAP) of 40±2 mmHg for 90 min, and were resuscitated. And mesenteric lymph drainage was performed in the shock+drainage group at the time of resuscitation. After three hours of resuscitation, the splenic tissues were harvested for the histological observation and protein and mRNA expression analysis of cytokines. Results: The spleen in the shock group revealed a significantly structural damage and increased mRNA expressions of MyD88 and TRAF6 and protein expressions of TIPE2, MyD88, TRIF and TRAF3 compared to the sham group. By contrast, the splenic pathological injury in the shock+drainage group was alleviated significantly, and the mRNA and protein expressions of TIPE2, MyD88, TRIF, TRAF3 and TRAF6 were significantly lower than those in the shock group. Conclusion: These results indicate that post-hemorrhagic shock mesenteric lymph drainage alleviates hemorrhagic shock-induced spleen injury and the expressions of inflammatory cytokines.

In vitro effect of uremic serum on barrier function and inflammation in human colonocytes / Efeito in vitro do soro urêmico sobre a função de barreira e inflamação em colonócitos humanos

ABSTRACT Introduction: In chronic kidney disease (CKD), it has been suggested that alterations within the gut are associated with an inflammatory state and uremic toxicity. Studies suggest that uremia may impair the function of the intestinal barrier via the promotion of increased intestinal permeability. To understand the mechanisms that are involved in intestinal barrier damage in the setting of uremia, we evaluated the in vitro effect of uremic serum on transepithelial electrical resistance (TER), inflammation, and apoptosis in intestinal epithelial cells (T84). Methods: Pools of serum from healthy individuals, patients not on dialysis, and patients on hemodialysis (Pre-HD and Post-HD) were prepared. T84 cells were incubated for 24 h in medium, of which 10% consisted of the pooled serum from each group. After incubation, the TER was measured and the following parameters were determined by flow cytometry: expression of toll-like receptors (TLRs), production of reactive oxygen species (ROS), and apoptosis. The level of IL-6 in the culture supernatant was determined by ELISA. Results: No difference was observed among the groups with respect to TER, apoptosis, and ROS or the expression of TLR-2, TLR-4, and TLR-9. IL-6 secretion was higher (p < 0.001) in cells that were incubated with pre- and post-HD serum. Conclusion: The results that were obtained from this model suggest that uremic serum per se does not seem to impair the integrity of intestinal epithelial cells. The increased IL-6 secretion by cells that were incubated with HD serum suggests a potential effect of uremia in the intestinal inflammatory response.

RESUMO Introdução: Tem sido sugerido que na doença renal crônica (DRC) a uremia pode causar alterações intestinais, tais como modificações na microbiota e danos à barreira intestinal, e que estas possíveis alterações podem ter uma relação importante com o estado inflamatório e a toxicidade urêmica apresentadas por pacientes com DRC. Objetivos: Avaliar o efeito in vitro do soro urêmico sobre a permeabilidade da monocamada de células epiteliais do intestino, inflamação e apoptose. Métodos: Pools de soro foram preparados a partir de soros de indivíduos saudáveis, pacientes em tratamento conservador e em hemodiálise (Pré e Pós-HD). As células T84 foram incubadas por 24 horas com os diferentes pools. Em seguida a TER foi medida e as células foram submetidas às seguintes análises: apoptose, produção de espécies reativas de oxigênio (EROs) e expressão de receptores toll-like (TLR) por citometria de fluxo e detecção de IL-6 no sobrenadante da cultura por ELISA. Resultados: Não foram encontradas diferenças, entre os grupos, com relação a TER, apoptose, EROs e expressão de TLR-2, TLR-4 e TLR-9. Já a secreção de IL-6 foi maior (p < 0,001) pelas células incubadas com soro pré-HD e pós-HD. Conclusão: Os resultados obtidos a partir deste modelo sugerem que a uremia per se parece não comprometer a integridade das células epiteliais do intestino. O aumento da secreção de IL-6 pelas células incubadas com soro HD (pré e pós) sugere um potencial efeito da uremia sobre a resposta inflamatória intestinal.

Malnutrition associated with inflammation in the chronic renal patient on hemodialysis

SUMMARY INTRODUCTION Malnutrition-Inflammation-Atherosclerosis Syndrome is very frequent in patients with chronic kidney disease on haemodialysis. In these patients, the inflammation associated with malnutrition is observed by the Malnutrition-Inflammation Score. OBJECTIVE To analyse the relationship between malnutrition-inflammation-atherosclerosis syndrome and anthropometric and biochemical parameters of patients on haemodialysis. METHODS A cross - sectional study was performed at the Haemodialysis Clinic of the Barão de Lucena Hospital, Recife, Brazil, between July and August 2016, with patients cared at the clinic for at least six months. Patients with amputees, hospitalized, visually impaired, HIV positive, with catheters in the neck, ascites and/or oedema, and those who were unable to provide information at the time of the interview were excluded. The patients were submitted to anthropometric evaluation for the classification of the nutritional status by waist circumference, neck circumference, body mass index, waist-to-hip ratio and waist-to-height ratio. Nutritional status related to inflammation was measured by the Malnutrition-Inflammation Score and nutritional status assessment using biochemical indicators that used urea, creatinine and albumin. RESULTS Twenty-seven individuals of both genders, adults and elderly, aged 51.3 ± 13.3 years old participated in the study. The anthropometric evaluation showed that most of the population presented cardiovascular risk. The biochemical evaluation reported low frequencies of malnutrition. Malnutrition-Inflammation-Atherosclerosis syndrome was evidenced in 3.7% of the patients. The Malnutrition-Inflammation Score had a moderate negative correlation with body mass index, waist circumference, neck circumference, waist-to-height ratio and creatinine. CONCLUSION The correlation seen among the parameters suggests that most of the parameters evaluated can be used as an indirect indicator of malnutrition-inflammation-atherosclerosis syndrome.

RESUMO INTRODUÇÃO A síndrome Desnutrição-Inflamação-Aterosclerose é frequente nos pacientes com doença renal crônica em hemodiálise, acarretando perda de proteínas corporais e produção de citocinas pró-inflamatórias. OBJETIVO Verificar, entre os indicadores nutricionais estudados, aqueles que melhor se correlacionam com a síndrome Desnutrição-Inflamação-Aterosclerose em pacientes submetidos à hemodiálise. MÉTODOS O estudo foi transversal, realizado na Clínica de Hemodiálise do Hospital Barão de Lucena, no Recife (PE), entre julho e agosto de 2016, com pacientes atendidos há pelo menos seis meses. Foram excluídos pacientes amputados, internados, com deficiência visual, cateter no pescoço, HIV positivo, ascite e/ou edema e aqueles incapazes de prestar informações no momento da entrevista. Os pacientes foram submetidos à avaliação antropométrica para a classificação do estado nutricional pela circunferência da cintura, perímetro do pescoço, índice de massa corporal, relação cintura-quadril e relação cintura-estatura. O estado nutricional relacionado à inflamação foi mensurado pelo escore Desnutrição-Inflamação e a avaliação do estado nutricional pelos indicadores bioquímicos: ureia, creatinina e albumina. RESULTADOS Participaram do estudo 27 indivíduos de ambos os sexos, adultos e idosos, com idade de 51,3 ± 13,3 anos. A avaliação antropométrica mostrou que a maior parte da população apresentava risco cardiovascular. A avaliação bioquímica relatou baixas frequências de desnutrição. Foi evidenciada síndrome Desnutrição-Inflamação-Aterosclerose em 3,7% dos pacientes. O escore Desnutrição-Inflamação apresentou correlação moderada negativa com o índice de massa corporal, circunferência da cintura, perímetro do pescoço, relação cintura-estatura e creatinina. CONCLUSÃO A correlação observada entre os parâmetros sugere que a maioria dos parâmetros avaliados pode ser utilizada como indicador indireto da síndrome Desnutrição-Inflamação-Aterosclerose.

Estado proinflamatorio en niños obesos / Proinflammatory state in obese children

INTRODUCCIÓN: La presencia de un estado de inflamación de bajo grado en niños obesos, se debería, entre otros factores, a que el tejido adiposo de los obesos produce moléculas proinflamatorias que contribuyen al desarrollo de aterosclerosis. OBJETIVO: Determinar en una población de niños obesos los niveles séricos de ligando CD-40 soluble (sCD40L), proteína quimioatractante de monocitos 1 (MCP-1), interleuquina 6 (IL-6), Factor de Necrosis tumoral a (TNF-a) y Proteína C Reactiva ultrasensible (PCR-us), comparados con un grupo control y analizar la correlación de estas moléculas con las variables antropométricas y metabólicas. PACIENTES Y MÉTODO: Estudio transversal de 37 niños obesos de 8 a 12 años y 20 niños con peso normal. A todos los pacientes se les realizó una historia clínica consignando edad, peso, talla, IMC, circunferencia de cintura, estadios de Tanner y antecedentes familiares. Se determinaron los niveles séricos de sCD40L, MCP-1, IL-6, TNF-a y PCR-us mediante ELISA, PCR-us por quimioluminiscencia, glucemia, insulina plasmática, perfil lipídico y se calculó el índice HOMA. Los datos se expresaron como la mediana y rango intercuartil y se utilizó el coeficiente de Spearman para investigar las correlaciones entre variables. RESULTADOS: Los niños obesos presentaron valores significativamente mayores de sCD40L, MCP-1, IL-6, TNF-a, PCR-us que los niños controles. El índice de masa corporal y la circunferencia de cintura se correlacionaron positivamente con sCD40L y MCP-1. CONCLUSIÓN: Los niveles elevados de las moléculas estudiadas sugieren la presencia de inflamación de bajo grado asociada a obesidad en esta población.

INTRODUCTION: Obesity is a chronic disease that affects adults as well as children and is associated with insulin resistance, type 2 diabetes and cardiovascular disease. One of the reasons for the presence of low-grade inflammation in these patients could be that adipose tissue of the obese produces proin flammatory molecules that favor the development of atherosclerosis. OBJECTIVE: To determine serum levels of soluble CD40 ligand (sCD40L), monocyte chemoattractant protein 1 (MCP-1), interleukin 6 (IL-6), Tumor Necrosis Factor alpha (TNF-Α) and high sensitivity CRP (hsCRP), in an obese chil dren population compared to a control group, also to analyze the correlation of these molecules with the anthropometric and metabolic variables. PATIENTS AND METHOD: A cross-sectional, observational study was carried out on 37 obese children, aged 8 to 12 years, and 20 children with normal weight. Serum levels of sCD40L, MCP-1, IL-6, TNF-Α and hsCRP were determined. Data were expressed as the median and interquartil range and Spearman coefficient was used to investigate correlations between variables. RESULTS: Compared to the control group, obese children presented significantly higher values of sCD40L, MCP-1, IL-6, TNF-Α, and hsCRP than control group. Body mass index and waist circumference correlated positively with sCD40L and MCP-1. CONCLUSION: Elevated levels of the studied molecules studied suggest the presence of low-grade inflammation associated with obesity in this population.

Impacto metabólico e inflamatorio de una comida rica en grasas saturadas y su relación con la obesidad abdominal / Metabolic and inflammatory postprandial effect of a highly saturated fat meal and its relationship to abdominal obesity

Resumen Introducción. La etapa posprandial se asocia con el incremento de marcadores relacionados con el riesgo cardiovascular, cuya intensidad depende del estado metabólico. Objetivo. Determinar el impacto de la ingestión de una comida rica en grasas saturadas sobre el perfil metabólico e inflamatorio y su relación con la obesidad abdominal. Materiales y métodos. Se hizo un ensayo clínico en 42 individuos (21 con obesidad abdominal). Se midieron, en sangre, la glucosa, la insulina, el perfil lipídico, la proteína C reactiva, los lipopolisacáridos y la interleucina 6, en ayunas y después de la ingestión. Resultados. Además de la obesidad, se registró la presencia de resistencia a la insulina y de niveles elevados de triacilglicéridos y proteína C reactiva en ayunas. Asimismo, se detectaron niveles posprandiales más elevados de glucosa, insulina y triacilglicéridos. La interleucina 6 disminuyó en el grupo de personas sin obesidad y los lipopolisacáridos aumentaron en ambos grupos. Conclusión. La ingestión de una comida rica en grasas saturadas produjo un mayor impacto en las variables glucémicas en el grupo con obesidad y, aunque afectó de forma similar los lípidos en ambos grupos, el incremento de triacilglicéridos fue mayor en presencia de una concentración basal elevada y promovió el aumento de lipopolisacáridos. El estado inflamatorio basal y posprandial afectó en mayor medida al grupo con obesidad. El momento posprandial reflejó el estado más frecuente de los individuos en un día normal y permitió evidenciar la capacidad de respuesta metabólica frente a la ingestión de alimentos, así como los estados tempranos de riesgo metabólico.

Abstract Introduction: The postprandial stage is associated with the increase of markers related to cardiovascular risk, and its intensity depends on the metabolic state. Objective: To determine the impact of a high-fat meal intake on the metabolic and inflammatory profile, and its relationship to abdominal obesity. Materials and methods: This clinical trial included 42 individuals (21 with abdominal obesity). We measured glucose, insulin, lipid profile, reactive C protein, lipopolysaccharides, and interleukin 6 in fasting blood, and four hours after eating. Results: Besides obesity, we found insulin resistance and higher levels of fasting triacylglycerides and C-reactive protein. There were higher postprandial responses to glucose, insulin, and triacylglycerides. Interleukin 6 decreased in the non-obese group, and lipopolysaccharides increased in both groups. Conclusions: A saturated high-fat food intake produced a greater impact on the glycemic variables in the group with obesity, while it affected the lipids in both groups. However, the increase of triacylglycerides was higher in the presence of a high basal concentration, and it promoted the increase of lipopolysaccharides. The basal and postprandial inflammatory state affected the group with obesity more. The postprandial moment reflected the most frequent state of the individuals on a normal day and evidenced the capacity of the metabolic response to food intake, as well as early metabolic risk states.

Effect of ozone oxidative preconditioning on inflammation and oxidative stress injury in rat model of renal transplantation

Abstract Purpose: To investigate the effect of ozone oxidative preconditioning (OzoneOP) on inflammation and oxidative stress injury in rat model of renal transplantation. Methods: Thirty six male Sprague Dawley (SD) rats were randomly divided into three groups. Sham group: rats were treated with opening and closing abdomen. Kidney transplantation group (KT group): SD rat received the donor's left kidney derived from another SD rat. Ozone oxidative preconditioning and kidney transplantation (OOP+KT group): donor SD rats received OzoneOP treatments by transrectal insufflations before kidney transplantation. After transplantation, parameters of renal function of recipients were determined. Morphology and pathological changes of renal allograft were examined. Expression of NF-κBp65, HMGB-1 were also determined by Western-blot. Results: Compared to KT group, the morphology and pathological damages of renal allograft were less serious in OOP+KT group. Meanwhile, levels of SOD and GSH-Px of renal allograft in OOP+KT group were higher than those in KT group respectively. Western-blot showed that the expressions of NF-κBp65 and HMGB-1 in OOP+KT group were obviously less than those in KT group. Conclusion: Ozone oxidative preconditioning could attenuate the inflammatory reaction and oxidative stress injury in renal allograft, which might be related with the enhancement of anti-oxidative system and suppression of inflammatory reaction.

Hemolysis and inflammatory response to extracorporeal circulation during on-pump cabg: comparison between roller and centrifugal pump systems

Abstract Objective: To compare the perioperative incidence rates of hemolysis and inflammatory response in patients undergoing coronary artery bypass grafting with the two main types of cardiopulmonary bypass, centrifugal and roller pumps, and establish correlations among hemolytic and inflammatory changes. Methods: This was a prospective, randomized trial of 60 patients assigned to either roller pump (G1, n=30) or centrifugal pump (G2, n=30) bypass. Markers of hemolysis (serum haptoglobin, lactate dehydrogenase [LDH]) and inflammation (interleukin [IL]1ß, IL-6, and TNF-α) were measured and analyzed. Results: There was no significant between-group difference in the variables of interest. In G1, there was a positive association with IL-6 and TNF-α (P<0.01 and P<0.05, respectively). In G2, there was a positive association with LDH in the postoperative period (P<0.5). At 24h post-cardiopulmonary bypass, there were positive associations between LDH and IL-1ß (P<0.05), LDH and TNF-α (P<0.01), haptoglobin and TNF-α (P<0.05), and LDH and TNF-α (P<0.01) in G1, and between LDH and IL-6 (P<0.01), LDH and TNF-α (P<0.01), and LDH and IL-6 (P<0.01) in G2. Conclusion: There were no significant between-group differences in markers of hemolysis or inflammation. IL-6 and TNF-α were positively associated with duration of cardiopulmonary bypass in G1, while LDH was positively associated with duration of cardiopulmonary bypass in G2. The rate of significant associations between markers of hemolysis and inflammation was higher in the roller pump group (G1). Registration number: ReBEC (RBR-92b9dg).

Dietas altas en grasas y sus efectos sobre el intestino / Diets high in fats and their effects on the intestine

El objetivo de esta revisión fue exponer el conocimiento actual sobre la relación existente entre dietas altas en grasa (DAG), alteraciones morfológicas de la mucosa intestinal, efectos inflamatorios y cáncer intestinal. Las DAG inicialmente producen aumento de la microbiota patógena, lo que reduce la cantidad y calidad de la secreción de los exocrinocitos caliciformes, disminuyendo la efectividad de la barrera intestinal. Las bacterias y sus lipopolisacaridos (LPS) promueven la secreción de citoquinas proinflamatorias activando vías de inflamación, que a su vez afectan la integridad de las uniones intercelulares alterando la barrera intestinal. Lo anterior, permite que los LPS ingresen a la lámina propia y circulación sanguínea produciendo inflamación local y sistémica. Así mismo, las DAG generan efectos nocivos en la morfología y función de la mucosa gastrointestinal lo que podría favorecer el desarrollo de cáncer. Lo anterior, podría deberse a que el consumo de DAG es capaz de aumentar la proliferación de células de la mucosa y el número y proliferación de células madres tumorales en el intestino.

The aim of this review was to present current knowledge about the relationship between high fat diets (HFD), morphological alterations of intestinal mucosa, inflammatory effects and intestinal cancer. The HFD initially produces an increase in the pathogenic microbiota, which reduces quantity and quality of secretion of goblet cells, decreasing the effectiveness of intestinal barrier. Bacteria and their lipopolysaccharides (LPS) stimulate the secretion of proinflammatory cytokines by activating inflammation pathways, which in turn affect the integrity of intercellular junctions by changing intestinal barrier. The above allows the LPS enter to lamina propria and blood circulation producing local and systemic inflammation. Likewise, HFD generate deleterious effects on morphology and function of gastrointestinal mucosa, which could favor the development of cancer. This could be due to the fact that consumption of HFD is capable of increasing proliferation of mucosal cells and number and proliferation of tumor stem cells in the intestine.

Inflammatory and nutritional statuses of patients submitted to resection of gastrointestinal tumors / Estado inflamatório e nutricional em pacientes submetidos à ressecção cirúrgica de tumores do trato gastrointestinal

ABSTRACT Objective: to evaluate the association between the nutritional and the inflammatory statuses of patients with cancer of the gastrointestinal tract undergoing surgical resection and to identify predictors of mortality in these patients. Methods: we conducted a prospective study of 41 patients with gastrointestinal tract cancer submitted to surgery between October 2012 and December 2014. We evaluated the nutritional status by subjective and objective methods. We assessed the inflammatory response and prognosis using the modified Glasgow Prognostic Score (mGPS), Neutrophil/Lymphocyte Ratio (NLR), Onodera Prognostic Nutritional Index (mPNI), Inflammatory-Nutritional Index (INI) and C-Reactive Protein/Albumin ratio (mPINI). Results: half of the patients were malnourished and 27% were at nutritional risk. There was a positive association between the percentage of weight loss (%WL) and the markers NLR (p=0.047), mPINI (p=0.014) and INI (p=0.015). Serum albumin levels (p=0.015), INI (p=0.026) and mPINI (p=0.026) were significantly associated with the PG-SGA categories. On multivariate analysis, albumin was the only inflammatory marker independently related to death (p=0.004). Conclusion: inflammatory markers were significantly associated with malnutrition, demonstrating that the higher the inflammatory response, the worse the PG-SGA (B and C) scores and the higher the %WL in these patients. However, further studies aimed at improving surgical outcomes and determining the role of these markers as predictors of mortality are required.

RESUMO Objetivo: avaliar a associação entre o estado nutricional e inflamatório em pacientes com câncer do trato gastrointestinal submetidos à ressecção cirúrgica e identificar variáveis preditoras de mortalidade nestes pacientes. Métodos: estudo prospectivo de 41 pacientes com câncer do trato gastrointestinal submetidos à cirurgia entre outubro de 2012 e dezembro de 2014. O estado nutricional foi avaliado por métodos subjetivos e objetivos. A resposta inflamatória e o prognóstico foram avaliados através do Escore Prognóstico de Glasgow modificado (mGPS), razão Neutrófilo/Linfócito (NLR), Índice Nutricional Prognóstico de Onodera (mPNI), Índice Inflamatório Nutricional (INI) e razão Proteína C-reativa/Albumina (mPINI). Resultados: metade dos pacientes estava desnutrida e 27% apresentavam-se em risco nutricional. Associação positiva foi encontrada entre percentual de perda de peso (%PP) e os marcadores NLR (p=0,047), mPINI (p=0,014) e INI (p=0,015) e os níveis séricos de albumina (p=0,015), INI (p=0,026) e mPINI (p=0,026) se associaram significativamente às categorias da ASG-PPP. Na análise multivariada, a albumina foi o único marcador inflamatório independentemente relacionado ao óbito (p=0,004). Conclusão: marcadores inflamatórios foram significativamente associados com a desnutrição, demonstrando que quanto maior a resposta inflamatória, piores foram os escores da ASG-PPP (B e C) e maior o %PP nesses pacientes. No entanto, mais estudos, com o objetivo de melhorar resultados cirúrgicos e determinar o papel desses marcadores como preditores de mortalidade são necessários.

Long non-coding RNA HOTAIR promotes UVB-induced apoptosis and inflammatory injury by up-regulation of PKR in keratinocytes

Excessive exposure to ultraviolet (UV) rays can cause damage of the skin and may induce cancer, immunosuppression, photoaging, and inflammation. The long non-coding RNA (lncRNA) HOX antisense intergenic RNA (HOTAIR) is involved in multiple human biological processes. However, its role in UVB-induced keratinocyte injury is unclear. This study was performed to investigate the effects of HOTAIR in UVB-induced apoptosis and inflammatory injury in human keratinocytes (HaCaT cells). Quantitative real-time polymerase chain reaction was performed to analyze the expression levels of HOTAIR, PKR, TNF-α, and IL-6. Cell viability was measured using trypan blue exclusion method and cell apoptosis using flow cytometry and western blot. ELISA was used to measure the concentrations of TNF-α and IL-6. Western blot was used to measure the expression of PKR, apoptosis-related proteins, and PI3K/AKT and NF-κB pathway proteins. UVB induced HaCaT cell injury by inhibiting cell viability and promoting cell apoptosis and expressions of IL-6 and TNF-α. UVB also promoted the expression of HOTAIR. HOTAIR suppression increased cell viability and decreased apoptosis and expression of inflammatory factors in UVB-treated cells. HOTAIR also promoted the expression of PKR. Overexpression of HOTAIR decreased cell viability and increased cell apoptosis and expression of inflammatory factors in UVB-treated cells by upregulating PKR. Overexpression of PKR decreased cell viability and promoted cell apoptosis in UVB-treated cells. Overexpression of PKR activated PI3K/AKT and NF-κB pathways. Our findings identified an essential role of HOTAIR in promoting UVB-induced apoptosis and inflammatory injury by up-regulating PKR in keratinocytes.