The Th17/IL-17 Axis and Kidney Diseases, With Focus on Lupus Nephritis.

Systemic lupus erythematosus (SLE) is a disease characterized by dysregulation and hyperreactivity of the immune response at various levels, including hyperactivation of effector cell subtypes, autoantibodies production, immune complex formation, and deposition in tissues. The consequences of hyperreactivity to the self are systemic and local inflammation and tissue damage in multiple organs. Lupus nephritis (LN) is one of the most worrying manifestations of SLE, and most patients have this involvement at some point in the course of the disease. Among the effector cells involved, the Th17, a subtype of T helper cells (CD4+), has shown significant hyperactivation and participates in kidney damage and many other organs. Th17 cells have IL-17A and IL-17F as main cytokines with receptors expressed in most renal cells, being involved in the activation of many proinflammatory and profibrotic pathways. The Th17/IL-17 axis promotes and maintains repetitive tissue damage and maladaptive repair; leading to fibrosis, loss of organ architecture and function. In the podocytes, the Th17/IL-17 axis effects include changes of the cytoskeleton with increased motility, decreased expression of health proteins, increased oxidative stress, and activation of the inflammasome and caspases resulting in podocytes apoptosis. In renal tubular epithelial cells, the Th17/IL-17 axis promotes the activation of profibrotic pathways such as increased TGF-ß expression and epithelial-mesenchymal transition (EMT) with consequent increase of extracellular matrix proteins. In addition, the IL-17 promotes a proinflammatory environment by stimulating the synthesis of inflammatory cytokines by intrinsic renal cells and immune cells, and the synthesis of growth factors and chemokines, which together result in granulopoiesis/myelopoiesis, and further recruitment of immune cells to the kidney. The purpose of this work is to present the prognostic and immunopathologic role of the Th17/IL-17 axis in Kidney diseases, with a special focus on LN, including its exploration as a potential immunotherapeutic target in this complication.

Immunity and Fibrogenesis: The Role of Th17/IL-17 Axis in HBV and HCV-induced Chronic Hepatitis and Progression to Cirrhosis.

Cirrhosis is a common final pathway for most chronic liver diseases; representing an increasing burden worldwide and is associated with increased morbidity and mortality. Current evidence has shown that, after an initial injury, the immune response has a significant participation in the ongoing damage, and progression from chronic viral hepatitis (CVH) to cirrhosis, driving the activation and maintenance of main fibrogenic pathways. Among immune deregulations, those related to the subtype 17 of T helper lymphocytes (Th17)/interleukin-17 (IL-17) axis have been recognized as key immunopathological and prognostic elements in patients with CVH. The Th17/IL-17 axis has been found involved in several points of fibrogenesis chain from the activation of stellate cells, increased expression of profibrotic factors as TGF-ß, promotion of the myofibroblastic or epithelial-mesenchymal transition, stimulation of the synthesis of collagen, and induction of imbalance between matrix metalloproteinases and tissue inhibitors of metalloproteinases (TIMPs). It also promotes the recruitment of inflammatory cells and increases the expression of proinflammatory cytokines such as IL-6 and IL-23. So, the Th17/IL-17 axis is simultaneously the fuel and the flame of a sustained proinflammatory and profibrotic environment. This work aims to present the immunopathologic and prognostic role of the Th17/IL-17 axis and related pathways in fibrogenesis and progression to cirrhosis in patients with liver disease due to hepatitis B virus (HBV) and hepatitis C virus (HCV).

Prevalence of cardiovascular risk factors among workers at a private tertiary center in Angola.

BACKGROUND: The burden of cardiovascular diseases (CVD) is increasing in most countries of sub-Saharan Africa. However, as there is a scarcity of data, little is known about CVD in Angola. This study aimed to determine the prevalence of prehypertension, hypertension, prediabetes, diabetes, overweight, and obesity among workers at a private tertiary center in Angola. METHODS: A cross-sectional study was conducted among 781 workers of Clínica Girassol, a tertiary health care center in Angola, during the month of November 2013. Demographic, anthropometric, and clinical variables were analyzed. RESULTS: Of the 781 participants studied, 50.44% were males and 78.11% were under 40 years old. The prevalence of hypertension and prehypertension was 17.93% (95% confidence interval [CI]: 15.24%-20.74%) and 54.03% (95% CI: 50.58%-57.62%), respectively. Among hypertensive subjects, 83.57% (117) were unaware of the diagnosis. Hypertension was associated with age (≥40 years) (odds ratio [OR]: 6.21; 95% CI: 4.18-9.24; P<0.001) and with overweight and obesity (OR: 2.32; 95% CI: 1.56-3.44; P<0.001). The prevalence of diabetes and prediabetes was 2.69% (95% CI: 1.54%-3.97%) and 7.94% (95% CI: 6.02%-9.99%), respectively. The prevalence of overweight was 34.44% (95% CI: 31.11%-37.90%) and 19.85% (95% CI: 17.03%-22.79%) for obesity. There was an association between overweight and obesity and the female sex (OR: 1.71; 95% CI: 1.29-2.28; P<0.001). The prevalence of family history of CVD, smoking, and alcoholism was 52.24%, 4.87%, and 45.33%, respectively. CONCLUSION: There was a high prevalence of cardiovascular risk factors in apparently healthy workers at the private tertiary center in Angola.

Immune Imbalances in Non-Alcoholic Fatty Liver Disease: From General Biomarkers and Neutrophils to Interleukin-17 Axis Activation and New Therapeutic Targets.

Non-alcoholic fatty liver disease (NAFLD) is an increasing problem worldwide and is associated with negative outcomes such as cirrhosis, hepatocellular carcinoma, insulin resistance, diabetes, and cardiovascular events. Current evidence shows that the immune response has an important participation driving the initiation, maintenance, and progression of the disease. So, various immune imbalances, from cellular to cytokines levels, have been studied, either for better compression of the disease pathophysiology or as biomarkers for severity assessment and outcome prediction. In this article, we performed a thorough review of studies that evaluated the role of inflammatory/immune imbalances in the NAFLD. At the cellular level, we gave special focus on the imbalance between neutrophils and lymphocytes counts (the neutrophil-to-lymphocyte ratio), and that which occurs between T helper 17 (Th17) and regulatory T cells as emerging biomarkers. By extension, we reviewed the reflection of these imbalances at the molecular level through pro-inflammatory cytokines including those involved in Th17 differentiation (IL-6, IL-21, IL-23, and transforming growth factor-beta), and those released by Th17 cells (IL-17A, IL-17F, IL-21, and IL-22). We gave particular attention to the role of IL-17, either produced by Th17 cells or neutrophils, in fibrogenesis and steatohepatitis. Finally, we reviewed the potential of these pathways as new therapeutic targets in NAFLD.

The Predictive Role of Inflammatory Biomarkers in Atrial Fibrillation as Seen through Neutrophil-Lymphocyte Ratio Mirror.

Atrial fibrillation (AF) is the most common arrhythmia and is responsible for significant disease burden worldwide. Current evidence has suggested that systemic inflammatory response plays a crucial role in the initiation, maintenance, and progression of AF. So, recent efforts have been directed in search of measurable inflammatory biomarkers as additional tools in severity and prognosis assessment of AF. A simple, and easily obtainable, inflammatory marker is the neutrophil-lymphocyte ratio (NLR), which has shown good performance in preliminary studies as a potential prognostic biomarker in patients with AF. In this work, we performed a thorough review of clinical studies that evaluated the role of C-reactive protein (CRP), interleukin-6 (IL-6), and NLR as predictors of outcomes in AF. We gave a particular emphasis on the NLR because it is a simpler, widely available, and inexpensive biomarker.

Prevalence of Peripheral Arterial Disease among Adult Patients Attending Outpatient Clinic at a General Hospital in South Angola.

Background. Peripheral arterial disease (PAD) is a common manifestation of atherosclerosis, whose prevalence is increasing worldwide, and is associated with all-cause mortality. However, no study has assessed this disease in Huambo. The aim of this study was to evaluate the prevalence of PAD in patients attending an outpatient clinic at a general hospital in Huambo, South Angola. Methods. A cross-sectional study, including 115 patients aged 40 years and older attending an outpatient service. The evaluation included a basic questionnaire for lifestyle and medical history and ankle-brachial index (ABI) measurement using hand-held Doppler. PAD was defined as an ABI ≤0.9 in either lower limb. Results. Of 115 patients, 62.60% were women with a median age of 52.5 (range of 40 to 91) years. The prevalence of PAD was 42.6% (95% confidence intervals [CI]: 95%: 33.91-52.17%). Among patients with PAD, 95.92% had mild disease and 4.08% moderate to severe disease. The main risk factor for PAD was age (≥60 years) (χ (2) = 3.917, P ≤ 0.05). The prevalence was slightly higher in men and hypertensive subjects, but without statistical significance with ORs of 1.5 (95% CI: 0.69-3.21) and 1.42 (95% CI: 0.64-3.17), respectively. Hypertension was also high in the group (66.95%). Conclusion. The prevalence of PAD was 42.6%, higher in those aged 60 years and older. More studies, with representative samples, are necessary to clarify PAD prevalence and associated risk factors.

The role of inflammation in cardiovascular diseases: the predictive value of neutrophil-lymphocyte ratio as a marker in peripheral arterial disease.

Peripheral arterial disease (PAD) is an important manifestation of atherosclerosis, with increasing prevalence worldwide. A growing body of evidence shows that the systemic inflammatory response is closely related to the development, progression, and prognosis of atherosclerosis. In the last decade, several studies have suggested the role of measured inflammatory biomarkers as predictors of severity and prognosis in PAD in an effort to stratify the risk of these patients, to improve treatment selection, and to predict the results after interventions. A simple inflammatory marker, more available than any other, is the neutrophil-lymphocyte ratio (NLR), which can be easily obtained in clinical practice, based on the absolute count of neutrophils and lymphocytes from the differential leukocytes count. Many researchers evaluated vigorously the NLR as a potential prognostic biomarker predicting pathological and survival outcomes in patients with atherosclerosis. In this work, we aim to present the role of NLR as a prognostic marker in patients with PAD through a thorough review of the literature.

Adenocarcinoma of the third and fourth portions of the duodenum: The capsule endoscopy value.

UNLABELLED: Primary adenocarcinoma of the small intestine occurs in over 50% of cases in the duodenum. However, its location in the third and fourth duodenal portions occurs rarely and is a diagnostic challenge. The aim of this work is to report an adenocarcinoma of the third and fourth duodenal portions, emphasizing its diagnostic difficulty and the value of video capsule endoscopy. A man, 40 years old, with no medical history, with abdominal discomfort and progressive fatigue, presented four months ago with one episode of moderate melena. The physical examination was normal, except for mucosal pallor. Blood tests were consistent with microcytic, hypochromic iron deficiency anemia with 7.8 g/dL hemoglobin. The upper and lower endoscopy were normal. Additional work-up with video capsule endoscopy showed a polypoid lesion involving the third and fourth portions of the duodenum. Biopsy showed a moderately differentiated adenocarcinoma. Abdominal computed tomography showed a wall thickening from the third duodenal portion to the proximal jejunum, without distant metastasis. The patient underwent segmental resection (distal duodenum and proximal jejunum) with duodenojejunostomy. The surgical specimen histology confirmed the biopsy diagnosis, with transmural infiltration, without nodal involvement. CONCLUSION: Adenocarcinoma of the third and fourth portions of the duodenum is difficult to diagnose and capsule endoscopy is of great value.

Prevalência de pré-hipertensão e hipertensão em crianças e adolescentes deuma escola de Blumenau, Santa Catarina, Brasil / Prevalence of prehypertension and hypertension in children and adolescents of one school, Blumenau, Santa Catarina, Brazil

Objetivo: Estudar a prevalência de pré-hipertensão ehipertensão em crianças e adolescentes de uma escolade Blumenau. Metodologia: Estudo transversal com alunosde uma escola de ensino fundamental. Foram mensuradosos dados antropométricos e pressão arterial. Foideterminado o percentil da pressão arterial colocandoo valor aferido em tabelas padronizadas por sexo, idadee percentil da estatura. Nos casos em que foi maiorou igual ao percentil 90 (p90), a aferição foi repetida emduas visitas posteriores. Considerou-se pré-hipertensãoquando a pressão arterial sistólica (PAS) e/ou pressão arterialdiastólica (PAD), aferida em três ocasiões separadas,foi maior ou igual ao percentil 90, mas menor queo percentil 95; e hipertensão quando foi maior ou igualao percentil 95. Pressão arterial ?120/80 em adolescentesfoi considerada pré-hipertensão independentedo percentil. Foi utilizado o teste qui-quadrado e testet de Student para analisar a associação com fatoressócio-demográficos e foi aceita significância estatísticaum valor de p <0,05. Resultados: Foram estudadas 120crianças e adolescentes; idade média de 11,1± 2,1 anos;73 (%) do sexo feminino; altura média de 146,9 cm. Dosestudados 19 (15,8%) estavam com pressão elevada(8,3% com pré-hipertensão e 7,5% com hipertensão). Amaior probabilidade de ter pressão elevada foi associadacom a idade ? 12 anos (p< 0,05). Conclusão: Identificamosuma prevalência de pressão elevada de 15,8% (8,3pré-hipertensão e 7,5% hipertensão); sendo o grupo demaior risco aqueles com idade ? 12 anos.

Objective: To study the prevalence of prehypertensionand hypertension in children and adolescents of aschool of Blumenau. Methods: Cross-sectional study ona basic school. We measured anthropometric data andblood pressure. We determined the blood pressure percentileby placing the value measured in standardizedtables by sex, age and height percentile. When it wasgreater or equal to 90th percentile (p90), the measurementwas repeated on two subsequent visits. It wasconsidered prehypertension when the systolic bloodpressure (SBP) and / or diastolic blood pressure (DBP),measured on three separate occasions, was greater orequal to 90th percentile, but less than the 95th percentile;and hypertension when it was greater or equalto 95th percentile. Blood pressure ? 120/80 in adolescentswas considered prehypertension regardless ofthe percentile. We used the chi-square and Student?st test for analyze the association with socio-demographicfactors, and we accepted statistical significance forp <0.05. Results: We studied 120 children and adolescents,mean age 11.1 ± 2.1 years; 73 (%) female, averageheight of 146.9 cm. Nineteen of studied (15.8%)had elevated blood pressure (8.3% with pre-hypertension,and 7.5% with hypertension). Most likely to havehigh blood pressure was age 12 years or older (p<0.05).Conclusions: We identified a prevalence of high bloodpressure of 15.8% (8.3% pre-hypertensionand 7.5% hypertension); and risk group comprised those aged 12years or older.