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OBJECTIVES: To compare serum levels of RAS components in women with RA versus healthy females and to investigate the association between these molecules and subclinical atherosclerosis. METHODS: A cross-sectional study involving female RA patients without ischemic CVD. Disease activity was assessed using the DAS28 and the CDAI. IMT of the common carotid artery was evaluated by ultrasonography. Serum levels of Ang II, Ang-(1-7), ACE and ACE2 were determined by enzyme immunoassay. RESULTS: Fifty women with RA, mean 48.2 (7.3) years, were compared to 30 healthy women, paired by age. RA patients had higher plasma levels of Ang II (p < .01), Ang-(1-7) (p < .01), and ACE (p < .01) than controls. The ratios of ACE to ACE2 were higher in RA patients, whereas Ang II/Ang-(1-7) ratios were lower in RA patients. The presence of hypertension and the treatment with ACE inhibitors did not significantly modify serum levels of Ang II, Ang-(1-7), ACE and ACE2 in patients with RA. Seven RA patients had altered IMT, and eight patients exhibited atherosclerotic plaque. There was a negative correlation between ACE2 levels and IMT (p = .041). IMT positively correlated with age (p = .022), disease duration (p = .012) and overall Framingham risk score (p = .008). Ang II concentrations positively correlated with DAS28 (p = .034) and CDAI (p = .040). CONCLUSION: Patients with RA had an activation of the RAS, suggesting an association with disease activity and cardiovascular risk. Rheumatological key messages Imbalance of both RAS axes may be associated with cardiovascular risk and disease activity in rheumatoid arthritis. Ultrasonography of the carotid arteries can identify early, subclinical atherosclerotic disease in rheumatoid arthritis patients. Angiotensin-converting enzyme inhibition or angiotensin 1 receptor blockade may be beneficial for rheumatoid arthritis patients.
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Enzima de Conversão de Angiotensina 2/sangue , Artrite Reumatoide , Aterosclerose , Espessura Intima-Media Carotídea , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/epidemiologia , Artrite Reumatoide/metabolismo , Doenças Assintomáticas/epidemiologia , Aterosclerose/sangue , Aterosclerose/diagnóstico , Aterosclerose/epidemiologia , Biomarcadores/sangue , Brasil/epidemiologia , Estudos Transversais , Diagnóstico Precoce , Feminino , Fatores de Risco de Doenças Cardíacas , Humanos , Pessoa de Meia-Idade , Gravidade do Paciente , Sistema Renina-AngiotensinaRESUMO
OBJECTIVE: The pathophysiology of autoimmune hepatitis (AIH) may involve the activation of immune cells and changes in the expression of cellular markers. The aim of the present study was to characterize the immunophenotype markers of lymphocytes and monocytes in the peripheral blood of children and adolescents with type 1 AIH and AIH overlap with sclerosing cholangitis (overlap syndrome [OS]). METHODS: This is a cross-sectional study of 20 children and adolescents diagnosed with type 1 AIH and 19 with OS. Fifteen healthy subjects were included as controls. Flow cytometric analysis was used to identify markers of inflammation and autoimmunity. RESULTS: The total number of CD4 T cells was higher in the AIH patients compared with the controls. The number of CD4 T cells expressing CCR3 and CD28 was higher in the AIH group than in the control group. CD45RO was more highly expressed in the AIH group, whereas CD45RA was more highly expressed in the OS group. In regard to CD8 T lymphocytes, the CCR3 expression was higher in both groups of patients. Patients with OS had the highest expression of CD45RA and CD25. In monocytes, human leukocyte antigen DR (HLA-DR) was less expressed in both groups of patients. CONCLUSIONS: Complex phenotype features may be involved in the pathophysiology of AIH, accounting for changes in immune system regulation mechanisms. In conclusion, even after good response to treatment, patients still have immune activity signals at the cellular level.
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Biomarcadores/sangue , Colangite Esclerosante/imunologia , Hepatite Autoimune/imunologia , Imunofenotipagem/métodos , Adolescente , Criança , Colangite Esclerosante/sangue , Estudos Transversais , Feminino , Citometria de Fluxo/métodos , Hepatite Autoimune/sangue , Humanos , Fígado/imunologia , Fígado/patologia , Linfócitos/imunologia , Masculino , Monócitos/imunologia , Adulto JovemRESUMO
OBJECTIVES: This is a cohort study of 134 children and adolescents with a known diagnosis of autoimmune hepatitis (AIH). During follow-up, some of them developed autoimmune sclerosing cholangitis (ASC). This study describes the characteristics of the patients upon diagnosis, and their response to treatment and any complications, and compares the patients who developed ASC during follow-up (ASC group) with those who did not (AIH group). METHODS: A total of 73.1% of the patients were girls with a median age upon diagnosis of 10.41 (7.41-12.53) years. RESULTS: Of 134 patients, 28 (20.9%) developed cholestatic manifestations, with features of ASC. A few differences were observed between the AIH and ASC groups when they were analyzed by χ test, such as the smaller predominance of girls in ASC group (Pâ=â0.04), and more common asymptomatic presentation in the ASC group (Pâ=â0.01). Cirrhosis was observed in 68% of biopsies, with no significant difference between groups (Pâ=â0.43). Of 16 deaths, 15 were in the AIH group and 1 in the ASC group (Pâ=â0.22). Of 11 transplants, 10 were in the AIH group and one in the ASC group (Pâ=â0.53). The presence of cirrhosis at baseline was associated with a smaller survival probability (Pâ=â0.015). The survival rate by Kaplan-Meier method was 94% at 5 years and 80% at 10 years, and was similar in both the groups (Pâ=â0.08). CONCLUSIONS: No statistically significant difference was observed between the groups in relation to prognosis and response to treatment.
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Colangite Esclerosante/complicações , Hepatite Autoimune/mortalidade , Adolescente , Azatioprina/uso terapêutico , Brasil , Criança , Serviços de Saúde da Criança , Estudos de Coortes , Feminino , Hepatite Autoimune/complicações , Hepatite Autoimune/diagnóstico , Hepatite Autoimune/tratamento farmacológico , Humanos , Masculino , Prednisona/uso terapêutico , Prognóstico , Fatores Sexuais , Análise de SobrevidaAssuntos
Albuminúria/etiologia , Albuminúria/urina , Anemia Falciforme/complicações , Peptidil Dipeptidase A/urina , Fatores Etários , Albuminúria/diagnóstico , Anemia Falciforme/diagnóstico , Enzima de Conversão de Angiotensina 2 , Biomarcadores , Criança , Suscetibilidade a Doenças , Humanos , Sistema Renina-AngiotensinaRESUMO
OBJECTIVE: There have been conflicting reports on the relationship between asthma and COVID-19 severity. This study aimed to compare the risk of death among children with asthma and healthy peers hospitalized due to COVID-19. METHODS: We carried out an analysis of all pediatric patients 2-19 years of age with asthma and COVID-19 registered in Influenza Epidemiological Surveillance Information System-Gripe, a Brazilian nationwide surveillance database, between February 2020 and March 2022. The primary outcome was time to death, which was evaluated considering discharge as a competitive risk using the cumulative incidence function. RESULTS: Among 30,405 hospitalized children with COVID-19, 21,340 (70.2%) had no comorbidities, 6444 (21.2%) had comorbidities other than asthma, 2165 (7.1%) had asthma, and 465 (1.5%) had asthma with other comorbidities. The estimated probability of a fatal outcome for each group was 4.1%, 14.9%, 2.1%, and 10.7%, respectively. After adjustment, children with asthma had a 60% reduction in the hazard of death than healthy peers (hazard ratio [HR] = 0.39, 95% confidence interval [CI], 0.29-0.53, p < 0.0001). Among children with asthma and no other comorbidities, two covariates were independently associated with in-hospital mortality, age ≥12 years, HR = 4.0, 95% CI, 2.5-6.4), and low oxygen saturation at admission (HR = 2.3, 95% CI, 1.4-3.2). CONCLUSION: Children with asthma and no comorbidities had a lower risk of death compared with healthy peers after controlling for clinical and demographic confounding factors.
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Asma , COVID-19 , Humanos , Criança , Adolescente , COVID-19/epidemiologia , Brasil/epidemiologia , SARS-CoV-2 , Asma/epidemiologia , Comorbidade , HospitalizaçãoRESUMO
BACKGROUND: Hyperkalemia leads to suboptimal use of evidence-based therapies in patients with heart failure (HF). Therefore, we aimed to assess whether new potassium binders are effective and safe to promote medical optimization in patients with HF. METHODS: MEDLINE, Cochrane, and Embase were searched for randomized controlled trials (RCTs) that reported outcomes after initiation of Patiromer or Sodium Zirconium Cyclosilicate (SZC) versus placebo in patients with HF at high risk of hyperkalemia development. Risk ratios (RR) with 95% confidence intervals (CI) were pooled with a random effects model. Quality assessment and risk of bias were performed according to Cochrane recommendations. RESULTS: A total of 1432 patients from 6 RCTs were included, of whom 737 (51.5%) patients received potassium binders. In patients with HF, potassium binders increased the use of renin-angiotensin-aldosterone inhibitors (RR 1.14; 95% CI 1.02-1.28; p = 0.021; I2 = 44%) and reduced the risk of hyperkalemia (RR 0.66; 95% CI 0.52-0.84; p < 0.001; I2 = 46%). The risk of hypokalemia was significantly increased in patients treated with potassium binders (RR 5.61; 95% CI 1.49-21.08; p = 0.011; I2 = 0%). There was no difference between groups in all-cause mortality rates (RR 1.13; 95% CI 0.59-2.16; p = 0.721; I2 = 0%) or in adverse events leading to drug discontinuation (RR 1.08; 95% CI 0.60-1.93; p = 0.801; I2 = 0%). CONCLUSION: The use of new potassium binders Patiromer or SZC in patients with HF at risk for hyperkalemia increased the rates of medical therapy optimization with renin-angiotensin-aldosterone inhibitors and reduced the incidence of hyperkalemia, at the cost of an increased prevalence of hypokalemia.
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Insuficiência Cardíaca , Hiperpotassemia , Hipopotassemia , Humanos , Hiperpotassemia/tratamento farmacológico , Hiperpotassemia/etiologia , Potássio , Hipopotassemia/complicações , Renina/farmacologia , Renina/uso terapêutico , Aldosterona/farmacologia , Aldosterona/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/tratamento farmacológico , Sistema Renina-Angiotensina , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Angiotensinas/farmacologia , Angiotensinas/uso terapêuticoRESUMO
BACKGROUND: We sought to compare cardiovascular outcomes, renal function, and diuresis in patients receiving standard diuretic therapy for acute heart failure (AHF) with or without the addition of SGLT2i. METHODS AND RESULTS: Systematic search of three electronic databases identified nine eligible randomized controlled trials involving 2,824 patients. The addition of SGLT2i to conventional therapy for AHF reduced all-cause death (odds ratio [OR] 0.75; 95% CI 0.56-0.99; p = 0.049), readmissions for heart failure (HF) (OR 0.54; 95% CI 0.44-0.66; p < 0.001), and the composite of cardiovascular death and readmissions for HF (hazard ratio 0.71; 95% CI 0.60-0.84; p < 0.001). Furthermore, SGLT2i increased mean daily urinary output in liters (mean difference [MD] 0.45; 95% CI 0.03-0.87; p = 0.035) and decreased mean daily doses of loop diuretics in mg of furosemide equivalent (MD -34.90; 95% CI [- 52.58, - 17.21]; p < 0.001) without increasing the incidence worsening renal function (OR 0.75; 95% CI 0.43-1.29; p = 0.290). CONCLUSION: SGLT2i addition to conventional diuretic therapy reduced all-cause death, readmissions for HF, and the composite of cardiovascular death or readmissions for HF. Moreover, SGLT2i was associated with a higher volume of diuresis with a lower dose of loop diuretics.
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Diabetes Mellitus Tipo 2 , Insuficiência Cardíaca , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Diabetes Mellitus Tipo 2/complicações , Diuréticos/efeitos adversos , Diuréticos/farmacologia , Diuréticos/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Rim/efeitos dos fármacos , Ensaios Clínicos Controlados Aleatórios como Assunto , Inibidores de Simportadores de Cloreto de Sódio e Potássio , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêuticoRESUMO
Several studies have demonstrated that non-O blood groups subjects present an increased VTE risk as compared to those carrying O blood group. The aim of this study was to investigate the ABO blood groups influence on factor VIII (FVIII) activity, von Willebrand factor (VWF), and ADAMTS13 plasma levels in patients undergoing hemodialysis (HD). Patients undergoing HD (N=195) and 80 healthy subjects (control group) were eligible for this cross-sectional study. The ABO blood group phenotyping was performed by the reverse technique. FVIII activity was measured through coagulometric method, and VWF and ADAMTS13 antigens were assessed by ELISA. FVIII activity and VWF levels were significantly higher and ADAMTS13 levels was decreased in HD patients, as compared to healthy subjects (P < 0.001, in three cases). HD patients carrying non-O blood groups showed a significant increase in FVIII activity (P = 0.001) and VWF levels (P < 0.001) when compared to carriers of O blood group. However, no significant difference was observed in ADAMTS13 levels (P = 0.767). In the control group, increased in FVIII activity (P = 0.001) and VWF levels (P = 0.002) and decreased in ADAMTS13 levels (P = 0.005) were observed in subjects carrying non-O blood groups as compared to carriers of O blood group.Our data confirmed that ABO blood group is an important risk factor for increased procoagulant factors in plasma, as FVIII and VWF. Admitting the possible role of kidneys in ADAMTS13 synthesis or on its metabolism, HD patients were not able to increase ADAMTS13 levels in order to compensate the increase of VWF levels mediated by ABO blood groups. Considering that non-O blood groups constitute a risk factor for thrombosis, it is reasonable to admit that A, B and AB HD patients need a careful and continuous follow-up in order to minimize thrombotic events.
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Sistema ABO de Grupos Sanguíneos/sangue , Proteínas ADAM/sangue , Fator VIII/metabolismo , Diálise Renal , Fator de von Willebrand/metabolismo , Proteína ADAMTS13 , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Trombose/sangue , Trombose/etiologiaRESUMO
Obesity is one of the major health problems of modem society. The prevalence of this condition has increased at an alarming rate, especially the most severe form (body mass index >40 kg/m2). The cardiovascular problems that generally accompany obesity are the focus of a large number of studies. Conventional echogram and more current modalities, such as tissue Doppler, strain and strain rate are valuable tools for the detection of subclinical dysfunction and the early diagnosis and treatment of patients.
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Ecocardiografia Doppler/métodos , Coração/fisiopatologia , Obesidade/fisiopatologia , HumanosRESUMO
OBJECTIVE: Angiotensin-converting-enzyme 2 (ACE2), the cell surface receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is found in a variety of reproductive tissues. The present study evaluated whether uterine fibroids and normal myometrium express ACE2 and, if so, at which tissue compartments. METHODS: We included 13 premenopausal women (age range 33-50 years, median 40 years) with uterine fibroids undergoing elective hysterectomy or myomectomy. Samples of leiomyoma (n = 12) and normal myometrial tissue (n = 8) were analyzed by immunohistochemistry for protein localization or by real time PCR for mRNA detection. RESULTS: In normal myometrium, ACE2 immunoreactivity was localized in smooth muscle fibers, arteriolar walls, and endothelial cells. In uterine leiomyoma, ACE2 staining was more intense in smooth muscle cells than in the extracellular matrix, and was also present in vascular endothelium. ACE2 mRNA was detected in myometrium as well as in fibroid samples. CONCLUSION: Human myometrium and uterine leiomyoma express ACE2 mRNA and have abundant distribution of ACE2 protein in their smooth muscle cells and microvasculature.
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AngII (angiotensin II), ACE (angiotensin I-converting enzyme) and the AT1 receptor (AngII type 1 receptor) are associated with the inflammatory process and microvascular dysfunction of AKI (acute kidney injury) induced by renal I/R (ischaemia/reperfusion). However, Ang-(1-7) [angiotensin-(1-7)], ACE2 (angiotensin I-converting enzyme 2) and the Mas receptor also play a role in renal disease models. Therefore, in the present study, we have examined the renal profile of Ang-(1-7), ACE2 and the Mas receptor in renal I/R and compared them with that of AngII, ACE and the AT1 receptor. Male Wistar rats were submitted to left nephrectomy and ischaemia (45 min) followed by reperfusion (2 or 4 h) in the right kidney. At 4 h of reperfusion, renal AngII was increased (P<0.01) and renal Ang-(1-7) was decreased substantially (P<0.05), although plasma levels of both angiotensins were unchanged. In addition, renal I/R decreased the renal mRNA expression of renin (P<0.05), AT1 receptors (P<0.001) and ACE2 (P<0.05). At 2 and 4 h of reperfusion, renal ACE activity was reduced (P<0.05). On the other hand, renal expression of the Mas receptor was greatly increased at 4 h of reperfusion (P<0.01), which was confirmed by immunohistochemical and Western blot analysis. In conclusion, increased renal expression of the Mas receptor associated with changes in the RAS (renin-angiotensin system)-related peptidases support an important role for the ACE2-Ang-(1-7)-Mas axis in AKI.
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Angiotensina II/metabolismo , Angiotensina I/metabolismo , Rim/irrigação sanguínea , Fragmentos de Peptídeos/metabolismo , Traumatismo por Reperfusão/enzimologia , Animais , Pressão Sanguínea/fisiologia , Rim/metabolismo , Masculino , Proto-Oncogene Mas , Proteínas Proto-Oncogênicas/metabolismo , Ratos , Ratos Wistar , Receptores Acoplados a Proteínas G/metabolismo , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/fisiopatologia , UrinaRESUMO
BACKGROUND: Antenatal hydronephrosis (ANH) affects â¼1-5% of pregnancies. The aim of this study was to develop a clinical prediction model of renal injury in a large cohort of infants with isolated ANH. METHODS: This is a longitudinal cohort study of 447 infants with ANH admitted since birth between 1989 and 2015 at a tertiary care center. The primary endpoint was time until the occurrence of a composite event of renal injury, which includes proteinuria, hypertension and chronic kidney disease (CKD). A predictive model was developed using a Cox proportional hazards model and evaluated by C-statistics. RESULTS: Renal pelvic dilatation (RPD) was classified into two groups [Grades 1-2 (n = 255) versus Grades 3-4 (n = 192)]. The median follow-up time was 6.4 years (interquartile range 2.8-12.5). Thirteen patients (2.9%) developed proteinuria, 6 (1.3%) hypertension and 14 (3.1%) CKD Stage 2. All events occurred in patients with RPD Grades 3-4. After adjustment, three covariables remained as predictors of the composite event: creatinine {hazard ratio [HR] 1.27, [95% confidence interval (CI) 1.05-1.56]}, renal parenchyma thickness at birth [HR 0.78(95% CI 0.625-0.991)] and recurrent urinary tract infections [HR 4.52 (95% CI 1.49-13.6)]. The probability of renal injury at 15 years of age was estimated as 0, 15 and 24% for patients assigned to the low-risk, medium-risk and high-risk groups, respectively (P < 0.001). CONCLUSION: Our findings indicate an uneventful clinical course for patients with Society for Fetal Urology (SFU) Grades 1-2 ANH. Conversely, for infants with SFU Grades 3-4 ANH, our prediction model enabled the identification of a subgroup of patients with increased risk of renal injury over time.
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One of the major chronic complications of sickle cell disease (SCD) is sickle cell nephropathy. The aim of this review is to discuss the pathophysiology, natural history, clinical manifestations, risk factors, biomarkers and therapeutic approaches for sickle cell nephropathy, focusing on studies with pediatric patients. The earliest manifestation of renal disease is an increase in the glomerular filtration rate. A finding that may also be observed in early childhood is microalbuminuria. Nephrin, KIM-1, VGFs, chemokines and renin-angiotensin system molecules have emerged as potential early markers of renal dysfunction in SCD. In regards to a therapeutic approach, renin-angiotensin system inhibitors and angiotensin receptor blockers seem to be effective for the control of albuminuria in adults with SCD, although new studies in children are needed. The precise moment to begin renoprotection in SCD patients who should be treated remains to be determined.
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Anemia Falciforme/complicações , Nefropatias/etiologia , Animais , Biomarcadores/metabolismo , Humanos , Nefropatias/metabolismo , Nefropatias/patologia , Nefropatias/fisiopatologia , Pediatria , Fatores de RiscoRESUMO
Oxidative stress is an important risk factor for cardiovascular disease and death in hemodialysis (HD) patients. However, whether biochemical and nutritional markers might be useful to stratify HD patients according to the risk of oxidative damage remains unclear. We investigated whether low-cost and easily available parameters such as the profile of nutrients intake, nutritional status, and antioxidant defenses can predict lipid and protein oxidation in HD patients. Forty-nine HD patients (women = 20, men = 29), ranging from 18 to 65 years of age (73.5%) were submitted to biochemical and nutritional analysis. At least 93.9% of HD patients had malnutrition. A patient's stratification according to nutritional risk was highly coherent with anthropometric parameters and nutrients intake, which were complementarily used as markers of malnutrition. Nutritional stratification was unable to reveal differences in the oxidative status. On the other hand, carbohydrate and zinc intake, serum zinc (Zn), glutathione peroxidase (GPx) activity, total antioxidant capacity (TAC), and nonprotein antioxidants (npAC) in serum were predictive markers of lipid (R 2 = 0.588, P < 0.001) and protein (R 2 = 0.581, P < 0.001) oxidation. Interestingly, GPx activity, TAC, and npAC exhibited good (>80% < 90%) or excellent (>90%) accuracy to estimate lipid oxidation (P ≤ 0.01). Regarding the prediction of protein oxidation, GPx activity and TAC presented regular accuracy (>70% < 80%), and Zn serum levels exhibited good sensitivity (P ≤ 0.01). Herein, we provided evidence that clinical characteristics relevant to predict different levels of lipid and protein oxidation in HD patients can be easily obtained, during routine hospital visits by means of the combined analyses of biochemical and nutritional parameters.
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Falência Renal Crônica/sangue , Adolescente , Adulto , Idoso , Antioxidantes/metabolismo , Biomarcadores/sangue , Creatinina/sangue , Ingestão de Energia/fisiologia , Feminino , Hemoglobinas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Oxirredução , Estresse Oxidativo/fisiologia , Diálise Renal , Ureia/sangue , Adulto Jovem , Zinco/sangueRESUMO
The pathogenesis of idiopathic nephrotic syndrome (INS) remains unknown. Several findings suggest a role for the immune system. This study aimed to evaluate immune mediators in INS by measuring plasma and urinary levels of transforming growth factor beta1 (TGF-beta1), monocyte chemoattractant protein-1 (MCP-1/CCL2), regulated on activation normal T-cell expressed and secreted (RANTES/CCL5) and IL-8 (IL-8/CXCL8) in pediatric patients with INS and in age-matched healthy controls. Patients were divided according to their response to corticosteroids: steroid-sensitive (SS, n = 8), or steroid-resistant (SR, n = 24). Immune mediators were also compared in regard with disease activity (relapse and remission). Immune mediators were measured by ELISA. Plasma TGF-beta1 levels in SR patients were approximately 2.8-fold higher than control values (p < 0.05). Urinary IL-8/CXCL8 was 2.9-fold higher in INS patients in relapse (proteinuria >100 mg/m2/24 h) when compared with patients in remission (p < 0.05), and levels had a positive correlation with individual proteinuria values (p < 0.05). Urinary IL-8/CXCL8 was significantly higher in relapsed SR than in SS patients in remission. No changes in MCP-1/CCL2 and RANTES/CCL5 levels were detected. Our findings suggest that IL-8/CXCL8 and TGF-beta1 are involved in the pathogenesis of INS: IL-8/CXCL8 associated with local changes in glomerular permeability and TGF-beta1 could be related to worse response to corticosteroids.
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Fatores Imunológicos , Interleucina-8/imunologia , Síndrome Nefrótica , Proteinúria/imunologia , Adolescente , Quimiocina CCL2/sangue , Quimiocina CCL2/urina , Quimiocina CCL5/sangue , Quimiocina CCL5/urina , Criança , Feminino , Humanos , Fatores Imunológicos/sangue , Fatores Imunológicos/imunologia , Fatores Imunológicos/urina , Interleucina-8/sangue , Interleucina-8/urina , Masculino , Síndrome Nefrótica/metabolismo , Síndrome Nefrótica/fisiopatologia , Proteinúria/sangue , Proteinúria/urina , Fator de Crescimento Transformador beta1/sangue , Fator de Crescimento Transformador beta1/urinaRESUMO
OBJECTIVE: To provide a systematic review investigating the role of inflammatory molecules and neurotrophic factors as biomarkers of neuropsychomotor development in preterm neonates. DATA SOURCE: Databases including PubMed, BIREME, and Scopus were systematically searched. Observational studies, as well as transversal, and cohort studies using human subjects published from 1990 to September 2017 were eligible for inclusion. Two authors independently identified eligible studies and analyzed their characteristics, quality, and accuracy in depth. DATA SYNTHESIS: 11 eligible studies clearly investigated the association between peripheral inflammation and motor and/or cognitive development in preterm infants. However, the selected populations differed in relation to the events associated with prematurity and the risk factors to abnormal motor and/or cognitive development. These studies measured circulating levels of cytokines, chemokines, adhesion molecules, acute phase proteins, and growth factors. The most commonly analyzed proteins were IL-1ß, IL-6, TNF, CCL5/RANTES, CXCL8/IL-8, IGFBP-1, and VEGF. In seven of the eligible studies, plasma levels of IL-6 correlated with development delay. Two studies reported correlation between CXCL8/IL-8 plasma levels with cognitive and motor delay. In one study, higher levels of MCP-1/CCL2 were associated with better cognitive and motor outcome. CONCLUSION: There is preliminary evidence indicating that circulating inflammatory molecules are associated with motor and cognitive development in preterm neonates, even considering different populations.
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Cognição/fisiologia , Citocinas/metabolismo , Recém-Nascido Prematuro/fisiologia , Fatores de Crescimento Neural/metabolismo , Desempenho Psicomotor/fisiologia , Criança , Desenvolvimento Infantil , Bases de Dados Bibliográficas , HumanosRESUMO
BACKGROUND: Parkinson´s Disease (PD) is a chronic, progressive condition, being the second most common neurodegenerative disorder worldwide. The classical features include: bradykinesia, resting tremor, rigidity and festination. These neurological alterations are probably due to the death of dopaminergic neurons in the Substantia Nigra pars compacta and consequent reduction of dopamine input into the striatum. The decrease of dopamine levels may also be involved in the emergence of non-motor symptoms, including cognitive impairment, anxiety and depression symptoms. Neurotrophic Factors (NF) are proteins that modulate neuronal function, development, and survival. It has been reported that NF might exert a protective role in PD. OBJECTIVE: We aim to discuss the emerging evidence from pre-clinical and clinical studies regarding the role of NF in PD as well as their potential as promising therapeutic strategies. METHODS: We carried out an extensive literature search in PubMed central. RESULTS: Pre-clinical studies using NF to treat PD are divergent probably due to several methodological differences, thus precluding any conclusion. Clinical studies findings obtained with the administration of NF in patients with PD were even more disappointed. On the other hand, pre-clinical and clinical studies generally support that physical activity is a low-cost, non-pharmacologic strategy with good results to treat PD. CONCLUSION: The use of NF as a treatment for PD is still a promise not incorporated in clinical practice. Methods to deliver NFs, doses and compounds administered, side effects, population characteristics and duration of disease may probably contribute to the unsuccessful results.
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Fatores de Crescimento Neural/farmacologia , Doença de Parkinson/tratamento farmacológico , Animais , Estudos Clínicos como Assunto , Avaliação Pré-Clínica de Medicamentos , Exercício Físico , Humanos , Fatores de Crescimento Neural/química , Fatores de Crescimento Neural/metabolismo , Doença de Parkinson/terapiaRESUMO
This study was designed to determine whether the levels of renin-angiotensin system (RAS) components are associated with Alzheimer's disease (AD) pathology. Cerebrospinal fluid levels of Angiotensin (Ang) II, Ang-(1-7), angiotensin-converting enzyme (ACE), ACE2, Amyloid-ß (Aß)40, Aß42, total tau (hTau), and phospho-tau (pTau) were measured in 18 patients with AD and 10 controls. Patients with AD presented decreased levels of ACE when compared with controls. We found a significant positive correlation between ACE and Aß42 levels among patients. Our results strengthen the hypothesis that ACE is associated with Aß pathology in AD.
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Doença de Alzheimer/líquido cefalorraquidiano , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Fragmentos de Peptídeos/líquido cefalorraquidiano , Peptidil Dipeptidase A/líquido cefalorraquidiano , Idoso , Enzima de Conversão de Angiotensina 2 , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas tau/líquido cefalorraquidianoRESUMO
AIM: The aim of this study is to evaluate the presence of a particular immunological profile in individuals long-term infected with HTLV-1, followed presenting different clinical courses. MATERIALS & METHODS: Forty-eight individuals were evaluated for 19 cytokines analyzed in cerebrospinal fluid and plasma of patients with HTLV-1 presenting with and without neurological symptoms. RESULTS: Proinflammatory cytokines and the chemokine ligand 11 (ITAC/CXCL11) were increased in individuals with HTLV-1 coursing with neurological symptoms. CONCLUSION: Different cytokines' expression profile in the presence of neurological symptoms may help to understand and characterize the progression for severe clinical presentations.
Assuntos
Citocinas/sangue , Citocinas/líquido cefalorraquidiano , Infecções por HTLV-I/complicações , Vírus Linfotrópico T Tipo 1 Humano/fisiologia , Doenças do Sistema Nervoso/sangue , Doenças do Sistema Nervoso/líquido cefalorraquidiano , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/complicações , Fatores de TempoRESUMO
OBJECTIVE: To compare the short-term efficacy of surfactant administration by laryngeal mask airway versus endotracheal tube. METHODS: Preterm infants (28-35 weeks of gestational age), weighing 1kg or more, with respiratory distress syndrome, requiring nasal continuous positive airway pressure, with increased respiratory effort and/or fraction of inspired oxygen (FiO2)≥0.40 to maintain oxygen saturation 91-95%, were randomized to receive surfactant by LMA following nCPAP or by ETT following mechanical ventilation (MV). The primary outcome was a clinical response defined as FiO2≤0.30 three hours after surfactant. Secondary outcomes for LMA group were: need of surfactant retreatment during the first 24h, MV requirement, and presence of surfactant in gastric content. RESULTS: Forty-eight patients were randomized; 26 in the LMA group and 22 in the ETT group. Six of 26 patients (23%) in the LMA group and five of 22 patients (22.7%) in the ETT group did not meet the primary outcome (p=0.977). Fourteen (53.8%) of the LMA patients were not intubated nor ventilated; 12 (46.1%) were ventilated: for surfactant failure (23%), for nCPAP failure (11.5%), and for late complications (11.5%). Groups were similar regarding prenatal status, birth conditions, and adverse events. No significant gastric content was found in 61.5% of the LMA patients. Oxygen and second dose surfactant requirements, arterial/alveolar ratio, and morbidities were similar among groups. CONCLUSIONS: Surfactant administration by LMA showed short-term efficacy, with similar supplementary oxygen need compared to surfactant by ETT, and lower MV requirement. Further studies with larger sample size are necessary to confirm these results.