Tania Maria de Andrade Rodrigues

IL-10 and ET-1 as biomarkers of rheumatic valve disease

Objective To evaluate the immunological profile and gene expression of endothelin-1 (ET-1) in mitral valves of patients with rheumatic fever originated from a reference service in cardiovascular surgery. Methods This was a quantitative, observational and cross-sectional study. Thirty-five subjects (divided into four groups) participated in the study, 25 patients with chronic rheumatic heart disease and ten control subjects. The mean age of the sample studied was 34.5 years. Seventeen of them (48.58%) were male and 18 (51.42%) were female. Inflammatory cytokines (TNF-α, IL-4 and IL-10) were measured and ten mitral valves of patients who underwent first valve replacement were collected for determination of gene expression of endothelin-1 by real time PCR. Results Among the groups studied (patients vs. controls), there was a statistically significant difference in IL-10 levels (P=0.002), and no differences in other cytokines. Expression of endothelin-1 was observed in 70% of samples. Quantitatively, average of ET-1 expression was 62.85±25.63%. Conclusion Inflammatory cytokine IL-10 participates in the maintenance of chronicity of rheumatic fever in patients who underwent valve replacement and those who are undergoing medical treatment. The expression of endothelin-1 in heart valve lesions in patients undergoing mitral valve replacement confirms its association with inflammatory activity in rheumatic fever.

Gene expression of endothelin receptors in replaced rheumatic mitral stenotic valves.

OBJECTIVES Rheumatic fever is a highly prevalent disease in Brazil, and it poses a major public health problem. It is the leading cause of acquired heart disease in childhood and adolescence. The aim of this study was to evaluate the gene expression of ET-3 and its receptors, in replaced rheumatic mitral valves. METHODS We studied the gene expression of endothelin-3 (ET-3) and its receptors, endothelin receptor A and endothelin receptor B (ETr-A and ETr-B), in the rheumatic mitral valves of 17 patients who underwent valve replacement surgery. The samples also underwent a histological analysis. RESULTS Our data showed that almost all patients, regardless of individual characteristics such as gender or age, expressed the endothelin receptor genes, but did not express the genes for ET-3. In quantitative analysis, the ETr-A/GAPDH mean ratio was 33.04 ± 18.09%; while the ETr-B/GAPDH mean ratio was 114.58 ± 42.30%. Regarding histopathological individual features, the frequency of fibrosis is 100%, 88.23% of mononuclear infiltrate, 52.94% of neovascularization, 58.82% of calcification and absence of ossification. CONCLUSION The presence of receptors ETr-A and ETr-B in rheumatic mitral valves suggests its interaction with the system of circulating endothelins, particularly ETr-B (known for acting in the removal of excess endothelin) detected in a greater proportion, which could explain the lack of expression of endothelin in rheumatic mitral valve, process to be elucidated.

Analysis of immunostaining and western blotting of endothelin 1 and its receptors in mitral stenosis

Introduction Rheumatic Fever represents a serious public health problem in developing countries, with thousands of new cases each year. It is an autoimmune disease, which occurs in response to infection by streptococcus A. Objective The aim of this study was to evaluate the immunolabeling and protein expression for endothelin-1 and 3 (ET-1, ET-3) and its receptors (ETA, ETB) in rheumatic mitral valves. Methods Immunohistochemistry was used to identify ET-1/ET-3 and ETA/ETB receptors in rheumatic and control mitral valves. Quantitative analysis of immunostaining for ET-1/ET-3 and ETA/ETB receptors was performed. In addition, western blot analysis was carried out to assess protein levels in tissue samples. Results ET-1 and ETA receptor immunostaining predominated in stenotic valves, mainly associated with fibrotic regions, inflammatory areas and neovascularization. Quantitative analysis showed that the average area with positive expression of ET-1 was 18.21±14.96%. For ETA and ETB, the mean expressed areas were respectively 15.06±13.13% and 9.20±11.09%. ET-3 did not have a significant expression. The correlation between the expression of both endothelin receptors were strongly positive (R=0.74, P=0.02), but the correlation between ET-1 and its receptor were negative for both ETA (R=-0.37, P=0.25), and ETB (R=-0.14, P=0.39). This data was supported by western blot analysis. Conclusion The strong correlation between ET-1 and its receptors suggests that both play a role in the pathophysiology of rheumatic mitral valve stenosis and may potentially act as biomarkers of this disease.

The Relationship between Different Types of Streptococci and Pharyngotonsillitis: A Systematic Review

Introduction: Streptococci were initially viewed by Louis Pasteur in 1879. Brown, in 1919, created the first systematized classification of streptococci in α, β and γ. Rebecca Lancefield contributed for knowledge of streptococcal polysaccharides discovering groups and M cell wall protein. Streptococci are gram positive, catalase and oxidase negative. Streptococci related to pathogenesis of acute sore throat are Streptococcus β-hemolytic of the groups A, B, C, F and G. Objective: Our objective was to make a review of the different types of streptococcus that can cause infection in the oropharynx. Review: Streptococcus pyogenes is belonging to the Lancefield grouping. Skin and mucous membranes of humans are the only known reservoir in the nature of streptococcus group A. Streptococcus of Group B (SGB) was originally isolated by Nocard in 1887. The primary habitat of these bacteria is the human colon, although it may colonize the oropharynx and especially, the vagina. For this reason, in mid-1960, the SGB has become a major cause of perinatal bacterial infection, including bacteremia and urinary tract infection in pregnant women. Group C is involved in purulent pharyngitis outbreaks. According to Fox et al, Streptococcus anginosus is the most common isolate β-hemolytic group C in the oropharynx. Streptococcus Group C (SGC) is reported as “pyogenes-like” because it shares important virulence factors such as hemolysins, extracellular enzymes and M proteins as well as the SGA. Conclusion: We conclude that it’s important to have knowledge about the different types of streptococci to better treat patients with sore throats and problems associated with this condition.

A Decade of Lipid Profiles: A Gender Focus

Introduction and Objectives: The lipid profile is an important predictor of the risk of coronary heart disease (CHD). Higher rates of total cholesterol (TC) and cholesterol of low-density lipoprotein (LDL-C) increase the chances of developing this disease. However, it is known that women due to hormonal factors would have fewer cardiovascular events. The main objective of this article is to assess the association among different parameters of the lipid profile between the different sexes in the population of a city in Brazil. Methods: This is a descriptive, longitudinal and retrospective study based on secondary data collected in the period from 2003 to 2013 in a medical laboratory in Aracaju, Brazil. The lipid profile was determined using the following markers: total cholesterol (TC); high-density lipoprotein cholesterol (HDL-C); low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG). Statistical analysis was performed using measures of central tendency and variance. The inferential analysis was performed by student’s t test and the p-value was 0.05. Results: The sample consists of 63,396 people, 24,425 male and 38,971 female, with mean age of 42.02±17.38 years. The mean value of total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and triglyceride was respectively, 193.39±43.62 mg/dl, 48.80±11.24 mg/dl, 118.35±36.75 mg/dl and 131.28±82.21 mg/dl. Between the genres, it was observed statistical significant differences between all parameters of lipid profile (p<0.0001). Conclusion: We concluded that women have higher rates of total cholesterol and low-density lipoprotein cholesterol; while men have lower rates of high-density lipoprotein cholesterol and higher of triglyceride, which predisposes males to the development of metabolic syndrome.

Evaluation of cytokines produced by β-hemolytic streptococcus in acute pharyngotonsillitis

INTRODUCTION The most common pathogen in bacteria lpharyngotonsillitis is group A β-hemolytic streptococcus, although groups B, C, F,and G have also been associated with pharyngotonsillitis. OBJECTIVE To assess the levels of the cytokines TNF-α, IL-6,IL-4, and IL-10 in bacterial pharyngotonsillitis caused by group A and non-A (groups B, C, F and G) β-hemolytic streptococcus. METHODS The study was conducted at a pediatric emergency care unit. The sample comprised children (5-9 years old) with acute bacterial pharyngotonsillitis diagnosed between December of 2011 and May of 2012. The research involved collection of blood samples from the patients, enzyme-linked immunosorbent assay detection of TNF-α, IL-6,IL-4, and IL-10, and collection of two oropharyngeal swabs for bacterial isolation. Additionally, the medical history of the study participants was also collected. RESULTS In the studied group (mean age: 5.93 years), higher pharyngotonsillitis incidence was observed in the female gender (64.76%). Higher incidence of tonsillar exudates was observed with groups A and C. No statistically significant differences in cytokine levels were observed among groups. However, the group A and the control group showed a difference in the IL-6 level (p=0.0016). CONCLUSIONS The Groups A and C showed higher cytokine levels than the Groups B and control, suggesting similar immunological patterns.

Evaluation of polymorphic genetic markers in patients with chronic periodontitis in a Brazilian population

Introduction: Chronic periodontitis (CP) is an inflammatory disease caused by the interaction among dental plaque and host immune responses. Interleukin-6 (IL-6) and matrix metalloproteinase-1 (MMP-1) play an important role in the periodontium destruction. Some authors have studied polymorphisms in these genes but the results were controversial. Objective: To evaluate the association of polymorphisms in the promoter region of genes IL-6 (-174) and MMP-1 (-1607) with CP in a Brazilian population. Material and methods: A case-control study of 64 cases of CP patients and 25 healthy subjects was performed. Genomic DNA was isolated from buccal mucosa and two single nucleotide polymorphism in IL-6 (-174 G/C) and MMP-1 (-1607 1G/2G) genes were analyzed using polymerase chain reaction followed by restriction fragment length polymorphism analysis. Results: There were no statistically significant differences between patients with CP and control group, nor to genotypes (p = 0.734) or to alleles (p = 0.763), with respect to IL-6 polymorphism. For MMP-1 polymorphism, also we found no statistically significant difference in genotype (p = 0.607) and allele (p = 0.237) distribution between the different groups. Conclusion: The polymorphisms of the studied genes were not associated with susceptibility to CP in this Brazilian population.