Influence of Neuropeptide Y and Neuropeptide Y 2 Receptor Variants in Acute Coronary Syndrome

Abstract Background The neuropeptide Y (NPY) is one of the most abundant neurotransmitters in the nervous system. NPY acts as a potent stimulator of angiogenesis, inflammation, and adipogenesis, through the NPY 2 receptor (NPY2R). Changes in the NPY signaling pathway have been linked to Acute Coronary Syndrome (ACS). Objectives The purpose of this study is to determine the association between variants in the NPY and NPY2R genes, as well as the severity of acute coronary syndrome (ACS). Methods Approximately 221 ACS patients and 278 healthy controls were selected for this study. Four variants in NPY and two variants in NPY2R genes were genotyped using Taqman allelic discrimination and sequencing. The Chi-square and Fisher's exact tests were used to verify the genotype frequencies. The logistic regression analyses were used for the evaluation of the studied variables. Haplotype analysis was used to evaluate the linkage disequilibrium (LD) between the variants (p<0.05). Results An association of NPY c.20T>C variant was found with the ACS group when compared to the healthy group. In the analysis between variants and risk factors in the ACS group, NPY c.84G>A was associated with hypertension. The analysis between TIMI risk showed a significance for NPY c.20T>C between the low and intermediate/high TIMI risk groups. In the haplotype analysis, strong linkage disequilibrium (LD) was found between the variants NPY c.150G>A and NPY c.-485T>C. Conclusion The NPY c.20T>C variant appears to contribute to the development of ACS. The NPY2R c.-1116A>G variant may contribute to the early development of ACS and the NPY c.84G>A variant appears to contribute to the development of hypertension. In addition, the NPY c.20T>C is associated with a protective effect in ACS severity.

Suckling by Schistosoma mansoni-infected mothers restored IgG2a and TGF-β production, but not IL-6 and delayed-type hypersensitivity in IL-12/IL-23-deficient mice

Abstract INTRODUCTION Suckling by schistosomotic mice improves anti-ovalbumin (OA) antibody production, while delayed-type hypersensitivity (DTH) remains unaffected. This property of milk from schistosomotic mice was investigated in IL-12/IL-23-deficient mice (IL-12p40KO). METHODS We compared anti-OA DTH, IgG2a and cytokines in wild-type and IL-12p40KO mice suckled by infected (SIM) or non-infected (CONTROL) mothers. RESULTS SIM mice showed similar intensity and eosinophils in the DTH, which was abolished in IL-12p40KO and IL-12p40KO-SIM mice. In IL-12p40KO-SIM, IgG2a and TGF-β levels were higher, but IL-6 levels were lower. CONCLUSIONS Milk from schistosomotic mothers may evoke IgG2a without eliciting DTH in IL-12/IL-23 deficiencies, by changing TGF-β/IL-6 levels.

Evaluation of Polymorphisms in IL8 and IL16 Genes in Patients with Acute Coronary Syndrome

Abstract Background: Acute coronary syndrome (ACS) is a cardiovascular disease caused by obstruction of coronary arteries by atheromatous plaque. Susceptibility to this disease may be related to genetic variations, such as single nucleotide polymorphisms (SNPs). Objective: In this study, we evaluated the relationship between SNPs in IL8 (rs4073; -251 A/T) and IL16 (rs11556218; T/G) genes and SCA in a Brazilian population. Materials and Methods: A sample of 200 patients with ACS and 50 non-ACS patients hospitalized at the Real Hospital Português, Recife - PE, Brazil, and 220 blood donors (donors) was used. Genotyping was carried out by polymerase chain reaction, and DNA sequencing. Statistical analyzes were performed using the Williams G, Chi-square and Kruskal Wallis tests, using the BioEstat 5.0 program, and the data with a value of p < 0.05 were considered significant. Results: In the IL8 gene, the AT genotype was the most frequent (p > 0.05) in all three groups. In the IL16 gene, genotypic distributions were different between patients with ACS and the donor group (p = 0.002), with the most frequent G allele in the second group (p = 0.0052). The IL-16 cytokine was higher in donors than in patients with ACS (p = 0.04) and the G (TG + GG) allele had higher values of this cytokine (p = 0.01). Conclusions: The results demonstrate the important role of the rs11556218 SNP in IL16 gene in SCA, evidencing that the G allele may be associated with a decreased risk of the disease.

Social conditions and immune response in human immunodeficiency virus-seropositive pregnant women: a cross-sectional study in Brazil

Abstract INTRODUCTION The functioning of the immune system during pregnancy is altered in both human immunodeficiency virus (HIV)-infected and uninfected women. Unfavorable socioeconomic conditions have been indicative of higher morbidity and mortality and worsening of the immune system. The aim of this study was to correlate social status with levels of interleukin (IL)-10 (non-inflammatory) and interferon-gamma (IFN-γ; inflammatory) cytokines. METHODS A cross-sectional study was conducted with three groups of women: 33 pregnant HIV-infected (G1); 40 non-pregnant, HIV-infected (G2); and 35 pregnant, HIV-uninfected. To measure the social status, a compound indicator called the social status index (SSI), was established using sociodemographic variables (i.e., education level, housing conditions, per capita income, and habitation and sanitary conditions). RESULTS The HIV-infected women had a higher proportion of unfavorable SSI (73% and 75% of G1 and G2, respectively). There were significantly lower IL-10 levels in the G1 group with both unfavorable and favorable SSI than in the other groups. No significant difference in IFN-γ levels was observed among groups. However, the G1 group had higher IFN-γ values among both favorable and unfavorable SSI groups. CONCLUSIONS Higher rates of unfavorable conditions, including lower education levels, IL-10 levels, and a trend for higher IFN-γ levels, were identified among HIV-infected women, pregnant and non-pregnant. These factors may interfere in health care and lead to poor outcomes during pregnancy. Therefore, we suggest that health policies could be created to specifically address these factors in this population.

New index for the diagnosis of liver fibrosis in Schistosomiasis mansoni / Novo índice biológico para o diagnóstico da fibrose hepática na Esquistossomose mansoni

ABSTRACT BACKGROUND Periportal fibrosis is the major pathological consequence of the Schistosoma mansoni infection. OBJECTIVE To evaluate the accuracy of serum markers and to construct an index to assess fibrosis. METHODS Patients (n=116) with schistosomiasis were evaluated by ultrasound scan and measurements of serum levels of aminotransferases, γ-glutamyl transferase, alkaline phosphatase, hyaluronic acid, cytokines and platelets. Ultrasound images were used to evaluate the fibrosis using Niamey's classification and identified 19 patients without periportal fibrosis (patterns A and B), 48 with mild to moderate fibrosis (C and D) and 49 with advanced fibrosis (E and F). RESULTS Using multivariate analysis, a model was created, which involved alkaline phosphatase and platelets and could separate patients with different patterns of fibrosis. This index showed a better performance in separating patients without fibrosis from with advanced periportal fibrosis. The biological index showed an area under the ROC curve of 1.000. Using values below the lowest or above the highest cut-off point, the presence or absence of advanced fibrosis could be predicted in all patients. CONCLUSION The index constructed can be used to separate patients with different patterns of periportal fibrosis, specially to predict advanced fibrosis in schistosomiasis patients.

RESUMO CONTEXTO A fibrose periportal é a maior consequência patológica da infecção pelo Schistosoma mansoni. OBJETIVO Avaliar a acurácia de marcadores séricos e construir um índice para avaliar a fibrose. MÉTODOS Pacientes (n=116) com esquistossomose foram avaliados pela ultrassonografia e dosados os níveis de aminotransferases, γ-glutamil transferase, fosfatase alcalina, ácido hialurônico, citocinas e plaquetas. Imagens de ultrasom foram utilizadas para avaliar a fibrose através de classificação de Niamey e identificados 19 pacientes sem fibrose periportal (padrão A e B), 48 com fibrose média a moderada (C e D) e 49 com fibrose avançada (E e F). RESULTADOS Através de análise multivariada, um modelo foi criado, que envolveu a fosfatase alcalina e plaquetas e conseguiu separar pacientes com diferentes padrões de fibrose periportal. Este índice mostrou um melhor desempenho em separar pacientes sem fibrose dos pacientes com fibrose avançada. O índice biológico mostrou uma área sob a curva ROC de 1,000. Usando valores infereiores e acima do ponto de corte, a presença ou ausência de fibrose avançada pode ser prevista em todos os pacientes. CONCLUSÃO O índice construído pode ser usado para separar os pacientes com diferentes padrões de fibrose periportal, especialmente para prever fibrose avançada em pacientes com esquistossomose.

Comparação do perfil clínico-epidemiológico entre homens e mulheres na síndrome coronariana aguda / Comparison of clinical and epidemiological profiles among men and women with acute coronary syndrome

Fundamentos: A doença isquêmica do coração é a principal causa de morte entre homens e mulheres no Brasil e em vários países de diferentes continentes. Verifica-se um crescimento acelerado da mortalidade nos países em desenvolvimento, sendo esta considerada uma das questões mais relevantes em saúde pública atualmente. Objetivo: Analisar e comparar o perfil clínico-epidemiológico de homens e mulheres na síndrome coronariana aguda.Métodos: Avaliado o perfil clínico-epidemiológico de 927 pacientes (60,0% homens), com média de idade 67,0±12,0 anos com diagnóstico de síndrome coronariana aguda (SCA), internados na unidade coronariana de um hospital da rede suplementar de saúde, de referência em cardiologia, na cidade de Recife, PE, Brasil, no período de setembro de 2009 a dezembro de 2012.Resultados: Dentre os fatores de risco, a hipertensão arterial sistêmica e o sedentarismo foram mais frequentes nas mulheres (p=0,001), enquanto o tabagismo e o alcoolismo foram mais frequentes nos homens (p=0,01). Ainda nos homens foram mais frequentes: o infarto agudo do miocárdio com supradesnivelamento do segmento do ST ou cirurgia de revascularização do miocárdio prévios (p=0,011) e também os níveis de troponina (p=0,006). Durante a hospitalização, os desfechos adversos e óbito foram mais frequentes nas mulheres (p=0,177).Conclusão: As mulheres com SCA apresentaram maior prevalência de hipertensão arterial sistêmica e sedentarismo e a maior ocorrência de desfechos adversos, indicando a necessidade de intervir mais precocemente e estimular o controle nos fatores de risco, visando a reduzir as complicações e a mortalidade hospitalar.

Background: Ischemic heart disease is the leading cause of death among men and women in Brazil and in several countries on different continents. A sharp upsurge in mortality rates has been noted in the developing countries, today constituting a major public health issue.Objective: To analyze and compare the clinical and epidemiological profiles of men and women with acute coronary syndrome.Methods: We studied 927 patients (60.0% men) with an average age of 67.0±12.0 years diagnosed with acute coronary syndrome (ACS) and admitted to the coronary unit of a cardiology reference hospital in the supplementary healthcare network between September 2009 and December 2012 in the city of Recife, Pernambuco State, Brazil.Results: Among the risk factors, hypertension and sedentary lifestyles were more frequent among women (p=0.001), while smoking and alcoholism were more frequent among men (p=0.01). Men also had more frequent acute myocardial infarctions with elevation of the ST segment or previous coronary artery bypass grafting (p=0.011) and higher troponin levels (p=0.006). During hospitalization, adverse outcomes and deaths were more frequent among women (p=0.177).Conclusion: Women with ACS present higher rates for hypertension and sedentary lifestyles, with more adverse outcomes among women underscoring the need for earlier intervention and encouragement for controlling risk factors, in order to lower in-hospital mortality rates with fewer complications.

Association between Schistosomiasis mansoni and hepatitis C: systematic review / Associacao entre esquistossomose mansonica e hepatite C: revisao sistematica / Asociacion entre esquistosomiasis mansoni y hepatitis C: revision sistematica

OBJECTIVE: To perform a systematic review of the prevalence of the HCV/ S. mansoni co-infection and associated factors in Schistosoma mansoni -infected populations. METHODS: The bibliographic search was carried out using the Medline, Lilacs, SciELO, Cochrane Library and Ibecs databases. The criteria for the studies' selection and the extraction data were based on systematic review methods. Forty five studies were found, with nine being excluded in a first screening. Thirteen articles were used for data extraction. RESULTS: The HCV infection rates in schistosomiasis populations range from 1% in Ethiopia to 50% in Egypt. Several studies had poorly defined methodologies, even in areas characterized by an association between hepatitis C and schistosomiasis, such as Brazil and Egypt, which meant conclusions were inconsistent. HCV infection rates in schistosomotic populations were heterogeneous and risk factors for acquiring the virus varied widely. CONCLUSIONS: Despite the limitations, this review may help to identify regions with higher rates of hepatitis C and schistosomiasis association. However, more studies are necessary for the development of public health policies on prevention and control of both diseases. .

OBJETIVO: Realizar revisão sistemática sobre a prevalência da confecção do vírus da hepatite C e Schistosoma mansoni e os fatores de risco associados a indivíduos com esquistossomose. MÉTODOS: Revisão realizada nas bases de dados Medline, Lilacs, SciELO, Biblioteca Cochrane e Ibecs. Os critérios de seleção e a obtenção dos dados foram baseados em métodos de revisão sistemática. Foram encontradas 45 referências relevantes, das quais nove foram excluídas na primeira triagem, 14 na leitura dos resumos e nove na leitura completa. Treze artigos foram selecionados para análise. RESULTADOS: A prevalência da associação entre vírus da hepatite C e Schistosoma mansoni variou de 1% na Etiópia a 50% no Egito. Alguns estudos apresentam metodologias pouco definidas, mesmo em áreas caracterizadas pela associação entre vírus da hepatite C e S. mansoni , como Brasil e Egito, o que não permitiu conclusões consistentes. As taxas de infecção pelo VHC em populações esquistossomáticas foram heterogêneas e os fatores de risco para adquirir o vírus foram variáveis. CONCLUSÕES: Apesar das limitações, esta análise pode ajudar a identificar regiões com maiores taxas dessa associação. Outros estudos serão necessários para o desenvolvimento de políticas públicas de prevenção e controle dessas doenças. .

OBJETIVO: Realizar revisión sistemática sobre la prevalencia de la co-infección del virus de la hepatitis C y Schistosoma mansoni y los factores de riesgo asociados a individuos con esquistosomosis. MÉTODOS: Revisión realizada en las bases de datos MEDLINE, LILACS, SciELO, Biblioteca Cochrane e IBECS. Los criterios de selección y la obtención de los datos fueron basados en métodos de revisión sistemática. RESULTADOS: Fueron encontradas 45 referencias relevantes, de las cuales, nueve fueron excluidas en la primera selección, 14 en la lectura de los resúmenes y nueve en la lectura completa. Trece artículos fueron seleccionados para análisis. La prevalencia de la asociación entre virus de la hepatitis C y Schistosoma mansoni varió de 1% en Etiopia, a 50% en Egipto. Algunos estudios presentan metodologías poco definidas, inclusive en áreas caracterizadas por la asociación entre el virus de la hepatitis C y S. mansoni, como Brasil y Egipto, lo que no permitió conclusiones consistentes. Los cocientes de infección por el VHC en poblaciones esquistosómicas fueron heterogéneos y los factores de riesgo para adquirir el virus fueron variables. CONCLUSIONES: A pesar de las limitaciones, este análisis pudo ayudar a identificar regiones con mayores cocientes de esa asociación. Otros estudios serán necesarios para el desarrollo de políticas públicas de prevención y control de estas enfermedades. .

Correlation of biological serum markers with the degree of hepatic fibrosis and necroinflammatory activity in hepatitis C and schistosomiasis patients

Liver biopsy is the gold-standard method to stage fibrosis; however, it is an invasive procedure and is potentially dangerous. The main objective of this study was to evaluate biological markers, such as cytokines IL-13, IFN-ã, TNF-á and TGF-â, platelets, bilirubins (Bil), alanine aminotransferase (ALT) and aspartate aminotransferase (AST), total proteins, ã-glutamil transferase (ã-GT) and alkaline phosphatase (AP), that could be used to predict the severity of hepatic fibrosis in schistosomiasis and hepatitis C (HC) as isolated diseases or co-infections. The following patient groups were selected: HC (n = 39), HC/hepatosplenic schistosomiasis (HSS) (n = 19), HSS (n = 22) and a control group (n = 13). ANOVA and ROC curves were used for statistical analysis. P < 0.05 was considered significant. With HC patients we showed that TNF-á (p = 0.020) and AP (p = 0.005) could differentiate mild and severe fibrosis. With regard to necroinflammatory activity, AST (p = 0.002), ã-GT (p = 0.034) and AP (p = 0.001) were the best markers to differentiate mild and severe activity. In HC + HSS patients, total Bil (p = 0.008) was capable of differentiating between mild and severe fibrosis. In conclusion, our study was able to suggest biological markers that are non-invasive candidates to evaluate fibrosis and necroinflammatory activity in HC and HC + HSS.

Cytokine profile associated with chronic and acute human schistosomiasis mansoni

The production and regulation of interleukin (IL) IL-13, IL-4 and interferon-gamma (IFN-³) was evaluated in 43 schistosomiasis patients with different clinical forms. Whole-blood cultures cytokine production in response to soluble egg antigen (SEA), soluble worm adult preparation (SWAP), mitogens, neutralizing antibodies or recombinant IL-13 were measured by ELISA. After SWAP stimulation, chronic patients, particularly hepatointestinals, produced higher levels of IL-4 in comparison with acute patients, suggesting the presence of a type 2 cytokine profile in these patients. Following SEA and SWAP stimulation, hepatosplenic (HS) patients showed increased levels of IFN-³ when compared with acute patients, indicating that HS disease in humans is associated with a type 1 cytokine response. The mechanisms of immune regulation are apparently different between the clinical stages of the disease, some of which are antigen-specific.

Preliminary results in the immunodiagnosis of tuberculosis in children based on T cell responses to ESAT-6 and PPD antigens

The aim of this work was to study the difference in interferon gamma (IFN-gamma) production by T lymphocytes after early secretory antigen target 6 (ESAT-6) or purified protein derivate (PPD) stimulation in whole blood culture supernatants from children with suspected tuberculosis (TB) disease (n = 21), latent TB infection (n = 16) and negative controls (NC) (n = 22) from an endemic area in Brazil. The concentration of IFN-gamma (pg/ml) was measured by enzyme linked immunosorbent assay and the differences in the IFN-gamma levels for each group were compared and evaluated using an unpaired Student's t-test; p values < 0.05 were considered significant. Measurement of IFN-gamma levels after ESAT-6 stimulation raised the possibility of early diagnosis in the latent TB group (p = 0.0030). Nevertheless, the same group showed similar responses to the NC group (p > 0.05) after PPD stimulation. The IFN-gamma assay using ESAT-6 as an antigenic stimulus has the potential to be used as a tool for the immunodiagnosis of early TB in children.

Treatment of human acute schistosomiasis with oxamniquine induces an increase in interferon-gamma response to Schistosoma mansoni antigens

Patients with acute schistosomiasis were studied before and after oxamniquine treatment. They had been exposed to cercariae 5 to 9 weeks before, and presented compatible clinical manifestations, eosinophilia, and high levels of total IgE. Interferon-gamma (IFN-gamma) and interleukin-4 were measured by ELISA in whole blood samples under soluble egg antigen or soluble adult worm preparation stimulation. After treatment, the reduction of leukocytosis and eosinophilia were not significant, but total IgE levels decreased significantly, in contrast to IFN-gamma levels that were significantly increased. The oxamniquine treatment of acute schistosomiasis patients is followed by an improvement of a Th1 response in vitro. If this response has a protective aspect is unknown, and some investigations need to be realized.

Preliminary results on interleukin-4 and interleukin-10 cytokine production in malnourished, inducible nitric oxide synthase-deficient mice with schistosomiasis mansoni infection

Schistosoma mansoni infected C57Bl/6 inducible nitric oxide synthase (iNOS)-deficient and non-deficient malnourished mice, both fed a balanced controlled diet were studied. Interleukins, IL-4 and IL-10 responses to soluble egg antigens (SEA) 90 days after infection, were determined. Our results suggest that in iNOS deficient, malnourished mice, 90 days after of infection, nitric oxide has a downregulating effect on IL-4 and IL-10 production. We are currently investigating the biological significance of these findings.

Preliminar evaluation of cytokines in the hepatitis C-schistosomiasis co-infection

Evaluation of hepatic fibrosis is usually performed by histopathological examination of biopsies. However, this is an invasive and potentially dangerous procedure. Several studies have proposed serum biological markers of hepatic fibrosis. This communication evaluates the use of serum cytokines as markers of hepatic fibrosis in hepatitis C, schistosomiasis, and co-infection.

The effect of Zymomonas mobilis culture on experimental Schistosoma mansoni infection

Camundongos C57Bl/10 do sexo masculino, infectados com Schistosoma mansoni foram distribuídos nos grupos misto, profilático e curativo. Cultura de Zymomonas mobilis foi administrada oralmente aos camundongos. Uma proteção de 61% foi observada no grupo curativo (p<0,05). Os estudos histopatológicos dos fígados e intestinos mostraram resultados similares.

Evaluation of tests based on the antibody response to keyhole limpet haemocyanin and soluble egg antigen to differentiate acute and chronic human schistosomiasis mansoni

Specific IgG and IgM responses to soluble egg antigen (SEA) and keyhole limpet haemocyanin (KLH) were measured by ELISA in patients with acute and chronic schistosomiasis. The tests based upon IgM and IgG antibodies responses to KLH presented the best diagnostic discrimination, and can be used in conjunction with clinical and epidemiological data to the differential diagnosis of acute schistosomiasis.

Perda protéica,intestinal em adolescentes e adultos jovens com esquistossomose mansônica submetidos a esplenectomia, ligadura da veia gástrica esquerda e auto-implante esplênico / Enteric protein loss in adolescents and young adults with schistosomiasis mansoni who had undergone splenectomy. Ligature, of the left vein ans splenic auto-implant

Com o objetivo de estudar a perda protéica instestinal, em adolescentes e adultos jovens, com esquistossomose mansônica, por meio da excreção fecal de alfa-1-at, foram analisados, 56 indivíduos, alocados em2 grupos: G1- 27 pacientes da forma hepatoesplênica, submetidos a esplenectomia, ligadura da veia gástrica esquerdae auto-implante esplênico; G2 -29 indivíduos sem esquistossomose (grupo de comparação). Como objetivos secundários, investigou-se a possível correlação entre alfa-1-at fecal e: o número de ovos de S. mansoni nas fezes e os graus de fibrose periportal, nos pacientes do G1. Foram excluídos do estudo pacientes comcardiopatias, nefropatias, outras hepatopatias, e positividade para o AgHBs. A alfa-1- at fecal foi dosada, pela técnica de imunodifusão radial, em placas de gel, LC Partigen Dade Behing, em amostras de fezes coletadas durante 48 horas, em todos os indivíduos. A análise estatística dos dados demonstrou que: não houve diferençã estatisticamente significante entre as média de alfa 1-at fecal, nos dois grupos estudados (t de Student: p>0,05); não houve correlação entre o valor de alfa-1 at fecal e a carga parasitária dos pacientes do G1 (coeficiente de correlação de Pearson: r=0,20: p=0,321), bem como as diferenças entre as médias de alfa-1-at fecal, segundo os graus de fibrose periportal, não foram estatisticamente significantes (ANOVA, p=0,225)

Studies on the production and regulation of interleukin, IL-13, IL-4 and interferon-gamma in human Schistosomiasis mansoni

The production and regulation of interleukin (IL) IL-13, IL-4 and interferon-gamma was evaluated in different clinical forms of human schistosomiasis. The mechanisms of immune regulation are apparently different in the various clinical stages of the disease, some of them being antigen specific

Partial molecular characterization of Sm8, a tegumental antigen of Schistosoma mansoni

Sm8 is a major tegumental antigen of Schistosoma mansoni. The partial cDNA was isolated and analyzed. Sequence analysis revealed transmembrane compatible hydrophobic domains and a putative leucine zipper pattern. The mRNA and the protein are predominantly expressed in adult worms

Preliminary results on the effects of CD40/CD40L interactions and SAC-induction on IFN-gamma expression in human schistosomiasis

In this communication the authors analyzed the pattern of expression of IFN-gamma as a surrogate type 1 response in different clinical forms of schistosomiasis in response to stimulation involving T-cell dependent and T-cell independent pathways, to investigate which pathways were functional in human schistosomiasis, and to further characterize the nature of Th1 response impairment in this parasitic disease