A vaccine against S. pyogenes: Design and experimental immune response

Streptococcus pyogenes causes severe invasive infections: the post-streptococcal sequelae of acute rheumatic fever (RF) and rheumatic heart disease (RHD), acute glomerulonephritis, and uncomplicated pharyngitis and pyoderma. Efforts to produce a vaccine against S. pyogenes began several decades ago, and different models have been proposed. Here, we describe the methodology used in the development of a new vaccine model, consisting of both T and B protective epitopes constructed as synthetic peptides and recombinant proteins. Two adjuvants were tested in an experimental inbred mouse model: a classical Freund`s adjuvant and a new adjuvant (AFCo1) that induces mucosal immune responses and is obtained by calcium precipitation of a proteoliposome derived from the outer membrane of Neisseria meningitides B. The StreptInCor vaccine epitope co-administrated with AFCo1 adjuvant induced mucosal (IgA) and systemic (IgG) antibodies as preferential Th1-mediated immune responses. No autoimmune reactions were observed, suggesting that the vaccine epitope is safe. (c) 2009 Elsevier Inc. All rights reserved.

TNF-alpha polymorphisms are associated with obsessive-compulsive disorder

Introduction: Several lines of evidence support an immunologic involvement in obsessive-compulsive disorder (OCD): the increased prevalence of OCD in patients with rheumatic fever (RF), and the aggregation of obsessive-compulsive spectrum disorders among relatives of RF probands. Tumor necrosis factor alpha is a proinflammatory cytokine involved in RF and other autoimmune diseases. Polymorphisms in the promoter region of the TNFA gene have been associated with RE Given the association between OCD and RF, the goal of the present study was to investigate a possible association between polymorphisms within the promoter region of TNFA and OCD. Materials and methods: Two polymorphisms were investigated: -308 G/A and -238 G/A. The allelic and genotypic frequencies of these polymorphisms were examined in 111 patients who fulfilled DSM-IV criteria for OCD and compared with the frequencies in 250 controls. Results: Significant associations were observed between both polymorphisms and OCD. For -238 G/A, an association between the A allele and OCD was observed (X-2 = 12.05, p = 0.0005). A significant association was also observed between the A allele of the -308 G/A polymorphism and OCD (X-2 = 7.09, p = 0.007). Finally, a haplotype consisting of genotypes of these two markers was also examined. Significant association was observed for the A-A haplotype (p = 0.0099 after correcting for multiple testing). Discussion: There is association between the -308 G/A and -238 G/A TNFA polymorphisms and OCD in our Brazilian sample. However, these results need to be replicated in larger samples collected from different populations. (c) 2008 Elsevier Ireland Ltd. All rights reserved.

Avaliação da adesão ao acompanhamento ambulatorial dos pacientes em profilaxia secundária da febre reumática no Hospital de Clínicas de Porto Alegre

A Febre Reumática (FR) é uma doença com significativa prevalência na população de pacientes em idade escolar. Constitui-se na principal causa de cardiopatia crônica em adultos jovens em países em desenvolvimento. A prevenção é de fácil manejo terapêutico, embora com reduzido índice de adesão. Até o momento, a melhor forma de evitarmos as seqüelas cardíacas é através da identificação e tratamento precoces e a manutenção de uma adequada profilaxia secundária. São raras as publicações referentes ao acompanhamento da profilaxia secundária após a alta hospitalar. O objetivo deste trabalho é avaliar a adesão ao acompanhamento dos pacientes com FR internados no Hospital de Clínicas de Porto Alegre, no período de janeiro de 1977 a junho de 1999. A coorte foi constituída de 112 indivíduos com FR que tinham indicação de retorno ao ambulatório após a alta. Quarenta pacientes (35,7%) foram atendidos no primeiro episódio de FR. A maioria apresentou seqüelas cardíacas (52,7%), ocorrendo registro de casos a partir de 8 anos de idade. As manifestações clínicas nos 40 pacientes atendidos no primeiro episódio de FR foram: 21 (52,5%) com cardite, 30 (75%) com artrite e 14 (35%) com coréia. Apenas 77 (68,7%) retornaram ao ambulatório após a alta e somente 13 (21% pelo método de Kaplan-Meier) mantiveram acompanhamento por no mínimo 5 anos. A idade menor ou igual a 16 anos foi fator preditivo de maior tempo de acompanhamento. Local de procedência, presença de seqüelas e renda familiar não mostraram associação significante. A interrupção do acompanhamento pela maioria dos pacientes e a verificação do pior prognóstico cardíaco nos pacientes com recidivas sugere a necessidade da adoção de um programa de orientação e busca para garantir a efetividade da profilaxia secundária.

Subtle Cognitive Deficits in Adults With a Previous History of Sydenham's Chorea During Childhood

Objective. To evaluate the neuropsychological profile and health-related quality of life (HRQOL) of adults who had rheumatic fever (RF) during childhood with and without Sydenham's chorea (SC).Methods. Three groups of patients were assessed: adults who had RF with SC during childhood (SC group), adults who had RF without SC during childhood (RF group), and controls (CT group). A range of neuropsychological tests looked at several cognitive domains. HRQOL was measured through a Brazilian version of the Short Form 36 (SF-36) health survey.Results. Twenty patients were included in the SC group, 23 patients in the RF group, and 19 patients in the CT group. The 3 groups were homogeneous regarding sex (P = 0.078), age (P = 0.799), schooling (P = 0.600), socioeconomic status (P = 0.138), intelligence quotient (P = 0.329), and scores for anxiety (P = 0.156) and depression (P = 0.076). The SC group demonstrated inferior performance in tests that assessed attention (Digit Span Forward [ P = 0.005], Corsi Block Forward [ P = 0.014]), speeded information processing (Trail Making A [ P = 0.009], Symbol Search [ P = 0.042]), and executive functions and working memory (Corsi Block Backward [ P = 0.028]), and higher scores for attention deficit scale (P = 0.030) when compared with the RF and CT groups. They also showed a tendency toward lower scores in the physical aspects, vitality, emotional aspects, and mental health domains of the SF-36. The RF group had a lower score for the general health domain than the CT group (P = 0.030).Conclusion. Patients who had SC during childhood can exhibit inferior performance in tasks that evaluate attention, speeded information processing, executive functions, and working memory in adult life. Therefore, there is indirect evidence of the persistence of dysfunction in cerebral circuits involved with the basal ganglia. They also presented a worse self-evaluation in HRQOL that was not related to cognitive impairments.

Faringotonsilites em crianças: visão de uma amostra de pediatras e otorrinolaringologistas

As faringotonsilites agudas são infecções das vias aéreas superiores comuns na infância. OBJETIVO: Analisar opiniões e condutas de pediatras e otorrinolaringologistas do Estado de São Paulo em relação ao diagnóstico, tratamento e prevenção das faringotonsilites e suas complicações em crianças. MATERIAL E MÉTODOS: Selecionamos aleatoriamente 1370 pediatras e 1000 otorrinolaringologistas do Estado de São Paulo. Aos especialistas foi enviado questionário por correio. DESENHO do ESTUDO: Estudo transversal. RESULTADOS: 95,8% dos pediatras e 91,5% dos otorrinos não solicitam rotineiramente exames para diagnóstico laboratorial das faringotonsilites agudas na criança. Os antimicrobianos mais prescritos pelos pediatras nas faringotonsilites bacterianas foram: penicilina por via oral durante 10 dias (33,6%) e penicilina benzatina em dose única (19,7%). Os antimicrobianos mais prescritos pelos otorrinos para tratamento foram: penicilina por via oral durante 10 dias (35,4%) e penicilina por via oral durante 7 dias (25,7%). A medida de prevenção das faringotonsilites bacterianas considerada muito eficaz por mais da metade dos pediatras e otorrinos foi a cirurgia de tonsilectomia. A faringotonsilite de repetição foi o principal motivo para os otorrinos indicarem cirurgia de tonsilectomia aos escolares e adolescentes (49,3% e 53,4%, respectivamente). CONCLUSÕES: É necessário uniformizar condutas de pediatras e otorrinos para diagnóstico e tratamento das faringotonsilites em crianças.

Apresentação e desfecho da febre reumática em uma série de casos

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Insuficiência aórtica subcrônica e vias centrais relacionadas à regulação da ingestão de sódio

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Validação dos questionários de qualidade de vida (CHAQ e CHQ-PF50®) em pacientes com febre reumática

Pós-graduação em Pediatria - FMB

Avalição do desfecho clínico da febre reumática durante duas décadas no Hospital das Clínicas de Botucatu

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Streptococcal acute pharyngitis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Antidepressivo em ratos com insuficiência aórtica pode modificar a expressão gênica de ocitocina e vasopressina centrais?

Aortic regurgitation (AR) leads to a left ventricle dilation and hypertrophy in response to a chronic volume overload. It is still very frequent in developing countries, for instance Brazil, and often as secondary to rheumatic fever. Usually, chronic AR is generally well tolerated for many years, when with the heart dilated the patient searches for treatment. Bidirectional association with depression and cardiovascular disease has been described. Selective serotonin reuptake inhibitors (SSRI) are widely prescribed to treat several affective disorders, especially for cardiovascular patients since they decrease arrhythmia probability. These SSRI improves cardiac function in rats submitted to stress protocols. Preliminary study from our laboratory showed that following 4 weeks of treatment with one SSRI (paroxetine) in subchronic AR rats there was a decreased in daily sodium intake and an improvement in systolic function. An increase in the central oxytocinergic transmission may be involved in this peripheral improvement to the heart. The investigations about the mechanisms underlying this improvement are necessary. Therefore the aims of this project is investigate the effects of 4 weeks of treatment of paroxetine, a SSRI, in rats with a subchronic AR over the central central gene expression of oxytocin and vasopressin using a reverse transcription polymerase chain reaction (RT-PCR)

Como estará a ingestão de sódio após uma sobrecarga de volume combinada ao tratamento com paroxetina?

Aortic regurgitation (AR) is still common in developing countries as secondary of rheumatic fever, and its incidence have increased in senile degenerative form. The AR develops severe myocardial hypertrophy. A common comorbidity associated with cardiovascular disease is depression. Among the most prescribed antidepressants in the world are the serotonin selective reuptake inhibitors (SSRIs). Central serotonergic pathways are involved with the inhibition of sodium intake and can be modify the excretion of this íon. Therefore, we investigated whether treatment with an antidepressants SSRI, the paroxetine, for four weeks can modfy the behavior of water and NaCl 0,3M intake, excretion of sodium and morphofunctional parameters of rats with AR induce. Wistar rats (280 - 300g) underwent surgery for AR (n=15) or control surgery (n=14). The AR was induced by retrograde puncture of valve leaflets. The animals were divided into 4 groups: AR + paroxetine (n=8), AR + control (n=7), control + paroxetine (n=7), control + control (n=7). From the 4th to the 8th week after inductuin of AR was administered paroxetine (10mg/kg pc) daily and subcutaneously. In the 4th and 8th week after induction of AR echocardiograms were performed to collect data morphofunctional. During the 4 weeks of treatment were analyzed intake of water and saline daily and once a week urine samples were collected for analysis by flame photometer of excretion of sodium and potassium. In the 10th week the animals were submitted to a challenge protocol hidromineral by combining furosemide (10 mg / kg bw) associated with the low dose of Captopril (5 mg / kg bw). During the challenged urine samples were collected for analysis by flame photometer of excretion of sodium and potassium at the time zero and after 2 hours of treatment. As a result we found that treatment with paroxetine in rats with AR determined an improvement in fractional shortening (shortening fraction: 52.7 ± 2.2% vs. RA ...

Antidepressivo modula o comportamento e a expressão gênica das cadeias de miosina, serca2 e fosfolambam em ratos com insuficiência aórtica?

Introduction: Aortic insufficiency (AoI), a volume overload, is characterized by the diastolic reflux of blood from the regurgitating aorta to the left ventricle. This effect results from malfunctioning aortic cusps. The main cause of AoI in developing countries is rheumatic fever, including Brazil, and valvar degeneration in developed countries. There is a strong association between cardiovascular diseases and depression. Selective serotonin reuptake inhibitors (SSRI) are one of the most prescribed antidepressants in the world. Previous studies of our laboratory showed that the utilization of a SSRI, paroxetine, improved cardiac function in rats with sub-chronic AoI and reduced the daily ingestion of hypertonic sodium (NaCl 0,3M). Cardiovascular diseases can determine behavior changes like increase of anxiety, and it is yet unknown if AoI would determine anxiety or anhedonia, incapacity of obtaining pleasure through physical or sensorial experiences. A possible target for SSRI action could be a change in the expression of enzyme isoforms that collaborate in the contractile function of the heart muscle, like the heavy chains of myosine, the sarcoplasmatic reticulum Ca2+/ATPase (SERCA) and its regulator protein, phospholamban (PLB). Objectives: Evaluation of behavior parameters for anxiety and anhedonia state and genic expression of a-myosine, b-myosine, SERCA2a and PLB in the heart tissue of rats with subchronic AoI that received treatment with an SSRI (paroxetine) for 4 weeks. Methods: Surgery to induce AoI was performed on male Wistar rats, anxiety was evaluated by the elevated plus-maze (EPM) and state of anhedonia was tested by ingestion of 2% sucrose solution. After euthanasia the heart tissue was collected and total RNA was extracted to be analyzed by the RT-qPCR method. Results: Heart fractional shortening was preserved in rats with AoI that were treated compared to rats with AoI that were not treated. There was no statistically ...

Efeito da penicilina G a cada três semanas sobre o surgimento de Streptococcus viridans resistentes à penicilina na microflora oral

FUNDAMENTO: Penicilina G benzatina a cada 3 semanas é o protocolo padrão para a profilaxia secundária para febre reumática recorrente. OBJETIVO: Avaliar o efeito da penicilina G benzatina em Streptococcus sanguinis e Streptococcus oralis em pacientes com doença valvular cardíaca, devido à febre reumática com recebimento de profilaxia secundária. MÉTODOS: Estreptococos orais foram avaliados antes (momento basal) e após 7 dias (7º dia) iniciando-se com penicilina G benzatina em 100 pacientes que receberam profilaxia secundária da febre reumática. Amostras de saliva foram avaliadas para verificar a contagem de colônias e presença de S. sanguinis e S. oralis. Amostras de saliva estimulada pela mastigação foram serialmente diluídas e semeadas em placas sobre agar-sangue de ovelhas seletivo e não seletivo a 5% contendo penicilina G. A identificação da espécie foi realizada com testes bioquímicos convencionais. Concentrações inibitórias mínimas foram determinadas com o Etest. RESULTADOS: Não foram encontradas diferenças estatísticas da presença de S. sanguinis comparando-se o momento basal e o 7º dia (p = 0,62). No entanto, o número existente de culturas positivas de S. oralis no 7º dia após a Penicilina G benzatina apresentou um aumento significativo em relação ao valor basal (p = 0,04). Não houve diferença estatística existente entre o momento basal e o 7º dia sobre o número de S. sanguinis ou S. oralis UFC/mL e concentrações inibitórias medianas. CONCLUSÃO: O presente estudo mostrou que a Penicilina G benzatina a cada 3 semanas não alterou a colonização por S. sanguinis, mas aumentou a colonização de S. oralis no 7º dia de administração. Portanto, a susceptibilidade do Streptococcus sanguinis e Streptococcus oralis à penicilina G não foi modificada durante a rotina de profilaxia secundária da febre reumática utilizando a penicilina G.

Association study between functional polymorphisms in the TNF-alpha gene and obsessive-compulsive disorder

Obsessive-compulsive disorder (OCD) is a prevalent psychiatric disorder of unknown etiology. However, there is some evidence that the immune system may play an important role in its pathogenesis. In the present study, two polymorphisms (rs1800795 and rs361525) in the promoter region of the cytokine tumor necrosis factor-alpha (TNFA) gene were genotyped in 183 OCD patients and in 249 healthy controls. The statistical tests were performed using the PLINK (R) software. We found that the A allele of the TNFA rs361525 polymorphism was significantly associated with OCD subjects, according to the allelic x association test (p=0.007). The presence of genetic markers, such as inflammatory cytokines genes linked to OCD, may represent additional evidence supporting the rote of the immune system in its pathogenesis.