Preventive and curative glycoside kaempferol treatments attenuate the TH2-driven allergic airway disease

Asthma is a chronic respiratory disease characterized by airway inflammation and airway hyperresponsiveness (AHR). One strategy to treat allergic diseases is the development of new drugs. Flavonoids are compounds derived from plants and are known to have antiallergic, anti-inflammatory, and antioxidant properties. To investigate whether the flavonoid kaempferol glycoside 3-O-[beta-D-glycopiranosil-(1 -> 6)-alpha-L-ramnopiranosil]-7-O-alpha-L-ramnopiranosil-kaempferol (GRRK) would be capable of modulating allergic airway disease (AAD) either as a preventive (GRRK P) or curative (GRRK C) treatment in an experimental model of asthma. At weekly intervals, BALB/c mice were subcutaneously (sc) sensitized twice with ovalbumin (OVA)/alum and challenged twice with OVA administered intranasally. To evaluate any preventive effects GRRK was administered 1 h (hour) before each OVA-sensitization and challenge, while to analyze the curative effects mice were first sensitized with OVA, followed by GRRK given at day 18 through 21. The onset: of AAD was evaluated 24 h after the last OVA challenge. Both treatments resulted in a dose-dependent reduction in total leukocyte and eosinophil counts in the bronchoalveolar lavage fluid (BAL). GRRK also decreased CD4(+), B220(+), MHC class II and CD40 molecule expressions in BAL cells. Histology and lung mechanic showed that GRRK suppressed mucus production and ameliorated the AHR induced by OVA challenge. Furthermore, GRRK impaired Th2 cytokine production (IL-5 and IL-13) and did not induce a Th1 pattern of inflammation. These findings demonstrate that GRRK treatment before or after established allergic lung disease down-regulates key asthmatic features. Therefore. GRRK has a potential clinical use for the treatment of allergic asthma. (C) 2009 Elsevier B.V. All rights reserved.

Maternal immunization with ovalbumin prevents neonatal allergy development and up-regulates inhibitory receptor Fc gamma RIIB expression on B cells

Background: Preconception allergen immunization prevents neonatal allergen sensitization in mice by a complex interaction between regulatory cells/factors and antibodies. The present study assessed the influence of maternal immunization with ovalbumin (OVA) on the immune response of 3 day-old and 3 week-old offspring immunized or non-immunized with OVA and evaluated the effect of IgG treatment during fetal development or neonatal period. Results: Maternal immunization with OVA showed increased levels of Fc gamma RIIb expression in splenic B cells of neonates, which were maintained for up to 3 weeks and not affected by additional postnatal OVA immunization. Maternal immunization also exerted a down-modulatory effect on both IL-4 and IFN-gamma-secreting T cells and IL-4 and IL-12-secreting B cells. Furthermore, immunized neonates from immunized mothers showed a marked inhibition of antigen-specifc IgE Ab production and lowered Th2/Th1 cytokine levels, whereas displaying enhanced Fc gamma RIIb expression on B cells. These offspring also showed reduced antigen-specific proliferative response and lowered B cell responsiveness. Moreover, in vitro evaluation revealed an impairment of B cell activation upon engagement of B cell antigen receptor by IgG from OVA-immunized mice. Finally, in vivo IgG transference during pregnancy or breastfeeding revealed that maternal Ab transference was able to increase regulatory cytokines, such as IL-10, in the prenatal stage; yet only the postnatal treatment prevented neonatal sensitization. None of the IgG treatments induced immunological changes in the offspring, as it was observed for those from OVA-immunized mothers. Conclusion: Maternal immunization upregulates the inhibitory Fc gamma RIIb expression on offspring B cells, avoiding skewed Th2 response and development of allergy. These findings contribute to the advancement of prophylactic strategies to prevent allergic diseases in early life.

CpG-Induced Th1-Type Response in the Downmodulation of Early Development of Allergy and Inhibition of B7 Expression on T Cells of Newborn Mice

Several differences have been described between neonatal and adult immune responses. The predisposition in early life to Th2-type response or tolerance makes it a susceptible period for infections and allergic sensitization. The aim of this work was to evaluate the effects of CpG-containing oligodeoxynucleotides on neonatal and adult immunization with ovalbumin and Blomia tropicalis extract and compare the CpG effects on B and T cells of neonatal and adult mice. Mice that received CpG showed reduced immunoglobulin E (IgE) antibody production in both neonatal and adult periods, in parallel to increased IgG2a antibody levels. We observed that spleen cells of mice that received CpG in early life produced increased amounts of interferon-gamma upon anti-CD3 stimulation. Negative regulation of IgE response was more pronounced in adult than neonate mice; further, CpG decreased anaphylactic antiovalbumin IgG1 only in adults. Also, an upregulation of toll-like receptor 9 expression was detected in adult B cells, but not in neonatal, upon CpG stimuli. Neonatal B cells showed enhanced interleukin (IL)-10 expression and decreased IL-6 levels than adult B cells in response to CpG. When we analyzed in vitro activation of CD4+ T cells, an increased expression of B7 molecules on T cells in neonates was suppressed by CpG. Altogether, we verified qualitative and quantitative evidences regarding CpG effect on neonatal and adult allergens immunizations, which points to the importance of understanding neonatal immune system to establish immunomodulatory strategies for prevention of allergic diseases.

Development of an animal model for allergic conjunctivitis: influence of genetic factors and allergen concentration on immune response

Purpose: Animal models of diseases are extremely important in the study of the physiopathogenesis of human diseases and for testing novel therapeutic interventions. The present study aimed to develop an animal model that simulates human allergic conjunctivitis and to study how allergic response may be influenced by the allergen dose used for immunization and by genetic factors. Methods: Sixty C57Bl/6 mice and 60 BALB/c mice were immunized with placebo, or 5 mu g or 500 mu g of allergen derived from Dermatophagoides pteronyssinus. After ocular challenge, the mice were examined in order to clinically verify the occurrence or not of conjunctivitis. Material obtained from animals was used for total and specific IgE and IgG1 dosage, for assays of Der p-specific lymphocyte proliferation and supernatant cytokine dosage, and for histopathological evaluation of conjunctiva. Results: We developed a murine model of allergic conjunctivitis induced by D. pteronyssinus. The model is similar to human disease both clinically and according to laboratory findings. In mouse, conjunctivitis was associated with a Th2 cytokine profile. However, IL-10 appeared to be involved with disease blockade. Mice of different strains have distinct immune responses, depending on the sensitization dose. Conclusions: The murine model developed is suitable for the study of immunopathogenesis and as a template for future therapies. Using BALB/c and C57BL/6 mice, we demonstrated that genetic factors play a role in determining susceptibility and resistance, as well as in establishing the allergen concentration needed to induce or to block disease development.

Functional interferences in host inflammatory immune response by airway allergic inflammation restrain experimental periodontitis development in mice

Aims Periodontal disease (PD) and airway allergic inflammation (AL) present opposing inflammatory immunological features and clinically present an inverse correlation. However, the putative mechanisms underlying such opposite association are unknown. Material and Methods Balb/C mice were submitted to the co-induction of experimental PD (induced by Actinobacillus actinomycetemcomitans oral inoculation) and AL [induced by sensitization with ovalbumin (OVA) and the subsequent OVA challenges], and evaluated regarding PD and AL severity, immune response [cytokine production at periodontal tissues, and T-helper transcription factors in submandibular lymph nodes (LNs)] and infection parameters. Results PD/AL co-induction decreased PD alveolar bone loss and periodontal inflammation while experimental AL parameters were unaltered. An active functional interference was verified, because independent OVA sensitization and challenge not modulate PD outcome. PD+AL group presented decreased tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 beta, -gamma, IL-17A, receptor activator of nuclear factor kappa-light-chain-enhancer of activated B cells ligand and matrix metalloproteinase (MMP)-13 levels in periodontal tissues, while IL-4 and IL-10 levels were unaltered by AL co-induction. AL co-induction also resulted in upregulated T-bet and related orphan receptor gamma and downregulated GATA3 levels expression in submandibular LNs when compared with PD group. Conclusion Our results demonstrate that the interaction between experimental periodontitis and allergy involves functional immunological interferences, which restrains experimental periodontitis development by means of a skewed immune response.

PENCALC: a program for penetrance estimation in autosomal dominant diseases

We present a computer program developed for estimating penetrance rates in autosomal dominant diseases by means of family kinship and phenotype information contained within the pedigrees. The program also determines the exact 95% credibility interval for the penetrance estimate. Both executable (PenCalc for Windows) and web versions (PenCalcWeb) of the software are available. The web version enables further calculations, such as heterozygosity probabilities and assessment of offspring risks for all individuals in the pedigrees. Both programs can be accessed and down-loaded freely at the home-page address http://www.ib.usp.br/~otto/software.htm.

Endothelial dysfunction in cardiovascular and endocrine-metabolic diseases: an update

The endothelium plays a vital role in maintaining circulatory homeostasis by the release of relaxing and contracting factors. Any change in this balance may result in a process known as endothelial dysfunction that leads to impaired control of vascular tone and contributes to the pathogenesis of some cardiovascular and endocrine/metabolic diseases. Reduced endothelium-derived nitric oxide (NO) bioavailability and increased production of thromboxane A2, prostaglandin H2 and superoxide anion in conductance and resistance arteries are commonly associated with endothelial dysfunction in hypertensive, diabetic and obese animals, resulting in reduced endothelium-dependent vasodilatation and in increased vasoconstrictor responses. In addition, recent studies have demonstrated the role of enhanced overactivation ofβ-adrenergic receptors inducing vascular cytokine production and endothelial NO synthase (eNOS) uncoupling that seem to be the mechanisms underlying endothelial dysfunction in hypertension, heart failure and in endocrine-metabolic disorders. However, some adaptive mechanisms can occur in the initial stages of hypertension, such as increased NO production by eNOS. The present review focuses on the role of NO bioavailability, eNOS uncoupling, cyclooxygenase-derived products and pro-inflammatory factors on the endothelial dysfunction that occurs in hypertension, sympathetic hyperactivity, diabetes mellitus, and obesity. These are cardiovascular and endocrine-metabolic diseases of high incidence and mortality around the world, especially in developing countries and endothelial dysfunction contributes to triggering, maintenance and worsening of these pathological situations.

Air pollution and hospital admissions for respiratory diseases in the subequatorial Amazon: a time series approach

The objective of the study is to evaluate the effect of the daily variation in concentrations of fine particulate matter (diameter less than 2.5µm - PM2.5) resulting from the burning of biomass on the daily number of hospitalizations of children and elderly people for respiratory diseases, in Alta Floresta and Tangará da Serra in the Brazilian Amazon in 2005. This is an ecological time series study that uses data on daily number of hospitalizations of children and the elderly for respiratory diseases, and estimated concentration of PM2.5. In Alta Floresta, the percentage increases in the relative risk (%RR) of hospitalization for respiratory diseases in children were significant for the whole year and for the dry season with 3-4 day lags. In the dry season these measurements reach 6% (95%CI: 1.4-10.8). The associations were sig-nificant for moving averages of 3-5 days. The %RR for the elderly was significant for the current day of the drought, with a 6.8% increase (95%CI: 0.5-13.5) for each additional 10µg/m3 of PM2.5. No as-sociations were verified for Tangara da Serra. The PM2.5 from the burning of biomass increased hospitalizations for respiratory diseases in children and the elderly.

Gender and schooling inequalities in risk and protective factors for chronic diseases among Brazilian adults, through telephone survey

OBJECTIVES: To assess risk and protective factors for chronic noncommunicable diseases (CNCD) and to identify social inequalities in their distribution among Brazilian adults. METHODS: The data used were collected in 2007 through VIGITEL, an ongoing population-based telephone survey. This surveillance system was implemented in all of the Brazilian State capitals, over 54,000 interviews were analyzed. Age-adjusted prevalence ratios for trends at different schooling levels were calculated using Poisson regression with linear models. RESULTS: These analyses have shown differences in the prevalence of risk and protective factors for CNCD by gender and schooling. Among men, the prevalence ratios of overweight, consumption of meat with visible fat, and dyslipidemia were higher among men with more schooling, while tobacco use, sedentary lifestyle, and high-blood pressure were lower. Among women, tobacco use, overweight, obesity, high-blood pressure and diabetes were lower among men with more schooling, and consumption of meat with visible fat and sedentary lifestyles were higher. As for protective factors, fruit and vegetables intake and physical activity were higher in both men and women with more schooling. CONCLUSION: Gender and schooling influence on risk and protective factors for CNCD, being the values less favorable for men. vigitel is a useful tool for monitoring these factors amongst the Brazilian population.

A feasibility study of cell phone and landline phone interviews for monitoring of risk and protection factors for chronic diseases in Brazil

The study objective was to evaluate the feasibility of interviews by cell phone as a complement to interviews by landline to estimate risk and protection factors for chronic non-communicable diseases. Adult cell phone users were evaluated by random digit dialing. Questions asked were: age, sex, education, race, marital status, ownership of landline and cell phones, health condition, weight and height, medical diagnosis of hypertension and diabetes, physical activity, diet, binge drinking and smoking. The estimates were calculated using post-stratification weights. The cell phone interview system showed a reduced capacity to reach elderly and low educated populations. The estimates of the risk and protection factors for chronic non-communicable diseases in cell phone interviews were equal to the estimates obtained by landline phone. Eligibility, success and refusal rates using the cell phone system were lower than those of the landline system, but loss and cost were much higher, suggesting it is unsatisfactory as a complementary method in such a context.

Gerenciamento participativo em saúde do trabalhador: uma experiência na atividade de controle de vetores

Este artigo apresenta a experiência de implantação de um sistema de gestão em Saúde do Trabalhador implantado na Superintendencia de Controle de Endemias (SUCEN), no período de 1998 a 2002, que operava na atividade de controle químico de vetores no Estado de São Paulo. OBJETIVO: Descrever o sistema de gestão participativa, as ações desenvolvidas e os principais resultados alcançados. MÉTODO: Relato da experiência vivenciada pela equipe usando abordagem qualitativa, análise de documentos e apresentação de dados quantitativos. RESULTADOS: Foram eleitas 11 Comissões de Saúde e Trabalho (COMSAT's) que em conjunto com a equipe técnica iniciaram a identificação dos riscos e de propostas para prevenção e controle dos riscos no trabalho. O mapeamento de riscos resultou em 650 recomendações, 45,7% das quais foram executadas. Foram identificadas como doenças relacionadas ao trabalho: reações alérgicas aos pesticidas, lesões por esforços repetitivos, distúrbios auditivos e patologias de coluna vertebral. Participaram dos cursos básicos de saúde do trabalhador 1.003 servidores (76,3% do total de servidores), sendo que 90,8% dos participantes os consideraram ótimos ou bons. CONCLUSÕES: O sistema de gerenciamento participativo coloca em prática os princípios de gestão democrática do Sistema Único de Saúde (SUS); incorpora, por meio do mapeamento de riscos, o saber do trabalhador; inclui os trabalhadores como sujeitos do processo de negociação e mudanças; pratica o direito à informação. As COMSAT's revelaram-se espaços adequados para a negociação das melhorias nas condições de trabalho. A aprovação do sistema de gestão culminou na validação legal por meio de um acordo tripartite assinado em março de 2002.

Prevalence and social distribution of risk factors for chronic noncommunicable diseases in Brazil

OBJETIVOS: Evaluar los factores de riesgo de enfermedades crónicas no transmisibles (ECNT) e identificar las desigualdades sociales relacionadas con su distribución en la población adulta brasileña.MÉTODOS: Se estudiaron los factores de riesgo de ECNT (entre ellos el consumo de tabaco, el sobrepeso y la obesidad, el bajo consumo de frutas y vegetales [BCFV], la insuficiente actividad física en el tiempo de ocio [IAFTO], el estilo de vida sedentario y el consumo excesivo de alcohol) en una muestra probabilística de 54369 adultos de 26 capitales estatales de Brasil y el Distrito Federal en 2006. Se utilizó el Sistema de Vigilancia de los Factores Protectores y de Riesgo para Enfermedades Crónicas No Transmisibles por Entrevistas Telefónicas (VIGITEL), un sistema de encuestas telefónicas asistido por computadora, y se calcularon las prevalencias ajustadas por la edad para las tendencias en cuanto al nivel educacional mediante la regresión de Poisson con modelos lineales. RESULTADOS: Los hombres informaron mayor consumo de tabaco, sobrepeso, BCFV, estilo de vida sedentario y consumo excesivo de alcohol que las mujeres, pero menos IAFTO. En los hombres, la educación se asoció con un mayor sobrepeso y un estilo de vida sedentario, pero con un menor consumo de tabaco, BCFV e IAFTO. En las mujeres, la educación se asoció con un menor consumo de tabaco, sobrepeso, obesidad, BCFV e IAFTO, pero aumentó el estilo de vida sedentario CONCLUSIONES: En Brasil, la prevalencia de factores de riesgo para ECNT (excepto IAFTO) es mayor en los hombres que en las mujeres. En ambos sexos, el nivel de educación influye en la prevalencia de los factores de riesgo para ECNT

Determination of banana fruit susceptibility to post-harvest diseases: wound anthracnose, quiescent anthracnose and crown rot

Introduction. This protocol aims at ( a) evaluating the resistance to post-harvest diseases within different genotypes of bananas, and ( b) comparing different origins of bananas ( geographic origin, physiological stage, etc.) for their susceptibility to post-harvest diseases. The principle, key advantages, starting plant material, time required and expected results are presented. Materials and methods. Materials required and details of the twelve steps of the protocol ( fruit sampling and inoculum preparation, wound anthracnose resistance study, quiescent anthracnose resistance study and crown-rot resistance study) are described. Results. Typical symptoms of the different diseases are obtained after artificial inoculation.

Measurement of fungicide efficacy on post-harvest diseases: wound anthracnose, quiescent anthracnose, crown rot

Introduction. This protocol aims at evaluating (a) the efficacy of new fungicides for the control of post-harvest diseases, (b) the efficacy of various application methods for the chemical control of post-harvest diseases, and (c) the quality of the fungicide solution during the same packing day where this solution is recycled. The principle, key advantages, starting plant material, time required and expected results are presented. Materials and methods. Materials required and details of the eighteen steps of the protocol (fruit sampling and inoculum preparation, wound anthracnose study, quiescent anthracnose study, and crown-rot study) are described. Results. Comparison between untreated control bananas and bananas treated with fungicide allows the calculation of the fungicide treatment efficacy.