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.

Qualidade da atenção aos pacientes com Diabetes Mellitus no Programa Mais Médicos, em um município da região metropolitana do Recife (PE), Brasil / Quality of care for patients with Diabetes Mellitus in the More Doctors Program, in a municipality in the metropolitan region of Recife (PE), Brazil

RESUMO Avaliou-se a qualidade da atenção aos pacientes com diabetes nas equipes do Programa Mais Médicos. Tratou-se de um estudo quantitativo, transversal, realizado em Goiana, Pernambuco, entre novembro de 2016 e agosto de 2017. Utilizaram-se entrevistas estruturadas a partir do Primary Care Assessment Tool. Foram entrevistados 41 profissionais de Equipes de Saúde da Família ligadas ao Programa Mais Médicos e 437 usuários com Diabetes Mellitus acompanhados por essas equipes. Os achados demonstram que a presença regular dos médicos pode ter ocasionado bons resultados quanto à longitudinalidade (usuários: 7,1; profissionais: 8,2) e à utilização dos serviços (usuários: 8,5). A qualidade do componente sistema de informações (usuários: 7,6; profissionais: 9,2) indica preenchimento e disponibilidade de informações sobre pacientes. Deficiência estrutural do município pode ter contribuído para o baixo desempenho da acessibilidade (usuários: 3,6; profissionais: 3,9). Resultados insatisfatórios para orientação familiar (4,6) e comunitária (2,88), segundo usuários, reforçam a necessidade de fortalecimento desses atributos, peculiares à Estratégia Saúde da Família. Ademais, por tratar-se de um programa, existe a possibilidade de sua descontinuidade, sobretudo no cenário da Emenda Constitucional nº 95, de 2016, podendo comprometer o acesso e a continuidade dos cuidados, especialmente aos usuários com doenças crônicas que utilizam frequentemente o sistema de saúde.

ABSTRACT The research evaluated the quality of care for patients with diabetes, cared for by the teams of the More Doctors Program. A quantitative, cross-sectional study was carried out in Goiana, Pernambuco, between November 2016 and August 2017. Structured interviews were used from the Primary Care Assessment Tool. 41 professionals from Family Health Teams linked to the More Doctors Program and 437 users with Diabetes Mellitus monitored by those teams were interviewed. The findings evidence that regularity in doctors' attendance may have lead to good results regarding longitudinality (users: 7,1; professionals: 8,2) and use of services (users: 8,5). Quality regarding the information system component (users: 7,6; professionals: 9,2) indicates that data about patients were complete and available. Structural deficiencies in the municipality may have contributed to the low performance of accessibility (users: 3,6; professionals: 3,9). Poor results for family (4,6) and community (2,88) counselling, according to users, reinforce the need to strengthen these attributes, specific to the Family Health Strategy. Additionally, as it is a program, there is the possibility of its discontinuity, due to the context created by Constitutional Amendment nº 95, 2016, which may compromise access and continuity of care, especially for users with chronic diseases who frequently use the health care system.

Alterations in the lipid profiles and circulating liver enzymes in individuals infected by Schistosoma mansoni

Abstract INTRODUCTION Portal hypertension and periportal fibrosis commonly occur in severe Schistosoma mansoni infection. Changes in lipid profile and elevated levels of circulating liver enzymes have also been described in infected individuals. The present study sought to assess the alterations in laboratory parameters associated with liver disorder in individuals infected by S. mansoni who visited a private routine laboratory service. Levels of circulating liver enzymes (gamma-glutamyl transferase [γ-GT], aspartate transaminase [AST], alanine transaminase [ALT], and alkaline phosphatase [ALP]) and a lipid panel (total cholesterol [COL], high-density lipoprotein [HDL], low-density lipoprotein [LDL], very low-density lipoprotein [VLDL], and triglycerides [TRI]) were evaluated in both infected and non-infected individuals and relative risk was used to measure associations. METHODS Data were collected for analysis from a total of 1,078 cases identified in 379,600 individuals who submitted samples to the Datalab Laboratory (Salvador, Bahia) between 2004 and 2008. RESULTS S. mansoni infection led to increased circulating levels of γ-GT in both women and men, AST (women), and ALP (men). S. mansoni infection was a protective factor against increased levels of TRI, CHO, and VLDL for individuals aged 19 years or older. The results of our analysis indicate that alterations in lipid metabolism and circulating liver enzymes in asymptomatic S. mansoni-infected individuals might be attributed to eggs lodged in the hepatic sinusoids. CONCLUSIONS Parasitological testing for S. mansoni should be indicated in endemic areas when this pattern of alterations is detected.

Low transformation growth factor-β1 production and collagen synthesis correlate with the lack of hepatic periportal fibrosis development in undernourished mice infected with Schistosoma mansoni

Undernourished mice infected (UI) submitted to low and long-lasting infections by Schistosoma mansoni are unable to develop the hepatic periportal fibrosis that is equivalent to Symmers’ fibrosis in humans. In this report, the effects of the host’s nutritional status on parasite (worm load, egg viability and maturation) and host (growth curves, biology, collagen synthesis and characteristics of the immunological response) were studied and these are considered as interdependent factors influencing the amount and distribution of fibrous tissue in hepatic periovular granulomas and portal spaces. The nutritional status of the host influenced the low body weight and low parasite burden detected in UI mice as well as the number, viability and maturation of released eggs. The reduced oviposition and increased number of degenerated or dead eggs were associated with low protein synthesis detected in deficient hosts, which likely induced the observed decrease in transformation growth factor (TGF)-β1 and liver collagen. Despite the reduced number of mature eggs in UI mice, the activation of TGF-β1 and hepatic stellate cells occurred regardless of the unviability of most miracidia, due to stimulation by fibrogenic proteins and eggshell glycoproteins. However, changes in the repair mechanisms influenced by the nutritional status in deficient animals may account for the decreased liver collagen detected in the present study.

Resposta imune celular e patologia hepática de camundongos desnutridos, infectados com Schistosoma mansoni / Cellular immune response and hepatic pathology in undernourished mice, infected with Schistosoma mansoni

O estado nutricional do hospedeiro parece ser importante cofator no agravamento da esquistossomose mansônica. O presente trabalho avaliou as características da resposta imune celular e a patologia hepática em camundongos isogênicos C57BL/6 desnutridos e infectados pelo Schistosoma mansoni, comparando-os com eutróficos infectados da mesma linhagem. A metodologia abordou produção das citocinas IFN-gama, IL-4 e IL-13 em sobrenadante de cultura de esplenócitos (fases aguda, intermediária e crônica da infecção), estado nutricional, carga parasitária, macroscopia do fígado e do baço, estudo histopatológico do fígado, morfometria dos granulomas hepáticos periovulares e mensuração bioquímica e morfométrica do colágeno hepático. Os animais desnutridos desenvolveram peso corporal inferior, comparados aos eutróficos. O estudo parasitológico revelou maior quantidade de parasitos no grupo eutrófico. Na relação percentual entre os pesos dos animais e dos órgãos (fígado e baço), os camundongos infectados apresentaram taxas superiores às dos animais sem infecção, caracterizando organomegalia típica dos estágios avançados da doença. A histopatologia revelou maior quantidade e tamanho dos granulomas nos animais eutróficos e intensa resposta inflamatória nos espaços-porta, com abundante infiltração eosinofílica nas fases aguda e intermediária, em ambos os grupos. Na fase crônica, 40 por cento dos eutróficos desenvolveram fibrose periportal, não sendo observada essa lesão nos desnutridos. A morfometria dos granulomas e a quantificação do tecido fibroso não revelaram diferenças entre os grupos. A imunidade celular dos animais eutróficos mostrou níveis mais elevados de IL-13 do que IFN-gama, na fase aguda, indicando perfil Th2. Essa resposta Th2 permanece nas fases intermediária e crônica da infecção, embora em níveis mais baixos. A cinética da produção de citocinas nesses animais evoluiu conforme descrito na literatura. Os camundongos desnutridos, todavia, produziram, na fase aguda, níveis mais elevados de IFN-gama do que IL-13, caracterizando um perfil Th1. Na fase intermediária o componente Th1 diminuiu e foram observados altos níveis de IL-13 e IL-4 (perfil Th2), que se reduziram com a cronicidade da infecção. Pode-se especular que essa cinética diferente dificulte a atuação das citocinas fibrogênicas, sendo uma das razões pelas quais camundongos desnutridos não conseguem desenvolver fibrose periportal murina.