Epithelial responses and Candida albicans pathogenicity are enhanced in the presence of oral streptococci

Abstract Experimental models that consider host-pathogen interactions are relevant for improving knowledge about oral candidiasis. The aim of this study was to assess the epithelial immune responses, Candida penetration of cell monolayers, and virulence during mixed species culture infections. Single species cultures of Candida albicans and mixed cultures (C. albicans, Streptococcus mutans, and Streptococcus sanguinis) were used to infect monolayers of HaCaT and FaDu ATCC HTB-43 cells for 12 h. After infection, IL-18 and IL-34 gene expression was measured to assess epithelial cell immune responses, and lactate dehydrogenase (LDH) activity was measured as an indicator of cell damage. Microscopy determined C. albicans morphology and penetration of fungal cells through the keratinocyte monolayer. Monolayers devoid of infection served as controls. Data were analyzed by an ANOVA one-way test followed by Tukey's post-hoc test (α = 0.05). The results found that IL-18 and IL-34 gene expression and LDH activity were significantly (p < 0.05) upregulated for both cell lines exposed to mixed species cultures compared with C. albicans alone. Candida albicans yeast and hyphae were evident in C. albicans only infections. In contrast, monolayers infected by C. albicans, S. mutans, and S. sanguinis exhibited higher microbial invasion with several hyphal aggregates detected. The presence of streptococci in C. albicans infection enhances the virulence and pathogenicity of the fungus with associated increased immune responses and tissue damage. Extrapolation of these findings to oral infection would indicate the added potential benefit of managing bacterial components of biofilms during treatment.

Resumo O objetivo deste estudo foi avaliar a resposta epithelial imune, a colonização da Candida albicans em monocamadas celulares e sua virulência em resposta a infecções de culturas de biofilme multiespécie. Culturas de biofilme monoespécie de C. albicans e culturas mistas (C. albicans, Streptococcus mutans e Streptococcus sanguinis) foram utilizadas para infectar monocamadas de células HaCaT e FaDu por 12 h. Após a infecção, a expressão dos genes IL-18 e IL-34 foi medida para avaliar as respostas imunes das células epiteliais. A atividade da lactato desidrogenase (LDH) foi medida como um indicador de dano celular. A microscopia determinou a morfologia de C. albicans e a penetração das células fúngicas através da monocamada de queratinócitos. Monocamadas em que não houve infecção serviram como controles. Os dados foram analisados por um teste ANOVA one-way seguido pelo teste post-hoc de Tukey (α = 0,05). Os resultados demonstraram que a expressão gênica de IL-18 e IL-34 e a atividade de LDH foram (p < 0,05) reguladas positivamente para ambas as linhagens de células expostas a culturas de espécies mistas em comparação com C. albicans isoladamente. Leveduras de C.albicans e hifas foram evidentes em infecções apenas por C. albicans. Entretanto, monocamadas infectadas por C. albicans, S. mutans e S. sanguinis exibiram maior invasão microbiana com vários agregados de hifas detectados. Dessa maneira, a presença de estreptococos na infecção por C. albicans aumentou a virulência e a patogenicidade do fungo com respostas imunes aumentadas associadas a danos nos tecidos. A extrapolação desses achados para a infecção oral indicaria o potencial benéfico do controle dos componentes bacterianos em biofilmes durante a terapia da candidíase

Antimicrobial activities of mycoleptodiscin B isolated from endophytic fungus Mycoleptodiscus sp. of Calamus thwaitesii Becc.

Endophytic fungi are a promising source of novel biologically active compounds including antimicrobials. Plant endophytic fungi of Sri Lanka, an island with exceptionally high biodiversity and endemism, are a vastly untapped resource. Therefore this study was initiated with the objective of examining the antimicrobial producing potential of the endophytic fungi of Calamus thwaitesii Becc. from Sri Lanka. This examination resulted in the isolation of 21 fungi with 7 of them exhibiting antimicrobial properties. Further investigation of the Mycoleptodiscus sp. isolated from the leaves, which showed the best activity among them, resulted in the isolation of the known alkaloid mycoleptodiscin B and its structure was elucidated and confirmed by mass and nuclear magnetic resonance spectral data. Mycoleptodiscin B showed promising antimicrobial activity against Bacillus subtilis (MIC 0.5 µg mL-1) and Staphylococcus aureus (MIC 1 µg mL-1), and was less potent against methicillin resistant Staphylococcus aureus (MRSA, MIC 32 µg mL-1) and the pathogenic fungus Candida albicans (MIC 64 µg mL-1). This is the first study to report the isolation, identification and antimicrobial properties of endophytic fungi of C. thwaitesii and the antimicrobial activities of the alkaloid mycoleptodiscin B.

New approaches & technologies of venomics to meet the challenge of human envenoming by snakebites in India.

The direct estimate of 46,000 snakebite deaths in India in 2005 (1 for every 2 HIV/AIDS deaths), based on verbal autopsies, renders unrealistic the total of only 47,000 snakebite deaths in the whole world in 2010, obtained indirectly as part of the “Global Burden of Disease 2010” study. Persistent underestimation of its true morbidity and mortality has made snakebite the most neglected of all the WHO’s “neglected tropical diseases”, downgrading its public health importance. Strategies to address this neglect should include the improvement of antivenom, the only specific antidote to envenoming. To accommodate increased understanding of geographical intraspecific variation in venom composition and the range of snake species that are medically important in India, the design of antivenoms (choice of venom sources and species coverage) should be reconsidered. Methods of preclinical and clinical testing should be improved. The relatively new science of venomics involves techniques and strategies for assessing the toxin composition of snake venoms directly through proteomics-centred approaches or indirectly via high-throughput venom gland transcriptomics and bioinformatic analysis. Antivenomics is translational venomics: a proteomics-based protocol to quantify the extent of cross-reactivity of antivenoms against homologous and heterologous venoms. These approaches could revolutionize the preclinical assessment of antivenom efficacy, leading to a new generation of antivenoms that are clinically more effective.

Racial discrimination & health: pathways & evidence.

This review provides an overview of the existing empirical research of the multiple ways by which discrimination can affect health. Institutional mechanisms of discrimination such as restricting marginalized groups to live in undesirable residential areas can have deleterious health consequences by limiting socio-economic status (SES) and creating health-damaging conditions in residential environments. Discrimination can also adversely affect health through restricting access to desirable services such as medical care and creating elevated exposure to traditional stressors such as unemployment and financial strain. Central to racism is an ideology of inferiority that can adversely affect non-dominant groups because some members of marginalized populations will accept as true the dominant society's ideology of their group's inferiority. Limited empirical research indicates that internalized racism is inversely related to health. In addition, the existence of these negative stereotypes can lead dominant group members to consciously and unconsciously discriminate against the stigmatized. An overview of the growing body of research examining the ways in which psychosocial stress generated by subjective experiences of discrimination can affect health is also provided. We review the evidence from the United States and other societies that suggest that the subjective experience of discrimination can adversely affect health and health enhancing behaviours. Advancing our understanding of the relationship between discrimination and health requires improved assessment of the phenomenon of discrimination and increased attention to identifying the psychosocial and biological pathways that may link exposure to discrimination to health status.

The concept and measurement of race and their relationship to public health: a review focused on Brazil and the United States

Race has been widely used in studies on health and healthcare inequalities, especially in the United States. Validity and reliability problems with race measurement are of concern in public health. This article reviews the literature on the concept and measurement of race and compares how the findings apply to the United States and Brazil. We discuss in detail the data quality issues related to the measurement of race and the problems raised by measuring race in multiracial societies like Brazil. We discuss how these issues and problems apply to public health and make recommendations about the measurement of race in medical records and public health research.

Fagocitosis de partículas de látex por macrófagos de ratón: influencia del tamaño de la partícula en su internación y en la liberación de lisozima / Phagocytosis of latex particles by mouse macrophages: influence of particle size on engulfment and lysozyme relase

Para determinar el comportamiento fagocítico de macrófagos en función del tamaño de partícula fagocitada, se cultivaron macrófagos peritoneales de ratón CBA in vitro durante 4, 24, 48, 72 y 96 h. Posteriormente se les incubó con partículas de látex opsonizadas (cinco grupos con partículas de 2, 6, 10, 15 y 25 µm de diámetro). En en grupo de 2 µg, 70.1 por ciento+ 5.7 de los macrófagos fagocitó las partículas, decreciendo progresivamente esta proporción (6 µm, 54.5 por ciento+ 4.9; 10 µm, 25.5 por ciento+ 6.6) hasta el grupo de 15 µm (0.33 por ciento + 0.2). La fagocitosis estuvo inversamente correlacionada al tamaño de las partículas (r=-0.9). No hubo fagocitosis en el ensayo de 25 µm. Mediante microscopía electrónica de barrido se pudo observar que en todos los grupos se estableció un contacto entre partículas de látex y macrófagos. En todos los grupos hubo liberación de lisozima, encontrándose que una mayor liberación estuvo asociada a un tamaño de partícula más grande (r=0.91). Nuestros resultados apoyan el concepto de que la fagocitosis está limitada por el tamaño de la partícula y que el contacto con éstas provoca degranulación, fenómeno que puede dar lugar a la muerte de organismo (p.ej., bacterias) cuando son atacados por enzimas liberadas por los macrófagos.