RESUMEN
Salmonella spp. is a prevalent pathogen that causes great public health concern worldwide. Bacteriophage-based cocktails have arisen as an alternative to antibiotics to inhibit the growth of Salmonella. However, the bactericidal effect of bacteriophage cocktails in vivo largely differs from their observed effect in vitro. This is partly because in vitro developments of cocktails do not always consider the bacterial diversity nor the environmental conditions where bacteriophages will have to replicate. Here, we isolated and sequenced 47 bacteriophages that showed variable degrees of lytic activity against 258 Salmonella isolates from a commercial broiler company in Brazil. Three of these bacteriophages were characterized and selected to assemble a cocktail. In vitro quantitative assays determined the cocktail to be highly effective against multiple serovars of Salmonella, including Minnesota and Heidelberg. Remarkably, the in vitro lytic activity of the cocktail was retained or improved in conditions that more closely resembled the chicken gut, such as anaerobiosis, 42°C, and Salmonella mono-strain biofilms. Analysis of bacterial cross-resistance between the 3 bacteriophages composing the cocktail revealed limited or no generation of cross-resistance. Our results highlight the relevance of an optimized flux of work to develop bacteriophage cocktails against Salmonella with high lytic efficacy and strong potential to be applied in vivo in commercial broiler farms.
Asunto(s)
Bacteriófagos , Salmonella enterica , Animales , Pollos/microbiología , Antibacterianos , BrasilRESUMEN
INTRODUÇÃO: Entre pacientes diagnosticados e em tratamento para osteoporose, acredita-se que há desconhecimento geral sobre a doença. Entre os pacientes em faixa etária de risco, não diagnosticados, crê-se que o desconhecimento é maior. OBJETIVO: Avaliar as considerações de mulheres sobre o conceito da osteoporose e sua prevenção. MÉTODOS: Estudo qualitativo, descritivo, realizado no Hospital das Clínicas da Universidade Federal de Minas Gerais, Belo Horizonte, com 10 pacientes portadores de osteoporose, e 10 pacientes sem. A tabulação dos dados ocorreu por meio da utilização de três figuras metodológicas: ideia central, expressões chave e o discurso sujeito coletivo. O estudo foi aprovado pelo Comitê de Ética e Pesquisa com Seres Humanos. RESULTADOS: Dentre as pacientes com diagnóstico, destacou-se como ideias centrais a vulnerabilidade às fraturas e os conceitos de apresentação da doença como osteopenia e osteoporose. No grupo sem diagnóstico, 40% desconhecia a doença. Na prevenção, observou-se maior conhecimento no grupo portador da doença, sendo as ideias centrais destacadas: os exercícios físicos, alimentação rica em cálcio e vitamina D, além da exposição solar. CONCLUSÃO: Evidenciou-se um conhecimento limitado sobre a osteoporose e suas formas de prevenção, sobretudo no grupo sem diagnóstico, porém em faixa etária de risco. Assim, conclui-se que, tratando-se de uma doença de elevada prevalência, de altos custos orçamentários para a saúde pública, e com riscos significativos uma vez não diagnosticados e não tratada, medidas resolutivas de maior esclarecimento sobre a doença devem ser praticadas em todas as esferas da saúde pública.
INTRODUCTION: Among patients diagnosed and under treatment for osteoporosis, it is believed that there is general ignorance about the disease. Among undiagnosed patients at risk, it is believed that the lack of knowledge is larger. OBJECTIVE: To evaluate the considerations of women about the concept of osteoporosis and its prevention. METHODS: A qualitative, descriptive study was carried out at Hospital das Clínicas da Universidade Federal de Minas Gerais, Belo Horizonte, Brazil, with 10 patients with osteoporosis and 10 patients without the disease. Data tabulation occurred using three methodological figures: central idea, key expressions and collective subject discourse. The study was approved by the Committee of Ethics and Research with Human Beings. RESULTS: Among the diagnosed patients, the central ideas were vulnerability to fractures and the concepts of disease presentation like osteopenia and osteoporosis. In the undiagnosed group, 40% were unaware of the disease. About prevention, greater knowledge was observed in the group with the disease, with the main ideas being highlighted: physical exercises, calcium and vitamin D rich food, as well as sun exposure. CONCLUSION: There was limited knowledge about osteoporosis and its prevention, especially in the group without diagnosis, but in the age group at risk. Thus, it is concluded that, in the case of a disease of high prevalence, of high budgetary costs for public health, and with significant risks once it is undiagnosed and untreated, resolute measures of greater clarity about the disease should be practiced in all spheres of public health.
Asunto(s)
Humanos , Femenino , Anciano , Osteoporosis , Osteoporosis/prevención & control , Salud de la Mujer , Prevención de Enfermedades , Salud del Anciano , Investigación CualitativaRESUMEN
Colorectal cancer is a deadly disease, which is frequently diagnosed at advanced stages, where conventional treatments are no longer effective. Cancer immunotherapy has emerged as a new form to treat different malignancies by turning-on the immune system against tumors. However, tumors are able to evade antitumor immune responses by promoting an immunosuppressive microenvironment. Single-stranded DNA containing M13 bacteriophages are highly immunogenic and can be specifically targeted to the surface of tumor cells to trigger inflammation and infiltration of activated innate immune cells, overcoming tumor-associated immunosuppression and promoting antitumor immunity. Carcinoembryonic antigen (CEA) is highly expressed in colorectal cancers and has been shown to promote several malignant features of colorectal cancer cells. In this work, we targeted M13 bacteriophage to CEA, a tumor-associated antigen over-expressed in a high proportion of colorectal cancers but largely absent in normal cells. The CEA-targeted M13 bacteriophage was shown to specifically bind to purified CEA and CEA-expressing tumor cells in vitro. Both intratumoral and systemic administration of CEA-specific bacteriophages significantly reduced tumor growth of mouse models of colorectal cancer, as compared to PBS and control bacteriophage administration. CEA-specific bacteriophages promoted tumor infiltration of neutrophils and macrophages, as well as maturation dendritic cells in tumor-draining lymph nodes, suggesting that antitumor T-cell responses were elicited. Finally, we demonstrated that tumor protection provided by CEA-specific bacteriophage particles is mediated by CD8+ T cells, as depletion of circulating CD8+ T cells completely abrogated antitumor protection. In summary, we demonstrated that CEA-specific M13 bacteriophages represent a potential immunotherapy against colorectal cancer.