RESUMO
INTRODUCTION: Human respiratory syncytial virus (hRSV) is an important cause of lower respiratory tract infections in the pediatric and the geriatric population worldwide. There is a substantial economic burden resulting from hRSV disease during winter. Although no vaccines have been approved for human use, prophylactic therapies are available for high-risk populations. Choosing the proper animal models to evaluate different vaccine prototypes or pharmacological treatments is essential for developing efficient therapies against hRSV. AREAS COVERED: This article describes the relevance of using different animal models to evaluate the effect of antiviral drugs, pharmacological molecules, vaccine prototypes, and antibodies in the protection against hRSV. The animal models covered are rodents, mustelids, bovines, and nonhuman primates. Animals included were chosen based on the available literature and their role in the development of the drugs discussed in this manuscript. EXPERT OPINION: Choosing the correct animal model is critical for exploring and testing treatments that could decrease the impact of hRSV in high-risk populations. Mice will continue to be the most used preclinical model to evaluate this. However, researchers must also explore the use of other models such as nonhuman primates, as they are more similar to humans, prior to escalating into clinical trials.
Assuntos
Infecções por Vírus Respiratório Sincicial , Vacinas contra Vírus Sincicial Respiratório , Vírus Sincicial Respiratório Humano , Idoso , Humanos , Camundongos , Animais , Criança , Bovinos , Vacinas contra Vírus Sincicial Respiratório/uso terapêutico , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Modelos Animais de Doenças , Gravidade do PacienteRESUMO
Despite significant research since it was discovered more than 50 years ago, respiratory syncytial virus (RSV) continues to be the leading agent causing infant hospitalization and respiratory distress worldwide. Although RSV normally does not cause mortality, this virus is recognized as a major public health and economic burden around the globe. RSV can modulate host immunity leading to an inflammatory response that produces lung damage and virus dissemination in the host airways. Remarkably, infection with the virus elicits poor immunity that in most cases fails to protect against subsequent exposures. Here, we review advances made on the understanding of the lifecycle of the virus, some of the molecular mechanisms it has evolved to cause pathology and ineffective immunity during infection. Hopefully, ongoing research will contribute to developing new drugs and candidate vaccines that will decrease the health burden caused by this virus.
Assuntos
Citocinas/metabolismo , Imunidade Inata , Infecções por Vírus Respiratório Sincicial/imunologia , Infecções por Vírus Respiratório Sincicial/terapia , Citocinas/imunologia , Humanos , Pulmão/imunologia , Pulmão/patologia , Infecções por Vírus Respiratório Sincicial/virologia , Vírus Sinciciais Respiratórios/patogenicidadeRESUMO
Dendritic cells (DCs) are professional antigen presenting cells (APCs) capable of linking innate and adaptive immunity during infection. After recognition of pathogen-associated molecular patterns (PAMPs), DCs can engulf, process and present bacteria-derived antigens on MHC molecules to T cells. Because of the key role that DCs play on the initiation of innate and adaptive immunity, alterations in their function could render the host susceptible to bacterial dissemination. Consistent with this notion, is the observation that several pathogenic bacteria have evolved mechanisms to impair the DC capacity to prime naïve T cells. One of such bacteria is Salmonella enterica serovar Typhimurium, which causes a typhoid-like disease in mice and gastroenteritis in humans. Recent studies have shown that virulent Salmonella can use intestinal DCs to spread inside the host, evading T cell priming. The avoidance of T cell recognition by Salmonella is in large part achieved by the activity of gene products encoded on Salmonella Pathogenicity Islands -1 and - 2. The understanding of some of the remarkable molecular virulence mechanisms displayed by Salmonella has contributed to the design of new vaccines capable of inducing protective immunity against this pathogen in mouse models. Here we describe recent data underscoring the virulence mechanisms used by Salmonella to exploit DC function and discuss strategies based on this new knowledge aimed at the design of new efficient and safe vaccines against this pathogen.
Assuntos
Infecções por Salmonella/imunologia , Vacinas contra Salmonella/imunologia , Salmonella typhimurium/imunologia , Fatores de Virulência/imunologia , Animais , Células Dendríticas/imunologia , Humanos , Imunidade/genética , Imunidade/imunologia , Infecções por Salmonella/microbiologia , Vacinas contra Salmonella/química , Salmonella typhimurium/patogenicidadeRESUMO
Dendritic cells (DCs) link innate and adaptive immunity by directly recognizing pathogen-associated molecular patterns (PAMPs) on bacteria. DCs can capture and degrade bacteria and present their antigens on MHC molecules to T cells. PAMP recognition promotes DC maturation, a phenotypic change that empowers them to prime naïve T cells. As a result, an adaptive immune response that specifically targets bacteria-derived antigens is initiated. Consequently, any impairment of DC function might contribute to bacterial survival and dissemination in the host. Therefore, the characterization of DC-bacteria interactions is required to understand the mechanisms used by virulent bacteria to avoid adaptive immunity. An example of a bacterial pathogen capable of interfering with DC function is Salmonella enterica serovar Typhimurium (S. Typhimurium), which causes a typhoid-like disease in mice. Virulent strains of S. Typhimurium are able to differentially modulate the entrance to DCs and avoid lysosomal degradation, to prevent antigen presentation on MHC molecules. These features of virulent S. Typhimurium are controlled by virulence factors encoded by Salmonella Pathogenicity Islands 1 and 2. Modulation of DC functions by the activity of these gene products is supported by several recent studies, which have shown that pathogenesis might depend on this attribute of virulent S. Typhimurium. Here we discuss recent data showing that several virulence factors from Salmonella are required to differentially modulate DC function and adaptive immunity in the host.
Assuntos
Células Dendríticas/imunologia , Infecções por Salmonella/microbiologia , Salmonella typhimurium/imunologia , Salmonella typhimurium/patogenicidade , Animais , Humanos , Fatores de Virulência/imunologiaRESUMO
Monoclonal antibodies (MAbs) have been used for therapies and some analytical procedures as highly purified molecules. Many techniques have been applied and studied, focusing on monoclonal antibodies purification. In this study, an immobilized metal affinity chromatography membrane was developed and evaluated for the purification of anti-TNP IgG(1) mouse MAbs from cell culture supernatant after precipitation with a 50% saturated ammonium sulfate solution. The chelating ligands iminodiacetic acid, carboxymethylated aspartic acid (CM-Asp), nitrilotriacetic acid, and tris (carboxymethyl) ethylenediamine in agarose gels with immobilized Ni(II) and Zn(II) ions were compared for the adsorption and desorption of MAbs. The most promising chelating ligand--CM-Asp--was then coupled to poly(ethylene vinyl alcohol) (PEVA) hollow fiber membranes. According to SDS-PAGE and ELISA analyses, a higher selectivity and a purification factor of 85.9 (fraction eluted at 500 mM Tris) were obtained for IgG(1) using PEVA-CM-Asp-Zn(II). The anti-TNP MAb could be eluted under mild pH conditions causing no loss of antigen binding capacity.
Assuntos
Anticorpos Monoclonais/isolamento & purificação , Quelantes/química , Cromatografia de Afinidade/métodos , Imunoglobulina G/isolamento & purificação , Metais/química , Adsorção , Anticorpos Monoclonais/química , Ácido Aspártico/química , Cromatografia de Afinidade/instrumentação , Etilenodiaminas/química , Iminoácidos/química , Imunoglobulina G/química , Ligantes , Membranas Artificiais , Níquel/química , Ácido Nitrilotriacético/química , Propriedades de Superfície , Zinco/químicaRESUMO
Neurological deficits in the offspring caused by human maternal hypothyroxinemia are thought to be irreversible. To understand the mechanism responsible for these neurological alterations, we induced maternal hypothyroxinemia in pregnant rats. Behavior and synapse function were evaluated in the offspring of thyroid hormone-deficient rats. Our data indicate that, when compared with controls, hypothyroxinemic mothers bear litters that, in adulthood, show prolonged latencies during the learning process in the water maze test. Impaired learning capacity caused by hypothyroxinemia was consistent with cellular and molecular alterations, including: 1) lack of increase of phosphorylated c-fos on the second day of the water maze test; 2) impaired induction of long-term potentiation in response to theta-burst stimulation to the Schaffer collateral pathway in the area 1 of the hippocampus Ammon's horn stratum radiatum, despite normal responses for input/output experiments; 3) increase of postsynaptic density protein 95 (PSD-95), N-methyl-D-aspartic acid receptor subunit 1, and tyrosine receptor kinase B levels in brain extracts; and 4) significant increase of PSD-95 at the PSDs and failure of this molecule to colocalize with N-methyl-D-aspartic acid receptor subunit 1, as it was shown by control rats. Our findings suggest that maternal hypothyroxinemia is a harmful condition for the offspring that can affect key molecular components for synaptic function and spatial learning.
Assuntos
Transtornos Cognitivos/fisiopatologia , Hipotireoidismo/fisiopatologia , Aprendizagem em Labirinto/fisiologia , Complicações na Gravidez/fisiopatologia , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Tiroxina/deficiência , Fatores Etários , Animais , Transtornos Cognitivos/etiologia , Proteína 4 Homóloga a Disks-Large , Feminino , Hipotireoidismo/complicações , Imidazóis , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Potenciação de Longa Duração/fisiologia , Masculino , Proteínas de Membrana/metabolismo , Fosforilação , Gravidez , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores de N-Metil-D-Aspartato/metabolismo , Percepção Espacial/fisiologia , Sinapses/fisiologia , Tiroxina/sangueAssuntos
Antirretrovirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , HIV-1/genética , Adulto , Brasil , DNA Viral/genética , Farmacorresistência Viral/genética , Feminino , Genótipo , Infecções por HIV/virologia , Humanos , Masculino , Dados de Sequência Molecular , Mutação/genética , Provírus/genética , RNA Viral/genéticaRESUMO
Os sucos de frutas são definidos como os líquidos obtidos por expressão ou extração de frutas maduras por processos tecnológicos adequados. Destes, o suco de laranja é o mais popular. No Brasil, devido às adversidades econômicas, surgiu uma nova forma de comercialização da laranja. Foi introduzido no mercado, um equipamento de pequeno porte para extração do suco, no qual são adicionadas as laranjas após lavagem das cascas. Estes sucos são engarrafados, distribuídos e vendidos em carrinhos de fibra de vidro sem refrigeração adequada. Portanto, o objetivo deste trabalho foi verificar as características físico-químicas e as condições higiênico-sanitárias dos sucos de laranja produzidos e comercializados por industrias de pequeno porte nas vias públicas da cidade de São José do Rio Preto-SP. Foram analisadas 10 amostras de 10 marcas comerciais de sucos de laranja in natura todas dentro do prazo de validade. Os resultados mostraram que das 10 marcas, 02 se encontraram acima dos padrões estabelecidos pela legislação para as contagens de bolores e leveduras podendo promover a produção de micotoxinas; 03 apresentaram altas contagens de microrganismos mesófilos sugerindo falta de higiene durante a fabricação. As análises físico-químicas mostraram que 01 amostra estava fora do padrão em relação aos sólidos solúveis (°Brix); 03 não preenchiam as exigências mínimas de densidade e todas não apresentavam o Ratio adequado. Portanto, a grande variação nestes parâmetros pode ser atribuída a qualidade das laranjas utilizadas ou mesmo adição de água nestes mesmos sucos.(AU)
Fruit juices are defined as liquids obtained by squeezing ripe fruits (or by extraction) by adequate technologicalprocesses. Among the fruit juices, the orange juice is the most popular. In Brazil, due to economical adversities, a new way to commercialize orange juice has been employed. The juice is extracted by placing the oranges, after washing them, inside a medium-sized equipment. The extracted juice is bottled and kept in carts made of fiber glass without adequate refrigeration, and sold. The objective of this study was to analyze the physical-chemical characteristics as well as the hygienic conditions of the orange juice produced by small sized industries and sold in the streets of São José do Rio Preto - SP Ten samples of orange juice in natura of ten different commercial brands have been analyzed, observing the respectives periods of shelf-life. Results have shown that, out of the ten samples, the fungus and yeast counts were above the levels accepted by law in two of them, thus indicating that they may produce mycotoxins; the count for mesophyllic microorganisms was high in three samples, indicating lack of hygiene during production. The physical-chemical analyses have shown that one sample did not meet the standards for soluble solids (OBrix ); three samples did not meet the minimal requirements for density, and all samples did not meet the adequate Ratio. Therefore, the high degree of variation of such parameters may be due to the quality of the orangesused or to the addition of water to the fruit juices. (AU)
Assuntos
Citrus sinensis , Frutas/microbiologia , Tecnologia de Alimentos , Qualidade de Produtos para o ConsumidorRESUMO
Os sucos de frutas são definidos como os líquidos obtidos por expressão ou extração de frutas maduras por processos tecnológicos adequados. Destes, o suco de laranja é o mais popular. No Brasil, devido às adversidades econômicas, surgiu uma nova forma de comercialização da laranja. Foi introduzido no mercado, um equipamento de pequeno porte para extração do suco, no qual são adicionadas as laranjas após lavagem das cascas. Estes sucos são engarrafados, distribuídos e vendidos em carrinhos de fibra de vidro sem refrigeração adequada. Portanto, o objetivo deste trabalho foi verificar as características físico-químicas e as condições higiênico-sanitárias dos sucos de laranja produzidos e comercializados por industrias de pequeno porte nas vias públicas da cidade de São José do Rio Preto-SP. Foram analisadas 10 amostras de 10 marcas comerciais de sucos de laranja in natura todas dentro do prazo de validade. Os resultados mostraram que das 10 marcas, 02 se encontraram acima dos padrões estabelecidos pela legislação para as contagens de bolores e leveduras podendo promover a produção de micotoxinas; 03 apresentaram altas contagens de microrganismos mesófilos sugerindo falta de higiene durante a fabricação. As análises físico-químicas mostraram que 01 amostra estava fora do padrão em relação aos sólidos solúveis (°Brix); 03 não preenchiam as exigências mínimas de densidade e todas não apresentavam o Ratio adequado. Portanto, a grande variação nestes parâmetros pode ser atribuída a qualidade das laranjas utilizadas ou mesmo adição de água nestes mesmos sucos.
Assuntos
Citrus sinensis , Qualidade de Produtos para o Consumidor , Tecnologia de Alimentos , Frutas , Fenômenos QuímicosRESUMO
Histidine was immobilized onto PEVA membrane to obtain an affinity support for human IgG removal from serum with a view to clinical apheresis for the treatment of autoimmune diseases. These membranes were able to remove in vitro several autoantibodies from the serum of SLE patients.