RESUMO
BACKGROUND: Dengue virus (DENV) is considered one of the most important pathogens in the world causing 390 million infections each year. Currently, the development of vaccines against DENV presents some shortcomings and there is no antiviral therapy available for its infection. An important challenge is that both treatments and vaccines must be effective against all four DENV serotypes. Nordihydroguaiaretic acid (NDGA), isolated from Larrea divaricata Cav. (Zygophyllaceae) has shown a significant inhibitory effect on a broad spectrum of viruses, including DENV serotypes 2 and 4. PURPOSE: We evaluated the in vitro virucidal and antiviral activity of NDGA on DENV serotype 1 (DENV1), including the study of its mechanism of action, to provide more evidence on its antiviral activity. METHODS: The viability of viral particles was quantified by the plaque-forming unit reduction method. NDGA effects on DENV1 genome and viral proteins were evaluated by qPCR and immunofluorescence, respectively. Lysosomotropic activity was assayed using acridine orange and neutral red dyes. RESULTS: NDGA showed in vitro virucidal and antiviral activity against DENV1. The antiviral effect would be effective within the first 2 h after viral internalization, when the uncoating process takes place. In addition, we determined by qPCR that NDGA decreases the amount of intracellular RNA of DENV1 and, by immunofluorescence, the number of cells infected. These results indicate that the antiviral effect of NDGA would have an intracellular mechanism of action, which is consistent with its ability to be incorporated into host cells. Considering the inhibitory activity of NDGA on the cellular lipid metabolism, we compared the antiviral effect of two inhibitors acting on two different pathways of this type of metabolism: 1) resveratrol that inhibits the sterol regulatory element of binding proteins, and 2) caffeic acid that inhibits the 5-lipoxygenase (5-LOX) enzyme. Only caffeic acid produced an inhibitory effect on DENV1 infection. We studied the lysosomotropic activity of NDGA on host cells and found, for the first time, that this compound inhibited the acidification of cell vesicles which would prevent DENV1 uncoating process. CONCLUSION: The present work contributes to the knowledge of NDGA activity on DENV. We describe its activity on DENV1, a serotype different to those that have been already reported. Moreover, we provide evidence on which stage/s of the viral replication cycle NDGA exerts its effects. We suggest that the mechanism of action of NDGA on DENV1 is related to its lysosomotropic effect, which inhibits the viral uncoating process.
Assuntos
Vírus da Dengue , Laranja de Acridina/farmacologia , Antivirais/farmacologia , Araquidonato 5-Lipoxigenase/genética , Ácidos Cafeicos , Corantes/farmacologia , Vírus da Dengue/fisiologia , Masoprocol/farmacologia , Vermelho Neutro/farmacologia , RNA , Resveratrol/farmacologia , Sorogrupo , Esteróis/farmacologia , Proteínas Virais , Replicação ViralRESUMO
An environmental survey was conducted in order to assess the frequency of detection of picobirnavirus (PBV), human adenovirus (HAdV) and infective enterovirus (iEV) as indicators of faecal contamination in freshwater, and to determine their potential as reporters of the presence of other enteric viruses, such as group A rotavirus (RVA). The study was carried out over a three-year period (2013-2015) in the San Roque Dam, Córdoba, Argentina. The overall frequency detection was 62.9% for PBV, 64.2% for HAdV and 70.4% for iEV. No significant differences were observed in the rates of detection for any of these viruses through the years studied, and a seasonal pattern was not present. Whenever there was RVA detection in the samples analyzed, there was also detection of iEV and/or HAdV and/or PBV. At least one of the viral groups analyzed was demonstrated in the 100% of the samples with faecal coliforms values within the guideline limits. In this setting, especially in those samples which reveal faecal indicator bacteria within the guideline limit, we propose to carry out a pathway, involving PBV, HAdV and iEV detection in order to enhance the evaluation of microbiological quality in freshwater in Argentina. The proposed methodological strategy could report faecal contamination in water, mainly of human origin, and the condition of the matrix to maintain viral viability. In addition, the viral groups selected could report the presence of RV.
Assuntos
Enterovirus , Rotavirus , Argentina , Fezes , Água Doce , Humanos , Microbiologia da ÁguaRESUMO
Chronic Hepatitis B (HBV) is the most important cause of liver disease worldwide. There is a need for low-cost tests to aid in diagnosis and management of HBV infection in resource-limited settings. We evaluated the utility of several rapid diagnostic tests (RDT) in three different continents (Europe, South America, Africa). The HBsAg RDT showed optimal sensitivity and specificity. The anti-HBeAb RDT showed acceptable sensitivity and excellent specificity. Our results suggest that these RDTs could be used for screening and management of HBV.
Assuntos
Anticorpos Anti-Hepatite B/sangue , Antígenos de Superfície da Hepatite B/sangue , Antígenos E da Hepatite B/sangue , Hepatite B Crônica/sangue , Hepatite B Crônica/diagnóstico , Adulto , Argentina , Técnicas de Diagnóstico do Sistema Digestório , Etiópia , Feminino , Antígenos de Superfície da Hepatite B/imunologia , Antígenos E da Hepatite B/imunologia , Humanos , Masculino , Países Baixos , Curva ROC , Fatores de TempoRESUMO
Water resources contaminated with wastewater are an important source for the dissemination of enteric viruses with an impact on the health of the population. The aim of the study was to assess the viral contamination of freshwater from a dam in Argentina by using infectious enterovirus detection, viral RNA amplification, and a genetic characterization of five enteric viruses associated with diarrhea and hepatitis. Enterovirus infectivity (iEV) was evaluated by cell culture and direct immunofluorescence. The detection of the viral genome of rotavirus (RV), human astrovirus (HAstV), norovirus (NoV), hepatitis A virus (HAV), and hepatitis E virus (HEV) was performed by reverse transcriptase PCR (RT-PCR). A total of 48 water samples from 4 monitoring points on the body of the dam from January to December 2012 and 66 water samples from 3 tourist beaches on the edge of the dam from October 2013 to October 2015 were collected monthly. During the first period, the overall viral frequency detection was 52.1% for group A RV, 50% for HAstV, 60.4% for NoV, 22.9% for HAV, 2.1% for HEV, and 64.6% for iEV. The overall frequency detection for the second sampling was 18.2% for RV and HAstV, 31.8% for NoV, 7.57% for HEV, and 66.7% for iEV. There was no detection of HAV during this period. The genotypes and genogroups detected through the study correlated with the most common genomic variants associated with human gastrointestinal and hepatitis illnesses. The results obtained could alert the health systems and environmental sanitation to make decisions for viral control and prevention in our environment.IMPORTANCE The study shows the impact of anthropic contamination of one of the most important tourist water resources in Argentina. This course of recreational water would be a favorable scenario for infection, as well as a reservoir for the enteric viruses, creating a risk for the population exposed to these waters. The results obtained could alert the health systems and environmental sanitation to make decisions for the control and prevention of viral diseases in this environment.
Assuntos
Água Doce/virologia , Vírus de RNA/isolamento & purificação , Águas Residuárias/virologia , Argentina , Monitoramento Ambiental , Técnicas de Amplificação de Ácido Nucleico , Vírus de RNA/genética , RNA Viral/análiseRESUMO
The capability to acquire context conditioning does not emerge until weaning, at least when the defining features of the context lack explicit and salient olfactory cues. Contextual learning deficits in preweanling rats have been associated with functional immaturity of the dorsal hippocampus. According to recent studies, the so-called context preexposure facilitation effect (CPFE) - a hippocampus-dependent effect - is not observed until postnatal day 23 (PD23). In these studies the footshock intensity employed was higher (1.5 mA) than in adult studies, and context conditioning was inferred from a single behavioral measure (percentage of freezing). The present study examined the CPFE on PD17 and PD23 by analyzing multiple dependent variables, including fecal boli and an ethogram covering the complete behavioral repertoire of the rat. A non-shocked control group was included in the design and two footshock intensities were employed (0.5 and 1.5 mA). Results showed clear evidence of contextual fear conditioning in preweanling and weanling rats, as well as evidence of conditioned fear in non-preexposed rats from both age groups. In some cases, some dependent variables, such as grooming or vertical exploration, were more sensitive than freezing for detecting evidence of memory. Strong fear responses were detected in weanling (but not preweanling) rats, when rats were evaluated in a different context from the one employed at conditioning. These results indicate that preweanling rats are capable of acquiring contextual conditioning, even in a context lacking explicit odor cues, and highlight the importance of multiple dependent variables for analyzing the ontogeny of memory.
Assuntos
Condicionamento Clássico/fisiologia , Medo/fisiologia , Generalização Psicológica/fisiologia , Fatores Etários , Análise de Variância , Animais , Animais Recém-Nascidos , Biofísica , Sinais (Psicologia) , Eletrochoque/efeitos adversos , Comportamento Exploratório/fisiologia , Fezes , Asseio Animal/fisiologia , Resposta de Imobilidade Tônica/fisiologia , Odorantes , Ratos , Ratos Wistar , Fatores de TempoRESUMO
Venezuelan equine encephalitis complex includes viruses considered emerging pathogens for humans and animals in the Americas. Two members of this complex have been detected previously in Argentina: Rio Negro Virus (RNV), detected in mosquitoes from Chaco province and rodents from Formosa province, and Pixuna Virus (PIXV), detected in mosquitoes from Chaco province. To carry out surveillance studies in other parts of the country, detection of a 195-bp fragment of alphaviruses by RT-nested PCR was performed in mosquito samples from San Miguel de Tucumán city. Four pools resulted positive and three were sequenced. Two amplicons grouped with RNV and one with PIXV. This is the first report of viral activity of members of the Venezuelan equine encephalitis complex in north-eastern Argentina.
Assuntos
Alphavirus/isolamento & purificação , Culicidae/virologia , Insetos Vetores/virologia , Alphavirus/classificação , Alphavirus/genética , Animais , Argentina , Vírus da Encefalite Equina Venezuelana/genética , Vírus da Encefalite Equina Venezuelana/isolamento & purificação , Filogenia , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Especificidade da EspécieRESUMO
Introducción: la violencia por motivos de género es una cuestión social que cobra un enorme precio en materia de salud mental y física. Es posible que la mitad de todas las mujeres estén sujetas en algún momento de su vida actos de violencia por motivos de género. Cada año, dos millones de niñas y mujeres corren riesgo de mutilación genital. La violencia puede ser evidente, como en el caso de los castigos físicos o las agresiones sexuales, o encubierta, como en el abandono o en maltrato emocional. Objetivo: Contribuir a la concientización del cuerpo profesional, a fin de hacerlo perceptivo a las necesidades de las víctimas de violaciones, pudiendo así lograr el desarrollo de un programa asistencial integral de las mismas. Material y método: Se realizó una revisión de los conceptos de definición y diagnósticos diferenciales de violación y abuso sexual. Se realizó el estudio comparativo entre distintos Códigos Penales (Españo, Argentino y su modificatoria del año 1999) de los principales artículos que reglamentan este tema. Se selecionaron las principales normativas vigentes que reglamentan los derechos humanos, la eliminación de las formas de discriminación de la mujer y los principios fundamentales de justicia para las víctimas de delitos. Resultados: Se conceptualizaron premisas profesionales, éticas y humanas que creemos fundamentales en el abordaje de esta problemática. Se plantea como necesidad una definición más abarcativa de violación de nuestro Código Penal, que permita instaurar una forma inequívoca la fellatio in ore como delito de violación. Se reseñan los principales indicadores específicos y de sospecha, así como los estudios infectológicos y la profilaxis a instaurar en caso de violación y abuso sexual. Conclusiones: No actuar para asegurar los derechos de la mujer es ponerse del lado del abuso y la violencia. Al ser indiferentes, resultaremos destructivos (AU)
Assuntos
Maus-Tratos Conjugais/legislação & jurisprudência , Maus-Tratos Conjugais/diagnóstico , Maus-Tratos Conjugais/terapia , Mulheres Maltratadas/legislação & jurisprudência , Síndrome da Criança Espancada , Estupro/diagnóstico , Abuso Sexual na Infância/diagnóstico , Abuso Sexual na Infância/legislação & jurisprudência , Abuso Sexual na Infância/terapia , Estupro/psicologia , Abuso Sexual na Infância/psicologiaRESUMO
Introducción: la violencia por motivos de género es una cuestión social que cobra un enorme precio en materia de salud mental y física. Es posible que la mitad de todas las mujeres estén sujetas en algún momento de su vida actos de violencia por motivos de género. Cada año, dos millones de niñas y mujeres corren riesgo de mutilación genital. La violencia puede ser evidente, como en el caso de los castigos físicos o las agresiones sexuales, o encubierta, como en el abandono o en maltrato emocional. Objetivo: Contribuir a la concientización del cuerpo profesional, a fin de hacerlo perceptivo a las necesidades de las víctimas de violaciones, pudiendo así lograr el desarrollo de un programa asistencial integral de las mismas. Material y método: Se realizó una revisión de los conceptos de definición y diagnósticos diferenciales de violación y abuso sexual. Se realizó el estudio comparativo entre distintos Códigos Penales (Españo, Argentino y su modificatoria del año 1999) de los principales artículos que reglamentan este tema. Se selecionaron las principales normativas vigentes que reglamentan los derechos humanos, la eliminación de las formas de discriminación de la mujer y los principios fundamentales de justicia para las víctimas de delitos. Resultados: Se conceptualizaron premisas profesionales, éticas y humanas que creemos fundamentales en el abordaje de esta problemática. Se plantea como necesidad una definición más abarcativa de violación de nuestro Código Penal, que permita instaurar una forma inequívoca la fellatio in ore como delito de violación. Se reseñan los principales indicadores específicos y de sospecha, así como los estudios infectológicos y la profilaxis a instaurar en caso de violación y abuso sexual. Conclusiones: No actuar para asegurar los derechos de la mujer es ponerse del lado del abuso y la violencia. Al ser indiferentes, resultaremos destructivos
Assuntos
Síndrome da Criança Espancada , Mulheres Maltratadas , Abuso Sexual na Infância , Maus-Tratos Conjugais , Estupro/diagnóstico , Abuso Sexual na Infância , Estupro/psicologiaRESUMO
Severe forms of dengue fever, dengue haemorrhagic fever, and dengue shock syndrome, were not prominent in the Americas until the epidemic of Cuba in 1981. Since that time, they have spread to other countries in Central and South America, correlating with the spread of dengue type 2 viruses related to Southeast Asian strains. We report here the complete genomic sequence of a dengue type 2 virus isolated during the epidemic in La Martinique in 1998. This constitutes the first complete genetic characterization of a dengue virus strain from French West Indies, and also the first molecular identification in this region of a dengue 2 strain phylogenetically related to the emerging American type 2 dengue viruses.
Assuntos
Vírus da Dengue/genética , Dengue/virologia , Genoma Viral , Substituição de Aminoácidos/genética , Doenças Transmissíveis Emergentes/epidemiologia , Doenças Transmissíveis Emergentes/virologia , Dengue/epidemiologia , Vírus da Dengue/química , Vírus da Dengue/classificação , Humanos , Filogenia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sequência , Sorotipagem , Índias Ocidentais/epidemiologiaRESUMO
Yellow fever was presumably imported to the Americas from West-Africa from the 16th to the 19th century. American and African genotypes of the virus are distinguishable, indicating separate evolution in different vector/host cycles. The complete nucleotide sequence of the yellow fever virus strain TRINID79A, isolated in Trinidad in 1979, has been established. It exhibits extensive homology with those of current West-African strains and attenuated strain FNV. However, a unique deletion of the 3' non-coding region (NCR) of the viral RNA has been identified. It indicates that RYF1 and RYF2 repeated sequences of the 3' NCR are not necessary to the replication of the virus.