RESUMO
Venezuelan equine encephalitis (VEE) is a viral disease transmitted by mosquitoes. The inflammation induced by the VEE virus is associated with a high mortality rate in mice. Angiotensin II (Ang II), a pro-inflammatory molecule, is produced in the normal rat brain. There is no information about the role of this molecule in the inflammatory events occurring during VEE and the effect of inflammation on the mortality rate in VEE-virus-infected rats. This study was designed to determine the role of Ang II in VEE and to analyze the effect of inflammation on mortality in infected rats. Two groups of rats were studied: 1) Virus-infected animals and controls (n = 60) were treated with losartan (a blocker of the Ang II-AT1 receptor) or with pyrrolidine dithiocarbamate (PDTC, an inhibitor of NF-κB) or left untreated and analyzed for morbidity and mortality. 2) Animals treated using the same protocol (n = 30) were sacrificed at day 4 postinfection and analyzed by immunohistochemistry and histopathology and for cytokine production. Increased expression of Ang II, ICAM-1, ED-1 and cytokines (IL-1α, MCP-1, IL-6 and IL-10) in infected animals was observed. The main histopathology findings were dilated capillaries and capillaries with endothelial detachment. Losartan and PDTC reduced the expression of IL-1α, MCP-1, and IL-10, and the number of dilated capillaries and capillaries with endothelial detachment. Survival analysis showed that 100% mortality was reached earlier in infected rats treated with losartan (day 14) or PDTC (day 11) than in untreated animals (day 19). These findings suggest that Ang II plays a role in VEE and that brain inflammation is protective against viral infection.
Assuntos
Angiotensina II/metabolismo , Vírus da Encefalite Equina Venezuelana/fisiologia , Encefalomielite Equina Venezuelana/metabolismo , Encefalomielite Equina Venezuelana/virologia , Angiotensina II/genética , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Vírus da Encefalite Equina Venezuelana/genética , Encefalomielite Equina Venezuelana/genética , Encefalomielite Equina Venezuelana/mortalidade , Humanos , Molécula 1 de Adesão Intercelular/genética , Molécula 1 de Adesão Intercelular/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Masculino , Camundongos , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND: Respiratory viral infections can induce different cytokine/chemokine profiles in lung tissues and have a significant influence on patients with asthma. There is little information about the systemic cytokine status in viral respiratory-infected asthmatic patients compared with non-asthmatic patients. OBJECTIVES: The aim of this study was to determine changes in circulating cytokines (IL-1ß, TNF-α, IL-4, IL-5) and chemokines (MCP1: monocyte chemoattractant protein-1 and RANTES: regulated on activation normal T cell expressed and secreted) in patients with an asthmatic versus a non-asthmatic background with respiratory syncytial virus, parainfluenza virus or adenovirus respiratory infection. In addition, human monocyte cultures were incubated with respiratory viruses to determine the cytokine/chemokine profiles. PATIENTS/METHODS: Patients with asthmatic (n = 34) and non-asthmatic (n = 18) history and respiratory infections with respiratory syncytial virus, parainfluenza, and adenovirus were studied. Healthy individuals with similar age and sex (n = 10) were used as controls. Cytokine/chemokine content in blood and culture supernatants was determined by ELISA. Monocytes were isolated by Hystopaque gradient and cocultured with each of the above-mentioned viruses. RESULTS: Similar increased cytokine concentrations were observed in asthmatic and non-asthmatic patients. However, higher concentrations of chemokines were observed in asthmatic patients. Virus-infected monocyte cultures showed similar cytokine/chemokine profiles to those observed in the patients. CONCLUSIONS: Circulating cytokine profiles induced by acute viral lung infection were not related to asthmatic status, except for chemokines that were already increased in the asthmatic status. Monocytes could play an important role in the increased circulating concentration of cytokines found during respiratory viral infections.
Assuntos
Infecções por Adenoviridae/imunologia , Citocinas/sangue , Infecções por Paramyxoviridae/imunologia , Infecções por Vírus Respiratório Sincicial/imunologia , Infecções Respiratórias/imunologia , Adenoviridae/imunologia , Infecções por Adenoviridae/patologia , Adolescente , Adulto , Idoso , Asma/complicações , Células Cultivadas , Criança , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Monócitos/imunologia , Infecções por Paramyxoviridae/patologia , Infecções por Vírus Respiratório Sincicial/patologia , Vírus Sinciciais Respiratórios/imunologia , Infecções Respiratórias/patologia , Respirovirus/imunologia , Soro/química , Adulto JovemRESUMO
The aim of this study was to determine the prevalence of cytomegalovirus (CMV) in pediatric patients with neurological disorders from Zulia State, Venezuela, during the period 2007-2008. Samples of cerebrospinal fluid (CSF) and serum were obtained from 186 patients with neurological symptoms and bacteriological negative CSF. The albumin CSF/serum content was determined to rule out contamination of CSF and optimal pairs were determined by ELISA of IgM and IgG anti-CMV antibodies in serum and IgG in CSF. Only 40.86% (76/186) of patients were optimal for this study. Serum samples positive for IgM antibodies (2/76; 2.6%) and IgG antibodies (71/76; 93.4%) were obtained. CSF IgG antibodies were observed in 24/76 patients (31.6%). Increased values of glucose in CSF (p < 0.05) were observed in 58.3% of CMV patients with meningoencephalitis. In addition, increased CSF protein concentration (p < 0.01) was observed in CSF anti-CMV antibodies positive patients with meningitis. This study shows high prevalence of acute CMV infection in pediatric patients with neurological affections suggesting an important role of this virus in this pathology during the studied period.
Assuntos
Viroses do Sistema Nervoso Central/epidemiologia , Viroses do Sistema Nervoso Central/virologia , Infecções por Citomegalovirus/epidemiologia , Encefalite Viral/epidemiologia , Meningite Viral/epidemiologia , Meningoencefalite/epidemiologia , Meningoencefalite/virologia , Adolescente , Criança , Pré-Escolar , Humanos , Lactente , Prevalência , Venezuela/epidemiologiaRESUMO
El objetivo de este estudio fue determinar la prevalencia de citomegalovirus en pacientes pediátricos con afecciones neurológicas, provenientes del Estado Zulia, Venezuela durante el período 2007-2008. Se recolectaron 186 muestras pareadas de líquido cefalorraquídeo (LCR) y suero, de pacientes entre 1 mes y 14 años de edad, que presentaron sintomatología clínica sugestiva de afectación del SNC y cuyo estudio bacteriológico convencional de LCR resultó negativo. Se determinó la relación albúmina LCR/suero a fin de descartar contaminación y a los pares óptimos se les determinó por la técnica de ELISA anticuerpos IgM e IgG en suero e IgG en LCR anti-CMV. Del total de muestras recolectadas 40,86% (76/186) resultaron óptimas para el análisis. De los 76 casos analizados, el 2,6% (2/76) de las muestras de suero resultaron positivas para IgM; 93,4% (71/76) fueron seropositivas a IgG mientras que el 31,6% (24/76) de las muestras de LCR presentaron anticuerpos IgG. En cuanto a los parámetros citoquímicos del LCR, se observaron valores de glucosa aumentados en el 58,3% (p<0,05) de los pacientes con CMV que presentaron meningoencefalitis. En los pacientes con meningitis que presentaron positividad de anticuerpos IgG anti-CMV en el LCR se observó un aumento significativo (p<0,01) en las proteínas del LCR. Se evidencia que una proporción de los pacientes pediátricos con afecciones neurológicas presentaron infección aguda por CMV, lo que demuestra una participación importante de este agente en pacientes del estado Zulia, Venezuela para el período en estudio.
The aim of this study was to determine the prevalence of cytomegalovirus (CMV) in pediatric patients with neurological disorders from Zulia State, Venezuela, during the period 2007-2008. Samples of cerebrospinal fluid (CSF) and serum were obtained from 186 patients with neurological symptoms and bacteriological negative CSF. The albumin CSF/serum content was determined to rule out contamination of CSF and optimal pairs were determined by ELISA of IgM and IgG anti-CMV antibodies in serum and IgG in CSF. Only 40.86% (76/186) of patients were optimal for this study. Serum samples positive for IgM antibodies (2/76; 2.6%) and IgG antibodies (71/76; 93.4%) were obtained. CSF IgG antibodies were observed in 24/76 patients (31.6%). Increased values of glucose in CSF (p<0.05) were observed in 58.3% of CMV patients with meningoencephalitis. In addition, increased CSF protein concentration (p<0.01) was observed in CSF anti-CMV antibodies positive patients with meningitis. This study shows high prevalence of acute CMV infection in pediatric patients with neurological affections suggesting an important role of this virus in this pathology during the studied period.
Assuntos
Adolescente , Criança , Pré-Escolar , Humanos , Lactente , Viroses do Sistema Nervoso Central/epidemiologia , Viroses do Sistema Nervoso Central/virologia , Infecções por Citomegalovirus/epidemiologia , Encefalite Viral/epidemiologia , Meningite Viral/epidemiologia , Meningoencefalite/epidemiologia , Meningoencefalite/virologia , Prevalência , Venezuela/epidemiologiaRESUMO
BACKGROUND: Respiratory syncytial virus (RSV) infection is associated to episodic exacerbations of asthma involving alveolar macrophages and chemokine production. OBJECTIVE: The aim of this study was to determine the circulating levels of monocyte chemotactic protein 1 (MCP-1), regulated on activation normal T cell expressed and secreted (RANTES), and substance P (SP) in patients with and without asthma with acute respiratory RSV infection and the chemokine profile in RSV- infected monocyte cultures from normal individuals and individuals with asthma. METHODS: In this regard, 31 adult patients with acute respiratory infection (15 patients with asthma) were studied. MCP-1, RANTES and SP were measured in serum and in supernatants from monocyte cultures by enzyme-linked immunosorbent assay (ELISA). RESULTS: Increased levels of MCP-1 and RANTES were observed in serum from patients with asthma related to RSV infection. RSV-infected monocyte cultures from healthy individuals showed increased content of those chemokines, and monocyte cultures from patients with asthma showed increased expression of MCP-1. CONCLUSION: These data show that RSV infection induces increased circulating level of chemokines in patients with asthma, and this finding could be mediated in part by the interaction virus-monocyte.
Assuntos
Asma/imunologia , Quimiocina CCL2/sangue , Monócitos/metabolismo , Infecções por Vírus Respiratório Sincicial/imunologia , Vírus Sincicial Respiratório Humano/imunologia , Linfócitos T/imunologia , Adulto , Idoso , Asma/metabolismo , Asma/fisiopatologia , Células Cultivadas , Quimiocina CCL5/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Infecções por Vírus Respiratório Sincicial/metabolismo , Infecções por Vírus Respiratório Sincicial/virologia , Substância P/sangue , Regulação para CimaRESUMO
Efficient synthesis of new structurally different 2-(het)aryl-4-amidyl-substituted tetrahydroquinolines 8-29 is reported. The synthesis based on BiCl(3)-catalyzed three-component Povarov reaction between anilines, (het)aryl aldehydes and enamides offers a fast, safe, and cheap way for efficient tetrahydroquinoline libraries construction. Using N-vinylamides (N-vinylpyrrolidin-2-one and N-vinylacetamide) in this reaction, it was possible to obtain two series of different cis tetrahydroquinolines with antioxidant properties. Among 14 tested compounds, 7 tetrahydroquinolines revealed a prominent anti-radical capacity, equal or higher than that of the commercial antioxidants. Being the most active molecule, the N-[2-(α-furanyl)-6-methoxy-1,2,3,4-tetrahydroquinolin-4-yl] acetamide 21 was ca. 2.2-fold more potent than the well-known antioxidant, vitamin E (α-tocopherol).
Assuntos
Amidas/química , Bismuto/química , Técnicas de Química Sintética/métodos , Cloretos/química , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/síntese química , Quinolinas/química , Quinolinas/síntese química , CatáliseRESUMO
Preparación simple de nuevas N-(6-metil-2-nitrofenil-1,2,3,4-tetrahidroquinolin-4-il) pirrolidin-2-onas y su análisis espectroscópico. Objetivos. Preparar nuevas moléculas N-(1,2,3,4-tetrahidroquinolin-4-il) 2-oxopirrolidínicas y caracterizarlas por métodos espectroscópicos. Materiales y métodos. Todos los reactivos usados son de Aldrich, grado comercial. La pureza de los productos y la composición de las mezclas de reacción fueron monitoreadas por cromatografía en capa fina sobre cromatoplacas de Silufol UV254 (0.25 mm). El aislamiento y purificación se realizó usando cromatografía en columna (SiO2), usando acetato de etilo. Resultados. La preparación de las nuevas N-(tetrahidroquinolin-4-il) pirrolidin-2-onas 4-nitrofenil (ó 2-nitrofenil) sustituidas en C-2 del anillo tetrahidroquinolínico, se realizóvía síntesis one-pot basada en la reacción de cicloadición imino Diels-Alder catalizada por BiCl3 entre toluidina, N-vinilpirrolidin-2-ona y 4-nitrobenzaldehído (3-nitrobenzaldehído). La estructura de los derivados pirrolidónicos fue confirmada por 1H RMN y 13C RMN, además de experimentos 2D RMN y difracción de rayos X de monocristal. Conclusiones. Una ruta eficiente, económica y rápida (reacción imino Diels-Alder multi-componente) fue empleada para la construcción de nuevas moléculas N-(tetrahidroquinolin-4-il) 2-oxopirrolidínicas, esqueleto muy atractivo y usado con estereoquímica bien definida...
Objectives. To prepare new N-(1,2,3,4-tetrahydroquinolin-4-yl) pyrrolidin-2-one molecules and to characterize them by spectroscopic methods. Materials and methods. All reagents were purchased from Aldrich, commercial grade. The purity of the products and the composition of the reaction mixtures were monitored by thin layer chromatography over Silufol UV254 chromatoplates (0.25 mm). Product isolation and purification were performed by column chromatography (SiO2) using ethyl acetate. Results. Preparation of new N-(2-nitrophenyl-1,2,3,4-tetrahydroquinolin-4-yl) pyrrolidin-2-ones has been achieved via the one-pot synthesis, based on a BiCl3-catalyzedimino Diels-Alder cycloaddition reaction of toluidine, N-vinylpyrrolidin-2-one and 4-nitro- or 3-nitrobenzaldehydes. The structure of the pyrrolidine derivatives was confirmed by 1H nmr and 13C nmr studies, in addition to inverse-detected 2D NMR experiments and monocrystal X-ray diffraction. Conclusions. An efficient, economic, and fast synthetic route (multi-component imino Diels-Alder reaction) was employed in the construction of several new tetrahydroquinoline derivatives, useful and attractive rigid skeleton with well-defined stereochemistry...
Preparação simples de novas N-(6-metil-2-nitrofenil-1,2,3,4-tetrahydroquinoline-4-il) pirrolidin-2-onas e sua análise espectroscópica. Objetivos. Preparar novas moléculas N-(1,2,3,4-tetrahydroquinoline-4-il) 2-oxopirrolidínicas e sua caracterização por espectroscopia. Materiais e métodos. Todos os reagentes utilizados são de Aldrich, de grau comercial. A pureza dos produtos e a composição das misturas de reação foram monitoradas por cromatografia em camada fina sobre cromatoplacas de Silufol UV254 (0,25 mm). O isolamento e purificação foi realizado utilizando cromatografia em coluna (SiO2), utilizando acetato de etila. Resultados. Preparação de novas N-(tetrahydroquinoline-4-il) pirrolidin-2-onas 4-nitrofenil (ou 2-nitrofenil) substituídas em C-2 do anel tetrahydroquinoline foi realizada através da síntese one pot baseada na reação de cicloadição imino Diels-Alder catalisada por BiCl3 entre toluidina, N-vinilpirrolidin-2-ona e 4 nitrobenzaldehyde (3 nitrobenzaldehyde). A estrutura dos derivados pirrolidónicos foi confirmada por 1H RMN y 13C RMN, experimentos 2D RMN, assim como difração de raios X e monocristais. Conclusões. Uma rota eficiente, econômica e rápida (reação imino Diels-Alder multi-componente) foi utilizada para a construção de novas moléculas N-(tetrahydroquinoline-4-il) 2-oxopirrolidínicas esqueleto muito atraente e usado com estereoquímica bem definida...
Assuntos
Composição de Medicamentos/classificação , Composição de Medicamentos/métodos , Composição de MedicamentosRESUMO
Acute respiratory infections (ARI) are pathologies that affect the respiratory tract from the proximal pharynx to the lungs, with an evolution of less than 15 days. They constitute the most frequent cause of morbimortality in the world. With the purpose of identifying the viral agents associated to this type of infections in patients of Zulia State, Venezuela, between February 2005 and July 2006, a total of 102 samples of the respiratory tract (oropharyngeal swab, nasopharyngeal swab, nasopharyngeal washing, spit and bronchoalveolar lavage) were studied. Viral isolation was made through a cellular culture and the identification of the pathogenic agents by the technique of direct immunofluorescence. Forty six positive samples were obtained (45%). The greater incidence was found in the groups of 41 to 64 years old patients, followed by lactanting babies (1 to 23 months). There were no significant differences between sexes. Within the isolated viral pathogens, Respiratory Syncytial Virus (RSV) was the agent most frequently found (32.6% p < 0.05), followed by Adenovirus (28.2%), Parainfluenza (23.9%) and Influenza (15.2%). The respiratory infections of the low respiratory tract were the most frequent (67.4%). A high incidence of associated viral agents to ARI in Zulia State is demonstrated. A high incidence in adult patients and the greatest positivity was found for RSV.
Assuntos
Infecções Respiratórias/epidemiologia , Viroses/epidemiologia , Doença Aguda , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Estudos Transversais , Feminino , Hospitais Públicos/estatística & dados numéricos , Humanos , Incidência , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Infecções por Vírus Respiratório Sincicial/epidemiologia , Vírus Sinciciais Respiratórios/isolamento & purificação , Infecções Respiratórias/virologia , Venezuela/epidemiologia , Viroses/virologia , Vírus/isolamento & purificação , Adulto JovemRESUMO
Las infecciones respiratorias agudas (IRA) son patologías que afectan el tracto respiratorio desde la faringe proximal hasta los pulmones, con una evolución de menos de 15 días y constituyen la causa más frecuente de morbimortalidad en el mundo. Con la finalidad de identificar los agentes virales asociados a este tipo de infecciones en pacientes del estado Zulia, Venezuela, entre febrero 2005 y julio de 2006, se estudiaron un total de 102 muestras provenientes del tracto respiratorio (hisopado nasal, faríngeo y/o nasofaríngeo, esputo y lavado broncoalveolar) de pacientes con clínica de IRA. El aislamiento viral se realizó a través del cultivo celular y la identificación del agente patógeno por la técnica de inmunofluorescencia directa. Se obtuvieron 46 muestras positivas (45%), la incidencia estuvo homogéneamente distribuida en todos los grupos de estudio aun cuando se observó predominio en el grupo de 41 a 64 años, seguido de los lactantes. No hubo diferencias significativas en cuanto al sexo. Dentro de los patógenos virales aislados el Virus Sincicial Respiratorio (VSR) fue el agente con mayor frecuencia (32,6%) (p<0,05), seguido de Adenovirus (28,2%), Parainfluenza (23,9%) e Influenza (15,2%). Las infecciones respiratorias del tracto inferior fueron las más frecuentes (67,4%). Se demuestra una alta incidencia de agentes virales asociados a IRA en el estado Zulia. Se destaca la alta frecuencia en pacientes adultos y la mayor positividad para VSR.
Acute respiratory infections (ARI) are pathologies that affect the respiratory tract from the proximal pharynx to the lungs, with an evolution of less than 15 days. They constitute the most frequent cause of morbimortality in the world. With the purpose of identifying the viral agents associated to this type of infections in patients of Zulia State, Venezuela, between February 2005 and July 2006, a total of 102 samples of the respiratory tract (oropharyngeal swab, nasopharyngeal swab, nasopharyngeal washing, spit and bronchoalveolar lavage) were studied. Viral isolation was made through a cellular culture and the identification of the pathogenic agents by the technique of direct immunofluorescence. Forty six positive samples were obtained (45%). The greater incidence was found in the groups of 41 to 64 years old patients, followed by lactanting babies (1 to 23 months). There were no significant differences between sexes. Within the isolated viral pathogens, Respiratory Syncytial Virus (RSV) was the agent most frequently found (32.6% p<0.05), followed by Adenovirus (28.2%), Parainfluenza (23.9%) and Influenza (15.2%). The respiratory infections of the low respiratory tract were the most frequent (67.4%). A high incidence of associated viral agents to ARI in Zulia State is demonstrated. A high incidence in adult patients and the greatest positivity was found for RSV.
Assuntos
Humanos , Masculino , Adulto , Feminino , Pessoa de Meia-Idade , Doenças Respiratórias/patologia , Técnica Direta de Fluorescência para Anticorpo/métodos , Técnicas de Cultura de Células/métodos , Viroses/etiologiaRESUMO
Diversos esfuerzos han sido dirigidos a fin de esclarecer los principales mecanismos de protección y recuperación en las infecciones virales agudas y el posible papel de las citocinas involucradas en la respuesta inmunitaria primaria inducida por una cepa epizoótica del virus de Encefalitis Equina Venezolana (EEV). En el presente estudio se determinaron las concentraciones de citocinas TH1 Interleucina-2 (IL-2) e Interferon-gamma (IFN-g), TH2 Interleucina-4 (IL-4), proinflamatorias (IL-1b) y el Factor de Necrosis Tumoral -alfa (TNF-a) en suero y cerebro de ratones infectados con el virus de EEV a diferentes períodos de infección. Se utilizaron ratones NMRI albinos machos infectados con una suspensión (10 DL50) de la cepa Guajira del virus de EEV, y un grupo control (sin infectar). En los días 1, 3 y 5 post-infección, se extrajo sangre completa de ratones para la obtención de suero y el cerebro previa perfusión, para la obtención de homogeneizados cerebrales. En ambas muestras se determinaron IL-2, IFN-g, IL-4, IL-1b, y TNF-a por la técnica de ELISA. Se observó un incremento significativo (p < 0,01) en suero y homogeneizados cerebrales al 1er, 3er y 5to día post-infección en las concentraciones de IL-1b, IFN-g y TNF-a, al compararlos con el grupo control. La cuantificación de IL-2 e IL-4, no arrojaron diferencias estadísticamente significativas al ser comparados con los controles. Estos resultados sugieren que la IL-1b, IFN-g y TNF-a, podrían estar involucradas en la respuesta inmunitaria temprana al virus de EEV durante la infección primaria.