Prevalencia de Corynebacterium spp. y factores asociados en mujeres del Valle de Aburrá / Prevalence of corynebacterium spp. and associated factors in women of Valle de Aburrá

Introducción: Corynebacterium spp. está presente en flujo vaginal de mujeres asintomáticas, perose ha encontrado asociado a procesos patológicos, generando confusión al momento de clasificarlo como microbiota o microorganismos patógenos. Nuestro objetivo fue determinar la prevalencia de Corynebacterium spp. y explorar su asociación con características clínicas y hábitos sexuales. Material y métodos: estudio descriptivo transversal en 511 mujeres del Valle de Aburrá durante 2012 y 2013. Los datos demográficos, clínicos y de comportamiento sexual se obtuvieron mediante encuestas; la información sobre el perfil microbiológico genital se obtuvo de muestra de flujo vaginal. El análisis descriptivo se hizo con frecuencias y medidas de resumen; para el análisis bivariado se usó χ cuadrado, prueba exacta de Fisher, U de Mann Whitney y se usó regresión logística para el análisis multivariado; los análisis se realizaron en el programa estadístico IBM SPSS Statistics versión 22. Resultados: la prevalencia de Corynebacterium spp fue 59%. Referente al comportamiento sexual durante el último mes previo a la toma de muestra, encontramos que las participantes tuvieron sexo con una persona en promedio (rango de 0 - 3 personas distintas); respecto a las prácticas durante el coito en el mismo mes, se observó que 58% de las mujeres tuvo sexo sin preservativo, a 61% le practicaron sexo oral y a 10% sexo anal. Se encontró asociación de Corynebacterium sppcon reacción leucocitaria. Conclusiones: la prevalencia de Corynebacterium spp. fue 59% y se encontró asociado a reacción leucocitaria; no se asoció a comportamientos sexuales específicos ni sintomatología ginecológica. (Acta Med Colomb 2015; 40: 234-240).

Introduction: Corynebacterium spp. is present in vaginal fluid of asymptomatic women, but it has been found associated with disease processes, creating confusion when classified as normal or pathogenic flora. Our objective was to determine the prevalence of Corynebacterium spp. and explore its association with clinical characteristics and sexual habits. Materials and Methods: descriptive cross-sectional study in 511 women of Valle de Aburrá in 2012 and 2013. Demographic, clinical and sexual behavioral data were obtained through surveys; information about genital microbiological profile was obtained from sample of vaginal discharge. Descriptive analysis was done with frequencies and summary measures; for bivariate analysis χ square, Fisher exact test and Mann Whitney U test were used, and logistic regression was used for multivariate analysis; analysis were performed in the statistical program SPSS Statistics version 22. Results: The prevalence of Corynebacterium spp was 59%. Regarding sexual behavior during the last pre-sampling month, we found that participants had sex with a person on average (range from 0-3 different people); regarding practices during intercourse in the same month, it was observed that 58% of women had sex without a condom, to 61% oral sex was practiced and to 10% anal sex. Association of Corynebacterium spp with leukocyte reaction was found. Conclusions: The prevalence of Corynebacterium spp was 59% and was found associated with leukocyte reaction; it was not associated to specific sexual behaviors or gynecological symptoms. (Acta Med Colomb 2015; 40: 234-240).

Efectos adversos del tratamiento antirretroviral en niños infectados por el virus de la inmunodeficiencia humana / Adverse effects of antiretroviral treatment in children infected by the human immunodeficiency virus

Desde que se conoció la infección por el virus de la inmunodeficiencia humana (VIH), se han diagnosticado más de 2,5 millones de niños infectados a nivel mundial. Con este conocimiento vino también la generación del tratamiento HAART (Highly Active Antiretroviral Therapy), que logró mejorar la calidad de vida y la expectativa de vida de los lactantes infectados. Sin embargo, los individuos que reciben tratamiento presentan condiciones particulares que los hacen constituir un grupo de individuos con necesidades de atención y cuidado diferentes. En esta revisión se abordan los aspectos clínicos más relevantes que aquejan a los niños infectados por VIH que reciben tratamiento antirretroviral altamente activo.

Since the human immunodeficiency virus (HIV) was known, more than 2.5 million infected children around the world have been diagnosed. With this knowledge also came the advent of the Highly Active Antiretroviral Therapy (HAART) which has achieved a better quality of life and greater life expectancy of unweaned infected babies. However, people receiving this therapy present particular conditions that make them a population with different attention and care needs. This review addresses the most relevant clinical aspects present in HIV infected children receiving HAART.

Chloroquine modulates HIV-1-induced plasmacytoid dendritic cell alpha interferon: implication for T-cell activation.

Plasmacytoid dendritic cells (pDC) contribute to antiviral immunity mainly through recognition of microbial products and viruses via intracellular Toll-like receptor 7 (TLR7) or TLR9, resulting in the production of type I interferons (IFNs). Although interferons reduce the viral burden in the acute phase of infection, their role in the chronic phase is unclear. The presence of elevated plasma IFN-alpha levels in advanced HIV disease and its association with microbial translocation in chronic HIV infection lead us to hypothesize that IFN-alpha could contribute to immune activation. Blocking of IFN-alpha production using chloroquine, an endosomal inhibitor, was tested in a novel in vitro model system with the aim of characterizing the effects of chloroquine on HIV-1-mediated TLR signaling, IFN-alpha production, and T-cell activation. Our results indicate that chloroquine blocks TLR-mediated activation of pDC and MyD88 signaling, as shown by decreases in the levels of the downstream signaling molecules IRAK-4 and IRF-7 and by inhibition of IFN-alpha synthesis. Chloroquine decreased CD8 T-cell activation induced by aldrithiol-2-treated HIV-1 in peripheral blood mononuclear cell cultures. In addition to blocking pDC activation, chloroquine also blocked negative modulators of the T-cell response, such as indoleamine 2,3-dioxygenase (IDO) and programmed death ligand 1 (PDL-1). Our results indicate that TLR stimulation and production of IFN-alpha by pDC contribute to immune activation and that blocking of these pathways using chloroquine may interfere with events contributing to HIV pathogenesis. Our results suggests that a safe, well-tolerated drug such as chloroquine can be proposed as an adjuvant therapeutic candidate along with highly active antiretroviral therapy to control immune activation in HIV-1 infection.

Papel de las prtteínas reguladoras y accesorias del vih-1 en la patogénesis de esa infección / Role of the regulatory and accesory proteins of HIV- 1 in its pathogenisis

Desde el descubrimiento del virus de inmunodeficiencia humana tipo 1 (VIH-1) como agente etiológico del síndrome de inmunodeficiencia adquirida (SIDA) se han descrito los procesos más importantes que hacen parte del ciclo replicativo del virus y que a su vez participan de la fisiopatología tan compleja que caracteriza a esta infección. A pesar de los avances realizados en el desarrollo de medicamentos antirretrovirales y de los logros alcanzados en el control de la replicación viral, hechos que se reflejan en un aumento en la expectativa y calidad de vida de los individuos infectados, la terapia actual no permite una reconstitución inmunológica total y está acompañada de efectos tóxicos secundarios y de la aparición de resistencia viral. Esto ha obligado a mantener la búsqueda constante de nuevos blancos terapéuticos que ofrezcan alternativas en la lucha contra esta pandemia. Hasta hace pocos años se creía que las proteínas accesorias y reguladoras del VIH1 no ejercían un papel significativo en el ciclo replicativo del virus y en la patogénesis de la infección; sin embargo, estudios recientes indican que estas proteínas ejercen funciones esenciales en diferentes etapas del proceso replicativo y por ende son responsables de muchos efectos asociados a la patogénesis viral. Por estos hallazgos, las proteínas accesorias y reguladoras del VIH-1 constituyen un blanco promisorio en el desarrollo de nuevos medicamentos que complementen los antirretrovirales disponibles en la actualidad. En esta revisión se describe la función de las proteínas reguladoras y accesorias del VIH-1 en el ciclo replicativo viral y su participación en el proceso patogénico de esta infección.

Since the discovery of HIV-1 as the etiological agent of the acquired immunodeficiency syndrome (AIDS), the main processes involved in its replication cycle and responsible for the complex physiopathology of this infection have been described. Despite the advances in the development of new antiretrovirals and their impact in the quality and life expectancy of infected individuals, the current therapy does not allow a complete immune reconstitution and is also associated with deleterious side effects and the appearance of viral resistance. Therefore the search for new therapeutic targets is required to face this pandemic. The role of the accessory and regulatory proteins of the HIV- 1 in the replication cycle and in the pathogenesis of the infection has been ignored for several years now; however, recent studies indicated that these proteins play essential roles in the replication cycle, being responsible for several processes associated to viral pathogenesis. These findings have underlined the importance of these proteins as promissory targets in the development of new therapeutic agents. In this review, we detailed the role of each one of the HIV-1’s regulatory and accessory proteins in the replicative cycle and in the pathogenesis of this infection.

Fetal-maternal HLA-A and -B discordance is associated with placental RNase expression and anti-HIV-1 activity.

The incidence of maternal-to-fetal human immunodeficiency virus type 1 (HIV-1) transmission is 25-30% in absence of antiretroviral therapy, and is inversely associated with Human leukocyte antigens (HLA) class-I discordance. Based on our earlier report that mixed lymphocyte reactions (MLR) induce a ribonuclease (RNase) that inhibits HIV-1 replication, we proposed that maternal-fetal alloantigen stimulation activates factors that protect the fetus against vertically-transmitted infections. We investigate here whether the degree of mother-infant HLA discordance associates with the ability to produce anti-HIV-1 alloantigen-stimulated factor (ASF), and affects placental RNases. We also determine whether such HLA association is influenced by the mother's HIV-1 status. Paired maternal and cord blood leukocytes were tested for the induction of ASF by MLR, and typed for HLA-A and -B. The placentas were tested for mRNA expression of three RNases. Neonate anti-mother, but not mother anti-neonate MLR generated supernatants with anti-HIV-1 activity, that was associated with HLA class I discordance. This HLA association was not seen in the HIV-infected cohort. HLA class I discordance was also associated with expression of placental RNase 1. Our findings are consistent with the hypothesis that HLA class I discordance induces expression of RNases in the placenta that contribute to innate host resistance to HIV-1 and other viral infections.

Characterization of quantitative and functional innate immune parameters in HIV-1-infected Colombian children receiving stable highly active antiretroviral therapy.

BACKGROUND: The immunological benefits of highly active antiretroviral therapy (HAART) in HIV-1-infected children include reconstitution of CD4+ T-cell count and functional activity. The effect of HAART on innate immune cells has not been well established. AIM: To characterize innate immune responses in HAART-treated HIV-1-infected children. PATIENTS AND METHODS: 23 HIV-1-infected children on stable HAART and 23 uninfected children were evaluated. The frequency of innate immune cells in peripheral blood was determined by flow cytometry and functional activity was evaluated using Toll-like receptor agonists. RESULTS: Compared with uninfected children, HAART-treated HIV-1-infected children exhibited a significant decrease in the frequency of plasmacytoid dendritic cells and natural killer and T-cell receptor (TCR)-invariant CD1d-restricted T cells. This deficiency of innate immune cells was observed mainly in children with detectable viral load. We also compared the magnitude of the quantitative restoration of those cells comparing HIV-1-infected children with HIV-1-infected adults and found a partial effect of HAART on immune restoration that was independent of age. In both pediatric and adult subjects Toll-like receptor agonists induced expression of costimulatory molecules and production of proinflammatory cytokines by dendritic cells. Peripheral blood mononuclear cells of HIV-1-infected children produced significantly reduced amounts of interferon-alpha compared with uninfected children. CONCLUSIONS: HAART administration to HIV-1-infected children does not lead to a complete increase of circulating innate immune cells, particularly in patients with incomplete suppression of HIV.

Ribunucleasas: su potencial terapeutico en infecciones virales / Ribonucleases: Theurapetical potential on Viral Infections

En la actualidad existe un gran interés por identificar proteínas o péptidos antimicrobianos que puedan ser herramientas terapéuticas que eviten el establecimiento o permitan el control de diferentes infecciones. Las ribonucleasas (RNasas), pertenecientes a la superfamilia Ribonucleasa A, son enzimas que participan en varios procesos fisiológicos, que van desde el procesamiento alternativo del RNA hasta la angiogénesis. Estas enzimas son expresadas por diferentes tejidos y exhiben especificidades variables contra diferentes sustratos de RNA. El potencial terapéutico de las RNasas se ha sugerido en procesos oncogénicos; adicionalmente, se ha descrito que tienen actividad antiviral directa y el potencial de activar células del sistema inmune innato induciendo su maduración y la producción de citoquinas proinflamatorias. Nuestro grupo de investigación ha realizado estudios que señalan la capacidad de cuatro RNasas recombinantes: EDN, 4EDN, RNasa A y angiogenina de inhibir la replicación del virus de la inmunodeficiencia humana tipo 1 en linfocitos T de sangre periférica activados. En este artículo se revisará la clasificación de las ribonucleasas que constituyen la superfamilia RNasa A y se describirá, en forma detallada, lo que se conoce de la función biológica, acción antiviral y mecanismo de acción de las RNasas a las que se les ha reportado actividad antiviral.