RESUMEN
Gestational diabetes mellitus (GDM) is recognized as a "window of opportunity" for the future prediction of such complications as type 2 diabetes mellitus and pelvic floor muscle disorders, including urinary incontinence and genitourinary dysfunction. Translational studies have reported that pelvic floor muscle disorders are due to a GDM-induced-myopathy (GDiM) of the pelvic floor muscle and rectus abdominis muscle (RAM). We now describe the transcriptome profiling of the RAM obtained by Cesarean section from GDM and non-GDM women with and without pregnancy-specific urinary incontinence (PSUI). We identified 650 genes in total, and the differentially expressed genes were defined by comparing three control groups to the GDM with PSUI group (GDiM). Enrichment analysis showed that GDM with PSUI was associated with decreased gene expression related to muscle structure and muscle protein synthesis, the reduced ability of muscle fibers to ameliorate muscle damage, and the altered the maintenance and generation of energy through glycogenesis. Potential genetic muscle biomarkers were validated by RT-PCR, and their relationship to the pathophysiology of the disease was verified. These findings help elucidate the molecular mechanisms of GDiM and will promote the development of innovative interventions to prevent and treat complications such as post-GDM urinary incontinence.
Asunto(s)
Diabetes Mellitus Tipo 2 , Diabetes Gestacional , Enfermedades Musculares , Incontinencia Urinaria , Embarazo , Humanos , Femenino , Diabetes Gestacional/metabolismo , Recto del Abdomen/metabolismo , Cesárea/efectos adversos , Diabetes Mellitus Tipo 2/complicaciones , Transcriptoma , Incontinencia Urinaria/genética , Biomarcadores , Perfilación de la Expresión GénicaRESUMEN
hRSV is the major causative agent of acute respiratory infections. Among its eleven proteins, M2-1 is a transcription antiterminator, making it an interesting target for antivirals. Quercetin is a flavonol which inhibits some virus infectivity and replication. In the present work, the M2-1 gene was cloned, expressed and the protein was purified. Thermal stability and secondary structure were analyzed by circular dichroism and the interaction with Quercetin was evaluated by fluorescence spectroscopy. Molecular docking experiments were performed to understand this mechanism of interaction. The purified protein is mainly composed of α-helix, with a melting temperature of 328.6K (≈55°C). M2-1 titration with Quercetin showed it interacts with two sites, one with a strong constant association K1 (site 1≈1.5×106M-1) by electrostatic interactions, and another with a weak constant association K2 (site 2≈1.1×105M-1) by a hydrophobic interaction. Ligand's docking shows it interacts with the N-terminus face in a more polar pocket and, between the domains of oligomerization and RNA and P protein interaction, in a more hydrophobic pocket, as predicted by experimental data. Therefore, we postulated this ligand could be interacting with important domains of the protein, avoiding viral replication and budding.
Asunto(s)
Fenómenos Biofísicos , Simulación del Acoplamiento Molecular , Quercetina/metabolismo , Virus Sincitial Respiratorio Humano , Proteínas Virales/metabolismo , Secuencia de Aminoácidos , Biología Computacional , Unión Proteica , Conformación Proteica , Proteínas Virales/químicaRESUMEN
Viruses are the major cause of lower respiratory tract infections in childhood and the main viruses involved are Human Respiratory Syncytial Virus (HRSV), Human Metapneumovirus (HMPV), Influenzavirus A and B (FLUA and FLUB), Human Parainfluenza Virus 1, 2 and 3 (HPIV1, 2 and 3) and Human Rhinovirus (HRV). The purposes of this study were to detect respiratory viruses in hospitalized children younger than six years and identify the influence of temperature and relative air humidity on the detected viruses. Samples of nasopharyngeal washes were collected from hospitalized children between May/2004 and September/2005. Methods of viral detection were RT-PCR, PCR and HRV amplicons were confirmed by hybridization. Results showed 54% (148/272) of viral positivity. HRSV was detected in 29% (79/272) of the samples; HRV in 23.1% (63/272); HPIV3 in 5.1% (14/272); HMPV in 3.3% (9/272); HPIV1 in 2.9% (8/272); FLUB in 1.4% (4/272), FLUA in 1.1% (3/272), and HPIV2 in 0.3% (1/272). The highest detection rates occurred mainly in the spring 2004 and in the autumn 2005. It was observed that viral respiratory infections tend to increase as the relative air humidity decreases, showing significant association with monthly averages of minimal temperature and minimal relative air humidity. In conclusion, viral respiratory infections vary according to temperature and relative air humidity and viral respiratory infections present major incidences it coldest and driest periods.
Asunto(s)
Humanos , Niño , Microbiología del Aire , Hibridación Genética , Técnicas In Vitro , Infecciones por Paramyxoviridae , Infecciones por Virus Sincitial Respiratorio , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Virosis , Virus Sincitial Respiratorio Humano/aislamiento & purificación , Aire , Humedad , Pacientes Internos , Métodos , TemperaturaRESUMEN
As infecções respiratórias agudas são importante causa de morbimortalidade em pediatria em todo o mundo, particularmente nos países em desenvolvimento. As infecções respiratórias são responsáveis por mais de 25 de todo o atendimento médico pediátrico ambulatorial e hospitalar e, em torno de 90 dessas infecções são relacionadas com agentes virais. O vírus sincicial respiratório (VSR)possui distribuição mundial e constitui a causa mais comum de pneumonia viral em crianças com menos de 5 anos de idade. A bronquiolite ou a pneumonia grave têm probabilidade elevada de ocorrência em lactantes com cerca de 6 semanas de idade, com incidência máxima aos 2 meses. A infecção pelo VSR em lactantes e crianças de mais idade resulta em infecção das vias respiratórias menos agressiva do que aquela observada em lactentes com menos de 6 meses de idade. No hemisfério setentrional, os surtos de infecção pelo VSR tendem a terseu pico no inverno. Nas regiões tropicais, as epidemias pelo VSR iniciamîse no outono e vão até a primavera. A reinfecção é freqüente, porém os sintomas resultantes são mais leves, envolvendo as vias aéreas superiores. Nesta revisão são abordados aspectos importantes das infecções respiratórias por VSR relativos às características do VSR, imunidade, transmissão, epidemiologia, clínica e patologia, prevenção, tratamento, e mortalidade