RESUMO
Objetivo: Correlacionar la incidencia de tuberculosis pulmonar, tuberculosis extrapulmonar y VIH con el índice de desarrollo humano por departamentos en Colombia entre los años 2005 y 2014. Métodos: Estudio ecológico en 29 departamentos de Colombia, con datos de las secretarias de salud, SIVIGILA y del Programa de las Naciones Unidas para el Desarrollo. Los análisis se realizaron con medidas de resumen, intervalos de confianza, Kruskal Wallis y correlación de Spearman en SPSS. Resultados: Se encuentra incremento en la incidencia de tuberculosis pulmonar y VIH en el lapso estudiado. Por otra parte, no se halló correlación entre el IDH con la tasa de tuberculosis pulmonar; sin embargo, con la tuberculosis extrapulmonar y el VIH se identificaron correlaciones positivas y significativas con Rho Spearman de 0,320 y 0,324 respectivamente. Conclusión: Este estudio puso de manifiesto una correlación positiva y significativa entre la infección por VIH, tuberculosis extrapulmonar e índice de desarrollo humano que indica que las regiones del país con mayor nivel de desarrollo presentan las mayores tasas de infección. Esta información es importante para que las autoridades sanitarias realicen acciones que ayuden a comprender las causas que explican este fenómeno.
Objective: To correlate the incidence of pulmonary tuberculosis, extrapulmonary tuberculosis and HIV with the human development index by departments in Colombia between 2005 and 2014. Methods: Ecological study in 29 departments of Colombia. The incidence data of pulmonary, extrapulmonary and HIV tuberculosis were obtained through the request to departmental health secretaries and data registered in SIVIGILA. The information on the human development index (HDI) was obtained from the United Nations Development Program. The description of the variables was made with measures of central tendency, position, dispersion and 95% confidence intervals. The variation of the disease rates over time was done with the H Kruskal Wallis test. The covariation between the rates of diseases and the HDI was evaluated with scatter plots and Spearman correlation coefficients. In all the analyzes p values lower than 0.05 were considered significant. Results: There is an increase in the incidence of pulmonary tuberculosis and HIV in the period studied. On the other hand, no correlation was found between the HDI with the rate of pulmonary tuberculosis; however, positive and significant correlations with Rho Spearman of 0.320 and 0.324 were found with extrapulmonary tuberculosis and HIV, respectively. Conclusion: this study showed a positive and significant correlation between HIV infection, extrapulmonary tuberculosis and human development index, which indicates that the regions of the country with the highest level of development have the highest infection rates. This information is important for the health authorities to carry out actions that help to understand the causes that explain this phenomenon.
Assuntos
Humanos , Masculino , Feminino , Gravidez , Adulto , Tuberculose , HIV , Indicadores de Desenvolvimento , Causas de Morte , Síndrome da Imunodeficiência Adquirida , Colômbia , Inibidores da Dissociação do Nucleotídeo Guanina rho-EspecíficoRESUMO
Protein disulfide isomerases (PDIs) support endoplasmic reticulum redox protein folding and cell-surface thiol-redox control of thrombosis and vascular remodeling. The family prototype PDIA1 regulates NADPH oxidase signaling and cytoskeleton organization, however the related underlying mechanisms are unclear. Here we show that genes encoding human PDIA1 and its two paralogs PDIA8 and PDIA2 are each flanked by genes encoding Rho guanine-dissociation inhibitors (GDI), known regulators of RhoGTPases/cytoskeleton. Evolutionary histories of these three microsyntenic regions reveal their emergence by two successive duplication events of a primordial gene pair in the last common vertebrate ancestor. The arrangement, however, is substantially older, detectable in echinoderms, nematodes, and cnidarians. Thus, PDI/RhoGDI pairing in the same transcription orientation emerged early in animal evolution and has been largely maintained. PDI/RhoGDI pairs are embedded into conserved genomic regions displaying common cis-regulatory elements. Analysis of gene expression datasets supports evidence for PDI/RhoGDI coexpression in developmental/inflammatory contexts. PDIA1/RhoGDIα were co-induced in endothelial cells upon CRISP-R-promoted transcription activation of each pair component, and also in mouse arterial intima during flow-induced remodeling. We provide evidence for physical interaction between both proteins. These data support strong functional links between PDI and RhoGDI families, which likely maintained PDI/RhoGDI microsynteny along > 800-million years of evolution.
Assuntos
Isomerases de Dissulfetos de Proteínas/genética , Isomerases de Dissulfetos de Proteínas/metabolismo , Sintenia , Inibidores da Dissociação do Nucleotídeo Guanina rho-Específico/genética , Inibidores da Dissociação do Nucleotídeo Guanina rho-Específico/metabolismo , Animais , Sequência de Bases , Sequência Conservada , Citoesqueleto/metabolismo , Evolução Molecular , Genômica , Humanos , Filogenia , Regiões Promotoras Genéticas/genética , Ligação ProteicaRESUMO
We aimed to compare the expression and function of molecular components of the RhoA/Rho-kinase signaling pathway in the contractile responses of detrusor, trigonal and urethral smooth muscle, using selective Rho-kinase inhibitors. Contractility studies and molecular approaches were employed to demonstrate the expression patterns and functional activity of the RhoA/Rho-kinase signaling pathway in the lower urinary tract. Frequency-response curves (1-32 Hz) and concentration-response curves (CRC) to carbachol (CCh, 0.01-30 microM), phenylephrine (PE, 0.01-300 microM) and endothelin-1 (ET-1, 0.01-100 nM) were significantly attenuated (p<0.01) following incubation with the Rho-kinase inhibitors H-1152 (0.1-1 microM), Y-27632 (1-10 microM) or HA-1077 (10 microM). Addition of Rho-kinase inhibitors also markedly reduced (p<0.01) the contractions evoked by either KCl (80 mM) or alpha,beta-methylene ATP (alpha,beta-mATP, 10 microM). Among the Rho-kinase inhibitors tested, H-1152 was approximately 9-16 times more potent than Y-27632 or HA-1077. In addition, basal tone of detrusor and trigonal strips was reduced following addition of Y-27632 (10 microM), H-1152 (1 microM) and HA-1077 (10 microM). The expression of RhoA, RhoGDI, leukemia-associated RhoGEF (LARG) and p115RhoGEF was similar among the detrusor, trigone and urethra, whereas Rho-kinase alpha, Rho-kinase beta and PDZ-RhoGEF protein levels were significantly lower in the urethra. Components of the RhoA/Rho-kinase signaling are expressed in detrusor, trigonal and urethral smooth muscle and dynamically regulate contraction and tone. Manipulation of RhoGEF expression may provide further understanding of mechanisms involving Ca(2+) sensitization in the lower urinary tract.