Antifungal Activity of Amphiphilic Perylene Bisimides

[EN] Perylene-based compounds, either naturally occurring or synthetic, have shown interesting biological activities. In this study, we report on the broad-spectrum antifungal properties of two lead amphiphilic perylene bisimides, compounds 4 and 5, which were synthesized from perylene-3,4,9,10-tetracarboxylic dianhydride by condensation with spermine and an ammonium salt formation. The antifungal activity was evaluated using a collection of fungal strains and clinical isolates from patients with onychomycosis or sporotrichosis. Both molecules displayed an interesting antifungal profile with MIC values in the range of 2-25 mu M, being as active as several reference drugs, even more potent in some particular strains. The ammonium trifluoroacetate salt 5 showed the highest activity with a MIC value of 2.1 mu M for all tested Candida spp., two Cryptococcus spp., two Fusarium spp., and one Neoscytalidium spp. strain. Therefore, these amphiphilic molecules with the perylene moiety and cationic ammonium side chains represent important structural features for the development of novel antifungals.This study was supported by grant 201680I008 (awarded to M.A.G.-C.) from the Spanish Government (Consejo Superior de Investigaciones Cientificas) and grant 3756 of the University of Antioquia.Roa-Linares, VC.; Mesa-Arango, AC.; Zaragoza, RJ.; González-Cardenete, MA. (2022). Antifungal Activity of Amphiphilic Perylene Bisimides. Molecules. 27(20):1-12. https://doi.org/10.3390/molecules27206890112272

Impact of Resistance to Fluconazole on Virulence and Morphological Aspects of Cryptococcus neoformans and Cryptococcus gattii Isolates

Cryptococcus spp. are responsible for around one million cases of meningitis every year. Fluconazole (FLU) is commonly used in the treatment of cryptococcosis, mainly in immunocompromised patients and the resistance is usually reported after long periods of treatment. In this study, the morphological characterization and virulence profile of FLU-susceptible and FLU-resistant clinical and environmental isolates of C. neoformans and C. gattii were performed both in vitro and in vivo using the Galleria mellonella model. FLU-susceptible isolates from C. neoformans were significantly more virulent than the FLU-resistant isolates. FLU-susceptible C. gattii isolates showed a different virulence profile from C. neoformans isolates where only the environmental isolate, CL, was more virulent compared with the resistant isolates. Cell morphology and capsule size were analyzed and the FLU-resistant isolates did not change significantly compared with the most sensitive isolates. Growth at 37°C was also evaluated and in both species, the resistant isolates showed a reduced growth at this temperature, indicating that FLU resistance can affect their growth. Based on the results obtained is possible suggest that FLU resistance can influence the morphology of the isolates and consequently changed the virulence profiles. The most evident results were observed for C. neoformans showing that the adaptation of isolates to antifungal selective pressure influenced the loss of virulence

Nueva metodología para probar el sistema nervioso autónomo en individuos hipertensos Sistema nervioso autónomo en hipertensos

RESUMEN Introducción y objetivo: Actualmente el Sistema Nervioso Autónomo está siendo apuntado como un factor importante en la génesis y desarrollo de la hipertensión arterial sistémica. Por esto, objetivamos estudiar el Sistema Nervioso Autónomo en esta patología, a través de una nueva metodología que utilice la frecuencia cardiacaMetodología: 45 sujetos fueron seleccionados (12 hipertensos y 33 sanos) para verificación de la presión arterial y frecuencia cardiaca a cada latido (2,5 min en reposo y 2,5 min después del ortostatismo). Falsos valores fueron retirados de las series temporales para posterior interpolación, debido a la falta de periodicidad de los latidos cardiacos. Posterior submuestro a 10Hz fue realizado y un filtro que respeta la frecuencia cardiaca fue aplicado. Análisis espectral en las series temporales fue realizado para posterior estimación de medianas y cuartiles. Finalmente, test de hipótesis con Wilcoxon rank sum test para verificar diferencias estadísticas entre grupos fue realizado.Resultados: Las medianas de las potencias porcentuales en las altas frecuencias, pre y post maniobra, de sanos fueron ligeramente inferiores pero no estadísticamente significativas al compararlas con los hipertensos (sanos: 42,69 y 32,39, hipertensos: 46,91 y 33,99). De otro lado, el mismo estimador en las bajas frecuencias fue levemente superior en sanos (sanos: 57,30 y 67,60 e hipertensos: 53,09 y 66). Adicionalmente, la diferencia en la respuesta autonómica de los hipertensos no fue significativa (p>0,01) mientras que en los sanos  esto si ocurrió.Conclusiones: El método ha demostrado potencial para identificar disfunción del autónomo en hipertensión. También se confirma una activación del simpático disminuida en sujetos hipertensos cuando se realiza una maniobra ortostática. Salud UIS 2010; 42:   Palabras clave: Barorreceptores, hipertensión arterial sistémica, sistema nervioso autónomo, electrofisiología ABSTRACT Introduction and objective: Currently the Autonomous Nervous System has been considered as an important factor in the genesis and the development of Arterial Systemic Hypertension. Because of that, aimed to study the Autonomous Nervous Sistem in this pathology through a new methodology which uses heart rate.Methodology: 45 subjects were selected (12 hypertensive and 31 healthy) to check the arterial pressure and heart rate beat by beat (2.5 min in rest and 2.5 min after the orthostatism) spurious values were retired from temporal series for interpolation because the lack of heart rate periodicity.  Then, sub sampling in 10Hz was realized and a filter that respect the heart rate was applied. Spectral analysis in the temporal series was realized by posterior median and quartile estimation. Finally, hypothesis test with Wilcoxon rank sum test to check statistical differences between groups was performed.Results: The medians of the percentage powers by the high frequencies, pre and post maneuver, in healthy individuals were a few inferior but not with statistical significance when are compared with hypertensive individuals (healthy:42.69 and 32.39; hypertensive:46.91 and 33.99). On the other hand, the same estimator by the low frequencies was a few superior in healthy individuals (healthy: 57.30 and 67.60; hypertensive: 53.09 and 66). Additionally, the difference in the autonomic response between hypertensive individuals was not significative (p>0.01) meanwhile in healthy individuals do.Conclusions: The methodology had demonstrated potential to identify autonomic disfunction in hypertensive. Also, it confirms a lower sympathetic activation in hypertensive individuals when the orthostatic maneuver is done. Salud UIS 2010; 42:   Keywords: Baroreceptors, arterial systemic hypertension, autonomic nervous system, electrophysiolog

Nueva metodología para probar el sistema nervioso autónomo en individuos hipertensos Sistema nervioso autónomo en hipertensos

RESUMEN Introducción y objetivo: Actualmente el Sistema Nervioso Autónomo está siendo apuntado como un factor importante en la génesis y desarrollo de la hipertensión arterial sistémica. Por esto, objetivamos estudiar el Sistema Nervioso Autónomo en esta patología, a través de una nueva metodología que utilice la frecuencia cardiacaMetodología: 45 sujetos fueron seleccionados (12 hipertensos y 33 sanos) para verificación de la presión arterial y frecuencia cardiaca a cada latido (2,5 min en reposo y 2,5 min después del ortostatismo). Falsos valores fueron retirados de las series temporales para posterior interpolación, debido a la falta de periodicidad de los latidos cardiacos. Posterior submuestro a 10Hz fue realizado y un filtro que respeta la frecuencia cardiaca fue aplicado. Análisis espectral en las series temporales fue realizado para posterior estimación de medianas y cuartiles. Finalmente, test de hipótesis con Wilcoxon rank sum test para verificar diferencias estadísticas entre grupos fue realizado.Resultados: Las medianas de las potencias porcentuales en las altas frecuencias, pre y post maniobra, de sanos fueron ligeramente inferiores pero no estadísticamente significativas al compararlas con los hipertensos (sanos: 42,69 y 32,39, hipertensos: 46,91 y 33,99). De otro lado, el mismo estimador en las bajas frecuencias fue levemente superior en sanos (sanos: 57,30 y 67,60 e hipertensos: 53,09 y 66). Adicionalmente, la diferencia en la respuesta autonómica de los hipertensos no fue significativa (p>0,01) mientras que en los sanos  esto si ocurrió.Conclusiones: El método ha demostrado potencial para identificar disfunción del autónomo en hipertensión. También se confirma una activación del simpático disminuida en sujetos hipertensos cuando se realiza una maniobra ortostática. Salud UIS 2010; 42:   Palabras clave: Barorreceptores, hipertensión arterial sistémica, sistema nervioso autónomo, electrofisiología ABSTRACT Introduction and objective: Currently the Autonomous Nervous System has been considered as an important factor in the genesis and the development of Arterial Systemic Hypertension. Because of that, aimed to study the Autonomous Nervous Sistem in this pathology through a new methodology which uses heart rate.Methodology: 45 subjects were selected (12 hypertensive and 31 healthy) to check the arterial pressure and heart rate beat by beat (2.5 min in rest and 2.5 min after the orthostatism) spurious values were retired from temporal series for interpolation because the lack of heart rate periodicity.  Then, sub sampling in 10Hz was realized and a filter that respect the heart rate was applied. Spectral analysis in the temporal series was realized by posterior median and quartile estimation. Finally, hypothesis test with Wilcoxon rank sum test to check statistical differences between groups was performed.Results: The medians of the percentage powers by the high frequencies, pre and post maneuver, in healthy individuals were a few inferior but not with statistical significance when are compared with hypertensive individuals (healthy:42.69 and 32.39; hypertensive:46.91 and 33.99). On the other hand, the same estimator by the low frequencies was a few superior in healthy individuals (healthy: 57.30 and 67.60; hypertensive: 53.09 and 66). Additionally, the difference in the autonomic response between hypertensive individuals was not significative (p>0.01) meanwhile in healthy individuals do.Conclusions: The methodology had demonstrated potential to identify autonomic disfunction in hypertensive. Also, it confirms a lower sympathetic activation in hypertensive individuals when the orthostatic maneuver is done. Salud UIS 2010; 42:   Keywords: Baroreceptors, arterial systemic hypertension, autonomic nervous system, electrophysiolog

Candida tropicalis antifungal cross-resistance is related to different azole target (Erg11p) modifications

ABSTARCT: Candida tropicalis ranks between third and fourth among Candida species most commonly isolated from clinical specimens. Invasive candidiasis and candidemia are treated with amphotericin B or echinocandins as first-line therapy, with extended-spectrum triazoles as acceptable alternatives. Candida tropicalis is usually susceptible to all antifungal agents, although several azole drug-resistant clinical isolates are being reported. However, C. tropicalis resistant to amphotericin B is uncommon, and only a few strains have reliably demonstrated a high level of resistance to this agent. The resistance mechanisms operating in C. tropicalis strains isolated from clinical samples showing resistance to azole drugs alone or with amphotericin B cross-resistance were elucidated. Antifungal drug resistance was related to mutations of the azole target (Erg11p) with or without alterations of the ergosterol biosynthesis pathway. The antifungal drug resistance shown in vitro correlated very well with the results obtained in vivo using the model host Galleria mellonella. Using this panel of strains, the G. mellonella model system was validated as a simple, nonmammalian minihost model that can be used to study in vitro-in vivo correlation of antifungals in C. tropicalis. The development in C. tropicalis of antifungal drug resistance with different mechanisms during antifungal treatment has potential clinical impact and deserves specific prospective studies

Primer trasplante de islotes realizado en Colombia, experiencia fundación Valle del Lili

Introducción De acuerdo con las estadísticas suministradas en el 2014 por la Federación Internacional de Diabetes, la prevalencia de pacientes con diabetes está en aumento a nivel mundial, actualmente alrededor de 382 millones de personas sufren de esta patología. En relación con la diabetes tipo 1 se estima que corresponde al 5% de todos los casos diagnosticados de diabetes en adultos. Para el caso de Colombia, la incidencia de diabetes tipo 1 es de 3-4 por 100.000 niños menores de 15 años y la prevalencia se estima en 0,07%. Para el municipio de Santiago de Cali, según datos de la oficina de estadística de la Secretaría de Salud Pública, la diabetes (tipo 1 y 2) se encuentra entre las diez primeras causas de muerte en la ciudad, ocupando el octavo lugar en el grupo de hombres y el séptimo entre las mujeres. Cabe resaltar que la prevalencia de diabetes para Cali es del 6,76%, seguida del 5,4% para el departamento del Valle del Cauca, cifra mucho más alta cuando se compara con la prevalencia nacional que es de 2%. Específicamente, cuando nos referimos a la diabetes tipo 1, es una patología autoinmune crónica, que se presenta con una predisposición genética específica y en un 0,4% aparece sin antecedentes familiares. Su presentación se hace de forma inesperada, a causa de la destrucción rápidamente progresiva de las células beta pancreáticas, por esta razón requiere la suplencia total de insulina exógena de forma crónica. Lo anterior ocasiona que la enfermedad esté ligada a una carga económica alta para los pacientes, sus familias y el sistema de salud. A nivel global se estima que más del 10% de la inversión en salud se destina a gastos relacionados directamente con diabetes. En cuanto al tratamiento médico de la diabetes tipo 1, la recomendación actual está basada en la terapia intensiva con insulina exógena, sin embargo, este tratamiento se caracteriza por ser de difícil adherencia, costoso, y por conllevar a un incremento considerable de los eventos de hipoglicemia severa. Estos eventos aumentan en alto grado el riesgo de sufrir deterioro cardiovascular y cognitivo. Por lo tanto, existe una gran necesidad de encontrar mejores alternativas de tratamiento para estos pacientes, que impliquen menores riesgos biológicos y ofrezcan mejor calidad de vida

Inducción a la formación profesional

Desarrolla a manera de módulos, la forma y la información que de se debe entregar a los aprendices al momento de que estos ingresen a la institución para conocer el contexto, deberes, derechos, entre otros, que los estarán rodeando en el ámbito académico.It develops as a module, the form and the information that must be given to the apprentices when they enter the institution to know the context, duties, rights, among others, that will be surrounding them in the academic field.Conocimiento e Integración Grupal -- Inducción al SENA -- Inducción a la Formación Profesional Integral -- Inducción al Centro, Programa o Proyecto -- Inducción al Programa de Formación Profesional -- Inducción a los Servicios al Alumnado -- Servicios al Alumnado: Biblioteca -- Servicios al Alumnado: Promoción y contratación de Aprendices -- Servicios al Alumnado: Trabajo Social -- Servicios al Alumnado: Capellanía -- Servicios al Alumnado: Registro y Certificación -- Servicios al Alumnado: Validación -- Servicios al Alumnado: Actividades Recreativas, Culturales y Deportivas.naPara sujetos de formación40 página

Chemical composition and antigenotoxic properties of Lippia alba essential oils

The present work evaluated the chemical composition and the DNA protective effect of the essential oils (EOs) from Lippia alba against bleomycin-induced genotoxicity. EO constituents were determined by Gas Chromatography/Mass Spectrometric (GC-MS) analysis. The major compounds encountered being citral (33% geranial and 25% neral), geraniol (7%) and trans-β-caryophyllene (7%) for L. alba specimen COL512077, and carvone (38%), limonene (33%) and bicyclosesquiphellandrene (8%) for the other, COL512078. The genotoxicity and antigenotoxicity of EO and the compounds citral, carvone and limonene, were assayed using the SOS Chromotest in Escherichia coli. The EOs were not genotoxic in the SOS chromotest, but one of the major compound (limonene) showed genotoxicity at doses between 97 and 1549 mM. Both EOs protected bacterial cells against bleomycin-induced genotoxicity. Antigenotoxicity in the two L. alba chemotypes was related to the major compounds, citral and carvone, respectively. The results were discussed in relation to the chemopreventive potential of L. alba EOs and its major compounds

Generational distribution of a Candida glabrata population: Resilient old cells prevail, while younger cells dominate in the vulnerable host.

Similar to other yeasts, the human pathogen Candida glabrata ages when it undergoes asymmetric, finite cell divisions, which determines its replicative lifespan. We sought to investigate if and how aging changes resilience of C. glabrata populations in the host environment. Our data demonstrate that old C. glabrata are more resistant to hydrogen peroxide and neutrophil killing, whereas young cells adhere better to epithelial cell layers. Consequently, virulence of old compared to younger C. glabrata cells is enhanced in the Galleria mellonella infection model. Electron microscopy images of old C. glabrata cells indicate a marked increase in cell wall thickness. Comparison of transcriptomes of old and young C. glabrata cells reveals differential regulation of ergosterol and Hog pathway associated genes as well as adhesion proteins, and suggests that aging is accompanied by remodeling of the fungal cell wall. Biochemical analysis supports this conclusion as older cells exhibit a qualitatively different lipid composition, leading to the observed increased emergence of fluconazole resistance when grown in the presence of fluconazole selection pressure. Older C. glabrata cells accumulate during murine and human infection, which is statistically unlikely without very strong selection. Therefore, we tested the hypothesis that neutrophils constitute the predominant selection pressure in vivo. When we altered experimentally the selection pressure by antibody-mediated removal of neutrophils, we observed a significantly younger pathogen population in mice. Mathematical modeling confirmed that differential selection of older cells is sufficient to cause the observed demographic shift in the fungal population. Hence our data support the concept that pathogenesis is affected by the generational age distribution of the infecting C. glabrata population in a host. We conclude that replicative aging constitutes an emerging trait, which is selected by the host and may even play an unanticipated role in the transition from a commensal to a pathogen state.post-print10768 K