Lymphocytes, apoptosis and sepsis: making the jump from mice to humans

Sepsis is an important clinical problem with a mortality rate of 20% to 30%. Lymphocyte apoptosis has been recognized as an important step in the pathogenesis of experimental sepsis, by inducing a state of 'immune paralysis' that renders the host vulnerable to invading pathogens. The importance of lymphocyte apoptosis in human disease is now confirmed by Weber and colleagues, who demonstrate extensive apoptosis in circulating lymphocytes from patients with severe sepsis. Weber and colleagues' data set the basis for further studies aimed at modulating lymphocyte apoptosis in sepsis

Glomus tumour of the lung: A case report and literature review

AbstractBackgroundGlomus tumours are neoplasms arising from cells of the neuromyoarterial glomus bodies, which almost always occur in a subungual location. A lung location is extremely rare, with few cases reported in the literature.Clinical caseThe case is presented of a 33 year-old male, with non-productive cough, dyspnoea at rest, intermittent fever, and mild pain in rib cage. A chest radiograph showed a consolidation in the left lung, and computed tomography revealed a lesion in the hilum that extended to the bronchus of the lingula obstructing, and causing post-obstructive pneumonia. A biopsy was obtained by rigid bronchoscopy biopsy, which showed a well circumscribed tumour constituted by intermediate-sized cells, and abundant cytoplasm that are arranged in a pattern surrounding numerous thin-walled blood vessels, with no pleomorphism, significant mitotic activity or necrosis. Immunohistochemistry revealed diffuse positivity with smooth muscle actin, vimentin, caldesmon; focal reactivity with desmin and CD117, CD34 highlights the vascular pattern. Ki67 proliferation rate was 1%. Synaptophysin, EMA and cytokeratin cocktail were negative, making the diagnosis of glomus tumour.ConclusionsGlomus tumours are rare neoplasms that usually appear in the dermis and subcutaneous tissue, where it is common to find glomus bodies. Occasionally glomus tumours can occur in extra-cutaneous sites such as the gastrointestinal tract, bone and respiratory system, with this case being a new case of rare lung location

Mechanical ventilation interacts with endotoxemia to induce extrapulmonary organ dysfunction

INTRODUCTION: Multiple organ dysfunction syndrome (MODS) is a common complication of sepsis in mechanically ventilated patients with acute respiratory distress syndrome, but the links between mechanical ventilation and MODS are unclear. Our goal was to determine whether a minimally injurious mechanical ventilation strategy synergizes with low-dose endotoxemia to induce the activation of pro-inflammatory pathways in the lungs and in the systemic circulation, resulting in distal organ dysfunction and/or injury. METHODS: We administered intraperitoneal Escherichia coli lipopolysaccharide (LPS; 1 μg/g) to C57BL/6 mice, and 14 hours later subjected the mice to 6 hours of mechanical ventilation with tidal volumes of 10 ml/kg (LPS + MV). Comparison groups received ventilation but no LPS (MV), LPS but no ventilation (LPS), or neither LPS nor ventilation (phosphate-buffered saline; PBS). RESULTS: Myeloperoxidase activity and the concentrations of the chemokines macrophage inflammatory protein-2 (MIP-2) and KC were significantly increased in the lungs of mice in the LPS + MV group, in comparison with mice in the PBS group. Interestingly, permeability changes across the alveolar epithelium and histological changes suggestive of lung injury were minimal in mice in the LPS + MV group. However, despite the minimal lung injury, the combination of mechanical ventilation and LPS resulted in chemical and histological evidence of liver and kidney injury, and this was associated with increases in the plasma concentrations of KC, MIP-2, IL-6, and TNF-α. CONCLUSION: Non-injurious mechanical ventilation strategies interact with endotoxemia in mice to enhance pro-inflammatory mechanisms in the lungs and promote extra-pulmonary end-organ injury, even in the absence of demonstrable acute lung injury

Factores clínicos e inmunológicos asociados a la nefritis lúpica en pacientes del noroeste de Colombia.

Este estudio transversal y multicéntrico investigó las características clínicas e inmunológicas asociadas con la nefritis lúpica en pacientes colombianos de Medellín. Se incluyeron treinta y nueve pacientes con nefritis lúpica y se compararon sus características con las de 100 pacientes con lupus eritematoso sistémico (LES) sin compromiso renal. Se realizó un análisis multivariado para evaluar los factores asociados con la nefritis lúpica. Los pacientes que desarrollaron nefritis presentaron, al inicio, más úlceras orales (41% vs. 21%, OR=3,1, IC95%: 1,3-7,5, p=0,01)y eritema malar (77% vs. 45%, OR=4,4, IC95%: 1,8-10,8, p=0,001) que aquellos pacientes sin nefropatía. La nefritis lúpica se observó en 77% de los casos durante el primer año de evolución del LES. La frecuencia de anticuerpos anti-ADN fue mayor en los pacientes con nefritis; sine mbargo, las diferencias no fueron significativas (83% vs. 64%, OR=2,57, IC95%:1,03-6,41,p=0,06). La presencia de otros anticuerpos (anti-Ro, anti-La, anti-RNP, anti-Sm y anticardiolipina)en el momento del diagnóstico fue similar en ambos grupos. El perfil de los autoanticuerpos permaneció sin modificación significativa durante el curso del LES. Los pacientes con nefritis lúpica presentaron una mayor prevalencia de hipertensión arterial (60% vs 10%, OR=13,7,IC95%: 5-37, p=0,00001) y dislipidemia (30% vs 7%, OR=8,1, IC95%: 2,5-27, p=0,0006) al inicio de la enfermedad que aquellos pacientes sin nefropatía. Los pacientes con nefritis lúpica requirieron más hospitalizaciones (>1) durante el curso de la enfermedad (89% vs 60%, OR=7,8,IC95%: 2,1-29, p=0,002). En conclusión, la nefritis lúpica se presenta tempranamente en el LES. El eritema malar, las úlceras orales, la hipertensión arterial y la dislipidemia son factores asociados. A su vez, la nefritis lúpica es un factor de riesgo de hospitalizaciones repetidas. Este estudio puede ser útil en la toma de decisiones de políticas de salud para beneficio de los pacientes y reducción de costos.A cross-sectional and multicenter study was undertaken to analyze the clinical andimmunological characteristics at diagnosis associated with nephritis in northwesternColombian patients with systemic lupus erythematosus (SLE). Thirty nine patients with lupusnephritis were included and were compared to 100 SLE patients without nephritis. A multivariateanalysis was performed. The patients who developed nephritis had a higher frequency of oralulcers (41% vs. 21%, OR=3.1, 95%CI: 1.3-7.5 p= 0.01) and malar erythema (77% vs. 45%,OR=4.4, 95%CI: 1.8-10.8 p=0.001). Lupus nephritis was observed in 77% of cases during thefirst year of the disease. The frequency of anti-DNA antibodies was higher in patients withnephritis, however, differences were not statistically significant (83% vs 64%, OR=2.6, 95%CI:1.03-6.41, p=0.06). The presence of other autoantibodies (anti-Ro, anti-La, anti-RNP, anti-Smand anticardiolipin) at diagnosis was similar in both groups. This autoantibody profile remainedunchanged throughout the evolution of the disease. Patients with lupus nephritis had a higherprevalence of arterial hypertension (60% vs 10%, OR=13.7, 95%IC: 5-37, p=0.00001) andhyperlipidemia (30% vs 7%, OR=8.1, 95%IC: 2.5-27, p=0.0006) at onset. Finally, patients withlupus nephritis required more hospitalizations (>1) over the course of disease (89% vs 60%,OR=7.8, 95%CI: 2.1–29, p=0.002). In conclusion, lupus nephritis appears early during thecourse of SLE. Malar erythema, oral ulcers, hypertension and hyperlipidemia at onset of diseaseare associated factors. Lupus nephritis is a major risk factor leading to repeatedhospitalizations. This study may help to assist in public health policies in our population inorder to improve patient outcomes while simultaneously reducing disease costs

Regulation of protein transport from the Golgi complex to the endoplasmic reticulum by CDC42 and N-WASP.

Actin is involved in the organization of the Golgi complex and Golgi-to-ER protein transport in mammalian cells. Little, however, is known about the regulation of the Golgi-associated actin cytoskeleton. We provide evidence that Cdc42, a small GTPase that regulates actin dynamics, controls Golgi-to-ER protein transport. We located GFP-Cdc42 in the lateral portions of Golgi cisternae and in COPI-coated and noncoated Golgi-associated transport intermediates. Overexpression of Cdc42 and its activated form Cdc42V12 inhibited the retrograde transport of Shiga toxin from the Golgi complex to the ER, the redistribution of the KDEL receptor, and the ER accumulation of Golgi-resident proteins induced by the active GTP-bound mutant of Sar1 (Sar1[H79G]). Coexpression of wild-type or activated Cdc42 and N-WASP also inhibited Golgito-ER transport, but this was not the case in cells expressing Cdc42V12 and N-WASP(AWA), a mutant form of N-WASP that lacks Arp2/3 binding. Furthermore, Cdc42V12 recruited GFP-NWASP to the Golgi complex. We therefore conclude that Cdc42 regulates Golgi-to-ER protein transport in an N-WASP¿dependent manner

Uso de aplicaciones Web 2.0 para Información de oficina

This work describes the results of a study carried out in the institutions and organizations of the city of Latacunga - Ecuador, punctually in urban parishes. The use of web 2.0 applications for office information management was investigated, later the design of web applications for entities with less technological access was proposed, these applications were implemented with content management systems (CMS), applying the development model in waterfall. First level students of the Information Systems degree of the Technical University of Cotopaxi (UTC) participated in the project from the academic cycle April - August 2018 until October 2018 - February 2019. Information was obtained from 106 entities (29 public and 77 private) obtaining among others, the following results: 1) 18% of private organizations in the commercial sector still keep their records only manually; 2) most organizations do not use web 2.0 applications for handling office information, and among the conventional applications they use most are: Office, Word and Excel; 3) 34% of entities claim to have sufficient knowledge about web 2.0 tools, and 14% have no knowledge; 4) Five organizations benefited from the implementation of web pages, where 11 people were also trained in the use of web 2.0 applications.Este trabajo describe los resultados de un estudio realizado en las instituciones y organizaciones de la ciudad de Latacunga – Ecuador, puntualmente en las parroquias urbanas. Se investigó sobre el uso de aplicaciones web 2.0 para administración de información de oficina, posteriormente se propuso el diseño de aplicaciones web para las entidades con menor acceso tecnológico, estas aplicaciones fueron implementadas con sistemas gestores de contenido (CMS), aplicando el modelo de desarrollo en Cascada. Participaron en el proyecto, estudiantes de primer nivel de la carrera de Sistemas de Información de la Universidad Técnica de Cotopaxi (UTC) desde el ciclo académico abril – agosto 2018 hasta octubre 2018 – febrero 2019. Se obtuvo información de 106 entidades (29 públicas y 77 privadas) con los siguientes resultados: 1) el 18% de organizaciones privadas del sector comercial aún llevan sus registros solo de forma manual; 2) la mayor parte de organizaciones no utilizan aplicaciones web 2.0 para el manejo de información de oficina, y entre las aplicaciones convencionales que más usan están: Office, Word y Excel; 3) el 34% de entidades afirman tener conocimiento suficiente sobre herramientas web 2.0, y el 14% no tener conocimientos; 4) cinco organizaciones se beneficiaron con la implementación de páginas web, donde además se ejecutaron procesos de capacitación a 11 personas sobre el uso de aplicaciones web 2.0.Este trabajo describe los resultados de un estudio realizado en las instituciones y organizaciones de la ciudad de Latacunga – Ecuador, puntualmente en las parroquias urbanas. Se investigó sobre el uso de aplicaciones web 2.0 para administración de información de oficina, posteriormente se propuso el diseño de aplicaciones web para las entidades con menor acceso tecnológico, estas aplicaciones fueron implementadas con sistemas gestores de contenido (CMS), aplicando el modelo de desarrollo en Cascada. Participaron en el proyecto, estudiantes de primer nivel de la carrera de Sistemas de Información de la Universidad Técnica de Cotopaxi (UTC) desde el ciclo académico abril – agosto 2018 hasta octubre 2018 – febrero 2019. Se obtuvo información de 106 entidades (29 públicas y 77 privadas) con los siguientes resultados: 1) el 18% de organizaciones privadas del sector comercial aún llevan sus registros solo de forma manual; 2) la mayor parte de organizaciones no utilizan aplicaciones web 2.0 para el manejo de información de oficina, y entre las aplicaciones convencionales que más usan están: Office, Word y Excel; 3) el 34% de entidades afirman tener conocimiento suficiente sobre herramientas web 2.0, y el 14% no tener conocimientos; 4) cinco organizaciones se beneficiaron con la implementación de páginas web, donde además se ejecutaron procesos de capacitación a 11 personas sobre el uso de aplicaciones web 2.0

Comparison of direct and indirect models of early induced acute lung injury

The animal experimental counterpart of human acute respiratory distress syndrome (ARDS) is acute lung injury (ALI). Most models of ALI involve reproducing the clinical risk factors associated with human ARDS, such as sepsis or acid aspiration; however, none of these models fully replicates human ARDS. To compare different experimental animal models of ALI, based on direct or indirect mechanisms of lung injury, to characterize a model which more closely could reproduce the acute phase of human ARDS. Adult male Sprague-Dawley rats were subjected to intratracheal instillations of (1) HCl to mimic aspiration of gastric contents; (2) lipopolysaccharide (LPS) to mimic bacterial infection; (3) HCl followed by LPS to mimic aspiration of gastric contents with bacterial superinfection; or (4) cecal ligation and puncture (CLP) to induce peritonitis and mimic sepsis. Rats were sacrificed 24 h after instillations or 24 h after CLP. At 24 h, rats instilled with LPS or HCl-LPS had increased lung permeability, alveolar neutrophilic recruitment and inflammatory markers (GRO/KC, TNF-α, MCP-1, IL-1β, IL-6). Rats receiving only HCl or subjected to CLP had no evidence of lung injury. Rat models of ALI induced directly by LPS or HCl-LPS more closely reproduced the acute phase of human ARDS than the CLP model of indirectly induced ALI

Tuberculosis en pacientes tratados con antagonistas del factor de necrosis tumoral alfa en un área endémica, ¿vale la pena el riesgo?

Tumor necrosis factor alpha antagonists (TNFA) are biological agents to treat chronic inflammatory and autoimmune diseases. However, their use is associated with an increased rate of tuberculosis, endemic mycoses, and intracellular bacterial infections. Since tuberculosis is moderately to highly endemic in Colombia, the risk of these infections in patients treated with TNFAs may be higher than previously reported in Colombia. Recently, four patients have developed tuberculosis during TNFA therapy. Tuberculosis appeared between 3 to 24 months after initiation of TFNA therapy and was independent of previous tuberculin skin test status. A review of the relevant literature and recommLos antagonistas del factor de necrosis tumoral alfa (infliximab, adalimumab y etanercept) son agentes biológicos utilizados en el tratamiento de enfermedades inflamatorias crónicas y autoinmunes. Sin embargo, su uso está asociado con el incremento de la tasa de tuberculosis, micosis endémicas e infecciones bacterianas intracelulares. Dado que la tuberculosis es moderada/altamente endémica en Colombia, el riesgo de esta infección en los pacientes tratados con estos agentes biológicos puede incrementarse y hacer dicha tasa mayor que la informada previamente (tanto en Colombia como en el mundo). Se presentan cuatro pacientes que desarrollaron tuberculosis durante el tratamiento con antagonistas del factor de necrosis tumoral alfa. La presentación de la tuberculosis ocurrió en promedio 15 meses después del inicio del agente biológico y fue independiente de la prueba de tuberculina. Se hace una revisión del tema y se plantea la necesidad de implementar guías y estrategias gubernamentales orientadas a la detección y profilaxis de tuberculosis en este grupo de pacientes

Factores clínicos y epidemiológicos asociados con nefritis lúpica en pacientes del noroccidente colombiano

A cross-sectional and multicenter study was undertaken to analyze the clinical and immunological characteristics at diagnosis associated with nephritis in northwestern Colombian patients with systemic lupus erythematosus (SLE). Thirty-nine patients with lupus nephritis were included and were compared to 100 SLE patients without nephritis. A multivariate analysis was performed. The patients who developed nephritis had a higher frequency of oral ulcers (41% vs. 21%, OR = 3.1, 95% CI: 1.3-7.5 p = 0.01) and malar erythema (77% vs. 45%, OR = 4.4, 95% CI: 1.8-10.8 p = 0.001). Lupus nephritis was observed in 77% of cases during the first year of the disease. The frequency of anti-DNA antibodies was higher in patients with nephritis, however, differences were not statistically significant (83% vs 64%, OR = 2.6, 95% CI: 1.03-6.41, p = 0.06). The presence of other autoantibodies (anti-Ro, anti-La, anti-RNP, anti-Sm and anticardiolipin) at diagnosis was similar in both groups. This autoantibody profile remained unchanged throughout the evolution of the disease. Patients with lupus nephritis had a higher prevalence of arterial hypertension (60% vs 10%, OR = 13.7, 95% IC: 5-37, p = 0.00001) and hyperlipidemia (30% vs 7%, OR = 8.1, 95% IC: 2.5-27, p = 0.0006) at onset. Finally, patients with lupus nephritis required more hospitalizations (> 1) over the course of disease (89% vs 60%, OR = 7.8, 95% CI: 2.1-29, p = 0.002). In conclusion, lupus nephritis appears early during the course of SLE. Malar erythema, oral ulcers, hypertension and hyperlipidemia at onset of disease are associated factors. Lupus nephritis is a major risk factor leading to repeated hospitalizations. This study may help to assist in public health policies in our population in order to improve patient outcomes while simultaneously reducing disease costs.Este estudio transversal y multicéntrico investigó las características clínicas e inmunológicas asociadas con la nefritis lúpica en pacientes colombianos de Medellín. Se incluyeron treinta y nueve pacientes con nefritis lúpica y se compararon sus características con las de 100 pacientes con lupus eritematoso sistémico (LES) sin compromiso renal. Se realizó un análisis multivariado para evaluar los factores asociados con la nefritis lúpica. Los pacientes que desarrollaron nefritis presentaron, al inicio, más úlceras orales (41% vs. 21%, OR=3,1, IC95%: 1,3-7,5, p=0,01) y eritema malar (77% vs. 45%, OR=4,4, IC95%: 1,8-10,8, p=0,001) que aquellos pacientes sin nefropatía. La nefritis lúpica se observó en 77% de los casos durante el primer año de evolución del LES. La frecuencia de anticuerpos anti-ADN fue mayor en los pacientes con nefritis; sin embargo, las diferencias no fueron significativas (83% vs. 64%, OR=2,57, IC95%:1,03-6,41, p=0,06). La presencia de otros anticuerpos (anti-Ro, anti-La, anti-RNP, anti-Sm y anticardiolipina) en el momento del diagnóstico fue similar en ambos grupos. El perfil de los autoanticuerpos permaneció sin modificación significativa durante el curso del LES. Los pacientes con nefritis lúpica presentaron una mayor prevalencia de hipertensión arterial (60% vs 10%, OR=13,7, IC95%: 5-37, p=0,00001) y dislipidemia (30% vs 7%, OR=8,1, IC95%: 2,5-27, p=0,0006) al inicio de la enfermedad que aquellos pacientes sin nefropatía. Los pacientes con nefritis lúpica requirieron más hospitalizaciones (>1) durante el curso de la enfermedad (89% vs 60%, OR=7,8, IC95%: 2,1-29, p=0,002). En conclusión, la nefritis lúpica se presenta tempranamente en el LES. El eritema malar, las úlceras orales, la hipertensión arterial y la dislipidemia son factores asociados. A su vez, la nefritis lúpica es un factor de riesgo de hospitalizaciones repetidas. Este estudio puede ser útil en la toma de decisiones de políticas de salud para beneficio de los pacientes y reducción de costos