Interleukin-6 and the Gut Microbiota Influence Melanoma Progression in Obese Mice.

There is a strong correlation between obesity and cancer. Here, we investigated the influence of IL-6 and gut microbiota of obese mice in melanoma development. We first evaluated B16F10 melanoma growth in preclinical models for obesity: mice deficient for leptin (ob/ob) or adiponectin (AdpKO) and in wild-type mice (WT, C57BL/6J) fed a high-fat diet (HFD; 60% kcal from fat) for 12 weeks. The survival rates of ob/ob and HFD-fed mice were lower than those of their respective controls. AdpKO mice also died earlier than WT control mice. We then verified the involvement of IL-6 signaling in obese mice that were inoculated with melanoma cells. Both ob/ob and AdpKO mice had higher circulating IL-6 levels than wild-type mice. Melanoma tumor volumes in IL-6 KO mice fed an HFD were reduced compared to those of WT mice subjected to the same diet. Also evaluated the effect of microbiota in tumor development. Cohousing and fecal matter transfer experiments revealed that microbiota from ob/ob mice can stimulate tumor development in lean WT mice. Taken together, our data show that in some conditions IL-6 and the gut microbiota are key mediators that link obesity and melanoma.

Cytokine Profile in Early Infection by Leptospira interrogans in A/J Mice.

Leptospirosis is considered a neglected disease with an estimated more than one million cases every year. Since rodents are at the same time the main reservoir and generally asymptomatic to Leptospira infection, understanding why some animal species are resistant and others are susceptible to this infection would shed some light in how to control this important zoonosis. The innate immune response against Leptospira is mainly dependent on phagocytosis and activation of the Complement System. In this context, cytokines may drive the early control of infection and the adaptive response. Since the Complement System is important to eliminate leptospires in vivo, we investigated if Complement C5 in A/J mice would modulate the cytokine production during infection by Leptospira interrogans serovar Kennewicki type Pomona Fromm (LPF). Thus, our aim was to investigate the systemic levels of pro- and anti-inflammatory cytokines during Leptospira infection in the blood, liver, lung, and kidney on the third and sixth days of infection in A/J C5+/+ and A/J C5-/- mice. Blood levels of TNF-α, IL-6, IFN-γ, and MCP-1 reached a peak on the third day. Although both mouse strains developed splenomegaly, similar histopathological alterations in the liver and the lung, levels of pro- and anti-inflammatory cytokines were different. A/J C5+/+ mice had higher levels of liver IL-10, IL-1ß, IL-12p40, and IL-12p70 and kidney IL-1ß, IL-12p40, and IL-12p70 on the sixth day of infection when compared to A/J C5-/- mice. Our results showed that in A/J genetic background, the Complement component C5 modulates a cytokine profile in the liver and kidney of infected mice, which may play a role in the control of disease progression.

Metformin exerts antitumor activity via induction of multiple death pathways in tumor cells and activation of a protective immune response.

The antitumor effect of metformin has been demonstrated in several types of cancer; however, the mechanisms involved are incompletely understood. In this study, we showed that metformin acts directly on melanoma cells as well as on the tumor microenvironment, particularly in the context of the immune response. In vitro, metformin induces a complex interplay between apoptosis and autophagy in melanoma cells. The anti-metastatic activity of metformin in vivo was assessed in several mouse models challenged with B16F10 cells. Metformin's activity was, in part, immune system-dependent, whereas its antitumor properties were abrogated in immunodeficient (NSG) mice. Metformin treatment increased the number of lung CD8-effector-memory T and CD4+Foxp3+IL-10+ T cells in B16F10-transplanted mice. It also decreased the levels of Gr-1+CD11b+ and RORγ+ IL17+CD4+ cells in B16F10-injected mice and the anti-metastatic effect was impaired in RAG-1-/- mice challenged with B16F10 cells, suggesting an important role for T cells in the protection induced by metformin. Finally, metformin in combination with the clinical metabolic agents rapamycin and sitagliptin showed a higher antitumor effect. The metformin/sitagliptin combination was effective in a BRAFV600E/PTEN tamoxifen-inducible murine melanoma model. Taken together, these results suggest that metformin has a pronounced effect on melanoma cells, including the induction of a strong protective immune response in the tumor microenvironment, leading to tumor growth control, and the combination with other metabolic agents may increase this effect.

Role of Murine Complement Component C5 in Acute in Vivo Infection by Pathogenic Leptospira interrogans.

Leptospirosis is considered one of the most important zoonosis worldwide. The activation of the Complement System is important to control dissemination of several pathogens in the host. Only a few studies have employed murine models to investigate leptospiral infection and our aim in this work was to investigate the role of murine C5 during in vivo infection, comparing wild type C57BL/6 (B6 C5+/+) and congenic C57BL/6 (B6 C5-/-, C5 deficient) mice during the first days of infection. All animals from both groups survived for at least 8 days post-infection with pathogenic Leptospira interrogans serovar Kennewicki strain Fromm (LPF). At the third day of infection, we observed greater numbers of LPF in the liver of B6 C5-/- mice when compared to B6 C5+/+ mice. Later, on the sixth day of infection, the LPF population fell to undetectable levels in the livers of both groups of mice. On the third day, the inflammatory score was higher in the liver of B6 C5+/+ mice than in B6 C5-/- mice, and returned to normal on the sixth day of infection in both groups. No significant histopathological differences were observed in the lung, kidney and spleen from both infected B6 C5+/+ than B6 C5-/- mice. Likewise, the total number of circulating leukocytes was not affected by the absence of C5. The liver levels of IL-10 on the sixth day of infection was lower in the absence of C5 when compared to wild type mice. No significant differences were observed in the levels of several inflammatory cytokines when B6 C5+/+ and B6 C5-/- were compared. In conclusion, C5 may contribute to the direct killing of LPF in the first days of infection in C57BL/6 mice. On the other hand, other effector immune mechanisms probably compensate Complement impairment since the mice survival was not affected by the absence of C5 and its activated fragments, at least in the early stage of this infection.

Complement C5 controls liver lipid profile, promotes liver homeostasis and inflammation in C57BL/6 genetic background.

Innate immunity contributes effectively to the development of alcoholic liver disease (ALD). In special, the activation of the complement system is involved in the pathogenesis of this disease. Here we investigated the contribution of complement C5 protein to the establishment and maintenance of ALD. Eight- to ten-week-old B6C5(+) and B6C5(-) male mice were fed with high fat diet (HFD) only or the same diet containing equicaloric supplements of ethanol (HFDE) or maltodextrin (HFDM) for 10 weeks. Serum parameters of liver function as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AP), albumin, glucose, triglycerides (TG) and cholesterol were evaluated. Liver tissue samples were collected for histopathological analysis, lipid extraction (TG and cholesterol), cytokines (TNF-α, IL-6, IL-1ß, IL-10, IL-12, IL-17, IFN-γ, TGF-ß) measurement and NO production. We observed that B6C5(-) mice HFDE-fed accumulated more liver cholesterol and TG, increased liver IL-17 and IL-10 levels and reduced liver TGF-ß levels when compared to HFD-fed mice. We also observed that serum AST, AP and albumin were increased in B6C5(-) mice. Liver IL-1ß, IL-6, IL-12 and IFN-γ were decreased in B6C5(-) mice independently of diet. We conclude that C5 acts in the control of serum TG and cholesterol, liver cholesterol deposition, liver homeostasis and C5 promotes a pro-inflammatory liver environment in our mouse model of ALD.

C57BL/6 and A/J Mice Have Different Inflammatory Response and Liver Lipid Profile in Experimental Alcoholic Liver Disease.

Alcoholic liver disease (ALD) is an important worldwide public health issue characterized by liver steatosis, inflammation, necrosis, and apoptosis of hepatocytes with eventual development of fibrosis and cirrhosis. Comparison of murine models with different inflammatory responses for ALD is important for an evaluation of the importance of genetic background in the interpretation of ethanol-induced phenotypes. Here, we investigated the role of inflammation and genetic background for the establishment of ALD using two different mouse strains: C57BL/6 (B6) and A/J. B6 and A/J mice were treated with a high fat diet containing ethanol (HFDE) and compared to the controls for 10 weeks. Hepatomegaly and steatohepatitis were similar in B6 and A/J mice, but only A/J mice were resistant to weight gain. On the other hand, HFDE-fed B6 accumulated more triglycerides (TG) and cholesterol and presented more intense cellular infiltrate in the liver when compared to HFDM-fed mice. Liver inflammatory environment was distinct in these two mouse strains. While HFDE-fed B6 produced more liver IL-12, A/J mice increased the TNF-α production. We concluded that mouse genetic background could dictate the intensity of the HFDE-induced liver injury.

Staphylococcus aureus manganese transport protein C (MntC) is an extracellular matrix- and plasminogen-binding protein.

Infections caused by Staphylococcus aureus--particularly nosocomial infections--represent a great concern. Usually, the early stage of pathogenesis consists on asymptomatic nasopharynx colonization, which could result in dissemination to other mucosal niches or invasion of sterile sites, such as blood. This pathogenic route depends on scavenging of nutrients as well as binding to and disrupting extracellular matrix (ECM). Manganese transport protein C (MntC), a conserved manganese-binding protein, takes part in this infectious scenario as an ion-scavenging factor and surprisingly as an ECM and coagulation cascade binding protein, as revealed in this work. This study showed a marked ability of MntC to bind to several ECM and coagulation cascade components, including laminin, collagen type IV, cellular and plasma fibronectin, plasminogen and fibrinogen by ELISA. The MntC binding to plasminogen appears to be related to the presence of surface-exposed lysines, since previous incubation with an analogue of lysine residue, ε-aminocaproic acid, or increasing ionic strength affected the interaction between MntC and plasminogen. MntC-bound plasminogen was converted to active plasmin in the presence of urokinase plasminogen activator (uPA). The newly released plasmin, in turn, acted in the cleavage of the α and ß chains of fibrinogen. In conclusion, we describe a novel function for MntC that may help staphylococcal mucosal colonization and establishment of invasive disease, through the interaction with ECM and coagulation cascade host proteins. These data suggest that this potential virulence factor could be an adequate candidate to compose an anti-staphylococcal human vaccine formulation.

Basal physiological parameters of two congenic mice strains: C5 deficient C57BL/6 and C5 sufficient A/J.

To investigate the in vivo role of complement component C5 it is common to compare the inflammatory response between C5-normal and C5-deficient inbred mice strains. Nevertheless, it should be expected that differences in the genetic backgrounds between those strains may affect several physiological parameters, complicating the correct interpretation of results. The use of congenic mice, developed by backcrossing, is therefore preferred. Still, several physiological parameters may be distinctive in the normal and deficient strains and therefore require careful analysis before animals are selected for investigation. We generated two congenic mouse strains: C57BL/6 (B6) C5(-), derived from the parental B6 C5(+) strain and A/J C5(+) mice derived from the parental A/J C5(-) strain. After confirmation by nucleotide sequencing, immunodiffusion and hemolytic activity analysis, several basal physiological parameters were analyzed in the congenic and parental strains before antigen exposition. Serum levels of liver alanine aminotransferase, alkaline phosphatase, albumin, triglycerides, cholesterol and uric acid were found to be different in C5-sufficient and C5-deficient mice from one or both genetic backgrounds (B6 and/or A/J). On the other hand, serum levels of liver aspartate aminotransferase, glucose and urea were not affected by the presence of C5 in either strain. Furthermore, in some cases, C5-dependent variations in these parameters were more evident in mice of the same gender. We conclude here that C5-deficient mice strains may present distinct systemic behaviors which should be taken in consideration before differences in the immune responses are attributed solely to the lack of circulating C5.

Comparación entre los métodos: cariograma de Bratthall 1-2-3 de Seif para la medición del riesgo cariogénico en los estudiantes del ciclo I de la Facultad de Odontología de la Universidad de El Salvador / Comparison between the methods: Seif's Bratthall 1-2-3 karyogram for the measurement of cariogenic risk in students of cycle I of the Faculty of Dentistry of the University of El Salvador

Esta investigación tiene como objetivo principal Comparar el Método Cariograma de Bratthall con el Sistema 1-2-3 de Seif para determinar cuál es más preciso en la medición del Riesgo Cariogénico en los estudiantes del ciclo I de la Facultad de Odontología de la Universidad de El Salvador. Otro de los objetivos es evaluar cuál de los dos métodos es más fácil en su aplicación clínica, también conocer si existe dificultad al trasladar la información obtenida en la aplicación clínica a cada uno de los métodos y comparar si todos los operadores llegan a clasificar de igual manera el Riesgo Cariogénico. Para la realización de dicha investigación se solicitó la colaboración de seis estudiantes de ciclo I de la Facultad de Odontología de la Universidad de El Salvador, la cual se hizo de manera aleatoria simple, a los cuales se les entregó una hoja en la cual se les informó en qué consistió la investigación y al mismo tiempo se les comprometió a cumplir con las indicaciones establecidas por el grupo investigador. Se requirió de la autorización de Dirección de Clínicas para que permitieran el uso de las instalaciones clínicas en el Área de Post-grado donde se realizó el paso de instrumentos. Al igual se solicitó la colaboración de Centro de Investigación (CENSALUD) para la utilización de una incubadora para el cultivo de pruebas bacterianas. Previo al paso de instrumento el Dr. Manuel Antonio Espinoza Molina, Máster en Prevención y Comunitaria, Catedrático de la Universidad Evangélica de El Salvador, certificado por la Academy of Dentistry International (ADY), capacitó y calibró a las tres investigadoras, docente directory seis docentes de la FOUES Dicha capacitación se realizó en tres días: Día 1: Se recibió toda la teoría de ambos métodos, la cual tuvo un tiempo de duración de tres horas que se llevó a cabo en las aulas de la FOUES. Día 2: Se calibró y se realizó la aplicación clínica de ambos métodos entre el grupo investigador en el área de Post-grado. Día 3: Este día se trasladaron los datos clínicos obtenidos a cada uno de los métodos. También se les explicó a los docentes el desarrollo de cómo se llevaría a cabo el paso de instrumentos. La comprobación de hipótesis, se hizo a través del método estadístico "Chi Cuadrado, que se utilizó para saber si la relación encontrada es significativa o no. En base a los resultados obtenidos se concluye que: Ambos métodos son de fácil aplicación clínica, en ninguno de los dos métodos presentó dificultad en traslado de la información clínica obtenida al Cariograma de Bratthall y al Sistema 1-2-3 de Seif. No todos los operadores llegaron a clasificar los diagnósticos de igual manera, pero el método en que hubo más coincidencias fue en el Sistema 1-2-3 de Seif. Como grupo investigador concluimos que ambos métodos son precisos para la medición del Riesgo Cariogénico ya que no hubo diferencias significativas en los resultados obtenidos por ambos métodos.

The main objective of this research is to compare the Bratthall Karyogram Method with the Seif 1-2-3 System to determine which is more accurate in measuring Cariogenic Risk in students of cycle I of the Faculty of Dentistry of the University of El Savior. Another objective is to evaluate which of the two methods is easier in its clinical application, also to know if there is difficulty in transferring the information obtained in the clinical application to each of the methods and to compare if all the operators manage to classify the same way the Cariogenic Risk. To carry out this research, the collaboration of six students of cycle I of the Faculty of Dentistry of the University of El Salvador was requested, which was done in a simple random manner, to which a sheet was given in which they were informed what the research consisted of and at the same time they were committed to comply with the indications established by the research group. The authorization of the Directorate of Clinics was required to allow the use of the clinical facilities in the Postgraduate Area where the passage of instruments was carried out. Likewise, the collaboration of the Research Center (CENSALUD) was requested for the use of an incubator for the cultivation of bacterial tests. Prior to the instrument, Dr. Manuel Antonio Espinoza Molina, Master in Prevention and Community, Professor at the Evangelical University of El Salvador, certified by the Academy of Dentistry International (ADY), trained and calibrated the three researchers, teacher directory six FOUES teachers This training was carried out in three days: Day 1: All the theory of both methods was received, which had a duration of three hours that was carried out in the FOUES classrooms. Day 2: The clinical application of both methods was calibrated and carried out among the research group in the Postgraduate area. Day 3: This day the clinical data obtained were transferred to each of the methods. The development of how the passage of instruments would be carried out was also explained to the teachers. Hypothesis testing was done through the "Chi Square" statistical method, which was used to find out if the relationship found was significant or not. Based on the results obtained, it is concluded that: Both methods are of easy clinical application, neither of the two methods presented difficulty in transferring the clinical information obtained to the Bratthall Karyogram and the Seif 1-2-3 System. Not all operators came to classify the diagnoses in the same way, but the method in which there were the most coincidences was in the Seif 1-2-3 System. As a research group we conclude that both methods are accurate for the measurement of Cariogenic Risk since there were no significant differences in the results obtained by both methods.

Densidade mamográfica assimétrica: como investigar? (Revisão de literatura e apresentação de rotina de investigação) / Mammographic asymmetric density: how to investigate? (Literature review and proposal of investigation routine)

A distribuição de tecido fibroglandular nas mamas ocorre em sua maioria de forma simétrica, e qualquer alteração nesta simetria pode ser indício de lesão oculta no parênquima. A avaliação da densidade assimétrica constitui, portanto, um dos principais desafios no dia-a-dia do radiologista, no sentido de diferenciar áreas de superposição de estruturas normais de lesões parenquimatosas verdadeiras. O conhecimento das diferentes técnicas e dos recursos que podem ser utilizados na investigação das densidades assimétricas é de grande importância, assim como o estabelecimento de protocolo de sua avaliação, para que a origem dessas densidades seja plenamente estabelecida, uma vez que elas podem representar a única manifestação de um câncer de mama oculto, clínica e radiograficamente.

Asistencia ventricular mecanica un nuevo reto para el profesional de enfermeria / Mechanical ventricular assistance and Nursing

La investigación clínica en dispositivos de asistencia ventricular mecánica, data de finales de los años 50. En 1966 Michael DeBakey obtiene resultados positivos asistiendo a un paciente durante 10 días. En la última década la tecnología ha evolucionado rápidamente pasando del balón de contrapulsación a los sistemas neumáticos. Para enfermería esta revolución tecnológica representa un gran reto, ya que el cuidado de los pacientes sometidos a asistencia ventricular significa además de una gran responsabilidad, el acceso a nuevas tecnologías, conocimientos y habilidades para el crecimiento profesional. Enfermería necesita trabajar mancomunadamente con otros profesionales para lograr su objetivo, como es el de mantener y/o mejorar la calidad de vida de los pacientes. La experiencia en asistencia ventricular mecánica en niños, es poca. La sobrevida de un paciente de 10 años sometido a asistencia ventricular derecha durante 48 horas, motiva este reporte de caso y pretende dar a conocer los aspectos más importantes tanto técnicos (manejo de consola, técnicas de canulación) como prácticos (indicaciones, técnicas de asistencia, contraindicaciones, complicaciones, principios fisiológicos y registro) necesarios para entender el funcionamiento de éstos dispositivos, finalmente plantear intervenciones de enfermería en términos de diagnósticos de enfermería...

Frecuencia, manejo y evolución de cáncer de cervix en el Hospital "Dr. Heriberto Pieter" / Frecuency, management and progression of cervix cancer in the Hospital \"Heriberto Pieter\"

Con el objetivo de determinar la frecuencia, manejo y evolucion existente de cancer de cervix en el Hospital "Dr. Heriberto Pieter", de Santo Domingo, durante el periodo comprendido entre enro 1984-diciembre 1988 se revisaron 1,137 expedientes de pacientes menores o iguales a 35 años de edad y se observo un total de 339 casos positivos con cancer de cervix para un 30 por ciento . La raza que predomino fue la meztiza con 332 casos equivalente a 97.94 por ciento . Las edades mas frecuentes del 1er. coito fueron de 15 a 17 años, la mayor incidencia fue la de mas de 2 conyuges con 100 casos constituyendo esto un 30 por ciento . Hubo una menor incidencia en las que se realizaban pruebas de papanicolaou y el tratamiento mas usado fue de la radioterapia