Identification of an inducible nitric oxide synthase in diaphragm mitochondria from septic miceIts relation with mitochondrial dysfunction and prevention by melatonin

Producción CientíficaSepsis provokes an induction of inducible nitric oxide synthase (iNOS) and melatonin down-regulates its expression and activity. Looking for an inducible mtNOS isoform, we induced sepsis by cecal ligation and puncture in both normal and iNOS knockout mice and studied the changes in mtNOS activity. We also studied the effects of mtNOS induction in mitochondrial function, and the role of melatonin against induced mtNOS and mitochondrial dysfunction. The activity of mtNOS and nitrite levels significantly increased after sepsis in iNOS+/+ mice. These animals showed a significant inhibition of the respiratory chain activity and an increase in mitochondrial oxidative stress, reflected in the disulfide/glutathione ratio, glutathione redox cycling enzymes activity and lipid peroxidation levels. Interestingly, mtNOS activity remained unchanged in iNOS-/- septic mice, and mitochondria of these animals were unaffected by sepsis. Melatonin administration to iNOS+/+ mice counteracted mtNOS induction and respiratory chain failure, restoring the redox status. The results support the existence of an inducible mtNOS that is likely coded by the same gene as iNOS. The results also suggest that sepsis-induced mtNOS is responsible for the increase of mitochondrial impairment due to oxidative stress in sepsis, perhaps due to the high production of NO. Melatonin treatment prevents mitochondrial failure at the same extend as the lack of iNOS gene

A Traditional Diet Is Associated with a Reduced Risk of Eczema and Wheeze in Colombian Children

Background: Diet might influence the risk of allergic diseases. Evidence from developing countries with high prevalence of childhood asthma is scant. Methods: Information on wheeze, rhinitis, and eczema was collected from 3209 children aged 6–7 years in 2005, who were taking part in the International Study on Asthma and Allergy in Children (ISAAC) in Colombia. Intake frequency of twelve food groups was assessed. Associations between each food group and current wheeze, rhino-conjunctivitis, and eczema were investigated with multiple logistic regressions, adjusting for potential confounders. Simes’ procedure was used to test for multiple comparisons. Results: 14.9% of children reported wheeze in the last 12 months, 16% rhino-conjunctivitis, and 22% eczema. Eczema was negatively associated with consumption of fresh fruits and pulses three or more times per week (adjusted Odds ratio (aOR): 0.64; 95% Confidence Interval (CI): 0.49 to 0.83; p value = 0.004; and aOR: 0.62, 95% CI: 0.47 to 0.80; p value < 0.001, respectively). Current wheeze was negatively associated with intake of potatoes (aOR: 0.44, 95% CI: 0.31 to 0.62, p value = 0.005), whilst this outcome was positively associated with consumption of fast food (aOR: 1.76, 95% CI: 1.32 to 2.35, p value = 0.001). These associations remained statistically significant after controlling for multiple comparisons. Conclusions: A traditional diet might have a protective effect against eczema and wheeze in Colombian children, whilst intake of fast foods increases this risk

Media for the appropriation of knowledge in educational institutions

The objective of this research study was to assess how media describes the appropriation of knowledge in educational institutions in the state of Magdalena (Colombia). Ten semi-structured interviews were conducted and analyzed using grounded theory. The results obtained respond to the use of means in learning spaces to generate competencies (use, interaction, and participation) of the human being in meaningful learning sessions. The results show that the communication process depends on the profile and work of the teacher, number of participants, available teaching tools, and structure of the institution. These create barriers and filters that limit learning. Interactive models, with emerging perspectives on knowledge, influence knowledge appropriation. It is concluded that educational media are affected by the teacher-student’s technological culture, which can cause knowledge gaps for proper educational media use.El objetivo de esta investigación fue examinar la descripción de los medios de comunicación para la apropiación del conocimiento en instituciones educativas del departamento de Magdalena, Colombia. Para tal fin, se realizaron diez entrevistas semiestructuradas, analizadas mediante la teoría fundamentada. Los resultados obedecen a la utilización de medios en espacios de aprendizajes para generar competencias (utilización, interacción y participación) del ser humano en sesiones de aprendizajes significativos. Los resultados muestran que el proceso de comunicación depende del perfil y labor del docente, número de participantes, herramientas didácticas disponibles y estructura de la institución, ocasionando barreras y filtros que limitan el aprendizaje. La apropiación del conocimiento está influenciada por modelos interactivos, con perspectivas emergentes sobre el saber. Se concluye que los medios de comunicación educativos se ven impactados por la cultura tecnológica del docente-estudiante, originando brechas de conocimiento para su adecuado uso

Impact of the sensory neurons on melanoma growth in vivo

Nerve endings are often identified within solid tumors, but their impact on the tumor growth and progression remains poorly understood. Emerging data suggests that the central nervous system may affect cancer development and spreading via the hypothalamic-pituitary-adrenal axis and autonomous nervous system. However, the role of the afferent sensory neurons in tumor growth is unclear, except some reports on perineural invasion in prostate and pancreatic cancer and cancer-related pain syndrome. Here, we provide the results of primary testing of the concept that the interaction between melanoma cells and sensory neurons may induce the formation of tumor-supporting microenvironment via attraction of immune regulatory cells by the tumor-activated dorsal root ganglion (DRG) neurons. We report that despite DRG cells not directly up-regulating proliferation of melanoma cells in vitro, presence of DRG neurons allows tumors to grow significantly faster in vivo. This effect has been associated with increased production of chemokines by tumor-activated DRG neurons and attraction of myeloid-derived suppressor cells both in vitro and in vivo. These initial proof-of-concept results justify further investigations of the sensory (afferent) nervous system in the context of tumorigenesis and the local protumorigenic immunoenvironment

Genetic and Morphological Features of Human iPSC-Derived Neurons with Chromosome 15q11.2 (BP1-BP2) Deletions

Producción CientíficaBackground: Copy number variation on chromosome 15q11.2 (BP1-BP2) causes deletion of CYFIP1, NIPA1, NIPA2 and TUBGCP5; it also affects brain structure and elevates risk for several neurodevelopmental disorders that are associated with dendritic spine abnormalities. In rodents, altered cyfip1 expression changes dendritic spine morphology, motivating analyses of human neuronal cells derived from iPSCs (iPSC-neurons). Methods: iPSCs were generated from a mother and her offspring, both carrying the 15q11.2 (BP1-BP2) deletion, and a non-deletion control. Gene expression in the deletion region was estimated using quantitative real-time PCR assays. Neural progenitor cells (NPCs) and iPSC-neurons were characterized using immunocytochemistry. Results: CYFIP1, NIPA1, NIPA2 and TUBGCP5 gene expression was lower in iPSCs, NPCs and iPSC-neurons from the mother and her offspring in relation to control cells. CYFIP1 and PSD95 protein levels were lower in iPSC-neurons derived from the CNV bearing individuals using Western blot analysis. At 10 weeks post-differentiation, iPSC-neurons appeared to show dendritic spines and qualitative analysis suggested that dendritic morphology was altered in 15q11.2 deletion subjects compared with control cells. Conclusions: The 15q11.2 (BP1-BP2) deletion is associated with reduced expression of four genes in iPSC-derived neuronal cells; it may also be associated altered iPSC-neuron dendritic morphology

Utilitat de la determinació del DNA del virus de l'hepatitis B en serum per hibridació molecular

Mediante una técnica de hibridación molecular, utilizando como sonda DNA-VHB purificado de un plasmido recombinante, se ha examinado la presencia de DNA-VHB en el suero de 82 portadores crónicos de HBsAg(RIA) sin evidenciashade infección Delta y en 80 sujetos HBsAg negativos (40 donantes de Sangre y 40 con hepatitis crónica o cirrosis no alcohólica). Se detectó DNA-VHB en cantidades variables en los 62 portadores crónicos(57 HBeAg positivo y 5 antiHBe positivo) con transaminasas elevadas, lesiones de hepatitis crónica y presencia de HBcAg en el tejido hepático (inmunoperoxidasa). En los 8 portadores con transaminasas elevadas, antiHBe positivo, lesiones de hepatitis crónica y HBcAg ausente del higado, se detectó DNA-VHB sérico en forma intermitente. El examen fue negativo en los 11 portadores crónicos con antiHBe positivo y transaminasas normales, así como en los sujetos HBsAg negativo. La presencia de DNA-VHB en el suero se asocia a la existencia de actividad inflamatoria y refleja la actividad replicativa del VHB con mayor fidelidad que la valoración del sistema antigénico HBe. Su examen constituye un elemento sumamente útil tanto para el estudio de la historia natural de la infección crónica por el VHB como para la valoración de agentes terapéuticos

How hepatitis C virus modifies the immunological profile of Sjögren syndrome: analysis of 783 patients.

Introduction: We conducted a study to analyze how infection by hepatitis C virus (HCV) may influence the immunological serum pattern of patients with Sjögren syndrome (SS). Methods: Since 1994, we have tested serum HCV-IgG antibodies in 783 patients with SS diagnosed according to the 1993 European classification criteria. The immunological profile at diagnosis was compared according to the presence or absence of HCV. Results: Of the 783 patients with SS, 105 (13.4 %) tested positive for HCV-IgG antibodies (88 females, 17 males,mean age at SS diagnosis: 62.9 years). Multivariate analysis showed that patients with SS-HCV had a higher mean age and a higher frequency of low C3/C4 levels, cryoglobulins, and hematological neoplasia compared with patients without HCV. The frequency of anti-La antibodies compared with anti-Ro antibodies was higher in patients with SS-HCV (17 % vs. 15 %) and lower in patients without HCV infection (30 % vs. 43 %). The frequency of concomitant detection of the three main cryoglobulin-related markers (cryoglobulins, rheumatoid factor activity, and C4 consumption) was threefold higher in patients with SS-HCV compared with patients without HCV. SS-HCV patients with genotype 1b showed the highest frequencies of immunological abnormalities related to cryoglobulins and the lowest frequencies of anti-Ro/La antibodies. Conclusions: We found HCV infection in 13 % of a large series of Spanish patients with SS. The HCV-driven autoimmune response was characterized by a lower frequency of anti-Ro/La antibodies, an abnormal predominance of anti-La among anti-Ro antibodies, and a higher frequency of cryoglobulinemic-related immunological markers in comparison with patients without HCV infection. This immunological pattern may contribute to the poor outcomes found in patients with SS-HCV

Mathematical model of a telomerase transcriptional regulatory network developed by cell-based screening: analysis of inhibitor effects and telomerase expression mechanisms

Cancer cells depend on transcription of telomerase reverse transcriptase (TERT). Many transcription factors affect TERT, though regulation occurs in context of a broader network. Network effects on telomerase regulation have not been investigated, though deeper understanding of TERT transcription requires a systems view. However, control over individual interactions in complex networks is not easily achievable. Mathematical modelling provides an attractive approach for analysis of complex systems and some models may prove useful in systems pharmacology approaches to drug discovery. In this report, we used transfection screening to test interactions among 14 TERT regulatory transcription factors and their respective promoters in ovarian cancer cells. The results were used to generate a network model of TERT transcription and to implement a dynamic Boolean model whose steady states were analysed. Modelled effects of signal transduction inhibitors successfully predicted TERT repression by Src-family inhibitor SU6656 and lack of repression by ERK inhibitor FR180204, results confirmed by RT-QPCR analysis of endogenous TERT expression in treated cells. Modelled effects of GSK3 inhibitor 6-bromoindirubin-3′-oxime (BIO) predicted unstable TERT repression dependent on noise and expression of JUN, corresponding with observations from a previous study. MYC expression is critical in TERT activation in the model, consistent with its well known function in endogenous TERT regulation. Loss of MYC caused complete TERT suppression in our model, substantially rescued only by co-suppression of AR. Interestingly expression was easily rescued under modelled Ets-factor gain of function, as occurs in TERT promoter mutation. RNAi targeting AR, JUN, MXD1, SP3, or TP53, showed that AR suppression does rescue endogenous TERT expression following MYC knockdown in these cells and SP3 or TP53 siRNA also cause partial recovery. The model therefore successfully predicted several aspects of TERT regulation including previously unknown mechanisms. An extrapolation suggests that a dominant stimulatory system may programme TERT for transcriptional stability

Are the health messages in schoolbooks based on scientific evidence? A descriptive study

<p>Abstract</p> <p>Background</p> <p>Most textbooks contains messages relating to health. This profuse information requires analysis with regards to the quality of such information. The objective was to identify the scientific evidence on which the health messages in textbooks are based.</p> <p>Methods</p> <p>The degree of evidence on which such messages are based was identified and the messages were subsequently classified into three categories: Messages with high, medium or low levels of evidence; Messages with an unknown level of evidence; and Messages with no known evidence.</p> <p>Results</p> <p>844 messages were studied. Of this total, 61% were classified as messages with an unknown level of evidence. Less than 15% fell into the category where the level of evidence was known and less than 6% were classified as possessing high levels of evidence. More than 70% of the messages relating to "Balanced Diets and Malnutrition", "Food Hygiene", "Tobacco", "Sexual behaviour and AIDS" and "Rest and ergonomics" are based on an unknown level of evidence. "Oral health" registered the highest percentage of messages based on a high level of evidence (37.5%), followed by "Pregnancy and newly born infants" (35%). Of the total, 24.6% are not based on any known evidence. Two of the messages appeared to contravene known evidence.</p> <p>Conclusion</p> <p>Many of the messages included in school textbooks are not based on scientific evidence. Standards must be established to facilitate the production of texts that include messages that are based on the best available evidence and which can improve children's health more effectively.</p