Microarray Analyses of Genes Differentially Expressed by Diet (Black Beans and Soy Flour) during Azoxymethane-Induced Colon Carcinogenesis in Rats

We previously demonstrated that black bean (BB) and soy flour (SF)-based diets inhibit azoxymethane (AOM)-induced colon cancer. The objective of this study was to identify genes altered by carcinogen treatment in normal-appearing colonic mucosa and those attenuated by bean feeding. Ninety-five male F344 rats were fed control (AIN) diets upon arrival. At 4 and 5 weeks, rats were injected with AOM (15 mg/kg) or saline and one week later administered an AIN, BB-, or SF-based diet. Rats were sacrificed after 31 weeks, and microarrays were conducted on RNA isolated from the distal colonic mucosa. AOM treatment induced a number of genes involved in immunity, including several MHC II-associated antigens and innate defense genes (RatNP-3, Lyz2, Pla2g2a). BB- and SF-fed rats exhibited a higher expression of genes involved in energy metabolism and water and sodium absorption and lower expression of innate (RatNP-3, Pla2g2a, Tlr4, Dmbt1) and cell cycle-associated (Cdc2, Ccnb1, Top2a) genes. Genes involved in the extracellular matrix (Col1a1, Fn1) and innate immunity (RatNP-3, Pla2g2a) were induced by AOM in all diets, but to a lower extent in bean-fed animals. This profile suggests beans inhibit colon carcinogenesis by modulating cellular kinetics and reducing inflammation, potentially by preserving mucosal barrier function

Vanadium pentoxide induces pulmonary inflammation and tumor promotion in a strain-dependent manner

<p>Abstract</p> <p>Background</p> <p>Elevated levels of air pollution are associated with increased risk of lung cancer. Particulate matter (PM) contains transition metals that may potentiate neoplastic development through the induction of oxidative stress and inflammation, a lung cancer risk factor. Vanadium pentoxide (V₂O₅) is a component of PM derived from fuel combustion as well as a source of occupational exposure in humans. In the current investigation we examined the influence of genetic background on susceptibility to V₂O₅-induced inflammation and evaluated whether V₂O₅functions as a tumor promoter using a 2-stage (initiation-promotion) model of pulmonary neoplasia in mice.</p> <p>Results</p> <p>A/J, BALB/cJ (BALB), and C57BL/6J (B6) mice were treated either with the initiator 3-methylcholanthrene (MCA; 10 μg/g; i.p.) or corn oil followed by 5 weekly aspirations of V₂O₅or PBS and pulmonary tumors were enumerated 20 weeks following MCA treatment. Susceptibility to V₂O₅-induced pulmonary inflammation was assessed in bronchoalveolar lavage fluid (BALF), and chemokines, transcription factor activity, and MAPK signaling were quantified in lung homogenates. We found that treatment of animals with MCA followed by V₂O₅promoted lung tumors in both A/J (10.3 ± 0.9 tumors/mouse) and BALB (2.2 ± 0.36) mice significantly above that observed with MCA/PBS or V₂O₅alone (<it>P </it>< 0.05). No tumors were observed in the B6 mice in any of the experimental groups. Mice sensitive to tumor promotion by V₂O₅were also found to be more susceptible to V₂O₅-induced pulmonary inflammation and hyperpermeability (A/J>BALB>B6). Differential strain responses in inflammation were positively associated with elevated levels of the chemokines KC and MCP-1, higher NFκB and c-Fos binding activity, as well as sustained ERK1/2 activation in lung tissue.</p> <p>Conclusions</p> <p>In this study we demonstrate that V₂O₅, an occupational and environmentally relevant metal oxide, functions as an <it>in vivo </it>lung tumor promoter among different inbred strains of mice. Further, we identified a positive relationship between tumor promotion and susceptibility to V₂O₅-induced pulmonary inflammation. These findings suggest that repeated exposures to V₂O₅containing particles may augment lung carcinogenesis in susceptible individuals through oxidative stress mediated pathways.</p

Stereotypies in the autism spectrum disorder: Can we rely on an ethological model?

Background: Stereotypic behaviour can be defined as a clear behavioural pattern where a specific function or target cannot be identified, although it delays on time. Nonetheless, repetitive and stereotypical behaviours play a key role in both animal and human behaviour. Similar behaviours are observed across species, in typical human developmental phases, and in some neuropsychiatric conditions, such as Autism Spectrum Disorder (ASD) and Intellectual Disability. This evidence led to the spread of animal models of repetitive behaviours to better understand the neurobiological mechanisms underlying these dysfunctional behaviours and to gain better insight into their role and origin within ASD and other disorders. This, in turn, could lead to new treatments of those disorders in humans. Method: This paper maps the literature on repetitive behaviours in animal models of ASD, in order to improve understanding of stereotypies in persons with ASD in terms of characterization, pathophysiology, genomic and anatomical factors. Results: Literature mapping confirmed that phylogenic approach and animal models may help to improve understanding and differentiation of stereotypies in ASD. Some repetitive behaviours appear to be interconnected and mediated by common genomic and anatomical factors across species, mainly by alterations of basal ganglia circuitry. A new distinction between stereotypies and autotypies should be considered. Conclusions: Phylogenic approach and studies on animal models may support clinical issues related to stereotypies in persons with ASD and provide new insights in classification, pathogenesis, and management

Efecto de la modificación del cociente foto-termal en el periodo crítico a causa de la época de siembra sobre el rendimiento de trigo en la región semiárida pampeana

En este trabajo se evaluó el efecto del cociente foto-termal (CFT) sobre el rendimiento del cultivo y el número de granos por m2 a través de la modificación de las fechas de siembra, en quince genotipos de trigo (Titicum aestivum L.). Se establecieron tres fechas de siembra con intervalos de treinta días, desde el 24 de mayo al 31 de julio del 2007. Se analizó la variación del cociente foto-termal en el cambio de la época de siembra y la humedad del suelo y se verificó la capacidad de predicción del mismo sobre el rendimiento en grano. Para los cálculos del cociente foto-termal se utilizó la metodología propuesta por Fischer (1985). El cociente foto-termalmostró escaso valor predictivo en la región semiárida pampeana tanto para el rendimiento en grano como para el número de granos por metro cuadrado. Los coeficientes de regresión entre el CFT y el rendimiento de grano fueron mayores para el riego (R2=0,321) que para secano (R2=0,095). Lo mismo ocurrió en el número de granos por m2, donde para riego el coeficiente de regresión fue de R2=0,404 y para secano R2=0,007, siendo estas demasiado bajas

Impact of lesion delineation and intensity quantisation on the stability of texture features from lung nodules on ct: A reproducible study

Computer-assisted analysis of three-dimensional imaging data (radiomics) has received a lot of research attention as a possible means to improve the management of patients with lung cancer. Building robust predictive models for clinical decision making requires the imaging features to be stable enough to changes in the acquisition and extraction settings. Experimenting on 517 lung lesions from a cohort of 207 patients, we assessed the stability of 88 texture features from the following classes: first-order (13 features), Grey-level Co-Occurrence Matrix (24), Grey-level Difference Matrix (14), Grey-level Run-length Matrix (16), Grey-level Size Zone Matrix (16) and Neighbouring Grey-tone Difference Matrix (five). The analysis was based on a public dataset of lung nodules and open-access routines for feature extraction, which makes the study fully reproducible. Our results identified 30 features that had good or excellent stability relative to lesion delineation, 28 to intensity quantisation and 18 to both. We conclude that selecting the right set of imaging features is critical for building clinical predictive models, particularly when changes in lesion delineation and/or intensity quantisation are involved

Immunogenicity of a Bivalent Adjuvanted Glycoconjugate Vaccine against Salmonella Typhimurium and Salmonella Enteritidis

Salmonella enterica serovars Typhimurium and Enteritidis are the predominant causes of invasive non-typhoidal Salmonella (iNTS) disease. Considering the co-endemicity of S. Typhimurium and S. Enteritidis, a bivalent vaccine formulation against both pathogens is necessary for protection against iNTS disease, thus investigation of glycoconjugate combination is required. In the present work, we investigated the immune responses induced by S. Typhimurium and S. Enteritidis monovalent and bivalent glycoconjugate vaccines adjuvanted with aluminum hydroxide (alum) only or in combination with cytosine-phosphorothioate-guanine oligodeoxynucleotide (CpG). Humoral and cellular, systemic and local, immune responses were characterized in two different mouse strains. All conjugate vaccines elicited high levels of serum IgG against the respective O-antigens (OAg) with bactericidal activity. The bivalent conjugate vaccine induced systemic production of antibodies against both S. Typhimurium and S. Enteritidis OAg. The presence of alum or alum + CpG adjuvants in vaccine formulations significantly increased the serum antigen-specific antibody production. The alum + CpG bivalent vaccine formulation triggered the highest systemic anti-OAg antibodies and also a significant increase of anti-OAg IgG in intestinal washes and fecal samples, with a positive correlation with serum levels. These data demonstrate the ability of monovalent and bivalent conjugate vaccines against S. Typhimurium and S. Enteritidis to induce systemic and local immune responses in different mouse strains, and highlight the suitability of a bivalent glycoconjugate formulation, especially when adjuvanted with alum + CpG, as a promising candidate vaccine against iNTS disease

Calidad microbiológica de hortalizas que se expenden en la Ciudad de Córdoba

El consumo de vegetales es una tendencia a nivel mundial en aumento. Particularmente, el consumo de hortalizas procesadas y envasadas está en expansión. Estos productos, son más perecederos que los vegetales intactos de los cuales proceden. Si el procesado no es realizado mediante Buenas Prácticas de Manufactura (BPM), pueden estar expuestos a diversas fuentes de contaminación durante el cultivo, cosecha, distribución o elaboración. Actualmente, la frecuencia de brotes de enfermedades transmitidas por alimentos (ETAs) asociadas al consumo de hortalizas se ha elevado como resultado de un incremento en el consumo. Esto es primordial porque las ETAs representan uno de los problemas de salud pública más importante. En este sentido, la Dirección de Calidad Alimentaria de la Municipalidad de Córdoba, realiza la vigilancia de hortalizas que se expenden en la ciudad para prevenir la aparición de ETAs. El Código Alimentario Argentino (CAA), mediante resolución vigente desde 2012 (art. 925 quater), recién exige el cumplimiento de ciertos parámetros microbiológicos para que estos alimentos sean considerados aptos. El objetivo fue evaluar la calidad microbiológica de hortalizas que se comercializan en el Mercado de Abasto y vegetales procesados y envasados que se expenden listos para el consumo en la ciudad de Córdoba. Se seleccionaron dos sitios de muestreo: el Mercado de Abasto (muestras de hortalizas mínimamente procesadas) y comercios (muestras de bandejas de hortalizas procesadas y envasadas). En el Mercado se tomaron 785 muestras y en comercios se obtuvieron 525 muestras y todos los muestreos se realizaron desde octubre de 2012 a diciembre de 2013. En cada muestra se determinó: a) Escherichia coli por NMP (BAM-FDA-2002) y b) Salmonella spp. (ISO 6579- 2002). En todos los casos se siguieron los criterios de muestreos establecidos según el CAA. Del total de muestras de hortalizas mínimamente procesadas (obtenidas del Mercado), sólo el 4,45 % fueron positivas para E. coli. En cambio, E. coli fue positiva en un 20,95 % de las muestras de bandejas obtenidas de los comercios. Los casos positivos para verduras mínimamente procesadas (Mercado) se encontraron siempre en los meses de verano (diciembre a marzo). En cambio, en el caso de las hortalizas en bandejas no hubo una asociación estacional con la detección de E. coli. En ninguno de los casos se detectó Salmonella spp. En conclusión, el mayor porcentaje de E. coli encontrado en hortalizas envasadas sugiere que las plantas elaboradoras de estos productos no están aplicando correctamente las BPM. Es crucial realizar en forma correcta el lavado y desinfección de las hortalizas, ya que reduce la carga microbiana inicial. Si esto no ocurre, los microorganismos seguirán multiplicándose durante el almacenamiento del producto hasta su consumo. Es necesario seguir con el control riguroso de las hortalizas, fortaleciendo los pilares de auditoría y capacitación en BPM y así evitar riesgos al consumidor.Fil: Manca, Liliana María. Universidad Nacional de Córdoba. Facultad de Odontología. Cátedra de Microbiología y Embriología; Argentina.Fil: Francavilla, A. Universidad Nacional de Córdoba; Argentina.Fil: Garcia-Ferreyra, C. Universidad Nacional de Córdoba; Argentina.Fil: Rondina, Alina. Municipalidad de Córdoba. Laboratorio de Alimentos; Argentina.Epidemiologí

Transcriptomic analysis of pathways regulated by toll-like receptor 4 in a murine model of chronic pulmonary inflammation and carcinogenesis

<p>Abstract</p> <p>Background</p> <p>Therapeutic strategies exist for human pulmonary neoplasia, however due to the heterogeneity of the disease, most are not very effective. The innate immunity gene, toll-like receptor 4 (TLR4), protects against chronic pulmonary inflammation and tumorigenesis in mice, but the mechanism is unclear. This study was designed to identify TLR4-mediated gene expression pathways that may be used as prognostic indicators of susceptibility to lung tumorigenesis in mice and provide insight into the mechanism.</p> <p>Methods</p> <p>Whole lung mRNA was isolated from C.C3H-<it>Tlr4</it>^{<it>Lps</it>-<it>d </it>}(BALB^{<it>Lps</it>-<it>d</it>}; <it>Tlr4 </it>mutant) and BALB/c (<it>Tlr4 </it>normal) mice following butylated hydroxytoluene (BHT)-treatment (four weekly ip. injections; 150-200 mg/kg/each; "promotion"). mRNA from micro-dissected tumors (adenomas) and adjacent uninvolved tissue from both strains were also compared 27 wks after a single carcinogen injection (3-methylcholanthrene (MCA), 10 μg/g; "control") or followed by BHT (6 weekly ip. injections; 125-200 mg/kg/each; "progression"). Bronchoalveolar lavage fluid was analyzed for inflammatory cell content and total protein determination, a marker of lung hyperpermeability; inflammation was also assessed using immunohistochemical staining for macrophages (F4/80) and lymphocytes (CD3) in mice bearing tumors (progression).</p> <p>Results</p> <p>During promotion, the majority of genes identified in the BALB^{<it>Lps</it>-<it>d </it>}compared to BALB/c mice (P < 0.05) were involved in epithelial growth factor receptor (EGFR) signaling (e.g. epiregulin (<it>Ereg</it>)), secreted phosphoprotein 1(<it>Spp1</it>)), which can lead to cell growth and eventual tumor development. Inflammation was significantly higher in BALB^{<it>Lps</it>-<it>d </it>}compared to BALB/c mice during progression, similar to the observed response during tumor promotion in these strains. Increases in genes involved in signaling through the EGFR pathway (e.g. <it>Ereg</it>, <it>Spp1</it>) were also observed during progression in addition to continued inflammation, chemotactic, and immune response gene expression in the BALB^{<it>Lps</it>-<it>d </it>}versus BALB/c mice (<it>P </it>< 0.05), which appears to provide more favorable conditions for cell growth and tumor development. In support of these findings, the BALB/c mice also had significantly reduced expression of many immune response and inflammatory genes in both the tumors and uninvolved tissue.</p> <p>Conclusion</p> <p>This transcriptomic study determined the protective effect of TLR4 in lung carcinogenesis inhibition of multiple pathways including EGFR (e.g. <it>Ereg</it>), inflammatory response genes (e.g. <it>Cxcl5)</it>, chemotaxis (e.g. <it>Ccr1</it>) and other cell proliferation genes (e.g. <it>Arg1</it>, <it>Pthlh</it>). Future studies will determine the utility of these pathways as indicators of immune system deficiencies and tumorigenesis.</p

Identification of Candidate Genes Downstream of TLR4 Signaling after Ozone Exposure in Mice: A Role for Heat-Shock Protein 70

Background: Toll-like receptor 4 (TLR4) is involved in ozone (O3)-induced pulmonary hyperpermeability and inflammation, although the downstream signaling events are unknown

INCONTINENCIA URINARIA DE ESFUERZO: COMPARACIÓN DE TRES ALTERNATIVAS QUIRÚRGICAS

Objetivo: Comparar tres técnicas quirúrgicas para el tratamiento de la incontinencia urinaria de esfuerzo (IOE), en pacientes con y sin cirugía de prolapso asociada. Material y métodos: Estudio retrospectivo de 393 pacientes con IOE, con o sin prolapso asociado, que fueron sometidas a corrección quirúrgica mediante alguna de las tres siguientes técnicas: 1) Cinta transobturatriz (TOT), 2) Colposuspensión de Burch (Burch) y 3) Cirugía por vía vaginal (CVV). Cuando hubo prolapso la corrección se asoció a histerectomía (HT), con o sin plastias según correspondiera. Resultados: La edad promedio, la paridad y el grado de prolapso de las pacientes sometidas a CVV fueron significativamente mayores en relación a las sometidas a TOT o Burch. Los tiempos operatorios y la estadía post operatoria promedio para TOT; Burch y CVV fueron 56,2 ± 26 min, 76,0 ± 53 min y 66,9 ± 21 min y 1,8 ± 0,7 días, 3,2 ± 1,3 días y 2,8±0,4 días siendo para TOT significativamente menor en relación a las otras dos técnicas. Hubo una tendencia no significativa a un menor número de complicaciones intra (4,2%, 6,5%, y 9,3%) y post operatorias inmediatas (25,0%, 34,9% y 44,2%) en el grupo de TOT. Conclusión: Nuestro trabajo sugiere que en relación a aspectos del intra y post operatorio inmediato el TOT es superior a CVV y a Burch en el tratamiento de la incontinencia urinaria de esfuerz