Immune sensitization of equine bronchus: glutathione, IL-1β expression and tissue responsiveness

BACKGROUND: Increasing clinical epidemiological and experimental evidence indicates that excess of production of reactive oxygen free radicals (ROS) induced by an oxidative stress is involved in the pathogenesis of a number of human airway disorders, as well as equine recurrent airway obstruction. Free-radicals modulate the activation of transcription factors, such as nuclear factor-(NF)-κB and activator protein (AP)-1, in several different cells. This activation leads to expression of many pro-inflammatory cytokines, including interleukin (IL)-1β. We have hypothesized that equine airway sensitization might induce an oxidative stress and increase the ROS production, which in turn might enhance a production of IL-1β and airway hyperresponsiveness. METHODS: We have examined the effect of passive sensitization on IL-1β mRNA expression and electrical field stimulation (EFS)-induced contraction in equine isolated bronchi, and the potential interference of reduced-glutathione (GSH), an antioxidant, with these responses. Bronchi passively sensitized with serum from animals suffering from heaves and having high total level of IgE, and control tissues, either pretreated or not with GSH (100 μM), were used to quantify IL-1β mRNA. Other tissues were used to study the effect of EFS (3–10–25 Hz). RESULTS: Mean IL-1β mRNA expression was higher in passively sensitized than in control rings. GSH significantly (p < 0.05) reduced the IL-1β mRNA expression only in passively sensitized bronchi. ELF induced a frequency-dependent contraction in both non-sensitized and passively sensitized tissues, with a significantly greater response always observed in sensitized tissues. GSH did not modify the EFS-induced contraction in non-sensitized bronchi, but significantly (p < 0.05) decreased it in passively sensitized tissues. CONCLUSION: Our data indicate that the passive sensitization of equine bronchi induces inflammation and hyperresponsiveness. These effects might be due to an oxidative stress because a pretreatment with GSH decreased the increased IL-1β mRNA expression and responsiveness to EFS of passively sensitized bronchi

The type and frequency of interactions that occur between staff and children outside in Early Years Foundation Stage settings during a fixed playtime period when there are tricycles available

This study reports on an investigation into adult and child interactions observed in the outdoor play environment in four Local Authority early years foundation stage settings in England. In this instance the common two features across the settings were the presence of tricycles and a timetabled outdoor play period. In total, across the four schools, there were 204 children. The study aimed to gain an understanding of the nature of the dialogues between staff and children, that is, the types of exchange that occurred when either the child approached an adult or the adult approached a child. The most frequent type of utterance was also analysed. The study concludes that adults in these settings spoke more than children and the greatest type of utterance was that of the adult about domestic matters. When the child initiated the conversation there were more extended child utterances than domestic utterances. This may suggest that children wish to be involved in conversations of depth and meaning and that staff need to become aware of how to develop this conversational language with children

Plant-Derived Polysaccharide Supplements Inhibit Dextran Sulfate Sodium-Induced Colitis in the Rat

Several plant-derived polysaccharides have been shown to have anti-inflammatory activity in animal models. Ambrotose complex and Advanced Ambrotose are dietary supplements that include aloe vera gel, arabinogalactan, fucoidan, and rice starch, all of which have shown such activity. This study was designed to evaluate these formulations against dextran sulfate sodium (DSS)-induced colitis in rats and to confirm their short-term safety after 14 days of daily dosing. Rats were dosed daily orally with vehicle, Ambrotose or Advanced Ambrotose. On day six groups of rats received tap water or 5% Dextran Sulfate sodium. Ambrotose and Advanced Ambrotose significantly lowered the disease scores and partially prevented the shortening of colon length. An increase in monocyte count was induced by dextran sulfate sodium and inhibited by Ambrotose and Advanced Ambrotose. There were no observable adverse effects after 14-day daily doses. The mechanism of action of the formulations against DSS-induced colitis may be related to its effect on monocyte count

Contrasting patterns of selection between MHC I and II across populations of Humboldt and Magellanic penguins

The evolutionary and adaptive potential of populations or species facing an emerginginfectious disease depends on their genetic diversity in genes, such as the major histocompatibilitycomplex (MHC). In birds, MHC class I deals predominantly with intracellularinfections (e.g., viruses) and MHC class II with extracellular infections (e.g.,bacteria). Therefore, patterns of MHC I and II diversity may differ between species andacross populations of species depending on the relative effect of local and global environmentalselective pressures, genetic drift, and gene flow. We hypothesize thathigh gene flow among populations of Humboldt and Magellanic penguins limits localadaptation in MHC I and MHC II, and signatures of selection differ between markers,locations, and species. We evaluated the MHC I and II diversity using 454 next-generationsequencing of 100 Humboldt and 75 Magellanic penguins from seven differentbreeding colonies. Higher genetic diversity was observed in MHC I than MHCII for both species, explained by more than one MHC I loci identified. Large populationsizes, high gene flow, and/or similar selection pressures maintain diversity but limitlocal adaptation in MHC I. A pattern of isolation by distance was observed for MHC IIfor Humboldt penguin suggesting local adaptation, mainly on the northernmost studiedlocality. Furthermore, trans-speciesalleles were found due to a recent speciationfor the genus or convergent evolution. High MHC I and MHC II gene diversity describedis extremely advantageous for the long-termsurvival of the species.Fil: Sallaberry Pincheira, Nicole. Pontificia Universidad Católica de Chile; Chile. Universidad Andrés Bello; ChileFil: González Acuña, Daniel. Universidad de Concepción; ChileFil: Padilla, Pamela Solange. Pontificia Universidad Católica de Chile; ChileFil: Dantas, Gisele P. M.. Pontificia Universidade Catolica de Minas Gerais.; BrasilFil: Luna Jorquera, Guillermo. Universidad Católica del Norte; ChileFil: Frere, Esteban. Universidad Nacional de la Patagonia Austral. Unidad Académica Caleta Olivia. Centro de Investigaciones Puerto Deseado; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Valdés Velásquez, Armando. Universidad Peruana Cayetano Heredia; PerúFil: Vianna, Juliana A.. Pontificia Universidad Católica de Chile; Chil

A Novel Multi-Antigen Virally Vectored Vaccine against Mycobacterium avium Subspecies paratuberculosis

BACKGROUND: Mycobacterium avium subspecies paratuberculosis causes systemic infection and chronic intestinal inflammation in many species including primates. Humans are exposed through milk and from sources of environmental contamination. Hitherto, the only vaccines available against Mycobacterium avium subspecies paratuberculosis have been limited to veterinary use and comprised attenuated or killed organisms. METHODS: We developed a vaccine comprising a fusion construct designated HAV, containing components of two secreted and two cell surface Mycobacterium avium subspecies paratuberculosis proteins. HAV was transformed into DNA, human Adenovirus 5 (Ad5) and Modified Vaccinia Ankara (MVA) delivery vectors. Full length expression of the predicted 95 kDa fusion protein was confirmed. PRINCIPAL FINDINGS: Vaccination of naïve and Mycobacterium avium subspecies paratuberculosis infected C57BL/6 mice using DNA-prime/MVA-boost or Ad5-prime/MVA-boost protocols was highly immunogenic resulting in significant IFN-gamma ELISPOT responses by splenocytes against recombinant vaccine antigens and a range of HAV specific peptides. This included strong recognition of a T-cell epitope GFAEINPIA located near the C-terminus of the fusion protein. Antibody responses to recombinant vaccine antigens and HAV specific peptides but not GFAEINPIA, also occurred. No immune recognition of vaccine antigens occurred in any sham vaccinated Mycobacterium avium subspecies paratuberculosis infected mice. Vaccination using either protocol significantly attenuated pre-existing Mycobacterium avium subspecies paratuberculosis infection measured by qPCR in spleen and liver and the Ad5-prime/MVA-boost protocol also conferred some protection against subsequent challenge. No adverse effects of vaccination occurred in any of the mice. CONCLUSIONS/SIGNIFICANCE: A range of modern veterinary and clinical vaccines for the treatment and prevention of disease caused by Mycobacterium avium subspecies paratuberculosis are needed. The present vaccine proved to be highly immunogenic without adverse effect in mice and both attenuated pre-existing Mycobacterium avium subspecies paratuberculosis infection and conferred protection against subsequent challenge. Further studies of the present vaccine in naturally infected animals and humans are indicated

Endothelin 1 levels in relation to clinical presentation and outcome of Henoch Schonlein purpura

<p>Abstract</p> <p>Background</p> <p>Henoch Schonlein purpura (HSP) is a common vasculitis of small vessels whereas endothelin-1 (ET-1) is usually reported elevated in vasculities and systematic inflammation. The aim of the present study was to investigate whether ET-1 levels are correlated with the clinical presentation and the outcome of HSP.</p> <p>Methods</p> <p>The study sample consisted of thirty consecutive patients with HSP. An equal number of healthy patients of similar age and the same gender were served as controls. The patients' age range was 2–12.6 years with a mean ± SD = 6.3 ± 3 years. All patients had a physical examination with a renal, and an overall clinical score. Blood and urinary biochemistry, immunology investigation, a skin biopsy and ET-1 measurements in blood and urine samples were made at presentation, 1 month later and 1 year after the appearance of HSP. The controls underwent the same investigation with the exception of skin biopsy.</p> <p>Results</p> <p>ET-1 levels in plasma and urine did not differ between patients and controls at three distinct time points. Furthermore the ET-1 were not correlated with the clinical score and renal involvement was independent from the ET-1 measurements. However, the urinary ET-1 levels were a significant predictor of the duration of the acute phase of HSP (HR = 0.98, p = 0.032, CI0.96–0.99). The ET-1 levels did not correlate with the duration of renal involvement.</p> <p>Conclusion</p> <p>Urinary ET-1 levels are a useful marker for the duration of the acute phase of HSP but not for the length of renal involvement.</p

Perceptions of mixed-race

The psychology of race is in its infancy, particularly in the United Kingdom and especially regarding mixed-race. Most use untimed explicit indexes and qualitative/self-report measures. Here, we used not only explicit responses (participants’ choice of response categories) but also implicit data (participants’ response times, RT). In a Stroop task, 92 Black, White, and mixed-race participants classified photographs of mixed-race persons. Photos were accompanied by a word, such as Black or White. Participants ignored the word, simply deciding whether to categorize photos as White or Black. Averaged across three different instructional sets, White participants categorized mixed-race slightly to the White side of the center point, with Black participants doing the converse. Intriguingly, mixed-race participants placed mixed-race photos further toward Black than did the Black group. But for RT, they now indicated midway between White and Black participants. We conclude that at the conscious (key-press) level, mixed-race persons see being mixed-race as Black, but at the unconscious (RT) level, their perception is a perfect balance between Black and White. Findings are discussed in terms of two recent theories of racial identity