Lubiprostone ameliorates the cystic fibrosis mouse intestinal phenotype

<p>Abstract</p> <p>Background</p> <p>Cystic fibrosis (CF) is caused by mutations in the <it>CFTR </it>gene that impair the function of CFTR, a cAMP-regulated anion channel. In the small intestine loss of CFTR function creates a dehydrated, acidic luminal environment which is believed to cause an accumulation of mucus, a phenotype characteristic of CF. CF mice have small intestinal bacterial overgrowth, an altered innate immune response, and impaired intestinal transit. We investigated whether lubiprostone, which can activate the CLC2 Cl^-channel, would improve the intestinal phenotype in CF mice.</p> <p>Methods</p> <p><it>Cftr^tm1UNC</it>(CF) and wildtype (WT) littermate mice on the C57BL/6J background were used. Lubiprostone (10 μg/kg-day) was administered by gavage for two weeks. Mucus accumulation was estimated from crypt lumen widths in periodic acid-Schiff base, Alcian blue stained sections. Luminal bacterial load was measured by qPCR for the bacterial 16<it>S </it>gene. Gastric emptying and small intestinal transit in fasted mice were assessed using gavaged rhodamine dextran. Gene expression was evaluated by Affymetrix Mouse430 2.0 microarray and qRT-PCR.</p> <p>Results</p> <p>Crypt width in control CF mice was 700% that of WT mice (<it>P </it>< 0.001). Lubiprostone did not affect WT crypt width but, unexpectedly, increased CF crypt width 22% (<it>P </it>= 0.001). Lubiprostone increased bacterial load in WT mice to 490% of WT control levels (<it>P </it>= 0.008). Conversely, lubiprostone decreased bacterial overgrowth in CF mice by 60% (<it>P </it>= 0.005). Lubiprostone increased gastric emptying at 20 min postgavage in both WT (<it>P </it>< 0.001) and CF mice (<it>P </it>< 0.001). Lubiprostone enhanced small intestinal transit in WT mice (<it>P </it>= 0.024) but not in CF mice (<it>P </it>= 0.377). Among other innate immune markers, expression of mast cell genes was elevated 4-to 40-fold in the CF intestine as compared to WT, and lubiprostone treatment of CF mice decreased expression to WT control levels.</p> <p>Conclusions</p> <p>These results indicate that lubiprostone has some benefits for the CF intestinal phenotype, especially on bacterial overgrowth and the innate immune response. The unexpected observation of increased mucus accumulation in the crypts of lubiprostone-treated CF mice suggests the possibility that lubiprostone increases mucus secretion.</p

A preliminary proteomic characterisation of extracellular vesicles released by the ovine parasitic nematode, Teladorsagia circumcincta

AbstractTeladorsagia circumcincta is a major cause of ovine parasitic gastroenteritis in temperate climatic regions. The development of high levels of anthelmintic resistance in this nematode species challenges its future control. Recent research indicates that many parasite species release extracellular vesicles into their environment, many of which have been classified as endocytic in origin, termed exosomes. These vesicles are considered to play important roles in the intercellular communication between parasites and their hosts, and thus represent potentially useful targets for novel control strategies. Here, we demonstrate that exosome-like extracellular vesicles can be isolated from excretory-secretory (ES) products released by T. circumcincta fourth stage larvae (Tci-L4ES). Furthermore, we perform a comparative proteomic analysis of vesicle-enriched and vesicle-free Tci-L4ES. Approximately 73% of the proteins identified in the vesicle-enriched fraction were unique to this fraction, whilst the remaining 27% were present in both vesicle-enriched and vesicle-free fraction. These unique proteins included structural proteins, nuclear proteins, metabolic proteins, proteolytic enzymes and activation-associated secreted proteins. Finally, we demonstrate that molecules present within the vesicles-enriched material are targets of the IgA and IgG response in T. circumcincta infected sheep, and could potentially represent useful targets for future vaccine intervention studies

Energy efficient network equipment for data centers

The dynamic development of IT performance combined with a growing demand of ICT services in public and private sectors is resulting in an increasing energy consumption of centralized IT equipment in data centers. Nevertheless, energy efficiency measurements for data centers today are still focusing mainly on cooling and power supply infrastructure. Therefore, the main goal of the Intelligent Energy Europe project PrimeEnergyIT is to enhance the market demand for energy efficient IT in data center, including server, storage and network equipment as well as new cooling and power management technologies. Compared to server and storage equipment the energy consumption allocated to networking equipment has a rather low impact with approximately 8 to 12 percent of the total data centers. With respect to the ongoing tremendous shift towards a centralized production of applications through the implementation of new concepts, such as e 'cloud computing' or virtualization, this w ill result in increased traffic volumes and performance requirements. This paper will present horizontal approaches as well as equipment related aspects to reduce the power consumption of data center networks

Increasing CO2 from subambient to superambient concentrations alters species composition and increases above-ground biomass in a C3/C4 grassland

The glacial-to-present increase in atmospheric CO2 concentration is likely to have stimulated plant production, but experimental tests in natural ecosystems are lacking

Procurement guidance for energy efficient server room and data centre equipment

Deliverable of the PrimeEnergyIT European projec

Diagnostic approach and management of cow's milk protein allergy in infants and children

OBJECTIVES:: This position paper provides recommendations for the diagnosis and management of suspected cow's milk protein allergy (CMPA) in Europe. It presents a practical approach with a diagnostic algorithm and is based on recently published evidence based guidelines on CMPA. DIAGNOSIS:: If CMPA is suspected by history and examination, strict allergen avoidance is initiated. In certain circumstances (e.g. a clear history of immediate symptoms or a life threatening reaction with a positive test for cow's milk protein (CMP) specific IgE) the diagnosis can be made without a milk challenge. In all other circumstances, a controlled oral food challenge (open or blind) under medical supervision is required to confirm or exclude the diagnosis CMPA. TREATMENT:: In breast-fed infants, the mother should start a strict CMP-free diet. Non-breast fed infants with confirmed CMPA should receive an extensively hydrolyzed protein based formula with proven efficacy in appropriate clinical trials; amino acids based formulae are reserved for certain situations. Soy protein formula, if tolerated, is an option beyond 6 months of age. Nutritional counseling and regular monitoring of growth is mandatory in all age groups requiring CMP exclusion. RE-EVALUATION:: Patients should be re-evaluated every 6-12 months to assess whether they have developed tolerance to CMP. This is achieved in >75% by three years and >90% by six years of age. Inappropriate or overly long dietary eliminations should be avoided. Such restrictions may impair the quality of life of both child and family, induce improper growth, and also incur unnecessary healthcare costs

Birch pollen rupture and the release of aerosols of respirable allergens

Backgound Birch pollen allergens have been implicated as asthma triggers; however, pollen grains are too large to reach the lower airways where asthmatic reactions occur. Respirable-sized particles containing birch pollen allergens have been detected in air filters, especially after rainfall but the source of these particles has remained speculative.Objective To determine the processes by which birch pollen allergens become airborne particles of respirable size with the potential to contribute to airways inflammation.Methods Branches with attached male catkins were harvested and placed in a controlled emission chamber. Filtered dry air was passed through the chamber until the anthers opened, then they were humidified for 5 h and air-dried again. Flowers were disturbed by wind generated from a small electric fan. Released particles were counted, measured and collected for immuno-labelling and high-resolution microscopy.Results Birch pollen remains on the dehisced anther and can rupture in high humidity and moisture. Fresh pollen takes as long as 3 h to rupture in water. Drying winds released an aerosol of particles from catkins. These were fragments of pollen cytoplasm that ranged in size from 30 nm to 4 &mu;m and contained Bet v 1 allergens.Conclusion When highly allergenic birch trees are flowering and exposed to moisture followed by drying winds they can produce particulate aerosols containing pollen allergens. These particles are small enough to deposit in the peripheral airways and have the potential to induce an inflammatory response.<br /