Protective Effects of Protegrin in Dextran Sodium Sulfate-Induced Murine Colitis

Cathelicidins, a class of antimicrobial peptides, have been widely studied for their antimicrobial role in innate immune responses during infection and inflammation. At sub-antimicrobial concentrations, various cathelicidins from different species have been reported to exert chemotactic activity on neutrophils, monocytes, dendritic cells and T-cells, and also enhance angiogenesis and wound healing. To date, the role of the pig cathelicidin, protegrin-1 (PG-1), in immune modulation and tissue repair in the intestinal tract has not been investigated. The aim of the present study was to examine the potential protective effects of recombinant PG-1 in a mouse dextran sodium sulfate (DSS)-induced colitis inflammation model. This is the first report showing the protective effects of PG-1 in its various forms (pro-, cathelin-, and mature-forms) in attenuating significant body weight loss associated with DSS-induced colitis (p < 0.05). PG-1 treatment improved histological scores (P < 0.05) and influenced the gene expression of inflammatory mediators and tissue repair factors such as trefoil factor 3 (TFF3) and mucin (MUC-2). Protegrin treatment also altered the metabolite profile, returning the metabolite levels closer to untreated control levels. These findings lay the foundation for future oral application of recombinant PG-1 to potentially treat intestinal damage and inflammation

Observational Study Design in Veterinary Pathology, Part 1: Study Design

Observational studies are the basis for much of our knowledge of veterinary pathology and are highly relevant to the daily practice of pathology. However, recommendations for conducting pathology-based observational studies are not readily available. In part 1 of this series, we offer advice on planning and conducting an observational study with examples from the veterinary pathology literature. Investigators should recognize the importance of creativity, insight, and innovation in devising studies that solve problems and fill important gaps in knowledge. Studies should focus on specific and testable hypotheses, questions, or objectives. The methodology is developed to support these goals. We consider the merits and limitations of different types of analytic and descriptive studies, as well as of prospective vs retrospective enrollment. Investigators should define clear inclusion and exclusion criteria and select adequate numbers of study subjects, including careful selection of the most appropriate controls. Studies of causality must consider the temporal relationships between variables and the advantages of measuring incident cases rather than prevalent cases. Investigators must consider unique aspects of studies based on archived laboratory case material and take particular care to consider and mitigate the potential for selection bias and information bias. We close by discussing approaches to adding value and impact to observational studies. Part 2 of the series focuses on methodology and validation of methods

The BLAST Survey of the Vela Molecular Cloud: Physical Properties of the Dense Cores in Vela-D

The Balloon-borne Large-Aperture Submillimeter Telescope (BLAST) carried out a 250, 350 and 500 micron survey of the galactic plane encompassing the Vela Molecular Ridge, with the primary goal of identifying the coldest dense cores possibly associated with the earliest stages of star formation. Here we present the results from observations of the Vela-D region, covering about 4 square degrees, in which we find 141 BLAST cores. We exploit existing data taken with the Spitzer MIPS, IRAC and SEST-SIMBA instruments to constrain their (single-temperature) spectral energy distributions, assuming a dust emissivity index beta = 2.0. This combination of data allows us to determine the temperature, luminosity and mass of each BLAST core, and also enables us to separate starless from proto-stellar sources. We also analyze the effects that the uncertainties on the derived physical parameters of the individual sources have on the overall physical properties of starless and proto-stellar cores, and we find that there appear to be a smooth transition from the pre- to the proto-stellar phase. In particular, for proto-stellar cores we find a correlation between the MIPS24 flux, associated with the central protostar, and the temperature of the dust envelope. We also find that the core mass function of the Vela-D cores has a slope consistent with other similar (sub)millimeter surveys.Comment: Accepted for publication in the Astrophysical Journal. Data and maps are available at http://blastexperiment.info

Proteomic 2D-DIGE Analysis of Milk Whey from Dairy Cows with Staphylococcus aureus Mastitis Reveals Overexpression of Host Defense Proteins

Bovine mastitis remains a primary focus of dairy cattle disease research due to its considerable negative economic impact on the dairy industry. Subclinical mastitis (SCM), commonly caused by Staphylococcus aureus, lacks overt clinical signs and the diagnosis is based on bacteriological culture and somatic cell counts of milk, both of which have limitations. The main objective of this study was to identify, characterize and quantify the differential abundance of milk whey proteins from cows with S. aureus SCM compared to whey from healthy cows. Using two-dimensional differential gel electrophoresis (2D-DIGE) coupled with liquid chromatography and tandem mass spectrometry, 28 high-abundant proteins were detected in whey from mastitic milk, 9 of which had host defense functions. These included acute phase proteins involved in innate immunity and antimicrobial functions (e.g., serotransferrin, complement C3, fibrinogen gamma-B chain and cathepsin B), and proteins associated with the immune response to pathogens (e.g., polymeric immunoglobulin receptor-like protein, MHC class I antigen and beta-2-microglobulin). These results provide a unique 2D map of the modulated milk proteome during S. aureus mastitis. The broader importance is that the identified proteins, particularly those with host-defense biological functions, represent potential candidate biomarkers of subclinical mastitis in dairy cows

Protective and Anti-Inflammatory Effects of Protegrin-1 on Citrobacter rodentium Intestinal Infection in Mice

Infectious intestinal colitis, manifesting as intestinal inflammation, diarrhea, and epithelial barrier disruption, affects millions of humans worldwide and, without effective treatment, can result in death. In addition to this, the significant rise in antibiotic-resistant bacteria poses an urgent need for alternative anti-infection therapies for the treatment of intestinal disorders. Antimicrobial peptides (AMPs) are potential therapies that have broad-spectrum antimicrobial activity due to their (1) unique mode of action, (2) broad-spectrum antimicrobial activity, and (3) protective role in GI tract maintenance. Protegrin-1 (PG-1) is an AMP of pig origin that was previously shown to reduce the pathological effects of chemically induced digestive tract inflammation (colitis) and to modulate immune responses and tissue repair. This study aimed to extend these findings by investigating the protective effects of PG-1 on pathogen-induced colitis in an infection study over a 10-day experimental period. The oral administration of PG-1 reduced Citrobacter rodentium intestinal infection in mice as evidenced by reduced histopathologic change in the colon, prevention of body weight loss, milder clinical signs of disease, and more effective clearance of bacterial infection relative to challenged phosphate-buffered saline (PBS)-treated mice. Additionally, PG-1 treatment altered the expression of various inflammatory mediators during infection, which may act to resolve inflammation and re-establish intestinal homeostasis. PG-1 administered in its mature form was more effective relative to the pro-form (ProPG-1). To our knowledge, this is the first study demonstrating the protective effects of PG-1 on infectious colitis