Antimicrobial Use on 36 Beef Feedlots in Western Canada: 2008-2012.

The accurate quantification of antimicrobial use (AMU) in production animals is critical for monitoring trends in exposure to antimicrobial drugs (AMD) over time and examining potential associations with antimicrobial resistance in bacteria. In this study, a census sample of cattle was used to quantify individually-dosed and in-feed AMU as both numbers of animal daily doses (nADD) and total grams of AMD (gAMD) used in cattle placed in 36 western Canadian feedlots between 1-November, 2008 and 31-October, 2012; representing about 21.5% of fed cattle in Canada during that time period. Of the ~2.6 million cattle placed during the 48-month period, 45% were calves, 63% were male, 62% arrived in the fall or winter, and 39% were assessed as high risk for developing bovine respiratory disease (BRD). The proportion of cattle categorized as high risk (HR) for developing BRD was consistent over the 4 years of placement cohorts. Both medically important AMU and ionophore use were summarized but presented separately. A decrease in AMU was observed over the study period, both as nADD and total gAMD, which was primarily driven by a decline in the in-feed administration of tetracyclines. Most in-feed AMU was directed toward prevention and control of liver abscesses. The majority of individually dosed AMU was administered as metaphylaxis to address BRD risks, with category III AMD (medium importance to human medicine as categorized by Health Canada Veterinary Drugs Directorate) used most frequently. Not surprisingly, risk level for developing BRD influenced parenteral AMD exposures, with 95% of cattle categorized as being HR for developing BRD receiving individually dosed AMD compared to 59% of cattle categorized as being low risk (LR) for developing BRD. Cattle categorized as HR for developing BRD were more likely to receive macrolides for BRD metaphylaxis compared to cattle categorized as LR for developing BRD, and cattle categorized as LR for developing BRD were more likely to receive tetracycline for the same purpose. In summary, these data provide an unprecedented representation of AMU in fed cattle in western Canada and direction for future monitoring of AMU in fed cattle.

Intracoronary allogeneic cardiosphere-derived stem cells are safe for use in dogs with dilated cardiomyopathy.

Cardiosphere-derived cells (CDCs) have been shown to reduce scar size and increase viable myocardium in human patients with mild/moderate myocardial infarction. Studies in rodent models suggest that CDC therapy may confer therapeutic benefits in patients with non-ischaemic dilated cardiomyopathy (DCM). We sought to determine the safety and efficacy of allogeneic CDC in a large animal (canine) model of spontaneous DCM. Canine CDCs (cCDCs) were grown from a donor dog heart. Similar to human CDCs, cCDCs express CD105 and are slightly positive for c-kit and CD90. Thirty million of allogeneic cCDCs was infused into the coronary vessels of Doberman pinscher dogs with spontaneous DCM. Adverse events were closely monitored, and cardiac functions were measured by echocardiography. No adverse events occurred during and after cell infusion. Histology on dog hearts (after natural death) revealed no sign of immune rejection from the transplanted cells.

Microstructure and elution of tetracycline from block copolymer coatings.

A critical metrology issue for pharmaceutical industries is the application of analytical techniques for the characterization of drug delivery systems to address interrelationships between processing, structure, and drug release. In this study, cast coatings were formed from solutions of poly(styrene-b-isobutylene-b-styrene) (SIBS) and tetracycline in tetrahydrofuran (THF). These coatings were characterized by several imaging modalities, including time-of-flight secondary ion mass spectrometry (TOF-SIMS) for chemical imaging and analysis, atomic force microscopy (AFM) for determination of surface structure and morphology, and laser scanning confocal microscopy (LSCM), which was used to characterize the three-dimensional structure beneath the surface. The results showed phase separation between the drug and copolymer regions. The size of the tetracycline phase in the polymer matrix ranged from hundreds of nanometers to tens of microns, depending on coating composition. The mass of drug released was not found to be proportional to drug loading, because the size and spatial distribution of the drug phase varied with drug loading and solvent evaporation rate, which in turn affected the amount of drug released.

Ankyrin G overexpression in Hutchinson-Gilford progeria syndrome fibroblasts identified through biological filtering of expression profiles.

Hutchinson-Gilford progeria syndrome (HGPS; MIM 176670) is a rare disease characterized by accelerated aging. In this study, light and immunofluorescence microscopy were used to assess morphological changes, measures of cell growth kinetics and gene expression profiles in HGPS cells and normal fibroblasts in culture. A filtering strategy was developed based on differentially expressed transcripts seen consistently across three culture stages based on cell passage number. This filtering strategy produced a list of 66 unique differentially expressed genes, of which approximately 40% were upregulated in HGPS cells compared to normal fibroblasts. The increased mRNA expression in HGPS cells that was seen for one gene defined using this strategy--namely ANK3--was validated using quantitative reverse-transcriptase amplification, Western analysis and immunofluorescence microscopy, all of which showed significantly increased ankyrin G expression. These findings demonstrate differences in morphology, growth kinetics and mRNA expression profiles in HGPS cells compared to normal fibroblasts in culture, including increased expression of ANK3/ankyrin G. Furthermore, other genes that co-clustered with ANK3 might provide mechanistic clues regarding senescence in cultured HGPS cells.

Mechanical properties of biomimetic tissue adhesive based on the microbial transglutaminase-catalyzed crosslinking of gelatin.

Fibrin sealants are a type of soft tissue adhesive that employs biochemical reactions from the late stages of the blood coagulation cascade. Intrinsic to these adhesives are a structural protein and a transglutaminase crosslinking enzyme. We are investigating an alternative biomimetic adhesive based on gelatin and a calcium-independent microbial transglutaminase (mTG). Rheological measurements show that mTG catalyzes the conversion of gelatin solutions into hydrogels, and gel times are on the order of minutes depending on the gelatin type and concentration. Tensile static and dynamic loading of the adhesive hydrogels in bulk form demonstrated that the Young's modulus ranged from 15 to 120 kPa, and these bulk properties were comparable to those reported for hydrogels obtained from fibrin-based sealants. Lap-shear adhesion tests of porcine tissue were performed using a newly published American Society for Testing and Materials (ASTM) standard for tissue adhesives. The gelatin-mTG adhesive bound the opposing tissues together with ultimate adhesive strengths of 12-23 kPa which were significantly higher than the strength observed for fibrin sealants. Even after failure, strands of the gelatin-mTG adhesive remained attached to both of the opposing tissues. These results suggest that gelatin-mTG adhesives may offer the benefits of fibrin sealants without the need for blood products.