Prevention of organ allograft rejection by a specific Janus kinase 3 inhibitor

Because of its requirement for signaling by multiple cytokines, Janus kinase 3 (JAK3) is an excellent target for clinical immunosuppression. We report the development of a specific, orally active inhibitor of JAK3, CP-690,550, that significantly prolonged survival in a murine model of heart transplantation and in cynomolgus monkeys receiving kidney transplants. CP-690,550 treatment was not associated with hypertension, hyperlipidemia, or lymphoproliferative disease. On the basis of these preclinical results, we believe JAK3 blockade by CP-690,550 has potential for therapeutically desirable immunosuppression in human organ transplantation and in other clinical settings.     

The effects of porcine somatotropin and dietary lysine on growth performance and carcass characteristics of finishing swine

Seventy-two finishing pigs (initial weight = 57.6 kg) were utilized to determine the effects of porcine somatotropin (pST) and dietary lysine level on growth performance and carcass characteristics. Pigs were injected daily with 4 mg pST in the extensor muscle of the neck and fed either a pelleted corn-sesame meal diet (.6% lysine, 17.8% CP) or diets containing .8, 1.0, 1.2 or 1.4% lysine provided by additions of L-lysine.HCl. All diets were formulated to contain at least twice the required amounts of other amino acids. Control pigs received a placebo injection and the .6%-lysine diet. Increasing levels of dietary lysine resulted in increased ADG and improved feed conversion (quadratic, P less than .01) for pST-treated pigs. The calculated daily lysine intake was 16.6, 13.6, 19.6, 25.1, 29.6 and 33.6 g for the control and pST-treated pigs fed .6, .8, 1.0, 1.2 and 1.4% lysine, respectively, over the entire experiment. Breakpoint analysis indicated that cumulative ADG and feed conversion were optimized at 1.19 and 1.22% lysine, respectively. Longissimus muscle area and trimmed ham and loin weights increased as dietary lysine was increased among pST-treated pigs (quadratic, P less than .01). Breakpoint analysis indicated that 1.11% lysine maximized longissimus muscle area, whereas trimmed ham and loin weights were maximized at .91 and .98% lysine, respectively. Adjusted backfat thickness was not affected by dietary lysine, but pST-treated pigs had less backfat (P less than .05) than control pigs did. Percentage moisture of the longissimus muscle increased (linear, P less than .05), as did percentage CP (quadratic, P less than .05), whereas fat content decreased (linear, P less than .05) as lysine level increased. Similar trends in composition were observed for muscles of the ham (semimembranosus, semitendinosus, and biceps femoris). Shear-force values from the longissimus and semimembranosus were lowest for control pigs, but they increased as dietary lysine level increased among pST-treated pigs. Sensory panel evaluations indicated that juiciness and tenderness decreased (linear, P less than .05) as dietary lysine level increased. Plasma urea concentrations decreased linearly (P less than .01) on d 28 as lysine level increased, whereas plasma lysine and insulin were increased (quadratic, P less than .01). Plasma glucose and free fatty acid concentrations on d 28 tended to increase (quadratic, P less than .10) with increasing dietary lysine level.(ABSTRACT TRUNCATED AT 400 WORDS)     

Validation of the BioPRYN enzyme‐linked immunosorbent assay for detection of pregnancy‐specific protein‐B (PSPB) and diagnosis of pregnancy in American bison (Bison bison)

This study assessed the accuracy of the commercial BioPRYN^® ELISA for the detection of pregnancy‐specific protein‐B (PSPB) using a single blood sample to determine pregnancy status in American bison (Bison bison). A total of 49 bison cows were used in the study, and sampled at two time‐points during the gestation period, fall and spring, correlating with early‐ to mid‐term gestation (average 62.9 days post‐mating) and mid‐ to late‐term gestation (average 229.2 days post‐mating), respectively. Sensitivity of the test during early‐ to mid‐term gestation sampling period (fall) was 87.1%, while specificity was 100%; sensitivity of the test during late‐term gestation sampling period (spring) was 96.3%, while specificity remained at 100%. In total, the test showed a total sensitivity of 91.4%, specificity of 100% and total accuracy of 93.8%, similar to domestic cattle. Use of the single‐sample BioPRYN^® ELISA in American Bison for pregnancy diagnosis is economical and practical, minimizing animal handling time, frequency and subsequent stress while providing accurate results for pregnancy diagnosis at 62 days post‐mating. This method should be considered over more traditional pregnancy diagnosis methods for use in managed bison herds.     

Hormonal therapy for sows weaned during fall and winter

Sows from five commercial herds were weaned in the fall and winter and used to ascertain the potential application of hormonal therapy to stimulate subsequent litter size born. At weaning sows within parity (1, 2, and 3 through 6) and lactation length classification (early weaned, < or = 14 d; conventionally weaned, > 14 d) were randomly assigned to treatment. Treatments were injection with P.G. 600 (400 IU PMSG with 200 IU hCG) at weaning or no treatment. Sows were individually observed for estrus and mated following protocol for each herd. Breeding, culling, and farrowing data were collected. Treatment with P.G. 600 did not change subsequent rebreeding performance for sows at parity 1 or parities 3 through 6. However, conventionally weaned parity-2 sows treated with P.G. 600 were more likely (P < .05) to return to estrus than conventionally weaned controls (99.0 vs 93.6%, respectively). For parity-1 and parity-2 sows, treatment did not significantly change the likelihood for farrow percentage. However, the likelihood to farrow a litter was greater (P < .05) among P.G. 600-treated sows at parities 3 to 6 that were conventionally weaned (84.4 vs 71.3%, respectively). Subsequent litter birth weight for parity-1 sows treated with P.G. 600 was lower (P < .02) than for controls (15.6 vs 16.6 kg, respectively). Subsequent litter size at birth was not affected by treatment for parity-1 or parity-2 sows compared with controls. However, early-weaned sows at parities 3 through 6 treated with P.G. 600 had more (P < .06) total number born than controls (12.4 vs 10.6, respectively). Treatment with P.G. 600 improved reproductive function within specific parity and lactation length classification for sows weaned in the fall and winter.     

Community people-pet programs that work

Excellent models exist for people-pet programs in institutions and in the community. Veterinarians should assess the needs of their local communities and adapt a model program to fit these needs.     

Predicting summer fin whale distribution in the Pelagos Sanctuary (north-western Mediterranean Sea) to identify dynamic whale–vessel collision risk areas

1. Mediterranean fin whales aggregating in the Pelagos Sanctuary in summer to feed are exposed to vessel collision risk, particularly from high-speed ferries.
2. This study developed models to predict summer fin whale distribution using a generalized additive model (GAM) and MaxEnt, with the aim of providing a tool to identify potential high whale–ferry collision risk areas along ferry routes within the Pelagos Sanctuary during summertime.
3. Models were trained using sightings data collected in the summer months of 2009–2018 on board ferries crossing the central area of the Pelagos Sanctuary. Environmental predictors were bathymetry and mean sea surface chlorophyll concentration of the annual spring bloom period.
4. The predictive ability of GAM and MaxEnt was assessed using existing knowledge of summer fin whale distribution in the region. GAM (deviance explained = 20.2%) predictions matched documented distributions more closely than that of MaxEnt, with highest predicted fin whale occurrence in deep offshore waters (>2000 m) encompassing the central north-western and western regions, and in the south-eastern region, consistent with known fin whale habitats within the Pelagos Sanctuary. Inter-annual variability was evident, influencing collision risk areas.
5. Collision risk was estimated as a function of the overlap between the predicted probability of fin whale occurrence and ferry density estimated from Automated Identification System data. Ferry routes that cross the northern and eastern regions of the Pelagos Sanctuary presented relatively higher collision risk.
6. Areas with changes in risk intensity between the years were temporally and spatially dynamic: some appeared intermittently throughout the study period while others persisted over consecutive years or recurred in different years.
7. Due to the vastness of the Pelagos Sanctuary, vessel speed reduction maybe a more practical measure to manage collision risk than re-routing shipping lanes. A combination of Seasonal Management Areas and Dynamic Management Areas approaches could be adopted for high-risk areas.

     

Effects of intravenous administration of formaldehyde on platelet and coagulation variables in healthy horses

OBJECTIVES: To assess safety and determine effects of IV administration of formaldehyde on hemostatic variables in healthy horses. ANIMALS: 7 healthy adult horses. PROCEDURE: Clinical signs and results of CBC, serum biochemical analyses, and coagulation testing including template bleeding time (TBT) and activated clotting time (ACT) were compared in horses given a dose of 0.37% formaldehyde or lactated Ringer's solution (LRS), IV, in a 2-way crossover design. In a subsequent experiment, horses received an infusion of 0.74% formaldehyde or LRS. In another experiment, horses were treated with aspirin to impair platelet responses prior to infusion of formaldehyde or LRS. RESULTS: Significant differences were not detected in any variable measured between horses when given formaldehyde or any other treatment. Infusion of higher doses of formaldehyde resulted in adverse effects including muscle fasciculations, tachycardia, tachypnea, serous ocular and nasal discharge, agitation, and restlessness. CONCLUSIONS AND CLINICAL RELEVANCE: Intravenous infusion of formaldehyde at doses that do not induce adverse reactions did not have a detectable effect on measured hemostatic variables in healthy horses.