Genetics of equine bleeding disorders

Genetic bleeding disorders can have a profound impact on a horse's health and athletic career. As such, it is important to understand the mechanisms of these diseases and how they are diagnosed. These diseases include haemophilia A, von Willebrand disease, prekallikrein deficiency, Glanzmann's Thrombasthenia and Atypical Equine Thrombasthenia. Exercise-induced pulmonary haemorrhage also has a proposed genetic component. Genetic mutations have been identified for haemophilia A and Glanzmann's Thrombasthenia in the horse. Mutations are known for von Willebrand disease and prekallikrein deficiency in other species. In the absence of genetic tests, bleeding disorders are typically diagnosed by measuring platelet function, von Willebrand factor, and other coagulation protein levels and activities. For autosomal recessive diseases, genetic testing can prevent the breeding of two carriers.     

A Combination Chemotherapy Protocol (VELCAP-L) for Dogs with Lymphoma

Ninety-eight dogs with lymphoma treated with a 5-drug combination chemotherapy regimen (vincristine, L-asparaginase. cyclophosphamide, doxorubicin, prednisone [VELCAP-L]) were evaluated for pretreatment characteristics predictive for response and remission duration. The complete remission rate was 69%, with a median remission duration of 55 weeks. Dogs with advanced stage of disease, constitutional signs, dogs that were older, and dogs that were dyspneic were less likely to achieve remission. Once in remission, small dogs and dogs without pretreatment thrombocytopenia were likely to have longer remission duration. Toxicoses were frequent, but rarely fatal, and no predictitive factors were found for a dog developing toxicoses. VELCAP-L is an effective treatment for dogs in stage I-III lymphoma, particularly in young, small animals.     

A weight‐of‐evidence approach for defining thermal sensitivity in a federally endangered species

1. Managing for threatened and endangered species under changing environmental conditions is a challenge faced by resource managers worldwide. Lack of basic knowledge of the biology and habitat requirements of these species can contribute to this difficulty but is exacerbated by the limitations of working with rare species (i.e. few individuals) or unrefined and non‐lethal methods for evaluating stress.
2. A weight‐of‐evidence approach was used to evaluate the thermal biology of the federally endangered dwarf wedgemussel (Alasmidonta heterodon), using cumulative results from multiple experimental assessments, co‐occurring species, and their host fish to begin defining the thermal limits and optimal conditions for the species.
3. Results suggest that dwarf wedgemussel and its host fish are thermally sensitive species compared with other Atlantic‐slope mussels, with a lower critical thermal maximum (CTM) and the selection of reduced temperatures during choice experiments.
4. Physiological studies resulted in a lack of statistical significance, primarily owing to low power, which was a function of sample size – an unavoidable problem when studying rare species. Given these limitations, thermal choice and CTM may be more useful end points than physiological processes such as clearance and respiration rates when dealing with sample‐size limitations.
5. These results suggest that management strategies that avoid exposing dwarf wedgemussel and its thermally sensitive host fish to extreme temperatures could be important for species conservation.

     

Assessing common bottlenose dolphin (Tursiops truncatus) population structure in Mississippi Sound and coastal waters of the north central Gulf of Mexico

1. Population structure of highly mobile marine organisms can be complex and difficult to study, but it is important to understand how populations partition themselves within their environment for accurate assessment of both natural and anthropogenic impacts and successful management. The 2010 Deepwater Horizon oil spill negatively impacted common bottlenose dolphins (Tursiops truncatus) within Mississippi Sound and the surrounding north central Gulf of Mexico (GOMx); however, little was known about their underlying population structure in these waters. Thus, it was unclear how many demographically independent populations were affected by the spill.
2. Common bottlenose dolphin samples were collected throughout inshore waters of Mississippi Sound and coastal waters of the north-central GOMx. Mitochondrial DNA control region sequence data and 19 nuclear microsatellite loci were analysed to determine how many populations are present and characterize their range throughout these waters.
3. Bayesian clustering and migration analyses identified two genetically distinct and demographically independent populations: one predominantly inhabiting Mississippi Sound and adjacent coastal waters, and a second population extending generally from offshore of Mobile Bay, Alabama, east along the Florida Panhandle. Neither of these populations align with the currently delineated management stocks previously used to estimate impacts from the oil spill on common bottlenose dolphins in this portion of the GOMx.
4. These results suggest that revisions may be necessary so that management stocks accurately represent the demographically independent populations present in these waters. Furthermore, better comprehension of underlying population structure will enhance impact assessments on common bottlenose dolphins and provide more appropriate baseline data to support future restoration and conservation objectives.

     

Identification and characterization of the enzymes responsible for the metabolism of the non‐steroidal anti‐inflammatory drugs,flunixin meglumine and phenylbutazone,in horses

The in vivo metabolism and pharmacokinetics of flunixin meglumine and phenylbutazone have been extensively characterized; however, there are no published reports describing the in vitro metabolism, specifically the enzymes responsible for the biotransformation of these compounds in horses. Due to their widespread use and, therefore, increased potential for drug–drug interactions and widespread differences in drug disposition, this study aims to build on the limited current knowledge regarding P450‐mediated metabolism in horses. Drugs were incubated with equine liver microsomes and a panel of recombinant equine P450s. Incubation of phenylbutazone in microsomes generated oxyphenbutazone and gamma‐hydroxy phenylbutazone. Microsomal incubations with flunixin meglumine generated 5‐OH flunixin, with a kinetic profile suggestive of substrate inhibition. In recombinant P450 assays, equine CYP3A97 was the only enzyme capable of generating oxyphenbutazone while several members of the equine CYP3A family and CYP1A1 were capable of catalyzing the biotransformation of flunixin to 5‐OH flunixin. Flunixin meglumine metabolism by CYP1A1 and CYP3A93 showed a profile characteristic of biphasic kinetics, suggesting two substrate binding sites. The current study identifies specific enzymes responsible for the metabolism of two NSAIDs in horses and provides the basis for future study of drug–drug interactions and identification of reasons for varying pharmacokinetics between horses.     

Longevity of protective immunity to experimental bovine herpesvirus-1 infection following inoculation with a combination modified-live virus vaccine in beef calves

OBJECTIVE: To determine whether a combination viral vaccine containing modified-live bovine herpesvirus-1 (BHV-1) would protect calves from infection with a recent field isolate of BHV-1. DESIGN: Randomized controlled trial. ANIMALS: Sixty 4- to 6-month-old beef calves. PROCEDURE: Calves were inoculated with a placebo 42 and 20 days prior to challenge (group 1; n = 10) or with the combination vaccine 42 and 20 days prior to challenge (group 2; 10), 146 and 126 days prior to challenge (group 3; 10), 117 and 96 days prior to challenge (group 4; 10), 86 and 65 days prior to challenge (group 5; 10), or 126 days prior to challenge (group 6; 10). All calves were challenged with BHV-1 via aerosol. Clinical signs, immune responses, and nasal shedding of virus were monitored for 14 days after challenge. RESULTS: Vaccination elicited increases in BHV-1-specific IgG antibody titers. Challenge with BHV-1 resulted in mild respiratory tract disease in all groups, but vaccinated calves had less severe signs of clinical disease. Extent and duration of nasal BHV-1 shedding following challenge was significantly lower in vaccinated calves than in control calves. In calves that received 2 doses of the vaccine, the degree of protection varied with the interval between the last vaccination and challenge, as evidenced by increases in risk of clinical signs and extent and duration of viral shedding. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that this combination vaccine provided protection from infection with virulent BHV-1 and significantly reduced nasal shedding of the virus for at least 126 days after vaccination.     

Rapid,non-destructive carbon analysis of forest soils using neutron-induced gamma-ray spectroscopy

Forest soils are pivotal to understanding global carbon (C) cycling and evaluating policies for mitigating global change. However, they are very difficult to monitor because of the heterogeneity of soil characteristics, the difficulty of representative sampling, and the slow time scale of response to environmental change. Here we demonstrate that use of gamma-ray spectroscopy facilitates in situ non-destructive analysis of C and other elements in forest soils. In this approach the element-specific gamma-rays are induced by fast and thermal neutrons interacting with the nuclei of the elements present in the soil. Background gamma-rays emanating from naturally occurring radionuclides in the forest are recorded as well. We applied this approach in a mature northern hardwood forest on glacial till soils at the Bartlett Experimental Forest in New Hampshire, USA. The inelastic neutron scattering (INS) system yielded strong signals in gamma-ray counts/h, from C and other elements present in the soil matrix that included silicon, oxygen, hydrogen, iron, aluminum, manganese and potassium. The INS sensitivity for carbon was 20.656 counts h⁻¹ kg⁻¹ C m⁻² based on current net C gamma-ray counts and the data for the O horizon and mineral soil to a depth of 30 cm obtained from a nearby quantitative soil pit (7.35 kg C m⁻²). We estimate the minimum detectable change to be ∼0.34 kg C m⁻², which is ∼5% of the current soil C content, and the minimum detectable limit to be ∼0.23 kg C m⁻². Eight % reproducibility from 11 measurements was limited, in part, by the large variability in the system counting geometry due to the uneven forest microtopography. The INS approach has the potential to revolutionize belowground monitoring of C and other elements, because the possibility of detecting a 5% change in forest soils has not been possible with destructive sampling methods.