Comparison of various doses of carbon 13-labeled aminopyrine for a carbon 13-labeled aminopyrine demethylation blood test in healthy dogs

OBJECTIVE: To determine an optimal dose of carbon 13 ((13)C)-labeled aminopyrine for use in a (13)C-aminopyrine demethylation blood test in healthy dogs. ANIMALS: 9 adult dogs. PROCEDURES: Food was withheld from each dog for 12 hours. A 2-mL baseline blood sample was obtained from each dog and placed into an evacuated tube containing sodium heparin. Carbon 13-labeled aminopyrine was administered IV at doses of 1, 2, 5, or 10 mg/kg. Additional blood samples (2 mL) were obtained and placed into evacuated tubes containing sodium heparin 30, 45, 60, and 75 minutes after (13)C-aminopyrine administration. Hydrochloric acid was used to extract CO(2) from blood samples. The extracted gas was analyzed by fractional mass spectrometry to determine the percentage dose of (13)C administered as (13)C-aminopyrine and recovered in extracted gas (PCD). RESULTS: Gross evidence of clinical adverse effects was not detected in any dog after administration of (13)C-aminopyrine. The mean coefficient of variation (CV) for PCD was significantly lower than the mean CV for the summation of PCD values up to a given sampling time (CUMPCD). Mean PCD values among the 4 doses for each sample time were not significantly different. Administration of (13)C-aminopyrine at a dose of 2 mg/kg resulted in the lowest interindividual variability. CONCLUSIONS AND CLINICAL RELEVANCE: The PCD is superior to CUMPCD for the quantification of aminopyrine demethylation. Administration of (13)C-(13)C-aminopyrine at a dose of 2 mg/kg is appropriate for use in the (13)C-aminopyrine demethylation blood test in healthy dogs.     

Serum complement activity in the three-toed amphiuma (Amphiuma tridactylum)

Some animals routinely endure serious injuries from predators or during intraspecific territorial conflicts. Such is the case for Amphiuma tridactylum, an aquatic salamander that lives in an environment rich in potentially infectious microbes, apparently with rare or no pathogenic infection. Some vertebrates possess innate immune mechanisms, but whether this is the case for Amphiuma is unknown. To assess this potential, plasma from 19 A. tridactylum was pooled and used for characterisation of serum complement activity. The ability of A. tridactylum plasma to hemolyse unsensitised sheep red blood cells (SRBCs) was titer-dependent, with low activity observed even at high plasma titers. The kinetic characterisation of SRBC hemolysis revealed that significant activity could be measured within 10 min of incubation, and maximal activity occurred within 60 min. The SRBC hemolysis by A. tridactylum plasma was also temperature-dependent, with maximal activity at 30 °C. In addition, this activity was sensitive to mild heat treatment, with 96% of activity inhibited by incubation at 56 °C for 30 min. The SRBC hemolysis could also be inactivated by pretreatment of the plasma with proteases, indicating that this activity was protein dependent. The activity required divalent metals ions, with activity inhibited by EDTA, citrate, or phosphate. However, the chelator-inhibited activity could be restored by the addition of excess Ca²⁺ or Mg²⁺, but not Cu²⁺ or Ba²⁺, indicating specificity of the divalent metal ion requirement. The sensitivity to heat, proteases, and divalent metal ion chelators strongly suggests that A. tridactylum plasma-mediated hemolysis of SRBCs is mediated by the serum complement system of proteins.     

Economic and Social Impacts of Wildfires and Invasive Plants in American Deserts: Lessons From the Great Basin

Research on the impacts of wildfire and invasive plants in rangelands has focused on biophysical rather than human dimensions of these environmental processes. We offer a synthetic perspective on economic and social aspects of wildfire and invasive plants in American deserts, focusing on the Great Basin because greater research attention has been given to the effects of cheatgrass expansion than to other desert wildfire/invasion cycles. We focus first on impacts at the level of the individual decision-maker, then on impacts experienced at the human community or larger socio-political scales. Economic impacts of wildfire differ from those of invasive grasses because although fire typically reduces forage availability and thus ranch profit opportunities, invasive grasses can also be used as a forage source and ranchers have adapted their grazing systems to take advantage of that circumstance. To reduce the threat of increased ranch bankruptcies, strategies are needed that can increase access to alternative early-season forage sources and/or promote diversification of ranch income streams by capturing value from ranch ecosystem services other than forage. The growth of low-density, exurban subdivisions in Western deserts influences not only the pattern and frequency of wildfire and plant invasions but also affects prevailing public opinion toward potential management options, and thereby the capacity of land management agencies to use those options. Outreach efforts can influence public opinion, but must be rooted in new knowledge about multiple impacts of invasion and increased wildfire in American deserts.     

A review of lameness attributable to the shoulder in the dog: part two

The scapulohumeral joint is a common site of forelimb lameness in the dog. Establishing a definitive diagnosis may be difficult because of the limitations of orthopedic examination and radiographs and the inherent elusiveness of the associated conditions. The intent of this review is to present, in a single reference, the pathophysiology, diagnosis, and treatment of reported causes of lameness intrinsically associated with the shoulder. Part One of this series discusses conditions associated with cartilage and bone maturation disorders and joint instability, while Part Two reviews tendon diseases, muscle disorders, synovial diseases, and soft-tissue mineralization disorders.     

Comparison of plasma and interstitial fluid concentrations of doxycycline and meropenem following constant rate intravenous infusion in dogs

OBJECTIVE: To compare plasma (total and unbound) and interstitial fluid (ISF) concentrations of doxycycline and meropenem in dogs following constant rate IV infusion of each drug. ANIMAL: 6 adult Beagles. PROCEDURE: Dogs were given a loading dose of doxycycline and meropenem followed by a constant rate IV infusion of each drug to maintain an 8-hour steady state concentration. Interstitial fluid was collected with an ultrafiltration device. Plasma and ISF were analyzed by high performance liquid chromatography. Protein binding and lipophilicity were determined. Plasma data were analyzed by use of compartmental methods. RESULTS: Compared with meropenem, doxycycline had higher protein binding (11.87% [previously published value] vs 91.75 +/- 0.63%) and lipophilicity (partition coefficients, 0.02 +/- 0.01 vs 0.68 +/- 0.05). A significant difference was found between ISF and plasma total doxycycline concentrations. No significant difference was found between ISF and plasma unbound doxycycline concentrations. Concentrations of meropenem in ISF and plasma (total and unbound) were similar. Plasma half-life, volume of distribution, and clearance were 4.56 +/- 0.57 hours, 0.65 +/- 0.82 L/kg, and 1.66 +/- 2.21 mL/min/kg, respectively, for doxycycline and 0.73 +/- 0.07 hours, 0.34 +/- 0.06 L/kg, and 5.65 +/- 2.76 mL/min/kg, respectively, for meropenem. The ISF half-life of doxycycline and meropenem was 4.94 +/- 0.67 and 2.31 +/- 0.36 hours, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: The extent of protein binding determines distribution of doxycycline and meropenem into ISF. As a result of high protein binding, ISF doxycycline concentrations are lower than plasma total doxycycline concentrations. Concentrations of meropenem in ISF can be predicted from plasma total meropenem concentrations.     

Development of a leukocytopenic baby guinea pig model with azathioprine and cyclophosphamide

Immunosuppressive agents were given to baby guinea pigs to develop a leukocytopenic baby guinea pig model. Azathioprine in different doses, and cyclophosamide and methylprednisolone combinations did not result in predictable leukocytopenia without significant mortality. A combination of azathioprine 20mg and cyclophosphamide 20mg administered once daily for 5 days to 42 baby guinea pigs resulted in a mean white blood cell count of 2531/mm³ ±1198 (a reduction of 3931 ± 1413 from pretreatment values). The mean counts for polymorphonuclear leukocytes and lymphocytes on day 6 were 398/mm³ and 2035/mm³, respectively. Only 7% mortality was seen in these animals. This model can be utilized to study a variety of bacterial and viral infections in “immunocompromised hosts”.