Monitoring response to aminobisphosphonate therapy in canine osteosarcoma using dual energy x‐ray absorptiometry (dexa)

Introduction: Palliative therapy is essential to improve the quality of life of dogs with osteosarcoma (OSA), when definitive therapy is not considered a valid option. Bisphosphonates, a novel class of antiosteoclastic drugs, are widely used in humans for several painful osteolytic conditions. Dual energy x‐ray absorptiometry (DEXA) is recognized as a reliable tool to measure bone mineral density (BMD), and to monitor treatment response to bisphosphonates in humans. A prospective evaluation of pamidronate, an injectable aminobisphosphonate, is ongoing in dogs with appendicular OSA. The potential value of DEXA for objective evaluation of BMD variations with palliative therapies is concurrently being assessed. Materials and Methods: Dogs with naturally occurring appendicular OSA treated with pamidronate constitute the patient population. A DEXA scan (QDR‐4500 W, Hologic, Bedford, MA) is performed on day 0 (baseline) and on every treatment day with pamidronate thereafter (every 28 days). For each dog, a whole body scan is performed, followed by a scan of the tumor, and contralateral normal bone. Three regions of interest are subsequently analyzed for BMD changes in tumor and normal bone. Statistical analysis was performed using Student t‐test and paired t‐tests, with significance being set at p < 0.05. Results: Nineteen dogs have been enrolled to date. Seven responders and 6 non‐responders have suitable data for analysis. A significant difference is observed (p = 0.04) between tumor BMD variations of responders and non‐responders at day 28 (mean variations +18.0% and ?4.6% respectively). The changes at day 28 are significant only in the responders (p = 0.038 vs p = 0.05 in non‐responders). When BMD of tumor and normal bone at day 84 is compared to day 0 in six responders, only tumor had a significant increase (p = 0.017 vs p = 0.279, respectively). Conclusions: Objective measurements of response to therapy are essential in pain palliation studies. Increased tumor bone BMD, as obtained by DEXA analysis, may correlate with subjective clinical improvement in pamidronate‐treated dogs with appendicular OSA.     

Bordetella bronchiseptica-reactive antibodies in Canadian polar bears

Bordetella bronchiseptica is a promiscuous bacterium that infects a variety of species but has not been reported in free-ranging polar bears (Ursus maritimus). Sera from 385 polar bears from the western Hudson Bay region, 1986 to 2017, were tested for reactivity to B. bronchiseptica with enzyme-linked immunosorbent assays using anti-canine IgG and Streptococcus protein G as secondary reagents. Sera from bears had variable reactivity to B. bronchiseptica antigens, and there was no difference among bears that had a history of coming near the town of Churchill, Manitoba, and bears that did not. Although the sources of exposure were not determined, equivalent results in both groups suggest that potential exposure to humans (aside from handling during sampling) and their animals (dogs) was not an important co-factor in sero-positivity to B. bronchiseptica.     

Serum antibody responses to vaccinal antigens in lean and obese geriatric dogs

The immune responses in control dogs [1 to 4 years of age, body condition score (BCS): 4 to 5 out of 9] were compared to those of aging dogs (based on breed and body size) either categorized as lean (BCS: 4 to 5 out of 9) or obese (BCS: 8 to 9 out of 9). Of interest were the serum titers to the following common agents found in vaccines, canine parainfluenza virus (CPIV), canine parvovirus (CPV), canine distemper virus (CDV), canine respiratory coronavirus (CRCoV), and Bordetella bronchiseptica. There were no statistical differences in the antibodies to CPIV, B. bronchispetica, and CRCoV, among the age/weight categories, nor among the age/weight categories and the time, in days, between the date of sample collection and the date of the last recorded vaccination for CPIV, B. bronchiseptica, CPV, and CDV. For CPV, the control dogs had significantly (P < 0.002) higher serum neutralization (SN) titers than the lean geriatric dogs and the obese geriatric dogs. For CDV SN titers, the only statistically significant (P = 0.01) difference was that the control dogs had higher SN titers than the lean geriatric dogs.     

Landscape‐scale modelling of erosion processes and soil carbon dynamics under land‐use and climate change in agroecosystems

Soil organic carbon (SOC) sequestration and soil redistribution are linked to soil properties, land use, farming system and climate. In a global‐change context, landscape and climate changes are expected and will most probably have impacts on changes in the soil. Soil change was simulated from 2010 to 2100 in an 86‐ha hedgerow landscape under different scenarios of landscape and climate changes. These scenarios combined contrasting land uses, hedgerow networks and climates. Two models were combined to evaluate the impact of these scenarios on soils: LandSoil, a soil redistribution model, and a SOC model based on RothC‐26.3. A soil thickness of 105 cm was considered. The results indicate that the main factor influencing soil degradation was land‐use change: when compared with the baseline business‐as‐usual landscape, the landscape with the most intensive agricultural systems had the greatest soil erosion (+0.26 t ha^?1 year^?1) and reduced mean SOC stocks (?17 t ha^?1 after 90 years). The second significant factor was climate change, followed by hedgerow network density. Sensitivity to climate change differed between landscapes, and the most sensitive were those with continuous winter wheat. The results indicate that a hedgerow landscape is well adapted to protect soil (regarding carbon storage and soil erosion) in a context of climate change. However, this type of landscape is highly sensitive to cropping intensification and should be protected.     

Some Pharmacokinetic Parameters of Eprinomectin in Goats following Pour-on Administration

Some pharmacokinetic parameters of eprinomectin were determined in goats following topical application at a dose rate of 0.5 mg/kg. The plasma concentration versus time data for the drug were analysed using a one-compartment model. The maximum plasma concentration of 5.60±1.01 ng/ml occurred 2.55 days after administration. The area under the concentration–time curve (AUC) was 72.31±11.15 ng day/ml and the mean residence time (MRT) was 9.42±0.43 days. Thus, the systemic availability of eprinomectin to goats was significantly lower than that for cows. The low concentration of eprinomectin in the plasma of goats suggests that the pour-on dose of 0.5 mg/kg would be less effective in this species than in cows. Further relevant information about the optimal dosage and residues in the milk of dairy goats is needed before eprinomectin should be used in this species.     

Investigating the in vitro interactive effects of ionizing radiation and pamidronate in a canine osteosarcoma cell line

Introduction: Dogs with osteosarcoma suffer intense bone pain. Conventional palliative treatment options include ionizing radiation with or without systemic chemotherapy. Intravenous pamidronate is a first‐line therapeutic agent in people with painful skeletal metastases and is currently being evaluated for the management of osteolytic pain associated with canine osteosarcoma. The theoretical combination of radiation and pamidronate for managing bone pain appears to be a rational treatment option, however, in vitro experiments demonstrating additive or supraadditve cytotoxic effects of these two modalities would further support the clinical institution of this novel combination therapy. The purpose of this study was to evaluate the in vitro cytotoxicity of ionizing radiation and pamidronate in a canine OSA cell line and to characterize the interaction between these two therapeutic modalities when used in combination. Methods: The canine osteosarcoma cell line, HMPOS, was subjected independently to varying doses of ionizing radiation (100 cGy, 300 cGy, 400 cGy, 600 cGy, 800 cGy, or 1000 cGy) or different concentrations of pamidronate (10, 25, 50, 66, 75, 100, 150, 200, and 250 μM). Cells were harvested following 48 hours of incubation and cell viability was assessed by flow cytometric analysis. Dose‐response curves were generated, and a theoretical ED₅₀ for each treatment modality calculated. An ED₅₀ isobologram was created to determine if different combinations of ionizing radiation and pamidronate (isoboles) would demonstrate subadditive, additive, or supraadditve cytotoxic effects. Results: The ED₅₀ of ionizing radiation and pamidronate were 614 cGy and 65.3 μM, respectively. Of the six different isobole combinations evaluated, three produced supraadditve effects, one produced a subadditive effect, and two produced additive effects. Conclusions: Both ionizing radiation and pamidronate independently exert in vitro cytotoxic effects. Positive interactive effects can be generated, but only with specific isobole combinations. The results from this in vitro study support the use of specific combinations of ionizing radiation and pamidronate in order to maximize the cytotoxic properties of both treatment modalities.     

Effects of calcium deficiency on nutrient concentration of xylem sap of excised tomato plants

The effects of calcium (Ca) deficiency on cation uptake and concentration of xylem sap from tomato roots after excision of the aerial parts, were studied. The measurements were made on tomato plants grown on nutrient solutions with +Ca or without‐Ca, over a period of 48 hours. Calcium deficiency entailed a significant increase of the flux of xylem sap between the 6th and 14th hour on the first day after excision. In spite of the lack of Ca in the nutrient solution, the Ca concentration in xylem sap was unaffected in regard to that of excised roots with +Ca. The maintenance of the Ca concentration in xylem sap of plants grown on a Ca deficient solution was related to a reuse of the Ca from the apoplastic root stores. So, this regulation indicates a possible translocation of the Ca available in the root supply and a mobility of this element out of the roots only during the early stages of exposure to a Ca deficiency. The presence of NH₄ ⁺ in xylem sap with both +Ca and‐Ca treatments confirms the nitrogenous reduction activity of tomato roots. The accumulation of free ammonium 24 h after excision in both xylem saps (+Ca and‐Ca) is likely to be evidence of an alteration process of protein synthesis which is related to the depletion of the root water soluble carbohydrate supply.     

Pharmacokinetics of metaflumizone and amitraz in the plasma and hair of dogs following topical application

Controlled laboratory studies have shown that a metaflumizone plus amitraz combination (ProMeris/ProMeris Duo for Dogs, Fort Dodge Animal Health, Overland Park, KS) applied topically is effective for the treatment and control of fleas and ticks on dogs. Two studies were conducted to determine the distribution of both metaflumizone and amitraz in the plasma and hair of dogs following treatment at the minimum recommended dose of approximately 20mg/kg of each active ingredient. Six purpose-bred, adult Beagle dogs were used in each study. Plasma or hair samples were collected from each dog just prior to dosing and periodically through 56 days after treatment. Samples were analyzed by HPLC methods validated for the simultaneous determination of metaflumizone and amitraz. Amitraz was detectable (>3.2ng/ml) but not quantifiable (<50ng/ml) in only two plasma samples, collected 1 and 2 days post-treatment from different dogs. Metaflumizone concentrations in plasma were generally detectable (>1.0ng/ml) but not quantifiable (<50ng/ml). Measurable levels were found in one dog 7 days post-treatment, increasing to a maximum of four dogs at 42 days after dosing, with a metaflumizone range of 59-138ng/ml. Analysis of hair samples indicated that both metaflumizone and amitraz were widely distributed at basically similar levels in the hair within 1-day after administration, reaching maximum concentrations between 2 and 7 days post-treatment. Low but quantifiable levels of both compounds were still present on hair at the end of the 56-day study. These studies indicate that the ectoparasitic activity is due to exposure of the parasites to metaflumizone and amitraz on the surface of the host (hair and/or skin), not to exposure via the circulatory system of the host.     

Single-agent pamidronate for palliative therapy of canine appendicular osteosarcoma bone pain

BACKGROUND: Canine appendicular osteosarcoma (OSA) causes focal bone destruction, leading to chronic pain and reduced quality-of-life scores. Drugs that inhibit pathologic osteolysis might provide additional treatment options for managing cancer-induced bone pain. Aminobisphosphonates induce osteoclast apoptosis, thereby reducing pain associated with malignant osteolysis in human patients with cancer. HYPOTHESIS: Treatment of dogs with pamidronate administered intravenously will alleviate bone pain and reduce pathologic bone turnover associated with appendicular OSA in dogs. ANIMALS: Forty-three dogs with naturally occurring appendicular OSA administered pamidronate intravenously. METHODS: Prospective study. Therapeutic responses in dogs treated with pamidronate administered intravenously and nonsteroidal anti-inflammatory drugs (NSAID) were evaluated by using a numerical cumulative pain index score (CPIS), and by quantifying urine N-telopeptide (NTx) excretion and relative primary tumor bone mineral density (rBMD) assessed with dual energy x-ray absorptiometry. In addition, variables, including pamidronate dose, skeletal mass, baseline and change for CPIS, urine NTx and rBMD during treatment, and baseline tumor volume and radiographic pattern were compared between dogs clinically responsive and nonresponsive to pamidronate therapy. RESULTS: Twelve of 43 dogs (28%) had pain alleviation for >4 months, lasting a median of 231 days. Changes in CPIS and rBMD during treatment were statistically different between responders and nonresponders (P = .046 and .03, respectively). CONCLUSIONS AND CLINICAL IMPORTANCE: Substantiated by reductions in CPIS and increases in rBMD, single-agent pamidronate administered intravenously with NSAID therapy relieves pain and diminishes pathologic bone turnover associated with appendicular OSA in a subset of dogs.     

Loss and fragmentation of mature woodland reduce the habitat niche breadth of forest birds

Context

Habitat loss and fragmentation may alter habitat occupancy patterns, for example through a reduction in regional abundance or in functional connectivity, which in turn may reduce the number of dispersers or their ability to prospect for territories. Yet, the relationship between landscape structure and habitat niche remains poorly known.

Objectives

We hypothesized that changes in landscape structure associated with habitat loss and fragmentation will reduce the habitat niche breadth of forest birds, either through a reduction in density-dependent spillover from optimal habitat or by impeding the colonization of patches.

Methods

We surveyed forest birds with point counts in eastern Ontario, Canada, and analyzed their response to loss and fragmentation of mature woodland. We selected 62 landscapes varying in both forest cover (15–45%) and its degree of fragmentation, and classified them into two categories (high versus low levels of loss and fragmentation). We determined the habitat niche breadth of 12 focal species as a function of 8 habitat structure variables for each landscape category.

Results

Habitat niche breadth was narrower in landscapes with high versus low levels of loss and fragmentation of forest cover. The relative occupancy of marginal habitat appeared to drive this relationship. Species sensitivity to mature forest cover had no apparent influence on relative niche breadth.

Conclusions

Regional abundance and, in turn, density-dependent spillover into suboptimal habitat appeared to be determinants of habitat niche breadth. For a given proportion of forest cover, fragmentation also appeared to alter habitat use, which could exacerbate its other negative effects unless functional connectivity is high enough to allow individuals to saturate optimal habitat.