Doxorubicin and BAY 12-9566 for the treatment of osteosarcoma in dogs: a randomized, double-blind, placebo-controlled study

BACKGROUND: This study was designed to assess the efficacy of a matrix metalloproteinase inhibitor in prolonging posttreatment survival for dogs with appendicular osteosarcoma after treatment with amputation and doxorubicin chemotherapy. HYPOTHESIS: Survival will be prolonged in dogs receiving BAY 12-9566. ANIMALS: The study included 303 dogs with appendicular osteosarcoma. METHODS: Dogs were treated with doxorubicin (30 mg/m2) every 2 weeks for 5 treatments starting 2 weeks after amputation. Dogs were randomly allocated to receive a novel nonpeptidic biphenyl inhibitor of matrix metalloproteinases (MMPs, BAY 12-9566; 4-[4-4-(chlorophenyl)phenyl]-4-oxo-2S-(phenylthiomethyl) butanoic acid) or placebo after doxorubicin chemotherapy. RESULTS: Median survival for all 303 dogs was 8 months; and 1-year, 2-year, and 3-year survival rates were 35%, 17%, and 9%, respectively. Treatment with BAY 12-9566 did not influence survival. Multivariate analysis revealed that increasing age (P = .004), increasing weight (P = .006), high serum alkaline phosphatase (ALP) (P = .012) and high bone ALP (P < .001) were independently associated with shorter median survival times. Additional analyses on available data indicated that as the number of mitotic figures in the biopsy increased (P = .013), and as plasma active MMP-2 concentrations increased (P = .027), the risk of dying increased. CONCLUSIONS AND CLINICAL IMPORTANCE: Doxorubicin is an effective adjuvant to amputation in prolonging survival for dogs with appendicular osteosarcoma.     

Drivers of plant species richness and phylogenetic composition in urban yards at the continental scale

Landscape Ecology - As urban areas increase in extent globally, domestic yards play an increasingly important role as potential contributors to ecosystem services and well-being. These benefits...     

Pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin in freshwater crocodiles (Crocodylus siamensis) after intravenous and intramuscular administration

To the best of the authors’ knowledge, pharmacokinetic information to establish suitable therapeutic plans for freshwater crocodiles is limited. Therefore, the purpose of this study was to clarify the pharmacokinetic characteristics of enrofloxacin (ENR) in freshwater crocodiles, Crocodylus siamensis, following single intravenous and intramuscular administration at a dosage of 5 mg/kg body weight (b.w.). Blood samples were collected at assigned times up to 168 hr. The plasma concentrations of ENR and its metabolite ciprofloxacin (CIP) were measured by liquid chromatography tandem–mass spectrometry. The concentrations of ENR and CIP in the plasma were quantified up to 144 hr after both the administrations. The half-life was long (43–44 hr) and similar after both administrations. The absolute i.m. bioavailability was 82.65% and the binding percentage of ENR to plasma protein ranged from 9% to 18% with an average of 10.6%. Percentage of CIP (plasma concentrations) was 15.9% and 19.9% after i.v. and i.m. administration, respectively. Based on the pharmacokinetic data, susceptibility break point and PK-PD indexes, i.m. single administration of ENR at a dosage of 5 mg/kg b.w. might be appropriate for treatment of susceptible bacteria (MIC > 1 μg/mL) in freshwater crocodiles, C. siamensis.     

Permeability of starch gel matrices and select films to solvent vapors

Volatile agrochemicals such as 2-heptanone have potential in safely and effectively controlling important agricultural pests provided that they are properly delivered. The present study reports the permeability of starch gel matrices and various coatings, some of which are agricultural-based, that could be used in controlled release devices. Low-density, microcellular starch foam was made from wheat, Dent corn, and high amylose corn starches. The foam density ranged from 0.14 to 0.34 g/cm3, the pore volume ranged from 74 to 89%, and the loading capacity ranged from 2.3 to 7.2 times the foam weight. The compressive properties of the foam were not markedly affected by saturating the pore volume with silicone oil. The vapor transmission rate (VTR) and vapor permeability (VP) were measured in dry, porous starch foam and silicone-saturated starch gels. VTR values were highest in foam samples containing solvents with high vapor pressures. Silicone oil-saturated gels had lower VTR and VP values as compared to the dry foam. However, the silicone oil gel did not markedly reduce the VP for 2-heptanone and an additional vapor barrier or coating was needed to adequately reduce the evaporation rate. The VP of films of beeswax, paraffin, ethylene vinyl alcohol, a fruit film, and a laminate comprised of beeswax and fruit film was measured. The fruit film had a relatively high VP for polar solvents and a very low VP for nonpolar solvents. The laminate film provided a low VP for polar and nonpolar solvents. Perforating the fruit film portion of the laminate provided a method of attaining the target flux rate of 2-heptanone. The results demonstrate that the vapor flux rate of biologically active solvents can be controlled using agricultural materials.     

Neospora caninum associated with septic peritonitis in an adult dog

A 7-year-old, male neutered Rhodesian Ridgeback dog was referred to the University of California-Davis Veterinary Medical Teaching Hospital with a 4-month history of peritonitis and episodic abdominal discomfort, lethargy, and weakness. Marked abdominal distension with a prominent fluid wave was noted on physical examination. Cytologic analysis of the abdominal fluid indicated a septic exudate with mixed bacteria and many protozoal zoites. Differentials for the identity of the protozoal zoites included Toxoplasma gondii, Sarcocystis neurona, and Neospora caninum. Indirect latex agglutination antigen testing, standard indirect fluorescent antibody testing, and PCR analysis were performed to identify the zoites. The dog's serum antibody titer for N caninum tachyzoites was 1:20,480, known polysera to N caninum reacted against zoites in the abdominal fluid, and PCR analysis of the abdominal fluid was positive for the presence of a known gene of N caninum. Based on the morphologic, immunologic, and molecular findings, the zoites were identified as N caninum. It remains unclear how the tachyzoites gained access to the peritoneal cavity. To the authors' knowledge, there are no reports of free N caninum in abdominal fluid of any species.     

Two major classes of target site insensitivity mutations confer resistance to organophosphate and carbamate insecticides

Interspecific comparisons of bioassay and biochemical data suggest two major patterns of target site resistance to carbamates and organophosphates. Pattern I resistance, which is generally more effective for carbamates, has been shown in two sub-species of mosquitoes to be due to a particular Gly-Ser mutation in the oxyanion hole within the active site of one of their two acetylcholinesterase enzymes. Intriguingly, different substitutions at the equivalent site confer organophosphate hydrolytic ability on other esterases responsible for metabolic resistance in some other species. In the case of the aphid, Myzus persicae, Pattern I resistance is due to a Ser-Phe mutation in the vicinity of the acyl pocket of acetylcholinesterase. Pattern II resistance is at least as effective for organophosphates as it is for carbamates and may even be specific to organophosphates in some cases. Molecular studies on this pattern of resistance in three higher Diptera show that it is due to changes that constrict the acetylcholinesterase active site gorge and limit binding of the insecticide to the catalytic residues at the base of the gorge. One case of Pattern II resistance in the mosquito, Culex tritaeniorhynchus, involves the same site near the acyl pocket of acetylcholinesterase, albeit a different substitution, as that involved in Pattern I resistance in M. persicae.     

Effects of soil storage on the microbial community and degradation of metsulfuron-methyl

The effect storage had on the microbial biomass in two soils (Trevino and Fargo) was compared to the effect storage had on each soil's capacity to degrade metsulfuron-methyl. Soils were collected from the field and used fresh (<3 weeks old) or stored at 20 and 4 degrees C for 3 or 6 months. The phospholipid fatty acid content of the soils was used to monitor changes in the microbial biomass during storage and incubation in a flow-through apparatus. In both soils, [phenyl-U-14C]metsulfuron-methyl was used to monitor changes in the route and rate of degradation along with 14CO2 evolution (mineralization). Total microbial biomasses in both soils were significantly reduced for soils incubated in the flow-through apparatus, whereas only the Trevino soil's microbial biomass was significantly reduced as a result of storage. The microbial communities of both soils were significantly different as a result of storage as shown by discriminant analysis. In both soils, degradation rate, pathway of degradation, and mineralization of metsulfuron-methyl were significantly affected by storage compared to fresh soil. The half-life of metsulfuron-methyl increased significantly (P < 0.05) in the Trevino soil from 45 days (fresh) to 63 days (stored soil), whereas in the Fargo soil half-lives increased significantly (P < 0.05) from 23 days (fresh) to 29 days (soils stored for 6 months). In both soils, mineralization of [14C]metsulfuron-methyl was significantly (P < 0.05) higher in fresh soils compared to stored soils. The degradation pathways of metsulfuron-methyl changed with storage as evidenced by the loss of formation of one biologically derived metabolite (degradate) in stored soils compared to fresh soils.     

Developing an Open Access Croplands Research Database Through Global Collaboration

This article describes the processes, challenges, and outcomes of a project undertaken by Kansas State University (K-State) Libraries and a global community of researchers. The project, initiated by librarians in the newly created Faculty and Graduate Services Department, involved collaboration with a K-State agronomist. The initial concept was to create an open access database of croplands research submitted by researchers from the Global Research Alliance Croplands Research Group, a consortium of over 30 countries. Due to the project's complexity, it was determined that a more manageable approach would be to pilot the project by including research from only the United States and Australia to resolve problems before scaling up to include all 34 countries in the GRA Croplands Research Group.     

Testing hypotheses about fecundity, body size and maternal condition in fishes

Recent research suggests that maternal condition positively influences the number of eggs spawned in fishes. These studies commonly choose a priori to use body length rather than weight as an explanatory variable of offspring production, even though weight is usually the better predictor of fecundity. We are concerned that consistent exclusion of body weight as a predictor of egg production inflates the variance in fecundity attributable to maternal condition. By analysing data on three populations of Atlantic cod (Gadus morhua, Gadidae) and 10 populations of brook trout (Salvelinus fontinalis, Salmonidae), we illustrate the need for a statistically defensible method of model selection to distinguish the effects of maternal condition on egg production from the effects of body size alone. Forward stepwise regression and null model analyses reveal how length‐based regressions can significantly over‐estimate correlations between condition and fecundity, leading us to conclude that the effect of condition on egg productivity may not be as ubiquitous or as biologically important as previously thought. Our work underscores the need for greater statistical clarity in analyses of the effects of maternal condition on reproductive productivity in fishes.