Treatment of Tumor-Bearing Dogs With Actinomycin D

Fifty dogs with advanced malignancies were treated with actinomycin D at doses ranging from 0.5 to 1.1 mg/m² every 3 weeks. The greatest number of responses was noted in dogs with lymphoma, including dogs that had received prior chemotherapy. Other responding tumor types included anal sac adenocarcinoma, perianal adenocarcinoma, squamous cell carcinoma, thyroid carcinoma, and transitional cell carcinoma. The median time to maximum response for dogs with lymphoma was 7 days, with a median duration of 42 days. Gastrointestinal toxicity was the most frequently observed side effect. A dose of 0.6 to 0.7 mg/m² appears to be appropriate for treating various malignancies in dogs.     

Regulatory Status of Therapeutants for Penaeid Shrimp Culture in the United States

The lack of approved drugs and chemicals needed to manage disease and pests in culture systems is the major constraint facing the penaeid shrimp culture industry in the United States. The industry needs the timely approval of the therapeutants for disease control for cost effectiveness and public safety. The approval process for the needed chemotherapeutants (drugs, parasiticides, disinfectants, and water quality agents) is administered by the US. Food and Drug Administration (FDA) and the US. Environmental Protection Agency (EPA). Both FDA and EPA have procedures for registration of compounds for minor use whereby needed approvals may be obtained at far less cost than is typical for uses in major agricultural industries.
Aquatrine® is the only compound with specific approval for use in shrimp culture. Three others—formalin, oxytetracycline, and trifluralin—have entered the approval process. Because of human safety concerns, replacements are needed for malachite green, chloramphenicol, and the nitrofurans. Candidates for replacing these compounds include trifluralin, oxolinic acid, nalidixic acid, the potentiated sulfonamides, erythromycin, and oxytetracycline. A need exists for an environmentally safe and effective agent to treat fusarium disease.
The U.S. Department of Agriculture Interregional Research Project Number 4 (IR-4), in conjunction with FDA, has begun addressing the problems of the aquaculture industry. Thus, the penaeid shrimp industry has an excellent opportunity to obtain the approvals of chemotherapeutants that are needed for continued growth toward a full potential in this country.     

Phase I and pharmacokinetic evaluation of the combination of orally administered docetaxel and cyclosporin A in tumor-bearing dogs

OBJECTIVE: To determine the maximum tolerated dose and characterize the pharmacokinetic disposition of an orally administered combination of docetaxel and cyclosporin A (CSA) in dogs with tumors. ANIMALS: 16 client-owned dogs with metastatic or advanced-stage refractory tumors. PROCEDURES: An open-label, dose-escalation, single-dose, phase I study of docetaxel administered in combination with a fixed dose of CSA was conducted. Docetaxel (at doses of 1.5, 1.625, or 1.75 mg/kg) and CSA (5 mg/kg) were administered concurrently via gavage twice during a 3-week period. Plasma docetaxel concentrations were quantified by use of high-performance liquid chromatography, and pharmacokinetic disposition was characterized by use of noncompartmental analysis. Dogs' clinical signs and results of hematologic and biochemical analyses were monitored for evidence of toxicosis. RESULTS: No acute hypersensitivity reactions were observed after oral administration of docetaxel. Disposition of docetaxel was dose independent over the range evaluated, and pharmacokinetic variables were similar to those reported in previous studies involving healthy dogs, with the exception that values for clearance were significantly higher in the dogs reported here. The maximum tolerated dose of docetaxel was 1.625 mg/kg. Gastrointestinal signs of toxicosis were dose limiting. CONCLUSIONS AND CLINICAL RELEVANCE: The absence of myelosuppression suggested that the docetaxel-CSA combination may be administered more frequently than the schedule used. Further studies are warranted to evaluate combination treatment administered on a biweekly schedule in dogs with epithelial tumors.     

Evaluation of the effects of dietary n-3 fatty acid supplementation on the pharmacokinetics of doxorubicin in dogs with lymphoma

OBJECTIVE: To determine the effect of dietary n-3 fatty acids on the pharmacokinetics of doxorubicin in dogs with lymphoma. ANIMALS: 23 dogs with lymphoma in stages IIIa, IVa, and Va. PROCEDURE: Dogs receiving doxorubicin chemotherapy were randomly allocated to receive food with a high (test group) or low (control group) content of n-3 fatty acids. Serum doxorubicin and doxorubicinol concentrations were measured via high-performance liquid chromatography before and 6 to 9 weeks after initiation of the diets. Lymph node concentrations of doxorubicin were assessed 6 hours after the initial treatment. Dogs' body composition was assessed by means of dual-energy x-ray absorptiometry scans. RESULTS: No significant differences in doxorubicin pharmacokinetics were detected between treatment groups. Significant differences existed between the first and second sampling times among all dogs for area under the curve, maximum serum concentration, and clearance. Differences in body composition did not affect measured pharmacokinetic variables. The terminal elimination half-life was longer in dogs in which a long-term remission was achieved than in dogs that did not have remission. CONCLUSIONS AND CLINICAL RELEVANCE: Dietary supplementation of n-3 fatty acids is common in veterinary patients with neoplasia, but supplementation did not affect doxorubicin pharmacokinetics in this population of dogs. Explanations for the beneficial effects of n-3 fatty acids other than alterations in the pharmacokinetics of chemotherapy drugs should be investigated. Dogs may metabolize drugs differently prior to remission of lymphoma than when in remission. The pharmacokinetics of doxorubicin at the time of the first administration may predict response to treatment.     

Evaluation of chemical and photochemical oxidation processes for degradation of phosmet on lowbush blueberries (Vaccinium angustifolium)

Chemical and photochemical oxidation processes were evaluated for their ability to degrade residual phosmet on lowbush blueberries and for their role in the conversion of phosmet to phosmet oxon--a toxic metabolite of phosmet. Chemical processes included 1 ppm of aqueous ozone, 1% hydrogen peroxide, 100 ppm of chlorine, and UV, whereas photochemical processes included hydrogen peroxide/UV, chlorine/UV, and ozone/hydrogen peroxide/UV. Phosmet applied as Imidan 2.5EC under laboratory conditions resulted in a mean residual concentration of 44.4 ppm, which was significantly degraded (p < 0.05) by ozone and chlorine, yielding reductions of 57.7 and 46%, respectively. Interaction between phosmet (Imidan 2.5EC) and any chemical or photochemical treatment did not result in conversion to phosmet oxon. Residual analysis of commercially grown blueberries revealed mean phosmet (Imidan 70W) levels of 10.65 ppm and phosmet oxon levels of 12.49 ppm. Treatment of commercial blueberries resulted in significant reductions in phosmet regardless of treatment type; however, only UV, hydrogen peroxide/UV, and ozone treatments degraded phosmet (Imidan 70W) to less toxic metabolites and reduced phosmet oxon levels. Treatment-induced conversion of phosmet to phosmet oxon was noticeably influenced by variations between phosmet formulations. Acceleration of photochemical degradation by UV was not observed. Selective oxidation by ozone represents a significant postharvest process for degrading residual phosmet on lowbush blueberries.     

Colloid transport of plutonium in the far-field of the Mayak Production Association, Russia

Sorption of actinides, particularly plutonium, onto submicrometer-sized colloids increases their mobility, but these plutonium colloids are difficult to detect in the far-field. We identified actinides on colloids in the groundwater from the Mayak Production Association, Urals, Russia; at the source, the plutonium activity is approximately 1000 becquerels per liter. Plutonium activities are still 0.16 becquerels per liter at a distance of 3 kilometers, where 70 to 90 mole percent of the plutonium is sorbed onto colloids, confirming that colloids are responsible for the long-distance transport of plutonium. Nano-secondary ion mass spectrometry elemental maps reveal that amorphous iron oxide colloids adsorb Pu(IV) hydroxides or carbonates along with uranium carbonates.     

Cerebrospinal fluid analysis and magnetic resonance imaging in the diagnosis of neurologic disease in dogs: a retrospective study

BACKGROUND: Diagnosis of central nervous system (CNS) abnormalities in dogs can be challenging antemortem. Historically, cerebrospinal fluid (CSF) analysis has been used for routine diagnostic evaluation of animals with suspected neurologic disease; however, with increasing availability of magnetic resonance (MR) imaging, the need for concurrent CSF analysis may be questioned. OBJECTIVE: The purpose of this study was to retrospectively assess and compare the diagnostic information contributed from MR imaging and CSF analysis in a population of dogs presenting with neurologic disease. METHODS: Results of concurrent MR imaging and CSF analysis were evaluated in dogs presented for neurologic diseases. Based on clinical diagnosis, the sensitivity of CSF analysis and MR imaging for detecting a nervous system abnormality was calculated. Dogs with diagnoses confirmed by other diagnostic modalities were also evaluated separately. RESULTS: A total of 256 dogs were included in the study. For clinical diagnoses in which abnormalities were expected, MR imaging abnormalities were found in 89% and CSF abnormalities in 75% of dogs; CSF abnormalities were more common than MR imaging abnormalities only in inflammatory CNS disease. The majority of CSF abnormalities were nonspecific; an etiologic diagnosis was determined in only 2% of CSF samples. MR imaging excelled in detecting structural disorders, revealing 98% of vertebral abnormalities. In confirmed cases (n = 55), 76% of MR images and 9% of CSF samples were diagnostic. When intervertebral disk disease (IVDD) and vertebral malformation were excluded from analysis (n = 16 remaining), 25% of MR images and 6% of CSF cytology results were highly indicative of the confirmed diagnoses; CSF titer results provided the diagnosis in 25% of these cases. CONCLUSION: CSF analysis may not be necessary when MR findings of IVDD or vertebral malformation/instability are obvious; however, when the cause of neurologic disorder is uncertain, concurrent MR imaging and CSF analysis provides the greatest assistance in establishing a clinical diagnosis.     

Carbon content variation in boles of mature sugar maple and giant sequoia

At present, a carbon (C) content of 50% (w/w) in dry wood is widely accepted as a generic value; however, few wood C measurements have been reported. We used elemental analysis to investigate C content per unit of dry matter and observed that it varied both radially and vertically in boles of two old-growth tree species: sugar maple (Acer saccharum Marsh.) and giant sequoia (Sequoiadendron giganteum (Lindl.) Bucholz). In sugar maple there was considerable variation in tree ring widths among four radii for particular annual layers of xylem, revealing that the annual rate of C assimilation differs around the circumference and from the base of each tree to its top, but the observed variation in C content was unrelated to diameter growth rate and strongly related to the calendar year when the wood was formed. Carbon content in sugar maple wood increased in an approximately linear fashion, from < 50 to 51% from pith to cambium, at both the base and top of the boles. In giant sequoia, C was essentially constant at > 55% across many hundreds of years of heartwood, but it declined abruptly at the sapwood-heartwood boundary and remained lower in all sapwood samples, an indication that heartwood formation involves anabolic metabolism. Factors that may be responsible for the different C contents and trends with age between sugar maple and sequoia trees are considered. Tree-ring data from this study do not support some of the key assumptions made by dendrochronology.     

Home-field advantage accelerates leaf litter decomposition in forests

Several leaf litter decay studies have indicated that decomposition occurs more rapidly when litter is placed beneath the plant species from which it had been derived than beneath a different plant species (i.e. home-field advantage, HFA), although support for this notion has not been universal. We provide the first quantification of HFA in relation to leaf litter decomposition using published litter mass loss data from forest ecosystems in North America, South America, and Europe. Our findings indicate that HFA is widespread in forest ecosystems; on average litter mass loss was 8% faster at home than away. We hypothesize that HFA results from specialization of the soil biotic community in decomposing litter derived from the plant above it. Climate and initial litter quality data can be used to explain about 70% of the variability in litter decomposition at a global scale, leaving about 30% unexplained. We suggest that HFA be recognized as a factor that explains some of this remaining variability.