In vitro effect of chlorambucil on human glioma cell lines (SF767 and U87-MG), and human microvascular endothelial cell (HMVEC) and endothelial progenitor cells (ECFCs), in the context of plasma chlorambucil concentrations in tumor-bearing dogs.

The objective of this study was to investigate a possible mechanism of action of metronomic chlorambucil on glioma by studying the in vitro cytotoxicity and anti-angiogenic effects on glioma and endothelial cells, respectively. The in vitro LD50 and IC50 of chlorambucil were determined using human SF767 and U87-MG glioma cell lines, human microvascular endothelial cells (HMVECs) and human endothelial colony forming cells (ECFCs). Results were analyzed in the context of chlorambucil concentrations measured in the plasma of tumor-bearing dogs receiving 4 mg m-2 metronomic chlorambucil. The LD50 and IC50 of chlorambucil were 270 µM and 114 µM for SF767, and 390 µM and 96 µM for U87-MG, respectively. The IC50 of chlorambucil was 0.53 µM and 145 µM for the HMVECs and ECFCs, respectively. In pharmacokinetic studies, the mean plasma Cmax of chlorambucil was 0.06 µM. Results suggest that metronomic chlorambucil in dogs does not achieve plasma concentrations high enough to cause direct cytotoxic or growth inhibitory effects on either glioma or endothelial cells.

Ependymal and periventricular magnetic resonance imaging changes in four dogs with central nervous system blastomycosis.

Rapid detection of central nervous system (CNS) involvement is important for dogs with blastomycosis, as this can affect antifungal drug selection and has been associated with an increased risk of death. Previous reports describing magnetic resonance imaging (MRI) characteristics of canine CNS blastomycosis primarily identified mass lesions. The purpose of this retrospective study was to determine whether other MRI characteristics of CNS blastomycosis may also occur. Medical records of the Purdue University Veterinary Teaching Hospital were searched and four dogs met inclusion criteria. Magnetic resonance imaging characteristics included periventricular edema, periventricular and meningeal contrast enhancement, and ventriculomegaly. Periventricular lesions most commonly involved the rostral horn of the lateral ventricles and the third ventricle. Increased meningeal contrast enhancement involved the cerebrum, thalamus, sella turcica, and brainstem. Findings indicated that, in addition to mass lesions, MRI characteristics of periventricular hyperintensity, contrast enhancement, and ventriculomegaly may also occur in dogs with CNS blastomycosis.

Effects of maternally-derived antibodies on serologic responses to vaccination in kittens.

The optimal vaccination protocol to induce immunity in kittens with maternal antibodies is unknown. The objective of this study was to determine the effects of maternally-derived antibody (MDA) on serologic responses to vaccination in kittens. Vaccination with a modified live virus (MLV) product was more effective than an inactivated (IA) product at inducing protective antibody titers (PAT) against feline panleukopenia virus (FPV). IA vaccination against feline herpesvirus-1 (FHV) and feline calicivirus (FCV) was more effective in the presence of low MDA than high MDA. Among kittens with low MDA, MLV vaccination against FCV was more effective than IA vaccination. A total of 15%, 44% and 4% of kittens had insufficient titers against FPV, FHV and FCV, respectively, at 17 weeks of age. Serologic response to vaccination of kittens varies based on vaccination type and MDA level. In most situations, MLV vaccination should be utilized and protocols continued beyond 14 weeks of age to optimize response by all kittens.

Effects of anesthesia and surgery on serologic responses to vaccination in kittens.

OBJECTIVE: To determine the effects of anesthesia and surgery on serologic responses to vaccination in kittens. DESIGN: Prospective controlled trial. ANIMALS: 32 specific-pathogen-free kittens. PROCEDURES: Kittens were assigned to 1 of 4 treatment groups: neutering at 7, 8, or 9 weeks of age or no neutering. All kittens were inoculated with modified-live virus vaccines against feline panleukopenia virus (FPV), feline herpesvirus (FHV), and feline calicivirus (FCV) at 8, 11, and 14 weeks of age and inactivated rabies virus (RV) at 14 weeks of age. Serum antibody titers against FPV, FHV, and FCV were determined at 8, 9, 11, 14, and 17 weeks of age; RV titers were determined at 14 and 17 weeks of age. RESULTS: Serologic responses of kittens neutered at the time of first vaccination (8 weeks) were not different from those of kittens neutered 1 week before (7 weeks) or 1 week after (9 weeks) first vaccination or from those of kittens that were not neutered. In total, 31%, 0%, 69%, and 9% of kittens failed to develop adequate titers against FPV, FCV, FHV, and RV, respectively, by 17 weeks of age. CONCLUSIONS AND CLINICAL RELEVANCE: Neutering at or near the time of first vaccination with a modified-live virus vaccine did not impair antibody responses in kittens. Many kittens that were last vaccinated at 14 weeks of age had inadequate antibody titers at 17 weeks of age. Kittens may be vaccinated in the perioperative period when necessary, and the primary vaccination series should be extended through at least 16 weeks of age.

Effect of vaccination on parvovirus antigen testing in kittens.

OBJECTIVE: To determine the frequency and duration of feline panleukopenia virus (FPV) vaccine-induced interference with fecal parvovirus diagnostic testing in cats. DESIGN: Prospective controlled study. ANIMALS: Sixty-four 8- to 10-week-old specific-pathogen-free kittens. PROCEDURES: Kittens were inoculated once with 1 of 8 commercial multivalent vaccines containing modified-live virus (MLV) or inactivated FPV by the SC or intranasal routes. Feces were tested for parvovirus antigen immediately prior to vaccination, then daily for 14 days with 3 tests designed for detection of canine parvovirus. Serum anti-FPV antibody titers were determined by use of hemagglutination inhibition prior to vaccination and 14 days later. RESULTS: All fecal parvovirus test results were negative prior to vaccination. After vaccination, 1 kitten had positive test results with test 1, 4 kittens had positive results with test 2, and 13 kittens had positive results with test 3. Only 1 kitten had positive results with all 3 tests, and only 2 of those tests were subjectively considered to have strongly positive results. At 14 days after vaccination, 31% of kittens receiving inactivated vaccines had protective FPV titers, whereas 85% of kittens receiving MLV vaccines had protective titers. CONCLUSIONS AND CLINICAL RELEVANCE: Animal shelter veterinarians should select fecal tests for parvovirus detection that have high sensitivity for FPV and low frequency of vaccine-related test interference. Positive parvovirus test results should be interpreted in light of clinical signs, vaccination history, and results of confirmatory testing. Despite the possibility of test interference, the benefit provided by universal MLV FPV vaccination of cats in high-risk environments such as shelters outweighs the impact on diagnostic test accuracy.