Treatment of leiomyosarcoma in a tiger (Panthera tigris) with stereotactic radiotherapy.

A 10-year-old male captive tiger (Panthera tigris) developed right-sided facial asymmetry and enlargement. Computed tomography revealed a destructive mass of the right maxillary bone with right nasal cavity involvement. Histopathology indicated a spindle cell sarcoma. A single fraction of 22 Gy using stereotactic radiotherapy was prescribed. After treatment, the facial conformation returned to normal and the tiger resumed normal behavior. Diagnostics 4 months later indicated severe metastatic disease. Humane euthanasia and necropsy were performed. This is the first case utilizing stereotactic radiotherapy for the treatment of cancer in a tiger.

The need for econometric research in laboratory animal operations.

The scarcity of research funding can affect animal facilities in various ways. These effects can be evaluated by examining the allocation of financial resources in animal facilities, which can be facilitated by the use of mathematical and statistical methods to analyze economic problems, a discipline known as econometrics. The authors applied econometrics to study whether increasing per diem charges had a negative effect on the number of days of animal care purchased by animal users. They surveyed animal numbers and per diem charges at 20 research institutions and found that demand for large animals decreased as per diem charges increased. The authors discuss some of the challenges involved in their study and encourage research institutions to carry out more robust econometric studies of this and other economic questions facing laboratory animal research.

Toll-like receptor 7 suppresses virus replication in neurons but does not affect viral pathogenesis in a mouse model of Langat virus infection.

Toll-like receptor 7 (TLR7) recognizes guanidine-rich viral ssRNA and is an important mediator of peripheral immune responses to several ssRNA viruses. However, the role that TLR7 plays in regulating the innate immune response to ssRNA virus infections in specific organs such as the central nervous system (CNS) is not as clear. This study examined the influence of TLR7 on the neurovirulence of Langat virus (LGTV), a ssRNA tick-borne flavivirus. TLR7 deficiency did not substantially alter the onset or incidence of LGTV-induced clinical disease; however, it did significantly affect virus levels in the CNS with a log(10) increase in virus titres in brain tissue from TLR7-deficient mice. This difference in virus load was also observed following intracranial inoculation, indicating a direct effect of TLR7 deficiency on regulating virus replication in the brain. LGTV-induced type I interferon responses in the CNS were not dependent on TLR7, being higher in TLR7-deficient mice compared with wild-type controls. In contrast, induction of pro-inflammatory cytokines including tumour necrosis factor, CCL3, CCL4 and CXCL13 were dependent on TLR7. Thus, although TLR7 is not essential in controlling LGTV pathogenesis, it is important in controlling virus infection in neurons in the CNS, possibly by regulating neuroinflammatory responses.

Evaluation of an internal research funding program in a school of veterinary medicine.

The present article describes a paradigm for evaluating the internal research funding program of a college or school of veterinary medicine, using as an example a similar exercise recently conducted at the Louisiana State University School of Veterinary Medicine (LSU SVM). The purpose of the exercise was to quantify and evaluate the effectiveness of the LSU SVM internal research funding mechanism known as the Competitive Organized Research Program (CORP). The evaluation resulted in several important observations that will allow us to further improve the effectiveness of our internal research funding program investment. Among the most important of these was the greater return on investment for CORP projects funded with smaller awards (approximately $10,000 US) compared to projects funded with larger awards (approximately $52,000 US). Other colleges and schools of veterinary medicine may find such an exercise similarly informative and beneficial.

A user-friendly approach to cost accounting in laboratory animal facilities.

Cost accounting is an essential management activity for laboratory animal facility management. In this report, the author describes basic principles of cost accounting and outlines steps for carrying out cost accounting in laboratory animal facilities. Methods of post hoc cost accounting analysis for maximizing the efficiency of facility operations are also described.

Comparison of selamectin and imidacloprid plus permethrin in eliminating Leporacarus gibbus infestation in laboratory rabbits (Oryctolagus cuniculus).

A shipment of New Zealand white rabbits was infested with Leporacarus gibbus, a rabbit fur mite. This study compared the effectiveness of selamectin with that of imidocloprid plus permethrin in eliminating the mite infestation. Rabbits were divided into 2 groups, and either selamectin or imidocloprid plus permethrin was applied topically. Visual and microscopic examinations were performed on days 0, 1, 2, 3, 4, 5, 6, 13, and 27 for 5 sites (the left and right gluteal areas, neck, ventral tail, and abdomen). Mean percentage effectiveness for each treatment was calculated for each time point. Positive and negative predictive value, sensitivity, and specificity of visual examination were determined relative to microscopic assessment. In addition, location prevalence for the mites was determined. Both treatments were 100% effective by day 13, but selamectin was 100% effective by day 3. The positive predictive value of visual examination was 96%, its negative predictive value was 86%, sensitivity was 75%, and specificity was 98%. Parasite burden was most prevalent on the right and left gluteal areas. We conclude that although both imidocloprid plus permethrin and selamectin were effective against L. gibbus, treatment with selamectin more rapidly eliminated the infestation.

Verminous myelitis in a pit bull puppy.

A 10-week-old, male pit bull dog presented to the referring veterinarian with hind limb paresis and epaxial muscle atrophy. No spinal lesions were identified at gross necropsy; however, histologically there was marked granulomatous myelitis in the spinal cord between T13 and L2 with occasional, intralesional nematode larvae. Based on morphologic characteristics, the nematode larvae were identified as Strongyloides spp., possibly Strongyloides stercoralis.

Toll-like receptor 7 is not necessary for retroviral neuropathogenesis but does contribute to virus-induced neuroinflammation.

Toll-like receptor 7 (TLR7) recognizes guanidine-rich single-stranded (ss) viral RNA and is an important mediator of peripheral immune responses to several ssRNA viruses. However, the role that TLR7 plays in regulating the innate immune response to ssRNA virus infections in specific organs is not as clear. This is particularly true in the central nervous system (CNS) where microglia and astrocytes are often the first cells responding to virus infection instead of dendritic cells. In the current study, we examined the mechanism by which TLR7 contributes to ssRNA virus-induced neuroinflammation using a mouse model of polytropic retrovirus infection. The authors found that TLR7 was necessary for the early production of certain cytokines and chemokines, including CCL2 and tumor necrosis factor (TNF) and was also involved in the early activation of astrocytes. However, TLR7 was not necessary for cytokine production and astrocyte activation at later stages of infection and did not alter viral pathogenesis or viral replication in the brain. This suggests that other pathogen recognition receptors may be able to compensate for the lack of TLR7 during retrovirus infection in the CNS.

Semen evaluation for verification of azoospermia after vasectomy in chimpanzees (Pan troglodytes).

Standards for the reproductive management of captive chimpanzees stipulate that chimpanzees admitted into the National Chimpanzee Sanctuary System must undergo vasectomy followed by laboratory confirmation of azoospermia. In light of the observations of ourselves and others, we questioned whether azoospermia is a necessary indicator of successful vasectomy. Therefore, the objectives of the present study were to assess how much time is required between vasectomy and semen evaluation for azoospermia to be reached and to determine the percentage of vasectomized chimpanzees that actually are azoospermic. The study population comprised 39 adult male chimpanzees that underwent vasectomy and subsequent semen examination at 0.5 to 24 mo afterward. Overall, spermatozoa were found in the semen of at least 1 chimpanzee in almost every month in which animals were evaluated. Of the animals evaluated repeatedly after vasectomy, 20% had no sperm at any examination, 60% were azoospermic then positive during at least 1 subsequent examination, 13.3% were positive at least once and then azoospermic, and 6.7% were positive at every examination. After 0.5 mo postvasectomy, all sperm observed were nonmotile. The results suggest that azoospermia is not a necessary indicator of successful vasectomy.

Synthesis, cellular uptake and animal toxicity of a tetra(carboranylphenyl)-tetrabenzoporphyrin.

A water-soluble nido-carboranyl-tetrabenzoporphyrin has been synthesized in 43% overall yield, by condensation of butanopyrrole with a carboranylbenzaldehyde, followed by metal insertion, oxidation, demetallation and deboronation reactions. This compound accumulated within human glioblastoma T98G cells to a significant higher extent than a structurally related nido-carboranylporphyrin, and localized preferentially in the cell lysosomes. Animal toxicity studies using male and female BALB/c mice revealed that both compounds are non-toxic even at a dose of 160 mg/kg, administered intraperitoneally as a single injection at a concentration of 4 mg/mL. It is concluded that the tetra(carboranylphenyl)-tetrabenzoporphyrin is a promising new sensitizer for the treatment of malignant tumors.

Effect of Eucommia ulmoides on systolic blood pressure in the spontaneous hypertensive rat.

Experiments were conducted to establish the safety and efficacy of Eucommia ulmoides (Du-Zhong) extract in the treatment of hypertension. Pilot experiments using rats demonstrated that E. ulmoides extract was safe to the saturation limits of the compound. The maximum tolerated dose (MTD) was 1200 mg/kg when administered by gastric gavage at a concentration of 1200 mg/ml. Also, rats given 200 mg/kg, 600 mg/kg or 1200 mg/kg doses of E. ulmoides extract daily for 28 days demonstrated no evidence of acute toxicity as determined by clinical appearance, histopathology and serum chemistry evaluation. Lastly, spontaneous hypertensive rats (SHRs) were administered E. ulmoides extract daily for 22 days. Systolic blood pressure (BP) was measured on treatment days 1, 8, 15 and 22 at 0, 1, 2 and 3 hours post-treatment. Beginning on day 8, E. ulmoides extract administered at the mid or high dosages lowered BP in male, but not female, rats. BP declined at a rate of approximately 10 mmHg per hour. The mid dosage of 600 mg/kg was found to be the minimum effective dose. In conclusion, E. ulmoides extract was non-toxic and effective in reducing systolic BP in the SHR.

Factors affecting gestation duration in the bitch.

A retrospective analysis was performed to determine the effects of age, breed, parity, and litter size on the duration of gestation in the bitch. Bitches at two locations were monitored from breeding to whelping. A total of 764 litters whelped from 308 bitches (36 large hounds, 34 Golden Retrievers, 23 German Shepherd Dogs (GSD), and 215 Labrador Retrievers). By breed, the number of whelpings was 152, 72, 58, and 482 for the hounds, Golden Retrievers, German Shepherd Dogs, and Labrador Retrievers, respectively. Whelping was predicted to be 57 d from the first day of cytologic diestrus in the hounds or 65 d from the initial progesterone rise in the other breeds. The average gestation duration (calculated as 8 d prior to Day 1 of cytologic diestrus in hounds or measured from the initial progesterone rise in other breeds) by breed (days +/- S.D.) was 66.0 +/- 2.8, 64.7 +/- 1.5, 63.6 +/- 2.1, and 62.9 +/- 1.3 for the hounds, Golden Retrievers, German Shepherd Dogs, and Labrador Retrievers, respectively. The relationship of age, breed, parity, and litter size with the difference in gestation duration was evaluated using log linear modeling. Age or parity had no effect on gestation duration. Compared to Labrador Retrievers, the German Shepherd Dogs, Golden Retrievers and hounds were more likely to have a longer gestation duration; three, four and nearly eight times as likely, respectively. Bitches whelping four or fewer pups were significantly more likely to have a longer gestation duration than those whelping five or more pups; the prolongation averaging 1 d.

Evaluation of Helicobacter hepaticus bacterial shedding in fostered and sex-segregated C57BL/6 mice.

Neonatal fostering has been evaluated as a means of eliminating Helicobacter hepaticus infection in laboratory mouse colonies. The purpose of the present study was to evaluate cross-fostering of neonatal C57BL/6 pups from experimentally infected dams after male-absent parturition and to determine the effects of sex and housing strategy on H. hepaticus populations. Approximately 20 C57BL/6 mice (age, 1 to 4 days) were fostered daily. In all fostered mice, fecal samples collected at 21 and 42 days of age and cecal samples collected at 42 days of age tested negative for H. hepaticus by polymerase chain reaction analysis. Our results demonstrate that removal of the male prior to parturition extends the fostering period to yield Helicobacter-free mice. In a second experiment, the effects of time of infection, housing strategy, and sex on fecal H. hepaticus shedding and cecal colonization were evaluated. Neither time nor housing strategy affected bacterial shedding. In contrast, fecal and cecal bacterial loads were higher in male mice versus female mice. A novel predictive algorithm was developed to predict cecal bacterial colonization levels in light of fecal bacterial loads. Our findings likely will prove useful in Helicobacter eradication efforts and in studies designed to further elucidate the role of H. hepaticus in disease.

Optimal age at fostering for derivation of Helicobacter hepaticus-free mice.

Helicobacter hepaticus is well established as an unwanted variable in laboratory rodent colonies. Historically, cesarean section and embryo transfer have been used to derive Helicobacter-free mouse colonies. Neonatal transfer of newborn mice onto Helicobacter-free foster dams was recently reported as an alternative method of deriving Helicobacter-free mice, but until now, the age by which pups must be fostered to remain Helicobacter-free was unknown. The purpose of the study reported here was to determine the age by which mouse pups must be fostered to remain free of H. hepaticus. Beginning on the day of birth, 20 C57BL/6 mice were fostered from H. hepaticus-positive parents onto Helicobacter-free BALB/c dams each day for 14 days for a total of 280 pups fostered. Fecal specimens collected at weaning, and fecal, liver, and cecal specimens collected at euthanasia were analyzed by use of polymerase chain reaction (PCR) analysis. No pup fostered within 24 h of birth became infected with H. hepaticus; however, many of those fostered after 24 h became infected. These results were supported by those of a large field trial, in which 201 litters representing 71 strains of mice were fostered within 24 h of birth. Follow-up fecal PCR analysis was performed on 52 mice or their progeny that were randomly sampled from the 201 fostered litters. All mice tested remained free of H. hepaticus approximately 100 days after fostering. The results indicate that mouse pups must be fostered within 24 h of birth to remain free of H. hepaticus. In addition, cecal and fecal PCR analyses detected more infections, than did liver PCR analysis, thus indicating that those specimens are preferred for detection of H. hepaticus infection.

A retrospective study of 11 cases of lungworm (Didelphostrongylus hayesi) infection in opossums (Didelphis virginiana).

A juvenile, female North American opossum (Didelphis virginiana) died of verminous pneumonia caused by Didelphostrongylus haysei despite aggressive treatment with oral fenbendazole, corticosteroids, and antibiotics. This prompted a retrospective study of lungworm infection in opossums, during which 19 additional necropsy reports from opossums were reviewed. Including the subject of this report, a total of 11 (55%) of these cases included a diagnosis of lungworm infection. This diagnosis was considered to have contributed to death in eight out of the 11 cases (73%). Histologically, 10 of the 11 (91%) opossums had granulomatous bronchopneumonia with small to moderate numbers of adult nematodes in the airways and parenchyma. Four of the 11 (36%) opossums had free larvae within the parenchyma or terminal airways. Inflammation was usually associated with larvae, degenerating parasites, and nonintact adult nematodes. Superimposed bacterial pneumonia was evident in three animals, and sections of lung examined from all the opossums were characterized by moderate to severe smooth-muscle hyperplasia in airways, including terminal respiratory bronchioles and alveolar ducts. Nine animals had prominent medial smooth-muscle hyperplasia in small- and medium-sized arterioles. Lesions in other organs, particularly in liver, heart, and gastrointestinal tract, were frequently identified. Three animals had concomitant septicemia or bacterial bronchopneumonia (or both), which contributed to the cause of death. Seven animals had gastric nematodosis (Physaloptera sp.), although three of them had been treated with a 14-day course of fenbendazole.

Combination therapy for footpad lesions in a captive Bengal tiger (Panthera tigris tigris).

A captive adult male Bengal tiger (Panthera tigris tigris) was treated for chronic footpad ulcers associated with pacing on concrete cage surfaces. Combination therapy of oral fluoxetine and acepromazine administration to diminate pacing behavior, daily application of moisturizing ointment, and oral vitamin E supplementation resulted in complete resolution of all footpad lesions. Subsequent clinical episodes completely resolved with similar treatments.