David G. Baker

Experimental oral inoculations in birds to evaluate potential definitive hosts of Neospora caninum

Experimental oral inoculations to evaluate potential definitive hosts of Neospora caninum were conducted by feeding infected rodent tissues to 9 carnivorous birds of 4 species. Birds included 2 red-tailed hawks (Buteo jamaicensis), 2 turkey vultures (Cathartes aura), 2 barn owls (Tyto alba), and 3 American crows (Corvus brachyrhynchus). The rodents (mice or rats) had been inoculated with 100,000 culture-derived tachyzoites of N. caninum 1-6 mo before feeding to the birds. Fecal samples were collected from each bird daily for 1 mo after feeding rodents and examined for oocysts by fecal flotation. In addition, processed aliquots from all avian fecal samples were fed to BALB/c mice. Five weeks after feeding, mice were bled and sera were tested for antibodies against N. caninum. One to two months later, mice were killed and brain tissue was examined microscopically for protozoal cysts. While occasional oocysts were found in avian fecal samples, these were likely not N. caninum because they were not infective to BALB/c mice. It was concluded that the bird species tested are not likely to be definitive hosts of N. caninum.

Factors That Can Influence Animal Research

Animal research involves the collection of data from carefully designed experiments. The validity of the research and the conclusions drawn from the data are influenced by many factors. Some of these factors may confound experimental results and therefore must be carefully considered and, where possible, controlled. This chapter describes potential intrinsic and extrinsic research confounders described in the scientific literature that can influence experimental outcomes. In order to obtain reliable, meaningful results, an attempt should be made to control or standardize all known biological, environmental, and social factors when conducting experiments involving animals.

Natural pathogens of laboratory animals

An essential resource for everyone working with laboratory animals. * Informs laboratory animal veterinarians, animal caretakers, and research scientists, and others, how natural pathogens of laboratory animals can alter host physiology and compromise the validity of research findings. * Provides descriptions of housing systems for pathogen exclusion or containment, and approaches to pathogen surveillance. * Includes information on the most common natural pathogens found in a wide variety of laboratory animals. This title is published by the American Society for Microbiology Press and distributed by Taylor and Francis in rest of world territories.

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.

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.

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.

Hepatic Toxicity and Recovery of Fischer 344 Rats Following Exposure to 2-Aminoanthracene by Intraperitoneal Injection

Humans may be exposed to 2-aminoanthracen e (2-AA), a substituted polycyclic aromatic hydrocarbon, and a recognized mutagen and carcinogen, through oral and respiratory routes from contact with a variety of environmental sources. For the present study, we sought to evaluate hepatic damage and recovery in Fischer 344 rats following multiple IP injections of 5 mg of 2-AA. Rats were injected weekly for up to 5 weeks. Subgroups were then allowed to recover for 1, 5, or 9 weeks, and biochemical and pathologic changes were evaluated. We observed that weight gains were reduced relative to controls for all groups receiving ≥ 2 injections. Serum enzyme levels indicative of liver damage were evident and included alterations in serum aspartate aminotransferase, alkaline phosphatase, total protein, albumin, and globulin. These alterations usually returned to normal by 5 weeks following cessation of 2-AA administration. In contrast, histologic liver changes, including hepatocyte hypertrophy, biliary hyperplasia with oval cell proliferation, altered foci, nodular hyperplasia, and one hepatocellular adenoma became more severe with time. This experiment demonstrates patterns of hepatic damage and recovery in rats exposed to 2-AA.

Occurrence and Species of Lice on Free-living and Captive Raptors in California

Abstract This study determined the occurrence and identity of chewing lice (Mallophaga) on 35 clinically healthy raptors presented with traumatic injuries at the California Raptor Center during the summers of 1993 and 1994. Samples of lice were collected and preserved in 70% ethanol during physical examinations within 24 hours of admission. Eleven species of chewing lice were collected and identified from 7 species of raptors, including 2 long-term captive birds. All louse species except 1 were on their usual, previously documented raptor hosts. Four of the 10 species of free-living birds examined had no lice, but their sample sizes were small (1–3 birds each). At least 1 bird from each of the other 6 raptor species harbored some lice, but only 2 species, an American kestrel (Falco sparverius) and a barn owl (Tyto alba) were sampled in useful numbers. One of 8 kestrels yielded lice (1 species), and 4 of 14 barn owls were infested with lice (representing 2 species). Two captive birds, a spotted owl (Strix occidentalis) and a Swainsons hawk (Buteo swainsoni), were infested with lice (1 species each) after 463 days and 1198 days in captivity, respectively.

A RETROSPECTIVE STUDY OF 11 CASES OF LUNGWORM (DIDELPHOSTRONGYLUS HAYESI) INFECTION IN OPOSSUMS (DIDELPHIS VIRGINIANA)

Abstract 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.

Establishment and validation of an isolated rat lung model for pulmonary metabolism studies

An isolated rat lung model was established and validated for use in pulmonary metabolism studies. During the establishment phase of the study, several problems were encountered and overcome in order to maintain the lungs in physiological condition. In the validation phase of the study, the lungs were removed, ventilated and perfused from 34 male Fischer 344 rats. After an equilibration period, lungs were ventilated and perfused for up to 4 h. Morphological, biochemical and functional parameters were evaluated to validate the physiological condition of the lungs. Morphological parameters included wet/dry lung weight ratios and gross and histological scoring for edema. Biochemical parameters included assays for tissue ATP and reduced glutathione content, glutathione reductase activity and glucose utilization. Functional parameters included changes in lung tidal volume, dynamic compliance and airway resistance. Results indicated that edema formation was only detected histologically, that lungs remained nearly biochemically normal for 210 min and that pulmonary function declined to about 80–90% of normal. Overall, these findings indicated that the isolated, perfused rat lung remained in acceptable physiological condition for ca. 210 min. This period of time should be adequate for conducting pulmonary metabolism studies with a variety of exogenous compounds. Copyright