Highly Pathogenic Avian Influenza A(H5N1) Virus Clade 2.3.4.4b Infections in Wild Terrestrial Mammals, United States, 2022.

We describe the pathology of natural infection with highly pathogenic avian influenza A(H5N1) virus of Eurasian lineage Goose/Guangdong clade 2.3.4.4b in 67 wild terrestrial mammals throughout the United States during April 1‒July 21, 2022. Affected mammals include 50 red foxes (Vulpes vulpes), 6 striped skunks (Mephitis mephitis), 4 raccoons (Procyon lotor), 2 bobcats (Lynx rufus), 2 Virginia opossums (Didelphis virginiana), 1 coyote (Canis latrans), 1 fisher (Pekania pennanti), and 1 gray fox (Urocyon cinereoargenteus). Infected mammals showed primarily neurologic signs. Necrotizing meningoencephalitis, interstitial pneumonia, and myocardial necrosis were the most common lesions; however, species variations in lesion distribution were observed. Genotype analysis of sequences from 48 animals indicates that these cases represent spillover infections from wild birds.

Distribution of canine distemper virus and nectin-4 in raccoon (Procyon lotor) skin.

Raccoons (Procyon lotor) are abundant in urban/wildland interfaces and are key sources of canine distemper virus (CDV) outbreaks in domestic, zoo, and free-ranging wildlife species. CDV is pantropic, which provides multiple potential routes of transmission (urine, respiratory secretions, feces), but the specific role of skin as a target of infection, as a diagnostic sample, or as a potential source of environmental persistence and transmission is unknown. We have characterized the distribution of CDV and its known receptor, nectin-4, in skin samples of 36 raccoons. Even with skin samples that were grossly and histologically normal, immunohistochemistry of skin was useful in the diagnosis of CDV infection, which was found in both epithelium and endothelium. Nectin-4 was codistributed with cellular targets of viral infection. Skin secretions, shed keratinocytes, and hair of CDV infected raccoons are all potential environmental fomites.

Eastern Equine Encephalitis Virus in Mexican Wolf Pups at Zoo, Michigan, USA.

During the 2019 Eastern equine encephalitis virus (EEEV) outbreak in Michigan, two 2-month old Mexican wolf pups experienced neurologic signs, lymphohistiocytic neutrophilic meningoencephalitis with neuronal necrosis and neuronophagia, and acute death. We identified EEEV by reverse transcription real-time PCR and in situ hybridization. Vector mosquitoes were trapped at the zoo.

PRESUMPTIVE CONGENITAL HYPOTHYROIDISM IN RED PANDAS (AILURUS FULGENS FULGENS) FROM FOUR SUCCESSIVE LITTERS.

High neonatal mortality among red pandas (Ailurus fulgens) challenges the long-term sustainability of the Species Survival Plan population. Congenital hypothyroidism (CH) is a rare condition in domestic animals, typically due to an inherited genetic defect. Nongoitrous CH was presumptively diagnosed in 75% (n = 6/8) of red panda neonates from four successive litters, with a common sire and two closely related dams. Antemortem diagnosis of CH was made in three cubs (n = 3/6) based on elevated thyroid stimulating hormone and decreased free thyroxine and total thyroxine levels. Affected cubs also had suggestive clinical signs, which included delayed growth with cretinous dwarf appearance, atonic bladder, delayed gastrointestinal motility, hypercholesterolemia, and hypocalcemia. With sodium levothyroxine therapy, two of the three cubs developed into normal adult red pandas in terms of body size, appearance, and behavior. On necropsy cubs (n = 4) were small with varying degrees of cretin dwarf appearance and hypoplastic thyroids with reduced to no colloid in follicles. These cases demonstrate the importance of collecting thyroid tissue, (or proximal trachea/larynx if gross visualization not possible), in neonates for histopathology. Further investigation into the role of thyroid disease in neonatal red panda mortality is warranted.

Disease Progression in Lake Trout (Salvelinus namaycush) Experimentally Infected With Epizootic Epitheliotropic Disease Virus (Salmonid Herpesvirus-3).

Epizootic epitheliotropic disease virus (salmonid herpesvirus-3; EEDV) is responsible for the death of millions of hatchery-raised lake trout (Salvelinus namaycush) in the Laurentian Great Lakes Basin. However, little is known about its biology, pathology, tropism, and host interactions. In this study, the presence and disease progression of EEDV were evaluated following exposure of naïve juvenile lake trout to EEDV via bath immersion under controlled laboratory conditions (n = 84 infected; n = 44 control). Individual tissues (n = 10 per fish), collected over 6 weeks, were analyzed for viral load by quantitative polymerase chain reaction, gross and histopathologic changes, and virus cellular targets using in situ hybridization. Skin, fin, and ocular tissues were the earliest viral targets and yielded the highest viral loads throughout the course of infection. Early gross lesions included exophthalmia, ocular hemorrhage, fin congestion, and hyperemia of visceral blood vessels. Advanced disease was characterized by multifocal to coalescing erosions and ulcerations of the skin, and congestion of visceral organs. Microscopically, there was cellular degeneration and necrosis in the epidermis and spleen, and lymphohistiocytic perivasculitis of the dermis, omentum, and the epicardium. EEDV DNA was first detected by in situ hybridization in epithelial cells of the epidermis, with subsequent labeling in the epithelial lining of primary and secondary gill lamellae. During advanced disease, EEDV was detected in endothelial and dendritic cells as well as blood monocytes. This study characterized EEDV tissue tropism and associated pathologic features, to guide research aimed at understanding EEDV disease ecology and improving strategies for disease control.

DNA Vaccination Partially Protects Muskellunge against Viral Hemorrhagic Septicemia Virus (VHSV-IVb).

A DNA vaccine containing the glycoprotein (G) gene of the North American viral hemorrhagic septicemia virus (VHSV) genotype IVb was developed to evaluate the immune response of fish following vaccination and evaluate its efficacy in protecting a susceptible species, the Muskellunge Esox masquinongy, against VHSV-IVb challenge. Seven weeks (539 degree-days) following vaccination with 10 µg of either pVHSivb-G or a control plasmid, Muskellunge were challenged by immersion with 105 plaque-forming units (pfu)/mL of VHSV-IVb. Fish vaccinated with pVHSivb-G had a relative percent survival (RPS) of 45%. Vaccinated fish also had significantly lower mean viral titers in tissues (4.2 × 102 pfu/g) and viral prevalence (4%) than fish receiving the plasmid control vaccine (3.3 × 105 pfu/g; 82%). Neutralizing antibodies were detected 28 d (308 degree-days) postchallenge (11 weeks postvaccination) in 100% of Muskellunge vaccinated with pVHSivb-G compared with only 12% of plasmid-control-vaccinated Muskellunge, suggesting robust induction of a secondary, adaptive immune response. In addition, pVHSivb-G-vaccinated Rainbow Trout Oncorhynchus mykiss challenged 7 d (100 degree-days) postvaccination with the heterologous novirhabdovirus, infectious hematopoietic necrosis virus (IHNV), experienced an RPS of 61%, compared to control fish, suggesting induction of an early and transient nonspecific antiviral immune response. This study provides an important starting point for VHSV-IVb vaccine development and useful information about the antiviral immune response elicited by DNA vaccination in a nondomesticated fish species. Received May 1, 2016; accepted September 1, 2016.

Bacterial Dose-Dependent Role of G Protein-Coupled Receptor Kinase 5 in Escherichia coli-Induced Pneumonia.

G protein-coupled receptor kinase 5 (GRK5) is a serine/threonine kinase previously shown to mediate polymicrobial sepsis-induced inflammation. The goal of the present study was to examine the role of GRK5 in monomicrobial pulmonary infection by using an intratracheal Escherichia coli infection model of pneumonia. We used sublethal and lethal doses of E. coli to examine the mechanistic differences between low-grade and high-grade inflammation induced by E. coli infection. With a sublethal dose of E. coli, GRK5 knockout (KO) mice exhibited higher plasma CXCL1/KC levels and enhanced lung neutrophil recruitment early after infection, and lower bacterial loads, than wild-type (WT) mice. The inflammatory response was also diminished, and resolution of inflammation advanced, in the lungs of GRK5 KO mice. In contrast to the reduced bacterial loads in GRK5 KO mice following a sublethal dose, at a lethal dose of E. coli, the bacterial burdens remained high in GRK5 KO mice relative to those in WT mice. This occurred in spite of enhanced plasma CXCL1 levels as well as neutrophil recruitment in the KO mice. But the recruited neutrophils (following high-dose infection) exhibited decreased CD11b expression and reduced reactive oxygen species production, suggesting decreased neutrophil activation or increased neutrophil exhaustion in the GRK5 KO mice. In agreement with the increased bacterial burden, KO mice showed poorer survival than WT mice following E. coli infection at a lethal dose. Overall, our data suggest that GRK5 negatively regulates CXCL1/KC levels during bacterial pneumonia but that the role of GRK5 in the clinical outcome in this model is dependent on the bacterial dose.

Severe necrotic dermatitis in the combs of line 63 chickens infected with Marek's disease virus.

Marek's disease virus (MDV), the aetiological agent of Mareks' disease (MD), is a highly cell-associated oncogenic α-herpesvirus that replicates in chicken lymphocytes and establishes a latent infection within CD4(+) T cells. We investigated the possible effect of MDV infection on the exacerbation of necrotic dermatitis in the combs of MD-susceptible (72) and MD-resistant (63) chicken lines at 21 days post infection. MDV-infected birds of line 63 are relatively resistant to tumour development but exhibit an unusual necrosis of combs, wattles, and footpads that is intensified when infected with MDV. Chickens from line 72, on the other hand, are highly susceptible to MDV infection and tumour development. Real-Time PCR analysis revealed that IL-6, IL-8, IL-12, IL-18, iNOS, and IFNγ were all up regulated in the comb tissues of MDV-infected susceptible line 72 with no visible necrotic damage. With the exception of IL-8 and iNOS, the expression of all the other tested genes was barely detected in the necrotic combs of the resistant line 63. Real-Time PCR analysis revealed the MDV meq oncogene transcripts in the spleen tissues of both infected lines but in the comb tissues of only the susceptible line 72. A significant infiltration of macrophages and lymphocytes was detected in the comb tissues of both resistant and susceptible lines. Histopathological analysis also showed thinning and erosion of epidermis and inflammation, lympho-plasmocytic infiltration, heterophilic, and histocytic cellulitis within the connective tissues of the necrotic combs. Gram stain of the sectioned frozen comb samples exposed the presence of Gram-positive micrococcus.

TREATMENT OF RENAL CARCINOMA IN A BINTURONG (ARCTICTIS BINTURONG) WITH NEPHRECTOMY AND A TYROSINE KINASE INHIBITOR.

A 13-yr-old female binturong ( Arctictis binturong ) presented with a 1 wk history of decreased appetite. The animal was thin, with hypercalcemia (calcium 12.2 mg/dl). A right renal mass was identified on ultrasound and removed via nephrectomy. Histopathology indicated a renal adenocarcinoma. Treatment with toceranib phosphate, a tyrosine-kinase inhibitor, was initiated and well tolerated by the animal. Four months after initial diagnosis radiographs indicated metastases to the lungs and the animal was euthanized. Necropsy revealed disseminated adenocarcinoma. Although treatment did not prevent metastasis, it was minimally invasive and well tolerated by the animal with minimal side effects. Review of records at the institution revealed that the cause of death for the primary case's dam and sire was disseminated renal carcinoma. These cases suggest that there may be a hereditary component to development of renal neoplasia in binturongs. Renal carcinoma should be considered an aggressive neoplasia in binturongs with a poor prognosis.

Immune Responses in Cecal Tonsils of Marek's Disease Virus-Infected Chickens.

Marek's disease (MD) is a lymphoproliferative disease of domestic chickens that is caused by a highly cell-associated oncogenic α-herpesvirus, Marek's disease virus (MDV). MDV replicates in chicken lymphocytes and establishes a latent infection within CD4+ T cells. Clinical signs of MD include depression, crippling, weight loss, bursal/thymic atrophy, neurologic disorders, and rapid onset of T cell lymphomas that infiltrate lymphoid tissues, visceral organs, and peripheral nerves. The cecal tonsils (CTs) are considered the largest lymphoid aggregates of avian gut-associated lymphoid tissue. Along with Peyer's patches, CTs elicit protective immune responses against bacterial and viral pathogens in the intestinal tract of avian species. In this study, we investigated the effect of MDV infection on toll-like receptor (TLR) gene expression in CTs of MD-susceptible (72) and resistant (63) chicken lines. Real-time PCR gene expression profiling revealed that of the 10 TLRs tested, TLR2A, TLR3, TLR5, and TLR15 displayed significant differential expression patterns at different time points postinoculation. The expression levels of the remaining six genes were minimally affected by MDV infection in either line. Immunohistochemical analysis showed a severe depletion of B cells and CD4+ T cells in the CTs of susceptible line at 5 days postinfection (dpi), which recovered by 21 dpi. The destruction of B and T cells in the CTs of the resistant line was minimal at 5 dpi, which also recovered by 21 dpi. A significant infiltration of macrophages was observed after the depletion of B and T cells in the infected birds of both lines that could account for the differential TLR gene expression in the infected birds. The data presented provide further insight into the mechanism of MDV pathogenesis and tissue-specific immunologic responses to viral infection.

Marek's disease virus-induced transient cecal tonsil atrophy.

Marek's disease (MD) is a lymphoproliferative disease of domestic chickens that is caused by a highly cell-associated oncogenic alpha-herpesvirus, Marek's disease virus (MDV). MDV replicates in chicken lymphocytes and establishes a latent infection within CD4+ T cells. MD is characterized by bursal and thymic atrophy and rapid onset of T cell lymphomas that infiltrate lymphoid tissues, visceral organs, and peripheral nerves with severe clinical symptoms that include transient paralysis, anemia, weight loss, and neurologic disorders. The cecal tonsils (CT) are considered the largest lymphoid aggregates of avian gut-associated lymphoid tissue (GALT). Along with Peyer's patches, CT elicits protective immune responses against bacterial and viral pathogens in the intestinal tract of avian species. In this study we investigated the effect of MDV infection on CT structural changes and cytokine gene expression in two MD-susceptible and resistant chicken lines. The histopathologic analysis revealed that MDV causes the loss of germinal follicular centers within the CT of the resistant line while inducing a severe, near-total lymphoid depletion in the susceptible line during cytolytic infection. The lymphoid depletion, however, recovered approximately 2 wk postinfection but the loss of germinal centers persisted during the latent phase of infection in both lines. The atrophy of this important GALT was transient and there were no visible differences between the CT of the infected and control birds of either line by 21 days postinfection. Of the genes tested, IFN-beta and IFN-gamma were up regulated in the CT of both infected lines during lytic infection. The expression levels of both genes were much higher in the susceptible line than in the resistant line. A similar pattern of expression was observed for IL-6, IL-10, IL-13, and iNOS. IL-12 was up regulated in the CT of birds of the susceptible line during all three phases of infection. An over expression of IL-18 was also observed in CT of the susceptible line during lytic and latent phases of infection. IL-8 was the only cytokine expressed at higher levels in the CT of the resistant line during the lytic and reactivation phases of infection. The histopathologic observations and gene expression profiling are further discussed.

Disseminated Mycobacterium haemophilum infection in an ASSAM trinket snake (Elaphe frenata).

A sub-adult male Assam trinket snake (Elaphe frenata) that was confiscated from an exotic animal dealer was found dead in its enclosure after a 17-mo quarantine. The snake had grown well during that period and had no physical examination or bloodwork abnormalities during the quarantine. On gross necropsy, masses were found in the epaxial musculature and stomach, the lung was diffusely thickened, the ventricular wall was mottled, and there was intracoelomic and pericardial effusion. Histopathology revealed diffusely disseminated granulomatous infiltrates throughout the lung interstitium and multifocal granulomatous infiltrates in the transmural gastric mass, within the myocardium and pericardial adipose tissue, in the liver and kidney parenchyma, in the cervical region surrounding the trachea and thyroid, and replacing the myofibers of the craniolateral epaxial muscles. Fite-Farracho acid-fast staining revealed numerous intracytoplasmic acid-fast bacilli within macrophages, and polymerase chain reaction testing on frozen tissues followed by nucleic acid sequencing of polymerase chain reaction amplicons identified Mycobacterium haemophilum.

Safety and efficacy evaluation of carnosine, an endogenous neuroprotective agent for ischemic stroke.

BACKGROUND AND PURPOSE: An urgent need exists to develop therapies for stroke that have high efficacy, long therapeutic time windows, and acceptable toxicity. We undertook preclinical investigations of a novel therapeutic approach involving supplementation with carnosine, an endogenous pleiotropic dipeptide. METHODS: Efficacy and safety of carnosine treatment was evaluated in rat models of permanent or transient middle cerebral artery occlusion. Mechanistic studies used primary neuronal/astrocytic cultures and ex vivo brain homogenates. RESULTS: Intravenous treatment with carnosine exhibited robust cerebroprotection in a dose-dependent manner, with long clinically relevant therapeutic time windows of 6 hours and 9 hours in transient and permanent models, respectively. Histological outcomes and functional improvements including motor and sensory deficits were sustained on 14th day poststroke onset. In safety and tolerability assessments, carnosine did not exhibit any evidence of adverse effects or toxicity. Moreover, histological evaluation of organs, complete blood count, coagulation tests, and the serum chemistry did not reveal any abnormalities. In primary neuronal cell cultures and ex vivo brain homogenates, carnosine exhibited robust antiexcitotoxic, antioxidant, and mitochondria protecting activity. CONCLUSIONS: In both permanent and transient ischemic models, carnosine treatment exhibited significant cerebroprotection against histological and functional damage, with wide therapeutic and clinically relevant time windows. Carnosine was well tolerated and exhibited no toxicity. Mechanistic data show that it influences multiple deleterious processes. Taken together, our data suggest that this endogenous pleiotropic dipeptide is a strong candidate for further development as a stroke treatment.

Comparison of destructive periodontal disease in blue iris mink to PCB 126-induced mandibular and maxillary squamous epithelial proliferation in natural dark mink.

Mink (Mustela vison) exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-like chemicals have been reported to develop mandibular and maxillary squamous cell proliferation that results in the destruction of alveolar bone and eventual tooth loss. This jaw lesion has been reported in wild mink collected from areas contaminated with TCDD-like compounds and is a potential biomarker for exposure to these chemicals. The blue iris strain of domestic mink is prone to develop severe periodontal disease, which results in destruction of bone and tooth loss that is grossly similar to the lesion induced by exposure to TCDD-like chemicals. A histological assessment of jaws from blue iris mink and natural dark mink exposed to 3,3',4,4',5-pentachlorobiphenyl (PCB 126) was done to determine whether the oral lesions are similar. The jaw tissue from the blue iris mink had lesions indicative of lymphoplasmacytic gingivitis and osteomyelitis, caused by inflammation entering the dental sulcus, while the jaw tissue from the mink exposed to PCB 126 exhibited squamous epithelial proliferation. Therefore, it was determined that the tooth loss and bone destruction seen in these mink are of different origin despite the similarity of the gross clinical signs.

Asiatic acid attenuates infarct volume, mitochondrial dysfunction, and matrix metalloproteinase-9 induction after focal cerebral ischemia.

BACKGROUND AND PURPOSE: Asiatic acid (AA) has been shown to attenuate cerebral infarction in a mouse model of focal ischemia and shows promise as a neuroprotective stroke therapy. To facilitate translation of these findings to clinical studies, we determined pharmacokinetics, a dose-response relationship, the therapeutic time window, and efficacy using multiple stroke models. We also explored potential mechanisms of action. METHODS: Escalating doses of intravenous AA were administered and serum concentrations were measured at multiple time points for the pharmacokinetic studies. Subsequently, a dose-response relationship was determined followed by administration at different intervals after the onset of ischemia to establish a therapeutic time window for neuroprotection. Outcome measurements included both histological and behavioral. Mitochondrial function and matrix metalloproteinase activity in controls and treated rats were also determined. RESULTS: The pharmacokinetic studies showed that AA (75 mg/kg) has a half-life of 2.0 hours. AA significantly decreased infarct volume and improved neurological outcome even when administration was at time points up to 12 hours after the onset of ischemia. Infarct volume was also significantly decreased in female rats and spontaneously hypertensive rats. AA attenuated mitochondrial dysfunction and reduced matrix metalloproteinase-9 induction. CONCLUSIONS: Our study shows AA is effective against multiple models of focal ischemia, has a long therapeutic time window, and is also effective in females and hypertensive animals. AA may mediate neuroprotection by protecting mitochondria and inhibiting matrix metalloproteinase-9 induction and activation. Taken together these data suggest that AA is an excellent candidate for development as a stroke therapy.

A natural outbreak of clinical toxoplasmosis in a backyard flock of guinea fowl in Mississippi.

A case of a naturally occurring infection with Toxoplasma gondii in a backyard flock of guinea fowl in north Mississippi is reported. To our knowledge, this is the first worldwide report of a natural clinical infection in a flock of guinea fowl. This case was two of seven birds lost out of approximately 20 guinea fowl present in the flock. Birds reportedly exhibited lethargy prior to death. Necropsy examinations were performed on two of the dead birds. There were no gross lesions; however, intralesional protozoan cysts suggestive of T. gondii were observed microscopically. One of two guinea fowl demonstrated dramatic microscopic pathology consisting of variable multifocal necrosis, fibrin exudation, and inflammation of spleen, lung, and heart associated with protozoa cysts and tachyzoites compatible with toxoplasmosis. The bone marrow also exhibited multifocal necrosis and fibrin exudation, as well as marked erythroid and lesser granulocytic hyperplasia with intralesional protozoan cysts. The diagnosis of toxoplasmosis was confirmed with immunohistochemistry and PCR.

Tissue Distribution of the Piscine Novirhabdovirus Genotype IVb in Muskellunge (Esox masquinongy).

A novel sublineage of the piscine novirhabdovirus (synonym: viral hemorrhagic septicemia virus), genotype IVb, emerged in the Laurentian Great Lakes, causing serious losses in resident fish species as early as 2003. Experimentally infected juvenile muskellunge (Esox masquinongy) were challenged with VHSV-IVb at high (1 × 105 PFU mL-1), medium (4 × 103 PFU mL-1), and low (100 PFU mL-1) doses. Samples from spleen, kidneys, heart, liver, gills, pectoral fin, large intestine, and skin/muscle were collected simultaneously from four fish at each predetermined time point and processed for VHSV-IVb reisolaton on Epitheliosum papulosum cyprini cell lines and quantification by plaque assay. The earliest reisolation of VHSV-IVb occurred in one fish from pectoral fin samples at 24 h post-infection. By 6 days post-infection (dpi), all tissue types were positive for VHSV-IVb. Statistical analysis suggested that virus levels were highest in liver, heart, and skin/muscle samples. In contrast, the kidneys and spleen exhibited reduced probability of virus recovery. Virus distribution was further confirmed by an in situ hybridization assay using a VHSV-IVb specific riboprobe. Heart muscle fibers, hepatocytes, endothelia, smooth muscle cells, and fibroblast-like cells of the pectoral fin demonstrated riboprobe labeling, thus highlighting the broad cellular tropism of VHSV-IVb. Histopathologic lesions were observed in areas where the virus was visualized.

GEOGRAPHIC SPREAD OF CANINE DISTEMPER IN WILD CARNIVORES IN MICHIGAN, USA: PATHOLOGY AND EPIDEMIOLOGY, 2008-18.

Canine distemper is a widespread disease affecting both domestic and wild carnivores. This investigation of the geographic distribution, wildlife species infected, and relative prevalence rates was conducted over an 11-yr period and helps to document the disease spread, most highly infected wildlife species, and histologic lesions. Animals were collected as found dead, hunter and trapper harvested, and euthanized for displaying signs of abnormal behavior or neurologic disease. This disease appeared to spread from the Lower Peninsula of Michigan into the Upper Peninsula, was most frequently documented in raccoons (Procyon lotor), striped skunks (Mephitis mephitis), and gray fox (Urocyon cinereoargenteus), but also involved additional wildlife species. Three unique wildlife virus strains were identified. Two of these grouped within a separate subclade of the America 2 lineage. A third strain appeared to be a unique sequence type that is not associated with any existing subclade of America 2. We recommend the combined use of routine histology and immunohistochemical staining to confirm the diagnosis, and further recommend that both the lungs and spleen be collected as the optimal tissues to utilize for surveillance purposes.

Pancreatic atrophy due to zinc toxicosis in two African ostriches (Struthio camelus).

Two of three captive adult African ostriches exhibited inappetance and weakness. In spite of treatment, the two birds were euthanized because of lack of clinical improvement. Postmortem examination demonstrated exocrine pancreatic degeneration, necrosis, and atrophy. Grossly, one ostrich had a markedly diminished pancreatic mass. Histologically, there was massive pancreatic acinar (exocrine) atrophy, marked interstitial fibrosis, and tubular complex formation in one animal, and the second ostrich had active pancreatic acinar necrosis. Toxicologic testing revealed markedly elevated liver zinc levels in the first two birds, whereas the third ostrich had normal serum levels of zinc and continues without apparent disease. This form of zinc toxicosis, while previously reported in different avian species, has been only rarely described in ratites.

Nephroblastoma in a Sprague Dawley rat unrelated to titanium dioxide nanoparticle exposure in utero.

Nephroblastoma is an embryonal tumour that has rarely been reported in laboratory rats. In this case report, a large nephroblastoma with peritoneal seeding was found during necropsy in an 11-month-old, female, Sprague Dawley rat. The rat had a history of indirect exposure to nano-TiO2 (titanium dioxide nanoparticles) during maternal gestation. A firm mass in the upper right abdominal quadrant was palpated. Four weeks later, the animal quickly declined. Nephroblastoma was confirmed by histopathology. Only one rat developed nephroblastoma among the ten littermates. Nephroblastomas in Sprague Dawley rats are typically spontaneous tumours with non-malignant mesenchymal elements. The capability to induce a nephroblastoma with nano-TiO2 is less likely in this case.