Simian homologues of human herpesviruses and implications for novel viral introduction to free-living mountain gorillas.

The endangered mountain gorilla (Gorilla beringei beringei) in Rwanda, Uganda, and the Democratic Republic of Congo is frequently in contact with humans through tourism, research activities, and illegal entry of people into protected gorilla habitat. Herpesviruses, which are ubiquitous in primates, have the potential to be shared in any setting where humans and gorillas share habitat. Based on serological findings and clinical observations of orofacial ulcerated lesions resembling herpetic lesions, an alpha-herpesvirus resembling human herpes simplex virus type 1 (HSV-1) has long been suspected to be present in human-habituated mountain gorillas in the wild. While the etiology of orofacial lesions in the wild has not been confirmed, HSV-1 has been suspected in captively-housed mountain gorillas and confirmed in a co-housed confiscated Grauer's gorilla (Gorilla beringei graueri). To better characterize herpesviruses infecting mountain gorillas and to determine the presence/absence of HSV-1 in the free-living population, we conducted a population-wide survey to test for the presence of orally shed herpesviruses. DNA was extracted from discarded chewed plants collected from 294 individuals from 26 groups, and samples were screened by polymerase chain reaction using pan-herpesvirus and HSV-1-specific assays. We found no evidence that human herpesviruses had infected free-ranging mountain gorillas. However, we found gorilla-specific homologs to human herpesviruses, including cytomegaloviruses (GbbCMV-1 and 2), a lymphocryptovirus (GbbLCV-1), and a new rhadinovirus (GbbRHV-1) with similar characteristics (i.e., timing of primary infection, shedding in multiple age groups, and potential modes of transmission) to their human counterparts, human cytomegalovirus, Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus, respectively.

Reproductive tract neoplasia in adult female Asian elephants (Elephas maximus).

Recent reports have highlighted a lower-than-expected prevalence of neoplasia in elephants and suggested mechanisms for cancer resistance. But despite infrequent reports in the literature, uterine neoplasia is common in managed Asian elephants (Elephas maximus). This study is an archival review of reproductive tract neoplasia in 80 adult female Asian elephant mortalities in managed care facilities in the United States from 1988 to 2019. Neoplasms occurred in 64/80 (80%) of cases. Most were in the uterus (63/64; 98%) with only a single case of ovarian neoplasia. Myometrial leiomyomas were present in 57/63 (90%) cases with uterine neoplasia. Uterine adenocarcinoma was present in 8/63 (13%) cases. Remaining cases included endometrial adenoma (2), focal carcinoma in situ in endometrial polyps (1), anaplastic carcinoma (1), endometrial hemangioma (1), primitive neuroectodermal tumor (PNET; 1), and angiosarcoma (1). One case with uterine adenocarcinoma had a separate pelvic mass histologically characterized as an anaplastic sarcoma. Distant metastases were documented in 5/8 (63%) cases of uterine adenocarcinoma, and in the uterine anaplastic carcinoma, PNET, and angiosarcoma. Four uterine adenocarcinomas and one carcinoma in situ were examined immunohistochemically for pan-cytokeratin, vimentin, and estrogen receptor. In all, neoplastic cells were pan-cytokeratin positive and vimentin negative, and in 2 cases were immunoreactive for estrogen receptor. Results show that female reproductive tract neoplasia, particularly of the uterus, is common in Asian elephants and is not limited to leiomyomas. Importantly, uterine neoplasms have the potential to impact fecundity and may represent obstacles to conservation in managed care.

Pathological lesions of the digestive tract in free-ranging mountain gorillas (Gorilla beringei beringei).

The finding of parasites and bacterial pathogens in mountain gorilla feces and oral lesions in gorilla skeletal remains has not been linked to pathological evidence of morbidity or mortality. In the current study, we conducted a retrospective study of digestive tracts including oral cavity, salivary glands, esophagus, stomach, intestines (gastrointestinal tract [GI]), liver, and pancreas of 60 free-ranging mountain gorillas from Uganda, Rwanda, and the Democratic Republic of Congo that died between 1985 and 2007. We reviewed clinical histories and gross pathology reports and examined histological sections. On histology, enteritis (58.6%), gastritis (37.3%), and colitis (29.3%) were the commonest lesions in the tracts. Enteritis and colitis were generally mild, and judged likely to have been subclinical. Gastritis was often chronic and proliferative or ulcerative, and associated with nematodiasis. A gastro-duodenal malignancy (carcinoid) was present in one animal. A number of incidental lesions were identified throughout the tract and cestodes and nematodes were frequently observed grossly and/or histologically. Pigmentation of teeth and tongue were a common finding, but periodontitis and dental attrition were less common than reported from past studies of skeletal remains. Despite observing numerous GI lesions and parasites in this study of deceased free-living mountain gorillas, we confirmed mortality attributable to gastroenteritis in just 8% (5/60) cases, which is less than that described in captive gorillas. Other deaths attributed to digestive tract lesions included cleft palate in an infant, periodontal disease causing systemic infection in an older adult and gastric cancer. Of all the parasitic infections observed, only hepatic capillariasis and gastric nematodiasis were significantly associated with lesions (hepatitis and gastritis, respectively). Understanding GI lesions in this endangered species is key in the management of morbidity associated with GI ailments.

Morbidity and mortality in infant mountain gorillas (Gorilla beringei beringei): A 46-year retrospective review.

Long-term studies of morbidity and mortality in free-ranging primates are scarce, but may have important implications for the conservation of extant populations. Infants comprise a particularly important age group, as variation in survival rates may have a strong influence on population dynamics. Since 1968, the Mountain Gorilla Veterinary Project (MGVP, Inc.) and government partners have conducted a comprehensive health monitoring and disease investigation program on mountain gorillas (Gorilla beringei beringei) in Rwanda, Uganda, and the Democratic Republic of the Congo. In an effort to better understand diseases in this species, we reviewed reliable field reports (n = 37), gross post-mortem (n = 66), and histopathology (n = 53) reports for 103 infants (less than 3.5 years) mountain gorillas in the Virunga Massif. Our aim was to conduct the first comprehensive analysis of causes of infant mortality and to correlate histological evidence with antemortem morbidity in infant mountain gorillas. Causes of morbidity and mortality were described, and compared by age, sex, and over time. Trauma was the most common cause of death in infants (56%), followed by respiratory infections and aspiration (13%). Gastrointestinal parasitism (33%), atypical lymphoid hyperplasia (suggestive of infectious disease) (31%), and hepatic capillariasis (25%) were the most significant causes of antemortem morbidity identified post-mortem. Identifying the causes of mortality and morbidity in infants of this critically endangered species will help to inform policy aimed at their protection and guide ante- and post-mortem health monitoring and clinical decision-making in the future.

Ectopic pregnancy with associated gestational choriocarcinoma in a California sea lion (Zalophus californianus).

A wild-born, captive-reared, 14 yr old, primiparous female California sea lion Zalophus californianus presented for anorexia of 14 d duration and abdominal distention. Routine complete blood cell count revealed leukocytosis with a neutrophilia, and serum chemistry revealed hypoalbumenemia and hyponatremia. Treatment with broad spectrum antibiotics and non-steroidal anti-inflammatories were started, but the animal continued to decline. Abdominal radiographs revealed a mature mineralized fetal skull and spine in the caudal abdomen and abdominal ultrasound revealed ascites but could not confirm the fetus. The patient was taken to surgery where a full term fetus was found outside of the uterus but within the fetal membranes, representing a secondary ectopic pregnancy. The patient passed away during surgery and was taken to necropsy. Gross necropsy revealed a diffuse peritonitis with yellow deposits over the serosal surfaces of the abdominal organs. The uterus appeared intact grossly and the ovaries appeared abnormal. The mesenteric, renal, and sub-lumbar nodes were enlarged and edematous. Histopathology revealed choriocarcinoma in the right uterine horn with evidence of chronic uterine rupture and protrusion of the placental tissue into the abdomen. The choriocarcinoma had metastasized locally as well as to the liver, spleen and lung. Choriocarcinoma is a highly malignant trophoblastic neoplasm that is rare in domestic animals. This case represents, to the authors' knowledge, the first report of gestational choriocarcinoma causing secondary ectopic pregnancy in a California sea lion and presents questions regarding pregnancy monitoring and management in a population of captive, minimally trained California sea lions.

Human herpes simplex virus type 1 in confiscated gorilla.

In 2007, we detected human herpes simplex virus type 1, which caused stomatitis, in a juvenile confiscated eastern lowland gorilla (Gorilla beringei graueri) that had a high degree of direct contact with human caretakers. Our findings confirm that pathogens can transfer between nonhuman primate hosts and humans.

Lethal effects of water quality on threatened California salamanders but not on co-occurring hybrid salamanders.

Biological invasions and habitat alteration are often detrimental to native species, but their interactions are difficult to predict. Interbreeding between native and introduced species generates novel genotypes and phenotypes, and human land use alters habitat structure and chemistry. Both invasions and habitat alteration create new biological challenges and opportunities. In the intensively farmed Salinas Valley, California (U.S.A.), threatened California tiger salamanders (Ambystoma californiense) have been replaced by hybrids between California tiger salamander and introduced barred tiger salamanders (Ambystoma tigrinum mavortium). We conducted an enclosure experiment to examine the effects habitat modification and relative frequency of hybrid and native California tiger salamanders have on recruitment of salamanders and their prey, Pacific chorus frogs (Pseudacris regilla). We tested whether recruitment differed among genetic classes of tiger salamanders (hybrid or native) and pond hydroperiod (seasonal or perennial). Roughly 6 weeks into the experiment, 70% (of 378 total) of salamander larvae died in 4 out of 6 ponds. Native salamanders survived (n = 12) in these ponds only if they had metamorphosed prior to the die-offs. During die-offs, all larvae of native salamanders died, whereas 56% of hybrid larvae died. We necropsied native and hybrid salamanders, tested water quality, and queried the California Department of Pesticide Regulation database to investigate possible causes of the die-offs. Salamander die-offs, changes in the abundance of other community members (invertebrates, algae, and cyanobacteria), shifts in salamander sex ratio, and patterns of pesticide application in adjacent fields suggest that pesticide use may have contributed to die-offs. That all survivors were hybrids suggests that environmental stress may promote rapid displacement of native genotypes.

Respiratory disease in mountain gorillas (Gorilla beringei beringei) in Rwanda, 1990-2010: outbreaks, clinical course, and medical management.

Between 1990 and 2010, 18 outbreaks of respiratory disease occurred in Rwanda's wild human-habituated mountain gorillas (Gorilla beringei beringei). An outbreak was defined as clinically observable respiratory illness involving at least one third of all the gorillas in a family group (> 30% morbidity) over the course of at least 7 days. Outbreaks lasted 2 wk to 4 mo and affected up to five different gorilla family groups, either concurrently or sequentially. An outbreak was considered over if no further clinical illness was observed in the same or another group for at least 1 mo. Clinical signs varied from nasal discharge, sneezing, and mild intermittent coughing (mild), to spasmodic coughing, lethargy, and partial anorexia (moderate), to dyspnea, tachypnea, respiratory distress, weakness, complete anorexia, and occasionally death (severe). Nearly every mountain gorilla group habituated for tourism or research in Rwanda experienced at least one outbreak, and they may be increasing in frequency. In the first 15 yr of the review period 1990-2005, there were nine outbreaks involving 16 gorilla groups; in the last 5 yr of the review period, 2006-2010, there were nine outbreaks involving 11 groups. Although most gorillas recovered without treatment, 41 veterinary procedures were required to medically manage 35 severely ill individuals. Given the rise of mountain gorilla ecotourism in Rwanda, the possibility that respiratory disease results from contact with infected humans is of great concern, and both the etiology and epidemiology of this problem are active areas of research. The observed clinical signs, response to antimicrobial therapy among the sickest individuals, and postmortem findings are most consistent with viral upper respiratory tract infections complicated in some cases by secondary bacterial infections. The current gorilla visitation rules have been designed to minimize the risk of disease transmission between humans and wild human-habituated great apes.

Squamous cell carcinoma of the anal sac in a spotted hyena (Crocuta crocuta).

A 25-yr-old spayed female spotted hyena (Crocuta crocuta) developed intermittent right pelvic limb lameness that persisted following conservative medical therapy. No obvious musculoskeletal lesions were noted on initial physical exam; however, spinal radiography was suspicious for possible intervertebral degenerative joint disease or discospondylitis. Despite prolonged medical therapy, the lameness progressed to minimal weight bearing and marked muscle atrophy of the right pelvic limb. Electromyography showed spontaneous activity in the muscles of right sciatic nerve distribution. Sensory and motor nerve conduction velocities in the right tibial and peroneal nerves were undetectable and markedly reduced, respectively. A magnetic resonance imaging (MRI) scan revealed a large, space-occupying mass on the right side of the sacrum and pelvis. Antemortem fine-needle aspiration of the mass and postmortem histopathology resulted in diagnosis of a high-grade squamous cell carcinoma of the anal sac. Squamous cell carcinoma of the anal sac is very rare in domestic dogs and previously unreported in spotted hyenas.

Human metapneumovirus infection in wild mountain gorillas, Rwanda.

The genetic relatedness of mountain gorillas and humans has led to concerns about interspecies transmission of infectious agents. Human-to-gorilla transmission may explain human metapneumovirus in 2 wild mountain gorillas that died during a respiratory disease outbreak in Rwanda in 2009. Surveillance is needed to ensure survival of these critically endangered animals.

T-cell chronic lymphocytic leukemia in a double yellow-headed Amazon parrot (Amazona ochrocephala oratrix).

An adult, male double yellow-headed Amazon parrot (Amazona ochrocephala oratrix) was diagnosed with chronic lymphocytic leukemia based on results of a complete blood cell count and cytologic examination of a bone marrow aspirate. Treatment with oral chlorambucil was attempted, but no response was evident after 40 days. The bird was euthanatized, and the diagnosis of chronic lymphocytic leukemia was confirmed on gross and microscopic examination of tissues. Neoplastic lymphocytes were found in the bone marrow, liver, kidney, testes, and blood vessels. Based on CD3-positive immunocytochemical and immunohistochemical immunophenotyping, the chronic lymphocytic leukemia was determined to be of T-cell origin.

Polyomavirus infection in a free-ranging California sea lion (Zalophus californianus) with intestinal T-cell lymphoma.

An adult female California sea lion (Zalophus californianus) that stranded in central California was found to have a small glossal polypoid mass on gross necropsy. Histologically, the mass was consistent with a fibropapilloma, and intranuclear inclusions were found within endothelial cells lining small arterioles within the mass. Electron microscopy revealed 40-nm virions within endothelial intranuclear inclusions. Rolling circle amplification was used to obtain a partial viral genomic sequence. Sequence analysis identified the virus as a novel polyomavirus, tentatively named California sea lion polyomavirus 1. In addition, the sea lion had a severely thickened small intestine and swollen pale kidneys on gross examination. Severe renal amyloidosis with chronic interstitial nephritis was diagnosed histologically as well as T-cell intestinal lymphoma, which was confirmed via immunophenotyping and molecular clonality. The relationship, if any, between polyomavirus infection and the other disease processes in this sea lion is not known, but it is considered unlikely that the polyomavirus induced the lymphoma.

West Nile virus infection in a green-winged macaw (Ara chloropterus).

A 29-year-old female green-winged macaw (Ara chloropterus) was presented for acute pelvic limb lameness. On physical examination the bird was found to be mildly dehydrated with paraparesis and proprioceptive deficits of the pelvic limbs. Antemortem diagnostics included a complete blood count and plasma biochemistry panel, fecal Gram and Ziehl-Neelsen acid fast stains, plasma heavy metal concentrations, reverse transcriptase (RT)-PCR testing for West Nile virus (WNV) RNA and PCR testing for Chlamydophila psittaci DNA from choanal/cloacal swabs, and survey radiography. Abnormal findings included a heterophilic leukocytosis, elevated kidney and muscle enzyme values, and a positive RT-PCR result for West Nile viral RNA. Although the bird showed some improvement with supportive care, on the fourth day it began having seizures and was euthanatized. There were no abnormal findings detected on gross necropsy; however, histopathology revealed mononuclear inflammatory cell infiltration in multiple organs including brain, heart, and pancreas. WNV antigen and RNA were detected using immunohistochemistry and RT-PCR in various tissues including brain, pancreas, and spleen. WNV was successfully isolated from brain, pancreas, spleen, and liver. To our knowledge, this is the first report characterizing WNV disease in a green-winged macaw and one of few reports of this disease in a psittacine bird.

Detection of a respiratory coronavirus from tissues archived during a pneumonia epizootic in free-ranging Pacific harbor seals Phoca vitulina richardsii.

In June 2000, 21 adult harbor seals Phoca vitulina richardsii were found dead along a localized section of the central California coast. Necropsy of 5 fresh carcasses revealed pulmonary congestion, consolidation, and hemorrhage. Histopathological changes in lungs from 2 of these seals included a necrotizing lymphocytic and histocytic lobar pneumonia with intra-lesional bacteria. A coronavirus (CoV) was detected in archived tissues from 1 of the 5 seals via a degenerate PCR for nidoviral RNA-dependent RNA polymerase (RdRp), and was subsequently confirmed via specific PCR. Based on the partial RdRp sequence, the CoV was identified as a novel, divergent member of the CoV group 1a. The virus is tentatively named harbor seal coronavirus (HSCoV). The clinical significance of HSCoV and its involvement in the etiology of the epizootic pneumonia and deaths of the harbor seals is uncertain.

Morphologic, immunohistochemical, and molecular characterization of a novel Lankesterella protozoan in two White's tree frogs (Litoria caerulea).

Two White's tree frogs (Litoria caerulea) housed at a zoological park died after a short period of lethargy, weight loss, and edema. Detailed postmortem examinations were performed on both frogs, including bacterial cultures and complete histologic examinations. Intracytoplasmatic as well as free protozoan parasites were identified in multiple organs from both frogs. The parasites were identified within erythrocytes, leukocytes, endothelial cells, and hepatocytes. Immunohistochemistry demonstrated a cross-reaction with Toxoplasma gondii antisera. Parasite ultrastructural analysis was performed by transmission electron microscopy. The parasites demonstrated an apical complex containing a conoid, rhoptries, and micronemes, demonstrating it was a member of the phylum Apicomplexa. In addition, the parasites had bipolar paranuclear bodies, organelles that are typical of coccidian sporozoites. The organisms were tentatively identified as members of the genus Lankesterella on the basis of histologic and ultrastructural morphology. A portion of the 18s ribosomal RNA (rRNA) gene was amplified via a polymerase chain reaction, sequenced, and used in a Basic Local Alignment Search Tool search of the GenBank database. The 18s rRNA gene sequence was found to be most similar to gene sequences isolated from Lankesterella organisms (88%). In aggregate, these data support the classification of these protozoa as a novel species of Lankesterella. A causal relationship between frog morbidity and protozoal parasitism was not determined. This is the first report of Lankesterella sp. in White's tree frogs.

Myxozoan parasitism in waterfowl.

Myxozoans are spore-forming, metazoan parasites common in cold-blooded aquatic vertebrates, especially fishes, with alternate life cycle stages developing in invertebrates. We report nine cases of infection in free-flying native and captive exotic ducks (Anseriformes: Anatidae) from locations across the United States and describe the first myxozoan in birds, Myxidium anatidum n. sp. We found developmental stages and mature spores in the bile ducts of a Pekin duck (domesticated Anas platyrhynchos). Spores are lens-shaped in sutural view, slightly sigmoidal in valvular view, with two polar capsules, and each valve cell has 14-16 longitudinal surface ridges. Spore dimensions are 23.1 microm x 10.8 microm x 11.2 microm. Phylogenetic analysis of the ssrRNA gene revealed closest affinity with Myxidium species described from chelonids (tortoises). Our novel finding broadens the definition of the Myxozoa to include birds as hosts and has implications for understanding myxozoan evolution, and mechanisms of geographical and host range extension. The number of infection records indicates this is not an incidental occurrence, and the detection of such widely dispersed cases suggests more myxozoans in birds will be encountered with increased surveillance of these hosts for pathogens.

Histopathology of the urinary bladders of cynomolgus monkeys treated with PPAR agonists.

Peroxisome proliferator-activated receptors (PPAR) are involved in the pathogenesis of insulin resistance, diabetes, hyperlipidemias, and related complications. Consequently, a mechanistic understanding of PPAR subtypes and their activation provides promising therapeutic targets for the management of type 2 diabetes mellitus and the metabolic syndrome. Available data from rodent carcinogenicity studies, however, demonstrate that PPAR agonists can be tumorigenic in one or more species of rodents at multiple sites. Sufficient data are not yet available to explain the mode(s) of action for most of these tumor types. There has been information presented by FDA that indicates there are urothelial changes in the monkey (and possibly the dog) in addition to the rat. Outstanding questions exist regarding potency, species differences, safety margins, and other issues. In 2005, the International Life Sciences Institute (ILSI) Health and Environmental Sciences Institute (HESI) PPAR Agonist Project Committee was established to advance research on the modes of action and potential human relevance of emerging rodent tumor data. Additionally, the HESI PPAR Agonist Project Committee authorized a Pathology Working Group (PWG) to examine the urinary bladder from cynomolgus monkeys. The focus of this PWG was to establish consistent diagnostic criteria for urothelial changes and to assess the potential relationship of these changes to treatment. Specific diagnostic criteria and nomenclature were recommended for the diagnosis of urothelial granules, vacuolation, hypertrophy, and hyperplasia in studies conducted with PPARgamma and dual alpha/gamma agonists in cynomolgus monkeys, which will assist investigators performing toxicity studies to provide data in a consistent manner between studies and laboratories. In this review of selected tissues, treatment with PPAR agonists was not associated with urothelial hypertrophy or hyperplasia, but there was an increased incidence in the size and frequency of vacuoles within the superficial urothelial and adjacent intermediate cell layers.

Disseminated lymphoma of presumptive T-cell origin in a great horned owl (Bubo virginianus).

A geriatric male great horned owl (Bubo virginianus) that was a resident at a raptor center was presented for examination because of stridor and weight loss. Results of physical examination, diagnostic imaging, and biopsy were consistent with disseminated lymphoma involving the oropharynx, neck region (including thyroid and parathyroid glands), keel, spleen, and liver. Attempts to treat the owl with chlorambucil failed, and the owl was euthanatized 5 months later. Neoplastic cells from this owl were immunoreactive to CD-3 antibody, suggesting the lymphoma was of T-cell origin.

Age-prevalence of Otarine Herpesvirus-1, a tumor-associated virus, and possibility of its sexual transmission in California sea lions.

Otarine Herpesvirus-1 (OtHV-1) is a gammaherpesvirus routinely detected in urogenital tumor tissues of adult sea lions dying during rehabilitation, To investigate the epidemiology of this virus and guide the development of a mathematical model of its role in the multifactorial etiology of cancer in California sea lions, polymerase chain reaction (PCR) amplification of an OtHV-1 specific fragment of the DNA polymerase gene was used to look for evidence of OtHV-1 infection in urogenital and pharyngeal swabs and peripheral blood mononuclear cells (PBMC) of sea lions of different ages. Samples were also examined from pregnant females and their late term in utero or aborted fetuses to investigate potential for vertical transmission. Prevalence of infection in 72 adult females was 22%, whereas it was 46% in 52 adult males, and was significantly lower in 120 juvenile animals (6%). OtHV-1 DNA was most often detected in the lower reproductive tract of the adult animals, especially the males, and rarely in the pharynx or urogenital tract of juvenile animals. These data suggest sexual transmission may an important route of transmission. Additional studies are required to confirm this mode of transmission. Additionally, the virus was detected in a single prematurely born pup, suggesting the possibility of perinatal transmission. No indication of a PBMC associated viremia was evident in adults using standard PCR or in juveniles using standard and real time PCR.

Assessment of melamine and cyanuric acid toxicity in cats.

The major pet food recall associated with acute renal failure in dogs and cats focused initially on melamine as the suspect toxicant. In the course of the investigation, cyanuric acid was identified in addition to melamine in the offending food. The purpose of this study was to characterize the toxicity potential of melamine, cyanuric acid, and a combination of melamine and cyanuric acid in cats. In this pilot study, melamine was added to the diet of 2 cats at 0.5% and 1%, respectively. Cyanuric acid was added to the diet of 1 cat at increasing doses of 0.2%, 0.5%, and 1% over the course of 10 days. Melamine and cyanuric acid were administered together at 0%, 0.2%, 0.5%, and 1% to 1 cat per dose group. No effect on renal function was observed in cats fed with melamine or cyanuric acid alone. Cats dosed with a combination were euthanized at 48 hours after dosing because of acute renal failure. Urine and touch impressions of kidneys from all cats dosed with the combination revealed the presence of fan-shaped, birefringent crystals. Histopathologic findings were limited to the kidneys and included crystals primarily within tubules of the distal nephron, severe renal interstitial edema, and hemorrhage at the corticomedullary junction. The kidneys contained estimated melamine concentrations of 496 to 734 mg/kg wet weight and estimated cyanuric acid concentrations of 487 to 690 mg/kg wet weight. The results demonstrate that the combination of melamine and cyanuric acid is responsible for acute renal failure in cats.