A Switch from Glial to Neuronal Gene Expression Alterations in the Spinal Cord of SIV-infected Macaques on Antiretroviral Therapy.

Despite antiretroviral therapy (ART), HIV-associated peripheral neuropathy remains one of the most prevalent neurologic manifestations of HIV infection. The spinal cord is an essential component of sensory pathways, but spinal cord sampling and evaluation in people with HIV has been very limited, especially in those on ART. The SIV/macaque model allows for assessment of the spinal cord at key time points throughout infection with and without ART.

Nodular and neoplastic skin lesions in an aquarium-managed group of Sabana Surinam toads Pipa parva.

Although skin disease is a common cause of morbidity and mortality in amphibians, published reports of integumentary conditions affecting skin-brooding anurans are extremely limited. This case series describes the clinical, macroscopic, and histopathologic features of nodular skin lesions in an aquarium-managed population of Sabana Surinam toads Pipa parva, a fully aquatic, skin-brooding species native to South America. The skin lesions represented an ongoing clinical concern in this group, affecting approximately 10-20% of animals throughout the study period, and were observed exclusively in females, suggesting an association with the females' specialized cutaneous reproductive anatomy.

SPINAL NEMATODIASIS IN A LINED FLAT-TAIL GECKO ().

A 5-y-old female lined flat-tail gecko () presented for acute onset of lethargy and paraplegia and was subsequently euthanized. Histologic examination of the spinal cord revealed a verminous myelitis comprising moderate, multifocal, necrotizing myelitis with intramedullary adult and larval nematodes. Molecular data and morphology indicate a cosmocercid nematode, most likely of the genus , a diverse taxon reported to parasitize reptiles, amphibians, and teleost fish.

A RETROSPECTIVE SURVEY OF NEOPLASIA IN MANAGED GIRAFFES ().

Giraffes () are commonly managed in zoos and conservation programs worldwide, but the current understanding of the occurrence and progression of neoplastic disease in this species is limited by the scarcity of published reports. This study collated documented cases of neoplasia on the basis of gross and histologic evaluation of ante- and postmortem samples. In total, 30 giraffes from 22 institutions across the United States were included.

Research-Relevant Background Lesions and Conditions in Common Avian and Aquatic Species.

Non-mammalian vertebrates including birds, fish, and amphibians have a long history of contributing to ground-breaking scientific discoveries. Because these species offer several experimental advantages over higher vertebrates and share extensive anatomic and genetic homology with their mammalian counterparts, they remain popular animal models in a variety of fields such as developmental biology, physiology, toxicology, drug discovery, immunology, toxicology, and infectious disease. As with all animal models, familiarity with the anatomy, physiology, and spontaneous diseases of these species is necessary for ensuring animal welfare, as well as accurate interpretation and reporting of study findings.

Upregulation of Superoxide Dismutase 2 by Astrocytes in the SIV/Macaque Model of HIV-Associated Neurologic Disease.

HIV-associated neurocognitive disorders (HAND) remain prevalent despite implementation of antiretroviral therapy (ART). Development of HAND is linked to mitochondrial dysfunction and oxidative stress in the brain; therefore, upregulation of antioxidant defenses is critical to curtail neuronal damage. Superoxide dismutase 2 (SOD2) is a mitochondrial antioxidant enzyme essential for maintaining cellular viability.

Association of persistent wild-type measles virus RNA with long-term humoral immunity in rhesus macaques.

Recovery from measles results in life-long protective immunity. To understand induction of long-term immunity, rhesus macaques were studied for 6 months after infection with wild-type measles virus (MeV). Infection caused viremia and rash, with clearance of infectious virus by day 14.

Characterization of an Unusual Mesenchymal Tumor in the Proventriculus of a Free-ranging Red-tailed Hawk ().

An adult, female red-tailed hawk () was presented for examination after being found unable to fly on a private citizen's property. Further diagnostic testing revealed a vascular, soft tissue mass arising from the serosal surface of the proximal proventriculus. Postmortem histological and immunohistochemical examination of the mass revealed an unusual mesenchymal tumor with features consistent with a leiomyoma or low-grade gastrointestinal stromal tumor.

Brain macrophages harbor latent, infectious simian immunodeficiency virus.

: The current review examines the role of brain macrophages, that is perivascular macrophages and microglia, as a potential viral reservoir in antiretroviral therapy (ART) treated, simian immunodeficiency virus (SIV)-infected macaques. The role, if any, of latent viral reservoirs of HIV and SIV in the central nervous system during ART suppression is an unresolved issue. HIV and SIV infect both CD4 lymphocytes and myeloid cells in blood and tissues during acute and chronic infection.

Amphibian Renal Disease.

Amphibians are a remarkably diverse group of vertebrates with lifestyles ranging from fully aquatic to entirely terrestrial. Although some aspects of renal anatomy and physiology are similar among all amphibians, species differences in nitrogenous waste production and broad normal variation in plasma osmolality and composition make definitive antemortem diagnosis of renal disease challenging. Treatment is often empirical and aimed at addressing possible underlying infection, reducing abnormal fluid accumulation, and optimizing husbandry practices to support metabolic and fluid homeostasis.

FATAL RANAVIRUS INFECTION IN A GROUP OF ZOO-HOUSED MELLER'S CHAMELEONS ().

A group of five juvenile Meller's chameleons () experienced 100% mortality over a period of 1 mo due to ranavirus infection. The index case was found dead without premonitory signs. The three subsequent cases presented with nonspecific clinical signs (lethargy, decreased appetite, ocular discharge) and were ultimately euthanatized.

Myeloid and CD4 T Cells Comprise the Latent Reservoir in Antiretroviral Therapy-Suppressed SIVmac251-Infected Macaques.

Human immunodeficiency virus (HIV) eradication or long-term suppression in the absence of antiretroviral therapy (ART) requires an understanding of all viral reservoirs that could contribute to viral rebound after ART interruption. CD4 T cells (CD4s) are recognized as the predominant reservoir in HIV type 1 (HIV-1)-infected individuals. However, macrophages are also infected by HIV-1 and simian immunodeficiency virus (SIV) during acute infection and may persist throughout ART, contributing to the size of the latent reservoir.

Histologic Findings in Captive American Horseshoe Crabs ().

Histopathology of 61 captive American horseshoe crabs (HSCs; ) is reviewed. HSC organs evaluated histologically included body wall (chitin, epidermis, dermis, and skeletal muscle), hepatopancreas, gut, gonads, book gills, eyes, heart, brain, and coxal gland. In descending order, lesions were most frequently identified in compound eye, body wall, book gills, hepatopancreas, chitinous gut, nonchitinous gut, heart, and brain; lesions were not observed in coxal gland or gonads.

Intraepidermal Nerve Fiber Analysis in Human Patients and Animal Models of Peripheral Neuropathy: A Comparative Review.

Analysis of intraepidermal nerve fibers (IENFs) in skin biopsy samples has become a standard clinical tool for diagnosing peripheral neuropathies in human patients. Compared to sural nerve biopsy, skin biopsy is safer, less invasive, and can be performed repeatedly to facilitate longitudinal assessment. Intraepidermal nerve fiber analysis is also more sensitive than conventional nerve histology or electrophysiological tests for detecting damage to small-diameter sensory nerve fibers.

Infectious Virus Persists in CD4 T Cells and Macrophages in Antiretroviral Therapy-Suppressed Simian Immunodeficiency Virus-Infected Macaques.

Understanding the cellular and anatomical sites of latent virus that contribute to human immunodeficiency virus (HIV) rebound is essential for eradication. In HIV-positive patients, CD4 T lymphocytes comprise a well-defined functional latent reservoir, defined as cells containing transcriptionally silent genomes able to produce infectious virus once reactivated. However, the persistence of infectious latent virus in CD4 T cells in compartments other than blood and lymph nodes is unclear.

SIV-Induced Immune Activation and Metabolic Alterations in the Dorsal Root Ganglia During Acute Infection.

Human immunodeficiency virus-associated sensory neuropathy (HIV-SN) remains a frequent neurologic complication of HIV infection. Little is known about alterations in the peripheral nervous system during the early stages of HIV, a time when neuroprotective interventions may be most beneficial. We performed Nanostring gene expression analysis on lumbar dorsal root ganglia (DRG) from 6 simian immunodeficiency virus (SIV)-infected pigtailed macaques killed at 7 days post-inoculation and 8 uninfected controls.

CAUSES OF MORTALITY IN CAPTIVE PANAMANIAN GOLDEN FROGS ( ATELOPUS ZETEKI) AT THE MARYLAND ZOO IN BALTIMORE, 2001-2013.

  The Maryland Zoo in Baltimore is home to the largest captive assurance population of the critically endangered Panamanian golden frog ( Atelopus zeteki). With the ongoing extinction that is occurring worldwide in amphibians, the need for amphibian captive assurance populations is growing, and few mortality reviews on amphibian species exist. Necropsy and histopathologic examination of animals that die in captivity can help identify population-level disease problems, direct research needs in amphibian medicine and husbandry, and improve the success of captive breeding programs.

CLINICAL EFFECT OF HEMOPARASITE INFECTIONS IN SNOWY OWLS ( BUBO SCANDIACUS).

Vector-borne hemoparasites are commonly found in avian species. Plasmodium spp., the causative agent of avian malaria, are intraerythrocytic parasites that can cause signs ranging from subclinical infection to severe acute disease.

Lymphocyte-Dominant Encephalitis and Meningitis in Simian Immunodeficiency Virus-Infected Macaques Receiving Antiretroviral Therapy.

A retrospective neuropathologic review of 30 SIV-infected pigtailed macaques receiving combination antiretroviral therapy (cART) was conducted. Seventeen animals with lymphocyte-dominant inflammation in the brain and/or meninges that clearly was morphologically distinct from prototypic SIV encephalitis and human immunodeficiency virus encephalitis were identified. Central nervous system (CNS) infiltrates in cART-treated macaques primarily comprised CD20 B cells and CD3 T cells with fewer CD68 macrophages.

An SIV/macaque model targeted to study HIV-associated neurocognitive disorders.

Simian immunodeficiency virus (SIV) infection of pigtailed macaques is a highly representative and well-characterized animal model for HIV neuropathogenesis studies that provides an excellent opportunity to study and develop prognostic markers of HIV-associated neurocognitive disorders (HAND) for HIV-infected individuals. SIV studies can be performed in a controlled setting that enhances reproducibility and offers high-translational value. Similar to observations in HIV-infected patients receiving antiretroviral therapy (ART), ongoing neurodegeneration and inflammation are present in SIV-infected pigtailed macaques treated with suppressive ART.

PIGMENTED VILLONODULAR SYNOVITIS IN A RETICULATED GIRAFFE (GIRAFFA CAMELOPARDALIS).

: A 17-yr-old, female, captive-born reticulated giraffe ( Giraffa camelopardalis ) presented with acute-onset lameness of the right metacarpophalangeal (fetlock) joint. Despite multiple courses of treatment, the lameness and swelling progressively worsened over a 3.5-yr period, and the giraffe was euthanized.

Tracking Epidermal Nerve Fiber Changes in Asian Macaques: Tools and Techniques for Quantitative Assessment.

Quantitative assessment of epidermal nerve fibers (ENFs) has become a widely used clinical tool for the diagnosis of small fiber neuropathies such as diabetic neuropathy and human immunodeficiency virus-associated sensory neuropathy (HIV-SN). To model and investigate the pathogenesis of HIV-SN using simian immunodeficiency virus (SIV)-infected Asian macaques, we adapted the skin biopsy and immunostaining techniques currently employed in human patients and then developed two unbiased image analysis techniques for quantifying ENF in macaque footpad skin. This report provides detailed descriptions of these tools and techniques for ENF assessment in macaques and outlines important experimental considerations that we have identified in the course of our long-term studies.

Persistent Peripheral Nervous System Damage in Simian Immunodeficiency Virus-Infected Macaques Receiving Antiretroviral Therapy.

Human immunodeficiency virus (HIV)-induced peripheral neuropathy is the most common neurologic complication associated with HIV infection. In addition to virus-mediated injury of the peripheral nervous system (PNS), treatment of HIV infection with combination antiretroviral therapy (cART) may induce toxic neuropathy as a side effect. Antiretroviral toxic neuropathy is clinically indistinguishable from the sensory neuropathy induced by HIV; in some patients, these 2 processes are likely superimposed.

Paving the path to HIV neurotherapy: Predicting SIV CNS disease.

HIV-induced damage to the CNS remains a major challenge for over 30 million people in the world despite the successes of combined antiretroviral therapy in limiting viral replication. Predicting development and progression of HIV-associated CNS disease is crucial because prevention and early intervention could be more effective than attempts to promote repair. The SIV/macaque model is the premier platform to study HIV neuropathogenesis, including discovery of predictive factors such as neuroprotective host genes and both blood and CSF biomarkers that precede and predict development of SIV CNS disease.