Neuroinflammatory diseases of the central nervous system of dogs: A retrospective study of 207 cases (2008-2019).

In this study we describe 207 cases of neuroinflammatory diseases of the central nervous system (CNS) in dogs autopsied at the Athens Veterinary Diagnostic Laboratory (University of Georgia, United States) from 2008 to 2019. Idiopathic and infectious diseases were diagnosed in 111 cases (53.6%) and 96 cases (46.4%), respectively. Idiopathic diseases consisted of granulomatous meningoencephalomyelitis (n = 42; 37.8% of idiopathic cases), nonspecific lymphoplasmacytic meningoencephalomyelitis (n = 39; 35.1%), necrotizing meningoencephalomyelitis (n = 22; 19.8%), presumed steroid-responsive meningitis-arteritis (n = 6; 5.4%), and necrotizing leukoencephalitis (n = 2; 1.8%). Infectious diseases consisted of bacterial infections (n = 49; 51% of infectious cases), viral infections (n = 39; 40.6%), fungal infections (n = 5; 5.2%), and parasitic infections (n = 3; 3.1%). Our study provides an overview of the most frequent neuroinflammatory diseases of the CNS of dogs in our diagnostic routine; indicates that a comprehensive diagnostic approach, including a thorough evaluation of the pathology findings and ancillary laboratory testing results, is important for an adequate diagnosis of neurologic diseases in dogs; and underscores the problems associated with the variability in tissue sample collection methods among cases. The great number of nonspecific lymphoplasmacytic meningoencephalitis also highlights the need for development of molecular laboratory tests to identify potential infectious agents in these cases.

Maladies neuro-inflammatoires du système nerveux central du chien : étude rétrospective de 207 cas (2008­2019). Dans cette étude, nous décrivons 207 cas de maladies neuro-inflammatoires du système nerveux central (SNC) chez des chiens autopsiés au Athens Veterinary Diagnostic Laboratory (University of Georgia, États-Unis) de 2008 à 2019. Des maladies idiopathiques et infectieuses ont été diagnostiquées dans 111 cas (53,6 %) et 96 cas (46,4 %), respectivement. Les maladies idiopathiques consistaient en : méningo-encéphalomyélite granulomateuse (n = 42; 37,8 % des cas idiopathiques), méningo-encéphalomyélite lymphoplasmocytaire non spécifique (n = 39; 35,1 %), méningo-encéphalomyélite nécrosante (n = 22; 19,8 %), méningite-artérite corticosensible présumée (n = 6; 5,4 %) et leucoencéphalite nécrosante (n = 2; 1,8 %). Les maladies infectieuses comprenaient des infections bactériennes (n = 49; 51 % des cas infectieux), des infections virales (n = 39; 40,6 %), des infections fongiques (n = 5; 5,2 %), et des infections parasitaires (n = 3; 3,1 %). Notre étude donne un aperçu des maladies neuro-inflammatoires du SNC des chiens les plus fréquentes dans notre routine de diagnostic; indique qu'une approche diagnostique complète, comprenant une évaluation approfondie des résultats de la pathologie et des résultats des tests de laboratoire auxiliaires, est importante pour un diagnostic adéquat des maladies neurologiques chez les chiens; et souligne les problèmes associés à la variabilité des méthodes de prélèvement d'échantillons de tissus entre les cas. Le grand nombre de méningo-encéphalites lymphoplasmocytaires non spécifiques souligne également la nécessité de développer des tests de laboratoire moléculaire pour identifier les agents infectieux potentiels dans ces cas.(Traduit par Dr Serge Messier).

The hepatic effects in dams that ingested 2-aminoanthracene during gestation and lactation.

Diabetes mellitus has been on a continual rise as one of the top chronic diseases to affect individuals worldwide. The goal of this study was to determine how exposure from a well-known toxicant, a polycyclic aromatic hydrocarbon called 2-aminoanthracene (2AA), could potentially lead to diabetes, damage the liver, and have negative effects to the offspring. Humans are exposed to 2AA from foods cooked in high heat and tobacco smoke, among others. To analyze the effects of 2AA, three groups of Sprague Dawley dams consumed an adulterated 2AA diet from gestation to their postnatal period. Timed-pregnant dams ingested 0 mg/kg (control group (C)), 50 mg/kg (low dose group (LD)), and 100 mg/kg (high dose group (HD)) 2AA. Hepatic gene expressions of Adam8, Bax, Ccng1, CD68, CD93, Cdkn1c, and Ddit4 indicated a significant overexpression of Bax, Ccng1, CD68, CD93, and Cdkn1c in treated groups. Although there was no significant difference in the damage to the liver architecture by 2AA, the positively stained CD68+ cells were slightly increased in treated rats. Significant decreases in the albumin and aspartate aminotransferase levels might indicate an inflammatory response from 2AA exposure in dams. Immunoglobulin A (IgA) concentration was also decreased, in contrast to studies of liver cirrhosis that reported increased serum IgA concentration. Overexpression of genes Ddit4, Cdkn1c, Ccng1, Bax, CD93, and CD68 point to hepatic inflammation and apoptosis. Overall results suggest a link between environmental 2AA exposure and adverse liver effects, which has potential to increase susceptibility to type 2 diabetes and other diseases.

Focal Segmental Glomerulosclerosis in Related Miniature Schnauzer Dogs.

Focal segmental glomerulosclerosis (FSGS) recently has been recognized as a common cause of proteinuria in dogs in general, and in Miniature Schnauzer dogs in particular. This study describes the morphologic features present in the kidneys of 8 related proteinuric Miniature Schnauzer dogs. The FSGS, characterized by solidification of portions of the capillary tuft, affected 32% to 49% of examined glomeruli in these dogs. Synechiae, often accompanied by hyalinosis, were present in 13% to 54% of glomeruli and were more prevalent in older dogs. Seven of 8 dogs had arteriolar hyalinosis. Ultrastructurally, all dogs had evidence of a podocytopathy in the absence of electron-dense deposits, glomerular basement membrane splitting, or fibrils. All dogs had multifocal to extensive podocyte foot process effacement. Other podocyte changes included microvillous transformation, the presence of vacuoles or protein resorption droplets, cytoplasmic electron-dense aggregates, and occasional binucleation. Variable amounts of intraglomerular lipid were present in all dogs. All dogs were proteinuric, with measured values for the urine protein-to-creatinine ratio ranging from 1.2 to 6.5. Azotemia was mild to absent and dogs were euthanatized at 5.1 to 14 years of age, in all cases due to nonrenal diseases. The underlying cause of FSGS in these Miniature Schnauzer dogs has yet to be determined, but contributors likely include genetic podocytopathy, lipid abnormalities, and glomerular hypertension.

Investigating the toxic effects of 2-aminoanthracene ingestion in pregnant Sprague Dawley dams.

Polycyclic aromatic hydrocarbons (PAHs) refer to organic compounds that are byproducts of incomplete combustion of fossil fuels and wood. One specific polycyclic aromatic hydrocarbon, 2-aminoanthracene (2AA), is a member of a broader group of compounds known as anthracenes, which have been classified by the United States Agency for Toxic Substances and Disease Registry (ASTDR) as one of a group of PAHs of top concern based on their greater potential risk for exposure and greater harmful effects to humans, compared to other PAHs. Previous research has shown that 2AA affects genes involved in carbohydrate and lipid metabolism, inflammatory stress responses, and immune system responses, among other processes. The objective of the present study was to examine the toxicity of dietary ingestion of 2AA from gestation through the postnatal period. Pregnant dams (Day 1) were purchased from Taconic Hudson, NY, and assigned into dose regimens of 0 mg/kg- (control-C), 50 mg/kg- (low dose-LD) and 100 mg/kg-diet (high dose-HD) 2AA. Dams were fed 2AA contaminated diet during the period of gestation and postpartum. Insulin and H&E immunohistochemical staining were undertaken and indicated no significant changes between control and treated groups. However, percent pancreatic islets (islets within the pancreas) were larger in the exposed groups. The value was 1.5% in the control dams compared to 3.2% and 4.3% low dose and high dose groups respectively. Serum concentrations of albumin and lactate dehydrogenase (LDH) were increased in the exposed groups, with the HD group experiencing the greater increase. Analyses of Fabp4, Mgmt , Fas, Nhej1, Aldh1a1 and Ncam1 were conducted via real-time quantitative polymerase chain reaction (RT-pPCR), using ß-Actin as the control gene. There was an up-regulation of the Mgmt and Nhej1 gene transcripts in the exposed groups, with the extent of upregulation being highest in the HD group. Taken together, a link between environmental exposure to 2AA and pancreatic effects appears to exist.

Assessment of the short-term toxicity of TiO2 nanofiber in Sprague Dawley rats.

Synthetic nanomaterials have many unique chemical and physical properties, mainly due to their high specific surface area and quantum confinement effect. Specifically, titanium dioxide (TiO2 ) nanomaterial has high stability, anticorrosive, and photocatalytic properties. However, there are concerns over adverse biological effects resulting from bioeffects. This study was to investigate adverse effects associated with acute ingestion of TiO2 nanofiber (TDNF). TDNF was fabricated via electrospinning method, followed by dissolution in water. Six- to seven-week-old male Sprague Dawley rats were exposed to a total of 0, 40, and 60 ppm of TDNF for 2 weeks via oral gavage. Serum total protein and weight gain during the course of this study displayed marginal concentration-dependent alterations. These findings were followed by a global gene expression analysis to identify which transcripts might be responsive to TNDF toxicity. Differentially expressed mRNA levels were dose-dependently higher in animals exposed to TNDF. The majority of the affected genes were biochemically involved in immune response and inflammation. We believe this is due to the fact that TNDF is unable to penetrate the cell and forms phagocytosis sites that trigger inflammatory and immune response. All results taken together, short-term ingestion of TNDF produced marginal effects indicative of inflammation. Finally, the broad gene expression data were validated through quantification of immunoglobulin heavy chain alpha (Igha). Igha gene was upregulated in treated groups, showing similar expression patterns to the global gene expression data.

Disseminated Yersinia pseudotuberculosis infection in a paca (Cuniculus paca).

A 2-yr-old paca (Cuniculus paca) was presented for necropsy with a history of sudden death. GrosS examination revealed multifocal, transmural, well-demarcated, white, soft nodules scattered along the length of the small intestine. The liver also had similar nodules associated with the capsular and cut surface. Histologic evaluation of several organs, including the intestine, liver, lung, kidney, adrenal gland, and lymph nodes, was consistent with disseminated yersiniosis. In addition, aerobic bacterial culture of liver and lung tissue yielded heavy growth of Yersinia pseudotuberculosis. Yersinia pseudotuberculosis is a Gram-negative, enteric pathogen that can cause disease in a variety of terrestrial species including humans. Although systemic infection has been observed in rodent species, to our knowledge this is the first report of disseminated Y pseudotuberculosis in a paca.

Pathology in Practice.

In collaboration with the American College of Veterinary Pathologists.

Short-Term Effects of Titanium Dioxide Nanofiber on the Renal Function of Male Sprague Dawley Rats.

Titanium dioxide nanofiber (TDNF) is widely used in the manufacture of various household products, including cosmetics. As a result, the possibility exists for TDNFs to affect human health. Because the kidneys are responsible for filtering out waste from the blood, the goal of the present study was to investigate the short-term effects of TDNF on kidney function of male Sprague Dawley rats. To achieve study objectives, 6- to 7-wk-old male rats were exposed via oral gavage to a total of 0, 40, and 60 parts per million of TDNF for 2 wk. The TDNF was fabricated by electrospinning and then dissolved in water. We measured serum concentration of lactate dehydrogenase, renal histopathology, identification of TDNF in kidney tissue via scanning electron microscopy, and quantitative amounts of titanium-47 in kidney tissue. We also measured specific gene-expression analysis of transcripts involved in apoptosis, inflammation, cell-division regulation, cell structure, and motility. Results showed a slight dose-dependent reduction in renal weight. In contrast, a concentration-dependent elevation in titanium-47 amounts was noted in kidney tissue. We found no significant differences in histopathological patterns. Gnat3 and Hepacam3 were up-regulated in TDNF-treated groups. Up-regulation of NF-κB likely indicated the involvement of renal-tissue inflammation via an independent mechanism. Similarly, Gadd45-α was significantly overexpressed in kidney tissues. This transcript was previously increased following stressful growth-arrest conditions and treatment with DNA-damaging agents. Our overall results suggest marginal renal toxicity in Sprague Dawley rats after ingesting TDNF.

Assessment of the link between in utero exposure to 2-aminoanthracene (2AA) and type-1 diabetes (T1D).

BACKGROUND: A recent diabetes report revealed an increased incidence in diabetes including type 1-diabetes (T1D). The increase in the numbers of T1D incidences are thought to be related to environmental reasons such as the exposure to environmental chemicals including arylamine 2-aminoanthracene (2AA). T1D is an autoimmune disease of the pancreatic islet in which insulin-producing beta cells are destroyed by auto-reactive T-cells and monocytic cells. METHODS: The purpose of this study is to examine the extent to which 2AA exposure contributes to T1D. Three groups of pregnant Sprague Dawley dams ingested various concentrations of dietary 2AA from gestation through the postnatal period. A select number of cytokines and adipokines previously noted to play a significant role in inflammatory response were analyzed in the pancreas of the pups for alteration. The anatomy of the pancreas was also evaluated to determine any histological changes. RESULTS: Results showed over-expression of pro-inflammatory protein IL-6. Up-regulation of humoral genes IL-7 and IL-21 were also noted. Pathologic characterization showed no significant changes. Moreover, serum total protein was significantly reduced in exposed groups. Elevated serum glucose concentration seems to correspond to slightly lower insulin levels in serum. Cumulative neonatal weight gain analysis showed no major alterations between the control and gestationally-exposed rats. CONCLUSION: It appears that systemic effects of 2AA ingestion were mild in the neonates. Further assessments of pups who lived longer than two weeks could be a useful way to measure the progression and possibly further support our hypothesis that 2AA can lead to systemic effects that are indicative of inducing T1D.

Investigating Susceptibility to Diabetes Using Features of the Adipose Tissue in Response to In Utero Polycyclic Aromatic Hydrocarbons Exposure.

BACKGROUND: In recent times, there has been an increase in the incidence of type 2 diabetes mellitus (T2DM) particularly in children. Adipocyte dysfunction provide a critical link between obesity and insulin resistance resulting in diabetes outcome. Further, environmental chemical exposure during early years of life might be a significant contributing factor to the increase in the incidence of T2DM. This study tests the idea that exposure to environmental contaminants (2-aminoanthracene [2AA]) in utero will show effects in the adipose tissue (AT) that signify T2DM vulnerability. 2AA is a polycyclic aromatic hydrocarbon found in a variety of products. METHODS: To accomplish the study objective, pregnant dams were fed various amounts of 2AA adulterated diets from gestation through postnatal period. The neonates and older offspring were analyzed for diabetic-like genes in the ATs and analysis of serum glucose. Furthermore, weight monitoring, histopathology and immunohistochemical (IHC) staining for CD68 in AT, adipocyte size determination and adiponectin amounts in serum were undertaken. RESULTS: Up-regulation of adiponectin and interleukin-6 genes were noted in the pups and older rats. Combination of intrauterine 2AA toxicity with moderate high fat diet exhibited gene expression patterns similar to those of the neonates. Elevated serum glucose levels were noted in treated groups. IHC of the AT indicated no significant malformations; however, CD68+ cells were greater in the animals treated to 2AA. Similarly, mean sizes of the adipocytes were larger in treated and combined 2AA and moderate high fat animals. Adiponectin was reduced in 2AA groups. CONCLUSION: From the preceding, it appears intrauterine 2AA disturbance, when combined with excess fat accumulation will lead to greater risk for the diabetic condition.

Inflammatory effect of 2-aminoanthracene (2AA) on adipose tissue gene expression in pregnant Sprague Dawley rats.

Adipocyte dysfunction may be a critical link between obesity and insulin resistance as a result of abnormal fat storage and mobilization. Adipocytes uniquely secrete adipokines and cytokines, such as leptin and TNFα, wich promote insulin sensitivity. Previously we reported insulin-signaling related altered gene expression in animals exposed to 2-Aminoanthracene (2AA). 2AA is an amino-substituted polycyclic aromatic hydrocarbon used in manufacturing dyes, chemicals, inks, resins, and polyurethanes. The objective of this study was to examine the inflammation related effects of 2AA exposure from gestation to postnatal period on dams that ingested 2AA. To examine 2AA effects, pregnant dams were assigned into dose regimens of 2AA. Dams were fed 2AA contaminated diet during the period of gestation and postpartum. The expression of key gene transcripts reported to be important in mediating inflammatory processes was examined via quantitative RT-PCR. Histologic examination of adipose tissue (AT) was also carried out to understand the anatomy of AT due to 2AA exposure during gestation and two weeks postpartum. Examination of the adipose tissue for microscopic changes revealed no alterations between control and low-dose animals. However, AT of the high-dose animals was infiltrated by increased numbers of CD68+mononuclear cells (macrophages) and small numbers of eosinophils and mast cells, consistent with inflammation. In addition, analysis of the mRNA expression of cytokines and adipokines demonstrated the importance of inflammation in AT dysfunction. For instance, TNFα, LEPTIN and IL-6 transcripts were relatively more expressed in the low dose animals than in the high dose and control rats. At the protein level, however, high amounts of cytokines were noted. The effects of 2AA on pregnant dams appear to be more pronounced in the high dose group than in the low dose group, possibly indicating increased susceptibility of rat offspring within this group to elicit a diabetic-type response.

Efficacy of parainfluenza virus 5 (PIV5)-based tuberculosis vaccines in mice.

Mycobacterium tuberculosis, the etiological agent of tuberculosis (TB), is an important human pathogen. Bacillus Calmette-Guérin (BCG), a live, attenuated variant of Mycobacterium bovis, is currently the only available TB vaccine despite its low efficacy against the infectious pulmonary form of the disease in adults. Thus, a more-effective TB vaccine is needed. Parainfluenza virus 5 (PIV5), a paramyxovirus, has several characteristics that make it an attractive vaccine vector. It is safe, inexpensive to produce, and has been previously shown to be efficacious as the backbone of vaccines for influenza, rabies, and respiratory syncytial virus. In this work, recombinant PIV5 expressing M. tuberculosis antigens 85A (PIV5-85A) and 85B (PIV5-85B) have been generated and their immunogenicity and protective efficacy evaluated in a mouse aerosol infection model. In a long-term protection study, a single dose of PIV5-85A was found to be most effective in reducing M. tuberculosis colony forming units (CFU) in lungs when compared to unvaccinated, whereas the BCG vaccinated animals had similar numbers of CFUs to unvaccinated animals. BCG-prime followed by a PIV5-85A or PIV5-85B boost produced better outcomes highlighted by close to three-log units lower lung CFUs compared to PBS. The results indicate that PIV5-based M. tuberculosis vaccines are promising candidates for further development.

Cholecystic adenocarcinoma and pancreatic insulinomas in a goat.

A 13-year-old female Boer goat with a history of chronic arthritis and recurrent episodes of recumbency, increased serum gamma-glutamyl transferase, and complete inability to stand was submitted for necropsy. Gross changes included the presence of a white, firm, smooth, 6 cm × 4 cm × 3 cm mass that diffusely expanded and partially effaced the gall bladder and infiltrated the adjacent hepatic parenchyma. On cut surface, the mass was pale yellow and had small, irregular, dark yellow areas. Scattered through the pancreas were 2 gray, well-demarcated, soft, homogeneous, 1 cm in diameter nodules that bulged out from the capsular surface. The right femoral head had a locally extensive area of cartilage erosion. Histological and immunohistochemical evaluation of the gall bladder and pancreatic nodules revealed a primary cholecystic adenocarcinoma and multifocal insulinomas, respectively. A metastatic focus from the gall bladder neoplasm was observed infiltrating the right adrenal gland medulla. The goat also had mild pulmonary infestation by Muellerius capillaris. Primary hepatobiliary and pancreatic neoplasia is rare in goats, and to the authors' knowledge, neither cholecystic adenocarcinoma nor pancreatic insulinomas have been previously reported in this species.