Inhibition of Myeloperoxidase Pro-Fibrotic Effect by Noscapine in Equine Endometrium.

Myeloperoxidase is an enzyme released by neutrophils when neutrophil extracellular traps (NETs) are formed. Besides myeloperoxidase activity against pathogens, it was also linked to many diseases, including inflammatory and fibrotic ones. Endometrosis is a fibrotic disease of the mare endometrium, with a large impact on their fertility, where myeloperoxidase was shown to induce fibrosis. Noscapine is an alkaloid with a low toxicity, that has been studied as an anti-cancer drug, and more recently as an anti-fibrotic molecule. This work aims to evaluate noscapine inhibition of collagen type 1 (COL1) induced by myeloperoxidase in equine endometrial explants from follicular and mid-luteal phases, at 24 and 48 h of treatment. The transcription of collagen type 1 alpha 2 chain (COL1A2), and COL1 protein relative abundance were evaluated by qPCR and Western blot, respectively. The treatment with myeloperoxidase increased COL1A2 mRNA transcription and COL1 protein, whereas noscapine was able to reduce this effect with respect to COL1A2 mRNA transcription, in a time/estrous cycle phase-dependent manner (in explants from the follicular phase, at 24 h of treatment). Our study indicates that noscapine is a promising drug to be considered as an anti-fibrotic molecule to prevent endometrosis development, making noscapine a strong candidate to be applied in future endometrosis therapies.

TGF-ß1 and CD68 immunoexpression in capsules formed by textured implants with and without mesh coverage: a study on female rats

Purpose: To evaluate fibrosis formation and number of macrophages in capsules formed around textured implants without and with mesh coverage. Methods: Fibrosis was analyzed through transforming growth factor-beta 1 (TGF-ß1) immunomarker expression and the number of macrophages through CD68 percentage of cells in magnified field. Sixty female Wistar rats were distributed into two groups of 30 rats (unmeshed and meshed). Each group was then subdivided into two subgroups for postoperative evaluation after 30 and 90 days. The p value was adjusted by Bonferroni lower than 0.012. Results: No difference was observed in fibrosis between meshed and unmeshed groups (30 days p = 0.436; 90 days p = 0.079) and from 30 to 90 days in the unmeshed group (p = 0.426). The meshed group showed higher fibrosis on the 90th day (p = 0.001). The number of macrophages was similar between groups without and with mesh coverage (30 days p = 0.218; 90 days p = 0.044), and similar between subgroups 30 and 90 days (unmeshed p = 0.085; meshed p = 0.059). Conclusions: In the meshed group, fibrosis formation was higher at 90 days and the mesh-covered implants produced capsules similar to microtextured ones when analyzing macrophages. Due to these characteristics, mesh coating did not seem to significantly affect the local fibrosis formation.

Cardiac assessments of bottlenose dolphins (Tursiops truncatus) in the Northern Gulf of Mexico following exposure to Deepwater Horizon oil.

The Deepwater Horizon (DWH) oil spill profoundly impacted the health of bottlenose dolphins (Tursiops truncatus) in Barataria Bay, LA (BB). To comprehensively assess the cardiac health of dolphins living within the DWH oil spill footprint, techniques for in-water cardiac evaluation were refined with dolphins cared for by the U.S. Navy Marine Mammal Program in 2018 and applied to free-ranging bottlenose dolphins in BB (n = 34) and Sarasota Bay, Florida (SB) (n = 19), a non-oiled reference population. Cardiac auscultation detected systolic murmurs in the majority of dolphins from both sites (88% BB, 89% SB) and echocardiography showed most of the murmurs were innocent flow murmurs attributed to elevated blood flow velocity [1]. Telemetric six-lead electrocardiography detected arrhythmias in BB dolphins (43%) and SB dolphins (31%), all of which were considered low to moderate risk for adverse cardiac events. Echocardiography showed BB dolphins had thinner left ventricular walls, with significant differences in intraventricular septum thickness at the end of diastole (p = 0.002), and left ventricular posterior wall thickness at the end of diastole (p = 0.033). BB dolphins also had smaller left atrial size (p = 0.004), higher prevalence of tricuspid valve prolapse (p = 0.003), higher prevalence of tricuspid valve thickening (p = 0.033), and higher prevalence of aortic valve thickening (p = 0.008). Two dolphins in BB were diagnosed with pulmonary arterial hypertension based on Doppler echocardiography-derived estimates and supporting echocardiographic findings. Histopathology of dolphins who stranded within the DWH oil spill footprint showed a significantly higher prevalence of myocardial fibrosis (p = 0.003), regardless of age, compared to dolphins outside the oil spill footprint. In conclusion, there were substantial cardiac abnormalities identified in BB dolphins which may be related to DWH oil exposure, however, future work is needed to rule out other hypotheses and further elucidate the connection between oil exposure, pulmonary disease, and the observed cardiac abnormalities.

Prevalence, risk factors and survival in dogs with myxomatous valve degeneration / [Prevalência, fatores de risco e sobrevivência em cães com degeneração mixomatosa valvar]

The objective of this study was to describe the prevalence, survival time, and risk factors of myxomatous mitral valve disease (MMVD) in dogs by a retrospective observational cohort study design of a Brazilian veterinary center, admitted from 2012 to 2018 (2.585 days). Considering the 105 dog files confirmed as MMVD, the prevalence of the disease was higher in small-breed dogs with ages from 10 to 19 years (30.3%). The survival time of the dogs at B1 stage (1.854 ± 145 days) was higher than the B2 (1.508+209) and C/D (930 ± 209). Higher risks of death (hazard ratio) were detected in the presence of syncope (2.5), pulmonary crackling (2.0), dyspnea (1.9), and higher values of vertebral heart scale (1.7), radiographic left atrium dimension (1.8), the ACVIM staging (1.7), and the duration of QRS complex (1.05). The results achieved demonstrated higher prevalence of MMVD in old small-breed dogs, associated with longer survival time in the B1 stage of the disease, and higher risk of death related to the presence of clinical signs, such as dyspnea, syncope, and pulmonary crackling, beyond some radiographic, echocardiographic, and electrocardiographic variables of heart or atrial enlargement.(AU)

O objetivo deste estudo foi descrever a prevalência, o tempo de sobrevivência e os fatores de risco da doença mixomatosa valvar mitral (DMVM) em cães, por meio de estudo de coorte observacional retrospectivo, os quais foram atendidos em um centro veterinário de 2012 a 2018 (2.585 dias). Considerando os 105 arquivos de cães com confirmação da DMVM, maior prevalência foi observada em raças pequenas com idades entre 10 e 19 anos (30,3%). O tempo de sobrevivência de cães em estágio B1 (1.854+145 dias) foi superior ao B2 (1.508+209) e ao C/D (930+209). Maior risco de morte (hazard ratio) foi observado na presença de síncope (2,5), crepitação pulmonar (2,0), dispneia (1,9), bem como de valores superiores de VHS (1,7), dimensão radiográfica do átrio esquerdo (1,8), estadiamento ACVIM (1,7) e duração do complexo QRS (1,05). Os resultados obtidos demonstraram maior prevalência de DMVM em cães idosos de raças pequenas, associada a maior tempo de sobrevida no estágio B1 da doença e a maior risco de morte relacionado à presença de sinais clínicos como dispneia, síncope e crepitação pulmonar, além de algumas variáveis radiográficas, ecocardiográficas e eletrocardiográficas de cardiomegalia ou aumento atrial esquerdo.(AU)

EFFECTS OF DOXYCYCLINE HYCLATE, ONE PERCENT POLIDOCANOL, AND ABSOLUTE ETHANOL ON THE CUTANEOUS AND SUBCUTANEOUS TISSUES OF CHICKENS (GALLUS GALLUS DOMESTICUS) AND THE POTENTIAL IMPLICATIONS IN TREATING CERVICOCEPHALIC DIVERTICULA RUPTURE.

The objective of this pilot study was to examine the histologic effects associated with three known sclerosing agents and their ability to induce fibrosis in the subcutaneous space between the cervicocephalic air sac and skin. In the future, these drugs may prove useful in treating birds experiencing cervicocephalic diverticula rupture. The agents used were 1% polidocanol, absolute ethanol, and doxycycline hyclate. Twelve healthy adult chickens (Gallus gallus domesticus) were used in this study. The chickens were randomly allocated into three groups denoting day of euthanasia (day 4, 7, or 14). On day 0, all agents were injected (0.2 ml) subcutaneously, in a four-point grid fashion, in both the cervical and pectoral region of each bird. After euthanasia, the skin and subcutaneous tissues corresponding to the injection sites were harvested for histologic assessment. Tissue sections were assessed for fibrosis and lymphocytic and histiocytic inflammation. A scoring system was established to rank sclerosing agents by fibrosing and inflammatory ability. In the cervical region of chickens, 1% polidocanol induced the greatest inflammatory changes by day 7. Data suggest that doxycycline hyclate may produce the greatest cutaneous and subcutaneous fibrosis overall among all groups of birds. No adverse reactions were associated with any injection. Sterile saline produced the least amount of inflammation when assessed with the scoring system. Further investigation is needed to determine the safety of injections of larger volume with these chemicals and whether these findings can be extrapolated to birds with disease.

Enhanced transforming growth factor-beta signaling and fibrosis in the pectoralis major muscle of broiler chickens affected by wooden breast myopathy.

Fibrosis has also been recorded as a prominent pathological feature within wooden breast (WB) myopathy of broiler chickens. This study was conducted to evaluate the accumulation of fibril collagen, deposition of the extracellular matrix (ECM) components, and the underlying mechanism mediating the pathogenic fibrotic process in the pectoralis major (PM) muscle of WB-affected birds. Broiler chickens were categorized into the control and WB groups based on the evaluation of myopathic lesions. Results indicated that the total content and area of collagen in cross-sections of the PM muscle, as well as the augmented expression of collagen-I and fibronectin in the ECM, were greatly increased in birds with WB. Wooden breast myopathy upregulated expressions of transforming growth factor-beta (TGF-ß) and the phosphorylation of Smad 2 and 3, thereby activating TGF-ß-mediated Smad signaling pathway, which further enhanced the transcription of profibrotic mediators. In addition, regulators involved in collagen biosynthesis and cross-linking including prolyl 4-hydroxylase, lysyl oxidase, lysyl hydroxylase, and decorin were increased in the WB muscle. Finally, the expressions of both matrix metalloproteinases (MMP) and tissue inhibitor of metalloproteinases (TIMP) were increased in the WB muscle, which might be related with reduced ECM remodeling. Overall, WB myopathy induces severe fibrosis by enhancing ECM deposition and collagen cross-linking in the PM muscle of broiler chickens, possibly via the activation of TGF-ß signaling and the dysregulation of the MMP and TIMP system.

CT findings in a dog with subacute myopathy and later fibrotic contracture of the infraspinatus muscle.

A 5-year-old Norwegian elkhound was referred due to an acute onset of lameness and persistent shoulder pain over a period of 3 weeks. Computed tomography demonstrated an enlarged, hypoattenuating right infraspinatus muscle with peripheral contrast enhancement and a nonenhancing center, without concurrent lesions in superficial structures or bones. The right infraspinatus muscle showed progressive atrophy on consecutive CT studies. The dog developed clinical symptoms compatible with fibrotic infraspinatus contracture 2 months after the initial presentation, and was treated with infraspinatus tenotomy. Histopathological diagnoses based on intraoperative biopsy samples were fibrotic muscle atrophy and muscle hypertrophy with regeneration.

Idiopathic multifocal myocardial atrophy with fibrosis and fatty infiltration involving Purkinje fibres in a 13-year-old Arabian broodmare: Histopathological features.

Myocardial atrophy with fibrosis and fatty infiltration involving the cardiac conduction system is relatively unusual in horses. We herein report of such a case in a 13-year-old Arabian broodmare that had spontaneously died on a paddock. An autopsy revealed multifocal myocardial atrophy with concomitant fibrosis and fatty infiltration in both the ventricles and interventricular septum. The Purkinje fibres in the ventricles and interventricular septum were surrounded by thick fibrous or adipose tissues adjacent to atrophic myocardial cells. Myocardial fibrosis and fatty infiltration were likely secondary to myocardial atrophy, occurring as a pathological response triggered by the repair of muscular wall injury. However, there were no major vascular pathologies (e.g. atherosclerosis and arteriosclerosis); hence, the pathogenesis of myocardial atrophy was unclear. There was no evidence of myocardial atrophy ̵ induced pathologies such as infarct, ischaemic lesions, myocardial degeneration, myocarditis and endocarditis. However, such an unusual histopathological pattern may be associated with rapid clinical deterioration and death.

Age-related changes of seminiferous tubule morphology, interstitial fibrosis and spermatogenesis in dogs.

There are age-related changes in testicular anatomy and physiology whereby there are modifications of sperm production and reproductive hormone functions. Effects of age on testicular microanatomy are well documented in humans, while there is limited understanding of these changes in dogs. The aim of this study was to evaluate age-related changes of seminiferous tubule morphology, interstitial fibrosis and spermatogenesis in dogs. Dogs (n = 32) were divided into four age groups: peripubertal (n = eight), relatively younger (n = seven), reproductively mature (n = seven) and relatively older (n = ten). Picrosirius Red stained sections were used for morphometrical analysis of testicular tissues, while the characteristics of seminiferous epithelium were assessed using a modified Johnsen scoring system for haematoxylin and eosin stained sections. Seminiferous epithelium and seminiferous tubule area increased from peripuberty to reproductive maturity, indicating there were changes during sexual maturation and subsequently there were decreases with further aging. There was a similar age-related trend for changes in seminiferous epithelium height with values being greatest in reproductively mature dogs; while there were no age-related differences in tubular diameter. Collagen content in the testicular interstitium gradually decreased from peripuberty to the age when dogs were reproductively mature and there were subsequent increases in relatively older dogs, thus, there was an association between the extent of testicular fibrosis and senescence. There was a decrease in spermatogenetic functions from relatively younger to older ages. Further investigations are warranted to establish mechanisms responsible for age-related changes of testicular morphology and related clinical implications.

Evaluation of profibrotic gene transcription in renal tissues from cats with naturally occurring chronic kidney disease.

BACKGROUND: Increased gene transcription of hypoxia-induced mediators of fibrosis in renal tissue has been identified in experimentally induced, ischemic chronic kidney disease (CKD). OBJECTIVE: To characterize hypoxia-induced profibrotic pathways in naturally occurring CKD in cats. ANIMALS: Twelve client-owned cats with CKD and 8 healthy control cats. METHODS: In this prospective, cross-sectional study, bilateral renal tissue samples were assessed histologically for inflammation, tubular atrophy, and fibrosis, and by reverse transcription-quantitative PCR for characterization of transcript levels of hypoxia-inducible factor-1α (HIF1A), matrix metalloproteinases-2 (MMP2), -7 (MMP7), and -9 (MMP9), tissue inhibitor of metalloproteinase-1 (TIMP1), transforming growth factor-ß1 (TGFB1), and vascular endothelial growth factor-A (VEGFA). Linear mixed models were used to compare gene transcription between diseased and healthy kidneys, and to examine the association between transcript levels and serum creatinine concentration for all cats, and between transcript levels and histologic scores of diseased kidneys. RESULTS: Kidneys from cats with CKD had significantly higher transcript levels of HIF1A, MMP2, MMP7, MMP9, TIMP1, and TGFB1 (all P < .001), and lower levels of VEGFA (P = .006) than those from control cats. Transcript levels of MMP7 (P = .05) and TIMP1 (P = .005) were positively associated with serum creatinine in cats with CKD, but not in control cats. In diseased kidneys, transcript levels of MMP2 (P = .002), MMP7 (P = .02), and TIMP1 (P = .02) were positively, whereas those of VEGFA (P = .003) were negatively, associated with histologic score severity. CONCLUSION AND CLINICAL SIGNIFICANCE: Evaluation of the expression of the corresponding proteins in larger populations could identify therapeutic targets and/or biomarkers of tubulointerstitial fibrosis in cats.

Myocardial Changes in Diabetic and Nondiabetic Nonhuman Primates.

Diabetic human patients have increased risk of heart failure compared to healthy subjects. The underlying mechanisms for this are not fully understood, and to help develop improved treatment strategies, well-characterized animal models are essential. To investigate cardiac dysfunction in diabetes, this study evaluated myocardial changes in 10 aging rhesus monkeys with and without diabetes. Based on evaluation of plasma glycosylated hemoglobin and glucose, 7 of 10 rhesus macaques had diabetes for a minimum of 11 months, while 3 of 10 were categorized as nondiabetic. A detailed histological examination of formalin-fixed left ventricular myocardial samples was followed by a semiquantitative evaluation of myocardial fibrosis and fat infiltration; digital quantifications of myocardial collagen, lipofuscin, and nuclear area fractions; and measurements of cardiomyocyte diameter. Histological myocardial evaluation revealed the presence of lipofuscin; large nuclei; interstitial, replacement, and vascular fibrosis; adipocyte infiltration; and vacuolar degeneration with atrophy of cardiomyocytes and fibrosis. However, there were no differences between groups for semiquantitative fat infiltration, fibrosis, cardiomyocyte size, collagen, or nuclear and lipofuscin area fraction. Lipofuscin area fraction correlated with plasma insulin, triglyceride, total cholesterol, and high-density lipoprotein cholesterol concentrations. In conclusion, myocardial pathological changes were found in left ventricular myocardium in aged rhesus macaques, independent of the stage of diabetes. The duration of diabetes might have been too short to cause differences between groups.

Expression of genes involved in the NF-κB-dependent pathway of the fibrosis in the mare endometrium.

Equine endometrosis is a multifactorial chronic degenerative condition, considered to be one of a major causes of equine infertility. The formation of periglandular fibrosis seems to be linked to chronic inflammation of the mare endometrium in a paracrine way and in a response to numerous forms of inflammatory stimuli elicit the net deposition of extracellular matrix (ECM) around the endometrial glands and stroma. We hypothesized some of these stimuli, such as monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), and hyaluronan synthases (HASs), may share the nuclear factor-κB (NF-κB) dependent activation pathway. This study aimed to determine whether mRNA expression of MCP-1, IL-6, HASs, and proteins of canonical (RelA/NK-κß1) and noncanonical (NK-κß2) signaling pathways for NF-kB would change in subsequent categories of endometrosis during the estrous cycle. The expression of selected genes was established in mare endometrium (n = 80; Kenney and Doig categories I, IIA, IIB, III), obtained in the follicular phase (FLP) and mid-luteal phase (MLP). The high expression of RelA mRNA was observed in III, whereas of NK-κß1 and NK-κß2 also in IIA, and IIA and IIB, respectively. The expression of MCP-1 mRNA occurred constantly, regardless of the category, whereas IL-6 mRNA was low in IIA, IIB, and III. The expression of HAS 1 was high in IIA and HAS 3 in IIA, IIB, and III. All those changes were observed in FLP, but not MLP. Our results suggest that NF-κB may be involved in progression of the chronic degenerative condition of the mare endometrium, on both canonical and noncanonical pathways. The most important changes in target genes expression were observed only in FLP, which may suggest the hormone-dependent activation of the NF-κB-dependent fibrosis pathway.

Thoracolumbar meningeal fibrosis in pugs.

BACKGROUND: Thoracolumbar myelopathies associated with spinal cord and vertebral column lesions, with a similar clinical phenotype, but different underlying etiologies, occur in pugs. OBJECTIVES: To further characterize the clinical and neuropathological characteristics of pugs with longstanding thoracolumbar myelopathy. ANIMALS: Thirty client-owned pure-bred pugs with a history of more than a month of ataxia and paresis of the pelvic limbs, suggesting a myelopathy localized to the thoracolumbar spinal cord, were included in the study. METHODS: Prospective clinicopathological study. Included pugs underwent a complete neurological examination and gross and histopathologic postmortem studies with focus on the spinal cord. Computed tomography (n = 18), magnetic resonance imaging (n = 17), and cerebrospinal fluid analysis (n = 27) were performed before or immediately after death. RESULTS: Twenty male and 10 female pugs had a median age at clinical onset of 84 months (interquartile range, 66-96). Affected pugs presented with a progressive clinical course and 80% were incontinent. There was circumferential meningeal fibrosis with concomitant focal, malacic, destruction of the neuroparenchyma in the thoracolumbar spinal cord in 24/30 pugs. Vertebral lesions accompanied the focal spinal cord lesion, and there was lympho-histiocytic inflammation associated or not to the parenchymal lesion in 43% of the pugs. CONCLUSIONS AND CLINICAL IMPORTANCE: Meningeal fibrosis with associated focal spinal cord destruction and neighboring vertebral column lesions were common findings in pugs with long-standing thoracolumbar myelopathy.

Idiopathic Myocardial Fibrosis in Captive Chimpanzees (Pan troglodytes).

Cardiovascular disorders and predominantly idiopathic myocardial fibrosis are frequently associated with mortality among zoo-housed chimpanzees (Pan troglodytes). Formalin-fixed whole hearts of deceased chimpanzees housed in zoos (n = 33) and an African sanctuary (n = 2) underwent detailed macroscopic and histopathologic examination using a standardized protocol. Archived histological slides from the hearts of 23 additional African sanctuary-housed chimpanzees were also examined. Myocardial fibrosis (MF) was identified in 30 of 33 (91%) of the zoo-housed chimpanzees but none of the 25 sanctuary-housed chimpanzees. MF was shown to be characterized by both interstitial and replacement fibrosis. Immunophenotyping demonstrated that the fibrotic lesions were accompanied by the increased presence of macrophages, alpha smooth muscle actin-positive myofibroblasts, and a minimal to mild T-cell-dominant leukocyte infiltration. There was no convincing evidence of cardiotropic viral infection or suggestion that diabetes mellitus or vitamin E or selenium deficiency were associated with the presence of the lesion. However, serum vitamin D concentrations among zoo-housed chimpanzees were found to be lower in seasons of low ultraviolet light levels.

Clinical-epidemiological, anatomic-pathological, histochemical and immunohistochemical characterization of renal cystadenocarcinoma-nodular dermatofibrosis syndrome in 11 German Shepherd dogs / Caracterização clínico-epidemiológica, anátomo-patológica, histoquímica e imuno-histoquímica da síndrome cistadenocarcinoma-dermatofibrose nodular em 11 cães Pastor Alemão

Eleven cases of renal cystadenoma/cystadenocarcinoma-nodular dermatofibrosis syndrome (RCND) are described in German Shepherd dogs diagnosed from January 1994 to January 2018 at the Veterinary Pathology Laboratory of the "Universidade Federal de Santa Maria" (LPV-UFSM). The study sample was composed of eight male and three female dogs at a ratio of 2.67:1. Age ranged from six to 12 years (mean=8.7 years). The main clinical signs reported in descending order of frequency were multiple cutaneous nodules (nodular dermatofibrosis), dyspnea, anorexia, weight loss, recurrent hematuria, vomiting, and polydipsia. Results demonstrated that it is not always easy to clinically recognize this syndrome, but its peculiar anatomical-pathological characteristics allow safe diagnosis. Histologically, it was possible to detect all phases (cysts, papillary intratubular hyperplasia, and cystadenomas or cystadenocarcinomas) of a possible pathological continuum of the renal lesions. Uterine leiomyomas were observed in only one of the cases. Through histochemical techniques, it was possible to identify the presence of type I collagen in both cutaneous and renal lesions and consider its possible involvement in the pathogenesis of renal cystadenocarcinoma. Immunohistochemistry (IHC) showed partially satisfactory results in the staining of epithelial cells of renal cysts and neoplasms for pan-cytokeratin.(AU)

São descritos 11 casos da síndrome cistadenoma/cistadenocarcinoma-dermatofibrose nodular (CR-DN) em cães Pastor Alemão, diagnosticados entre janeiro de 1994 e janeiro de 2018 no Laboratório de Patologia Veterinária da Universidade Federal de Santa Maria (LPV-UFSM). Os cães afetados foram oito machos e três fêmeas, estabelecendo-se uma relação de 2,67:1. A idade variou de seis a 12 anos, sendo a média de idade de 8,7 anos. Os principais sinais clínicos relatados foram, em ordem decrescente de frequência, múltiplos nódulos cutâneos (dermatofibrose nodular), dispneia, anorexia, emagrecimento, hematúria recorrente, vômito e polidipsia. Este estudo permitiu estabelecer que o reconhecimento clínico da síndrome nem sempre é fácil, porém suas características anátomo-patológicas peculiares permitem um diagnóstico com segurança. Histologicamente, foi possível detectar todas as fases (cistos, hiperplasia intratubular papilífera, cistadenomas ou cistadenocarcinomas) de um possível continuum patológico das lesões renais. Leiomiomas uterinos foram observados somente em um caso. Através das técnicas histoquímicas foi possível estabelecer que o colágeno tipo I está presente em ambas as lesões, cutâneas e renais, e cogitar seu possível envolvimento na patogênese dos cistadenocarcinomas renais. A técnica de IHQ mostrou resultados parcialmente satisfatórios na imunomarcação das células epiteliais dos cistos e dos neoplasmas renais para pancitoceratina.(AU)

The Causes of Canine Myocarditis and Myocardial Fibrosis Are Elusive by Targeted Molecular Testing: Retrospective Analysis and Literature Review.

Myocarditis can cause death or permanent heart damage. As epidemiologic and etiopathologic data for canine myocarditis are lacking, we performed a retrospective study using nucleic acid extracted from archived (2007 to 2015) tissues from myocarditis cases and control dogs without myocardial lesions. Heart tissue from pediatric/juvenile and adult dogs was tested with a comprehensive panel of conventional and real-time polymerase chain reaction (PCR) assays targeting recognized agents of canine myocarditis based on a literature review and informed by the comparative epidemiology of human myocarditis. The PCR screen, which included canine parvovirus 2 (CPV-2), canine distemper virus, canine herpesvirus, Borrelia spp, West Nile virus, adenovirus, parainfluenza virus, pneumovirus, respiratory coronavirus, influenza virus, Bartonella spp, Rickettsia spp, Mycoplasma spp, and Neospora caninum, did not detect agents in 35 of 66 cases (53%; 95% confidence interval [CI], 41%-65%) and was frequently negative in adults (21/26); by comparison, agents were not detected in 27 of 57 controls (47%; 95% CI, 35%-60%). Canine distemper virus, herpesvirus, adenovirus, coronavirus, parainfluenza virus, Mycoplasma haemocanis, and N. caninum were occasionally detected in both cases and controls; thus, PCR detection was not considered to indicate causation. We previously reported that CPV-2 continues to be associated with myocarditis in young dogs despite widespread vaccination; in adults, CPV-2 was detected in 2 of 26 cases and 4 of 22 controls. As several agents were similarly detected in cases and controls, it is unclear if these are cardiopathogenic, incidental, or latent. West Nile virus was detected at the analytic limit in 1 adult case. We did not detect Borrelia spp, Bartonella spp, Rickettsia spp, or influenza A virus in the myocarditis cases. These data demonstrate the limitations of current targeted diagnostic tests and the need for additional research to identify unknown agents and develop testing strategies for canine myocarditis.

Fatal pulmonary hemorrhage in a horse during bronchoalveolar lavage - single case report.

BACKGROUND: Pulmonary hemorrhage is a rare cause of death in horses. Hemorrhage within the respiratory tract has many causes, including mycosis of the guttural pouch, invasive procedures causing serious trauma to nasal conchae, or lung biopsy. We report on a rare case of a fatal pulmonary hemorrhage in a horse after a severe cough during bronchoalveolar lavage. To the best of our knowledge, this is the first report of spontaneous hemorrhage in a horse during bronchoalveolar lavage. CASE PRESENTATION: A 21-year-old mare which belonged to the didactic herd of The Faculty of Veterinary Medicine underwent BAL procedure for training purposes. Clinical examination prior to the procedure did not reveal any abnormalities and the horse had been classified as healthy. The horse was sedated with 0.01 mg/kg of detomidine and 0.01 mg/kg of butorphanol. The silicon BAL catheter was passed through the nasal passage into the trachea and then into the bronchus. Before catheter was wedged, the mare began to cough heavily and massive haemorrhage from mouth and nostrils occurred. Despite fluid therapy, shock occurred within 15 min and the mare was euthanized. Upon necropsy, site of hemorrhage was identified in the left lobar caudal bronchi, from a large blood vessel running directly beneath the bronchial wall. Upon histology, a chronic lympho-plasmocytic inflammatory process in left bronchi was identified. Moreover, Masson's trichrome staining revealed severe, perivascular fibrosis. CONCLUSION: Although BAL is a relatively safe procedure, and such complications should be treated as extremely rare, this case indicates that, in some individuals with specific subclinical problems, even mild physical force such as a cough can lead to rupture of the artery.

Ultrasonographic and histopathological features in 8 cats with fibrotic small intestinal stricture.

Benign stricture is an uncommon cause of chronic small intestinal obstruction in the cat. The purpose of this retrospective case series was to describe the ultrasonographic features, histopathological findings, and clinical presentation in a group of cats with benign small intestinal stricture. Inclusion criteria were cats presenting during the period 2010-2017, and that had ultrasonography and small intestinal stricture confirmed at surgery. For each cat, clinical data and ultrasonographic findings were retrieved from the medical record, and histopathology, where available, was reviewed. Eight cats met the inclusion criteria. The location of strictures was duodenum (1/8), mid- to distal jejunum (4/8), and ileum (3/8). Ultrasonographic findings included gastric distension (8/8) and generalized (3/8) or segmental (5/8) intestinal dilation consistent with mechanical obstruction. Ingesta did not propagate beyond the strictured segment. Wall thickening was mild to moderate (3-6 mm). Normal wall layering was disrupted in all cats. Strictures were predominantly hypoechoic (7/8) and associated with hyperechoic peri-intestinal mesentery (6/8). Annular strictures (5/8) were less than 15 mm in length whereas long-segment strictures (3/8) were greater than 15 mm in length. Histopathology showed transmural disease with fibrosis and inflammation (8/8), often (6/8) extending into the bordering mesentery. The mucosa was the most severely affected layer and epithelial injury accompanied the mucosal fibrosis/inflammation. Clinical presentation reflected delayed diagnosis of chronic bowel obstruction with debilitation (8/8), marked weight loss (8/8), and prerenal azotemia (5/8). Benign fibrostenotic stricture should be considered a differential diagnosis in debilitated young cats presenting with chronic bowel disease and ultrasonographic features of intestinal obstruction.

Fat, Cartilage, and Bone Metaplasia in Lungs of Cattle With Caudal Pleural Lesions and Subjacent Interstitial Fibrosis.

The changes associated with condemned lungs in cattle with chronic pleural lesions of the caudal lobes were characterized by histology and immunohistochemistry (IHC). Fibroproliferative pleural lesions were microscopically confirmed. Occasionally, the pleural lesions also included adipose, chondroid, and osseous metaplasia that were covered by mesothelial cells, mostly in the absence of inflammation. Other lungs also showed fibrosis in the subpleural interstitium and interlobular septa. In both condemned and noncondemned lungs, immunoreactivity to Wilms tumor 1 (WT1) was normally observed on surface mesothelial cells but not on the submesothelial fibroblasts and myofibroblasts. Conversely, the myofibroblasts beneath the pleura, but not the mesothelial cells, showed immunoreactivity to alpha smooth muscle actin and calponin. However, in the lungs with myofibroblastic foci in the pleura, the proliferated cells maintained WT1 immunoreactivity similar to those of some metaplastic cells. These findings may reflect the plasticity of mesothelial cells in vivo.