αv integrins on mesenchymal cells regulate skeletal and cardiac muscle fibrosis.

Mesenchymal cells expressing platelet-derived growth factor receptor beta (PDGFRß) are known to be important in fibrosis of organs such as the liver and kidney. Here we show that PDGFRß+ cells contribute to skeletal muscle and cardiac fibrosis via a mechanism that depends on αv integrins. Mice in which αv integrin is depleted in PDGFRß+ cells are protected from cardiotoxin and laceration-induced skeletal muscle fibrosis and angiotensin II-induced cardiac fibrosis. In addition, a small-molecule inhibitor of αv integrins attenuates fibrosis, even when pre-established, in both skeletal and cardiac muscle, and improves skeletal muscle function. αv integrin blockade also reduces TGFß activation in primary human skeletal muscle and cardiac PDGFRß+ cells, suggesting that αv integrin inhibitors may be effective for the treatment and prevention of a broad range of muscle fibroses.

Concurrent Transitional Meningioma and Ceruminous Gland Adenocarcinoma in a Scottish Wildcat Hybrid (Felis silvestris).

The Scottish wildcat (Felis silvestris) is an iconic and endangered subpopulation of the European wildcat (F. silvestris silvestris). There is much research devoted to the ecology, genetics and conservation of this animal, but little published information on pathology and disease. The investigation and reporting of such information is vital to furthering understanding of the effects of hybridization, a factor that is crucial if we are to secure a future for the Scottish wildcat. This report describes the clinical presentation, gross post-mortem and histological findings in an elderly Scottish wildcat hybrid with concurrent transitional meningioma and ceruminous gland adenocarcinoma.

Early-life perturbations in glucocorticoid activity impacts on the structure, function and molecular composition of the adult zebrafish (Danio rerio) heart.

BACKGROUND: Transient early-life perturbations in glucocorticoids (GC) are linked with cardiovascular disease risk in later life. Here the impact of early life manipulations of GC on adult heart structure, function and gene expression were assessed. METHODS AND RESULTS: Zebrafish embryos were incubated in dexamethasone (Dex) or injected with targeted glucocorticoid receptor (GR) morpholino knockdown (GR Mo) over the first 120 h post fertilisation (hpf); surviving embryos (>90%) were maintained until adulthood under normal conditions. Cardiac function, heart histology and cardiac genes were assessed in embryonic (120 hpf) and adult (120 days post fertilisation (dpf)) hearts. GR Mo embryos (120 hpf) had smaller hearts with fewer cardiomyocytes, less mature striation pattern, reduced cardiac function and reduced levels of vmhc and igf mRNA compared with controls. GR Mo adult hearts were smaller with diminished trabecular network pattern, reduced expression of vmhc and altered echocardiographic Doppler flow compared to controls. Dex embryos had larger hearts at 120 hpf (Dex 107.2 ± 3.1 vs. controls 90.2 ± 1.1 µm, p < 0.001) with a more mature trabecular network and larger cardiomyocytes (1.62 ± 0.13 cells/µm vs control 2.18 ± 0.13 cells/µm, p < 0.05) and enhanced cardiac performance compared to controls. Adult hearts were larger (1.02 ± 0.07 µg/mg vs controls 0.63 ± 0.06 µg/mg, p = 0.0007), had increased vmhc and gr mRNA levels. CONCLUSION: Perturbations in GR activity during embryonic development results in short and long-term alterations in the heart.

Primitive neuroectodermal tumour in a striped dolphin (Stenella coeruleoalba) with features of ependymoma and neural tube differentiation (Medulloepithelioma).

Primary brain tumours in cetaceans are rare with only four reported cases of intracranial tumours in the scientific literature. A juvenile female, striped dolphin live-stranded at Whitepark Bay, Co Antrim, Northern Ireland, UK, and died after an unsuccessful attempt at refloatation. Necropsy examination revealed a large, soft, non-encapsulated friable mass, which expanded and replaced the frontal lobes, corpus callosum and caudate nucleus of the brain and extended into the lateral ventricles, displacing the thalamus caudally. Microscopically, this comprised moderately pleomorphic neoplastic cells arranged variably in dense monotonous sheets, irregular streams, ependymal rosettes, 'ependymoblastomatous rosettes' and multilayered to pseudostratified tubules. Liquefactive necrosis, palisading glial cells, haemorrhage and mineralization were also observed. Immunohistochemically, the neoplastic cells expressed vimentin but not S100, glial fibrillary acidic protein, cytokeratin, neuron-specific enolase or synaptophysin. Based on these findings a diagnosis of primitive neuroectodermal tumour was made. Monitoring and recording such cases is crucial as neoplasia may be related to viral, carcinogenic or immunosuppressive chemical exposure and can ultimately contribute to assessing the ocean health.

European outbreaks of atypical myopathy in grazing equids (2006-2009): spatiotemporal distribution, history and clinical features.

REASONS FOR PERFORMING STUDY: Improved understanding of the epidemiology of atypical myopathy (AM) will help to define the environmental factors that permit or support the causal agent(s) to exert toxicity. OBJECTIVES: This European survey of AM aimed to describe spatiotemporal distribution, survival, clinical signs, circumstances in which AM develops and its different expressions between countries and over time. METHODS: The spatiotemporal distribution, history and clinical features of AM cases reported to the Atypical Myopathy Alert Group from 2006 to 2009 were described. Comparisons of data from the most severely affected countries and from the large outbreaks were made with Fisher's exact and Welch's tests with Bonferroni correction. RESULTS: Of 600 suspected cases, 354 met the diagnostic criteria for confirmed or highly probable AM. The largest outbreaks occurred during the autumns of 2006 and 2009 in Belgium, France and Germany. For the first time, donkeys, zebras and old horses were affected, and clinical signs such as gastrointestinal impaction, diarrhoea, penile prolapse, buccal ulceration and renal dysfunction were observed. Affected horses spent >6 h/day on pastures that almost always contained or were surrounded by trees. The latency period was estimated at up to 4 days. Overall survival rate was 26%. Although differences between countries in affected breeds, body condition, horse management and pasture characteristics were recognised, the common presenting clinical signs and mortality were similar between countries. CONCLUSIONS AND POTENTIAL RELEVANCE: This study describes new data on case details, history and clinical course of AM that is of preventive, diagnostic and therapeutic value. However, the true impact of the findings of this study on the development of or severity of AM should be tested with case-control studies.

European outbreaks of atypical myopathy in grazing horses (2006-2009): determination of indicators for risk and prognostic factors.

REASONS FOR PERFORMING STUDY: Appropriate management of atypical myopathy (AM) requires the establishment of an accurate diagnosis and prognosis. Furthermore, preventive measures to avoid AM need to be refined. OBJECTIVES: The aims of the study were as follows: 1) to improve the diagnosis of AM; 2) to identify prognostic predictors; and 3) to refine recommended preventive measures based on indicators of risk factors. METHODS: An exploratory analysis of cases in Europe between 2006 and 2009 reported to the Atypical Myopathy Alert Group was conducted. Based on clinical data, reported cases were allocated into 2 groups: confirmed or highly probable AM (AM group; further divided into survivors and nonsurvivors); and cases with a low probability of having AM or with another final diagnosis (non-AM group). Using Welch's test and odds ratios corrected for multiple comparisons, the AM vs. non-AM groups were compared to identify indicators for diagnosis and risk factors, and survivors vs. nonsurvivors in the AM group were compared to identify prognostic factors. Sensitivity, specificity and positive and negative predictive values were calculated for specific clinical signs related to final diagnosis and outcome. RESULTS: From 600 reported cases, 354 AM cases (survival rate of 26%) and 69 non-AM cases were identified, while there were insufficient data to categorise the remainder. Variables valuable for diagnosing AM compared with similar diseases were as follows: presence of dead leaves and wood and/or trees on pastures; sloping pastures; full-time pasture access; no food supplementation; normal body condition; pigmenturia; normothermia; and congested mucous membranes. Nonsurvival was associated with recumbency, sweating, anorexia, dyspnoea, tachypnoea and/or tachycardia. Survival was associated with remaining standing most of the time, normothermia, normal mucous membranes, defaecation and vitamin and antioxidant therapy. CONCLUSIONS AND POTENTIAL RELEVANCE: This study refines the list of risk factors for AM. Clinical signs valuable for diagnosis and prognosis have been identified, enabling clinicians to improve management of AM cases.

The fate of Lernaeocera branchialis (L.) (Crustacea; Copepoda) in Atlantic cod, Gadus morhua L.

Lernaeocera branchialis, a copepod crustacean parasite of gadoids, represents a potential threat to both wild and farmed cod, Gadus morhua. The pathological changes associated with the early stages of experimental infection have previously been reported in detail, and this article describes the lesions associated with later chronic stages of experimental infection. Chronic infection is characterised by extravascular granuloma formation and proliferation of fibrovascular tissue around intact and fragmented, degenerate parasites within both the gill arch and cardiac region. The majority of parasite granulomas are located within connective tissues of the gill arch or pericardium; however, low numbers are present within the wall of large vessels. The intraluminal parasites and thrombi of early stage infection are largely absent in these later lesions. We propose that organisation and incorporation of the parasite thrombus into the vessel wall with subsequent granuloma formation and extrusion into the surrounding connective tissue leads to the elimination of the parasite from the vascular system. Thus, rather than being a negative consequence of infection thrombosis is protective, allowing the host to survive the substantial initial vascular insult.

The first report of disease in a basking shark (Cetorhinus maximus).

Few diseases have been reported in any species of shark and none in the basking shark (Cetorhinus maximus) despite the latter being the subject of targeted hunting for over two centuries. This is the first report to describe the clinical signs and gross and microscopical pathology in a diseased basking shark that was live-stranded on the east coast of Scotland. Pyogranulomatous meningoencephalitis was present together with multifocal, predominantly non-suppurative, myocarditis with myocyte necrosis, oedema and haemorrhage. Additionally, there was full thickness ulcerative and fibrinonecrotizing dermatitis with underlying granulomatous inflammation. The aetiology could not be determined, but the lesions were suggestive of an infectious process, possibly bacterial.

The pathology of chronic erosive dermatopathy in Murray cod, Maccullochella peelii peelii (Mitchell).

Chronic erosive dermatopathy (CED) is a disease of intensively farmed Murray cod in Australia that has been reported in association with the use of groundwater (mechanically extracted from shallow boreholes) supplies. CED results in focal ulceration of the skin overlying sensory canals of the head and flanks. Trials were conducted at an affected fish farm to study the development of the condition, both in Murray cod and in goldfish, and also to assess the reported recovery of lesions when affected fish were transferred to river water. Grossly, lesions began after 2-3 weeks with degeneration of tissue at the periphery of pores communicating with the sensory canals. Widening of these pores along the axis of the canals resulted from a loss of tissue covering the canal. Histopathologically, hyperplasia of the canal epithelial lining was seen after 3 weeks in borehole water and subsequent necrosis and sloughing of this tissue resulted in the loss of the canal roof. Canal regeneration occurred when fish were transferred from borehole water into river water. The lack of lesions in other organs and the pattern of lesion development support exposure to waterborne factors as the most likely aetiology.

Morphological and functional effects of 16,16-dimethyl-prostaglandin-E2 on mucosal adaptation after massive distal small bowel resection in the rat.

The ability of 16,16-dimethyl-prostaglandin-E2 (PGE) to augment mucosal adaptation 14 days after a 70% distal small bowel resection in the rat was evaluated. In resected (R) and sham operated (S) animals, subcutaneous PGE 75 mg/kg, 2 X/day, induced significant (p less than 0.05) increases in mucosal protein, DNA, and disaccharidase concentrations per centimetre of bowel. The respective per cent increases in the residual proximal small intestine compared with their respective untreated controls were: protein, R = 60%, S = 66%; DNA, R = 69%, S = 29%; maltase, R = 57%, S = 5%. The uptake of leucine by intestinal rings was significantly higher (50%) in the PGE treated group at a concentration of 2 mmol/l of substrate, while the uptake of glucose was similar in all groups. The drug appears to be an effective agent in stimulating morphological and functional adaptation after massive distal small bowel resection.