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Laboratory animals are widely used in imaging studies, including infection, heart, and brain research. Compared with rodents, pigs are especially useful because of their large organ sizes, ability to tolerate long-term anesthesia, and substantial blood volume, which allows repeated blood sampling. These factors are particularly important in positron emission tomography studies of potential new radioactive tracers, because the scans often are prolonged; in addition, kinetic studies involving repeated blood sampling may be performed to establish the optimal scan time. However, protracted studies may affect the cardiovascular system, brain, and other organs. This raises the question of how to monitor and counteract the effects of longterm anesthesia in pigs in a typical experimental setting yet prevent introducing bias into the experiment. To address this question, we investigated the effects of long-term anesthesia (maximum, 18 h), repeated blood sampling (maximum of 20 mL blood per kilogram body weight), and road transportation (as long as 1.5 h between 2 imaging centers) on key variables of lung, heart, and brain function in the context of a well-established pig model of Staphylococcus aureus infection. Pulse rate, oxygen saturation, body temperature, arterial pressure of CO2, and urine production were stable during anesthesia for at least 16 h, whereas blood glucose slowly decreased. Hct and leukocyte count decreased due to repeated blood sampling. During road transportation, blood lactate levels increased 5 fold and arterial pressure of O2 decreased by 50%. Repeated CT scans, necropsy results, and histopathology findings documented progressive lung changes and acute cardiac necrosis. No lesions indicative of hypoxia were found in brain. The study data show that the typical monitoring parameters do not fully depict the cardiovascular state of pigs during prolonged anesthesia. We recommend streamlining experimental protocols for imaging studies in pigs to avoid organ pathology.

For the first time in > 30 years of routine sampling under the Arctic Monitoring and Assessment Program, a parasite was found in the liver of ringed seals (Phoca hispida) collected near Qaanaaq (Thule), Northwest Greenland, in 2008 and 2014. Concerns regarding changes to parasite occurrence, possibly related to climate change and bioaccumulation of immunomodulating anthropogenic pollutants, spurred further investigations into parasite characterization, and implications for wildlife health and seal hunters. Microscopic, molecular, and morphometric analyses are presented herein. Of 40 seals, 6 (15%) were infected, and 5 of 6 of these seals had severe infections. The parasite was identified morphologically as Orthosplanchnus arcticus Odhner, 1905 (Trematoda; Digenea: Brachycladiidae). Macro- and microscopic pathologic study indicated mild-to-severe biliary hyperplasia associated, stasis associated, and fibrosis associated with trematode infections. Molecular analysis of the trematode confirmed its classification within the Brachycladiidae using sequencing and comparing Internal Transcribed Spacer-1, mitochondrial-NADH Dehydrogenase 3, 18S ribosomal DNA, and Cyclooxygenase-1 regions. This is the first ever report of O. arcticus in ringed seals from Qaanaaq and is one of the most northern records of this parasite. We found significant liver pathology in severely infected seals, but its effects on health of seals in this population are unknown. Host-specificity and the lifecycle of O. arcticus are unknown, but transmission may involve subsistence and commercially harvested Arctic fish species. Further work is needed to answer these questions. Surveying parasites in Arctic wildlife is important in order to assess potential effects on wildlife and human health (i.e., zoonoses).

The main objective of the study was to identify early risk factors associated with the development of umbilical outpouchings (UOs) in pigs. Secondly, to describe 1) the nature of UOs, 2) the age when UOs become visible, and 3) at which age UOs spontaneously may regress and disappear. A longitudinal study following pigs (n=3031) from birth to slaughter was carried out in two commercial Danish herds. In total, 8 % (n=255) of the pigs developed an UO between birth and death (spontaneous, euthanasia or slaughter). The odds for developing an UO was significantly lower for males than females (OR, 0.7; 95% CL, 0.5-0.9). Pigs born immature (OR, 3.4; 95% CL, 1.3-8.2) or observed with: 1) clinical sign of omphalitis (OR, 1.8; 95% CL, 1.1-2.8), 2) a elongated moist umbilical cord at birth (OR, 5.1; 95% CL, 2.6-9.8) or 3) a healed or healing protruding umbilicus in the second week after birth (OR, 1.9; 95% CL, 1.4-2.6) were associated with significant higher odds of developing an UO. No significant association (p-value >0.05) was found between the development of UOs and sow parity, litter size, birth weight and length of the umbilical cord. The nature of the UOs were mainly due to umbilical herniation and/or formation of abscesses or fibrosis. The majority of UOs became visible within the first 10 weeks of age (80%, n=234). Spontaneous regression of the UOs occurred in 14% (n=36) of the pigs; 83% (n=30) disappeared between the 4th and 14th week. Identifying piglets with high odds of developing UOs makes it possible to identify to which pig special attention should be paid during the daily management.

The aim of the study was to characterize the different types of muscle hemorrhages in the ham and tenderloin of CO2-stunned slaughter pigs. The distinct types of hemorrhages were characterized according to their distribution and size. The hemorrhages in the ham were multiple, pinpoint hemorrhages predominantly distributed in the caudal part of the muscle. The hemorrhages in the tenderloin were single and circular, located either at the tip or the head. Histologically, three distinct types of hemorrhages were observed. Type 1, which was peracute ( 4 h old), and restricted to the ham. Type 3 contained bone marrow and cartilage, was peracute (< 4 h old) and restricted to the tenderloin.

Ischaemic brain lesions and brain abscesses are frequent in both human and animal cases of septic embolic stroke. However, existing models of brain infection do not reflect central aspects of septic embolic stroke. Our aim was to compare septic and non-septic embolic stroke in order to identify gene expressions, inflammatory mediators and brain damage in a rat model.We created precisely located focal brain infarcts in a rat model of Staphylococcus aureus infected embolic stroke. To cause septic embolic stroke we used a fibrin-rich embolus with bacteria, while every rat in the control group received a non-infected embolus. 64 rats were randomized to receive sham-surgery, sterile embolic stroke or septic embolic stroke. All groups were compared for brain pathology, mortality, gene expressions and inflammatory mediators using histology and reverse transcription quantitative real-time PCR.Although infarct volumes did not differ, septic embolic stroke caused higher mortality than sterile embolic stroke (p= 0.002). Brain abscesses were observed only in the septic group. Approximately 400-500 fold increases were observed for Orm1 and Cxcl2 respectively (1.00E-08 p 1.92E-07) in the septic group compared to the sterile group, and these were the most dramatically regulated genes in septic embolic stroke compared to sterile embolic stroke.Septic embolic stroke caused brain abscesses, increased mortality and upregulated Orm1 and Cxcl2 gene expressions compared to non-infected embolic stroke. The dramatic Orm1 increase observed in the septic group is unprecedented and suggests a significant biological role of Orm1 during septic neuroinflammation.

There is inadequate morphological nomenclature and definition of organ pathology when using wild fish in biomonitoring of environmental pollution. The aim of this investigation was to provide a guide that assesses histology of Shorthorn (Myoxocephalus scorpius) and Fourhorn (Myoxocephalus quadricornis) sculpins obtained from a study using these two fish species as bioindicator organisms to evaluate environmental impact attributed to a dumpsite located in East Greenland. Specific histopathological lesions were quantified on the basis of Bernet et al. (1999) and all lesions were photomicrographed, evaluated and placed into specific categories of 5 reaction patterns. These were circulatory disturbances, regressive changes, progressive alterations, inflammation and tumors based upon anatomical location, type and severity. This method is postulated to enable an objective assessment of the histological integrity of fish gills and liver; thus, making it possible to compare sculpin pathology and reaction patterns at different locations. Data suggest that this updated histological guide might be used for identification and quantification of histological lesions when applying sculpins in biomonitoring programs in Greenland and other Arctic regions.

For many years, the sculpin has been utilized as a sentinel monitoring species for anthropogenic impacts on the marine environment. To further develop its potential as a screening model body burden of several trace elements, including cadmium (Cd), copper (Cu), mercury (Hg), lead (Pb) and selenium (Se), were investigated. In addition, histopathology in shorthorn sculpins (Myoxocephalus scorpius; n = 20) and fourhorn sculpins (Myoxocephalus quadricornis; n = 10) were examined at three sites around the Scoresby Sound settlement in Central East Greenland. Fourhorn sculpins caught at the most distant site from the settlement, contained significantly higher hepatic Cu and Cd concentrations as well as significantly elevated gill Pb levels compared to the shorthorn sculpins collected at two other sites closer to the settlement. Histological examinations showed that fish with significantly higher concentrations of hepatic Cd and Se exhibited greater nuclear alterations, interstitial hyperplasia/hypertrophy, interstitial mononuclear infiltrations and granulomas. Further, fish with higher Cd and Cu gill tissue levels displayed a significantly higher number of cytoplasmic alterations and lamellar epithelium lifting, hypertrophic and hyperplastic epithelium along with mucus cell hyperplasia. While the presence of liver lesions were not species or sex-specific, the presence of gill lesions decreased in the order female fourhorn sculpins > female shorthorn sculpins > male fourhorn sculpins > male shorthorn sculpins. Hepatic Hg concentrations exceeded known lowest observable effect doses (LOED) for fish (0.1–0.5 μg g−1 ww) in 27% of fish, while liver Cd residues in 80% exceeded LOED (0.42–1.8 μg g−1 ww). Based upon these results, data suggest that using the sculpin as a valuable sentinel fish species histopathology may serve as a reliable tool for assessing marine ecosystem exposure to trace metals. However, confounding physiological and ecological factors also need to be considered.

Muscle hemorrhages are regularly observed in especially the tip of the tenderloin muscles of slaughter pigs. In order to characterize the hemorrhages, a macro- and microscopic examination of tenderloins with (n=5) and without (n=4) hemorrhages and the associated vertebral column was carried out. Furthermore, all columns were radiographed and two were CT scanned. Histologically, the muscle hemorrhages contained cells from bone marrow and growth line cartilage. Ventral epiphysiolysis in either the cranial or caudal epiphysis of the first lumbar vertebrae (L1) in 8 out of the 9 vertebral columns was present. In the 5 cases with tenderloin hemorrhage, similar hemorrhage with growth line cartilage was found within the fracture of the epiphysis. The hemorrhages develop secondarily to epiphysiolysis in the lumbar vertebrae, where the tenderloin attaches to the spine. The lesions probably develop around the time of stunning.

There is inadequate morphological nomenclature and definition of organ pathology when using wild fish in biomonitoring of environmental pollution. The aim of this investigation was to provide a guide that assesses histology of Shorthorn (Myoxocephalus scorpius) and Fourhorn (Myoxocephalus quadricornis) sculpins obtained from a study using these two fish species as bioindicator organisms to evaluate environmental impact attributed to a dumpsite located in East Greenland. Specific histopathological lesions were quantified on the basis of Bernet et al. and all lesions were photomicrographed, evaluated, and placed into specific categories of five reaction patterns. These were circulatory disturbances, regressive changes, progressive alterations, inflammation, and tumors based on anatomical location, type, and severity. This method is postulated to enable an objective assessment of the histological integrity of fish gills and liver; thus, making it possible to compare sculpin pathology and reaction patterns at different locations. Data suggest that this updated histological guide might be used for identification and quantification of histological lesions when applying sculpins in biomonitoring programs in Greenland and other Arctic regions.

The former lead-zinc mine at Mestersvig, Greenland, continues to contaminate the surrounding environment despite its operations ceasing over 50 years ago. Elevated concentrations of heavy metals are found in water, sediment and biota in the terrestrial, freshwater and marine environments. To shed light on the present contamination and its potential effects on local fish we investigated gill and liver histology of sculpins (Myoxocephalus spp.) around the former mining area. Two species of sculpins were caught; shorthorn sculpins (M. scorpius; n = 16) and fourhorn sculpins (M. quadricornis; n = 17) at a contaminated site, Nyhavn, and shorthorn sculpins (M. scorpius; n = 25) at the reference site. In a previous study we found histopathological changes in the tissues of the sculpins, and we suspected this to be related to elevated heavy metal tissue concentrations. Concentrations of Fe, Hg, Mn, Pb, Se and Zn were significantly higher in sculpins at Nyhavn compared to the reference site. Reference NOED and LOEC thresholds for biochemistry, tissue lesions, growth, survival and reproduction for hepatic Hg, As, Cd and Pb from the ERED database were exceeded in both sculpin species. Histopathological investigations of the sculpins gills revealed significant increases in the prevalence of hyperplastic epithelium, inflammation, intensity of neutral and total mucus cells and chloride cells along with an increased infection of colonial Peritricha. At the contaminated Nyhavn site, fourhorn sculpins had a significantly higher prevalence of chondroplastic tissue and intensity of neutral, mixed and total mucus cells in the gills compared to the shorthorn sculpins. The data indicate that both sculpin species could be useful indicator species for environmental monitoring of metal pollution in Arctic areas. However, confounding effects of gender and species should be investigated further. Effects on other biomarkers as well as baseline measurements should be included in future environmental monitoring efforts around mining activities in Greenland.

Narwhals (Monodon monoceros) are at the top of the Arctic food web and therefore might biomagnify high total mercury (Hg) concentrations in organs and tissues. The aim of this study was to determine histopathology and Hg concentrations in liver and kidneys from 15 North East Greenland narwhals (3 subadult females, 8 adult females, 3 subadult males, and 1 adult male) and compare data with previous observations of 12 North West Greenland specimens (1 subadult female, 4 adult females, 1 subadult male, and 6 adult males). The zoological length was significantly larger and hepatic and renal concentrations significantly higher in adults compared to subadults. When comparing tissues, the Hg levels were significantly the highest in liver, while a correlation between metal levels in liver and kidneys was positive and significant. Histological examination of renal tissues presented four types of glomerular lesions (capillary dilatation [0-100%], membrane thickening [0-100%], dilatation of space [0-80%], and sclerosis [0-70%]) and two tubular lesions (atrophy/hyalinization [0-40%] and casts [0-60%]). Hepatic tissues exhibited three portal lesions (fibrosis [0-33%], cell infiltrates [0-40%], and bile duct proliferation [0-40%]) and two parenchymal lesions (steatosis [83-100%] and lipid-filled Ito cells [0-33%]). All 12 lesions were found in adult whales from North West Greenland while eight were present in adult whales from North East Greenland. Six lesions were detected in subadults from North East Greenland and four in subadults from North West Greenland. A significantly higher frequency of dilatation and hyalinization of Bowman's space and capsule and glomerular capillary dilatation was found in adult narwhals from West Greenland. There was no marked difference in Hg concentrations in whales with and without histological lesions. In conclusion, the prevalence of histological changes and Hg levels were the highest in adults and therefore both age and metal are important factors to include when evaluating liver and kidney lesions in narwhals.

Segmental arterial mediolysis, a rare arteriopathy first reported in humans, is described in the kidneys of 36 pigs slaughtered in an abattoir in Jutland, Denmark. The kidney changes presented themselves macroscopically as one or more cortical wedge-shaped hemorrhagic or pale lesions. The arterial lesions involved the interlobar and arcuate arteries and exhibited injurious and reparative phases of development. Two types of injurious lesions occurred: (1) a tearing separation of the outer media from the adventitia with fibrin, erythrocytes, and edema fluid filling the formed space, causing collapse of the arterial wall, and (2) outer and mid-medial foci showing irregularly bordered cytoplasmic vacuolar change containing membranous and organelle debris or smooth muscle shrinkage with nuclear loss. In the reparative phase, granulation tissue filled and expanded tear sites and zones of arterial medial muscle loss and extended into the adventitia and through the intima into the arterial lumen. Sequelae, including dissecting hematomas and arterial occlusions causing renal infarcts, were found. Although repartitioning agents widely used in animal husbandry in many countries may potentially cause segmental arterial mediolysis, no such link could be identified. The causation of segmental arterial mediolysis in these pigs is currently unknown but is being further investigated.

Mitochondrial dysfunction and oxidative stress are important players in the development of various cardiovascular diseases, but their roles in hypertrophic cardiomyopathy (HCM) remain unknown. We examined whether mitochondrial oxidative phosphorylation (OXPHOS) capacity was impaired with enhanced mitochondrial oxidative stress in HCM. Cardiac and skeletal muscles were obtained from 9 domestic cats with spontaneously occurring HCM with preserved left ventricular systolic function and from 15 age-matched control cats. Mitochondrial OXPHOS capacities with nonfatty acid and fatty acid substrates in permeabilized fibers and isolated mitochondria were assessed using high-resolution respirometry. ROS release originating from isolated mitochondria was assessed by spectrofluorometry. Thiobarbituric acid-reactive substances were also measured as a marker of oxidative damage. Mitochondrial ADP-stimulated state 3 respiration with complex I-linked nonfatty acid substrates and with fatty acid substrates, respectively, was significantly lower in the hearts of HCM cats compared with control cats. Mitochondrial ROS release during state 3 with complex I-linked substrates and thiobarbituric acid-reactive substances in the heart were significantly increased in cats with HCM. In contrast, there were no significant differences in mitochondrial OXPHOS capacity, mitochondrial ROS release, and oxidative damage in skeletal muscle between groups. Mitochondrial OXPHOS capacity with both nonfatty acid substrates and fatty acid substrates was impaired with increased mitochondrial ROS release in the feline HCM heart. These findings provide new insights into the pathophysiology of HCM and support the hypothesis that restoration of the redox state in the mitochondria is beneficial in the treatment of HCM.

Graphical abstract, Highlights • Pigs with seizures had larger amount of collagen compared to pigs without seizures. • Collagen is likely to play a role in the pathogenesis of seizures in neurocysticercosis. • Pigs can serve as a model for studying the pathogenesis of seizures in neurocysticercosis., Neurocysticercosis caused by infection with Taenia solium is a significant cause of epilepsy and seizures in humans. The aim of this study was to assess the association between seizures and the deposition of collagen in brain tissue in pigs with T. solium neurocysticercosis. In total 78 brain tissue sections from seven pigs were examined histopathologically i.e. two pigs with epileptic seizures and T. solium cysts, four pigs without seizures but with cysts, and one non-infected control pig. Pigs with epileptic seizures had a larger amount of collagen in their brain tissue, showing as large fibrotic scars and moderate amount of collagen deposited around cysts, compared to pigs without seizures and the negative control pig. Our results indicate that collagen is likely to play a considerable part in the pathogenesis of seizures in T. solium neurocysticercosis.

The effects of tagging on small cetaceans are difficult to assess due to logistical difficulties in recapturing the whales. In this study two narwhals, Monodon monoceros, and five harbor porpoises, Phocoena phocoena, were recaptured between 297 and 767 days after instrumentation with satellite transmitters. The transmitters were mounted by pins that were pushed through the fins of the porpoises or the backs of the narwhals. Overall body condition seemed unaffected by the instrumentations. Macroscopical examination revealed that umbilicalization of the tissue surrounding the pins was almost complete. On one of the narwhals the reepithelialization created a closed tunnel where the pins were isolated from the subdermal tissue, however the reepithelialization was incomplete around the middle of the pin and a low-grade inflammation increased with decreasing thickness of epidermis. The inflammation consisted of mononuclear cells, mainly lymphocytes. With increasing inflammation the number of neutrophils and macrophages increased. In the lymphoid follicular hyperplasia macrophages and a few neutrophils were found, in one case accompanied by Splendore-Hoeppli material with radiating eosinophilic clubs and Gram-positive cocci. Immunohistochemical staining of the cocci for Staphylococcus aureus was positive. The observations from the recaptured cetaceans suggest that the instrumentations caused only temporary and low-grade inflammatory responses.

Japanese quails (Coturnix japonica) were exposed in ovo to tris(1,3-dichloro-2-propyl) phosphate (TDCIPP; 500 ng/µl), Dechlorane Plus (DP; 500 ng/µl), or a 1:1 mixture of these two to investigate the effects on liver and thyroid gland morphology. Histological examination of 14-day-old quails showed that exposure to TDCIPP or the mixture induced hepatic sinusoidal dilatation. No marked effects were seen for DP alone. In addition, the mixture produced divergence of thyroid gland follicles and proliferation of follicular cells. Our study is the first demonstrating histopathological alterations as a result of exposure during early development to the flame retardants TDCIPP or a TDCIPP–DP mixture suggesting the need for further research efforts to investigate potential adverse health effects associated with exposure to these environmental chemicals in wild birds. This is an accepted manuscript of an article published by Taylor & Francis in [Journal of Toxicology and Environmental Health, Part A: Current Issues] on [11 Jul 2017], available at http://www.tandfonline.com/doi/full/10.1080/15287394.2017.1336414. Locked until 11.7.2018 due to copyright restrictions.

Background: Segmental arterial mediolysis (SAM) a rare arteriopathy causing massive bleeding or ischemic symptoms, is suspected of representing a vascular disease of the peripheral sympathetic nervous system. It is initiated by the supra physiological release of norepinephrine from the efferent branches of the peripheral sympathetic nerves that innervate the large and medial sized muscular arteries targeted in SAM. Recognized stimuli for this response are iatrogenic sympathomimetic agonists and some B-2 agonists. However, these stimuli were not always apparent in published cases of SAM casting doubt on this hypothesis. Methods and findings: SAM, reported in kidneys of slaughtered pigs, was believed to represent a dysfunctional development in a fight and flight response. Additionally some stenotic renal arteries described in cases of pheochromocytomas reportedly were caused by arterial spasm and fibromuscular dysplasia changes found in the evolution of SAM. Varying degrees of mesangial cell hyperplasia accompanied SAM in swine, dog and scattered human cases of SAM. Segmental sclerosis of glomerular loops accompanied the mesangial cell hyperplasia in a few cases of SAM. The hyperplasia was not extensive so that its role in regulating blood flow and urine volume through glomerular capillaries was probably inconsequential. It represented a collateral lesion created by SAM’s norepinephrine driven pathogenesis. Conclusion: These findings provide indirect evidence that SAM additionally may be initiated by conditions causing the adrenal medulla to release supra physiologic levels of circulating norepinephrine. Supra physiologic release of norepinephrine from the peripheral sympathetic nerves also can cause mesangial hyperplasia that can be accompanied with segmental glomerular loop sclerosis-making it another precursor lesion of focal segmental glomerulosclerosis.

Neurocysticercosis (NCC) caused byTaenia soliumcysts is a frequent but neglected parasitic disease of the central nervous system (CNS) worldwide. The aim of this study was to describe anatomical locations of cysts in the CNS and the corresponding inflammation. A total of 17 naturally infected pigs were used to evaluate the distribution of cysts and, of these, seven were used to evaluate the corresponding inflammation further, through histopathology. Clinical signs in the pigs included dullness, sluggishness, somnolence, apathy and loss of consciousness. Cysts were distributed in all cerebral lobes, i.e. 39.7% in the frontal lobe, 20.3% in the parietal lobe, 20.0% in the occipital lobe and 19.7% in the temporal lobe, and only 0.4% in the cerebellum. No cysts were found in the spinal cord. Cysts were localized as follows: 47.9% in the dorsal subarachnoid, 46.9% in the parenchyma, 4.4% in the subarachnoid base and 0.9% in the ventricles. The results of the histopathology revealed lesions in an early inflammatory stage, i.e. stage I, in all anatomical locations except for two, which showed more of an inflammatory reaction, stage III, in one pig. It was concluded that clinical signs in pigs were neither pathognomonic nor consistent. These signs, therefore, cannot be used as a reliable indicator of porcine NCC. Furthermore,T. soliumcysts were found to be in abundance in all cerebral lobes, and only a few were found in the cerebellum. Regarding the inflammatory response, no significant differences were found in the location and total number of cysts. Thus, further studies are needed to explain the determinants of cyst distribution in the CNS and assess in detail clinical signs associated with porcine NCC.

The objective of this study was to identify the specific localization of interleukin-8 (IL-8) in cells in situ in a variety of inflammatory processes in different tissues from pigs. Our hypothesis was that IL-8 primarily is a neutrophil related cytokine present in all extravascular neutrophils while expression also occurs in other cell types in response to an inflammatory stimulus. Using IL-8 immunohistochemistry we discovered that neutrophils were the predominant IL-8 positive cell population while epithelial cell types and endothelium of postcapillary venules could be positive when situated in close vicinity of an inflammatory lesion. Furthermore, endothelial cells of newly formed vessels in granulation tissue were positive in some specimens. Some sub-populations of inflammatory neutrophils were, however, IL-8 negative which could reflect some phase of neutrophil swarming.

Background Strongylus vulgaris is re-emerging in horses kept under surveillance-based parasite control regimens. Information on nonstrangulating intestinal infarction associated with S. vulgaris is needed to improve recognition of the condition. Objective To describe the typical clinical presentation, laboratory findings, gross pathology, treatment and outcome of horses with nonstrangulating intestinal infarction. Study design Retrospective case series. Methods Nonstrangluating intestinal infarction was diagnosed in 30 horses with a localised intestinal infarction with concurrent signs of S. vulgaris migration and no signs of intestinal strangulation or enterocolitis. Data were obtained from medical records in the period 2008-2016. Long-term follow-up information was obtained by telephonic interviews. Levels of S. vulgaris-specific antibodies were retrospectively assessed. Associations between nonstrangulating intestinal infarction and selected variables were evaluated using Fisher's exact and Mann-Whitney U tests. Results The most consistent findings at admission were mild colic of >24 h duration without signs of shock or strangulated intestine, increased peritoneal fluid WBC (>5 × 109 /L), increased serum amyloid A (SAA) concentration and a positive S. vulgaris-specific antibody titre. Medical treatment was attempted in nine horses with none surviving. Exploratory laparotomy was performed in 21 horses. Eleven horses were subjected to euthanasia intraoperatively due to the presumed poor prognosis. Of the nine horses, three (33%) undergoing intestinal resection survived to discharge. The surviving horses were alive and returned to athletic function for at least 2 years following discharge. Main limitations Only nine of the 30 horses underwent resection of the infarcted intestine, and the prognosis for surgical intervention in nonstrangulating intestinal infarction is, therefore, difficult to estimate. Conclusions In areas where S. vulgaris is prevalent, nonstrangulating intestinal infarction should be considered as a differential diagnosis in horses presenting with mild colic and peritonitis. Survival of nonstrangulating intestinal infarction is possible in cases where surgical intervention with resection of the infarcted intestine is feasible. The summary is available in Spanish - see Supporting Information.

In order to further characterize the immune response around the viable or degenerating Taenia solium cysts in the pig brain, the involvement of cysteine protease in the immune evasion was assessed. Brain tissues from 30 adult pigs naturally infected with T. solium cysticercosis were subjected to histopathology using hematoxylin and eosin stain, and immunohistochemistry using caspase-3 antibodies. Histopathological evaluation revealed lesions of stage I which was characterized by presence of viable parasite surrounded with minimal to moderate inflammatory cells and stage III characterized by the presence of a disintegrating parasite surrounded with high inflammatory cells. The results of immunohistochemistry indicated caspase-3 positive cells interspaced between inflammatory infiltrate mainly in stage I lesions, indicating the presence of cysteine protease. This result confirms the earlier hypothesis that cysteine protease may play a role in inducing immune evasion through apoptosis around viable T. solium cysts.

Lung emphysema is a central feature of chronic obstructive pulmonary disease (COPD), a frequent human disease worldwide. Cigarette smoking is the major cause of COPD, but genetic predisposition seems to be an important factor. Mutations in surfactant protein genes have been linked to COPD phenotypes in humans. Also, the catalytic activities of metalloproteinases (MMPs) are central in the pathogenesis of emphysema/COPD. Especially MMP9, but also MMP2, MMP7, and MMP12 seem to be involved in human emphysema. MMP12−/− mice are protected from smoke-induced emphysema. ITGB6−/− mice spontaneously develop age-related lung emphysema due to lack of ITGB6-TGF-β1 regulation of the MMP12 expression. A mutated pig phenotype characterized by age-related lung emphysema and resembling the ITGB6−/− mouse has been described previously. To investigate the emphysema pathogenesis in this pig model, we examined the expression of MMP2, MMP7, MMP9, MMP12, and TGF-β1 by quantitative PCR (qPCR). In addition, immunohistochemical stainings of the lungs with SP-B, SP-C, MMP9, and MMP12 antibodies were performed. The haematologic/immunologic status of the pigs also was studied. The qPCR study showed no difference between pigs with and without emphysema, and no systemic differences were indicated by the haematologic and immunologic studies. However, the immunohistochemical stainings showed an increased expression of MMP9 and MMP12 in older, mutated pigs (with emphysema) compared with normal and young mutated pigs (without emphysema). The pig model is comparable to human emphysema patients and the ITGB6−/− mouse model with respect to both morphology and functionality.

ObjectiveNon-ischemic mitral regurgitation (MR) is primarily caused by myxomatous mitral valve (MV) disease leading to adaptive remodeling, enlargement, and dysfunction of the left ventricle. The aim of this study was to examine the regulation of plasma markers and several cardiac key genes in a novel porcine model of non-ischemic MR.Methods and resultsTwenty-eight production pigs (Sus scrofa) were randomized to experimental MR or sham surgery controls. MR was induced by external suture(s) through the posterior MV leaflet and quantified using echocardiography. The experimental group was subdivided into mild MR (mMR, MR=20–50%, n=10) and moderate/severe MR (sMR, MR >50%, n=6) and compared with controls (CON, MR ≤10%, n=12). Eight weeks postoperatively, follow-up examinations were performed followed by killing. Circulating concentrations of pro-atrial natriuretic peptide (proANP), l-arginine, asymmetric dimethylarginine, and symmetric dimethylarginine (SDMA) were measured. MV, anterior papillary muscle, and left ventricular free wall tissues were collected to quantify mRNA expression of eNOS (NOS3), iNOS (NOS2), MMP9, MMP14, ANP (NPPA), BNP (NPPB), and TGFB1, 2, and 3 and five microRNAs by quantitative real-time PCR. Pigs with sMR displayed markedly increased plasma proANP and SDMA concentrations compared with both controls and mMR (PmiR-21 and miR-133a were differently expressed among the experimental groups (PConclusionsPlasma proANP and SDMA levels and tissue expression of miR-21 and miR-133a are associated with severity of chronic MR in an experimental porcine model.

The knowledge of systemic inflammation and local cytokine expression in porcine endocarditis models is limited, though it could provide valuable information about the pathogenesis and comparability to human endocarditis. Analyses of bacteriology and hematology were performed on blood samples from pigs with non-bacterial thrombotic endocarditis (NBTE, n = 11), Staphylococcus aureus infective endocarditis (IE, n = 2), animals with S. aureus sepsis without endocarditis (n = 2) and controls (n = 2). Furthermore, immunohistochemistry was used to examine the local expression of IL-1β and IL-8. Bacterial blood cultures were continuously positive in IE pigs from inoculation to euthanasia, and negative in all other pigs at all times. The total white blood cell counts and total neutrophil counts were massively elevated in pigs with IE. Local IL-1β and IL-8 expression in IE pigs were moderate to high, and high, respectively. In addition, slight local expression of IL-1β and IL-8 was present in some NBTE pigs. In the IE model, both the systemic inflammatory response and the high local expression of IL-8 were comparable to the human disease. Furthermore, the results indicate IL-1β and IL-8 as important contributors in the endocarditis pathogenesis.

Staphylococcus aureus is a common cause of skin and soft tissue infections in animal and humans. In the current study, we hypothesized that early host responses to S. aureus infection leading to the recruitment of neutrophils and control of the bacterium at the site of infection depend on the expression of Serpine-1 and Tissue inhibitor of metalloproteinase type-1, two important endogenous proteinase inhibitors that possess regulatory properties on a variety of pathophysiological conditions. Using a mouse model of skin infection and single-gene and double-gene knockout mice, however, our observations showed that Serpine-1 and Tissue inhibitor of metalloprotease type-1 did not impact the number of bacteria accumulating at the site of infection. Double-gene knockout mice further had the same volume of accumulating host cells at the site of infection, while single Tissue inhibitor of metalloprotease type-1 knockout mice showed a decreased number of cells. Follow-up studies demonstrated changes in Serpine-1, Tissue inhibitor of metalloprotease type-1 and IL-6 plasma levels following challenge. In addition, double-gene knockout mice did not differ from wild-type mice in white blood cell, granulocyte and leucocyte counts, while single-gene genotypes differed in these phenotypes.

A new inoculation technique has been developed and applied in a porcine model of juvenile hematogenous osteomyelitis. Following the success of the model, we describe the inoculation technique in detail to enable its replication in future studies. The technique was based on an anatomical feature of the femoral artery that enables inoculation into the artery using a simple surgical procedure. Inoculation in the femoral artery is advantageous because the localization of lesions constitutes a discriminative model of the naturally occurring hematogenous osteomyelitis in long bones, usually involving femur and tibia in children. The procedure was performed under general anesthesia and consisted of five major steps: (1) Exposure of the right femoral artery, (2) retrograde catheterization, (3) inoculation of bacteria, (4) hemostasis of the arterial puncture site using compression, and (5) suturing of the wound in two layers.

Tumors of the adrenal glands are among the most frequent tumors in cattle; however, few studies have been conducted to describe their characteristics. The aim of this study was to classify 41 bovine adrenal neoplasms from 40 animals based on macroscopic and histologic examination, including electron microscopy and immunohistochemistry for melan A, synaptophysin, chromogranin A, vimentin, pan-cytokeratin, 2′,3′-cyclic nucleotide-3′-phosphohydrolase (CNPase), and Ki-67. The tumors were classified as 23 adrenocortical adenomas, 12 adrenocortical carcinomas, 2 schwannomas, 2 pheochromocytomas (1 malignant), and 1 ganglioneuroma. Five histologic features were characteristic of metastasizing adrenocortical tumors: invasion of the capsule, vascular invasion, diffuse growth pattern, spindle-cell morphology, and nuclear pleomorphism. Adrenocortical tumors with at least 3 of these features were classified as malignant. Immunohistochemically, adrenocortical tumors expressed melan A (16/19), vimentin (14/26), cytokeratin (11/26), and chromogranin A (9/27), whereas pheochromocytomas expressed chromogranin A (2/2), synaptophysin (2/2), and vimentin (1/2). Both schwannomas expressed CNPase. An immunohistochemistry panel consisting of antibodies against melan A, synaptophysin, and CNPase was considered most useful to classify bovine adrenal tumors. However, the distinction between benign and malignant adrenocortical tumors was based on histologic features as in human medicine.

Organohalogen contaminants bioaccumulate to high concentrations in tissues of polar bears (Ursus maritimus). The exposure levels are in the order to be toxic to inner organs like liver and kidney. We therefore investigated the temporal development of lesions in liver (n=115) and kidney (n=122) samples from East Greenland polar bears taken over the 12 year period from 1999 to 2010. Seven liver and seven kidney lesions were observed of which six were age-related. Controlling for this, the analyses showed that hepatic steatosis and renal cell infiltrations, glomerular sclerosis and tubular hyperplasia decreased over the investigated time period (all p

Introduction Elephant endotheliotropic herpesvirus-1 (EEHV-1) is one of the major causes of fatality in juvenile Asian elephants (Elephas maximus). On occasions, other EEHV genotypes, i.e. EEHV-3, -4 and -5, have also been reported as the cause of Asian elephant deaths. In this case report we describe the investigation into a juvenile Asian elephant fatality in a European zoo. Case Presentation: A fatal case of haemorrhagic disease in a juvenile Asian elephant from a European zoo was diagnosed with co-infection of EEHV-1 and -4. EEHV-4 had a wider organ distribution and a higher viral load; both viruses presented the highest load in the mesenteric lymph nodes. Conclusion: Detection of EEHV-4 in this fatal case in Europe underlines the importance of inclusion of all known Asian EEHVs in routine blood monitoring to facilitate early therapeutic intervention.

Summary Matrix metalloproteinases (MMPs) play a variety of roles during organogenesis, in the immune response and during acute and chronic diseases as well as in tissue remodelling. During the last decade, the pig has become used increasingly as a model for human diseases; however, studies on the expression of porcine MMPs are limited. In the present study species-specific antibodies were produced to investigate the expression of MMP-9 and MMP-12 immunohistochemically in lungs from pigs infected with Actinobacillus pleuropneumoniae , Pasteurella multocida and Staphylococcus aureus . The immunolabelling of lung tissues (one infected and one control pig representing each infection) was evaluated for cellular distribution and intensity, which was scored semiquantitatively. When compared with healthy, non-infected controls, the expression of both MMP-9 and MMP-12 was higher in infected lungs. The highest expressions were seen in the alveolar epithelium (MMP-9) and alveolar macrophages (MMP-12). These results are in accordance with studies of human lungs.

Left-sided valvular endocarditis (LSVE) is a common finding in slaughter pigs. The lesion is often associated with renal thromboembolism, but information on embolization to other organs is sparse. This study focuses on the presence and type of endocarditis-associated brain lesions (EABLs). The brains of 20 slaughter pigs with spontaneously arising LSVE and 11 controls were examined by sectioning half of a formalin-fixed brain into 4mm slices for histological examination. The aetiology of the endocarditis was determined by bacteriological and, in some cases, by fluorescence in-situ hybridization examinations. These examinations identified 11 cases of Streptococcus suis, six cases of Erysipelothrix rhusiopathiae, one Streptococcus spp. and two cases that remained aetiologically undetermined. One of the S. suis cases had a dual infection with S. suis in the aortic valve lesions and Streptococcus dysgalactiae subsp. equisimilis in the atrioventricular valve lesions. Renal infarcts were present in eight cases. Focal encephalitis was found in 12 cases, with the number of lesions ranging from one to 11. Most pigs had less than four microscopical lesions. Acute lesions were characterized by focal microabscesses without observable bacteria. Chronic lesions were characterized by astrocytosis and focal accumulation of mononuclear leucocytes. An infarct was observed in one animal. Perivascular inflammation was seen in 14 cases, mostly as two or three lesions, while focal leptomeningitis was found in eight cases. EABLs are therefore common in slaughter pigs with LSVE. The number of lesions per animal is small, which may explain the limited attention paid to this sequela of LSVE. EABLs have rarely been reported in domestic animals and mostly in patients with neurological signs. The frequent occurrence of EABLs in slaughter pigs suggests that this pathology should be investigated in other animal species with LSVE.

Thyroid gland histology was examined in 20 organohalogen contaminant (OHC)-exposed East Greenland polar bears (Ursus maritimus). OHC concentrations measured in subcutaneous adipose tissue were between 3556 and 28,670 ng g−1 lw for polychlorinated biphenyls (ΣPCB51), 9 and 3403 ng g−1 lw for the sum of organochlorine pesticides (hexachlorocyclohexanes, hexachlorobenzene, chlordanes, dichlorodiphenyltrichloroethanes, and dieldrin), and from 21 to 130 ng g−1 lw for polybrominated diphenyl ethers. Histological examinations revealed that 12 of the bears (10 males aged 3–19 years and two females aged 4–7 years) had normal thyroid tissue while eight bears (40%) of varying ages and genders (three males aged 3–9 years and five females aged 4–25 years) showed clear histological lesions including parafollicular C-cell proliferation, nodular hyperplasia, and interstitial fibrosis. No significant differences were found in prevalence of thyroid gland lesions between males and females. Similarly, no marked difference wa...

A porcine model of acute, haematogenous, localized osteomyelitis was established. Serial dilutions of Staphylococcus aureus [5-50-500-5000-50 000 CFU/kg body weight (BW) suspended in saline or saline alone] were inoculated into the right brachial artery of pigs (BW 15 kg) separated into six groups of two animals. During the infection, blood was collected for cultivation, and after the animals were killed from day 5 to 15, they were necropsied and tissues were sampled for histopathology. Animals receiving ≤500 CFU/kg BW were free of lesions. Pigs inoculated with 5000 and 50 000 CFU/kg BW only developed microabscesses in bones of the infected legs. In the centre of microabscesses, S. aureus was regularly demonstrated together with necrotic neutrophils. Often, bone lesions resulted in trabecular osteonecrosis. The present localized model of acute haematogenous osteomyelitis revealed a pattern of development and presence of lesions similar to the situation in children. Therefore, this model should be reliably applied in studies of this disease with respect to e.g. pathophysiology and pathomorphology. Moreover, because of the regional containment of the infection to a defined number of bones, the model should be applicable also for screening of new therapy strategies.

To establish a simple and uniform classification of bovine peripheral nerve sheath tumors (PNSTs), 63 tumors from 44 cattle were examined histologically and immunohistochemically with antibodies against S100 protein and 2′,3′-cyclic nucleotide-3′-phosphohydrolase (CNPase). Immunohistochemically, all the tumors were positive for S100 protein, CNPase, or both. Four types of PNST were recognized: 35 schwannomas, 9 neurofibromas, 14 hybrid (neurofibroma–schwannoma) tumors, and 5 malignant PNSTs. Axons were identified by immunohistochemistry for neurofilament in a proportion of tumors of each type of PNST. In conclusion, bovine PNSTs commonly have both schwannomatous and neurofibromatous areas. Moreover, the Schwann cell markers S100 protein and CNPase, in combination with antibodies against neurofilament, are valuable diagnostic tools to classify bovine PNSTs.

The associations between blood organohalogen contaminant (OHC) concentrations and thyroid gland histology were studied in 10 adult female glaucous gulls (Larus hyperboreus) from the Norwegian Arctic (Bjornoya) during the incubation period. This histological investigation was undertaken as previous glaucous gull studies from the same area reported negative relationships between circulating OHC concentrations and thyroid hormone levels. Organohalogen concentrations have previously been associated with altered blood plasma thyroid hormone concentrations, as a result of parenchymal thyroid gland alterations and perturbation of the hypothalamic-pituitary-thyroid (HPT)-axis. In this study, PCB (range: 186–1027 ng g−1ww), DDT (77–203 ng g−1ww) and chlordane (18–65 ng g−1ww) concentrations dominated the blood plasma OHC profile in incubating female glaucous gulls. High density of small follicles accompanied by follicular epithelial cell proliferations was seen in thyroid glands in seven of 10 gulls. Focal thyroid...

This study investigated whether low-level, long-term in utero and post-natal exposure to organohalogen pollutants disrupts male reproductive organ morphology and testosterone production in Greenland sledge dogs (Canis familiaris), as a model of Arctic top predators feeding on marine mammals. Six male dogs were followed for 1 year and testosterone concentrations, testes/baculum morphology and baculum bone mineral density (BMD) was determined. Three males were exposed to organohalogenated contaminants (OHCs) in utero through maternal dietary intake of minke whale blubber (Balaenoptera acutorostrata), with a post-weaning ∑OHC intake of 10.4–11.7 µg kg−1 day−1 resulting in an adipose tissue range of ∑OHC 4518–5729 ng (g lw)−1 after 1 year. Three control males were exposed to very low concentrations of OHCs through pork fat. No significant differences were seen in plasma testosterone concentrations, baculum weight, BMD, and testicular length in the six male dogs (control, n = 3 and exposed, n = 3) measured at ...

Long-finned pilot whales (Globicephala melas) from the Faroe Islands are known to be heavily polluted with contaminants, such as mercury (Hg) and organochlorine compounds (OC). This is postulated to exert adverse health effects on whales as well as the human population who rely on its meat and blubber as food sources. It was therefore decided to conduct a screening pilot study to determine contaminant concentrations and histopathology of liver and renal tissues in a total of 14 specimens from this subpopulation. In blubber, the mean ∑OC concentration was 31,887 ng g−1 lw (range: 18,170–47,425 ng g−1 lw) of which ∑PCB concentration was 23,416 ng g−1 lw (range: 13,947–34,543 ng g−1 lw; n = 3). In liver, mean Hg concentration was 138 µg−1 ww (range: 54–351 µg g−1 ww; n = 7) and mean cadmium (Cd) concentration 15 µg g−1 ww (range: 7–31 µg g−1 ww; n = 7). In the kidney, the mean Cd concentration was 36 µg g−1 ww (range: 23–47 µg g−1 ww; n = 7). Of the liver Hg concentrations, two were at the suggested toxic th...

The aim of this study was to assess the effect of treating Taenia solium infected pigs with oxfendazole (OFZ) on viability and clearance of cysticerci and the corresponding persistence of specific antibody isotypes (IgG(total), IgG1, IgG2 and IgA) and circulating cysticercal antigen (CCA). Antibody isotypes and CCA responses were measured by antibody-ELISA (Ab-ELISA) and antigen ELISA (Ag-ELISA), respectively. Correlations were made between antibodies, CCA and the total number of cysticerci enumerated at necropsy. Forty pigs with cysticercosis were randomly allocated into two groups: Treatment group (n=20) was treated with OFZ at 30 mg/kg orally while the treatment control group (n=20) was not treated. Five uninfected pigs served as negative controls. Pigs were killed at 1, 4, 8 and 26 weeks post-treatment (wkpt). Overall, the mean total cyst count in treated pigs was 2904+/-5397 (mean+/-S.D.) while in the controls it was 6235+/-6705. Mean cyst viability was 5+/-11% (mean+/-S.D.) and 97+/-4% in treated and control pigs, respectively. Results showed that OFZ killed muscular cysticerci over a period of 4 weeks but failed to kill cerebral cysticerci. Antibodies, CCA responses and clearance of dead cysts from the meat, depended on the cyst intensity of individual pigs at time of treatment since both antibody and CCA correlated with intensity of cysticerci at necropsy (r=0.441, P=0.005; r=0.654, P

SUMMARYTo assess whether apoptosis occurs in pig brain granulomas due toTaenia soliumcysticerci, brain tissues from 30 pigs naturally infected withT. soliumcysticercosis were evaluated by terminal deoxynucleotidyl transferase-end labelling (TUNEL) staining. In addition, tissues were stained with CD3 marker to identify T lymphocytes. Examination of TUNEL-stained tissues showed apoptotic cells in early lesions that contained viable cysticerci. Apoptotic cells were primarily found interspersed with normal cell types, and were mostly located in the inflammatory infiltrate. Late or advanced granulomas with disintegrated scolices did not show TUNEL-positive cells. CD3+ cells were found in both early and advanced lesions and apoptosis mainly co-localized with CD3+ T lymphocytes. This suggests that these cells are constantly undergoing apoptosis and thus die as soon as they arrive at the site of infection. Apoptosis indeed may be one way by whichT. soliumcysticerci down-regulate the host's cellular immune response in early cysticercosis. Therefore, further research is needed to establish if other cells besides T-lymphocytes are also a target for destruction by cysticerci in early cysticercosis as well as studies to assess if cysteine protease is expressed by viable cysticerciin situ.

The effects of persistent organic pollutants on renal and liver morphology in farmed arctic fox (Vulpes lagopus) were studied under experimental conditions. Control animals received a diet containing pork (Sus scrofa) fat with low amounts of persistent organic pollutants, while the diet of the exposed animals contained whale blubber, 'naturally' contaminated with persistent organic pollutants. Polychlorinated biphenyls (PCB) and organochlorine pesticide (OCP) concentrations in the whale blubber were 488 and 395 ng/g wet weight, respectively. Animals were sacrificed and sampled when they were at their fattest (winter) as well as their lowest body weight (summer). The results show that PCB and OCP exposure causes renal (and probably also liver) lesions in arctic foxes. The prevalence of glomerular, tubular and interstitial lesions was significantly highest in the exposed group (chi-square: all p0.05). The frequency of liver lesions (steatosis, intravascular granulocyte accumulations, interstitial cell infiltrations, lipid granulomas, portal fibrosis and bile duct hyperplasia) were also highest in the exposed group, although not significantly (chi-square: all p0.05). The prevalence of lesions was not significantly different between lean (winter) and fat (summer) foxes for any of the lesions (chi-square: all p0.05). We suggest that wild arctic foxes exposed to an environmental cocktail of persistent organic pollutants, such as PCBs and OCPs, in their natural diet are at risk for developing chronic kidney and liver damage. Whether such lesions may have an impact on age and health of the animals remains uncertain.

Sexual organs and their development are susceptible to atmospheric transported environmental xenoendocrine pollutants and climate change (food availability). We therefore investigated sexual organs from 55 male and 44 female East Greenland polar bears (Ursus maritimus) to obtain information about growth/size and sexual maturity. Then, the genitalia size was compared with those previously reported from Canadian and Svalbard polar bears. Growth models showed that East Greenland male polar bears reached sexual maturity around 7 years of age and females around 4 years of age. When comparing East Greenland and Svalbard polar bears, the size of baculum and uterus were significantly lower in the East Greenland polar bears (ANOVA: all p < 0.05). Based on previously published baculum mean values from Canadian polar bears, a similar baculum pattern was found for East Greenland vs. Canadian polar bears. It is speculated whether this could be a result of the general high variation in polar bear body size, temporal distribution patterns of anthropogenic long-range transported persistent organic pollutants or climate change (decreasing food availability). The present investigation represents conservation and background data for future spatial and temporal assessments of hunting, pollution and climate change scenarios.

Persistent organic pollutants such as Polychlorinated biphenyls (PCB) and dichloro diphenyl trichloroethane (DDT) are known to exert various adverse health effects in wildlife mammals. The impact from dietary intake of minke whale (Balaenoptera acutorostrata) blubber high in organohalogen and other chemical contaminants on renal morphology and function was investigated via a controlled study on West Greenland sledge dogs (Canis familiaris). Our results showed significantly higher frequencies of glomerular, tubular, and interstitial lesions in the exposed group. Furthermore, higher urine protein : creatinine ratio and plasma urea levels were found in the exposed group, which indicated a negative impact on kidney function via tubular and glomerular dysfunctions. The lesions were similar to those observed in top predator marine species–such as seals and polar bears–and humans exposed via diet to persistent environmental pollutants. The lesions may have impacts on the overall health of these animals. It is re...

Summary The inflammatory response in liver tissue from piglets congenitally infected with Schistosoma japonicum was examined at two different timepoints after infection. The piglets, which were the offspring of three sows infected with 9000 S. japonicum cercariae in the 10th week of gestation, were allocated into two groups ( n = 9 and 17) killed 5 or 11 weeks after birth, respectively. All piglets developed a low level infection,with no significant difference between the groups. Inflammatory lesions in the liver consisted mainly of granulomas in portal areas, often obliterating the portal veins, and frequently with central eggs or egg remnants. The granulomatous reaction consisted of epithelioid cells and occasional giant cells surrounded by layers of lymphocytes, eosinophils, plasma cells, and various amounts of collagen and fibroblasts. Mild to moderate infiltration of portal and septal connective tissue with eosinophils and lymphocytes was common, but the connective tissue was generally not increased. At the two timepoints, slight differences were observed in the numbers of eosinophils and lymphocytes in the granulomas and in the size of the granulomatous reaction. The same pattern of immunohistochemical labelling was seen in both groups. CD79α+ B cells were scarce except in granuloma-associated lymphoid follicles;the majority of lymphocytes in granulomas and at other sites were CD3e+ T cells. The granulomatous reaction in the livers of piglets to schistosoma eggs from prenatal S. japonicum infection was similar to that seen in postnatal infection. Signs of immunomodulation of granulomas between the two timepoints of infection were not demonstrable.

Serotonin (5-hydroxytryptamine, 5-HT) signalling is implicated in the pathogenesis of myxomatous mitral valve disease (MMVD) through 5-HT1B receptor (R), 5-HT2AR and 5-HT2BR-induced myxomatous pathology. Based on increased tryptophan hydroxylase-1 (TPH-1) and decreased serotonin re-uptake transporter (SERT) in MMVD-affected valves, increased valvular 5-HT synthesis and decreased clearance have been suggested. It remains unknown how haemodynamic changes associated with mitral regurgitation (MR) affect 5-HT markers in the mitral valve, myocardium and circulation. Twenty-eight pigs underwent surgically induced MR or sham-operation, resulting in three MR groups: control (CON, n = 12), mild MR (mMR, n = 10) and severe MR (sMR, n = 6). The gene expression levels of 5-HT1BR, 5-HT2AR, 5-HT2BR, SERT and TPH-1 were analysed using quantitative PCR (qPCR) in the mitral valve (MV), anterior papillary muscle (AP) and left ventricle (LV). MV 5-HT2BR was also analysed with immunohistochemistry (IHC) in relation to histological lesions and valvular myofibroblasts. All 5-HTR mRNAs were up-regulated in MV compared to AP and LV (P

Porcine melanomas have proven interesting in a wider biological perspective due to a common phenomenon of spontaneous regression, which is characterized by infiltration of macrophages, among others. Separation of neoplastic melanocytes from pigment-laden macrophages may, however, be challenging as the morphology of melanocytes varies considerably and sometimes resembles macrophages. The aim of this study was correspondingly to characterize and differentiate the cells in 20 porcine melanocytomas and regional lymph nodes by histologic examination and immunohistochemistry for melan A, PNL2, S100, lysozyme, alpha-1-antitrypsin, and ionized calcium binding adaptor molecule 1 (Iba1). Grossly, the melanocytomas were divided into 2 distinct types: pigmented maculae ( n = 7) and raised tumors ( n = 13). In the maculae, the pigmented cells were mainly melanocytes reactive for melan A, PNL2 and S100. In contrast, the majority of the cells in the raised tumors were melanophages, which expressed Iba1, alpha-1-antitrypsin, and lysozyme. Yet, cells histomorphologically indistinguishable from the melanophages expressed melan A and PNL2. These cells were Iba1 and S100 negative, and ultrastructurally, they were devoid of lysosomal bodies and filled with stage III and IV melanosomes. In the regional lymph nodes, melanocytes were present in the trabecular sinuses. In focally or diffusely black lymph nodes, pigmentation was, however, mainly due to aggregates of melanophages, which were confined to the trabeculae, deep cortex, and peripheral lymphoreticular tissue. Normal and neoplastic porcine melanocytes express melan A and PNL2, and immunohistochemical staining for melan A, PNL2, and Iba1 was found useful to identify and distinguish melanocytes and melanophages in porcine melanotic lesions.

A nine-year-old, neutered female beagle was presented with a history of progressive myoclonic jerks. Clinical signs included mental depression and paroxysmal jerks of the head and forelimbs, apparently elicited by changes in light, noise or movements. Electroencephalographic findings were in accordance with myoclonus epilepsy. Postmortem histopathological findings included multiple periodic acid-Schiff-positive inclusion bodies throughout the central nervous system, but especially in the cerebellum, confirming the suspected diagnosis of Lafora's disease.

The former Black Angel lead-zinc mine in Maarmorilik, West Greenland, is a historic example of how mining activity may result in a significant impact on the surrounding fjord system in terms of elevated concentrations of especially lead (Pb) and zinc (Zn) in seawater, sediments and surrounding biota. In order to shed light on the present contamination and possible effects in the fjord we initiated a range of studies including a pilot study on gill and liver morphology of common sculpins (Myoxocephalus scorpius) around Maarmorilik. Sculpins were caught and sampled at five different stations known to represent a gradient of Pb concentrations. Fish livers from all specimens were analyzed for relevant elements in the area: Fe, Zn, As, Cu, Se, Cd, Pb, Ag, Hg, Co and Ni. Lead, As and Hg showed significant differences among the five stations. For 20% of the sculpins, Hg concentrations were in the range of lowest observed effect dose (LOED) of 0.1-0.5μg/gww for toxic threshold on reproduction and subclinical endpoints. Likewise LOEDs for tissue lesions, LOEDs for biochemistry, growth, survival and reproduction were exceeded for Cd (0.42-1.8μg/gww) and for As (11.6μg/gww) in 28% and 85% of the sculpins, respectively. Similar to this, the no observed effect dose (NOED) for biochemistry was exceeded for Pb (0.32μg/gww) and for growth, mortality and reproduction for Zn (60-68μg/gww) in 33% and 24% of the sculpins, respectively. For all sculpins, females were significantly larger than males and for five of the elements (Fe, Co, Ni, Cu, Se) females had higher concentrations. The chronic lesions observed in liver (mononuclear cell infiltrates, necrosis, vacuolar hepatocytes, portal fibrosis, bile duct hyperplasia, active melanomacrophage centers) and gills (fusion and edema of secondary lamellae, laminar telangiectasis, mononuclear cell infiltrates, blebs) were similar to those in the literature studies for both wild and laboratory exposed sculpins and other fish species carrying similar or higher Hg concentrations. Ignoring sex and size, specimens with hepatic cell infiltrates had the highest concentrations of most elements, a relation that was also found for gill telangiectasis and Hg (all p

Strong association between activated valvular interstitial cells and histopathological lesions in porcine model of induced mitral regurgitation☆ S.E. Cremer , N.E. Zois , S.G. Moesgaard , N. Ravn , S. Cirera , J.L. Honge , M.H. Smerup , J.M. Hasenkam , E. Sloth , P.S. Leifsson , T. Falk , M.A. Oyama , C. Orton , T. Martinussen , L.H. Olsen a,⁎,1 a Department of Veterinary Disease Biology, University of Copenhagen, Frederiksberg, Denmark b Department of Clinical Biochemistry, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark c Novo Nordisk A/S, Maaloev, Denmark d Department of Cardiothoracic and Vascular Surgery, Aarhus University Hospital, Aarhus, Denmark e Department of Veterinary Clinical and Animal Sciences, University of Copenhagen, Frederiksberg, Denmark f Department of Anaesthesiology and Intensive Care Medicine, Aarhus University Hospital, Aarhus, Denmark g Department of Clinical Studies, University of Pennsylvania, Philadelphia, PA, USA h Department of Clinical Sciences, Colorado State University, Fort Collins, CO, USA i Department of Biostatistics, University of Copenhagen, Copenhagen, Denmark