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The aim of this study was to summarize and evaluate clinical appearance, laboratory parameters, special ancillary diagnostic tests, treatments and post-mortem pathological findings of chronic gastric impaction and dilatation in horses. Chronic gastric impaction and dilatation is a rare, progressive disease, which is usually detected in its advanced stage. Its aetiology has not yet been fully clarified. Acute primary gastric impaction (from excess volume intake) and secondary gastric impaction (from reflux from the small intestine) must be differentiated from chronic gastric impaction and dilatation. Suspected causes of chronic gastric impaction and dilatation include pyloric stenosis, gastric ulcers, gastric tumours, indigestible feed, feed with high fibre content and dental problems. Motility disorders with resulting gastric impaction and dilatation have also been described in the context of liver diseases. Additional theories suggest damage to the vagus nerve or the intramural nervous system of the stomach and aplasia of the autonomous ganglia of the myenteric and submucosal plexus. It is a retrospective case study of four cases of chronic gastric impaction and dilatation between 2010 and 2013 concerning clinical appearance, laboratory parameters, ancillary diagnostic tests, treatment options and post-mortem pathological findings. For comparison, an additional case of delayed gastric emptying with successful conservative treatment is presented. In one case, nerve degeneration was confirmed and could possibly explain the chronic gastric impaction. A recurrent finding was the adaptive enlargement of the stomach with significant thinning of the muscularis, which was evident in all cases. This is likely to be the result of chronic dilation with a gradually prolonged filling of the stomach leading to ‘stretching' of the stomach wall and therefore also a loss of motility, which could be equated to dilated cardiomyopathy, where cardiac output volume decreases with dilation. Gross pathology revealed greatly enlarged stomachs with dry impacted feed material of 43kg, 46kg and 108kg. The treatment options for the disease, whether conservative or surgical depend on the severity and cause of the gastric impaction, and are said to have a very poor or unfavourable prognosis. Chronic gastric impaction can lead to a rupture of the stomach and therefore the prognosis is generally suspected to be grave. Perhaps early identification of delayed gastric emptying and chronic gastric impaction via repetitive gastroscopy could allow for a more successful treatment. [ABSTRACT FROM AUTHOR]

The safety of veterinary vaccines is assessed in clinical trials in Europe. The assessment of the local tissue reaction to vaccination by magnetic resonance imaging (MRI) could reduce the number of animals needed because repeated examinations can be performed in the same animal over time. The present study compared the evaluation of local tissue reactions to vaccination using MRI in live pigs with histopathology of porcine tissue, the current gold standard in regulatory safety testing. Eight piglets each were administered one of two commercial vaccines into marked injection sites. All animals were sedated and scanned repeatedly by MRI using a contrast agent up to day 29 after vaccination. On day 29, the animals were euthanized and underwent a pathological examination. The MRI results were compared with the pathomorphological findings at the injection site by regression analysis. The MR images and the pathological examinations yielded matching results concerning the sizes of the affected tissue volumes or areas. The use of MRI for regulatory safety testing can reduce the number of animals needed to 8 per examination group. The volume of a local reaction and its progression over time can be evaluated and documented. If persistent lesions develop a final pathomorphological examination is needed to identify the kind and local distribution of the reaction. [ABSTRACT FROM AUTHOR]

Mutations in the insulin (INS) gene may cause permanent neonatal diabetes mellitus (PNDM). Ins2 mutant mouse models provided important insights into the disease mechanisms of PNDM but have limitations for translational research. To establish a large animal model of PNDM, we generated INSC94Y transgenic pigs. A line expressing high levels of INSC94Y mRNA (70-86% of wild-type INS transcripts) exhibited elevated blood glucose soon after birth but unaltered β-cell mass at the age of 8 days. At 4.5 months, INSC94Y transgenic pigs exhibited 41% reduced body weight, 72% decreased β-cell mass (253% relative to body weight), and 60% lower fasting insulin levels compared with littermate controls. β-cells of INSC94Y transgenic pigs showed a marked reduction of insulin secretory granules and severe dilation of the endoplasmic reticulum. Cataract development was already visible in 8-day-old INSC94Y transgenic pigs and became more severe with increasing age. Diabetes-associated pathological alterations of kidney and nervous tissue were not detected during the observation period of 1 year. The stable diabetic phenotype and its rescue by insulin treatment make the INSC94Y transgenic pig an attractive model for insulin supplementation and islet transplantation trials, and for studying developmental consequences of maternal diabetes mellitus. [ABSTRACT FROM AUTHOR]

Morphological lesions in kidneys and brain are all too often considered diagnostic for confirmation of encephalitozoonosis in rabbits. The current study evaluated the diagnostic value of histology versus other etiological tests, including immunohistochemistry and real-time polymerase chain reaction (PCR) for Encephalitozoon cuniculi infection diagnosis. Samples of brain, heart, lungs, intestine, liver, and kidneys from 81 rabbits were examined for morphological lesions attributed to E. cuniculi infection as well as for the presence of spores and E. cuniculi antigen. Of these, 55 rabbits were tested for E. cuniculi DNA. Histological changes consistent with E. cuniculi infection were seen in 33 rabbits (41%, 33/81) representing 87% (33/38) of all rabbits with confirmed E. cuniculi infection. Brains of these rabbits displayed 6 different types of focal lesions corresponding to the stage of infection and specific tissue response. In 5 rabbits that were tested positive, histology was either inconclusive or inconspicuous. Etiological diagnosis was based on histological spore detection in 16% (6/38) of infected rabbits. Immunohistochemistry was more sensitive (42%, 16/38) than histological spore detection, and real-time PCR proved to be the most sensitive of all investigated methods (30/35, 86% of the examined rabbits with E. cuniculi infection). Encephalitozoon cuniculi infection rarely occurs without characteristic kidney and brain lesions. However, the spectrum of brain changes is wider than previously reported. Based on these findings, confirmation of pathogenic E. cuniculi infection should include standard histology of the predilection sites and a specific etiological assay, preferably real-time PCR. [ABSTRACT FROM PUBLISHER]

Changes in lifestyle and environmental conditions give rise to an increasing prevalence of liver and lung fibrosis, and both have a poor prognosis. Promising results have been reported for recombinant angiotensin-converting enzyme 2 (ACE2) protein administration in experimental liver and lung fibrosis. However, the full potential of ACE2 may be achieved by localized translation of a membrane-anchored form. For this purpose, we advanced the latest RNA technology for liver- and lung-targeted ACE2 translation. We demonstrated in vitro that transfection with ACE2 chemically modified messenger RNA (cmRNA) leads to robust translation of fully matured, membrane-anchored ACE2 protein. In a second step, we designed eight modified ACE2 cmRNA sequences and identified a lead sequence for in vivo application. Finally, formulation of this ACE2 cmRNA in tailor-made lipidoid nanoparticles and in lipid nanoparticles led to liver- and lung-targeted translation of significant amounts of ACE2 protein, respectively. In summary, we provide evidence that RNA transcript therapy (RTT) is a promising approach for ACE2-based treatment of liver and lung fibrosis to be tested in fibrotic disease models., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)