An Equine Model for Vaccination against a Hepacivirus: Insights into Host Responses to E2 Recombinant Protein Vaccination and Subsequent Equine Hepacivirus Inoculation

Equine hepacivirus (EqHV) is the closest known genetic homologue of hepatitis C virus. An effective prophylactic vaccine is currently not available for either of these hepaciviruses. The equine as potential surrogate model for hepacivirus vaccine studies was investigated, while equine host responses following vaccination with EqHV E2 recombinant protein and subsequent EqHV inoculation were elucidated. Four ponies received prime and booster vaccinations (recombinant protein, adjuvant) four weeks apart (day −55 and −27). Two control ponies received adjuvant only. Ponies were inoculated with EqHV RNA-positive plasma on day 0. Blood samples and liver biopsies were collected over 26 weeks (day −70 to +112). Serum analyses included detection of EqHV RNA, isotypes of E2-specific immunoglobulin G (IgG), nonstructural protein 3-specific IgG, haematology, serum biochemistry, and metabolomics. Liver tissue analyses included EqHV RNA detection, RNA sequencing, histopathology, immunohistochemistry, and fluorescent in situ hybridization. Al-though vaccination did not result in complete protective immunity against experimental EqHV inoculation, the majority of vaccinated ponies cleared the serum EqHV RNA earlier than the control ponies. The majority of vaccinated ponies appeared to recover from the EqHV-associated liver insult earlier than the control ponies. The equine model shows promise as a surrogate model for future hepacivirus vaccine research

An Equine Model for Vaccination against a Hepacivirus: Insights into Host Responses to E2 Recombinant Protein Vaccination and Subsequent Equine Hepacivirus Inoculation

Equine hepacivirus (EqHV) is the closest known genetic homologue of hepatitis C virus. An effective prophylactic vaccine is currently not available for either of these hepaciviruses. The equine as potential surrogate model for hepacivirus vaccine studies was investigated, while equine host responses following vaccination with EqHV E2 recombinant protein and subsequent EqHV inoculation were elucidated. Four ponies received prime and booster vaccinations (recombinant protein, adjuvant) four weeks apart (day −55 and −27). Two control ponies received adjuvant only. Ponies were inoculated with EqHV RNA-positive plasma on day 0. Blood samples and liver biopsies were collected over 26 weeks (day −70 to +112). Serum analyses included detection of EqHV RNA, isotypes of E2-specific immunoglobulin G (IgG), nonstructural protein 3-specific IgG, haematology, serum biochemistry, and metabolomics. Liver tissue analyses included EqHV RNA detection, RNA sequencing, histopathology, immunohistochemistry, and fluorescent in situ hybridization. Al-though vaccination did not result in complete protective immunity against experimental EqHV inoculation, the majority of vaccinated ponies cleared the serum EqHV RNA earlier than the control ponies. The majority of vaccinated ponies appeared to recover from the EqHV-associated liver insult earlier than the control ponies. The equine model shows promise as a surrogate model for future hepacivirus vaccine research

In vivo Evaluierung eines Nanocomposites auf seine osteoinduktiven Eigenschaften im heterotopen Implantationsmodell

In der vorliegenden Studie sollte die osteoinduktive Eigenschaft eines synthetischen Nanocomposites evaluiert und mit einer Positiv- sowie Negativkontrolle verglichen werden. Hierzu wurden Ratten Implantate in Subkutan- und Muskeltaschen eingesetzt. 3 Ratten erhielten das Composite NanoBone®, das Allograft Nexus IC® oder den Knochenwerkstoff betaGran®. 3 Ratten bekamen 2 Mal jedes Produkt implantiert. Es wurde Calcein grün appliziert. Die Ratten wurden euthanasiert und die Proben makroskopisch sowie histologisch ausgewertet. Die Operationen und die postoperative Phase verliefen komplikationslos. Das NanoBone® zeigte eine bindegewebig-zelluläre Kolonisation und die Ablagerung einer matrixartigen Schicht, die kalzifizierte. In allen Fällen war eine Bindegewebskapsel um das Material darstellbar. Zellulär dominierten Makrophagen und Fremdkörperriesenzellen, gefolgt von Lymphozyten und Plasmazellen. Im Vergleich zur demineralisierten Knochenmatrix lagen die Apposition und Kalzifikation signifikant niedriger. Gegenüber dem β-Trikalziumphosphat waren Materialbesiedlung, Infiltration, Apposition und Kalzifikation nicht vergleichbar, da dies bei der Schnittherstellung herausbröckelte. Osteoid und enchondrale Ossifikation konnten nur bei der DBM angesprochen werden. Zusammenfassend kann gesagt werden, dass nicht von Osteoinduktion im klassischen Sinn gesprochen werden kann aber die Matrixapposition und deren Kalzifikation lassen einen die Induktion positiv beeinflussenden Prozess vermuten. In vivo evaluation of a nanocomposite due to its osteoinductive properties in a heterotopic implantation model ABSTRACT In the present study the osteoinductive properties of a synthetic bone graft material was evaluated and compared to positive and negative controls. For this purpose rats received implants inserted in muscle or subcutaneous pouches. 3 of them obtained the nanocomposite NanoBone®, the allograft Nexus IC® or the bone substitute betaGran® and the other 3 animals received two implants of each material respectively. Calcein green was applied. The rats were euthanasized and the specimens were evaluated macroscopically and histologically. There were no complications in surgery and in the postoperative phase. The nanocomposite showed a material colonisation characterized by a fibro- cellular infiltration and an apposition of a matrix-like layer could be visualized, which started to calcify. In all cases a capsule of connective tissue surrounding the material could be demonstrated. The dominating cells were macrophages and foreign body cells, followed by lymphocytes and plasma cells. Compared to the demineralised bone matrix the apposition and calcification was significantly lower. In terms of material colonisation, infiltration, apposition and calcification a comparison to β-tricalciumphosphate was not possible because of its disintegration during the slicing procedure. Osteoid and enchondrale ossification could be seen in DBM. In conclusion the bone substitute showed no osteoinduction in a classical meaning but there is an evidence for a positive influence for the induction process

Vergleich des Effektes von zwei Ringer-Laktat-Infusionslösungen auf den Elektrolyt-, Laktat- und Säure-Basen-Status bei Pferden während einer balancierten Langzeitanästhesie mit Isofluran und Medetomidin

Ziel der Studie war es, den Effekt von zwei Ringer-Laktat-Lösungen (Fresenius®=RLF, Bichsel®=RLB) auf Elektrolytund Laktatkonzentration sowie Säure-Basen-Status beim Pferd während einer 6-stündigen Allgemeinanästhesie zu untersuchen. Zehn Pferde wurden mit 10ml/kg/h RLF oder RLB während der Allgemeinanästhesie infundiert. Natrium (Na), Kalium (K), Chlorid (Cl), ionisiertes Kalzium (iCa), Laktat, pH, pCO2 und Basenüberschuss (BE) wurden vor und alle 30 Minuten nach Einleitung bestimmt (M30–M360). Unterschiede zwischen den Gruppen wurden mittels Mann-Whitney-U-Tests analysiert. Statistische Signifikanz wurde bei p<0,05 festgelegt. Es gab keine signifikanten Unterschiede für Na, K, Cl, pH und BE. Das iCa war bei M150 signifikant höher mit RLF (p=0,025), war jedoch in beiden Gruppen bereits bei M30 tief und fiel bis M360 weiter ab. Die Laktatkonzentration stieg über die Zeit an und war bei M120 (p=0,016) und M360 (p=0,036) signifikant höher mit RLB. Es konnten keine klinisch relevanten Unterschiede nach Verabreichung von RLF oder RLB bei den Elektrolyt- und Laktatkonzentrationen sowie beim Säure-Basen-Status über eine Allgemeinanästhesiezeit von 6h gezeigt werden

Diagnosis of severe traumatic brain injury using multimodal imaging in a donkey

A 6-month-old donkey presented with recumbency after rearing and falling over. A presumptive diagnosis of traumatic brain injury secondary to a skull fracture was made following the clinical examination, although a fracture could not be identified on radiography. To provide a definitive diagnosis, for planning any surgical intervention and to obtain prognostic information, computed tomography and magnetic resonance imaging were performed. An occipital depression skull fracture with secondary haemorrhage and oedema of the cerebellum and brainstem were identified. The imaging findings were confirmed at pathological examination. This report describes the imaging features of a traumatic brain injury in a donkey

Management of acute bleeding in a shetland pony during surgery for foreign body removal

A 180-kg, male neutered 15-year-old shetland pony was referred to the authors’ clinic with a chronic purulent wound on the left flank and mild weight loss. Surgical treatment under sedation with local anaesthesia was already attempted twice, but each time within two months a new fistula was evident. Abdominal ultrasound exam revealed a possible abscess in the abdomen with no clear margins, indicative of extension of infected tissue or the presence of a foreign body. General anaesthesia for wound curettage surgery was scheduled. Complication during anaesthesia was a massive unexpected acute bleeding from adhesions of the abscess to the spleen, caused by a foreign body which had probably perforated the stomach

Validation of the Accutrend Plus point-of-care triglyceride analyzer in horses, ponies, and donkeys

OBJECTIVE: To assess the accuracy and reliability of a point-of-care (POC) triglyceride analyzer and to establish reference intervals for blood ([TRIG]POC/WB ) and plasma triglyceride concentrations ([TRIG]POC/PL ) in horses, ponies, and donkeys. DESIGN: Prospective study. SETTING: University teaching hospital. ANIMALS: 120 adult healthy equids (78 horses and ponies, 42 donkeys) and 79 equids suffering from hypertriglyceridemia (73 horses and ponies, 6 donkeys). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: [TRIG]POC/WB and [TRIG]POC/PL were measured using a POC analyzer and plasma triglyceride concentrations were measured using a standard laboratory assay ([TRIG]LAB/PL ). Reference intervals were determined. Test accuracy was assessed by Bland-Altman comparison of POC measurements with standard laboratory measurements and by evaluating linearity of dilutional series. Test reliability was assessed by repeated serial measurements. [TRIG]POC/WB and [TRIG]POC/PL were below the analytic range of the POC assay (<0.8 mmol/L [<70 mg/dL]) in healthy horses and ponies, whereas the reference intervals were 0.82-3.14 mmol/L (73-278 mg/dL) and 0.87-3.02 mmol/L (77-267 mg/dL), respectively, in donkeys. The POC analyzer systematically overestimated triglyceride concentrations when compared to a standard laboratory assay. The difference between [TRIG]POC/WB and [TRIG]POC/PL was small and clinically negligible. The coefficient of variation of repeated measures performed on the POC analyzer was below 10% for [TRIG]POC/WB and [TRIG]POC/PL , both in horses and donkeys and at all concentration ranges. CONCLUSIONS: The POC analyzer allows accurate and reliable measurement of [TRIG]POC/WB and [TRIG]POC/PL in horses, ponies, and donkeys in clinical settings. Assay-specific reference intervals should be determined for diagnosis and clinical monitoring of hypertriglyceridemia in equids

Comparison of non-assisted versus head and tail rope-assisted recovery after emergency abdominal surgery in horses

The objective of this study was to compare anaesthetic recoveries without assistance (group NA) to a head and tail rope-assisted technique (group A) after emergency abdominal surgery in horses. Additionally, possible risk factors for the quality of recovery (S: safe, NS: non-safe) were investigated and possible complications associated to the head and tail rope technique recorded. For that purpose 200 anaesthetic protocols (100NA, 100A) from horses that all received a standardised medetomidine-isoflurane balanced anaesthesia regime and medetomidine in combination with morphine for recovery were analysed retrospectively. No significant difference regarding recovery score was detected between NA and A horses. Fatalitalities (3/100 in each group) were similarly distributed between groups. However, in group NA only one horse died because of trauma during recovery. The other two horses died before attempting to stand up. All 3 horses that died in group A were euthanized because of trauma. Hypoxemia (defined as arterial oxygen partial pressure <60mmHg) during anaesthesia was a risk factor for non-safe recoveries. No influence was detected for age, weight, duration of general anaesthesia, reason of colic surgery, recovery technique (A, NA), hypotension during anaesthesia, time in lateral recumbency, time in sternal recumbency and time until standing. Several technical complications (material fail, twisting of ropes, halters slipping off and loss of ropes) were observed using the head and tail ropes, probably being partially responsible for the unexpectedly high number of dangerous and fatal recoveries observed in group A. The present study could not demonstrate that the head and tail rope technique can reduce fatalities or improve anaesthetic recovery scores after emergency abdominal surgery in horses. Hypoxemia during general anaesthesia increases the risk of non-safe recovery

Balloon valvuloplasty of valvular pulmonary stenosis in a neonatal foal

In a 1-day old filly with a loud heart murmur, transthoracic echocardiography revealed right ventricular hypertrophy associated with severe pulmonary valvular stenosis and a transvalvular pressure gradient (between right ventricle and pulmonary artery) of 125 mmHg. Computed tomographic angiography confirmed the finding, with no evidence of other relevant concurrent abnormalities. Balloon valvuloplasty was performed using a single balloon technique. The foal recovered well from anaesthesia. Following the procedure, the right ventricle-pulmonary artery transvalvular gradient decreased to 38 mmHg. At follow up examinations after 1 month, 1 year and 2 years, the filly showed normal exercise capacity and echocardiography confirmed the persistent substantial improvement in the transvalvular outflow gradient