Immunocompatibility and non-thrombogenicity of gelatin-based hydrogels.

Immunocompatibility and non-thrombogenicity are important requirements for biomedical applications such as vascular grafts. Here, gelatin-based hydrogels formed by reaction of porcine gelatin with increasing amounts of lysine diisocyanate ethyl ester were investigated in vitro in this regard. In addition, potential adverse effects of the hydrogels were determined using the "Hen's egg test on chorioallantoic membrane" (HET-CAM) test and a mouse model.The study revealed that the hydrogels were immunocompatible, since complement activation was absent and a substantial induction of reactive oxygen species generating monocytes and neutrophils could not be observed in whole human blood. The density as well as the activation state of adherent thrombocytes was comparable to medical grade polydimethylsiloxane, which was used as reference material. The HET-CAM test confirmed the compatibility of the hydrogels with vessel functionality since no bleedings, thrombotic events, or vessel destructions were observed. Only for the samples synthesized with the highest LDI amount the number of growing blood vessels in the CAM was comparable to controls and significantly higher than for the softer materials. Implantation into mice showed the absence of adverse or toxic effects in spleen, liver, or kidney, and only a mild lymphocytic activation in the form of a follicular hyperplasia in draining lymph nodes (slightly increased after the implantation of the material prepared with the lowest LDI content). These results imply that candidate materials prepared with mid to high amounts of LDI are suitable for the coating of the blood contacting surface of cardiovascular implants.

Estimation of total collagen volume: a T1 mapping versus histological comparison study in healthy Landrace pigs.

Right ventricular biopsy represents the gold standard for the assessment of myocardial fibrosis and collagen content. This invasive technique, however, is accompanied by perioperative complications and poor reproducibility. Extracellular volume (ECV) measured through cardiovascular magnetic resonance (CMR) has emerged as a valid surrogate method to assess fibrosis non-invasively. Nonetheless, ECV provides an overestimation of collagen concentration since it also considers interstitial space. Our study aims to investigate the feasibility of estimating total collagen volume (TCV) through CMR by comparing it with the TCV measured at histology. Seven healthy Landrace pigs were acutely instrumented closed-chest and transported to the MRI facility for measurements. For each protocol, CMR imaging at 3T was acquired. MEDIS software was used to analyze T1 mapping and ECV for both the left ventricular myocardium (LVmyo) and left ventricular septum (LVseptum). ECV was then used to estimate TCVCMR at LVmyo and LVseptum following previously published formulas. Tissues were prepared following an established protocol and stained with picrosirius red to analyze the TCVhisto in LVmyo and LVseptum. TCV measured at LVmyo and LVseptum with both histology (8 ± 5 ml and 7 ± 3 ml, respectively) and T1-Mapping (9 ± 5 ml and 8 ± 6 ml, respectively) did not show any regional differences. TCVhisto and TCVCMR showed a good level of data agreement by Bland-Altman analysis. Estimation of TCV through CMR may be a promising way to non-invasively assess myocardial collagen content and may be useful to track disease progression or treatment response.

Tumour, but not Age-associated, Increase of Senescence Markers γH2AX and p21 in the Canine Eye.

Senescent cells display an irreversible cell cycle arrest with resistance to apoptosis. They are known to accumulate with age in mice, monkeys and man, and are suspected to drive the development and progression of neoplasia. Eyes develop age-associated changes, most commonly in the retina, cornea and lens. The aim of this study was to test whether senescent cells increase with age in the canine eye in general and in the microenvironment of ocular tumours in particular. The senescence markers γH2AX and p21 were tested in young (n = 10, age ≤2 years) versus old (n = 9, age range 9.5-12.4 years) canine eyes, as well as in the microenvironment of intraocular tumours, namely uveal melanocytomas (n = 13) and ciliary body adenomas (n = 9). To consider a potential association of senescence with biological behaviour, we compared the expression of both markers in tumour cells of benign uveal melanocytomas (n = 13) versus malignant conjunctival melanomas (n = 7). Canine eyes showed no age-dependent changes in senescent cells. However, a significant increase of the percentage of γH2AX- or p21-labelled cells was found in the retina, uvea and lens of tumour-bearing eyes. Tumour cells in conjunctival melanomas had a significantly increased percentage of p21-expressing cells compared with uveal melanocytomas. We conclude, that senescent cells do not accumulate with age in otherwise normal canine eyes and that a senescent microenvironment of intraocular tumours is unlikely to be age driven. In addition, as in man, the percentage of p21-positive cells was increased in melanomas, supporting the theory that malignant tumours may override the senescence-associated cell cycle arrest.

Characterization of 22 Canine Pancreatic Carcinomas and Review of Literature.

Pancreatic carcinomas are rare in dogs and clinical signs are mostly non-specific. The literature on clinically and pathologically characterized canine exocrine pancreatic tumours is limited to 76 cases reported since 1963. This retrospective study analysed formalin-fixed samples of pancreatic carcinomas from 22 dogs, obtained during elective exploratory surgery (n = 16) or if the dog was humanely destroyed (n = 6). Tumours were diagnosed according to the World Health Organization classification of tumours of the pancreas of domestic animals. In seven cases, blood samples taken during or shortly before surgery were analysed for concentrations of alpha-amylase, 1,2-o-dilauryl-rac-glycero-3-glutaric acid-(6'-methylresorufin) ester lipase (DGGR lipase), C-reactive protein (CRP), alanine aminotransferase, glutamate dehydrogenase, alkaline phosphatase (ALP), canine trypsin-like immunoreactivity (cTLI) and canine pancreatic lipase immunoreactivity (cPLI). Neutrophil and lymphocyte numbers were determined as part of a complete blood count. Clinical signs were non-specific and included vomiting, inappetence and diarrhoea. Acinar carcinomas were most common (19/22) and observed growth patterns included: solid (n = 14), acinar (n = 5), clear cell (n = 3), mucinous (n = 2), trabecular (n = 1) or rosette-like (n = 1), occurring as a single pattern or in combination. Ductal carcinomas were identified in three cases. Pancreatitis was a common additional histological finding; five dogs had mild and nine dogs had severe pancreatitis. cPLI, DGGR lipase, cTLI and CRP were elevated in 5/5 acinar carcinomas. All liver enzymes were elevated in three of these five animals and ALP was increased in 4/5 dogs. Two dogs with ductal pancreatic carcinomas showed normal cPLI concentrations. One had increased CRP, liver enzymes and leucocytosis with neutrophilia, the other had elevated DGGR lipase and cTLI concentrations. Clinical findings in canine pancreatic carcinomas were non-specific and simultaneous inflammation can mask the detection of the underlying neoplasm in clinical examination and laboratory testing.

Genital Tract Pathology in Female Pet Guinea Pigs (Cavia porcellus): a Retrospective Study of 655 Post-mortem and 64 Biopsy Cases.

Disorders of the female genital tract are among the most common disorders in pet guinea pigs (Cavia porcellus); however, knowledge of many aspects of these disorders is sparse, especially regarding their incidence and age distribution. Ovarian cysts, as the most common genital tract disorder in guinea pigs, have been investigated in detail; however, information on the nature of these cysts is inconsistent. The present study reviewed genital tract disorders occurring within 655 full post-mortem examinations of intact female pet guinea pigs and 64 female genital tract biopsies examined over a 22.5 year period. Age distribution was determined from 550 post-mortem examinations of animals of known age. Genital tract disorders were found in 295 post-mortem examinations (45.0%) in animals with a median age of 52 months. Additionally, disorders were found in all genital tract biopsy samples from guinea pigs with a median age of 48 months. The incidence of genital tract diseases increased from 1.5% in guinea pigs ≤6 months of age to up to 77.8% in animals >6 years of age. Ovarian cysts were the most common genital tract disorder, found in 245 of the 655 post-mortem cases (37.4%) and 38 of 43 ovarian biopsy samples (88.4%). The incidence of ovarian cysts increased with advancing age, reaching 75.6% in animals >6 years. In 119 cases, histopathology and immunohistochemistry confirmed cystic rete ovarii as the only cyst type. A Fallopian tube adenoma was found in a single case, so disorders of the Fallopian tube should be considered rare. Uterine disorders were diagnosed in 17.4% of the post-mortem examinations and 98.1% of uterine biopsy samples. Uterine neoplasia, hyperplasia and inflammation were common, but occurred at different ages. The incidence of uterine neoplasia and hyperplasia was higher in older animals (>15% in guinea pigs >6 years), while the incidence of uterine inflammation was the highest (17.9%) in animals aged 7-12 months. An association between ovarian cysts and uterine neoplasia or hyperplasia was not evident. Vaginal disorders were rare and included leiomyoma, polyps and vaginitis.

Genital Tract Pathology in Female Pet Rabbits (Oryctolagus cuniculus): a Retrospective Study of 854 Necropsy Examinations and 152 Biopsy Samples.

Genital tract disorders, especially uterine disorders, are the most common conditions of the female pet rabbit (Oryctolagus cuniculus); however, there have been few large studies of diseases of the female genital tract of this species. The present study examined diseases of the ovaries, Fallopian tubes, uterus and vagina, retrospectively over a period of 22 years, and included 854 full post-mortem examinations of female pet rabbits and 152 female genital tract biopsy samples. The age distribution of uterine neoplasia, endometrial hyperplasia and uterine inflammation was determined in the post-mortem cases. Uterine disorders were a common finding, occurring in 26.8% of all full necropsy examinations and in almost all genital tract biopsy samples. Uterine tumours (n = 205) were the most common uterine pathology, with adenocarcinoma being the most frequent tumour type. Metastasis was found in 46.2% of rabbits with uterine adenocarcinomas diagnosed at post-mortem examination, with metastatic spread to the lung occurring in 79.1% of these animals. The second most common uterine pathology was endometrial hyperplasia, which was glandular-cystic in most cases. The incidence of uterine tumours and endometrial hyperplasia increased with age, while endometrial hyperplasia was found more commonly in slightly younger animals. In contrast, uterine inflammation, the third most common finding, was found predominately in young to middle-aged rabbits. Ovarian disorders were found rarely at post-mortem examinations (3.3% of all animals), but comprised 16.9% of biopsy samples. Of these, ovarian cysts, especially follicular cysts, and secondary tumours were found most frequently. Disorders of the Fallopian tube and the vagina were found in <1% of cases and should be considered rare.

Influence of intrauterine administration of Lactobacillus buchneri on reproductive performance and pro-inflammatory endometrial mRNA expression of cows with subclinical endometritis.

Potential beneficial effects of lactic acid bacteria on the genital health of cows become of particular interest when considering the importance of an optimal uterine health status for the success of breeding in dairy farming. Therefore, the aim of the present study was to analyse the influence of an intrauterine administration of the Lactobacillus buchneri DSM 32407 on reproductive performance, uterine health status, endometrial mRNA expression of pro-inflammatory factors of cows with signs of subclinical endometritis (SCE). L. buchneri DSM 32407 (n = 56; [LAC]) or a placebo (n = 60; [PLA]) was administered on day 24-30 postpartum. Endometrial cytobrush samples of cows with SCE were taken before the administration and at three following weeks (n = 16 cows each for LAC/SCE and PLA/SCE). A higher proportion of cows of the LAC and LAC/SCE group was pregnant after the first service and median days to conception for cows pregnant on day 200 pp were shorter. Three weeks after the administration, the endometrial mRNA expression of CXCL1/2, CXCL3, CXCR2, IL1B, IL8 and PTPRC was lower in the LAC/SCE group compared with the PLA/SCE group. These findings suggest that the presence of L. buchneri DSM 32407 contributes to a uterine environment that results in a better reproductive performance.

Evaluation of clinical, laboratory, imaging findings and outcome in 99 dogs with leptospirosis.

OBJECTIVE: To report clinical, laboratory and diagnostic imaging features and prognostic factors in dogs with leptospirosis from North-East Germany. MATERIALS AND METHODS: Medical records of dogs diagnosed with leptospirosis from 2006 to 2013 were evaluated retrospectively. RESULTS: The study included 99 dogs. At initial presentation, the most common clinical signs were lethargy (96%), anorexia (88%), vomiting (85%), painful abdomen (39%), diarrhoea (38%), oliguria (27%) and tachypnoea (26%). Abnormal laboratory findings included anaemia (63%), thrombocytopenia (63%), leucocytosis (57%), increase of plasma urea (84%) and creatinine concentrations (81%), increased liver enzyme activities (80%), hyperbilirubinaemia (69%), hyperphosphataemia (67%), hyponatraemia (64%), hypoalbuminaemia (55%) and hypokalaemia (29%). Radiological pulmonary changes were detected in 57% of the dogs initially or during the course of disease. Severe dyspnoea, oliguria, azotaemia, hyperbilirubinaemia and severe radiological pulmonary changes were more often found in dogs that did not survive. There was renal, hepatic and pulmonary involvement in 95, 92 and 58% of the dogs, respectively, and multi-organ lesions in 98 dogs (98%); 32 dogs died or were euthanased. CONCLUSION: Several clinical and laboratory abnormalities were associated with a negative outcome; severe lung involvement was specifically associated with high mortality.

Spontaneously Arising Tumours and Tumour-like Lesions of the Cervix and Uterus in 83 Pet Guinea Pigs (Cavia porcellus).

Tumours and tumour-like lesions are rare findings in the genital system of guinea pigs. The aim of the present study was to characterize nodular lesions in the cervix and uterus of guinea pigs submitted for histopathological diagnosis. Samples from 83 pet animals were investigated. Cases included 64 surgically excised masses including complete uteri (n = 37), parts from uteri containing masses (n = 8), complete masses (n = 12) or samples from masses (n = 7) and 19 complete necropsy examinations. In 55 of the cases, only solitary changes were observed; in 28 cases two or more lesions were diagnosed. Histopathological diagnoses included polyps in the vagina, cervix or uterus (n = 8), hyperplastic lesions of the endocervix (n = 10) and seven adenomas and two adenocarcinomas of the endocervix. Endometrial alterations included single small glandular cysts (n = 3), nodular glandular-cystic hyperplasia (n = 8), adenoma (n = 20) and adenocarcinoma (n = 3). Four placentas, 10 focal decidualizations and six deciduomas were found. Furthermore, 18 leiomyomas and nine leiomyosarcomas were diagnosed. Uterine malignant mixed Müllerian tumours were observed in seven cases. Overall, benign lesions outnumbered malignant tumours in the female genital tract of pet guinea pigs. Therefore, surgical excision or ovariohysterectomy should be recommended as therapy.

The pathology of the foreign body reaction against biomaterials.

The healing process after implantation of biomaterials involves the interaction of many contributing factors. Besides their in vivo functionality, biomaterials also require characteristics that allow their integration into the designated tissue without eliciting an overshooting foreign body reaction (FBR). The targeted design of biomaterials with these features, thus, needs understanding of the molecular mechanisms of the FBR. Much effort has been put into research on the interaction of engineered materials and the host tissue. This elucidated many aspects of the five FBR phases, that is protein adsorption, acute inflammation, chronic inflammation, foreign body giant cell formation, and fibrous capsule formation. However, in practice, it is still difficult to predict the response against a newly designed biomaterial purely based on the knowledge of its physical-chemical surface features. This insufficient knowledge leads to a high number of factors potentially influencing the FBR, which have to be analyzed in complex animal experiments including appropriate data-based sample sizes. This review is focused on the current knowledge on the general mechanisms of the FBR against biomaterials and the influence of biomaterial surface topography and chemical and physical features on the quality and quantity of the reaction. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 927-940, 2017.

Macrophage reaction against biomaterials in the mouse model - Phenotypes, functions and markers.

UNLABELLED: The foreign body reaction (FBR) is a response of the host tissue against more or less degradation-resistant foreign macromolecular material. The reaction is divided into five different phases which involve most aspects of the innate and the adaptive immune system: protein adsorption, acute and chronic inflammation, foreign body giant cell formation and fibrosis. It is long known, that macrophages play a central role in all of these phases except for protein adsorption. Initially it was believed that the macrophage driven FBR has a complete negative effect on biocompatibility. Recent progress in biomaterial and macrophage research however describe macrophages as more than pure antigen phagocytosing and presenting cells and thus pro-inflammatory cells involved in biomaterial encapsulation and failure. Quite contrary, both, pro-inflammatory M1 macrophages, the diverse regulatory M2 macrophage subtypes and even foreign body giant cells (FBGC) are after necessary for integration of non-degradable biomaterials and degradation and replacement of degradable biomaterials. This review gives a comprehensive overview on the taxonomy of the currently known macrophage subtypes. Their diverging functions, metabolism and markers are summarized and the relevance of this more diverse macrophage picture for the design of biomaterials is shortly discussed. STATEMENT OF SIGNIFICANCE: The view on role of macrophages in the foreign body reaction against biomaterials is rapidly changing. Despite the initial idea that macrophage are mainly involved in undesired degradation and biomaterial rejection it becomes now clear that they are nevertheless necessary for proper integration of non-degradable biomaterials and degradation of placeholder, degradable biomaterials. As a pathologist I experienced a lack on a good summary on the current taxonomy, functions and phenotypes of macrophages in my recent projects on the biocompatibility of biomaterials in the mouse model. The submitted review therefore intends to gives a comprehensive overview on the taxonomy of the currently known macrophage subtypes. Their diverging functions, metabolism and markers are summarized and the relevance of this more diverse macrophage picture for the design of biomaterials is shortly discussed.

Histopathological and Immunohistochemical Studies of Cowpox Virus Replication in a Three-Dimensional Skin Model.

Human cowpox virus (CPXV) infections are rare, but can result in severe and sometimes fatal outcomes. The majority of recent cases were traced back to contacts with infected domestic cats or pet rats. The aim of the present study was to evaluate a three-dimensional (3D) skin model as a possible replacement for animal experiments. We monitored CPXV lesion formation, viral gene expression and cell cycle patterns after infection of 3D skin cultures with two CPXV strains of different pathogenic potential: a recent pet rat isolate (RatPox09) and the reference Brighton red strain. Infected 3D skin cultures exhibited histological alterations that were similar to those of mammal skin infections, but there were no differences in gene expression patterns and tissue damage between the two CPXV strains in the model system. In conclusion, 3D skin cultures reflect the development of pox lesions in the skin very well, but seem not to allow differentiation between more or less virulent virus strains, a distinction that is made possible by experimental infection in suitable animal models.

IL-10 downregulates CXCR3 expression on Th1 cells and interferes with their migration to intestinal inflammatory sites.

Inflammatory bowel disease (IBD) is characterized by chronic, uncontrolled inflammation in the intestinal mucosa. Although the etiology is poorly understood, it is widely accepted that loss of tolerance is involved in the development of IBD. Therefore, re-establishing tolerance or gut homeostasis is one of the key features in the development of new therapeutic strategies. Here we show that antigen targeting to DEC-205 on dendritic cells leads to an interleukin (IL)-10-dependent downregulation of C-X-C chemokine receptor 3 (CXCR3) expression on differentiated antigen-specific T helper type 1 (Th1) cells in vivo. This downregulation interferes with the migration of Th1 cells into the gut and protects mice against severe acute and relapsing intestinal inflammation. Moreover, CD4(+)CXCR3(+) T cells are highly enriched in the inflamed mucosa of IBD patients. Interference with this pathway may therefore be a promising approach for the treatment of IBD. In conclusion, we propose a hitherto undescribed mechanism by which IL-10 can act on effector T cells and orchestrate intestinal immune responses.

Mechanisms of tumour resistance against chemotherapeutic agents in veterinary oncology.

Several classes of chemotherapy drugs are used as first line or adjuvant treatment of the majority of tumour types in veterinary oncology. However, some types of tumour are intrinsically resistant to several anti-cancer drugs, and others, while initially sensitive, acquire resistance during treatment. Chemotherapy often significantly prolongs survival or disease free interval, but is not curative. The exact mechanisms behind intrinsic and acquired chemotherapy resistance are unknown for most animal tumours, but there is increasing knowledge on the mechanisms of drug resistance in humans and a few reports on molecular changes in resistant canine tumours have emerged. In addition, approaches to overcome or prevent chemotherapy resistance are becoming available in humans and, given the overlaps in molecular alterations between human and animal tumours, these may also be relevant in veterinary oncology. This review provides an overview of the current state of research on general chemotherapy resistance mechanisms, including drug efflux, DNA repair, apoptosis evasion and tumour stem cells. The known resistance mechanisms in animal tumours and the potential of these findings for improving treatment efficacy in veterinary oncology are also explored.

Equine atypical myopathy caused by hypoglycin A intoxication associated with ingestion of sycamore maple tree seeds.

REASONS FOR PERFORMING STUDY: Evidence suggest there is a link between equine atypical myopathy (EAM) and ingestion of sycamore maple tree seeds. OBJECTIVES: To further evaluate the hypothesis that the ingestion of hypoglycin A (HGA) containing sycamore maple tree seeds causes acquired multiple acyl-CoA dehydrogenase deficiency and might be associated with the clinical and pathological signs of EAM. STUDY DESIGN: Case report. METHODS: Necropsy and histopathology, using hematoxylin and eosin and Sudan III stains, were performed on a 2.5-year-old mare that died following the development of clinical signs of progressive muscle stiffness and recumbency. Prior to death, the animal ingested sycamore maple tree seeds (Acer pseudoplatanus). Detection of metabolites in blood and urine obtained post mortem was performed by rapid ultra-performance liquid chromatography-tandem mass spectrometry. Data from this case were compared with 3 geldings with no clinical history of myopathy. RESULTS: Macroscopic examination revealed fragments of maple tree seeds in the stomach and severe myopathy of several muscle groups including Mm. intercostales, deltoidei and trapezii. Histologically, the affected muscles showed severe, acute rhabdomyolysis with extensive accumulation of finely dispersed fat droplets in the cytoplasm of degenerated skeletal muscle cells not present in controls. Urine and serum concentrations of several acyl carnitines and acyl glycines were increased, and both contained metabolites of HGA, a toxic amino acid present in sycamore maple tree seeds. CONCLUSIONS: The study supports the hypothesis that ingestion of HGA-containing maple tree seeds may cause EAM due to acquired multiple acyl-CoA dehydrogenase deficiency.

Impact of high dietary zinc on zinc accumulation, enzyme activity and proteomic profiles in the pancreas of piglets.

The exocrine pancreas plays an important role in zinc homeostasis. Feeding very high (2000-3000mgzinc/kg diet) levels of zinc oxide to piglets for short periods is a common practice in the swine industry to improve performance and prevent diseases. The impact on pancreatic function and possible side effects during long-term feeding of high dietary zinc levels are still poorly understood. A total of 54 weaned piglets were either fed with low (57mg/kg, LZn), normal (164mg/kg, NZn) or high (2425mg/kg, HZn) zinc concentration in the diets. After 4 weeks of feeding, ten piglets per treatment were euthanized and pancreas samples were taken. Tissue zinc concentration and metallothionein abundance was greater with HZn compared with NZn and LZn (P<0.05). Similarly, activity of α-amylase, lipase, trypsin and chymotrypsin was higher with HZn as compared with NZn and LZn diets (P<0.05), whereas elastase activity was unchanged. Total trolox equivalent antioxidative capacity of pancreas tissue was higher with HZn diets compared with the other treatments (P<0.05). Pancreatic protein profiles of NZn and HZn fed piglets were obtained by 2D-DIGE technique and revealed 15 differentially expressed proteins out of 2100 detected spots (P<0.05). The differentially expressed proteins aldose reductase, eukaryotic elongation factor II and peroxiredoxin III were confirmed by immunoblotting. Identified proteins include zinc finger-containing transcription factors and proteins mainly associated with oxidative stress response and signal transduction in HZn compared with NZn pigs. Histologic examination however showed no morphologic changes. The results suggest that long-term supply of very high dietary zinc increases zinc and metallothionein concentration, and digestive enzyme activity, but also triggers oxidative stress reactions in the pancreas of young pigs. The data provide new insights into pancreatic function under outbalanced zinc homeostasis.

Expression of an engineered soluble coxsackievirus and adenovirus receptor by a dimeric AAV9 vector inhibits adenovirus infection in mice.

Immunosuppressed (IS) patients, such as recipients of hematopoietic stem cell transplantation, occasionally develop severe and fatal adenovirus (Ad) infections. Here, we analyzed the potential of a virus receptor trap based on a soluble coxsackievirus and Ad receptor (sCAR) for inhibition of Ad infection. In vitro, a dimeric fusion protein, sCAR-Fc, consisting of the extracellular domain of CAR and the Fc portion of human IgG1 and a monomeric sCAR lacking the Fc domain, were expressed in cell culture. More sCAR was secreted into the cell culture supernatant than sCAR-Fc, but it had lower Ad neutralization activity than sCAR-Fc. Further investigations showed that sCAR-Fc reduced the Ad infection by a 100-fold and Ad-induced cytotoxicity by ~20-fold. Not only was Ad infection inhibited by sCAR-Fc applied prior to infection, it also inhibited infection when used to treat ongoing Ad infection. In vivo, sCAR-Fc was delivered to IS mice by an AAV9 vector, resulting in persistent and high (>40 µg ml(-1)) sCAR-Fc serum levels. The sCAR-Fc serum concentration was sufficient to significantly inhibit hepatic and cardiac wild-type Ad5 infection. Treatment with sCAR-Fc did not induce side effects. Thus, sCAR-Fc virus receptor trap may be a promising novel therapeutic for treatment of Ad infections.