Publications by authors named "Llorenç Grau-Roma"

28 Publications

  • Page 1 of 1

Histological and immunohistochemical investigation of canine prostate carcinoma with identification of common intraductal carcinoma component.

Vet Comp Oncol 2021 May 7. Epub 2021 May 7.

BioDiscovery Institute, University of Nottingham, Nottingham, UK.

A limited number of species, including men and dogs, spontaneously develop prostate cancer (PC). The histological and molecular relevance of canine PC as a model for the disease in men remains controversial. To address this challenge, this study aimed to assess the histomorphology and expression of basal cell, urothelial and neuroendocrine markers [p63, high molecular weight cytokeratin (HMWCK), Uroplakin 3 (UPIII), neuron-specific enolase (NSE)] in canine PC (n = 41). Based on histomorphology, 10/41 (24%), 21/41 (51%) and 9/41 (22%) were classified as adenocarcinoma (AC), urothelial carcinoma (UC), and mixed carcinoma, respectively. Tumour inflammation was common, frequently severe [20/41 (49%)], and associated with neutering (p < .02) and urothelial differentiation (p < .02). Most (36/40, 90%) cancers contained only rare cells with basal cell marker expression or were negative. The expression of UPIII was absent or weak in the majority (33/38, 87%) of tumours, with moderate to strong staining in the remaining cases. NSE expression in PC was rare and limited to 2/14 (14%) cases. Tumour extension into benign ducts and glands was a common finding with presence in 17/39 (44%) of carcinomas with and without urothelial differentiation. In conclusion, we confirm that canine PC is characterized by absent or weak expression of basal cell and urothelial markers. Although rare, NSE expression, potentially indicating neuroendocrine differentiation, is reported for the first time in canine PCa. Intraductal carcinoma of the prostate with concurrent invasive PCa (IDCP-inv) is a frequent, not previously described, finding in dogs with PC.
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http://dx.doi.org/10.1111/vco.12704DOI Listing
May 2021

Phenotypic and Genomic Analysis of Cystic Hygroma in Pigs.

Genes (Basel) 2021 Jan 31;12(2). Epub 2021 Jan 31.

Clinic for Swine, Vetsuisse Faculty, University of Bern, 3012 Bern, Switzerland.

Cystic hygroma is a malformation of the lymphatic and vascular system and is recognized as a benign congenital tumor that affects humans and animals in the perinatal period. This congeni-tal disorder is rarely described in animals, and until today, cystic hygroma in pigs has not been described in the literature. In a purebred Piètrain litter with twelve live-born piglets, cystic hy-groma was noticed on the rump of two male pigs within the first week of life. In addition, a third case of a crossbred weaner (Large White × Landrace) was detected during a herd examina-tion. To rule out common differential diagnoses, e.g., abscess or hematoma, further clinical and pathological investigations were conducted. During clinical examination, a painless and soft mass, which was compressible, was detected on the rump of all affected animals. The ultra-sonographic examination revealed a fluid-filled and cavernous subcutaneous structure. In addi-tion, a puncture of the cyst was conducted, revealing a serosanguinous fluid with negative bacte-riological culture. In all cases, a necropsy was performed, showing that the animals had fluid-filled cysts lined by well-differentiated lymphatic endothelium. Based on the clinicopathological examination, cystic hygroma was diagnosed. Furthermore, SNP array genotyping and whole-genome sequencing was performed and provided no evidence for a chromosomal disorder. In the Piètrain family, several genome regions were homozygous in both affected piglets. None-theless, a dominant acting de novo germline variant could not be ruled out, and therefore differ-ent filtering strategies were used to find pathogenic variants. The herein presented lists of pri-vate variants after filtering against hundreds of control genomes provide no plausible candidate and no shared variants among the two sequenced cases. Therefore, further studies are needed to evaluate possible genetic etiology. In general, systematic surveillance is needed to identify ge-netic defects as early as possible and to avoid the occurrence of losses in the pig population.
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http://dx.doi.org/10.3390/genes12020207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7911466PMC
January 2021

-Associated Necrotic Enteritis-Like Disease in Coconut Lorikeets ().

Vet Pathol 2021 Mar 19;58(2):423-427. Epub 2020 Nov 19.

Institute of Animal Pathology, Vetsuisse Faculty, 27210University of Bern, Bern, Switzerland.

Several outbreaks of necrotic enteritis-like disease in lorikeets, from which was consistently isolated, are described. All lorikeets had acute, segmental, or multifocal fibrinonecrotizing inflammatory lesions in the small and/or the large intestine, with intralesional gram-positive rods. The gene encoding alpha toxin was detected by PCR (polymerase chain reaction) on formalin-fixed, paraffin-embedded (FFPE) tissues in 20 out of 24 affected lorikeets (83%), but it was not amplified from samples of any of 10 control lorikeets ( < .0001). The second most prevalent toxin gene detected was the beta toxin gene, which was found in FFPE from 7 out of 24 affected lorikeets (29%). The other toxin genes were detected inconsistently and in a relatively low number of samples. These cases seem to be associated with , although the specific type involved could not be determined.
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http://dx.doi.org/10.1177/0300985820971788DOI Listing
March 2021

Pathological findings in genital organs of bulls naturally infected with Besnoitia besnoiti.

Parasitol Res 2020 Jul 26;119(7):2257-2262. Epub 2020 May 26.

IRTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA-UAB), Campus de la Universitat Autònoma de Barcelona, Bellaterra, 08193, Barcelona, Catalonia, Spain.

Bulls chronically affected by bovine besnoitiosis can suffer from sterility. There is limited information about the distribution of Besnoitia cysts and their associated lesions within the male genital organs. This work describes the gross and histological abnormalities in the genital organs of 6 bulls chronically infected with Besnoitia besnoiti, including both clinically (n = 4) and subclinically (n = 2) affected cases. Parasitic cysts were observed in the genital organs of all the clinically affected bulls. The tissue cysts were most commonly found within the pampiniform plexus (4/4), where they were often seen within venous vascular walls and associated with vasculitis, followed by epididymis (3/4), tunica albuginea (2/4), and penis (1/4). In decreasing order of their frequency, observed abnormalities included seminiferous tubule degeneration, testicular fibrosis, testicular necrosis, lack of/or diminished numbers of spermatozoa, testicular atrophy, and Leydig cell hyperplasia. Only one of the subclinically infected bulls had few Besnoitia cysts within the pampinoform plexus, which was associated to small areas of necrosis and mineralization in the ipsilateral testicle. Results indicate that Besnoitia cysts and genital abnormalities are frequent in bulls chronically affected by bovine besnoitiosis, while they are mild and scarce in subclinically affected ones. Moreover, present data show that Besnotia-associated testicular lesions can occur without the presence of cysts within the testicular parenchyma. B. besnoiti cysts seem to have a tropism for the vascular structures of the spermatic chord, which may cause testicular abnormalities via vascular damage, reduced blood flow, and/or impaired thermoregulation and subsequently lead to the observed testicular lesions.
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http://dx.doi.org/10.1007/s00436-020-06695-3DOI Listing
July 2020

Retrospective study on transmissible viral proventriculitis and chicken proventricular necrosis virus (CPNV) in the UK.

Avian Pathol 2020 Feb 21;49(1):99-105. Epub 2019 Oct 21.

IRTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA-UAB), Barcelona, Spain.

Chicken proventricular necrosis virus (CPNV) is a recently described birnavirus, which has been proposed to be the cause of transmissible viral proventriculitis (TVP). The understanding of the epidemiology of both the virus and the disease is very limited. A retrospective investigation on TVP and CPNV in broiler chicken submissions from the UK from between 1994 and 2015 was performed with the aims of assessing the longitudinal temporal evolution of TVP and CPNV, and to review the histological proventricular lesions in the studied chickens. Ninety-nine of the 135 included submissions (73.3%) fulfilled the TVP-diagnostic criteria, while the remaining 36 submissions (26.7%) displayed only lymphocytic proventriculitis (LP). The first detection of CPNV by PCR dated from 2009. Results showed a rise in the number of both TVP and positive CPNV RT-PCR submissions from 2009 with a peak in 2013, suggesting that they may be an emerging or re-emerging disease and pathogen, respectively. Twenty-two out of the 99 submissions displaying TVP lesions (22%) and four out of the 36 (11%) submissions with LP gave positive CPNV RT-PCR results, further supporting the association between CPNV and TVP and confirming that CPNV is present in a low proportion of proventriculi that do not fulfil the TVP-diagnostic criteria. In addition, intranuclear inclusion bodies were observed in 22 of the submissions with TVP. The vast majority of these cases (21 of 22, 96%) gave negative CPNV RT-PCR results, raising the question of whether a virus other than CPNV is responsible for some of these TVP-affected cases.TVP and CPNV have been present in British broilers since at least 1994 and 2009, respectively.TVP and CPNV seem to be an emerging and re-emerging disease and pathogen, respectively.CPNV was detected in proventriculi with both TVP and LP-lesions.Viruses other than CPNV may be responsible for some TVP-affected cases.
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http://dx.doi.org/10.1080/03079457.2019.1677856DOI Listing
February 2020

Spongiform leucoencephalomyelopathy in border terriers: clinical, electrophysiological and imaging features.

Vet Rec 2019 09 25;185(12):375. Epub 2019 Jul 25.

Neurology Service, Dovecote Veterinary Hospital, Derby, UK.

A novel spongiform leucoencephalomyelopathy was reported in border terrier puppies in 2012 causing a shaking puppy phenotype, but no information regarding clinical progression, imaging or electrophysiological findings were available. The aim of the present study was to describe the clinical, electrophysiological and MRI features of this disease in seven dogs and compare them with human white matter disorders. All cases presented with cerebellar ataxia and severe generalised coarse body tremors, which started at three weeks of age. The three cases that were not euthanased showed slow but progressive improvement over several months. Brainstem auditory evoked response demonstrated a normal wave I, reduced amplitude of wave II and an absence of waves III-VII. MRI revealed bilateral and symmetrical T2-weighted hyperintensities affecting the brainstem and cerebellar white matter. Histological examination of the brain and spinal cord showed spongiform change affecting the white matter of the cerebellum, brainstem and spinal cord with decreased myelin content. In summary, this leucoencephalomyelopathy has a pathognomonic clinical presentation with defining MRI and electrophysiological characteristics, and it is the first report to describe a long-term improvement of this condition.
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http://dx.doi.org/10.1136/vr.105240DOI Listing
September 2019

Mucosal injury following short-term tracheal intubation: A novel animal model and composite tracheal injury score.

Laryngoscope Investig Otolaryngol 2018 Aug 9;3(4):257-262. Epub 2018 Aug 9.

Department of Anaesthetics Nottingham University Hospitals NHS Trust Nottingham UK.

Objectives: Postintubation laryngotracheal injury is common. Assessment of histopathological changes currently requires animal models. We set about developing a viable, resource effective animal model to study these effects and to develop a detailed tissue injury score.

Methods: Six pigs were anesthetized using a standard regimen. We intubated the tracheas using a standard endotracheal tube modified to include optical sensors. Animals were anesthetized for a duration of two to four hours, and their lungs were ventilated using a normoxic gas mixture. Following euthanasia, the tracheas were removed and underwent histological assessment by two independent veterinary pathologists. The histological lesions, including controls, were described and quantified, and two pathologists classified tissues according to a novel injury score.

Results: Mean duration of tracheal intubation was 191 minutes (SD ± 41.6). In all except one animal, cuff pressures were maintained in the range of 25-45 cmH20. Histopathological findings in all study animals showed more extensive changes than previously described with short-term intubation. Changes were seen in all mucosal layers consistent with acute, suppurative, and ulcerative tracheitis. The range of scores of the developed composite scoring system among the animals was wider than in earlier descriptions. There was a high percentage of agreement between both pathologists.

Conclusions: We have described a novel tracheal injury score to assess pathological changes following short term intubation in a viable animal model. The scoring system distinguished between the test animals as well as controls and may be appropriate for continuing study of intubation injury.

Level Of Evidence: 3.
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http://dx.doi.org/10.1002/lio2.168DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6119797PMC
August 2018

The dog as an animal model for bladder and urethral urothelial carcinoma: Comparative epidemiology and histology.

Oncol Lett 2018 Aug 30;16(2):1641-1649. Epub 2018 May 30.

School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington, LE12 5RD, UK.

Despite the recent approval of several novel agents for patients with metastatic urothelial carcinoma (UC), survival in this setting remains poor. As such, continued investigation into novel therapeutic options remains warranted. Pre-clinical development of novel treatments requires an animal model that accurately simulates the disease in humans. The aim of the present study was to evaluate the dog as an animal model for human UC. A total of 260 cases of spontaneous, untreated canine primary urethral and urinary bladder UC, were epidemiologically and histologically assessed and classified based on the current 2016 World Health Organization (WHO) tumor classification system. Canine data was compared with human data available from scientific literature. The mean age of dogs diagnosed with UC was 10.22 years (range, 4-15 years), which is equivalent to 60-70 human years. The results revealed a high association between UC diagnosis with the female sex [odds ratio (OR) 3.51; 95% confidence interval (CI) 2.57-4.79; P<0.001], surgical neutering (OR 4.57; 95% CI 1.87-11.12; P<0.001) and breed (OR 15.11 for Scottish terriers; 95% CI 8.99-25.41; P<0.001). Based on the 2016 WHO tumor (T), node and metastasis staging system, the primary tumors were characterized as T1 (38%), T2a (28%), T2b (13%) and T3 (22%). Non-papillary, flat subgross tumor growth was strongly associated with muscle invasion (OR 31.00; P<0.001). Irrespective of subgross growth pattern, all assessable tumors were invading beyond the basement membrane compatible with infiltrating UC. Conventional, not further classifiable infiltrating UC was the most common type of tumor (90%), followed by UC with divergent, squamous and/or glandular differentiation (6%). Seven out of the 260 (2.8%) cases were classified as non-urothelial based on their histological morphology. These cases included 5 (2%) squamous cell carcinomas, 1 (0.4%) adenocarcinoma and 1 (0.4%) neuroendocrine tumor. The 2 most striking common features of canine and human UC included high sex predilection and histological tumor appearance. The results support the suitability of the dog as an animal model for UC and confirm that dogs also spontaneously develop rare UC subtypes and bladder tumors, including plasmacytoid UC and neuroendocrine tumor, which are herein described for the first time in a non-experimental animal species.
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http://dx.doi.org/10.3892/ol.2018.8837DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6036476PMC
August 2018

Meningeal carcinomatosis and spinal cord infiltration caused by a locally invasive pulmonary adenocarcinoma in a cat.

JFMS Open Rep 2017 Jul-Dec;3(2):2055116917742812. Epub 2017 Nov 23.

Department of Neurology / Neurosurgery, Pride Veterinary Centre, Derby, UK.

Case Summary: A 12-year-old domestic shorthair cat was presented with acute non-painful hindlimb proprioceptive ataxia localising to T3-L3 spinal cord segments. MRI revealed paravertebral muscular hyperintensity on T2-weighted images at the level of T7-T8 vertebrae. The cat improved on conservative management but deteriorated 3 months later. Repeated MRI showed meningeal enhancement at the same level and hyperintensity of the paravertebral musculature extending to the right thoracic wall and pleural space on short tau inversion recovery images. Thoracic CT showed mineralised lesions of the right lung, restricted pleural effusion and expansile bone lesions affecting multiple ribs. The cat had been treated for pyothorax 5 years earlier but manifested no current respiratory signs. Cerebrospinal fluid (CSF) examination showed lymphocytic pleocytosis but no neoplastic cells. Biopsy of the affected muscles and cytology of the lung and pleural lesions suggested a malignant epithelial cell tumour. Post-mortem examination confirmed a pulmonary adenocarcinoma locally infiltrating the thoracic wall, T7-T8 vertebrae and the spinal cord white matter. Meningeal carcinomatosis was detected with neoplastic cells invading the ventral median fissure of the spinal cord. No metastases were observed in other organs, indicating that neoplastic cells reached the spinal cord by direct extension.

Relevance And Novel Information: Spinal meningeal carcinomatosis has not been reported in dogs or cats with extraneural tumours but is a well-recognised condition in humans. A metastatic cause of meningeal enhancement should be considered in patients with neurological signs of unknown origin. Imaging findings and CSF results can be non-specific.
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http://dx.doi.org/10.1177/2055116917742812DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5703112PMC
November 2017

Comparative review of human and canine osteosarcoma: morphology, epidemiology, prognosis, treatment and genetics.

Acta Vet Scand 2017 Oct 24;59(1):71. Epub 2017 Oct 24.

Faculty of Medicine and Health Sciences, School of Veterinary Medicine and Science, The University of Nottingham, Sutton Bonington Campus, Loughborough, LE12 5RD, UK.

Osteosarcoma (OSA) is a rare cancer in people. However OSA incidence rates in dogs are 27 times higher than in people. Prognosis in both species is relatively poor, with 5 year OSA survival rates in people not having improved in decades. For dogs, 1 year survival rates are only around ~ 45%. Improved and novel treatment regimens are urgently required to improve survival in both humans and dogs with OSA. Utilising information from genetic studies could assist in this in both species, with the higher incidence rates in dogs contributing to the dog population being a good model of human disease. This review compares the clinical characteristics, gross morphology and histopathology, aetiology, epidemiology, and genetics of canine and human OSA. Finally, the current position of canine OSA genetic research is discussed and areas for additional work within the canine population are identified.
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http://dx.doi.org/10.1186/s13028-017-0341-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5655853PMC
October 2017

Occurrence of primary lymphocytic hypophysitis in two horses and presence of scattered T-lymphocytes in the normal equine pituitary gland.

J Vet Diagn Invest 2017 Jan 16;29(1):115-121. Epub 2016 Nov 16.

School of Veterinary Medicine and Sciences, University of Nottingham, Sutton Bonington Campus, Loughborough, UK (Grau-Roma, de Brot).

The postmortem examination of a 14-y-old Appaloosa gelding with clinically diagnosed pituitary pars intermedia dysfunction showed a unique finding of moderate multifocal lymphocytic hypophysitis (LH). The pituitary glands of 24 horses submitted for postmortem examination were examined grossly and examined histologically for the presence of lymphocytes. Of these 23 horses, 1 additional case suffered from moderate LH. The 2 cases with LH tested negative for Equid herpesvirus 1 and 4 by polymerase chain reaction and immunohistochemistry (IHC), and no viral particles were observed by electron microscopy in 1 case examined. The cause of LH remains unknown, but based on the T-lymphocytic nature of the inflammation and the human literature, an immune-mediated origin is hypothesized. In addition, the review of 24 cases revealed that 10 horses had few and small multifocal lymphocytic infiltrates within the pituitary gland; the remaining 12 horses showed no evident lymphocytes when examined by hematoxylin and eosin. IHC for CD3 showed the presence of a small number of individual T-lymphocytes scattered through the gland in all examined horses, which appears therefore to be a normal feature of the pituitary gland in horses.
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http://dx.doi.org/10.1177/1040638716676292DOI Listing
January 2017

Detection of transmissible viral proventriculitis and chicken proventricular necrosis virus in the UK.

Avian Pathol 2017 Feb 1;46(1):68-75. Epub 2016 Dec 1.

c IRTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA-UAB) , Barcelona , Spain.

Increasing evidence suggests that a new birnavirus, named chicken proventricular necrosis virus (CPNV), is the aetiological agent of transmissible viral proventriculitis (TVP). The present work aimed to explore the possible presence of both TVP and CPNV in the UK. Forty-four chickens showing TVP-compatible gross lesions were classified into three groups based on the histological lesions: (i) TVP-affected chickens: lymphocytic infiltration and glandular necrosis (n = 15); (ii) lymphocytic proventriculitis (LP)-affected chickens: lymphocytic infiltration without necrosis (n = 18); and (iii) without proventriculitis (WP): no lymphocytic infiltration or necrosis (n = 11). Nine proventriculi (seven out of 15 corresponding to TVP, and two out of 11 corresponding to LP) were positive for CPNV by reverse transcriptase polymerase chain reaction (RT-PCR). These results support the previously suggested idea of CPNV as causative agent of TVP. Moreover, these data show that CPNV can also be detected in a number of cases with LP, which do not fulfil the histological TVP criteria. Phylogenetic analysis of partial sequences of gene VP1 showed that British CPNV sequences were closer to other European CPNV sequences and might constitute a different lineage from the American CPNV. TVP cases with negative CPNV PCR results may be due to chronic stages of the disease or to the reduced PCR sensitivity on formalin-fixed paraffin-embedded tissues. However, involvement of other agents in some of the cases cannot totally be ruled out. As far as the authors are aware, this is the first peer-reviewed report of TVP as well as of CPNV in the UK, and the first exploratory CPNV phylogenetic study.
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http://dx.doi.org/10.1080/03079457.2016.1207751DOI Listing
February 2017

Remote effects of acute kidney injury in a porcine model.

Am J Physiol Renal Physiol 2016 Feb 25;310(4):F259-71. Epub 2015 Nov 25.

School of Veterinary Medicine and Science, University of Nottingham, Loughborough, United Kingdom; Renal and Transplant Unit, Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom; and.

Acute kidney injury (AKI) is a common and serious condition with no specific treatment. An episode of AKI may affect organs distant from the kidney, further increasing the morbidity associated with AKI. The mechanism of organ cross talk after AKI is unclear. The renal and immune systems of pigs and humans are alike. Using a preclinical animal (porcine) model, we tested the hypothesis that early effects of AKI on distant organs is by immune cell infiltration, leading to inflammatory cytokine production, extravasation, and edema. In 29 pigs exposed to either sham surgery or renal ischemia-reperfusion (control, n = 12; AKI, n = 17), we assessed remote organ (liver, lung, brain) effects in the short (from 2- to 48-h reperfusion) and longer term (5 wk later) using immunofluorescence (for leukocyte infiltration, apoptosis), a cytokine array, tissue elemental analysis (e.g., electrolytes), blood hematology and chemistry (e.g., liver enzymes), and PCR (for inflammatory markers). AKI elicited significant, short-term (∼24 h) increments in enzymes indicative of acute liver damage (e.g. , AST: ALT ratio; P = 0.02) and influenced tissue biochemistry in some remote organs (e.g., lung tissue [Ca(2+)] increased; P = 0.04). These effects largely resolved after 48 h, and no further histopathology, edema, apoptosis, or immune cell infiltration was noted in the liver, lung, or hippocampus in the short and longer term. AKI has subtle biochemical effects on remote organs in the short term, including a transient increment in markers of acute liver damage. These effects resolved by 48 h, and no further remote organ histopathology, apoptosis, edema, or immune cell infiltration was noted.
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http://dx.doi.org/10.1152/ajprenal.00389.2015DOI Listing
February 2016

Serum haptoglobin dynamics in pigs vaccinated or not vaccinated against porcine circovirus type 2.

Porcine Health Manag 2015 16;1. Epub 2015 Apr 16.

Centre de Recerca en Sanitat Animal (CReSA), UAB-IRTA, Campus de la Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), 08193 Barcelona, Spain.

The present work describes the serum haptoglobin (Hp) dynamics in piglets vaccinated and non-vaccinated with a commercial porcine circovirus type 2 (PCV2) vaccine at 3 weeks of age, and its relationship with the average daily weight gain (ADWG). The field study was carried out on two farms (A and B) with a previous clinical history of PCV2-systemic disease (PCV2-SD). The aim of the study was to assess whether Hp could be used as a surrogate marker of PCV2 vaccine efficacy. PCV2 infection was confirmed by quantitative real time PCR (qPCR) in pigs from both farms, but PCV2-SD was only diagnosed in farm A. No statistically significant relation was found between serum Hp concentration and the percentage of qPCR positive animals and the treatment applied (PCV2 vaccination) in both farms. On the other hand, using linear regression analysis, a significant negative correlation between the area under the curve of Hp (AUC) and ADWG was observed for farm A (p < 0.00001) and B (p = 0.01). Based on the obtained determination coefficient (R) values, AUC explained 20.0 and 11.6% of the observed ADWG for farms A and B, respectively. The present study supports that the measurement of acute phase proteins may be an indicator of ADWG in pig farms, but it was not apparently feasible to use the serum Hp concentration as a surrogate marker of PCV2 vaccine efficacy.
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http://dx.doi.org/10.1186/2055-5660-1-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5375125PMC
April 2015

Pigs naturally exposed to porcine circovirus type 2 (PCV2) generate antibody responses capable to neutralise PCV2 isolates of different genotypes and geographic origins.

Vet Res 2014 Mar 6;45:29. Epub 2014 Mar 6.

Centre de Recerca en Sanitat Animal (CReSA), UAB-IRTA, Campus de la Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain.

Porcine circovirus type 2 (PCV2) is the essential infectious agent for PCV2-systemic disease (PCV2-SD, formerly known as postweaning multisystemic wasting syndrome) and other pathological conditions. Recent studies indicated antigenic variability amongst different PCV2 isolates and suggested that single amino acid changes within the capsid protein determine differences in the level of neutralization by specific monoclonal antibodies. The objective of the present study was to examine the cross-reactivity of PCV2 antibodies induced in the context of a natural infection against different PCV2 isolates belonging to genotypes PCV2a and PCV2b. Sera taken from several farms from animals of varying health status (PCV2-SD and age-matched healthy pigs and a set of slaughter-aged animals) were assayed for neutralizing activity against four PCV2 isolates from both predominant genotypes (PCV2a and PCV2b) and of differing geographic origins (Europe and North-America). Results showed that most of studied pigs (79 out of 82) contained neutralizing antibodies (NA) able to neutralize all four studied viral strains. Overall, pigs had significantly higher NA titres against PCV2a than against PCV2b (P < 0.001). Accordingly, studied serums were able to better neutralize Burgos390L4 and Stoon-1010 strains (PCV2a) than L-33-Sp-10-54 and MO/S-06 strains (PCV2b) (P < 0.001). No differences between capabilities of seroneutralization of viruses from different geographic origin were observed. Present data suggests that sequence differences between PCV2 isolates translate to functional antigenic differences in viral neutralization in vivo.
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http://dx.doi.org/10.1186/1297-9716-45-29DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3996031PMC
March 2014

Occurrence of osteochondromatosis (multiple cartilaginous exostoses) in a domestic pig (Sus scrofa domesticus).

J Vet Diagn Invest 2013 Sep 11;25(5):599-602. Epub 2013 Jul 11.

1Simone de Brot, Institute of Veterinary Pathology, Vetsuisse Faculty, University of Zurich, Winterthurerstrasse 268, CH-8057 Zurich, Switzerland.

Osteochondromatosis is a condition in which multiple benign, cartilage-capped tumors arise from the surface of bones formed by endochondral ossification. The current report describes the presence of 4 prominent exophytic masses, measuring between 4 and 13 cm in diameter, arising from the surface of the ribs, and located within the thoracic cavity, in a 2-year-old female domestic pig (Sus scrofa domesticus). Histological studies revealed that masses were well-differentiated, cartilage-capped proliferations with an orderly pattern of endochondral mineralization toward deeper areas. The observed gross and microscopic findings are characteristic of osteochondromatosis.
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http://dx.doi.org/10.1177/1040638713495545DOI Listing
September 2013

Imaging diagnosis--ultrasonographic appearance of small bowel metastasis from canine mammary carcinoma.

Vet Radiol Ultrasound 2014 Mar-Apr;55(2):208-12. Epub 2013 Jun 13.

Fundació Hospital Clínic Veterinary, Facultat de Veterinària, Universitat Autònoma de Barcelona, Bellaterra (Barcelona), Spain.

A 10-year-old entire female Beagle dog was evaluated for an acute history of lethargy, anorexia, and diarrhea. Mammary tumors were detected during physical examination. Ultrasonographic scanning revealed the presence of a unique pattern of multiple, well-defined and well-marginated hypoechoic nodules in the muscularis layer of the jejunum. These nodules were not associated with changes in the rest of the normal intestinal layering and were not causing signs of intestinal obstruction. Mammary carcinoma metastases to the intestinal muscularis layer were diagnosed based on histopathological examination.
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http://dx.doi.org/10.1111/vru.12061DOI Listing
November 2014

Infectious risk factors for individual postweaning multisystemic wasting syndrome (PMWS) development in pigs from affected farms in Spain and Denmark.

Res Vet Sci 2012 Dec 9;93(3):1231-40. Epub 2012 Aug 9.

Departament de Sanitat i Anatomia Animals, Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain.

Two prospective longitudinal studies in 13 postweaning multisystemic wasting syndrome (PMWS)-affected farms from Spain (n=3) and Denmark (n=10) were performed. Blood samples from pigs were longitudinally collected from 1st week until the occurrence of the PMWS outbreak. Wasted and healthy age-matched pigs were euthanized, necropsied and histopathologically characterised. PMWS diagnosis was confirmed by means of lymphoid lesions and detection of porcine circovirus type 2 (PCV2) in these tissues by in situ hybridization or immunohistochemistry. Serological analyses were performed in longitudinally collected serum samples to detect antibodies against, PCV2, porcine reproductive and respiratory syndrome virus (PRRSV), porcine parvovirus (PPV), swine influenza virus (SIV) and Lawsonia intracellularis (law), Mycoplasma hyopneumoniae, Aujeszky's disease virus (ADV) and Salmonella spp. A Cox proportional hazards model was used to investigate the simultaneous effects of seroconversion and maternal immunity against the studied pathogens. Results showed that high levels of maternal immunity against PCV2 had a protecting effect in farms from both countries. Moreover, for the Danish dataset, seroconversion against law had an overall protecting effect, but for animals with very low levels of maternal antibody levels against this pathogen, the effect appeared neutral or aggravating. Otherwise, for the Spanish dataset, maternal immunity against PPV and PRRSV gave protective and aggravating effects, respectively. In conclusion, the present study reflects the complex interaction among different pathogens and their effects in order to trigger PMWS in PCV2 infected pigs.
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http://dx.doi.org/10.1016/j.rvsc.2012.07.001DOI Listing
December 2012

Multiple cutaneous mast cell tumors in a pig.

J Vet Diagn Invest 2011 Nov 24;23(6):1222-5. Epub 2011 Oct 24.

Departament de Sanitat i Anatomia Animals, Universitat Autònoma Barcelona, 08193, Bellaterra, Barcelona, Spain.

Cutaneous tumors are not usually observed in pigs, and mast cell tumors, in particular, have been rarely described. The current report describes numerous, pink to red, elevated, 1-5-cm nodules in the skin of a 6-month-old slaughter pig. The histopathology of the nodules revealed well-demarcated, but poorly differentiated, populations of round cells that extended from the dermis into subcutaneous tissues. The presence of eosinophils and the observation, at high magnification, of cells with cytoplasmic metachromatic granules, after toluidine blue staining, confirmed the diagnosis of multiple cutaneous mast cell tumors.
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http://dx.doi.org/10.1177/1040638711425574DOI Listing
November 2011

Inactivated PCV2 one shot vaccine applied in 3-week-old piglets: improvement of production parameters and interaction with maternally derived immunity.

Vaccine 2012 Mar 14;30(11):1986-92. Epub 2012 Jan 14.

Centre de Recerca en Sanitat Animal, UAB-IRTA, Campus de la Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain.

The present study describes the effects of a commercially available vaccine against Porcine circovirus type 2 (PCV2) on clinical, pathological and virological outcomes of 3-week-old piglets from two farms with a clinical history of postweaning multisystemic wasting syndrome (PMWS). The study was a controlled, double-blinded, parallel group (1:1) and randomized trial (with a negative control) involving a total of 1239 animals. The study period comprised from weaning age (time of vaccination or PBS inoculation) until the first shipment of pigs to the slaughterhouse. The vaccine product was able to reduce clinical signs, PCV2 viral load in sera and faeces, and overall mortality in nurseries and fattening units. Moreover, average daily gain was significantly higher in vaccinated versus non-vaccinated piglets during the trial period. On the other hand, it was shown that maternally derived antibodies interfered with the development of an active humoral immune response after PCV2 vaccination.
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http://dx.doi.org/10.1016/j.vaccine.2012.01.008DOI Listing
March 2012

Theoretical and experimental approaches to estimate the usefulness of pooled serum samples for the diagnosis of postweaning multisystemic wasting syndrome.

J Vet Diagn Invest 2011 Mar;23(2):233-40

Joaquim Segalés, Centre de Recerca en Sanitat Animal, UAB-IRTA, Universitat Autònoma de Barcelona, Campus Bellaterra, Cerdanyola del Vallès, Barcelona 08193, Spain.

Classical postweaning multisystemic wasting syndrome (PMWS) diagnosis is based on postmortem findings (histopathology plus viral detection in lymphoid tissues). Because one of the major differences between PMWS-affected and nonaffected pigs is Porcine circovirus-2 (PCV-2) load in serum and tissues, real-time quantitative polymerase chain reaction (qPCR) has been suggested as a potential diagnostic technique for the disease. The objective of the present study was to assess the applicability of qPCR to quantify PCV-2 loads in pooled serum samples as an easy-to-use PMWS diagnostic tool at the herd level. The experimental design included two simulation studies with several serum pool sizes from pigs already screened for PMWS (by histopathology and detection of PCV-2 by qPCR). Several qPCR thresholds were defined and validated with experimental pools created in the laboratory. Quantitative PCR on pooled serum samples did not result in a sufficiently reliable alternate method to the classical PMWS diagnosis method based on individual clinical, histopathological, and PCV-2 detection criteria. However, serum pools seemed to be an alternative at a low economic cost for the quantification of PCV-2 loads in suspicious herds. A targeted (including only clinically diseased animals) sampling approach did not give better estimates compared with a random sampling approach.
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http://dx.doi.org/10.1177/104063871102300206DOI Listing
March 2011

Recent advances in the epidemiology, diagnosis and control of diseases caused by porcine circovirus type 2.

Vet J 2011 Jan 7;187(1):23-32. Epub 2010 Mar 7.

Centre de Recerca en Sanitat Animal (CReSA), UAB-IRTA, Campus de la Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain.

Post-weaning multisystemic wasting syndrome (PMWS) emerged as a significant disease affecting pig production in the 1990s although the causal agent, porcine circovirus type 2 (PCV2), and the disease itself, had existed in swine for many years prior to this. The important multifactorial 'triggers' of PMWS include the immune and infection status of the sow, the timing of PCV2 infection, variations in the virulence of PCV2, co-infections, immune modulation as well as host genetics and management factors. In terms of diagnosis, histopathological examination and the detection of PCV2 within lymphoid tissue remains the 'gold standard' as quantitative PCR techniques are currently not specific or sensitive enough. The recent commercial availability of PCV2 vaccines provides an excellent tool for reducing the impact of PMWS and other porcine circovirus-related diseases. This review assesses recent advances in the epidemiology, diagnosis and control of PMWS.
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http://dx.doi.org/10.1016/j.tvjl.2010.01.018DOI Listing
January 2011

Infection, excretion and seroconversion dynamics of porcine circovirus type 2 (PCV2) in pigs from post-weaning multisystemic wasting syndrome (PMWS) affected farms in Spain and Denmark.

Vet Microbiol 2009 Mar 17;135(3-4):272-82. Epub 2008 Oct 17.

Centre de Recerca en Sanitat Animal (CReSA), UAB-IRTA, Campus de la Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain.

Longitudinal case-control studies were performed in post-weaning multisystemic wasting syndrome (PMWS) affected farms from Denmark and Spain using similar designs. Fourteen independent batches of 100-154 pigs per batch were monitored from birth to PMWS outbreak occurrence. Pigs displaying PMWS-like signs and matched healthy cohorts were euthanized during the clinical outbreak. PMWS was diagnosed according to internationally accepted criteria and pigs were classified as: (i) PMWS cases, (ii) wasted non-PMWS cases and (iii) healthy pigs. Porcine circovirus type 2 (PCV2) quantitative PCR (qPCR) and serology techniques were applied to analyse longitudinally collected sera and/or nasal and rectal swabs. Results showed that PCV2 load increased in parallel to waning maternal antibody levels, reaching the maximum viral load concurrent with development of clinical signs. PMWS affected pigs had higher PCV2 prevalence and/or viral load than healthy pigs in all collected samples at necropsy (p<0.0001-0.05) and even in sera and nasal swabs at the sampling prior to PMWS outbreak (p<0.01-0.05). Danish farms had a higher PCV2 prevalence in young piglets as well as an earlier PMWS presentation compared to Spanish farms. PMWS diagnoses were confirmed by laboratory tests in only half of pigs clinically suspected to suffer from PMWS. Positive and significant correlations were found among PCV2 viral loads present in sera, nasal swabs, rectal swabs and lymphoid tissues (R=0.289-0.827, p<0.0001-0.01), which indicates that nasal and rectal swabs were suitable indicators of PCV2 excretion. Sensitivity and/or specificity values observed from both tests used separately or combined suggested that qPCR and/or serology tests are not apparently able to substitute histopathology plus detection of PCV2 in tissues for the individual PMWS diagnosis within PMWS affected farms. However, qPCR appears to be a potential reliable technique to diagnose PMWS on a population basis.
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http://dx.doi.org/10.1016/j.vetmic.2008.10.007DOI Listing
March 2009

Development of two Trichoplusia ni larvae-derived ELISAs for the detection of antibodies against replicase and capsid proteins of porcine circovirus type 2 in domestic pigs.

J Virol Methods 2008 Dec 21;154(1-2):167-74. Epub 2008 Sep 21.

Centre de Recerca en Sanitat Animal (CReSA), UAB-IRTA, Campus de la Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain.

The main aim of the present study was to describe new methods for the identification of antibodies against the PCV2 capsid (Cap) and replicase (Rep) proteins in pig sera. Specifically, two new indirect enzyme-linked immunosorbent assays (ELISA) were developed based on recombinant PCV2 Cap (rCap) and Rep/Rep' (rRep) proteins expressed in baculovirus and produced in Trichoplusia ni insect larvae. Both assays were validated by testing serum samples in a longitudinal study of 107 animals with different clinico-pathological features of PCV2 infection: pigs with postweaning multisystemic wasting syndrome (PMWS), wasted pigs without a diagnosis of PMWS and healthy animals. Longitudinal antibody profiles indicated that healthy animals had significantly higher anti-Cap and anti-Rep antibody levels than the rest of the animal groups at 11 weeks of age. Moreover, PMWS affected pigs could be distinguished from the rest of the pig groups by their lower anti-Rep antibody levels at 11 weeks of age and at necropsy. The results demonstrate the potential of these two ELISAs for large-scale serological studies. This study represents the first longitudinal study of the induction of anti-Cap and anti-Rep antibodies in farms affected by PMWS, from 1 week of age until the occurrence of disease.
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http://dx.doi.org/10.1016/j.jviromet.2008.07.034DOI Listing
December 2008

Detection of porcine reproductive and respiratory syndrome virus, porcine circovirus type 2, swine influenza virus and Aujeszky's disease virus in cases of porcine proliferative and necrotizing pneumonia (PNP) in Spain.

Vet Microbiol 2007 Jan 22;119(2-4):144-51. Epub 2006 Sep 22.

Centre de Recerca en Sanitat Animal (CReSA), Edifici CReSA, Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain.

Proliferative and necrotizing pneumonia (PNP) is a severe form of interstitial pneumonia characterised by hypertrophy and proliferation of pneumocytes type 2 and presence of necrotic cells within alveoli lumen. Many viral agents have been linked to PNP aetiology, with especial emphasis on porcine reproductive and respiratory syndrome virus (PRRSV). To gain knowledge on PNP causality, a retrospective study on 74 PNP cases from postweaning pigs from Spain was carried out. Coupled with histopathological examinations, the presence of porcine circovirus type 2 (PCV2) by in situ hybridization (ISH), and PRRSV, swine influenza virus (SIV) and Aujeszky's disease virus (ADV) by immunohistochemical (IHC) methods, were investigated. PCV2 was the most prevalent viral agent in PNP cases (85.1%) followed by PRRSV (44.6%); 39.1% of PNP cases showed PCV2 as the solely detected agent, while only 4.1% had PRRSV as the unique pathogen. SIV and ADV were very sporadically detected in PNP cases, and always in co-infection with PCV2. Therefore, present data indicate that PCV2 is the most important aetiological agent in PNP cases from Spain and that PRRSV is not essential for the development of PNP. Taking into account the presented results and available literature, we suggest that PCV2 is possibly the main contributor to PNP cases in Europe while PRRSV could play a similar role in North America.
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http://dx.doi.org/10.1016/j.vetmic.2006.09.009DOI Listing
January 2007