Publications by authors named "Luca Aresu"

64 Publications

Relationship of diagnostic accuracy of renal cortical echogenicity with renal histopathology in dogs and cats, a quantitative study.

BMC Vet Res 2017 Jan 17;13(1):24. Epub 2017 Jan 17.

Department of Animal Medicine, Production and Health, Clinical Section, Radiology Unit, University of Padua, Viale dell'Università 16, Legnaro, 35020, Padua, Italy.

Background: Renal cortical echogenicity is routinely evaluated during ultrasonographic investigation of the kidneys. Both in dog and cat previous ex-vivo studies have revealed a poor correlation between renal echogenicity and corresponding lesions. The aim of this study was to establish the in-vivo relationship between renal cortical echogenicity and renal histopathology.

Results: Thirty-eight dogs and fifteen cats euthanized for critical medical conditions were included in the study. Ultrasonographic images of both kidneys were acquired ante mortem at standardized ultrasonographic settings. The echogenicity was quantified by means of Mean Gray Value (MGV) of the renal cortex measured with ImageJ. A complete histopathological examination of both kidneys was performed. Five kidneys were excluded because histopathology revealed neoplastic lesions. Only samples affected by tubular atrophy showed statistically different values in dog, and histopathology explained 13% of the total variance. MGV was not correlated neither to the degeneration nor to the inflammation scores. However, significant differences were identified between mildly and severely degenerated samples. Overall, the classification efficiency of MGV to detect renal lesions was poor with a sensitivity of 39% and a specificity of 86%. In cats, samples affected by both tubular vacuolar degeneration and interstitial nephritis were statistically different and histopathology explained 44% of the total variance. A linear correlation was evident between degeneration and MGV, whereas no correlation with inflammation was found. Statistically significant differences were evident only between normal and severely degenerated samples with a sensitivity of 54.17% and a specificity of 83.3% and MGV resulted scarce to discriminate renal lesions in this species.

Conclusions: Renal cortical echogenicity shows low relevance in detecting chronic renal disease in dog whereas it results worth to identify severe renal damage in cat.
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http://dx.doi.org/10.1186/s12917-016-0941-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5240265PMC
January 2017

Canine Lymphoma, More Than a Morphological Diagnosis: What We Have Learned about Diffuse Large B-Cell Lymphoma.

Authors:
Luca Aresu

Front Vet Sci 2016 31;3:77. Epub 2016 Aug 31.

Department of Comparative Biomedicine and Food Science, University of Padova , Legnaro , Italy.

Diffuse large B-cell lymphoma (DLBCL) is the most common canine aggressive B-cell lymphoma worldwide, and new recent molecular approaches have shown that DLBCL constitutes a heterogeneous tumor that cannot be unraveled by morphology and immunophenotype. DLBCL behaves aggressively, typically progressing over a short period of time, and the therapy response may be difficult to be predicted. Recently, the rate of bone marrow infiltration by flow cytometry has been demonstrated to be prognostic, but more sensible markers are needed. As the clinical behavior is different, there is vast clinical and basic research devoted to identifying prognostically or biologically distinct DLBCL subgroups. Transcriptomic analysis by gene expression profile, copy number variations by array comparative genomic hybridization and epigenetic perturbations have tentatively described this heterogeneity. Molecular subgroups using oncogenic pathways and target genes have also been correlated to different outcome in a small number of cases. The objectives of this review are to summarize the current knowledge on the biology, clinical, and pathological characteristics of canine DLBCL. To date, DLBCL probably is the most investigated tumor in veterinary medicine, and its relevance as spontaneous model for human DLBCL has been confirmed by these studies. In future, these discoveries will ultimately lead to a better understanding of the underlying disease mechanisms, possibly translating into more effective therapeutic strategies.
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http://dx.doi.org/10.3389/fvets.2016.00077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5006005PMC
September 2016

Aortic stenting in the growing sheep causes aortic endothelial dysfunction but not hypertension: Clinical implications for coarctation repair.

Congenit Heart Dis 2017 Jan 7;12(1):74-83. Epub 2016 Sep 7.

Pediatric Cardiology Unit, Department of Women's and Children's Health, University of Padua, Padova, Italy.

Background: Stent implantation is the treatment of choice for adolescents and adults with aortic coarctation (CoAo). Despite excellent short-term results, 20%-40% of the patients develop arterial hypertension later in life, which was attributed to inappropriate response of the aortic baroreceptors to increased stiffness of the ascending aorta (ASAO), either congenital or induced by CoAo repair. In particular, it has been hypothesized that stent itself may cause or sustain hypertension. Therefore, we aimed to study the hemodynamic and structural impact following stent implantation in the normal aorta of a growing animal.

Methods: Eight female sheep completed the study and a stent was implanted in four. Every 3 mo we measured blood pressure of the anterior and posterior limbs and left ventricular function by echocardiography. Twelve months later invasive pressure was measured under baseline and simulated stress conditions. Expression of genes indicating oxidative stress (OS), endothelial dysfunction (ED) and stiffness, as well as pathological examination were performed in ascending (ASAO) and descending aorta (DSAO).

Results: SOD1 and MMP9 gene expression were higher in ASAO of the stented animals, compared to DSAO and controls, while NOS3 was decreased. No differences were found in blood pressure and echocardiographic parameters. No histological differences were found in the aorta of the two groups of animals.

Conclusions: Stent does not affect central and peripheral hemodynamics, cardiac structure and function even in the long term. However, the finding of markers of OS and increased stiffness of ASAO, proximal to the stent, points to molecular mechanisms for increased cardiovascular risk of patients with stented CoAo.
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http://dx.doi.org/10.1111/chd.12406DOI Listing
January 2017

The Development of a Recombinant scFv Monoclonal Antibody Targeting Canine CD20 for Use in Comparative Medicine.

PLoS One 2016 19;11(2):e0148366. Epub 2016 Feb 19.

University of Edinburgh, Institute of Genetic and Molecular Medicine and School of Veterinary Medicine, Edinburgh, EH4 2XR, United Kingdom.

Monoclonal antibodies are leading agents for therapeutic treatment of human diseases, but are limited in use by the paucity of clinically relevant models for validation. Sporadic canine tumours mimic the features of some human equivalents. Developing canine immunotherapeutics can be an approach for modeling human disease responses. Rituximab is a pioneering agent used to treat human hematological malignancies. Biologic mimics that target canine CD20 are just being developed by the biotechnology industry. Towards a comparative canine-human model system, we have developed a novel anti-CD20 monoclonal antibody (NCD1.2) that binds both human and canine CD20. NCD1.2 has a sub-nanomolar Kd as defined by an octet red binding assay. Using FACS, NCD1.2 binds to clinically derived canine cells including B-cells in peripheral blood and in different histotypes of B-cell lymphoma. Immunohistochemical staining of canine tissues indicates that the NCD1.2 binds to membrane localized cells in Diffuse Large B-cell lymphoma, Marginal Zone Lymphoma, and other canine B-cell lymphomas. We cloned the heavy and light chains of NCD1.2 from hybridomas to determine whether active scaffolds can be acquired as future biologics tools. The VH and VL genes from the hybridomas were cloned using degenerate primers and packaged as single chains (scFv) into a phage-display library. Surprisingly, we identified two scFv (scFv-3 and scFv-7) isolated from the hybridoma with bioactivity towards CD20. The two scFv had identical VH genes but different VL genes and identical CDR3s, indicating that at least two light chain mRNAs are encoded by NCD1.2 hybridoma cells. Both scFv-3 and scFv-7 were cloned into mammalian vectors for secretion in CHO cells and the antibodies were bioactive towards recombinant CD20 protein or peptide. The scFv-3 and scFv-7 were cloned into an ADEPT-CPG2 bioconjugate vector where bioactivity was retained when expressed in bacterial systems. These data identify a recombinant anti-CD20 scFv that might form a useful tool for evaluation in bioconjugate-directed anti-CD20 immunotherapies in comparative medicine.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0148366PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4760772PMC
July 2016

Histological and immunohistochemical characterization of feline renal cell carcinoma: a case series.

J Vet Med Sci 2016 Jul 18;78(6):1039-43. Epub 2016 Feb 18.

Department of Comparative Biomedicine and Food Science, University of Padua, Viale dell'Università 16, 35020, Agripolis, Legnaro (PD), Italy.

Four feline renal cell carcinomas (RCCs) were examined using histopathological and immunohistochemical procedures. Specimens were classified by predominant histological pattern according to WHO criteria. A panel of antibodies including β-catenin, C-KIT, VEGF and VEGF-R2 and double immunostaining for vimentin/cytokeratin and for E-cadherin/CD10 was selected to characterize the tumors. Neoplasms were classified as tubular (3/4) and papillary (1/4). Neoplastic epithelial cells were cytokeratin, vimentin, E-cadherin, VEGF-R2 positive and C-KIT negative; 3 cases were β-catenin positive, whereas only 2 tumors were CD10 and VEGF positive. No correlation with histotype was evident. Our results confirm the low frequency of RCCs in cats and suggest a histological pattern similar to canine RCCs. In contrast, a peculiar immunohistochemical profile different from both canine and human RCCs is identified.
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http://dx.doi.org/10.1292/jvms.15-0697DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4937140PMC
July 2016

Quantitative analysis of ultrasonographic images and cytology in relation to histopathology of canine and feline liver: An ex-vivo study.

Res Vet Sci 2015 Dec 19;103:164-9. Epub 2015 Oct 19.

Department of Animal Medicine, Production and Health, University of Padua, Viale dell'Università 16, Legnaro, PD 35020, Italy. Electronic address:

The aims of the present study were to investigate, in a standardized experimental condition, the usefulness of histogram analysis on ex-vivo ultrasonographic images of the liver of dogs and cats compared with histological alterations and to evaluate whether the combination of histogram parameters and cytology might improve diagnostic accuracy referring to optical microscopy as gold standard. Histogram-based parameters were calculated on ultrasonographic images of liver tissue samples collected from the cadavers of 68 dogs and 31 cats. Standard deviation of the histogram (SDH) had a higher sensitivity and specificity in the detection of the lesions in cat compared with dog. Matched results of cytology and SDH improved sensitivity and specificity in dog where as no substantial improvement was evident in cat. Quantitative analysis of ultrasonographic images of the liver in dog and cat could become a potentially useful tool in the distinction between normal and pathological organs.
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http://dx.doi.org/10.1016/j.rvsc.2015.10.002DOI Listing
December 2015

Transformation of Canine Lymphoma/Leukemia to More Aggressive Diseases: Anecdotes or Reality?

Front Vet Sci 2015 7;2:42. Epub 2015 Oct 7.

Centro Oncologico Veterinario , Sasso Marconi , Italy.

Transformation is the evolution of an indolent lymphoma/leukemia to an aggressive lymphoma, typically harboring a very poor prognosis. This phenomenon is well described in humans, but underestimated in dogs although recognized as a possible evolution of indolent lymphomas/leukemias. In canine chronic leukemias, blast crisis (mainly in myeloid) and Richter syndrome (transformation into a high grade lymphoma) (mainly in B-cell lymphocytic leukemia) have been reported. Transformation is a possible event also in canine low grade lymphomas, although rare. The increased knowledge has also generated new questions and posed challenges that need to be addressed to improve outcome, including the recognition of the clinical characteristics at diagnosis associated with a higher risk of transformation in an attempt of anticipating the typical evolution.
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http://dx.doi.org/10.3389/fvets.2015.00042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4672227PMC
December 2015

Analytical and diagnostic validation of a flow cytometric strategy to quantify blood and marrow infiltration in dogs with large B-cell lymphoma.

Cytometry B Clin Cytom 2016 11 3;90(6):525-530. Epub 2016 Feb 3.

Department of Veterinary Sciences and Public Health, University of Milan, Italy.

Background: Lymph node (LN), peripheral blood (PB), and bone marrow (BM) samples are commonly analyzed by flow cytometry (FC) for the immunophenotyping and staging of canine lymphomas. A prognostic value for FC BM infiltration in dogs with large B-cell lymphoma (LBCL) was demonstrated. Aim of this study was to define the analytical performances of this technique, and to establish a cutoff suitable to safely discriminate between infiltrated and noninfiltrated PB and BM samples.

Methods: Large B-cells were added to control PB and BM samples, to achieve twelve different large B-cells concentrations, ranging from 0 to 50%. The percentage of large B-cells was recorded for each dilution, using a BD Accuri C6 FC. Accuracy was evaluated by Passing-Bablok regression analysis. Intra-assay precision was assessed at 0%, 1, 3, and 10% dilutions evaluating the CVs of 10 repeated acquisitions. ROC curves were drawn to identify the cutoffs most suitable to discriminate between 25 infiltrated (PARR-positive) and 25 noninfiltrated (PARR-negative) PB and BM samples, respectively.

Results: Optimal analytical accuracy and precision were achieved. Almost all CVs were <10%. Negative controls had up to 0.5% large B-cells, with 50 and 22% CV in PB and BM samples, respectively, 0.56 and 2.45% cutoffs were selected based on the ROC curves for PB and BM samples, respectively.

Conclusions: Quantification of large B-cells in PB and BM samples by FC is reliable and analytical performances met the acceptance criteria. Assessment of performances of different instruments and protocols is warranted. © 2016 International Clinical Cytometry Society.
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http://dx.doi.org/10.1002/cyto.b.21353DOI Listing
November 2016

Peripheral blood lymphocyte/monocyte ratio as a useful prognostic factor in dogs with diffuse large B-cell lymphoma receiving chemoimmunotherapy.

Vet J 2015 Nov 14;206(2):226-30. Epub 2015 Jul 14.

Department of Comparative Biomedicine and Food Science, University of Padova, Viale dell'Università 16, 35020 Agripolis Legnaro (PD), Italy.

Diffuse large B-cell lymphoma (DLBCL) is the most frequent canine lymphoid neoplasm. Despite treatment, the majority of dogs with DLBCL experience tumour relapse and consequently die, so practical models to characterise dogs with a poor prognosis are needed. This study examined whether the lymphocyte/monocyte ratio (LMR) can predict outcome in dogs with newly diagnosed DLBCL with regard to time-to-progression (TTP) and lymphoma specific survival (LSS). A retrospective study analysed the prognostic significance of LMR obtained at diagnosis by flow cytometry (based on morphological properties and CD45 expression) in 51 dogs that underwent complete staging and received the same treatment, comprising multi-agent chemotherapy and administration of an autologous vaccine. Dogs with an LMR ≤ 1.2 (30% of all cases) were found to have significantly shorter TTP and LSS, and it was concluded that LMR was a useful independent prognostic indicator with biological relevance in dogs with DLBCL treated with chemoimmunotherapy.
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http://dx.doi.org/10.1016/j.tvjl.2015.07.009DOI Listing
November 2015

Characterization of Proteinuria in Dogue de Bordeaux Dogs, a Breed Predisposed to a Familial Glomerulonephropathy: A Retrospective Study.

PLoS One 2015 16;10(7):e0133311. Epub 2015 Jul 16.

Department of Companion Animal Clinical Sciences, Faculty of Veterinary Medicine, University of Liège, Liège, Belgium.

Dogue de Bordeaux dog has been reported to be predisposed to a familial glomerulonephropathy that displays some morphological modifications reported in focal and segmental glomerulosclerosis. Prevalence of quantitatively abnormal renal proteinuria was recently reported to be 33% in this breed. The nature of the proteinuria was assessed by sodium dodecyl sulfate-agarose gel electrophoresis and determinations of urinary markers (urinary retinol-binding protein, urinary N-acetyl-β-glucosaminidase, urinary albumin and urinary immunoglobulin G) on stored specimens. Diagnostic performances of sodium dodecyl sulfate-agarose gel electrophoresis to identify dogs with elevated urinary biomarkers were assessed. Samples from 102 adult Dogue de Bordeaux dogs (47 non-proteinuric [urine protein-to-creatinine ratio ≤ 0.2], 20 borderline-proteinuric [0.2< urine protein-to-creatinine ratio ≤ 0.5] and 35 proteinuric dogs [urine protein-to-creatinine ratio >0.5]) were used, of which 2 were suffering from familial glomerulonephropathy. The electrophoretic protein patterns, for all but one proteinuric dog, were indicative of a glomerular origin and, in all dogs, the urinary albumin concentration related to creatinine concentration and the urinary immunoglobulin G concentration related to creatinine concentration were above the upper limit of the reference interval established for the breed. Sensitivity and specificity of sodium dodecyl sulfate-agarose gel electrophoresis identifying dogs with elevated urinary albumin concentration were 94% and 92%, respectively, while diagnostic performance of sodium dodecyl sulfate-agarose gel electrophoresis in detecting dogs with elevated urinary immunoglobulin G concentration yielded sensitivity and specificity of 90% and 74%, respectively. These results suggest that all proteinuric and some borderline-proteinuric Dogue de Bordeaux dogs likely have underlying glomerular lesions and that sodium dodecyl sulfate-agarose gel electrophoresis and urinary markers might be useful to screen dogs with borderline-proteinuria. Additional investigations are warranted to assess if these findings are related to the familial glomerulonephropathy.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0133311PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4504498PMC
April 2016

Correlation of renal histopathology with renal echogenicity in dogs and cats: an ex-vivo quantitative study.

BMC Vet Res 2015 Apr 25;11:99. Epub 2015 Apr 25.

Department of Comparative Biomedicine and Food Science, University of Padua, Viale dell'Università 16, Legnaro (PD), 35020, Italy.

Background: Increased cortical or cortical and medullary echogenicity is one of the most common signs of chronic or acute kidney disease in dogs and cats. Subjective evaluation of the echogenicity is reported to be unreliable. Patient and technical-related factors affect in-vivo quantitative evaluation of the echogenicity of parenchymal organs. The aim of the present study is to investigate the relationship between histopathology and ex-vivo renal cortical echogenicity in dogs and cats devoid of any patient and technical-related biases.

Results: Kidney samples were collected from 68 dog and 32 cat cadavers donated by the owners to the Veterinary Teaching Hospital of the University of Padua and standardized ultrasonographic images of each sample were collected. The echogenicity of the renal cortex was quantitatively assessed by means of mean gray value (MGV), and then histopathological analysis was performed. Statistical analysis to evaluate the influence of histological lesions on MGV was performed. The differentiation efficiency of MGV to detect pathological changes in the kidneys was calculated for dogs and cats. Statistical analysis revealed that only glomerulosclerosis was an independent determinant of echogenicity in dogs whereas interstitial nephritis, interstitial necrosis and fibrosis were independent determinants of echogenicity in cats. The global influence of histological lesions on renal echogenicity was higher in cats (23%) than in dogs (12%).

Conclusions: Different histopathological lesions influence the echogenicity of the kidneys in dogs and cats. Moreover, MGV is a poor test for distinguishing between normal and pathological kidneys in the dog with a sensitivity of 58.3% and specificity of 59.8%. Instead, it seems to perform globally better in the cat, resulting in a fair test, with a sensitivity of 80.6% and a specificity of 56%.
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http://dx.doi.org/10.1186/s12917-015-0415-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4413530PMC
April 2015

Perspectives on the design of clinical trials for targeted therapies and immunotherapy in veterinary oncology.

Vet J 2015 Aug 3;205(2):238-43. Epub 2015 Mar 3.

Department of Comparative Biomedicine and Food Science, University of Padova, Viale dell'Università 16, 35020 Agripolis Legnaro (PD), Italy.

The field of oncology research has undergone major changes in recent years. Progress in molecular and cellular biology has led to a greater understanding of the cellular pathways and mechanisms of cell proliferation and tissue invasion associated with cancer. New classes of cancer therapies are becoming available or are in development but these new agents require a paradigm shift in the design of oncology clinical trials. This review provides an overview of clinical trial designs for the development of tumour vaccines and targeted therapeutic agents. In addition, some of the successes, limitations and challenges of these trials are discussed, with a special emphasis on the difficulties and particularities that are encountered in veterinary medicine compared to similar work in human patients.
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http://dx.doi.org/10.1016/j.tvjl.2015.02.020DOI Listing
August 2015

Array-based comparative genomic hybridization analysis reveals chromosomal copy number aberrations associated with clinical outcome in canine diffuse large B-cell lymphoma.

PLoS One 2014 5;9(11):e111817. Epub 2014 Nov 5.

Department of Comparative Biomedicine and Food Science, University of Padova, Padova, Italy.

Canine Diffuse Large B-cell Lymphoma (cDLBCL) is an aggressive cancer with variable clinical response. Despite recent attempts by gene expression profiling to identify the dog as a potential animal model for human DLBCL, this tumor remains biologically heterogeneous with no prognostic biomarkers to predict prognosis. The aim of this work was to identify copy number aberrations (CNAs) by high-resolution array comparative genomic hybridization (aCGH) in 12 dogs with newly diagnosed DLBCL. In a subset of these dogs, the genetic profiles at the end of therapy and at relapse were also assessed. In primary DLBCLs, 90 different genomic imbalances were counted, consisting of 46 gains and 44 losses. Two gains in chr13 were significantly correlated with clinical stage. In addition, specific regions of gains and losses were significantly associated to duration of remission. In primary DLBCLs, individual variability was found, however 14 recurrent CNAs (>30%) were identified. Losses involving IGK, IGL and IGH were always found, and gains along the length of chr13 and chr31 were often observed (>41%). In these segments, MYC, LDHB, HSF1, KIT and PDGFRα are annotated. At the end of therapy, dogs in remission showed four new CNAs, whereas three new CNAs were observed in dogs at relapse compared with the previous profiles. One ex novo CNA, involving TCR, was present in dogs in remission after therapy, possibly induced by the autologous vaccine. Overall, aCGH identified small CNAs associated with outcome, which, along with future expression studies, may reveal target genes relevant to cDLBCL.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0111817PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4221131PMC
July 2015

Minimal residual disease detection by flow cytometry and PARR in lymph node, peripheral blood and bone marrow, following treatment of dogs with diffuse large B-cell lymphoma.

Vet J 2014 May 31;200(2):318-24. Epub 2014 Mar 31.

Centro Oncologico Veterinario, via San Lorenzo 1-4, 40037 Sasso Marconi (BO), Italy.

The most promising techniques for detecting minimal residual disease (MRD) in canine lymphoma are flow cytometry (FC) and polymerase chain reaction amplification of antigen receptor genes (PARR). However, the agreement between these methods has not been established. MRD was monitored by FC and PARR following treatment of dogs affected with diffuse large B-cell lymphoma (DLBCL), comparing results in lymph node (LN), peripheral blood (PB) and bone marrow (BM) samples. The prognostic impact of MRD on time to relapse (TTR) and lymphoma-specific survival (LSS) was also assessed. Fourteen dogs with previously untreated DLBCL were enrolled into the study; 10 dogs eventually relapsed, while four dogs with undetectable MRD were still in remission at the end of the study. At diagnosis, the concordance rate between FC and PARR was 100%, 78.6%, and 64.3% for LN, PB and BM, respectively. At the end of treatment, the agreement rates were 35.7%, 50%, and 57.1% for LN, PB and BM, respectively. At least one of the follow-up samples from dogs experiencing relapse was PARR(+); conversely, FC was not able to detect MRD in seven of the dogs that relapsed. PARR was more sensitive than FC in predicting TTR, whereas the combination of PARR and FC was more sensitive than either technique alone in predicting LSS using PB samples. The results suggest that immunological and molecular techniques should be used in combination when monitoring for MRD in canine DLBCL.
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http://dx.doi.org/10.1016/j.tvjl.2014.03.006DOI Listing
May 2014

Epigenetic silencing of TFPI-2 in canine diffuse large B-cell lymphoma.

PLoS One 2014 2;9(4):e92707. Epub 2014 Apr 2.

Department of Comparative Biomedicine and Food Science, University of Padova, Padova, Italy.

Epigenetic modifications are important early events during carcinogenesis. In particular, hypermethylation of CpG islands in the promoter region of tumor suppressor genes is a well-known mechanism of gene silencing that contributes to cancer development and progression. Tissue factor pathway inhibitor 2 (TFPI-2) is a tumor suppressor involved in invasiveness inhibition. Although TFPI-2 transcriptional silencing, through promoter hypermethylation, has been widely reported in several human malignancies, it has never been explored in lymphoma. In the present study TFPI-2 methylation and gene expression have been investigated in canine Diffuse Large B-cell lymphomas (cDLBCL). The methylation level of 23 CpGs located within the TFPI-2 promoter was investigated by bisulfite-specific PCR and next generation amplicon deep sequencing (GS Junior 454, Roche) in 22 cDLBCLs and 9 controls. For the same specimens, TFPI-2 gene expression was assessed by means of Real-time RT-PCR. Sequence analysis clearly demonstrated that TFPI2 is frequently hypermethylated in cDLBCL. Hypermethylation of the TFPI-2 promoter was found in 77% of DLBCLs (17 out of 22) and in one normal lymph node. Globally, dogs with DLBCL showed a mean methylation level significantly increased compared to controls (p<0.01) and analysis of hypermethylation by site identified 19 loci out of 23 (82%) with mean methylation levels from 2- to 120-fold higher in cDLBCL. Gene expression analysis confirmed a significant down-regulation of TFPI-2 (p<0.05) in DLBCLs compared with normal lymph nodes, suggesting that TFPI-2 hypermethylation negatively regulates its transcription. In addition, a significant positive correlation (p<0.01) was found between TFPI-2 methylation levels and age providing the first indication of age-associated epigenetic modifications in canine DLBCL. To conclude, our findings demonstrated that epigenetic dysregulation of TFPI-2, leading to its reduced expression, is frequently detected in canine DLBCL. In the next future, the aberrant TFPI-2 promoter hypermethylation may be considered in association with prognosis and therapy.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0092707PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3973630PMC
February 2015

Randomized, placebo-controlled, double-blinded chemoimmunotherapy clinical trial in a pet dog model of diffuse large B-cell lymphoma.

Clin Cancer Res 2014 Feb 3;20(3):668-77. Epub 2013 Dec 3.

Authors' Affiliations: Centro Oncologico Veterinario, Sasso Marconi, Bologna; Department of Veterinary Sciences and Public Health, University of Milan; Department of Comparative Biomedicine and Food Science, University of Padova, Italy; Urodelia, St Lys, France; and Epidemiology advisor, London, United Kingdom.

Purpose: Active immunotherapy is a promising antitumoral strategy; however its use in combination with chemotherapy in dogs with large B-cell lymphoma (DLBCL) remains largely untested. Heat shock proteins (HSP) bind the small peptides they chaperone (HSPPC), allowing for immunization of the host against a large repertoire of tumor-associated antigens. Hydroxylapatite vehicles HSPPCs and acts as an immunologic adjuvant. The aim of this study was to show that an autologous vaccine with hydroxylapatite and tumor-derived HSPPCs is safe and therapeutically effective in dogs with DLBCL.

Experimental Design: Nineteen dogs with naturally occurring DLBCL were entered into a prospective randomized placebo-controlled double-blinded trial of HSPPCs-hydroxylapatite plus chemotherapy versus chemotherapy alone. Endpoints included time to progression (TTP), lymphoma-specific survival (LSS), and incidence of toxicoses.

Results: Median first TTP after randomization to the vaccine arm was 304 days versus 41 days for the control arm (P = 0.0004). There was also a statistically significant difference in duration of second remission between the two groups (P = 0.02). Median LSS was 505 days for the vaccinated dogs versus 159 days for the unvaccinated dogs (P = 0.0018). Six vaccinated dogs achieved molecular remission, as shown by clonal immunoglobulin H (IgH) rearrangement. Toxicoses were comparable between the two treatment arms.

Conclusions: The results of this trial demonstrate that the autologous vaccine tested here is safe and efficacious in prolonging TTP and LSS in dogs with DLBCL when used in combination with dose-intense chemotherapy. On the basis of these results, additional evaluation of this novel therapeutic strategy is warranted in human DLBCL.
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http://dx.doi.org/10.1158/1078-0432.CCR-13-2283DOI Listing
February 2014

Assessment of bone marrow infiltration diagnosed by flow cytometry in canine large B cell lymphoma: prognostic significance and proposal of a cut-off value.

Vet J 2013 Sep 2;197(3):776-81. Epub 2013 Jun 2.

Centro Oncologico Veterinario, via San Lorenzo 1-4, 40037 Sasso Marconi, BO, Italy. Electronic address:

The aims of this study were to assess the prognostic significance of bone marrow (BM) infiltration in canine large B cell lymphoma (LBCL) and to establish cut-off values for designating the BM as infiltrated by lymphoid blasts. The degree of BM infiltration by large CD21 positive cells in dogs with LBCL was assessed by flow cytometry (FC) and related to time to progression (TTP) and lymphoma-specific survival (LSS). Forty-six dogs were prospectively enrolled, staged and treated with a dose-intense chemotherapeutic protocol. BM infiltration was directly correlated with peripheral blood infiltration (P=0.001), high lactate dehydrogenase activity (P=0.0024) and substage b disease (P<0.001). In the univariate analysis, there was a significant association between BM infiltration diagnosed by FC and both TTP (P=0.001) and LSS (P<0.001). Substage was the only factor associated with TTP in the multivariate analysis (P=0.002), whereas substage (P<0.001) and anaemia (P=0.008) were associated with LSS. A cut-off of 3% BM infiltration had the strongest prognostic value, since it discriminated between dogs with a poorer prognosis (median TTP 69 days; median LSS 155 days) and dogs with a better prognosis (median TTP 149 days; median LSS 322 days). BM analysis is an essential step in the staging of LBCL. The presence of BM infiltration by FC at diagnosis is a negative prognostic indicator in canine LBCL.
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http://dx.doi.org/10.1016/j.tvjl.2013.05.003DOI Listing
September 2013

The role of vascular endothelial growth factor and matrix metalloproteinases in canine lymphoma: in vivo and in vitro study.

BMC Vet Res 2013 May 3;9:94. Epub 2013 May 3.

Department of Comparative Biomedicine and Food Science, University of Padova, Viale dell'Università 16, Agripolis Legnaro, PD, Italy.

Background: Canine lymphoma represents the most frequent haematopoietic cancer and it shares some similarities with human non-Hodgkin lymphoma. Matrix metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF) play a coordinated role during invasion and proliferation of malignant cells; however, little is known about their role in canine haematologic malignancies. The aim of this study was to investigate the mRNA and protein expression of VEGF and the most relevant MMPs in canine lymphoma. Lymph node aspirates from 26 B-cell and 21 T-cell lymphomas were collected. The protein expression levels of MMP-9, MMP-2 and VEGF-A were evaluated by immunocytochemistry, and the mRNA levels of MMP-2, MMP-9, MT1-MMP, TIMP-1, TIMP-2, RECK, VEGF-A and VEGF-164 were measured using quantitative RT-PCR.

Results: MT1-MMP, TIMP-1 and RECK mRNA levels were significantly higher in T-cell lymphomas than in B-cell lymphomas. Higher mRNA and protein levels of MMP-9 and VEGF-A were observed in T-cell lymphomas than in B-cell lymphomas and healthy control lymph nodes. A positive correlation was found between MMP-9 and VEGF-A in T-cell lymphomas. Moreover, MMP-9, MT1-MMP, TIMP-1 and VEGF-A were expressed at the highest levels in high-grade T-cell lymphomas.

Conclusions: This study provides new information on the expression of different MMPs and VEGF in canine lymphoma, suggesting a possible correlation between different MMPs and VEGF, immunophenotype and prognosis.
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http://dx.doi.org/10.1186/1746-6148-9-94DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3659052PMC
May 2013

Use of quantitative contrast-enhanced ultrasonography to detect diffuse renal changes in Beagles with iatrogenic hypercortisolism.

Am J Vet Res 2013 Jan;74(1):70-7

Department of Veterinary Medical Imaging and Small Animal Orthopedics, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.

Objective: To determine the feasibility of quantitative contrast-enhanced ultrasonography (CEUS) for detection of changes in renal blood flow in dogs before and after hydrocortisone administration.

Animals: 11 Beagles.

Procedure: Dogs were randomly assigned to 2 treatment groups: oral administration of hydrocortisone (9.6 mg/kg; n = 6) or a placebo (5; control group) twice a day for 4 months, after which the dose was tapered until treatment cessation at 6 months. Before treatment began and at 1, 4, and 6 months after, CEUS of the left kidney was performed by IV injection of ultrasonography microbubbles. Images were digitized, and time-intensity curves were generated from regions of interest in the renal cortex and medulla. Changes in blood flow were determined as measured via contrast agent (baseline [background] intensity, peak intensity, area under the curve, arrival time of contrast agent, time-to-peak intensity, and speed of contrast agent transport).

Results: Significant increases in peak intensity, compared with that in control dogs, were observed in the renal cortex and medulla of hydrocortisone-treated dogs 1 and 4 months after treatment began. Baseline intensity changed similarly. A significant increase from control values was also apparent in area under the curve for the renal cortex 4 months after hydrocortisone treatment began and in the renal medulla 1 and 4 months after treatment began. A significant time effect with typical time course was observed, corresponding with the period during which hydrocortisone was administered. No difference was evident in the other variables between treated and control dogs.

Conclusions And Clinical Relevance: Quantitative CEUS allowed detection of differences in certain markers of renal blood flow between dogs treated orally with and without hydrocortisone. Additional studies are needed to investigate the usefulness of quantitative CEUS in the diagnosis of diffuse renal lesions.
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http://dx.doi.org/10.2460/ajvr.74.1.70DOI Listing
January 2013

Matrix metalloproteinases and vascular endothelial growth factor expression in canine leukaemias.

Vet J 2013 May 8;196(2):260-2. Epub 2012 Nov 8.

Department of Comparative Biomedicine and Food Science, University of Padova, Viale dell'Università 16, 35020 Agripolis Legnaro (PD), Italy.

Matrix metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF) play a coordinated role during neoplastic invasion and proliferation. VEGF and MMPs expression was investigated in canine leukaemias by immunocytochemistry (MMP-9, MMP-2, VEGF-A) and quantitative RT-PCR (MMP-2, MMP-9, MT1-MMP, TIMP-1, TIMP-2, RECK, VEGF-A, VEGF-164). Blood samples were obtained from dogs with acute leukaemia (AL; n = 11) and chronic lymphocytic leukaemia (CLL; n = 12). Levels of MMP-9, TIMP-1 and VEGF-A were higher in CLL than AL and controls. Expression of TIMP-2 and MT1-MMP mRNA was significantly higher in AL than CLL. Significant positive correlations were found between MMP-9 and TIMP-1 and between MMP-9 and VEGF-A in CLL. These results suggest a potential role of MMP-9, MT1-MMP, TIMP-1, TIMP-2 and VEGF in tissue migration and angiogenesis in canine leukaemia.
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http://dx.doi.org/10.1016/j.tvjl.2012.10.004DOI Listing
May 2013

The role of inflammation and matrix metalloproteinases in equine endometriosis.

J Vet Sci 2012 Jun;13(2):171-7

Dipartimento di Sanità Pubblica, Patologia Comparata e Igiene Veterinaria, Facoltà di Medicina Veterinaria, Viale dell'Università, 16-35020-Legnaro (Padova) 049-8272963, Italy.

Equine endometriosis is a multifactorial disease considered to be a major cause of equine infertility. The purpose of this study was to evaluate the reliability of histomorphological grading for biopsy-like samples compared to entire uterine wall samples, to examine the association between the degree of endometriosis with animal age, and to investigate the role of inflammation in endometriosis and the expression of different matrix metalloproteinases in equine endometrium. Histomorphological lesions in 35 uterine samples were examined while comparing biopsy-like samples and entire-wall samples. Seventeen uterine samples were stained with antibodies against MMP-2, MMP-9, MMP-14, and TIMP-2. The morphologic evaluation results of the biopsy-like tissue and entire-wall samples were significantly correlated. Endometriosis in older mares (>12 years of age) was more severe than in young mares (2 ~ 4 years of age), confirming the positive correlation between animal age and disease severity, while inflammation was poorly related to the degree of endometriosis. MMP-2 and MMP-14 were detected in stromal cells, while MMP-9 and TIMP-2 were both found in stromal and glandular epithelial cells. There were no significant differences in MMPs expression between the two groups (young vs. old mares). Additional studies on the activity of MMPs could further define the role of these enzymes in equine endometriosis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3386342PMC
http://dx.doi.org/10.4142/jvs.2012.13.2.171DOI Listing
June 2012

Physiological performance of a detergent decellularized heart valve implanted for 15 months in Vietnamese pigs: surgical procedure, follow-up, and explant inspection.

Artif Organs 2012 Jun 18;36(6):E138-50. Epub 2012 Apr 18.

Department of Cardiac, Thoracic, and Vascular Science, University of Padova, 2 via Giustiniani, Padua, Italy.

This study features the longest experimental follow-up for decellularized heart valves implanted in an animal model. Porcine aortic heart valves were decellularized according to a disclosed standardized method in which TRITON X-100 and sodium cholate (TRICOL) are used in succession, followed by a further treatment with the endonuclease Benzonase to completely remove the nucleic acid remnants. Experimental animals (n = 17), represented by Vietnamese pigs (VPs), received a decellularized aortic allograft as a substitute for the replacement of their right ventricular outflow tract. The surgical implantation of the TRICOL-treated aortic valve conduit was successful in 11 VPs, while perioperative or postoperative complications occurred in the remaining six animals. In the sham-operated group (n = 4), the native pulmonary root was excised and immediately reimplanted orthotopically in the same animal. Echocardiography demonstrated a satisfactory hemodynamic performance of the TRICOL-treated valves during follow-up as well as the absence of relevant leaflet alterations concerning thickness and motility or valve insufficiency. At explantation, macroscopic inspection of tissue-engineered heart valve conduits did not evidence calcifications and showed a decreased wall thickness, comparable to that of the reimplanted native pulmonary roots. Noteworthy, extended functional performance, recovery of DNA content, and active extracellular matrix precursor incorporation are apparently compatible with the properties of a living self-supporting substitute.
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http://dx.doi.org/10.1111/j.1525-1594.2012.01447.xDOI Listing
June 2012

Renal function and morphology in aged Beagle dogs before and after hydrocortisone administration.

PLoS One 2012 29;7(2):e31702. Epub 2012 Feb 29.

Department of Small Animal Medicine and Clinical Biology, Faculty of Veterinary Medicine, Ghent University, Salisburylaan, Merelbeke, Belgium.

Objectives of this study were to evaluate glomerular filtration rate (GFR), renal structural changes and proteinuria in aged Beagle dogs before and after hydrocortisone (HC) administration. Eleven Beagle dogs ≥10 years old were treated with either hydrocortisone (HC group, n = 6) or placebo (control group, n = 5). Urinary markers, GFR and kidney biopsies were evaluated before (T0), during (T16 wks) and after discontinuing HC administration (T24 wks). Results indicate that HC administration causes a significant increase in GFR. At all time points except T16 wks, proteinuria was higher in the control group than in the HC group, and there was no significant difference in urinary markers between groups. At T16 wks, proteinuria, urinary albumin-to-creatinine (c) ratio, immunoglobulin G/c and retinol-binding protein/c were higher compared to baseline in the HC group. At T0, rare to mild renal lesions were detected in all HC dogs and rare to moderate changes in all control dogs. Glomerulosclerosis progressed in both groups until T24 wks. Tubular atrophy was detected in three HC dogs at T16 wks and T24 wks, but also in five control dogs throughout the study. At every time point, five HC dogs and all control dogs had rare to moderate interstitial inflammation. Rare to mild interstitial fibrosis was found in up to three HC dogs at T16 wks and T24 wks, and severe fibrosis in one HC dog at T24 wks. Up to four control dogs had rare to mild fibrosis at all time points. These findings indicate that clinically healthy, aged Beagle dogs may have considerable renal lesions and proteinuria, which could have implications for experimental or toxicological studies. Additional research is needed to elucidate glucocorticoid effects on renal structure, but functional changes such as hyperfiltration and proteinuria warrant attention to kidney function of canine patients with Cushing's syndrome or receiving exogenous glucocorticoids.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0031702PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3290534PMC
July 2012

Juvenile nephropathy in a Boxer dog resembling the human nephronophthisis-medullary cystic kidney disease complex.

J Vet Med Sci 2011 Dec 11;73(12):1669-75. Epub 2011 Aug 11.

Centro Nefrologico Veterinario, Catania, Italy.

A juvenile nephropathy in a 4-year-old male Boxer dog, closely resembling the Nephronophthisis (NPHP)-Medullary Cystic Kidney Disease Complex (MCKD) in humans is described. Gross examination of the kidneys revealed several multiple cysts at the corticomedullary junction and in the medulla. Histological examination was characterized by a widespread tubular atrophy and dilatation, with a marked thickening of the tubular basement membrane, interstitial lymphocytic infiltration and fibrosis. Ultrastructural studies revealed dilated tubules with irregular basement membrane thickening and splitting. Lectin histochemistry investigation revealed that the cysts originated in the distal convoluted tubule and collecting duct. Having excluded all other known cystic diseases of the kidney, and based on the lectin histochemistry results, the macroscopic and histological findings of our case are highly compatible with a diagnosis of the NPHP-MCKD complex. To our knowledge, this is the first report describing this particular lesion.
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http://dx.doi.org/10.1292/jvms.10-0551DOI Listing
December 2011

Matrix metalloproteinases and their inhibitors in canine mammary tumors.

BMC Vet Res 2011 Jul 4;7:33. Epub 2011 Jul 4.

Dipartimento di Sanità Pubblica, Patologia Comparata e Igiene Veterinaria, Facoltà di Medicina Veterinaria, Università degli Studi di Padova, Padova, Italy.

Background: Malignant canine mammary tumors represent 50% of all neoplasms in female dogs. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are thought to be involved in tumor progression, and they are also associated with the reactive stroma, which provides structural and vascular support for tumor growth.

Results: MMP-2, MMP-9 and MT1-MMP were expressed at both the mRNA and protein levels in tumor samples. MMP-2 and MMP-9 immunohistochemical reactions were evident both in the epithelial tumor cells and in the stromal compartment to varying degrees; in particular, the intensity of the MMP-2 staining was stronger in the stromal fibroblasts close to epithelial tumor cells in simple carcinomas than in adenomas. These data were supported by gelatin-zymography; bands for the active form of MMP-2 were found in 94% of carcinoma samples, compared with 17% of benign tumor samples. The gene expression and immunohistochemical results for MT1-MMP were comparable to those for MMP-2. The immunoreactivity for MMP-13 and TIMP-2 was lower in carcinomas than in adenomas, confirming the mRNA data for MMP-13 and the other MMP inhibitors that were evaluated. The active form of MMP-9, but not the active form of MMP-2, was identified in the plasma of all of the tested dogs.

Conclusions: Our findings suggest that MMP-9, MMP-2 and MT1-MMP, which are synthesized by epithelial cancer cells and cancer-associated fibroblasts, play an important role in malignant canine mammary tumors. The reduction of MMP-13 and TIMP-2 could also be a significant step in malignant transformation. MMP-2 and MT1-MMP could be further evaluated as future biomarkers for predicting the progression and prognosis of canine mammary tumors.
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http://dx.doi.org/10.1186/1746-6148-7-33DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3141405PMC
July 2011

Heartworm (Dirofilaria immitis) infection in a leopard (Panthera pardus pardus) housed in a zoological park in north-eastern Italy.

Parasit Vectors 2010 Apr 8;3(1):25. Epub 2010 Apr 8.

Dipartimento di Scienze Sperimentali Veterinarie, Università degli Studi di Padova; Viale dell'Università, 16 - 35020, Legnaro (Padova), Italy.

Canine heartworm (cHW) disease is now recognised as potential cause of serious disease in cats and other felids, especially in endemic areas. In March 2009, a 23-years-old male African leopard (Panthera pardus pardus) housed in a zoological park located in the Province of Padova (Veneto Region), a cHW endemic area of the north-eastern Italy, died and was immediately necropsied. A cloth completely occluding the pyloric lumen was considered the presumptive cause of death. During necropsy, six nematodes (4 males and 2 females) were found within the right ventricle of the heart and the pulmonary artery. Diagnosis of HW (Dirofilaria immitis) infection was carried out by morphological features of adult worms and microfilariae, and then confirmed by detection of circulating HW antigens using a commercial SNAP kit (IDEXX Laboratories inc., USA). D. immitis infection was also confirmed by PCR amplification of the 5S ribosomal spacer region, performed on worm fragments and microfilaraemic blood samples obtained from the right ventricle of the heart. A glomerulonephritis of immuno-mediated origin and most likely associated with the HW infection is also reported. HW chemoprophylaxis and annual serological testing on wild felids housed outdoors in endemic cHW disease areas are recommended. This is the first diagnosis of D. immitis infection in an exotic felid in Italy.
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http://dx.doi.org/10.1186/1756-3305-3-25DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2858128PMC
April 2010

Suppurative adenitis of preputial glands associated with Corynebacterium mastitidis infection in mice.

J Am Assoc Lab Anim Sci 2010 Jan;49(1):69-74

Department of Veterinary Pathology, Hygiene, and Public Health, Faculty of Veterinary Medicine, Università degli Studi di Milano, Milan, Italy.

Suppuration of the preputial gland in mice occurs as a septic complication of fight wounds around the external genitalia. Currently reported bacterial isolates from these lesions are limited to Staphylococcus aureus, Pasteurella pneumotropica, and Klebsiella oxytoca. In the context of a pilot experiment aimed at defining the aging phenotype of estrogen receptor beta knockout (BERKO) mice, 2 male mice (1 of the BERKO line and the other from the age- and sex-matched wild-type control group) were discovered at necropsy to have preputial gland lesions. In both cases, histopathologic examination confirmed severe suppuration and abscesses of the preputial glands associated with systemic reactive (secondary) amyloidosis. Both Gram staining and Bacillus Calmette-Guérin immunohistochemistry highlighted the presence of numerous bacillary to rod-shaped bacteria within the preputial lesions. Subsequent PCR analysis coupled with denaturing gradient gel electrophoresis identified Corynebacterium mastitidis in the preputial gland abscesses. This organism is isolated infrequently from the milk of sheep with subclinical mastitis and was identified as part of the normal microflora of the human ocular surface. No information regarding the epidemiology and pathogenesis of C. mastitidis infection in laboratory animals is currently available, and to our knowledge this report is the first description of C. mastitidis infection in mice.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2824971PMC
January 2010

Administration of miltefosine and meglumine antimoniate in healthy dogs: clinicopathological evaluation of the impact on the kidneys.

Toxicol Pathol 2009 Oct 18;37(6):770-5. Epub 2009 Aug 18.

In canine leishmaniosis (CanL), kidneys are affected in virtually all dogs. Treatment of CanL is limited in Europe to meglumine antimoniate and miltefosine. This study evaluated the pharmacological, toxicological, and pathological effects of both drugs in healthy beagle dogs. Four male and four female dogs were divided into two groups. The animals in Group 1 were administered an oral solution of 2% of miltefosine at 2 mg/kg b.w. once a day, for twenty-eight days. The animals in Group 2 were administered a preparation of meglumine antimoniate at 100 mg/kg b.w. subcutaneously once a day for twenty-eight days. After treatment, all dogs were followed-up for a further twenty-eight days. Dogs were observed daily and clinically examined ten times throughout the study. On days -1 and 55 a renal biopsy was performed on all dogs and analyzed by light microscopy, immunofluorescence, and electron microscopy. All the examinations failed to demonstrate any lesions in the miltefosine-treated dogs. Conversely, all the meglumine antimoniate-treated dogs demonstrated severe tubular damage, characterized by tubular cell necrosis and apoptosis. In conclusion, although no clinical signs of renal disease were evident, the use of meglumine antimoniate in the pharmacological treatment approach of CanL-affected dogs should be carefully considered.
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http://dx.doi.org/10.1177/0192623309344088DOI Listing
October 2009

Dog as model for down-expression of E-cadherin and beta-catenin in tubular epithelial cells in renal fibrosis.

Virchows Arch 2008 Dec 24;453(6):617-25. Epub 2008 Oct 24.

Dipartimento di Sanità Pubblica, Patologia Comparata e Igiene Veterinaria, Facoltà di Medicina Veterinaria, Università degli Studi di Padova, Agripolis, Padova, Italy.

Mechanism of renal fibrosis leading to end stage kidney remains still a challenge of interest in humans. The pathogenesis of chronic kidney disease is characterized by progressive loss of kidney function and fibrosis. The mechanism of epithelial-mesenchymal transition (EMT) has been predominantly studied in in vitro studies, and we previously demonstrated the EMT of tubular epithelial cells in dogs. In this study, we examined and quantified the modifications of cadherin-catenin complex by immunohistochemistry of E-cadherin and beta-catenin and the mesenchymal marker vimentin in 25 dogs with three different spontaneous inflammatory renal diseases. Results showed a significant down-expression of levels of E-cadherin and beta-catenin directly correlated with the tubular-interstitial damage (TID). In TID grades 2 and 3, E-cadherin expression was significantly reduced (p < 0.001). beta-catenin expression was overall similar to E-cadherin. The mesenchymal-associated protein, vimentin, was de novo identified in tubules within areas of inflammation. In this work, we identified the loss of cadherin or catenin expression as a progressive mechanism in tubulo-interstitial fibrosis, which allows dissociation of structural integrity of renal epithelia and loss of epithelial polarity. The dog might result more significant as model for new therapies.
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http://dx.doi.org/10.1007/s00428-008-0684-8DOI Listing
December 2008

Bilateral juvenile renal dysplasia in a Norwegian Forest Cat.

J Feline Med Surg 2009 Apr 22;11(4):326-9. Epub 2008 Oct 22.

Dipartimento di Patologia Animale, Università degli Studi di Torino, via L. Da Vinci 44, 10095 Grugliasco, Torino, Italy.

Renal dysplasia is defined as a condition of disorganised development of renal parenchyma due to abnormal differentiation. The case of a 5-month-old intact male Norwegian Forest Cat with a history of polyuria and polydipsia is reported. Ultrasonographic examination showed a slight enlargement of kidneys. Biochemical parameters, haematological examinations and clinical signs were compatible with chronic renal failure (CRF). Histological examination was correlated with a primary tubular disorganisation and modification of glomerular compartment. The clinical history together with the histological lesions is consistent with bilateral juvenile renal dysplasia in this cat. To our knowledge, feline renal dysplasia has been reported in fetal infections with panleukopenia virus; no reports indicate the idiopathic origin in feline dysplastic lesions.
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http://dx.doi.org/10.1016/j.jfms.2008.08.004DOI Listing
April 2009