Impact of body weight and sex in selected dog breeds on the canine adrenal gland dimensions measured by computed tomographic imaging.

BACKGROUND: The present study aimed to investigate possible influences of body weight and sex on adrenal gland size in endocrinologically healthy dogs. Possible factors influencing the adrenal size are discussed in relation to a universal upper reference value from the literature of 7.4 mm as the thickness in the caudal pole of the adrenal gland. The adrenal size was measured by computed tomography (CT) from 66 normal dogs of six different breeds (Labrador Retriever (n = 16), German Shepherd (n = 10), Boxer (n = 8), Beagle (n = 14), Dachshund (n = 6) and Jack Russell Terrier (n = 12); male n = 38 (thereof neutered n = 23), female n = 28 (thereof neutered n = 17)) based on volume quantification and linear measurements using the data processing software Amira. For interbreed comparability, a ratio consisting of the third root of adrenal volume to aortic diameter (Ratio volume-aorta, RVA) was introduced. Additionally, breed-related attenuation values in contrast-enhanced CT data sets were measured. RESULTS: The measured volumes ranged from 0.34 to 1.93 cm3 for the right and from 0.39 to 2.23 cm3 for the left adrenal gland. The present study was able to demonstrate a body weight effect on the adrenal volume as well as on length and height. In terms of adrenal size, no significant differences between male and female, nor between intact and neutered dogs were obtained due to the RVA. In addition, for the weight classes, a breed independent threshold for dogs less (left 1.4; right gland 1.5) or more than 20 kg body weight (left 1.1; right gland 1.2) based on RVA was defined. Breed-related significant differences with respect to attenuation were determined only for the left adrenal gland, with lower attenuation values in large dog breeds. CONCLUSION: The present study points out the importance of weight-related data when assessing CT data of the canine adrenal gland regarding volume, size and attenuation. The use of a universal reference value for the assessment of adrenal size appears unsuitable considering weight-related volume and linear measurements. Sex seems not to affect adrenal gland size.

Left Ventricular Wall Reconstruction with Autologous Vascularized Tunica Muscularis of Stomach in a Porcine Pilot Model.

INTRODUCTION: Surgical replacement of dysfunctional cardiac muscle with regenerative tissue is an important option to combat heart failure. But, current available myocardial prostheses like a Dacron or a pericardium patch neither have a regenerative capacity nor do they actively contribute to the heart's pump function. This study aimed to show the feasibility of utilizing a vascularized stomach patch for transmural left ventricular wall reconstruction. METHODS: A left ventricular transmural myocardial defect was reconstructed by performing transdiaphragmatic autologous transplantation of a vascularized stomach segment in six Lewe minipigs. Three further animals received a conventional Dacron patch as a control treatment. The first 3 animals were followed up for 3 months until planned euthanasia, whereas the observation period for the remaining 3 animals was scheduled 6 months following surgery. Functional assessment of the grafts was carried out via cardiac magnetic resonance tomography and angiography. Physiological remodeling was evaluated histologically and immunohistochemically after heart explantation. RESULTS: Five out of six test animals and all control animals survived the complex surgery and completed the follow-up without clinical complications. One animal died intraoperatively due to excessive bleeding. No animal experienced rupture of the stomach graft. Functional integration of the heterotopically transplanted stomach into the surrounding myocardium was observed. Angiography showed development of connections between the gastric graft vasculature and the coronary system of the host cardiac tissue. CONCLUSIONS: The clinical results and the observed physiological integration of gastric grafts into the cardiac structure demonstrate the feasibility of vascularized stomach tissue as myocardial prosthesis. The physiological remodeling indicates a regenerative potential of the graft. Above all, the connection of the gastric vessels with the coronary system constitutes a rationale for the use of vascularized and, therefore, viable stomach tissue for versatile tissue engineering applications.

MDR1 Inhibition Reverses Doxorubicin-Resistance in Six Doxorubicin-Resistant Canine Prostate and Bladder Cancer Cell Lines.

Acquired chemoresistance during chemotherapy, often accompanied by cross- and multi-resistance, limits therapeutic outcomes and leads to recurrence. In order to create in vitro model systems to understand acquired doxorubicin-resistance, we generated doxorubicin-resistant sublines of canine prostate adenocarcinoma and urothelial cell carcinoma cell lines. Chemoresistance to doxorubicin, cross-resistance to carboplatin, and the reversibility of the acquired resistance by the specific MDR1-inhibitor tariquidar were quantified in metabolic assays. Resistance mechanisms were characterized by expression of the efflux transporters MDR1 and RALBP1, as well as the molecular target of doxorubicin, TOP2A, with qPCR and Western blotting. Six out of nine cell lines established stable resistance to 2 µM doxorubicin. Drug efflux via massive MDR1 overexpression was identified as common, driving resistance mechanism in all sublines. MDR1 inhibition with tariquidar extensively reduced or reversed the acquired, and also partly the parental resistance. Three cell lines developed additional, non-MDR1-dependent resistance. RALBP1 was upregulated in one resistant subline at the protein level, while TOP2A expression was not altered. Combination therapies aiming to inhibit MDR1 activity can now be screened for synergistic effects using our resistant sublines. Nevertheless, detailed resistance mechanisms and maintained molecular target expression in the resistant sublines are still to be examined.

RNA-seq of nine canine prostate cancer cell lines reveals diverse therapeutic target signatures.

BACKGROUND: Canine prostate adenocarcinoma (PAC) and transitional cell carcinoma (TCC) are typically characterized by metastasis and chemoresistance. Cell lines are important model systems for developing new therapeutic strategies. However, as they adapt to culturing conditions and undergo clonal selection, they can diverge from the tissue from which they were originally derived. Therefore, a comprehensive characterization of cell lines and their original tissues is paramount. METHODS: This study compared the transcriptomes of nine canine cell lines derived from PAC, PAC metastasis and TCC to their respective original primary tumor or metastasis tissues. Special interests were laid on cell culture-related differences, epithelial to mesenchymal transition (EMT), the prostate and bladder cancer pathways, therapeutic targets in the PI3K-AKT signaling pathway and genes correlated with chemoresistance towards doxorubicin and carboplatin. RESULTS: Independent analyses for PAC, PAC metastasis and TCC revealed 1743, 3941 and 463 genes, respectively, differentially expressed in the cell lines relative to their original tissues (DEGs). While genes associated with tumor microenvironment were mostly downregulated in the cell lines, patient-specific EMT features were conserved. Furthermore, examination of the prostate and bladder cancer pathways revealed extensive concordance between cell lines and tissues. Interestingly, all cell lines preserved downstream PI3K-AKT signaling, but each featured a unique therapeutic target signature. Additionally, resistance towards doxorubicin was associated with G2/M cell cycle transition and cell membrane biosynthesis, while carboplatin resistance correlated with histone, m- and tRNA processing. CONCLUSION: Comparative whole-transcriptome profiling of cell lines and their original tissues identifies models with conserved therapeutic target expression. Moreover, it is useful for selecting suitable negative controls, i.e., cell lines lacking therapeutic target expression, increasing the transfer efficiency from in vitro to primary neoplasias for new therapeutic protocols. In summary, the dataset presented here constitutes a rich resource for canine prostate and bladder cancer research.

Reference ranges for standard-echocardiography in pugs and impact of clinical severity of Brachycephalic Obstructive Airway Syndrome (BOAS) on echocardiographic parameters.

BACKGROUND: Echocardiographic measurements may be influenced by breed-specific characteristics. Therefore, this study aims to establish reference values for standard echocardiographic measurements in pugs by investigating the influence of age, sex, heart rate, body weight and Brachycephalic Obstructive Airway Syndrome (BOAS). Sixty-two privately owned pugs underwent physical examination, blood sample collection, non-invasive blood pressure measurements and echocardiography. Influences of independent variables on echocardiographic measurements were examined using a multiple linear regression analysis model. For the entire study population, 95% prediction intervals were generated. Further, reference ranges for subcategories of clinical severities of BOAS were provided. Selected echocardiographic measurements of pugs were compared to reference values of previous studies generated from various breeds. RESULTS: In the study, a total of fifty-one privately owned pugs aged between two and 10 years were included for establishing reference ranges. Mainly body weight, but also age, sex and heart rate had influence on several echocardiographic parameters. The clinical grading of BOAS was conducted in 42 pugs. Except for pulmonic peak velocity (Pvel), which declined with increasing severity of BOAS, clinical symptoms of upper airway disease did not have significant impact on echocardiographic measurement results. Significant deviations, however, of left ventricular (LV) internal dimension (LVID), interventricular septum (IVS), LV posterior wall (LVPW), and tricuspid annular plane systolic motion excursion (TAPSE) compared to interbreed reference values were observed. CONCLUSIONS: Breed-specific reference ranges for echocardiographic values with special regard to BOAS are provided to enable a more accurate assessment of cardiac health in pugs.

Evaluation of new and old biomarkers in dogs with degenerative mitral valve disease.

BACKGROUND: Dogs with degenerative mitral valve disease are commonly presented to small animal clinicians. Diagnosis, clinical staging, and therapeutic design are based on a combination of clinical examination, radiography, and echocardiography. To support diagnosis and clinical monitoring, a multi-marker-based approach would be conceivable. The aim of this study was to investigate the suitability of Galectin-3 and interleukin-1 receptor-like 1 protein (ST2) in dogs with degenerative mitral valve disease in accordance with N-terminal-prohormone-B-type natriuretic peptide (NT-proBNP) and cardiac troponin I (cTnI). For this purpose, serum concentrations of Galectin-3 and ST2 of 64 dogs with different stages of mitral valve disease and 21 dogs without cardiac disease were analyzed at the first examination and six months later. Echocardiography, blood cell count and clinical chemistry were performed and established biomarkers NT-proBNP and cTnI were measured additionally. Differences in the biomarker concentrations between all groups at both timepoints and the change in biomarker concentrations from first to second evaluation was investigated. Furthermore, correlations of each biomarker, between biomarkers and echocardiographic measurements, were calculated. Finally, the receiver-operating characteristic curve and the area under the curve analysis were performed to differentiate between disease stages and controls. RESULTS: Serum concentrations of Galectin-3 and ST2 were not statistically different between canine patients in the respective stages of mitral valve disease or in comparison to dogs in the control group at any timepoint. A significant increase in ST2 concentrations from the baseline to the follow-up examination was observed in dogs classified as stage B1 and the control group. The concentrations of NT-proBNP and cTnI in stage C dogs were significantly increased in comparison to the other groups. CONCLUSIONS: In this study, no relation between Galectin-3 and ST2 levels to the presence or stage of mitral valve disease could be detected. Nevertheless, considering the increase in ST2 concentrations from the first to second measurement, its value on monitoring disease progress could be feasible. In agreement with previous studies, NT-proBNP and cTnI have once more proven their utility in assessing disease severity. The approach of examining new cardiac biomarkers in dogs is still worth pursuing.

Circulating Soluble Fms-like Tyrosine Kinase in Renal Diseases Other than Preeclampsia.

Soluble Fms-like tyrosine kinase (sFlt-1/sVEGFR1) is a naturally occurring antagonist of vascular endothelial growth factor (VEGF). Despite being a secreted, soluble protein lacking cytoplasmic and transmembrane domains, sFlt-1 can act locally and be protective against excessive microenvironmental VEGF concentration or exert autocrine functions independently of VEGF. Circulating sFlt-1 may indiscriminately affect endothelial function and the microvasculature of distant target organs. The clinical significance of excess sFlt-1 in kidney disease was first shown in preeclampsia, a major renal complication of pregnancy. However, circulating sFlt-1 levels appear to be increased in various diseases with varying degrees of renal impairment. Relevant clinical associations between circulating sFlt-1 and severe outcomes (e.g., endothelial dysfunction, renal impairment, cardiovascular disease, and all-cause mortality) have been observed in patients with CKD and after kidney transplantation. However, sFlt-1 appears to be protective against renal dysfunction-associated aggravation of atherosclerosis and diabetic nephropathy. Therefore, in this study, we provide an update on sFlt-1 in several kidney diseases other than preeclampsia, discuss clinical findings and experimental studies, and briefly consider its use in clinical practice.

The effect of treatment with pimobendan in dogs with preclinical mitral valve disease - a placebo-controlled double-blinded crossover study.

BACKGROUND: Pimobendan is a widely used medication for the treatment of dogs with congestive heart failure (CHF) and preclinical degenerative mitral valve disease (DMVD) with cardiomegaly. The benefit of a treatment in dogs with preclinical DMVD but without cardiomegaly has not yet been elucidated. Some positive effects concerning life quality and a decrease in cardiac biomarkers could be verified. This study aimed to further investigate these results using a placebo-controlled double-blinded crossover design. Out of a total of 15 dogs, eight were allocated to sequence-group AB, in which dogs received pimobendan (A) during the first treatment period and placebo (B) during the second period. Accordingly, sequence-group BA was treated first with placebo followed by pimobendan. Each treatment period lasted six months and included a baseline investigation and follow-ups after 90 and 180 days. The investigations included a questionnaire completed by the owners, echocardiographic examination, and measurements of NT-proBNP, cTnI and lactate before and after a standardised submaximal exercise test. RESULTS: NT-proBNP values decreased significantly during the treatment period with pimobendan, and the post-exercise increase was attenuated at day 180. No significant treatment effects could be verified for cTnI and lactate, neither pre- nor post-exercise. Left ventricular size decreased under treatment, whereas no significant changes in left atrial size were detected. The owners described their dogs under treatment with pimobendan as being more active at day 90 (11/15) and day 180 (12/15). Those animals treated with placebo were described as being more active at day 90 (2/15) and day 180 (5/15). CONCLUSIONS: Pimobendan had reducing effects on the concentrations of pre- and post-exercise cardiac biomarkers and the size of the left ventricle in dogs with DMVD ACVIM B1. Exercise testing in addition to an assessment of cardiac biomarkers might improve the decision when to initiate pimobendan treatment in dogs with DMVD.

Ablation of Red Stable Transfected Claudin Expressing Canine Prostate Adenocarcinoma and Transitional Cell Carcinoma Cell Lines by C-CPE Gold-Nanoparticle-Mediated Laser Intervention.

Claudin (CLDN) proteins are commonly expressed in cancers and targeted in novel therapeutic approaches. The C-terminal of Clostridium perfringens enterotoxin (C-CPE) efficiently binds several claudins. In this study, recombinant C-CPE conjugated to gold nanoparticles (AuNPs) has been used for prostate adenocarcinoma (PAC) and transitional cell carcinoma (TCC) cell killing in vitro using gold-nanoparticle-mediated laser perforation (GNOME-LP). A PAC and TCC cell lines, as well as red fluorescence variants, allowing deep tissue imaging, were used. CLDN-3, -4, and -7 expression was confirmed by qPCR and immunofluorescences. The binding of C-CPE-AuNPs complexes on the cell surface was examined by scanning electron microscopy (SEM). Further, transcriptome analysis was carried out to evaluate the effect of C-CPE binder on the biological response of treated cells. Directed C-CPE-AuNP binding verified the capability to target CLDN receptors. Transcriptome analysis showed that C-CPE binding may activate immune and inflammatory responses but does not directly affect cell survival. Cancer cells ablation was demonstrated using a combination of GNOME-LP and C-CPE-AuNPs treatment reducing tumor cell viability to less than 10% depending on cell line. The fluorescent cell lines and the verified proof of concept in vitro provide the basis for perspective xenograft studies in an animal model.

An RNA-Seq-Based Framework for Characterizing Canine Prostate Cancer and Prioritizing Clinically Relevant Biomarker Candidate Genes.

Prostate cancer (PCa) in dogs is a highly malignant disease akin to its human counterpart. In contrast to the situation in humans, multi-gene approaches facilitating risk stratification of canine PCa are barely established. The aims of this study were the characterization of the transcriptional landscape of canine PCa and the identification of diagnostic, prognostic and/or therapeutic biomarkers through a multi-step screening approach. RNA-Sequencing of ten malignant tissues and fine-needle aspirations (FNA), and 14 nonmalignant tissues and FNAs was performed to find differentially expressed genes (DEGs) and deregulated pathways. The 4098 observed DEGs were involved in 49 pathways. These 49 pathways could be grouped into five superpathways summarizing the hallmarks of canine PCa: (i) inflammatory response and cytokines; (ii) regulation of the immune system and cell death; (iii) cell surface and PI3K signaling; (iv) cell cycle; and (v) phagosome and autophagy. Among the highly deregulated, moderately to strongly expressed DEGs that were members of one or more superpathways, 169 DEGs were listed in relevant databases and/or the literature and included members of the PCa pathway, oncogenes, prostate-specific genes, and druggable genes. These genes are novel and promising candidate diagnostic, prognostic and/or therapeutic canine PCa biomarkers.

BTK and PI3K Inhibitors Reveal Synergistic Inhibitory Anti-Tumoral Effects in Canine Diffuse Large B-Cell Lymphoma Cells.

Bruton's tyrosine kinase (BTK) and phosphoinositide 3-kinase (PI3K) in the B-cell receptor (BCR) signaling pathway are considered potential therapeutic targets for the treatment of B-cell lymphomas, among which, diffuse large B-cell lymphoma (DLBCL) is the most common type. Herein, we comparatively evaluated the single and combined application of the BTK inhibitor ibrutinib and the selective PI3Kγ inhibitor AS-605240 in the canine DLBCL cell line CLBL-1. For further comparison, key findings were additionally analyzed in canine B-cell leukemia GL-1 and human DLBCL cell line SU-DHL-4. While ibrutinib alone induced significant anti-proliferative effects on all cell lines in a dose-dependent manner, AS-605240 only induced anti-proliferative effects at high concentrations. Interestingly, ibrutinib and AS-605240 acted synergistically, reducing cell proliferation and increasing apoptosis/necrosis in all cell lines and inducing morphological changes in CLBL-1. Moreover, the combined application of ibrutinib and AS-605240 reduced relative phosphorylation and, in some instances, the levels of the BTK, AKT, GSK3ß, and ERK proteins. Comparative variant analysis of RNA-seq data among canine B- and T-lymphoid cell lines and primary B-cell lymphoma samples revealed potentially high-impact somatic variants in the genes that encode PI3K, which may explain why AS-605240 does not singly inhibit the proliferation of cell lines. The combination of ibrutinib and AS-605240 represents a promising approach that warrants further in vivo evaluation in dogs, potentially bearing significant value for the treatment of human DLBCL.

Establishment and characterization of stable red, far-red (fR) and near infra-red (NIR) transfected canine prostate cancer cell lines.

BACKGROUND: Canine prostate cancer represents a unique model for human prostate cancer. In vitro systems offer various possibilities but Xenograft in vivo imaging allows studying complex tasks as tumor progression and drug intervention longitudinal. Herein, we established three canine prostate carcinoma cell lines stably expressing fluorescent proteins allowing deep tissue in vivo imaging. METHODS: Three canine prostate carcinoma (cPC) cell lines were stably transfected with fluorescent proteins in red, far-red and near infra-red spectrum, followed by G418 selection. Fluorescent protein expression was demonstrated by microscopy, flow cytometry and a NightOWL LB 983 in vivo imaging system. Cellular and molecular characteristics of the generated cell lines were compared to the parental cell line CT1258. Cell proliferation, metabolic activity and sphere formation capacity were analyzed. Stem cell marker expression was examined by qPCR and genomic copy number variation by genomic DNA whole genome sequencing. RESULTS: Three stably fluorescent protein transfected cPC cell lines were established and characterized. Compared to the parental cell line, no significant difference in cell proliferation and metabolic activity were detected. Genomic copy number variation analyses and stem cell marker gene expression revealed in general no significant changes. However, the generated cell line CT1258-mKate2C showed uniquely no distal CFA16 deletion and an elevated metabolic activity. The introduced fluorescencent proteins allowed highly sensitive detection in an in vivo imaging system starting at cell numbers of 0.156 × 106. Furthermore, we demonstrated a similar sphere formation capacity in the fluorescent cell lines. Interestingly, the clone selected CT1258-mKate2C, showed increased sphere formation ability. DISCUSSION: Starting from a well characterized cPC cell line three novel fluorescent cell lines were established showing high cellular and molecular similarity to the parental cell line. The introduction of the fluorescent proteins did not alter the established cell lines significantly. The red fluorescence allows deep tissue imaging, which conventional GFP labeling is not able to realize. CONCLUSION: As no significant differences were detected between the established cell lines and the very well characterized parental CT1258 the new fluorescent cell lines allow deep tissue in vivo imaging for perspective in vivo evaluation of novel therapeutic regimens.

Increased soluble fms-like tyrosine kinase 1 after ischemia reperfusion contributes to adverse clinical outcomes following kidney transplantation.

Renal ischemia reperfusion injury (IRI) adversely affects clinical outcomes following kidney transplantation. Understanding the cellular mechanisms and the changes in gene/protein expression following IRI may help to improve these outcomes. Serum soluble fms-like tyrosine kinase 1 (sFlt-1), a circulating antiangiogenic protein, is increased in the first week following kidney transplantation. We evaluated the casual relationship of elevated sFlt-1 levels with renal microvascular dysfunction following IRI in a longitudinal study of 93 kidney transplant recipients and in several animal models. Transplant recipients with higher sFlt-1 levels had higher odds of delayed graft function, graft rejection, impaired graft function, and death. In a subgroup of 25 participants who underwent kidney biopsy within 4 months of kidney transplantation, peritubular capillary area was lower in those with elevated serum sFtl-1 levels. The administration of recombinant sFlt-1 into rodents resulted in significant structural and functional changes of the renal microvasculature, including reduced peritubular capillary density and intracapillary blood volume, and lead to increased expression of inflammatory genes and increased fibrosis. In a murine model of IRI, the kidney was a site of sFlt-1 production, and systemic neutralization of sFlt-1 preserved peritubular capillary density and alleviated renal fibrosis. Our data indicate that high sFlt-1 levels after IRI play an important role in the pathogenesis of microvascular dysfunction, thereby contributing to adverse clinical outcomes following kidney transplantation.

Evaluation of canine prostate volume in calculated tomographic images - comparison of two assessment methods.

BACKGROUND: Since most prostatic diseases are associated with the organ's enlargement, evaluation of prostatic size is a main criterion in the diagnosis of prostatic state of health. While enlargement is a non-uniform process, volumetric measurements are believed to be advantageous to any single dimensional parameter for the diagnosis of prostatomegaly. In a previous study, volume was analysed with a slice addition technique (SAT), which was validated as highly accurate. Irrespective of high accuracy, SAT represents a complex and time-consuming procedure, which limits its clinical use. Thus, demand exists for more practical volume assessment methods. In this study, the prostatic volume of 95 canine patients (58 intact males, 37 neutered males) were analysed retrospectively by using the ellipsoid formula (Formula) and an imaging "wrap" function tool (Wrap) to help assess accuracy and applicability. Accuracy was checked against phantom measurements and results were compared to SAT measurements of the same patient pool obtained from a previously published paper. Patients were grouped according to prostatic structure (H = homogeneous, I = inhomogeneous, C = cystic) and volume using the SAT (volume group = vg: 1, 2 and 3). RESULTS: High correlation between the Formula or Wrap volume and the phantom volume was found, the values being higher for the Formula. Mean Formula volumes (vg 1: 2.2 cm3, vg 2: 14.5 cm3, vg 3: 109.4 cm3, respectively) were significantly underestimated, while mean Wrap volumes (vg 1: 3.8 cm3, vg 2: 19.5 cm3, vg 3: 159.2 cm3) were statistically equivalent to SAT measurements (vg 1: 3.1 cm3, vg 2: 18.6 cm3, vg 3: 157.2 cm3, respectively). Differences between Formula and SAT volumes ranged from 22.4-31.1%, while differences between Wrap and SAT volumes were highest in small prostates (vg 1: 22.1%) and fell with increasing prostatic size (vg 3: 1.3%). CONCLUSION: The Wrap function is highly accurate, less time-consuming and complex compared to SAT and could serve as beneficial tool for measuring prostatic volume in clinical routine after further validation in future studies. The Formula method cannot be recommended as an alternative for volumetric measurements of the prostate gland due to its underestimation of volumes compared to SAT results.

Validation of canine prostate volumetric measurements in computed tomography determined by the slice addition technique using the Amira program.

BACKGROUND: Prostatic diseases are common and mostly associated with enlargement of the accessory gland. Thus, determining the prostate size has become a main criterion for evaluating prostate health status. Computed tomography (CT) is recommended as a beneficial tool for evaluating prostate size, morphology and surrounding tissues. The purpose of this study was to establish an accurate procedure for volume estimation and afterwards evaluate the prostate volume in CT. Data of 95 dogs were analysed (58 male intact, 37 male neutered) using the slice addition technique with the Amira program. Accuracy of volumetric measurements by CT was validated by comparing them with those of phantoms of known volume. Patients were grouped according to age (< 4 yrs., 4-8 yrs., > 8 yrs) and prostate morphology in CT (H = homogeneous, I = inhomogeneous, C = cystic). The length of the sixth lumbar vertebra was measured to relate prostate volume to body size. This ratio was generated to compare prostate volume between the groups, irrespective of body size (ratio volume = Rv). RESULTS: A high correlation between the CT-derived and phantom volume was found. Overall, the mean prostate volume was 58.6 cm3. The mean ratio volume was 1.3 in intact male dogs, this being significantly higher than in neutered dogs (0.7). The lowest ratio volume values were found in group H for intact (Rv = 0.9) and neutered dogs (Rv = 0.6), followed by group I (intact: Rv = 1.1; neutered: Rv = 0.7) and C (intact: Rv = 1.4; neutered: Rv = 0.8). The length of the sixth lumbar vertebra was well correlated with the prostate volume (intact: r = 0.63, p < 0.001; neutered: r = 0.48, p = 0.003), while age exhibited a correlation only in intact dogs (r = 0.52, p < 0.001). CONCLUSION: The present study is pioneering in applying a slice addition technique to volumetric measurements of the prostate gland in CT, resulting in a highly precise method. Volumetric measurements of the canine prostate gland in CT images provide information about the prostate structure, castration status, age and body size of the patients. Therefore, prostate volume is a relevant parameter for evaluating prostate health status.

Effect of Pimobendan on NT-proBNP and c troponin I before and after a submaximal exercise test in dogs with preclinical mitral valve disease without cardiomegaly - a randomised, double-blinded trial.

BACKGROUND: Exercise testing in conjunction with measurement of cardiac biomarkers NT-proBNP and cTnI is a useful tool for monitoring the effect of treatment on cardiac patients. Administering Pimobendan in dogs with degenerative mitral valve disease (DMVD) and cardiomegaly results in delaying the onset of clinical symptoms and prolonging life. Its effect in dogs with DMVD without cardiomegaly has not been well examined. The aim of the current study was to investigate the effect of administering Pimobendan in dogs with DMVD without cardiomegaly using exercise testing in conjunction with measuring cardiac biomarkers in addition to echocardiography. Twenty-one dogs with asymptomatic DMVD without echocardiographic signs of cardiomegaly participated in a randomised, double-blinded trial. Dogs were divided into a Pimobendan-group (n = 11) and a placebo-group (n = 10) in a double-blinded study design and underwent a standardised submaximal exercise test (SSET). One dog in the Pimobendan-group was retrospectively removed from the study after being diagnosed with Leishmaniosis. Cardiac biomarkers NT-proBNP and cTnI were measured before and after exercise. Follow-up appointments were performed at days 90 and 180. RESULTS: Dogs in the Pimobendan-group had significantly lower post-exercise NT-proBNP-levels after being administered Pimobendan than at the beginning of the study. They also had lower pre- and post-exercise-NT-proBNP-levels than those dogs in the placebo-group. There was neither a significant difference regarding the measured cTnI levels nor an increase in cTnI between the groups at any time. CONCLUSIONS: Pimobendan lowers NT-proBNP in dogs with presymptomatic mitral valve disease without cardiomegaly before and after submaximal exercise. This indicates a reduction in cardiac wall stress. If dogs with asymptomatic DMVD without cardiomegaly benefit from treatment with Pimobendan (for example, through a longer survival time) warrants further investigation.

Isoquinolinamine FX-9 Exhibits Anti-Mitotic Activity in Human and Canine Prostate Carcinoma Cell Lines.

Current therapies are insufficient for metastatic prostate cancer (PCa) in men and dogs. As human castrate-resistant PCa shares several characteristics with the canine disease, comparative evaluation of novel therapeutic agents is of considerable value for both species. Novel isoquinolinamine FX-9 exhibits antiproliferative activity in acute lymphoblastic leukemia cell lines but has not been tested yet on any solid neoplasia type. In this study, FX-9's mediated effects were characterized on two human (PC-3, LNCaP) and two canine (CT1258, 0846) PCa cell lines, as well as benign solid tissue cells. FX-9 significantly inhibited cell viability and induced apoptosis with concentrations in the low micromolar range. Mediated effects were highly comparable between the PCa cell lines of both species, but less pronounced on non-malignant chondrocytes and fibroblasts. Interestingly, FX-9 exposure also leads to the formation and survival of enlarged multinucleated cells through mitotic slippage. Based on the results, FX-9 acts as an anti-mitotic agent with reduced cytotoxic activity in benign cells. The characterization of FX-9-induced effects on PCa cells provides a basis for in vivo studies with the potential of valuable transferable findings to the benefit of men and dogs.

Kinematic adaptions to induced short-term pelvic limb lameness in trotting dogs.

BACKGROUND: Lameness due to paw injuries is common in the clinical practice. Although many studies investigated gait adaptations to diseases or injuries, mainly of the hip and knee, our understanding of the biomechanical coping mechanisms that lame dogs utilize is limited. Therefore, this study evaluated the kinematic changes associated with an induced, load-bearing pelvic limb lameness in healthy dogs trotting on a treadmill. Kinematic analysis included spatio-temporal comparisons of limb, joint and segment angles of all limbs. Key parameters compared between sound and lame conditions were: angles at touch-down and lift-off, minimum and maximum joint angles and range of motion. RESULTS: Significant differences were identified in each limb during both stance and swing phases. The most pronounced differences concerned the affected pelvic limb, followed by the contralateral pelvic limb, the contralateral thoracic limb and, to the least degree, the ipsilateral thoracic limb. The affected limb was retracted more, while the contralateral limb was protracted more, consistent with this limb bearing more body weight in lame dogs. CONCLUSIONS: Kinematic adaptations involved almost all segment and joint angles in the pelvic limbs, while they exclusively concerned distal parts of the thoracic limbs. Comparisons with tripedal locomotion reveal several striking similarities, implying that dogs use similar principles to cope with a partial or a total loss in limb function. Because kinematic alterations occurred in all limbs and not just the affected one, all limbs should be included in routine follow-ups and be part of the diagnostic and therapeutic care of canine patients.

Intraocular pressure in the smallest primate aging model: the gray mouse lemur.

OBJECTIVE: The aim of this study was to assess the practicability of common tonometers used in veterinary medicine for rapid intraocular pressure (IOP) screening, to calibrate IOP values gained by the tonometers, and to define a reference IOP value for the healthy eye in a new primate model for aging research, the gray mouse lemur. STUDIED ANIMALS AND PROCEDURES: TonoVet® and the TonoPen™ measurements were calibrated manometrically in healthy enucleated eyes of mouse lemurs euthanized for veterinary reasons. For comparison of the practicability of both tonometers as a rapid IOP assessment tool for living mouse lemurs, the IOP of 24 eyes of 12 animals held in the hand was measured. To define a standard reference value for IOP in mouse lemurs, 258 healthy animals were measured using the TonoVet® . RESULTS: Intraocular pressure measurements for the TonoVet® can be corrected using the formula: y = 0.981 + (1.962*TonoVet® value), and those for the TonoPen™ using that of y = 5.38 + (1.426*TonoPen™ value). The calibrated IOP for a healthy mouse lemur eye was 20.3 ± 2.8 mmHg. The TonoVet® showed advantages in practicability, for example, small corneal contact area, short and painless corneal contact, shortened total time spent on investigation, as well as the more accurate measured values. IOP measurements of healthy mouse lemur eyes were not affected by age, sex, eye side, or colony. CONCLUSION: Tonometry using TonoVet® is the more practicable assessment tool for IOP measurement of the tiny eyes of living mouse lemurs. Pathological deviations can be identified based on the described reference value.

The prevalence of medial coronoid process disease is high in lame large breed dogs and quantitative radiographic assessments contribute to the diagnosis.

Medial coronoid process disease is a common leading cause of thoracic limb lameness in dogs. Computed tomography and arthroscopy are superior to radiography to diagnose medial coronoid process disease, however, radiography remains the most available diagnostic imaging modality in veterinary practice. Objectives of this retrospective observational study were to describe the prevalence of medial coronoid process disease in lame large breed dogs and apply a novel method for quantifying the radiographic changes associated with medial coronoid process and subtrochlear-ulnar region in Labrador and Golden Retrievers with confirmed medial coronoid process disease. Purebred Labrador and Golden Retrievers (n = 143, 206 elbows) without and with confirmed medial coronoid process disease were included. The prevalence of medial coronoid process disease in lame large breed dogs was calculated. Mediolateral and craniocaudal radiographs of elbows were analyzed to assess the medial coronoid process length and morphology, and subtrochlear-ulnar width. Mean grayscale value was calculated for radial and subtrochlear-ulnar zones. The prevalence of medial coronoid process disease was 20.8%. Labrador and Golden Retrievers were the most affected purebred dogs (29.6%). Elbows with confirmed medial coronoid process disease had short (P < 0.0001) and deformed (∼95%) medial coronoid process, with associated medial coronoid process osteophytosis (7.5%). Subtrochlear-ulnar sclerosis was evidenced in ∼96% of diseased elbows, with a significant increase (P < 0.0001) in subtrochlear-ulnar width and standardized grayscale value. Radial grayscale value did not differ between groups. Periarticular osteophytosis was identified in 51.4% of elbows with medial coronoid process disease. Medial coronoid process length and morphology, and subtrochlear-ulnar width and standardized grayscale value varied significantly in dogs with confirmed medial coronoid process disease compared to controls. Findings indicated that medial coronoid process disease has a high prevalence in lame large breed dogs and that quantitative radiographic assessments can contribute to the diagnosis.