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Introduction: Human neurodevelopmental and neurodegenerative diseases (NDevDs and NDegDs, respectively) encompass a broad spectrum of disorders affecting the nervous system with an increasing incidence. In this context, the nematode C. elegans , has emerged as a benchmark model for biological research, especially in the field of neuroscience., Areas Covered: The authors highlight the numerous advantages of this tiny worm as a model for exploring nervous system pathologies and as a platform for drug discovery. There is a particular focus given to describing the existing models of C. elegans for the study of NDevDs and NDegDs. Specifically, the authors underscore their strong applicability in preclinical drug development. Furthermore, they place particular emphasis on detailing the common techniques employed to explore the nervous system in both healthy and diseased states., Expert Opinion: Drug discovery constitutes a long and expensive process. The incorporation of invertebrate models, such as C. elegans , stands as an exemplary strategy for mitigating costs and expediting timelines. The utilization of C. elegans as a platform to replicate nervous system pathologies and conduct high-throughput automated assays in the initial phases of drug discovery is pivotal for rendering therapeutic options more attainable and cost-effective.

The management of unowned cats is an emerging problem, with public institutions and citizens' concerns regarding their care and arrangement. Little is known regarding the outcome of traumatic orthopedic injuries in these patients. Indeed, complete functional recovery (CFR) should be the goal of treatment for return to their original location or adoption. The aim was to identify clinical factors influencing CFR in traumatized unowned cats with orthopedic lesions. This category of cats referred by the veterinary public service over three years was enrolled. Various clinical variables were retrospectively collected from the medical records and evaluated by nominal logistic analysis. Forty-eight unowned cats were enrolled, with a median estimated age of 24 (1-180) months and a body weight of 3 (0.7-5) kg. Thirty-four (71%) patients reached CFR. Estimated age, body weight, time from trauma to therapeutic intervention, spine involvement, presence of comorbidities, hospitalization time, and the radiographic score results were significantly associated with CFR. A longer time to therapeutic intervention seemed to be associated with a better outcome. Probably, cats severely traumatized did not live long enough to be evaluated and treated. Lighter cats experienced more severe consequences following blunt trauma. Younger and lighter cats bore a higher risk of panleukopenia-related death.

The tumor microenvironment is considered one of the main players in cancer development and progression and may influence the behavior of cancer cells. Periostin (POSTN) is an extracellular matrix protein, and its main functions are induction of fibrillogenesis, fibroblastic cell proliferation and migration, enhancing regeneration in normal tissue, and promoting metastasis in case of neoplasia. POSTN has already been studied in humans in several normal tissues, inflammatory processes, and neoplasms, revealing an important role in tumor progression in various types of cancer, such as colon, lung, head and neck, breast, ovarian, and prostate. In these latter, high levels of POSTN are usually associated with a more aggressive tumor behavior, tumor advanced stages, and poor prognosis, while in human bladder urothelial carcinoma (BUC), unlike in most tumors, POSTN expression seems to be downregulated. The expression of this marker has been poorly investigated in veterinary medicine; thus, this study aimed to immunohistochemically investigate the presence and the intensity of POSTN expression in canine BUCs and to determine a possible relationship between POSTN expression and histopathological features such as mitotic count and muscular and vascular invasions. For the present retrospective study, archived samples from 45 canine BUCs and 6 non-neoplastic canine bladders were considered for histological evaluation and immunohistochemical examination for the expression of POSTN. POSTN expression was semi-quantitatively assessed considering both the percentage of the neoplastic stroma positive for POSTN and the intensity of the immunohistochemical labeling. Histologically, 38 out of 45 tumors were papillary and 7 out of 45 were non-papillary. All tumors were infiltrating, being that 21 were muscle-invasive, and a significant correlation between this feature and vascular invasion emerged ( P = 0.0001). In normal bladder tissue, as reported in humans, a thick and strongly positive belt of POSTN was visible, and in canine BUCs, stating that the expression is comparable with human benign as well as malignant bladder tissue, a general decrease in POSTN expression was observed except for a strongly labeled ring of POSTN observed around some neoplastic nodules infiltrating the muscle layer. Moreover, POSTN expression and mitotic count were significatively inversely correlated ( P = 0.0015). The fact that POSTN protein is less expressed in urothelial carcinomas than in the normal bladder supports what was reported in human BUCs and, together with the negative correlation between mitotic count and protein expression that emerged in the present retrospective study, encourages further prospective follow-up studies to verify the possible role of POSTN in canine BUCs as a prognostic marker, and also as a possible target for the development of future anticancer therapies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Brambilla, Ciaputa, Crepaldi, Dzimira, Nowak, Dziegiel, Piotrowska, Mollica Govoni, Fonseca-Alves, Laufer-Amorim, Stefanello, Romussi and Grieco.)

Echocardiography is the most widely accepted diagnostic tool for assessment of cardiac function and morphology in dogs and is usually performed in lateral recumbency. However, in some situations or in stressed patients, it is necessary to perform it in a standing position. Only one study evaluated the effects of animal position on selected two-dimensional and M-mode echocardiographic variables in four healthy dogs of different breeds, but not in brachycephalic breeds. In these breeds echocardiographic evaluation is sometimes needed in standing position due to the severity of brachycephalic obstructive airway syndrome and the impossibility of managing them in lateral recumbency without causing stress and choking danger. The objectives of this prospective, observational study were to (a) evaluate the effects of lateral recumbency versus standing positions on echocardiographic M-mode, two-dimensional, Doppler flow measurements, and Tissue Doppler imaging in healthy French bulldogs (FBs); (b) assess the intra- and interoperator variability of the standing echocardiographic examination; and (c) compare the obtained results with the available data from the literature. Forty healthy FBs (20 females/20 males) were sampled. The median age and weight were 2.45 years (IQR 25-75 , 1.18-4.16) and 12.7 kg (IQR 25-75 , 10.88-13.46). There were no differences between lateral recumbency and standing position measurements (P > 0.05). Intraoperator coefficients of variation (CVs) ranged from 0.5% to 10.1%, whereas interoperator CVs ranged from 1% to 14.2%. Only E wave peak velocity, aortic, and pulmonary flows were consistent with the previously published reference ranges in lateral recumbency. In conclusion, echocardiography in a standing position could be a useful tool in FBs., (© 2023 The Authors. Veterinary Radiology & Ultrasound published by Wiley Periodicals LLC on behalf of American College of Veterinary Radiology.)

Objectives: To evaluate if the functional grading system (Cambridge classification) of brachycephalic obstructive airways syndrome (BOAS) and the temperament score can be useful tools in predicting the feasibility of echocardiographic examination in lateral recumbency. The hypothesis is that the temperament of the dog, rather than the severity of BOAS alone, can exacerbate respiratory symptoms (dyspnea, stertor, stridor and/or cyanosis) during lateral containment., Methods: Prospective cross-sectional study. Twenty-nine French Bulldogs were included and classified according to the Cambridge classification for the BOAS and to the Maddern score for the temperament. Receiver operating characteristic analysis was used to evaluate the sensitivity (Se) and specificity (Sp) of the Cambridge classification, of the temperament score and their sum to predict the feasibility of the echocardiography in lateral recumbency without dyspnea/cyanosis., Results: 8 females (27.59%) and 21 (72.41%) males French Bulldogs of 3 years (IQR25-75 1-4), and 12.45 kg (IQR25-7511.5-13.25) were included. The Cambridge classification alone was not predictive for the possibility of performing the echocardiography in lateral recumbency, unlike temperament score and the sum of the two classification indices. The diagnostic accuracy of Cambridge classification (AUC 0.81, Se 50%, Sp 100%), temperament score (AUC 0.73, Se 75%, Sp 69%), and their sum (AUC 0.83, Se 75%, Sp 85%) cut-offs was moderate for each score., Clinical Significance: The dog's temperament, and therefore its susceptibility to stress, rather than the severity of BOAS (Cambridge classification) alone, is a good predictor of the possibility of performing the echocardiographic examination in standing instead of lateral recumbency., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Bagardi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Post-surgical management is an important issue in veterinary medicine, requiring biomarkers with high sensitivity and specificity for timely and effective treatment. Emerging evidence suggests that miRNAs are promising stress- and pain-related markers. The aims were to profile the circulating miRNA signature in plasma of turtles (Trachemys scripta) and point out potential candidate biomarkers to assess the status of the animal. The plasma of female turtles underwent surgical gonadectomy were collected 24 h pre-surgery, and 2.5 h and 36 h post-surgery. The expression of miRNAs was profiled by Next Generation Sequencing and the dysregulated miRNAs were validated using RT-qPCR. The diagnostic value of miRNAs was calculated by ROC curves. The results showed that 14 miRNAs were differentially expressed over time. RT-qPCR validation highlighted that 2-miR-499-3p and miR-203-5p-out of 8 miRNAs tested were effectively modulated. The Area Under the Curve (AUC) of miR-203-5p was fair (AUC 0.7934) in discriminating pre- and 36 h post-surgery samples and poor for other time points; the AUC of miR-499-3p was excellent (AUC 0.944) in discriminating pre-surgery and 2.5 h post-surgery samples, and fair in discriminating pre-surgery and 36 h post-surgery (AUC 0.7292) and 2.5 h and 36 h post-surgery (AUC 0.7569) samples. In conclusion, we demonstrated for the first time that miRNAs profile changes in plasma of turtles underwent surgical oophorectomy and identified miR-203-5p and miR-499-3p as potential candidate biomarkers to assess animals' status. Further studies are necessary to confirm their diagnostic value and to investigate functional and mechanistic networks to improve our understanding of the biological processes., (© 2021. The Author(s).)

Echocardiographic evaluation is a diagnostic tool for the in vivo diagnosis of heart diseases. Specific and unique anatomical characteristics of the ophidian heart such as the single ventricular cavity, a tubular sinus venosus opening into the right atrium, the presence of three arterial trunks and extreme mobility in the coelomic cavity during the cardiac cycle directly affect echocardiographic examination. Twenty-one awake, healthy ball pythons (Python regius) were analysed based on guidelines for performing echocardiographic examinations. Imaging in the sagittal plane demonstrated the caudal vena cava, sinus venosus valve (SVV) and right atrium and the various portions of the ventricle, horizontal septum, left aortic arch and pulmonary artery. Transverse imaging depicted the spatial relationship of the left and right aortic arches, the pulmonary artery and the horizontal septum. Basic knowledge of cardiac blood flow in reptiles is necessary to understand the echocardiographic anatomy. The flow of the arterial trunks and SVV was analysed using pulsed-wave Doppler based on the approach used for humans and companion mammals. The walls and diameters of the cavum arteriosum, cavum venosum and cavum pulmonale were also evaluated. This study should improve the veterinarian's knowledge of ophidian heart basal physiology and contribute to the development of cardiology in reptiles., (© 2021 The Authors. Veterinary Medicine and Science Published by John Wiley & Sons Ltd.)

The use of long-acting gonadotropin-releasing hormone (GnRH) agonists to suppress fertility has been poorly investigated in reptiles, and the few available studies show inconsistent results. The efficacy of single and double intramuscular 4.7 mg deslorelin acetate implants in captive pond sliders ( Trachemys scripta ) was investigated, with 20 animals divided into three groups: a single-implant group (6 animals), a double-implant group (6 animals), and a control group (no implant). During one reproductive season (March to October), plasmatic concentration of sexual hormones (estradiol, progesterone, and testosterone) and ovarian morphometric activity via computed tomography were monitored about every 30 days. A significative decrease in the number of phase II ovarian follicles was detected in the double-implant group compared with the control group, but no significant difference was noted in the number of phase III and phase IV follicles, egg production, and plasmatic concentration of sexual hormones. Results show that neither a single nor a double deslorelin acetate implant can successfully inhibit reproduction in female pond sliders during the ongoing season, but the lower number of phase II follicles in the double-implant group can possibly be associated with reduced fertility in the following seasons.

Ovariectomy via the prefemoral fossa is a well-described technique for sterilization in chelonians. The choice between lateral and dorsal recumbency is generally left to the surgeon's preference, with no data supporting an objective superiority of one over the other. Twenty-four sexually mature female pond sliders ( Trachemys scripta ) were enrolled for elective prefemoral endoscope-assisted oophorectomy, and were randomly divided in two groups: 12 animals were placed in right lateral recumbency with a left fossa approach (Group A), and 12 in dorsal recumbency with a right fossa approach (Group B). Scoring systems were applied to assess the ease of access to the coelomic cavity, and the ease of identification of the ovary opposite to the surgical incision. A negative correlation was found between the body weight of the animals and the ease of access to the coelom ( p = 0.013), making the access easier in smaller animals. No significant difference was found between the two groups in terms of ease of access to the coelomic cavity, first ovary removal time, ease of identification of the second ovary, second ovary removal time, or total surgery time.

Objective: To report the long-term outcome of permanent tracheostomy for the management of severe laryngeal collapse secondary to brachycephalic airway obstructive syndrome., Study Design: Retrospective case series., Animals: Fifteen brachycephalic dogs with severe laryngeal collapse treated with permanent tracheostomy., Methods: Follow-up data were obtained from medical records or via telephone conversation with the owners. The Kaplan-Meier estimator was used to calculate median survival time. Death was classified as related or unrelated to tracheostomy surgery. Complications were classified as major when they were life-threatening or required revision surgery. Owners were asked to classify the postoperative quality of life as improved, unchanged, or worse and the management of the stoma as simple or demanding., Results: The median survival time was 100 days. Major complications were diagnosed in 12 of 15 (80%) dogs, resulting in death in 8 (median survival time 15 days) and revision surgery in 4 dogs. Seven of 15 (47%) dogs died of unrelated causes or were alive at the end of the study (median survival time 1982 days). The postoperative quality of life of 9 dogs was judged as markedly improved. Stoma management was defined as simple in 8 dogs and demanding in 4., Conclusion: Permanent tracheostomy was associated with a high risk of complications and postoperative death in brachycephalic dogs. However, long-term survival (exceeding 5 years) with a good quality of life was documented in 5 of 15 dogs., Clinical Significance: Permanent tracheostomy is a suitable salvage option in brachycephalic dogs with severe laryngeal collapse that did not improve following more conservative surgeries., (© 2018 The American College of Veterinary Surgeons.)

Background: In Italy, Angiostrongylus vasorum, an emergent parasite, is being diagnosed in dogs from areas considered free of infection so far. As clinical signs are multiple and common to other diseases, its diagnosis can be challenging. In particular, in areas where angiostrongylosis and dirofilariosis overlap, a misleading diagnosis of cardiopulmonary dirofilariosis might occur even on the basis of possible misleading outcomes from diagnostic kits., Case Presentation: Two Cavalier King Charles spaniel dogs from an Italian breeding in the Northwest were referred to a private veterinary hospital with respiratory signs. A cardiopulmonary dirofilariosis was diagnosed and the dogs treated with ivermectin, but one of them died. At necropsy, pulmonary oedema, enlargement of tracheo-bronchial lymphnodes and of cardiac right side were detected. Within the right ventricle lumen, adults of A. vasorum were found. All dogs from the same kennel were subjected to faecal examination by FLOTAC and Baermann's techniques to detect A. vasorum first stage larvae; blood analysis by Knott's for Dirofilaria immitis microfilariae, and antigenic tests for both A. vasorum (Angio Detect™) and D.immitis (DiroCHEK® Heartworm, Witness®Dirofilaria). The surviving dog with respiratory signs resulted positive for A. vasorum both at serum antigens and larval detection. Its Witness® test was low positive similarly to other four dogs from the same kennel, but false positive results due to cross reactions with A. vasorum were also considered. No dogs were found infected by A. vasorum. Eventually, the investigation was deepened by browsing the pathological database of Veterinary Pathology Laboratories at Veterinary School of Milan University through 1998-2016, where 11 cases of angiostrongylosis were described. Two out of 11 dogs had a mixed infection with Crenosoma vulpis., Conclusion: The study demonstrates the need for accurate surveys to acquire proper epidemiological data on A. vasorum infection in Northwestern Italy and for appropriate diagnostic methods. Veterinary clinicians should be warned about the occurrence of this canine parasite and the connected risk of a misleading diagnosis, particularly in areas endemic for cardiopulmonary dirofilariosis.

Aim: Veterinarians have frequently to deal with wounds to the skin, subcutis, and underlying muscle. The aim was to explore the application of hyaluronic acid (HA)-containing dressing on open skin wounds in dogs. The progress of healing was assessed by wound area reduction and two scoring scales applied in human medicine., Materials and Methods: Ten client-owned dogs with 12 cutaneous open wounds healed by the second intention were included. All wounds were treated using available in commerce HA-containing wound dressing from admission to complete re-epithelialization. At every clinical examination, wound area and scale scoring assessments were performed., Results: After debridement, an increased wound size was obtained while an improvement was determined by both grading systems. The median numbers of return to the clinic for bandage change were 5 times. The median time to complete wound healing was 34.5 days. The mean wound area at day 7, 14, 21, and 28 were, respectively, 90.4%, 47.7%, 22.4%, and 14.8% of the original size (for linear measurement) and 95.5%, 54.4%, 23.10%, and 14.8% of the original size (for software measurement). Regarding wound healing assessment tools, the agreement between two operators was considered high for both scales., Conclusions: HA-containing dressing may be a possible wound treatment for cutaneous open wounds in dogs. The assessment of wound quality using scale scoring system could be useful especially in the 1(st) week and to direct clinical decision-making process.

A 1-year-old female Labrador retriever was referred with a few days history of haematic-like vulvar discharge. Physical examination, vaginal inspection and palpation did not reveal any remarkable finding. Transabdominal ultrasound showed echogenic fluid accumulation in the vagina suggesting haemato-pyocolpos. An exploratory laparotomy was performed: a well-delimited ectasic vagina was identified. Ovariohysterectomy and partial vaginectomy and vaginoplasty were performed to spay the bitch and to remove the ectasic vagina. Post-operative recovery and 12-month follow-up were uneventful. Clinical, morphological and histological findings were consistent with a congenital abnormality of the muscular layer of the vagina complicated by haemato-pyocolpos. The disorganization of the vaginal tunica muscularis may have acted as locus minoris resistentiae in the vaginal wall. The organ was dilated and atonic due to the gradual accumulation of physiological fluids complicated by an overgrowth of genital bacteria. This congenital disorder has to be taken into account as differential diagnosis of haemato-pyocolpos with vaginal discharge in young bitches., (© 2015 Blackwell Verlag GmbH.)

A thickened and abnormally long soft palate is mostly involved in the pathogenesis of both nasopharyngeal and oropharyngeal narrowing, affecting the respiratory activity in virtually all of the brachycephalic dogs suffering from Brachycephalic Airway Obstructive Syndrome (BAOS). The morphology of the soft palate in adult mesaticephalic and brachycephalic dogs has been previously described. In this article specimens from brachycephalic dog neonates (N=10) dead from one to 3 hr after birth of unrelated conditions were collected and histologically evaluated at three transverse levels to describe the microscopic aspect of the caudal part of the soft palate. The soft palate of neonate brachycephalic dogs was histologically characterized by a musculo-connective axis containing salivary glands and coated by a mucosal layer on both the nasopharyngeal and the oral side. Quali-quantitative features, such as thickened superficial epithelium, broad oedema of the lamina propria, mucous gland hyperplasia and diverse muscular modifications described in adult brachycephalic dogs, were not observed in the soft palate of brachycephalic neonate dogs. The lack of tissue lesions in the soft palate of newborn brachycephalic dogs further supports the hypothesis that inspiratory depression during the inspiratory phase causes chronic vibration and microtrauma, which lead to soft palate alterations in adult brachycephalic dogs starting from the earliest grade of the respiratory syndrome. Overall, this study provides baseline information for the comprehension of the pathogenesis of BAOS., (© 2014 Wiley Periodicals, Inc.)

Mixed germ cell sex cord stromal tumours (MGSCTs) are composed of seminiferous tubules, filled with admixed neoplastic Sertoli cells (SCs) and germ cells (GCs). The aim of the present study was to describe 13 canine testicular MGSCTs and to investigate the histochemical features and the immunophenotype of the neoplastic GCs and SCs. Neoplastic SCs were always diffusely labelled for vimentin (VIM), neuron specific enolase (NSE), inhibin (INH)-α and anti-Müllerian hormone (AMH). Cytokeratins AE1/AE3 (CK) and desmin (DES) were expressed in 6/13 and 8/13 cases, respectively. Neoplastic GCs were labelled for placental alkaline phosphatase (PLAP) in 7/13 cases and for CD117 (KIT) in 8/13 cases, while 10 cases were stained uniformly by periodic acid-Schiff (PAS). Immature canine SCs are known to express CK, DES, INH-α and AMH, while immature GCs are stained by PAS and express PLAP and KIT. This GC phenotype also distinguishes between classical and spermatocytic seminoma, with the latter being negative for these markers. The results of the present study show that both neoplastic SCs and GCs in MGSCTs have a de-differentiated phenotype., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

The purpose of this retrospective study is to evaluate the frequency and further characterize the pathological features of common and uncommon histological lesions in 111 canine prostatic samples. Benign prostatic hyperplasia, suppurative and non-suppurative prostatitis, and prostate cancer were observed individually or in combination in 45, 11, 68 and 50 samples, respectively. Six growth patterns of prostatic carcinoma were differentiated: papillary, cribriform, solid, small acinar/ductal, signet ring, mucinous. In a few cases, perineurial invasion and collagenous micronodules were observed. Lesions considered preneoplastic in men, such as high-grade prostatic intraepithelial neoplasia (HGPIN) and prostatic inflammatory atrophy (PIA), were observed in 27 and 21 histological samples, respectively. This study represents a detailed characterization of the different histological subtypes of canine prostate cancer. The awareness of the unusual patterns might be critical in avoiding diagnostic misinterpretation. The high prevalence of PIA and HGPIN underlines the reasonable chance of their detection in routine biopsy specimens., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Forty dogs presented for brachycephalic airway obstructive syndrome with laryngeal collapse not over 1st degree (saccule eversion) underwent glottis endoscopic and radiographic skull measurements before surgery. Fifteen Pugs, fifteen French and ten English Bulldogs were included. The goals were prospectively to compare three common brachycephalic breeds for anatomical differences regarding glottis and skull measurements, and to assess if any correlation between glottis and skull measurements was present. Linear measurements were used to obtain glottis and skull indices. Correlations between glottis and skull indices and glottic measurements were evaluated. Finally, glottis indices were compared among the three breeds., Results: No correlation was found for glottis and skull indices. The glottic index differed among the three breeds (smaller in Pugs and higher in English Bulldogs), ultimately representing a morphologic indicator of the different larynx shape in the three breeds (more rounded in English Bulldogs, more elliptical in Pugs and in-between in French Bulldogs)., Conclusions: The lack of correlation between skull/glottic indices does not support skull morphology as predictor of glottic morphology. As Pugs had the lowest glottic index, it may be speculated that Pugs' original narrow glottic width may predispose to further progressive respiratory deterioration more easily than in the other two breeds.

Objective: To evaluate plasma concentrations of inflammatory mediators in dogs with brachycephalic airway obstruction syndrome, identify a possible role for these mediators in the syndrome, and investigate the relationship between plasma concentrations of inflammatory mediators and severity of clinical signs., Animals: 17 dogs with brachycephalic airway obstruction syndrome and 10 mesocephalic (control) dogs., Procedures: A blood sample was collected once from each dog. Plasma concentrations of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-6, IL-17A, IL-10, and IL-13 were measured with ELISAs. Nitric oxide (NO) concentrations were determined with a Griess test. For analysis, brachycephalic dogs were categorized into groups depending on weight (small [< 16 kg]) and large [≥ 16 kg]) or on whether they required medical or surgical treatment., Results: Compared with control dog values, plasma concentrations of TNF-α, IL-10, IL-13, and IL-17A were significantly higher in brachycephalic dogs and markedly so for brachycephalic dogs that required surgery; findings for small and large brachycephalic dogs did not differ. A similar pattern of differences between control and brachycephalic dogs was identified for plasma NO concentration. Plasma IL-1β and IL-6 concentrations in control and brachycephalic dogs did not differ., Conclusions and Clinical Relevance: In brachycephalic dogs, plasma TNF-α, IL-10, IL-13, L-17A, and NO concentrations were higher than values in control dogs and appeared to be associated with disease severity. These variables may be useful as indicators of inflammatory processes associated with brachycephalic airway obstruction syndrome in dogs.

Laryngeal saccule eversion has been widely reported as an important component of brachycephalic airway obstructive syndrome (BAOS). The authors hypothesised that saccules affected by acute histological changes in patients showing marked improvement following palate and nares surgery might spontaneously return to normal; moreover, spontaneous resolution of the eversion in patients with fibrotic saccules and/or without clinical improvement following BAOS surgery might be impossible and, on the contrary, the persistence of turbulent airflow and associated ongoing inflammation might lead to aberrant tissue proliferation after resection. In order to demonstrate our hypotheses, the authors decided to perform a unilateral sacculectomy and to postpone and assess the need for the execution of the contralateral saccule resection according to the findings of a second-look laryngoscopy. Ten dogs were enrolled. None of the saccules left in situ underwent spontaneous resolution of the eversion. In one dog, after sacculectomy, proliferation of a soft tissue lesion endoscopically similar to a newly formed saccule occurred. The results of the present study suggest that spontaneous resolution of saccule eversion is uncommon, even after the correction of the primary abnormalities (palate, nares). Resection of the saccules can relieve ventral rima glottidis obstruction; however, secondary intention healing might occasionally result in the recurrence of the obstruction.

Background: Most cases of canine chronic intranasal disease cannot be differentiated based on clinical examination alone, and biopsy is often required for a definitive diagnosis. Nonsurgical cytologic and histologic biopsy techniques represent desirable diagnostic approaches., Objective: The aim of this retrospective study was to determine the diagnostic accuracy of brush cytology in differentiating non-neoplastic and neoplastic diseases in dogs with chronic intranasal disease., Methods: Cytologic samples of lesions in dogs with chronic intranasal disease were obtained by brushing over a 12-year period. All dogs had complete physical examinations as well as radiographic, rhinoscopic, and cytologic evaluation. Histologic diagnosis, follow-up clinical information, or both were used as the gold standard, and dogs free of disease or with no progression of disease at 1 year were considered negative for neoplasia. Indicators of performance of brush cytology in detecting neoplasia were calculated and included sensitivity, specificity, positive and negative likelihood ratios, and diagnostic odds ratio., Results: Samples of nasal brushings from 138 dogs were evaluated. Of 62 cases of neoplastic disease, true-positive and false-negative diagnoses were made using cytologic evaluation in 44 (71.0%) and 18 (29.0%) cases, respectively. False-negative diagnoses of neoplasia were not attributed to low cellularity, but to the presence of inflammatory cells that masked neoplastic cells. Brush cytology had a sensitivity of 0.71, specificity of 0.99, positive likelihood ratio of 53.94, negative likelihood ratio of 0.29, and diagnostic odds ratio of 188.33., Conclusions: Brush cytology has good diagnostic accuracy for chronic intranasal lesions in dogs., (© 2012 American Society for Veterinary Clinical Pathology.)

In brachycephalic dogs, the skull bone shortening is not paralleled by a decreased development of soft tissues. Relatively longer soft palate is one of the main factors contributing to pharyngeal narrowing during normal respiratory activity of these dog breeds, which are frequent carriers of the brachycephalic airway obstructive syndrome (BAOS), which affects most part of them during their postnatal life. No histological studies assessing the morphology and the normal tissue composition of the soft palate in brachycephalic dogs are available, neither has ever been determined whether the elongated soft palate is a primary or secondary event. Aim of this study was to describe the morphology of the caudal soft palate in brachycephalic dogs with Grade I BAOS to identify potential features possibly favoring the pathogenesis of BAOS. Specimens from brachycephalic dogs (N = 11) that underwent preventive surgery were collected from surgery, processed for histology, and examined at six transversal levels. The brachycephalic soft palates showed peculiar features such as thickened superficial epithelium, extensive oedema of the connective tissue, and mucous gland hyperplasia. Several muscular alterations were evidenced in addition. The results of this investigation add to the general knowledge of the anatomy of soft palate in the canine species and establish baseline information on the morphological basis of the soft palate thickening in brachycephalic dogs., (Copyright © 2011 Wiley-Liss, Inc.)

The gross anatomy and overall structure of the soft palate has been described in the average dog's head, however, no descriptive microanatomical studies of the dog soft palate are available, despite their possible utility in view of the manifold and important repercussions of this organ physiology. This is the first of two companion papers, dealing with the caudal part of the soft palate in the canine species, in mesaticephalic and brachycephalic dogs. Specimens from mesaticephalic healthy dogs (N = 8) were collected after euthanasia, processed for histology and sectioned at six transversal levels. Morphological stainings were used for a microscopic evaluation of the tissue layers composing the distal part of the soft palate in adult mesaticephalic dogs, and histochemical reactions were applied to assess mucin types within glandular tissue and to investigate the connective tissues. The organ was characteristically organized into a major deep musculo-connective axis mixed with salivary glands and covered by the mucosal lining on either the nasopharyngeal or the oral sides. The results of this investigation add to the general knowledge of the anatomy of soft palate in the canine species and establish baseline information for the parallel study on the long and thickened soft palate, which is typical of adult brachycephalic dogs., (Copyright © 2011 Wiley-Liss, Inc.)

The three-dimensional histology technique is used in human medicine for the evaluation of complete lateral and deep surgical margins. In this study, the technique was applied to 48 excised feline injection-site sarcoma specimens. The predictive value of the histological margin status and tumour grading on local recurrence was investigated. In 32/48 cases, the margins were non-infiltrated, whilst in the remaining 16 cases, they were infiltrated. Overall, 6/32 (19%) tumours with non-infiltrated margins and 11/16 (69%) with infiltrated margins recurred. Tumours with infiltrated margins recurred about 10 times more frequently compared to tumours with non-infiltrated margins (P=0.0011). No statistically significant correlation was observed between grading and recurrence. The assessment of margin status using the 3D histology technique showed a good predictivity for post-surgical tumour recurrence. Extensive application of the 3D histology technique is recommended to standardise the evaluation of histological margins and to allow comparison between results from different laboratories., (Copyright © 2009 Elsevier Ltd. All rights reserved.)

Background: In the clinical staging of cutaneous mast cell tumors (cMCT), the diagnosis of metastasis is controversial based on cytological examination of lymph nodes, spleen, liver, bone marrow, and blood., Objectives: To define the prognostic role of ultrasound-guided cytology of spleen and liver in cMCT. The results of cytological evaluation were compared in relation with survival time., Animals: Fifty-two client-owned dogs with a diagnosis of cMCT., Methods: Selection of cases was based on cytological evaluation of liver and spleen to detect infiltration at distant sites. The Kaplan Meier method was used to compare survival in dogs with and without infiltration of spleen and liver (log-rank test P < .05)., Results: Ten dogs with cMCT had mast cell infiltration of spleen, liver, or both and 4 of these dogs had involvement of the regional lymph nodes. The majority of dogs had 2 or more ultrasonographically abnormal findings simultaneously in spleen and liver. Nine dogs had grade II cMCT, and 1 had grade III cMCT. Dogs with positive evidence of mast cell infiltration to spleen, liver, or both had shorter survival times (34 versus 733 days) compared with dogs negative for mast cell infiltration at distant sites., Conclusion and Clinical Importance: Dogs with evidence of mast cell infiltration at distant sites have a shorter survival times than dogs without evidence of infiltration at distant sites. This study suggests that cytology of spleen and liver is indicated either for ultrasonographically normal or for ultrasonographically abnormal spleen and liver in dogs with cMCT.

Objective: To evaluate recurrence rate and disease-free interval (DFI) of dogs with low-grade soft tissue spindle cell sarcoma of the extremities treated by marginal excision., Study Design: Retrospective study., Animals: Dogs (n=35) with soft tissue low-grade spindle cell sarcoma., Methods: Medical records were reviewed and dogs that had marginal surgical resection of low-grade soft tissue spindle cell sarcoma at or distal to elbow and stifle were included., Results: Histopathologic margins were dirty (12 dogs), clean but close (12), and clean (11). Follow-up after surgery occurred from 210 to 2202 days (minimum, 180 days). Local recurrence and metastatic rates were 10.8% and 0%, respectively. Median DFI and survival time were not reached, because <50% of dogs died of disease-related events. Mean DFI and mean survival time were 697.8 days (95% CI: 559.7-836 days) and 703.5 days (95% CI: 566.6-840.5 days), respectively. There were no significant differences among survival functions stratified by histologic margins., Conclusion: Marginal surgical excision without adjuvant treatment of low-grade soft tissue spindle cell sarcoma of the extremities results in a low local recurrence rate., Clinical Relevance: Low-grade spindle cell sarcomas located at or distal to the elbow and stifle joints can be excised without need for wide or radical surgery.

An 18-month-old, female Cane Corso dog was presented with a suspected primary tumor of the tibia. Plain radiographs and computed tomography (CT) of the tibia were highly suggestive of a primary bone neoplasm. A diagnosis of malignant melanoma was made by cytology. Total body survey radiographs, CT scan of the thorax, and abdominal ultrasound excluded the presence of neoplastic lesions other than in the tibia. Limb amputation was performed. Histology and immunohistochemical analysis of the tibial neoplasm confirmed the diagnosis of a melanoma with secondary metastasis to the popliteal lymph node. The dog was alive and in good physical condition 43 months after surgery.

An 8-year-old neutered male Boxer was presented with tenesmus, hemorrhagic urethral discharge, and dysuria. Abdominal ultrasound and radiographic examinations revealed irregular prostatic enlargement. Laparotomy was performed and intraoperative cytology was done on imprint smears of a biopsy specimen obtained from a prostatic mass. The cytologic preparation was highly cellular and contained a predominant population of atypical, large, loosely cohesive spindle cells, with rare multinucleated cells and mitotic figures. The cytologic findings were consistent with undifferentiated sarcoma. At necropsy, a large cystic prostatic mass and numerous satellite nodules in the soft tissues around the pelvis were found. On histologic examination the tumor was composed primarily of bundles of neoplastic spindle cells. Rare pseudo-acinar structures and signet-ring cells also were observed. On immunohistochemical examination, the neoplastic cells co-expressed cytokeratin and vimentin. Based on histologic and immunohistochemical findings, the tumor was diagnosed as primary prostatic sarcomatoid carcinoma. This is a rare tumor in dogs, in which biphasic morphology of epithelial and mesenchymal cells can complicate the diagnosis, requiring immunochemical stains for confirmation.

The role of oestrogens and their receptors (ERs) in prostatic growth and differentiation and in the progression of prostatic carcinoma has been well investigated in human medicine. In dogs, however, available reports on the expression of ERs in normal, hyperplastic or neoplastic prostates are few and controversial, or completely lacking. Three normal, three hyperplastic and nine neoplastic canine prostates were examined histologically, and immunohistochemically with a polyclonal antibody directed against human ERs. Evaluation of the percentage of immunolabelled cells was performed by digital image analysis. The study showed that ERs were expressed in the nuclei of epithelial and stromal cells in normal, hyperplastic and neoplastic prostates. All nuclei in normal and hyperplastic prostates were strongly and homogeneously immunolabelled by the antibody used. However, the percentages of immunolabelled nuclei in the nine prostatic carcinomas were greatly reduced, ranging from 36.34% to 66.73%. The severe loss of ER expression in canine prostatic carcinomas may account for the relative lack of differentiation of these tumours in the dog.

Both canine and human seminomas are typically associated with leucocytic infiltration, the role of which remains poorly understood. In this study, leucocytes infiltrating 10 canine seminomas were characterized. Monoclonal antibodies directed against CD18, CD11a, CD11b, CD11c, CD21, CD3, CD4, CD8 and Major Histocompatibility Complex class I and II (MHC I and MHC II) were also employed. Infiltrating leucocytes were located around vessels, adjacent to the thin fibrous septa between neoplastic lobules, and were also scattered singly amongst neoplastic cells. The more profuse infiltrates often had the appearance of follicular aggregates. Immunohistochemically, all the samples showed generally similar results. Most of the infiltrating cells were positive for CD18 and CD11a. Infiltrating cells were mainly T lymphocytes (CD3+), particularly of the CD8+ subset. B lymphocytes (CD21+) were detectable in almost all infiltrates; in the follicular aggregates they were centrally located, whereas T lymphocytes (CD3+) lined the periphery. CD11c+ cells were always more numerous than CD11b+ cells, demonstrating that if macrophages and antigen-presenting cells (APCs) were well represented, monocytes and granulocytes were practically absent. Almost all of the infiltrating cells were positive for both MHC I and MHC II antigens and, in nine samples, a large number of neoplastic cells expressing MHC I were detected. A few neoplastic cells expressing MHC II were observed in seven cases. The presence of CD8+ lymphocytes, together with the large number of both infiltrating and neoplastic cells expressing MHC I, suggests that the lymphocytes mediate a cytotoxic reaction against the neoplastic cells. This hypothesis may underlie the favourable prognosis frequently associated with canine seminomas.

Intermediate filament expression in the canine prostate, unlike that in human prostate, is represented in the literature by only a few reports. In this study, the expression of cytokeratin (CK) and vimentin was examined in three normal canine prostates and 11 canine prostatic carcinomas. Monoclonal antibodies directed against vimentin, CK AE1/AE3, CK 18-8 (for luminal epithelial cells), CK 5, CK clone 8.12 and CK 14 (for basal cells) were employed. As in man, normal canine prostatic luminal cells were positive for CK 8-18. Basal cells were positive for CK 5 and CK clone 8.12 but, in contrast to findings in man, were negative for CK 14. Luminal cells were vimentin-negative, whereas in man they have been reported as vimentin-positive. The majority of carcinomas showed an undifferentiated histological pattern and all were positive for CK AE1/AE3 and for vimentin. Ten tumours were positive for CK 8-12, but six of them showed many cells co-expressing CK 14. Moreover, in two of these six cases a large number of neoplastic cells also reacted with CK clone 8.12 antibody, and in one of them co-expression of CK 5 was detectable. This co-expression, of luminal and basal cytokeratins, suggests a possible origin of the tumours from prostatic epithelial stem cells. Vimentin expression is an inconstant finding in human prostatic carcinomas; its almost uniform occurrence in canine carcinomas suggests a lesser degree of differentiation than in the human neoplasm.

This paper describes four cases of canine rhinosporidiosis which occurred in Italy in 1994 and 1995. Four dogs with a history of exposure to the muddy environment of rice fields, developed respiratory signs. Rhinoscopy revealed nasal polypoid lesions with a characteristic gross appearance due to the presence of multiple, tiny, white-yellowish spots representing sporangia filled with spores. In cytological samples obtained by brushing, many spores were present in an inflammatory background. Histologically, the polyps consisted of fibrovascular tissue embedding sporangia in different developmental stages, and free spores which elicited a severe pyogranulomatous inflammation. All the dogs were treated surgically and the condition did not recur in two cases during a year's follow-up and in the other two cases during two years.

Brush cytology was used as a diagnostic aid in 85 cats affected with chronic intranasal disease. Fifty-three of these cases, sampled over a five-year period, were included in this study, while the other cases were excluded due to poor cellularity of the cytological samples (nine cases) or a lack of histological or follow-up data (23 cases). Thirty-six brush samples were classified by cytology as inflammatory. Subsequent histological examination revealed a false negative diagnosis of neoplasia in six cats, two of which had malignant tumours (one adenocarcinoma and one lymphoma), the remaining four having benign tumours (two adenomas and two osteochondromas). Seventeen samples were classified by brush cytology as neoplastic. This was confirmed in 16 of these cases by histology or follow-up (nine epithelial malignant tumours, six lymphomas and one osteosarcoma). In the remaining case, a false positive diagnosis of lymphoma was made. The procedure had an overall 86.8 per cent (46/53) agreement between the diagnosis of inflammatory conditions versus neoplasia, with a sensitivity of 72.7 per cent, a specificity of 96.8 per cent, a predictive value of a positive test of 94.1 per cent and a predictive value of a negative test of 83.3 per cent.