MRI ischemic and hemorrhagic lesions in arterial and venous territories characterize central nervous system intravascular lymphoma in dogs.

Intravascular lymphoma (IVL) is characterized by the proliferation of large malignant lymphocytes within the lumen of blood vessels. This retrospective, multi-center, case series study aimed to describe the MRI features of confirmed central nervous system IVL in dogs and compare them with histopathological findings. Medical record databases from seven veterinary centers were searched for cases of histologically confirmed IVL. Dogs were included if an MRI was performed. The MRI studies and histopathology samples were reviewed to compare the MRI changes with the histopathological findings. Twelve dogs met the inclusion criteria (12 brains and three spinal cords). Imaging of the brains revealed multifocal T2-weighted/FLAIR hyperintense and T1-weighted iso-hypointense lesions, with variable contrast enhancement; areas of abnormal diffusion both in arterial and venous territories in diffusion-weighted imaging; and meningeal enhancement. On gradient echo images (GRE), the changes comprised tubular susceptibility artifacts, consistent with the "susceptibility vessel sign", and additional variably sized/shaped intraparenchymal susceptibility artifacts. Spinal cord lesions presented as fusiform T2-weighted hyperintensities with scattered susceptibility artifacts on GRE and variable parenchymal and meningeal contrast enhancement. On histopathology, subarachnoid hemorrhages and neuroparenchymal areas of edema and necrosis, with or without hemorrhage, indicating ischemic and hemorrhagic infarctions, were found. These lesions were concurrent with severely dilated meningeal and parenchymal arteries and veins plugged by neoplastic lymphocytes and fibrin. Due to the unique angiocentric distribution of IVL, ischemic and hemorrhagic infarcts of variable chronicity affecting both the arterial and venous territories associated with thrombi formation can be detected on MRI.

Pharmacological Activation of Nrf2 Enhances Functional Liver Regeneration.

BACKGROUND AND AIMS: The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) regulates an array of cytoprotective genes, yet studies in transgenic mice have led to conflicting reports on its role in liver regeneration. We aimed to test the hypothesis that pharmacological activation of Nrf2 would enhance liver regeneration. APPROACH AND RESULTS: Wild-type and Nrf2 null mice were administered bardoxolone methyl (CDDO-Me), a potent activator of Nrf2 that has entered clinical development, and then subjected to two-thirds partial hepatectomy. Using translational noninvasive imaging techniques, CDDO-Me was shown to enhance the rate of restoration of liver volume (MRI) and improve liver function (multispectral optoacoustic imaging of indocyanine green clearance) in wild-type, but not Nrf2 null, mice following partial hepatectomy. Using immunofluorescence imaging and whole transcriptome analysis, these effects were found to be associated with an increase in hepatocyte hypertrophy and proliferation, the suppression of immune and inflammatory signals, and metabolic adaptation in the remnant liver tissue. Similar processes were modulated following exposure of primary human hepatocytes to CDDO-Me, highlighting the potential relevance of our findings to patients. CONCLUSIONS: Our results indicate that pharmacological activation of Nrf2 is a promising strategy for enhancing functional liver regeneration. Such an approach could therefore aid the recovery of patients undergoing liver surgery and support the treatment of acute and chronic liver disease.

Pulmonary bleeding in racehorses: A gross, histologic, and ultrastructural comparison of exercise-induced pulmonary hemorrhage and exercise-associated fatal pulmonary hemorrhage.

Exercise-induced pulmonary hemorrhage (EIPH) is a common condition of Thoroughbred racehorses that is usually responsible for reduced performance, while exercise-associated fatal pulmonary hemorrhage (EAFPH) is characterized by severe pulmonary bleeding of unknown pathogenesis resulting in sudden death during strenuous exercise. The aim of the study was to characterize and compare anamnestic data together with pulmonary gross, histologic, and ultrastructural findings in racehorses with EIPH (n = 10), EAFPH (n = 10), and control horses (n = 5). No differences in anamnesis were identified between the 3 groups. Grossly cranial lobe reddening and edema scores were significantly more prevalent and severe in the EAFPH group compared with the EIPH and control groups. Histologically, hemorrhage scores were higher in the EAFPH group, while hemosiderophages, iron encrustations of collagen and elastin fibers, and vascular remodeling scores were significantly higher in EIPH group compared with the EAFPH and control groups. In all groups, caudal lung locations exhibited a significantly higher score for vascular remodeling, hemosiderophage accumulation, iron encrustation, and type II pneumocyte hyperplasia when compared with cranial, dorsal, and ventral locations. Ultrastructural analysis of perivascular collagen showed fibrils with significantly larger diameters in the EAFPH group compared with the EIPH group but not compared with the control group. This study demonstrates that lungs of horses that experienced EAFPH show significantly less vascular remodeling and other long-term pulmonary abnormalities that characterize horses with EIPH.

Gastric Intravascular Lymphoma in a Dog: Case Report and Literature Review.

Intravascular lymphoma (IVL) is a rare, high-grade, extranodal lymphoma characterized by selective proliferation of neoplastic lymphocytes within the lumen of small vessels. A 10 yr old female intact mixed-breed dog was presented with a 7 mo history of vomiting and anorexia. Physical examination revealed abdominal discomfort. Ultrasonography and endoscopy identified a submucosal gastric mass. Excision was performed by partial gastrectomy and histopathology and immunohistochemistry confirmed a T-cell IVL. The owner declined chemotherapy, and the dog was instead treated palliatively with prednisolone. Two months after surgery, vomiting recurred and abdominal ultrasonography revealed a large gastric ulcer with focal peritonitis. The dog was euthanized 4 mo after initial presentation and postmortem examination confirmed IVL recurrence in the stomach and an isolated nodule of neoplastic cells in the omentum. No involvement of other organs was found following histopathological examination. This is the first description of primary gastric intravascular lymphoma causing chronic vomiting in a dog.

Long-term follow-up of single crowns supported by short, moderately rough implants-A prospective 10-year cohort study.

OBJECTIVES: To evaluate prospectively the clinical and radiographic outcomes after ten years of short (6 mm) implants with a moderately rough surface supporting single crowns in the posterior region. MATERIAL AND METHODS: Forty 6 mm modified sandblasted large-grit acid-etched (mod-SLA), soft tissue level implants were installed in the distal segments of 35 consecutive patients. After 6 weeks of healing, abutments were tightened, and single porcelain-fused-to-metal crowns were cemented. Implant survival, marginal bone loss, and clinical crown/implant ratio were evaluated at various time intervals up to 10 years after loading. RESULTS: Two out of the 40 implants were lost before loading, one implant was lost after 7 years because of peri-implantitis. One patient with two implants died and was excluded from analysis. Two patients did not come at the 10-year follow-up and were considered as drop out (2 implants). The survival rate was 91.7% (n = 36). Thirty-three implants were available for marginal bone loss evaluation. A mean marginal bone loss after 10 years of function was 0.8 ± 0.7 mm. Between 5 and 10 years, the loss was 0.2 ± 0.4 mm. No technical complications were registered during the 10-year period. The clinical crown/implant ratio increased with time from 1.6 at the delivery of the prosthesis to 2.0 after 10 years of loading with no increase between 5 and 10 years. CONCLUSION: Short (6 mm) implants with a moderately rough surface supporting single crowns in the posterior region and loaded after 6-7 weeks maintained full function for at least 10 years with low marginal bone resorption.

6-mm-long implants loaded with fiber-reinforced composite resin-bonded fixed prostheses (FRCRBFDPs). A 5-year prospective study.

AIM: To evaluate the clinical and radiographic outcomes and the survival rates of fiber-reinforced composite resin-bonded fixed prostheses (FRCRBFDPs) placed in the posterior area supported by two short (6 mm) implants. MATERIALS AND METHODS: Twenty consecutive patients received 40 SLActive 6-mm-long implants with a diameter of 4.1 mm (n = 29) or 4.8 mm (n = 11). Insertion torques and RFA (Resonance Frequency Analysis) were measured at implant installation. The prosthetic rehabilitation was performed after 8 weeks from insertion with a screw-retained two- or three-unit fixed dental prosthesis fabricated of FRCRBFDPs. Implant survival rates and marginal bone levels were evaluated at various time intervals until 5 years after loading. RESULTS: Two of 20 patients lost four implants supporting two FRCRBFDPs between the second and the third year of follow-up (cumulative survival rate: 90% after 5 years). Four patients suffered a fracture of the prosthetic reconstruction, and the success rate of the rehabilitation was 70% after 5 years. A mean marginal bone loss of 0.30 ± 0.34 mm was found after 5 years of function at the remaining implants. CONCLUSION: The survival of short implants was 90% owing to two bridges losses in the maxilla. However, the success rate of FRCRBFDPs over 5 years was only at 70%.

Herpes simplex encephalitis is linked with selective mitochondrial damage; a post-mortem and in vitro study.

Herpes simplex virus type-1 (HSV-1) encephalitis (HSE) is the most commonly diagnosed cause of viral encephalitis in western countries. Despite antiviral treatment, HSE remains a devastating disease with high morbidity and mortality. Improved understanding of pathogenesis may lead to more effective therapies. Mitochondrial damage has been reported during HSV infection in vitro. However, whether it occurs in the human brain and whether this contributes to the pathogenesis has not been fully explored. Minocycline, an antibiotic, has been reported to protect mitochondria and limit brain damage. Minocycline has not been studied in HSV infection. In the first genome-wide transcriptomic study of post-mortem human HSE brain tissue, we demonstrated a highly preferential reduction in mitochondrial genome (MtDNA) encoded transcripts in HSE cases (n = 3) compared to controls (n = 5). Brain tissue exhibited a significant inverse correlation for immunostaining between cytochrome c oxidase subunit 1 (CO1), a MtDNA encoded enzyme subunit, and HSV-1; with lower abundance for mitochondrial protein in regions where HSV-1 was abundant. Preferential loss of mitochondrial function, among MtDNA encoded components, was confirmed using an in vitro primary human astrocyte HSV-1 infection model. Dysfunction of cytochrome c oxidase (CO), a mitochondrial enzyme composed predominantly of MtDNA encoded subunits, preceded that of succinate dehydrogenase (composed entirely of nuclear encoded subunits). Minocycline treated astrocytes exhibited higher CO1 transcript abundance, sustained CO activity and cell viability compared to non-treated astrocytes. Based on observations from HSE patient tissue, this study highlights mitochondrial damage as a critical and early event during HSV-1 infection. We demonstrate minocycline preserves mitochondrial function and cell viability during HSV-1 infection. Minocycline, and mitochondrial protection, offers a novel adjunctive therapeutic approach for limiting brain cell damage and potentially improving outcome among HSE patients.

Integrated transcriptomic and proteomic analyses uncover regulatory roles of Nrf2 in the kidney.

The transcription factor Nrf2 exerts protective effects in numerous experimental models of acute kidney injury, and is a promising therapeutic target in chronic kidney disease. To provide a detailed insight into the regulatory roles of Nrf2 in the kidney, we performed integrated transcriptomic and proteomic analyses of kidney tissue from wild-type and Nrf2 knockout mice treated with the Nrf2 inducer methyl-2-cyano-3,12-dioxooleano-1,9-dien-28-oate (CDDO-Me, also known as bardoxolone methyl). After 24 h, analyses identified 2561 transcripts and 240 proteins that were differentially expressed in the kidneys of Nrf2 knockout mice, compared with those of wild-type counterparts, and 3122 transcripts and 68 proteins that were differentially expressed in wild-type mice treated with CDDO-Me, compared with those of vehicle control. In the light of their sensitivity to genetic and pharmacological modulation of renal Nrf2 activity, genes/proteins that regulate xenobiotic disposition, redox balance, the intra/extracellular transport of small molecules, and the supply of NADPH and other cellular fuels were found to be positively regulated by Nrf2 in the kidney. This was verified by qPCR, immunoblotting, pathway analysis, and immunohistochemistry. In addition, the levels of NADPH and glutathione were found to be significantly decreased in the kidneys of Nrf2 knockout mice. Thus, Nrf2 regulates genes that coordinate homeostatic processes in the kidney, highlighting its potential as a novel therapeutic target.

Early loading of 6-mm-short implants with a moderately rough surface supporting single crowns--a prospective 5-year cohort study.

AIM: To evaluate prospectively the clinical and radiographic outcomes after 5 years of early loading of 6-mm implants with a moderately rough (SLActive(®) ) surface supporting single crowns in the posterior regions. MATERIAL AND METHODS: Thirty-five consecutive patients received 40 SLActive(®) (Straumann) 6-mm implants with a diameter of 4.1 mm (n = 19) or 4.8 mm (n = 21). Insertion torque and resonance frequency analysis (RFA) were measured at implant installation. RFA was also measured at abutment connection. SynOcta abutments were tightened with 35 Ncm after 6 weeks of healing, and single porcelain fuse to metal crowns was cemented within 1 week. Implant survival rate and marginal bone loss were evaluated at various time intervals until 5 years after loading. The clinical crown/implant ratio was calculated as well. RESULTS: Two of 40 implants were lost before loading (incorporation rate 95%), and no further implant loss or technical complications were encountered during the 5-year follow-up period. A mean marginal bone loss of 0.7 ± 0.6 mm was found after 5 years of function. The clinical crown/implant ratio increased with time from 1.6 at the delivery of the prosthesis to 2 after 5 years of loading. CONCLUSION: Six millimeter implants with a SLActive(®) moderately rough surface supporting single crowns in the posterior region and loaded after 6-7 weeks maintained full function for at least 5 year with low marginal bone resorption.

Influence on alveolar resorption of the buccal bony plate width in the edentulous ridge expansion (E.R.E.)--an experimental study in the dog.

OBJECTIVE: To compare the hard tissue changes at implants installed applying edentulous ridge expansion (E.R.E.) at sites with a buccal bony wall thickness of 1 or 2 mm. MATERIAL AND METHODS: In six Labrador dogs, the first and second maxillary incisors were extracted, and the buccal alveolar bony plates and septa were removed. After 3 months of healing, partial-thickness flaps were dissected, and the E.R.E. was applied bilaterally. Hence, an expansion of the buccal bony crest was obtained in both sides of the maxilla with a displacement of either a 1- or a 2-mm-wide buccal bony plate at the test and control sites, respectively. After 3 months of healing, biopsies were obtained for histological analyses. RESULTS: A buccal vertical resorption of the alveolar crest of 2.3 ± 0.8 and 2.1 ± 1.1 mm, and a coronal level of osseointegration at the buccal aspect of 2.7 ± 0.5 and 2.9 ± 0.9 mm were found at the test (1 mm) and control (2 mm) sites, respectively. The differences did not reach statistical significance. The mean values of the mineralized bone-to-implant contact (MBIC%) ranged from 62% to 73% at the buccal and lingual sites. No statistically significant differences were found. Horizontal volume gains of 1.8 and 1.1 mm were observed at the test and control sites, respectively, and the difference being statistically significant. CONCLUSIONS: Implants installed using the E.R.E. technique yielded a high degree of osseointegration. It is suggested that the displacement of buccal bony plates of 1 mm thickness is preferable compared with that of wider dimensions.

A case of epithelioid glioblastoma with lung metastases in a young Cane Corso dog.

Astrocytomas are relatively common primary brain tumours of humans and companion animals. In dogs, they represent approximately 17-28% of primary central nervous system tumours. However, extracranial metastasis is extremely rare. This case report describes a grade IV astrocytoma (glioblastoma) in the cerebrum of a young Cane Corso dog with pulmonary metastases. The diagnosis was obtained via histopathological morphology and immunophenotyping, which showed strong positivity for glial fibrillary acidic protein, vimentin and connexin-43. The glioblastoma in this Cane Corso had epithelioid morphology with histological features of malignancy including high mitotic count, microvascular proliferation, serpentine necrosis and subventricular zone involvement. Epithelioid glioblastoma is a rare subtype that has only relatively recently been formally acknowledged in human medicine and it can also pose a diagnostic challenge in veterinary medicine.

Anti-fibrotic effects of fresh and cryopreserved human amniotic membrane in a rat liver fibrosis model.

The human amniotic membrane (hAM), thanks to its favorable properties, including anti-inflammatory, anti-fibrotic and pro-regenerative effects, is a well-known surgical material for many clinical applications, when used both freshly after isolation and after preservation. We have shown previously that hAM patching is a potential approach to counteract liver fibrosis. Indeed, when fresh hAM was used to cover the liver surface of rats with liver fibrosis induced by the bile duct ligation (BDL) procedure, the progression and severity of fibrosis were significantly reduced. Since cryopreservation enables safety and long-term storage of hAM but may influence its functional properties, here we compared the anti-fibrotic effects of fresh and cryopreserved hAM in rats with BDL-induced liver fibrosis. After BDL, the rat liver was covered with a piece of fresh or cryopreserved hAM, or left untreated. Six weeks later, the degree of liver fibrosis was assessed histologically using the Knodell and the METAVIR scoring systems. Digital image analysis was used to quantify the percentage of the areas of each liver section displaying ductular reaction, extracellular matrix (ECM) deposition, activated myofibroblasts and hepatic stellate cells (HSCs). Liver collagen content was also determined by spectrophotometric technique. The degree of liver fibrosis, ductular reaction, ECM deposition, and the number of activated myofibroblasts and HSCs were all significantly reduced in hAM-treated rats compared to control animals. Fresh and cryopreserved hAM produced the same anti-fibrotic effects. These findings indicate that cryopreservation maintains the anti-fibrotic properties of hAM when used as a patch to reduce the severity of liver fibrosis.

In Vivo Tumorigenicity of the 20q11.21 Amplicon in an Engraftment Model of hPSCs and Differentiated Liver Cells.

Human pluripotent stem cells (hPSCs) are a promising source of somatic cells for clinical applications and disease modelling. However, during culture they accumulate genetic aberrations such as amplification of 20q11.21 which occurs in approximately 20% of extensively cultured hPSC lines and confers a BCL2L1-mediated survival advantage. During the production of the large number of cells required for transplantation and therapy these aberrations may become unavoidable which has important safety implications for therapies and may also impact upon disease modelling. Presently, these risks are poorly understood; whilst it is apparent that large-scale genetic aberrations can pose an oncogenic risk, the risks associated with smaller, more insidious changes have not been fully explored. In this report, the effects of engraftment of human embryonic stem cells (hESCs) and hESC-derived hepatocyte-like cells (HLCs) with and without amplification of the 20q11.21 minimal amplicon and isochromosome 20q (i20q) in SCID-beige mice are presented. The cells were tracked in vivo using a luminescent reporter over a period of approximately four months. Intrasplenic injection of hESCs showed greater engraftment potential and the formation of more severely disruptive lesions in the liver and spleen of animals injected with cells containing 20q11.21 compared with i20q and wild type. HLCs with 20q11.21 engrafted more successfully and formed more severely disruptive lesions than wild type cells or cells with i20q. These results reinforce the notion that karyotyping of therapeutic hPSC is required for transplant, and suggest that screening for known common aberrations is necessary. Further work to identify commonly arising genetic aberrations should be performed and routine screening for hPSCs intended for therapeutic use should be used.

Disseminated Nocardiosis Caused by Nocardia farcinica in Two Puppy Siblings.

Systemic nocardiosis due to Nocardia farcinica has not been reported in canine outbreaks. Two 14-week-old female Dogue de Bordeaux siblings presented with fever and severe, acute onset limb lameness; traumatic lesions with evidence of infection were identified over the lame limbs of both dogs. The patients were euthanised owing to lack of therapeutic response and rapid escalation to systemic infection with central nervous system manifestations. The post-mortem changes consisted of multiple disseminated abscesses, mainly affecting the skin and subcutis at the limb traumatic injuries, local and hilar lymph nodes, lung, kidney and brain. Bacterial culture and identification via MALDI-TOF and 16S rRNA sequencing revealed Nocardia farcinica from several of these sites in both dogs. Clinical significance of the isolate was supported by cytology of the post-mortem organs' impression smears showing numerous branching filamentous bacteria associated with inflammation. The organism displayed marked multidrug-resistance. No history of immunosuppression was available, and immunohistochemistry ruled out viral pathogens as canine distemper and parvovirus. N. farcinica should be considered as a potential differential cause of sudden lameness and systemic infection in dogs with traumatic skin lesions over the limbs. This is the first reported small-scale outbreak of systemic nocardiosis in dogs due to N. farcinica.

Quantitative histologic evaluation reveals different degree of liver atrophy in cachectic and starved dogs.

Cases of neglect in dogs are among the forensic cases submitted most commonly for postmortem examination. Starvation is a form of primary protein-energy malnutrition in which the availability of food is severely restricted or absent; cachexia is a form of protein-energy malnutrition secondary to progressive metabolic derangement during chronic diseases. Despite both conditions leading to an emaciated appearance of the cadaver, discrimination between the two is crucial in forensic cases. We hypothesized that among emaciated dogs, the degree of liver atrophy in starved animals is higher than in cachectic ones, and that this can be investigated microscopically, regardless of the degree of cadaver decomposition. We studied 46 animals: 23 starved, 11 cachectic, and 12 control dogs. Portal tracts were identified by the presence of a bile duct and associated vascular structures recognizable by a thin rim of collagen still visible regardless of the degree of cadaver decomposition. The number of portal tracts per lpf (10×) was used as an indirect measure of atrophy. The number of portal tracts in starved dogs was significantly higher (p < 0.01) compared to both cachectic and control dogs, indicating a higher degree of liver atrophy in starvation. Measuring the density of portal tracts offers a reliable additional tool for discrimination between starvation and cachexia.

Leukocyte numbers and intestinal mucosal morphometrics in horses with no clinical intestinal disease.

Healthy horses and other animals have large numbers of resident leukocytes in the intestinal wall, but there is scant information regarding which and how many leukocytes are normally present in the equine intestinal wall. Our aim was to provide a reference range of leukocytes in the intestinal mucosal and submucosal propria of normal horses. We included in our study intestinal tissues from 22 Thoroughbred racehorses with no clinical intestinal disease, which had been euthanized because of catastrophic musculoskeletal injuries. Neutrophils, lymphocytes, eosinophils, macrophages, and plasma cells were counted in 5 random 17,600-µm2 areas of villus lamina propria of the duodenum, jejunum, and ileum, and deep lamina propria of the duodenum, jejunum, ileum, right ventral colon, left ventral colon, left dorsal colon, right dorsal colon, and small colon. Other features investigated in the same intestinal segments included villus height and width (small intestine), presence of ciliated protozoa, Paneth cells number, subcryptal leukocyte layers (number of leukocyte layers between the bottom of the crypts and the muscularis mucosae), and submucosal leukocytes. Lymphocytes were the most numerous cells in all segments analyzed, followed by plasma cells, eosinophils, macrophages, and neutrophils. Eosinophil numbers were significantly higher in both lamina propria and submucosa of the large intestine than in the small intestine. The duodenum had shorter and thinner villi than either jejunum or ileum. The data provided from our study will be useful for diagnosticians examining inflammatory processes in the intestinal tract of horses.

Elephant Endotheliotropic Herpesvirus 4 and Clostridium perfringens Type C Fatal Co-Infection in an Adult Asian Elephant (Elephas maximus).

Elephant endotheliotropic herpesvirus hemorrhagic disease (EEHV-HD) is an acute, often fatal, multisystemic hemorrhagic disease and one of the most significant causes of mortality of Asian elephants in captivity. Most fatal cases of EEHV-HD are associated with EEHV1A and EEHV1B in juveniles. This case report describes the clinical and pathological features of a fatal co-infection of Clostridium perfringens type C and EEHV-HD, caused by EEHV4, in an adult female Asian elephant. Although fatal clostridial enterotoxemia has been occasionally reported in elephants, this report highlights the importance of having both EEHV-HD and clostridial enterotoxemia as potential differential diagnoses in cases of widespread tissue necrosis and internal hemorrhage in elephants, regardless of the animal age group, due to their macroscopic similarities, frequent co-occurrence and cumulative morbid potential.

Microcystic meningioma of the fourth ventricle in a dog.

A 5-year-old female cross-breed dog was presented with a 1-month history of progressive changes in the posture of the head and in the gait. At neurological examination the dog showed a central vestibular syndrome lateralized to the left. MRI showed a space occupying lesion within the fourth ventricle, characterized by iso- to hypointensity in T1 and hyperintensity in T2 with a heterogeneous contrast uptake. Histologically, a neoplasia composed of meningothelial cells forming compact whorls with slight atypia, and stellate cells delimitating microcysts containing eosinophilic fluid was observed. Neoplastic cells were positive for vimentin and negative for GFAP and FVIII. A diagnosis of intraventricular microcystic meningioma was achieved. Intraventricular meningiomas in dogs are rarely encountered and reports of meningiomas within the fourth ventricle have not yet been described. Although choroid plexus tumor is the most frequent neoplasia localized in the fourth ventricle, intraventricular meningioma should be included in the differential diagnoses.

The use of Corticotropin-releasing factor (CRF) as a marker of agonic stress in abused dogs: Preliminary results.

In Veterinary Forensic Medicine, determination of the degree of animal suffering is an essential element for the prosecution of perpetrators of animal abuse. The purpose of this study is to find a suitable immunohistochemical marker for the assessment of suffering to be routinely used in Veterinary Forensic Pathology, by analyzing the expression of Corticotropin-releasing factor (CRF) in formalin-fixed brains of dogs as a measurement of the agonic stress. CRF, a key peptide element in exogenous and endogenous stressors adaptation, can regulate endocrine-behavioral responses to stress stimulating pituitary ACTH release and consequent adrenal secretion of glucocorticoids. Since CRF acts in days or weeks, this study investigates its role as a potential distinctive marker between sudden death and death associated with a longer agonic period. The study used immunohistochemistry (IHC) to evaluate the CRF expression in the brain of dogs that suffered sudden death, as compared to dogs that died after long-term agonic stress. IHC labelling analysis was performed with machine-learning-based software and the results were statistically evaluated. Our results demonstrate for the first time that CRF is a promising marker of stress in abused patients also in Veterinary Medicine.

A Case Series of Five Horses with Superficial Digital Flexor Tendon Lesions in the Carpal Canal.

This case series discusses the clinical presentation, ultrasonographic findings, treatment, and outcome of 5 horses with superficial digital flexor tendon (SDFT) lesions within the carpal canal. The horses' ages ranged from 11-28 years, and presented with an acute, unilateral forelimb lameness which worsened following proximal limb flexion. The presence of a lesion within the SDFT of the carpal canal was accompanied by a mild swelling of the palmar carpal region in most cases. Diagnostic anesthesia of the ulnar nerve, when performed, abolished the lameness. Ultrasound evaluation revealed an increased cross-sectional area (CSA) of the superficial digital flexor tendon compared to the contralateral, sound limb and a loss of tendon fiber architecture within the palmar aspect of the affected tendon, most readily identifiable upon longitudinal ultrasound images. Three out of the five horses returned to their previous level of performance, and two were euthanized. A back at the knee carpal region conformation was associated with a poorer prognosis in these cases. An intratendinous fibroma was identified on histopathological analysis of one-horse following euthanazia, which has been recorded in a complementary short communication.