Predictive Factors for Two-Year Survival in Dogs with Hepatobiliary Diseases: Importance of Clinical and Laboratory Monitoring.

Long-term outcomes and survival predictors for different clinicopathologies (idiopathic chronic hepatitis, liver fibrosis, vacuolar hepatopathy) in dogs with hepatobiliary diseases are poorly described. In this study, ninety dogs were followed up for up to five years to investigate clinical factors that predict two-year survival in canine patients after liver biopsy. Univariate and multivariate analyses were performed based on clinical and laboratory data to determine the association between clinical and laboratory data and mortality rates. Overall, the one-, two-, and five-year mortality rates were 28.9%, 45.6%, and 78.9%, respectively. Univariate analysis indicated that male gender, ascites, elevated serum gamma-glutamyl transpeptidase (GGT), hypercholesterolemia, hypoalbuminemia, prolonged activated partial thromboplastin clotting time (aPTT), and prolonged thrombin clotting time (TT) were associated with an increased two-year mortality rate. Results from multivariate analysis demonstrated a significant association between male gender (p = 0.022), elevated serum GGT (p < 0.001), hypoalbuminemia (p < 0.001), and prolonged aPTT (p < 0.001) and an increased two-year mortality rate, regardless of the specific type of liver pathology. Elevated GGT was associated with the highest risk for increased two-year mortality (95% CI: hazard ratio 6.02-41.21). In conclusion, various clinical factors in dogs with liver diseases are useful for prognosis prediction.

Feline Cyst-like Lymphocytic Cholangiohepatitis in a Cat: First Case Report.

A 5-year-old female neutered domestic short-haired cat presented with abdominal enlargement. An abdominal ultrasound revealed that large multiple hepatic cysts with irregular walls, hypoechoic fluid, and internal septations occupied most of the liver parenchyma. Serum liver enzymes, bilirubin, and bile acids concentrations were within normal limits. A fecal examination using simple floatation and formalin-ether sedimentation techniques was negative for liver fluke (Platynosomum fastosum), intestinal protozoa, and other helminth eggs. Praziquantel was prescribed for two distinct courses one month apart without obvious improvement of the hepatic cysts. An abdominal laparotomy and histopathological examination finally enabled diagnosis of cyst-like lymphocytic cholangiohepatitis of the liver tissue. Twelve weeks of oral prednisolone resulted in marked ultrasonographic improvement of the hepatic cysts. The liver parenchyma was heterogeneous and filled with multiple small anechoic cavities. Twenty-three months after ceasing the prednisolone, there was no recurrence of hepatic cysts.

Changes in Serum Lipid Profiles among Canine Patients Suffering from Chronic Hepatitis.

Hyperlipidemia is a risk factor for nonalcoholic fatty liver disease (NAFLD) in humans. However, the association between serum lipids and canine chronic hepatitis remains unknown. In this study, serum lipids, hepatic profiles, and hepatic ultrasound scores of healthy dogs and dogs with chronic hepatitis were evaluated. Serum triglyceride and cholesterol concentrations were significantly higher (p < 0.01) in dogs with chronic hepatitis. There were 62.2% of dogs with chronic hepatitis accompanied by hypertriglyceridemia, hypercholesterolemia, or both. Positive correlations were observed between serum ALT and cholesterol (r = 0.8287, p < 0.01), serum ALP and cholesterol (r = 0.8436, p < 0.01), serum GGT and cholesterol (r = 0.5640, p < 0.01), serum bile acid and cholesterol (r = 0.3310, p < 0.01) and serum ALP and triglycerides (r = 0.2582, p < 0.05). No significant differences were found between ultrasound scores of diseased dogs with and without hypertriglyceridemia and diseased dogs with and without hypercholesterolemia. Canine chronic hepatitis is associated with hyperlipidemia. A significant positive association was identified between hyperlipidemia, especially hypercholesterolemia, liver enzymes, and bile acid concentration in dogs suffering from chronic hepatitis. The underlying mechanisms connecting hyperlipidemia and canine chronic hepatitis remain elusive.

A descriptive study of the histopathologic and biochemical liver test abnormalities in dogs with liver disease in Thailand.

The present study describes the serum biochemical alterations and histopathological abnormalities in the liver tissue of dogs with liver disease. A survey of hepatic lesions was conducted using ultrasound-guided percutaneous needle biopsies. The hematologic and biochemical changes in dogs with liver lesions were recorded. Chronic hepatitis was the most common liver histopathologic finding (37.9%). Other common findings included liver fibrosis (19.5%), vacuolar hepatopathy (10.3%), cholangiohepatitis (9.2%), hepatocellular carcinoma (4.6%), cholangitis (3.4%), cholangiocarcinoma (2.3%), and congestive hepatopathy (2.3%). Greater than 2-fold elevation of serum alanine aminotransferase (ALT) was a useful indicator, with a sensitivity of 40% to 65% for diagnosing all liver pathologies. Greater than 2-fold elevation of serum alkaline phosphatase (ALP) without significant elevation of ALT was useful for diagnosing liver diseases affected by inflammatory or regressive changes (sensitivity of 40% to 50%). Elevation of ALT, ALP, or a combination of ALT and ALP had a high sensitivity of up to 90% for identifying dogs with liver pathology. Hepatic injury and cholestasis enzymes should be interpreted together with patient history, clinical signs, and liver ultrasonographic appearance before performing a liver biopsy.

La présente étude vise à décrire les modifications biochimiques sériques et les anomalies histopathologiques dans le tissu hépatique de chiens avec des maladies du foie. Une analyse des lésions hépatiques fut menée en utilisant des biopsies à l'aiguille percutanées guidées par échographie. Les changements hématologiques et biochimiques chez les chiens avec des lésions hépatiques furent notés. L'hépatite chronique était la trouvaille histopathologique du foie la plus fréquente (37,9 %). D'autres trouvailles fréquentes incluaient la fibrose du foie (19,5 %), l'hépatopathie vacuolaire (10,3 %), la cholangio-hépatite (9,2 %), le carcinome hépatocellulaire (4,6 %), la cholangite (3,4 %), le cholangiocarcinome (2,3 %) et l'hépatopathie congestive (2,3 %). Une augmentation de plus du double de l'alanine aminotransférase sérique (ALT) était un indicateur utile, avec une sensibilité de 40 % à 65 % pour diagnostiquer toutes les pathologies du foie. Une augmentation de plus du double de la phosphatase alcaline sérique (ALP) sans augmentation significative d'ALT était utile pour diagnostiquer des maladies hépatiques avec des changements inflammatoires ou régressifs (sensibilité de 40 % à 50 %). Une augmentation d'ALT, d'ALP ou une combinaison d'ALT et d'ALP avait une sensibilité élevée jusqu'à 90 % à identifier les chiens avec une pathologie du foie. Les blessures hépatiques et les enzymes d'une cholestase devraient être interprétés conjointement avec l'histoire du patient, les signes cliniques et l'apparence échographique du foie avant d'effectuer une biopsie du foie.(Traduit par Docteur Serge Messier).

Evaluation of hepatobiliary ultrasound scores in healthy dogs and dogs with liver diseases.

BACKGROUND AND AIM: Ultrasonography is the first-line method for examining the canine liver. Hepatic ultrasound scoring systems are widely described in human medicine, yet there is no information on the use of semi-quantitative ultrasound scoring systems in canine liver diseases. This study aimed to evaluate the hepatobiliary ultrasound scores between physically healthy dogs and dogs with primary liver diseases confirmed by clinical, biochemical, and histological parameters. We also evaluated the putative correlations between ultrasound scores and ALT or ALP levels. Moreover, the severity of ultrasound scoring and fold changes in liver enzymes was also evaluated. MATERIALS AND METHODS: A cross-sectional study design was conducted to compare the results of the six different parameters (liver surface, echogenicity of parenchyma, nodularity of parenchyma, gallbladder wall thickness, amount of gall sludge, and visibility of bile duct) of ultrasound scores between dogs with and without liver disease. RESULTS: Our results showed that 17.4%, 88.2%, and 100% of dogs with liver diseases were identified according to the ultrasound severity classified as mild (total score 0-2), moderate (total score 3-5), and severe (total score 6-12). Approximately 30% of patients with chronic hepatitis, the most common canine liver disease, presented with normal or mild ultrasound score category, whereas most of the patients with vacuolar hepatopathy and steroid-induced hepatopathy due to secondary reactive changes had moderate-to-severe ultrasound score category. There were 75% of patients with tumor and 80% of patients with hepatic fibrosis that were identified with severe ultrasound score category. Dogs with moderate-to-severe ultrasound scores had significant liver enzyme elevation (both alanine aminotransferase [ALT] and alkaline phosphatase [ALP]) compared to those of dogs with mild ultrasound scores. Ultrasound score was moderately associated with ALT and highly associated with ALP levels (p=0.553 and p=0.730, respectively). CONCLUSION: Our semi-quantitative, simplified ultrasonographic scoring system may have potential to be used as a screening tool to detect some groups of liver diseases.

Morphological characterization of canine retrobulbar lymphoma.

This report characterized seven cases of canine retrobulbar lymphoma that have been diagnosed during 2008 to 2014 by immunophenotyping of CD3 and Pax5. Classification of lymphoma were performed according to the revised WHO guidelines. Four retrobulbar lymphomas were of T-cell origin, while the others were of B-cell. Out of 7 cases, four subtypes were diagnosed in this study; T-cell-rich large B-cell lymphoma (3/7), T-cell lymphoblastic lymphoma (2/7), peripheral T-cell lymphoma (1/7), and cutaneous nonepitheliotropic lymphoma (1/7). T-cell-rich large B-cell lymphoma was found to be the most frequent subtype found.

Dacryops of the Third Eyelid in a cat.

A 9-month-old female Domestic Short-haired cat was presented with a mass of three-month duration at the base of the third eyelid of the right eye (OD). Fine-needle aspiration was carried out at another clinic, revealing clear fluid. The mass soon reformed, and the cat was referred. Ophthalmic examination revealed a pale-pink, smooth, oval mass under the conjunctiva on the anterior aspect of the third eyelid. Surgical removal of the mass was performed. Histopathology revealed a large dilated cyst together with a number of small cysts lined by simple cuboidal, and low squamous epithelium with some secretory cells. Dacryops of the third eyelid lacrimal gland was diagnosed. The eye healed uneventfully after surgery, and no recurrence was seen during one year of follow-up.

Tobacco Mosaic Virus Functionalized Alginate Hydrogel Scaffolds for Bone Regeneration in Rats with Cranial Defect.

Plant viruses have been highlighted among material research due to their well-defined structures in nanoscale, monodispersity, stability, and chemical functionalities. Each of the thousands coat protein subunits on a viral nanoparticle can be homogeneously modified, chemically and genetically, with a functional ligand leading to a high-density and spatial distribution of ligands on each particle (multivalency). Previous reports from our group have evidenced that substrates coated with Tobacco mosaic virus (TMV) and its mutant promote early osteogenesis of mesenchymal stem cells (MSCs). We then fabricated a three-dimensional (3D) biopolymeric scaffold with rod-like TMV in the form of a sponge-like hydrogel for tissue engineering purposes. The hydrogel was functionalized with the cellular recognition peptide, arginine-glycine-aspartic acid (RGD), through an incorporation of an RGD mutant of TMV (TMV-RGD). The virus-functionalized hydrogel materials were shown to aid bone differentiation of MSCs in vitro. Herein, we performed an in vivo study based on the TMV and TMV-RGD hydrogels in Sprague-Dawley rats with cranial bone defects. This report substantiated the hypothesis that TMV-functionalized hydrogel scaffolds did not cause systemic toxicity when implanted in the defect site and that the TMV-based hydrogel platform can support cell localization and can be further optimized for bone regeneration and repair.

Loss of NDRG2 expression activates PI3K-AKT signalling via PTEN phosphorylation in ATLL and other cancers.

Constitutive phosphatidylinositol 3-kinase (PI3K)-AKT activation has a causal role in adult T-cell leukaemia-lymphoma (ATLL) and other cancers. ATLL cells do not harbour genetic alterations in PTEN and PI3KCA but express high levels of PTEN that is highly phosphorylated at its C-terminal tail. Here we report a mechanism for the N-myc downstream-regulated gene 2 (NDRG2)-dependent regulation of PTEN phosphatase activity via the dephosphorylation of PTEN at the Ser380, Thr382 and Thr383 cluster within the C-terminal tail. We show that NDRG2 is a PTEN-binding protein that recruits protein phosphatase 2A (PP2A) to PTEN. The expression of NDRG2 is frequently downregulated in ATLL, resulting in enhanced phosphorylation of PTEN at the Ser380/Thr382/Thr383 cluster and enhanced activation of the PI3K-AKT pathway. Given the high incidence of T-cell lymphoma and other cancers in NDRG2-deficient mice, PI3K-AKT activation via enhanced PTEN phosphorylation may be critical for the development of cancer.

A new host record of Sphaerospora epinepheli (Myxosporea: Bivalvulida) occurring on orange-spotted grouper Epinephelus coioides from Thailand: epidemiology, histopathology and phylogenetic position.

In 1991, the first record of Sphaerospora epinepheli was described as a kidney parasite of wild and cultured malabar grouper, Epinephelus malabaricus, along coastlines of Thailand, the Gulf of Thailand and the Andaman Sea. However, the present study detected high infection of this parasite in kidney renal tubes of orange spotted grouper, Epinephelus coioides, collected from Andaman Sea. The highest infection rate of 36.82% was observed during the rainy season in 2009 in Phang-Nga Bay, in the north of Andaman Sea, which is an important grouper production site in Thailand. The biological and histopathological data of the parasite in this new host record are presented. Species classification is described based on morphological data of mature spore and molecular analysis of myxosporean 18S rDNA phylogeny including that of S. epinepheli which infected E. malabaricus. The genetic position of this parasite found in two host species was also studied. The phylogenetic tree analysis of small-subunit rDNA sequences of S. epinepheli from both infected hosts was constructed using two algorithms, maximum likelihood (ML) and Bayesian inference (BI). They were placed in the clustered basal sphaerosporid clade that contain four long SSU rDNA sphaerosporid species including Sphaerospora truttae, Sphaerospora elegans, Sphaerospora ranae, Sphaerospora fugu and Bipteria formosa with strong bootstrap supports. Histopathologically, renal intratubular myxosporean spores were associated with tubulonephosis, tubular necrosis, chronic interstitial nephritis and mimic membranoproliferative glomerulonephritis. This myxosporean parasite appears to be a significant pathogen on the basis of pathological changes in the renal tubules and is highly distributed in orange-spotted grouper.