Long-term follow-up of portal vein thrombosis in an American Cocker Spaniel with lobular dissecting hepatitis: a case report.

BACKGROUND: Lobular dissecting hepatitis (LDH) is a rare form of canine liver cirrhosis that may be accompanied by portal hypertension in American Cocker Spaniels. In human patients with liver cirrhosis, portal vein thrombosis (PVT) is a common complication. However, PVT has not been reported in dogs with LDH. Herein, we describe the long-term follow-up of PVT in an American Cocker Spaniel with LDH. CASE PRESENTATION: An 8-year-old neutered male American Cocker Spaniel presented with a 1-month history of severe abdominal effusion. The dog was histopathologically diagnosed with LDH and treated with low-dose prednisolone on day 14. On day 115, computed tomography angiography (CTA) confirmed the presence of a thrombus in the portal vein. Therefore, the dog was subcutaneously administered with the anticoagulant dalteparin, and low-dose prednisolone was continued. As a follow-up for PVT, CTA examinations were performed on days 207, 515, 886, and 1168, and the dog's antithrombin and D-dimer levels were measured. Following anticoagulant therapy, the dog was confirmed to have gradually increased antithrombin activity and decreased D-dimer concentrations. In addition, although the thrombus was confirmed to be in the same area of the portal vein system by CTA, atrophy and increased CT values due to organization were observed during the follow-up period. The dog's condition remained stable without clinical signs until day 1112 when it developed hepatic encephalopathy. The dog died on day 1208. On postmortem examination, histopathologically, the liver showed marked bile duct hyperplasia and fibrosis with chronic thrombus in the portal vein. CONCLUSIONS: This case demonstrated that low-dose glucocorticoid combined with dalteparin allowed long-term follow-up of PVT in an American Cocker Spaniel with LDH.

High-mobility group box 1 induces bone destruction associated with advanced oral squamous cancer via RAGE and TLR4.

Bone destruction of maxillary and mandibular bone by invasive oral squamous cell cancer (OSCC) raises various problems in the management of patients, resulting in poor outcomes and survival. However, the mechanism behind bone destruction by OSCC remains unclear. High-mobility group box 1 (HMGB1), a highly conserved ubiquitous nuclear non-histone DNA-binding protein, has been demonstrated to be secreted by aggressive cancers and regulate osteoclastogenesis, a central player during bone destruction. We therefore reasoned that HMGB1 secreted by OSCCs contributes to bone destruction. Our results showed that HMGB1 is produced by human cell lines of OSCC and promotes osteoclastogenesis via up-regulation of the expression of receptor activator of nuclear factor kappa-Β ligand in osteoblasts and osteocytes, and consequently osteoclastic bone destruction in mice. Further, we found that these actions of HMGB1 are mediated via the receptor for advanced glycation end products and toll-like receptors. These findings suggest that HMGB1 of OSCC and its down-stream signal pathways are potential targets for the treatment of bone destruction associated with advanced OSCC.

Successful management of portal vein thrombosis in a Yorkshire Terrier with protein-losing enteropathy.

BACKGROUND: Portal vein thrombosis (PVT) is a rare presentation in dogs with protein-losing enteropathy (PLE). Rivaroxaban, an oral, selective, direct factor Xa inhibitor, has not been reported to be administrated for canine PVT and the effect is unclear in dogs with PLE. CASE PRESENTATION: An 11-year-old Yorkshire Terrier presented with moderate ascites. The dog had severe hypoalbuminemia (1.2 g/dL), and a portal vein thrombus was confirmed on computed tomographic angiography (CTA). On endoscopic examination, it became apparent that the hypoalbuminemia was caused by PLE, which was consequent of lymphatic dilation and lymphoplasmacytic enteritis. Therefore, the dog was initially treated with oral administrations of spironolactone and clopidogrel, with dietary fat restriction. However, a follow-up CTA showed no changes in the ascites, thrombus, and portal vein to aorta (PV/Ao) ratio. Therefore, the dog was additionally prescribed rivaroxaban and low-dose prednisolone for the portal vein thrombus and hypoalbuminemia due to lymphoplasmacytic enteritis, respectively. Following the treatment, the PV/Ao ratio decreased because of a decrease in the thrombus and the ascites disappeared completely with an elevation of albumin concentration (1.9 g/dL). CONCLUSIONS: This case report demonstrated that oral administration of rivaroxaban combined with low-dose glucocorticoid was effective management for PVT in a dog with PLE.

The relationship between physical function in the elderly and judgment error in walking speed.

[Purpose] "Judgment error," defined as a difference between the actual and the imagined performance, is often observed in elderly persons. The aims of this study were to assess subjective judgment errors in elderly persons, and to evaluate the relationship between physical function and judgment error in walking speed. [Subjects and Methods] A total of 106 community-dwelling elderly individuals participated. Subjects observed video footage of a model walking an obstacle course, and were asked to subjectively compare the model's gait speed with their own gait speed. When the subjective comparison differed from the actual difference, it was considered as a judgment error. Physical function was compared between those with and without judgment error. [Results] Significant interaction effects between the actual performance and subjective perception were found for the walking time on the obstacle course and the Activities-specific Balance Confidence Scale score (utilized as an index of self-confidence in own balance ability and a fear of falling). [Conclusion] The results demonstrate that some elderly persons tend to overestimate their balance and ambulation function compared to another person, even though they had low physical function and low self-confidence in terms of balance. These elderly individuals might have a high risk of accidents.

Characteristics of tasks utilized for evaluation of judgment errors in the elderly.

[Purpose] The present study compared assessments utilized to evaluate judgment errors in the elderly. [Subjects and Methods] A total of 94 community-dwelling elderly participants in an examination of physical fitness for health promotion and health guidance in a rural area in Japan were included. Spatially and temporally predictive tasks were used to evaluate judgment errors. Distances measured on the Functional Reach and upward reaching tests were used to assess spatial prediction, and times measured on the Timed Up and Go test and Standardized Walking Obstacle Course were used to assess temporal prediction. Differences between the self-predicted values and actual results were deemed judgment errors. [Results] Significant differences were observed between self-predicted abilities and the patients' performances. Participants underestimated their abilities in spatially predictive tasks and overestimated them in temporally predictive tasks. On comparing the four tasks, there were significant differences in judgment error ratios between them. Statistical analysis indicated a significant difference in the judgment error ratio for the Standardized Walking Obstacle Course correlated with a history of falls. [Conclusion] Judgment errors were identified using both spatially and temporally predictive tasks. A temporally predictive task like the Standardized Walking Obstacle Course might better evaluate judgment errors in the elderly.

Terrein Exhibits Anti-tumor Activity by Suppressing Angiogenin Expression in Malignant Melanoma Cells.

BACKGROUND/AIM: Malignant melanoma is a tumor with a poor prognosis that can metastasize distally at an early stage. Terrein, a metabolite produced by Aspergillus terreus, suppresses the expression of angiogenin, an angiogenic factor. However, the pharmacological effects of natural terrein have not been elucidated, because only a small amount of terrein can be extracted from large fungal cultures. In this study, we investigated the antineoplastic effects of terrein on human malignant melanoma cells and its underlying mechanisms. MATERIALS AND METHODS: Human malignant melanoma cell lines were cultured in the presence of terrein and analyzed. Angiogenin production was evaluated using ELISA. Ribosome biosynthesis was evaluated using silver staining of the nucleolar organizer region. Intracellular signaling pathways were analyzed using western blotting. Malignant melanoma cells were transplanted subcutaneously into the backs of nude mice. The tumors were removed at 5 weeks and analyzed histopathologically. RESULTS: Terrein inhibited angiogenin expression, proliferation, migration, invasion, and ribosome biosynthesis in malignant melanoma cells. Terrein was shown to inhibit tumor growth and angiogenesis in animal models. CONCLUSION: This study demonstrated that terrein has anti-tumor effects against malignant melanoma. Furthermore, chemically synthesized non-natural terrein can be mass-produced and serve as a novel potential anti-tumor drug candidate.

Quantitative targeted absolute proteomic analysis of transporters, receptors and junction proteins for validation of human cerebral microvascular endothelial cell line hCMEC/D3 as a human blood-brain barrier model.

Human cerebral microvascular endothelial cell line hCMEC/D3 is an established model of the human blood-brain barrier (BBB). The purpose of the present study was to determine, by means of quantitative targeted absolute proteomics, the protein expression levels in hCMEC/D3 cells of multiple transporters, receptors and junction proteins for comparison with our previously reported findings in isolated human brain microvessels. Among 91 target molecules, 12 transporters, 2 receptors, 1 junction protein and 1 membrane marker were present at quantifiable levels in plasma membrane fraction of hCMEC/D3 cells. ABCA2, MDR1, MRP4, BCRP, GLUT1, 4F2hc, MCT1, ENT1, transferrin and insulin receptors and claudin-5 were detected in both hCMEC/D3 cells and human brain microvessels. After normalization based on Na(+)/K(+) ATPase expression, the differences in protein expression levels between hCMEC/D3 cells and human brain microvessels were within 4-fold for these proteins, with the exceptions of ENT1, transferrin receptor and claudin-5. ABCA8, LAT1, LRP1 and γ-GTP were below the limit of quantification in the cells, but were found in human brain microvessels. ABCA3, ABCA6, MRP1 and ATA1 were found only in hCMEC/D3 cells. Furthermore, compared with human umbilical vein endothelial cells (HUVECs) as reference nonbrain endothelial cells, MDR1 was found only in hCMEC/D3 cells, and GLUT1 expression was 15-fold higher in hCMEC/D3 cells than in HUVECs. In conclusion, this is the first study to examine the suitability and limitations of the hCMEC/D3 cell line as a BBB functional model in terms of quantitative expression levels of transporters, receptors and tight junction proteins.

Plasma renin activity and aldosterone concentration in dogs with acquired portosystemic collaterals.

BACKGROUND: The renin-angiotensin-aldosterone system (RAAS) is activated in humans with portal hypertension (PH) associated with liver disease. However, involvement of RAAS in dogs with intrahepatic PH is not clear. OBJECTIVE: To measure plasma renin activity (PRA) and plasma aldosterone concentration (PAC) in dogs with PH (chronic hepatitis [CH] and primary hypoplasia of the portal vein [PHPV]), dogs with extrahepatic congenital portosystemic shunt (EH-CPSS), and healthy dogs and to determine whether the RAAS is activated in dogs with PH. ANIMALS: Twenty-seven dogs with acquired portosystemic collaterals (APSCs; 15 dogs with CH, 12 dogs with PHPV), 9 dogs with EH-CPSS, and 10 healthy dogs. METHODS: Retrospective study. Plasma renin activity and PAC were measured by radioimmunoassay. RESULTS: Plasma renin activity was significantly higher in the CH group (median, 4.4 ng/mL/h) than in the EH-CPSS (median, 1.0 ng/mL/h; P < .01) and the healthy (median, 1.1 ng/mL/h; P < .01) groups. No significant differences were found between the PHPV group (median, 2.2 ng/mL/h) and other groups. Plasma aldosterone concentration was significantly higher in the CH (median, 111.0 pg/mL) and PHPV (median, 89.5 pg/mL) groups than in the EH-CPSS (median, 1.0 pg/mL; P < .001, P < .01, respectively) and healthy (median, 14.5 pg/mL; P < .001, P < .05, respectively) groups. CONCLUSIONS AND CLINICAL IMPORTANCE: Activation of the RAAS contributes to the pathophysiology of intrahepatic PH in dogs, suggesting that spironolactone may not only be effective for the treatment of ascites but also for the suppression of intrahepatic PH.

Diagnostic utility of computed tomographic angiography in dogs with portal vein thrombosis.

Computed tomographic (CT) angiography, the gold standard for diagnosing portal vein thrombosis (PVT) in humans, is poorly documented in dogs. Therefore, we retrospectively reviewed dogs with PVT diagnosed by CT angiography. Medical records of 13 client-owned dogs diagnosed with PVT by CT angiography were reviewed. All dogs had chronic PVT, and the most frequent clinical sign was vomiting (5/13), with pancreatitis the most frequent concurrent disease (6/13). All dogs tested for plasma D-dimer concentration (12/12) revealed elevated levels. On CT angiography, a thrombus was detected as a non-contrast enhancement structure in the portal vessel of 13 dogs. There was no evidence of complete obstruction of the portal vein in any of the dogs. The median luminal filling of the portal vein was 60.4%. The thrombus extension was variable among dogs, with a median of 34.9 mm. CT angiography identified the thrombus in the main portal vein of 12/13 dogs and multiple thrombus formation other than the main portal vein in 9/13 dogs. CT angiography provided specific information such as detecting the presence, location, and number of PVT in dogs. Therefore, CT angiography might be useful for the diagnosis and follow-up evaluation of PVT in dogs.

Three minimally invasive methods of measuring of portal vein pressure in healthy dogs.

We compared wedged hepatic venous pressure (WHVP), splenic pulp pressure (SPP) and trans-splenic portal vein pressure (TSPVP) in healthy dogs. We found that portal blood pressure could be measured in dogs using any of these techniques. The WHVP, SPP and TSPVP were 7.8 ± 1.0, 6.2 ± 0.8 and 6.8 ± 1.2 mmHg, respectively. Measuring SPP using ultrasound is most simple and minimally invasive, and it might be useful for evaluating portal hypertension in dogs with liver diseases.