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Objective: To evaluate the agreement between cardiac output (CO) values obtained using a transpulmonary thermodilution technique (TPTDCO) and conventional thermodilution technique (TDCO) in anaesthetized dogs with fluid overload., Study Design: Prospective experimental study., Animals: Six healthy Beagle dogs aged 7-8 years., Methods: Dogs were anaesthetized with sevoflurane in oxygen, and catheters were inserted for TPTDCO and TDCO measurement. After instrumentation, baseline CO was measured using each technique at a central venous pressure (CVP) of 3-7 mmHg. Dogs were subsequently administered lactated Ringer's solution and 6% hydroxyethyl starch to induce fluid overload. CO measurements were obtained using each technique at CVP values of 8-12 mmHg, 13-17 mmHg, 18-22 mmHg and 23-27 mmHg. Agreements between CO measurements obtained with the respective techniques were analysed using Dunnett's test, Pearson's correlation coefficient and Bland-Altman analysis., Results: Thirty pairs of CO values were obtained, ranging from 1.45 L minute(-1) to 4.69 L minute(-1) for TPTDCO and from 1.30 L minute(-1) to 4.61 L minute(-1) for TDCO. TPTDCO and TDCO values correlated strongly (r(2)  = 0.915, p < 0.001). The bias and mean relative bias between TPTDCO and TDCO were 0.26 ± 0.30 L minute(-1) (limits of agreement - 0.29 to 0.81 L minute(-1) ) and 9.7%, respectively., Conclusions and Clinical Relevance: TPTDCO and TDCO measurements obtained in anaesthetized dogs during fluid overload exhibited good agreement. Accordingly, transpulmonary thermodilution provides an accurate measurement of CO in dogs with fluid overload., (© 2015 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.)

Aims: Many studies of human subjects have demonstrated the utility of assessing serum levels of endothelin-1 (ET-1) and big ET-1 as clinical biomarkers in cardiopulmonary and neoplastic diseases. In this study we explored the feasibility of using serum big ET-1 as a reliable veterinary marker in dogs with various cardiopulmonary and neoplastic diseases., Main Methods: Serum big ET-1 levels were measured by ELISA in dogs with cardiopulmonary (n=21) and neoplastic diseases (n=57). Dogs exhibiting cardiopulmonary disease were divided into two groups based on the velocity of tricuspid valve regurgitation (3.0>m/s) measured by ultrasound: without and with pulmonary hypertension. Big ET-1 levels for the dogs with the diseases were compared with levels in normal healthy dogs (n=17)., Key Findings: Dogs with cardiopulmonary disease (4.6±4.6 pmol/l) showed a significantly (P<0.01) higher level of big ET-1 than healthy control dogs (1.1±0.53 pmol/l). Serum levels in the dogs with pulmonary hypertension (6.2±5.3 pmol/l) were significantly (P<0.01) higher than those without pulmonary hypertension (2.0±0.6 pmol/l). Dogs with hemangiosarcoma (5.6±2.2 pmol/l), adenocarcinoma (2.0±1.8 pmol/l), histiocytic sarcoma (3.3±1.9 pmol/l), chondrosarcoma or osteosarcoma (3.0±1.6 pmol/l) and hepatocellular carcinoma (2.7±1.8 pmol/l) showed significantly (P<0.05) higher levels than healthy control dogs., Significance: These findings point to the potential of serum big ET-1 as a clinical marker for cardiopulmonary and neoplastic diseases in dogs., (Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.)

L-type amino acid transporter 1 (LAT1), an isoform of amino acid transport system L, transports branched or aromatic amino acids essential for fundamental cellular activities such as cellular growth, proliferation and maintenance. This amino acid transporter recently has received attention because of its preferential and up-regulated expression in a variety of human tumors in contrast to its limited distribution and low-level expression in normal tissues. In this study, we explored the feasibility of using LAT1 inhibitor as a new therapeutic agent for human malignant melanomas (MM) using canine spontaneous MM as a model for human MM. A comparative study of LAT expression was performed in 48 normal tissues, 25MM tissues and five cell lines established from MM. The study observed LAT1 mRNA levels from MM tissues and cell lines that were significantly (P<0.01) higher than in normal tissues. Additionally, MM with distant metastasis showed a higher expression than those without distant metastasis. Functional analysis of LAT1 was performed on one of the five cell lines, CMeC-1. [(3)H]l-Leucine uptake and cellular growth activities in CMeC-1 were inhibited in a dose-dependent manner by selective LAT1 inhibitors (2-amino-2-norbornane-carboxylic acid, BCH and melphalan, LPM). Inhibitory growth activities of various conventional anti-cancer drugs, including carboplatin, cyclophosphamide, dacarbazine, doxorubicin, mitoxantrone, nimustine, vinblastine and vincristine, were significantly (P<0.05) enhanced by combination use with BCH or LPM. These findings suggest that LAT1 could be a new therapeutic target for MM., (Copyright © 2013 Elsevier Inc. All rights reserved.)