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Simple Summary: Since there is a lack of information regarding how epoprostenol, a prostacyclin, affects canine renal blood flow (RBF), we investigated the effects of short-term administration of epoprostenol at human doses of 2, 5, and 10 ng/kg/min intravenously for 20 min on RBF in six healthy dogs under anesthesia. The effects of short-term administration were investigated. As the dose of epoprostenol increased, peak systolic and end diastolic velocities of the renal arteries, maximum and minimum venous flow velocities of the interlobular and renal veins, and heart rate all tended to increase. However, these increases were not significant. These results indicate that the administration of human doses of epoprostenol to dogs does not produce significant changes in renal or systemic circulation. Prostacyclin is an in vivo bioactive substance that regulates renal blood flow (RBF). Information regarding how epoprostenol, a prostacyclin preparation, affects RBF in dogs is lacking. We investigated the effects of short-term epoprostenol administration on RBF in six healthy dogs under anesthesia by administering it intravenously at human doses—2, 5, and 10 ng/kg/min for 20 min. RBF was evaluated before and during epoprostenol administration using pulsed Doppler ultrasonography, and renal perfusion was evaluated using contrast-enhanced ultrasonography. Effects on renal and systemic circulation were evaluated by measuring systolic arterial, mean arterial, diastolic arterial, pulmonary arterial, mean right atrial, and pulmonary capillary wedge pressures; heart rate; and cardiac output. Kruskal–Wallis and Bonferroni multiple comparison tests and Spearman's rank correlation coefficient were used for statistical analyses. As epoprostenol dosage increased, the peak systolic and end diastolic velocity of the renal artery, maximum and minimum venous flow velocities of the interlobular and renal veins, and heart rate all tended to increase, although not significantly. Our results indicate that human-dose epoprostenol administration in dogs does not cause significant changes in renal or systemic circulation. However, the human doses used may have been too low to produce a clinical effect in dogs. [ABSTRACT FROM AUTHOR]

Objective: Acidosis decreases myocardial contractile and myofibrillar responsiveness by reducing the calcium sensitivity of contractile proteins, which could reduce the effectiveness of pimobendan. We aimed to assess the cardiovascular effects of pimobendan in dogs subjected to acute respiratory acidosis. Design: Randomized crossover study with a 2‐week washout period. Setting: University Laboratory. Animals: Six healthy research Beagle dogs. Interventions: Anesthetized dogs were administered 2 doses of IV pimobendan during conditions of eucapnia (Paco2 35–40 mm Hg) and hypercapnia (Paco2 90–110 mm Hg). Eucapnia was maintained by positive pressure ventilation and hypercapnia was induced by adding exogenous CO2 to the anesthesia circuit. Heart rate (HR), systemic arterial blood pressure, cardiac output (CO), systemic and pulmonary vascular resistance (SVR and PVR, respectively), and pulmonary arterial pressure (PAP) were measured at baseline and 60 min after administering 0.125 mg/kg (low) and 0.25 mg/kg (high) pimobendan intravenously. Blood gas and biochemical analyses were performed at baseline and at the end of the experiment. Measurements and Main Results: The median baseline blood pH was 7.41 (range: 7.33–7.45) and 7.03 (range: 6.98–7.09) under conditions of eucapnia and hypercapnia, respectively. The serum concentrations of epinephrine and norepinephrine and the HR, CO, and PAP were higher, and SVR was lower at baseline in hypercapnic dogs. Pimobendan dose‐dependently increased CO in eucapnia (baseline: 3.6 ± 0.2 L/kg/m2 [mean ± SE], low: 5.0 ± 0.4 L/kg/m2, high: 5.8 ± 0.5 L/kg/m2, P < 0.001) and hypercapnia (baseline: 4.9 ± 0.5 L/kg/m2, low: 5.8 ± 0.5 L/kg/m2, high: 6.2 ± 0.5 L/kg/m2, P < 0.001), and increased HR and decreased SVR and PVR under both conditions (P < 0.001). In hypercapnia, the degree of increase or decrease of these cardiovascular measurements (except for PAP) by pimobendan was less than that in the eucapnic dogs. Conclusions: Pimobendan maintains function as an inodilator in anesthetized dogs with induced respiratory acidosis. [ABSTRACT FROM AUTHOR]

In acidosis, catecholamines are attenuated, and higher doses are often required to improve cardiovascular function. Colforsin activates adenylate cyclase in cardiomyocytes without beta-adrenoceptor. Here, six beagles were administered colforsin or dobutamine four times during eucapnia (partial pressure of arterial carbon dioxide 35–40 mm Hg; normal) and hypercapnia (ibid 90–110 mm Hg; acidosis) conditions. The latter was induced by CO2 inhalation. Anesthesia was induced with propofol and maintained with isoflurane. Cardiovascular function was measured by thermodilution and a Swan-Ganz catheter at baseline and 60 min after 0.3 μg/kg/min (low), 0.6 μg/kg/min (middle), and 1.2 μg/kg/min (high) colforsin administration. The median pH was 7.38 [range 7.33–7.42] and 7.01 [range 6.96–7.08] at baseline in the Normal and Acidosis conditions, respectively. Endogenous adrenaline and noradrenaline levels at baseline were significantly (P < 0.05) higher in the Acidosis than in the Normal condition. Colforsin induced cardiovascular effects similar to those caused by dobutamine. Colforsin increased cardiac output in the Normal condition (baseline: 3.9 ± 0.2 L/kg/m2 [mean ± standard error], low: 5.2 ± 0.4 L/kg/min2, middle: 7.0 ± 0.4 L/kg/m2, high: 9.4 ± 0.2 L/kg/m2; P < 0.001) and Acidosis condition (baseline: 6.1 ± 0.3 L/kg/m2, low: 6.2 ± 0.2 L/kg/m2, middle: 7.2 ± 0.2 L/kg/m2, high: 8.3 ± 0.2 L/kg/m2; P < 0.001). Colforsin significantly increased heart rate and decreased systemic vascular resistance compared to values at baseline. Both drugs increased pulmonary artery pressure, but colforsin (high: 13.3 ± 0.6 mmHg in Normal and 20.1 ± 0.2 mmHg in Acidosis) may have lower clinical impact on the pulmonary artery than dobutamine (high: 19.7 ± 0.6 in Normal and 26.7 ± 0.5 in Acidosis). Interaction between both drugs and experimental conditions was observed in terms of cardiovascular function, which were similarly attenuated with colforsin and dobutamine under acute respiratory acidosis. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Highlights: [•] LAT1 is highly expressed in tumors but at low levels in normal tissues. [•] We examine LAT1 expression and function in malignant melanoma (MM). [•] LAT1 expression in MM tissues and cell lines is higher than those in normal tissues. [•] LAT1 selective inhibitors inhibit amino acid uptake and cell growth in MM cells. [•] New chemotherapeutic protocols including LAT1 inhibitors are effective for treatment. [ABSTRACT FROM AUTHOR]

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 ( r2 = 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. [ABSTRACT FROM AUTHOR]

Haemangiosarcoma (HSA) is an important malignant neoplasm of dogs that originates from vascular endothelial cells. This study explored the suitability of using serum big endothelin-1 (ET-1) as a tumour marker for canine spontaneous HSA. Serum big ET-1 was measured in dogs with splenic HSA ( n  = 14), splenic malignant tumours other than HSA ( n  = 10), benign splenic lesions ( n  = 11) and normal healthy dogs ( n  = 17) by ELISA. Serum big ET-1 levels in dogs with HSA were significantly ( P  < 0.01) higher than in other dogs. High sensitivity (100%, 95% confidence interval 86–100%) and specificity (95%, 95% confidence interval 86–95%) for HSA diagnosis were obtained using a cut-off of 17 pg/mL according to receiver operating characteristic (ROC) curves (area under ROC curve 0.93). PPET1 , ETA, VEGF and Hif1-α mRNA expression, measured by real-time PCR, were elevated in HSA compared with normal tissues. These findings suggest that elevated serum big ET-1 could be used as a diagnostic marker for canine HSA. [ABSTRACT FROM AUTHOR]

We have developed a novel method to predict the success of PCR amplification for a specific primer set and DNA template based on the relationship between the primer sequence and the template. To perform the prediction using a recurrent neural network, the usual double-stranded formation between the primer and template nucleotide sequences was herein expressed as a five-lettered word. The set of words (pseudo-sentences) was placed to indicate the success or failure of PCR targeted to learn recurrent neural network (RNN). After learning pseudo-sentences, RNN predicted PCR results from pseudo-sentences which were created by primer and template sequences with 70% accuracy. These results suggest that PCR results could be predicted using learned RNN and the trained RNN could be used as a replacement for preliminary PCR experimentation. This is the first report which utilized the application of neural network for primer design and prediction of PCR results. [ABSTRACT FROM AUTHOR]

• Inflammatory/anti-inflammatory cytokines are elevated in Miniature Dachshund ICRP • Tregs and Iba-1-positive macrophages are increased in polypoid lesions • IL-10 upregulation is correlated with Treg distribution in polypoid lesions of ICRP • Relative IL-1β , IL-6 , and IL-8 upregulation in ICRP is greater than that of IL-10. Inflammatory colorectal polyp (ICRP) is an emerging disease in Miniature Dachshunds (MDs). Animals with this disease exhibit multiple polyps with severe neutrophil infiltration that respond to immunosuppressive therapy. Macrophages in polypoid lesions have been described to play an important role in neutrophil infiltration in the lesion by producing IL-8. In contrast, IL-10, an anti-inflammatory cytokine, was also reported to be upregulated in polypoid lesions, but its significance in the pathogenesis of ICRP has not been clarified. Regulatory T cells (Tregs) are the main source of IL-10 production and contribute to the maintenance of intestinal homeostasis. Therefore, the objective of this research was to compare the distribution of Tregs in polypoid lesions of ICRPs and the association between the distribution and expression of pro- or anti-inflammatory cytokines. Tissue biopsy specimens of polypoid lesions were collected from 28 MDs with ICRP. Those of macroscopically non-polypoid colonic mucosa from 24 MDs with ICRPs and 21 control dogs were further included as controls. Real-time quantitative polymerase chain reaction was used to quantify gene expression of IL-1β , IL-4 , IL-6 , IL-8 , IL-10 , IL-17 , IL-22 , IFN-γ , TNF-α , TGF-β , and forkhead box protein P3 (Foxp3) in each tissue sample. The numbers of Foxp3-positive cells (Tregs) and ionized calcium binding adapter molecule 1 (Iba-1)-positive cells (macrophages) were determined by immunohistochemistry. The gene expression of IL-1β , IL-6 , IL-8 , TNF-α , IFN-γ , IL-17 , IL-10 , TGF-β , and Foxp3 was significantly upregulated in polypoid lesions relative to control levels. The numbers of Foxp3-positive Tregs and Iba-1-positive macrophages were significantly increased in polypoid lesions compared to those in the non-polypoid colonic mucosa of MDs with ICRPs and control dogs. The upregulation of IL-10 was moderately correlated with the distribution of Tregs in polypoid lesions from MDs with ICRPs. In addition, the relative upregulation of IL-1β , IL-6 , and IL-8 in polypoid lesions, compared to expression in non-polypoid colonic mucosa of MDs with ICRPs, was significantly greater than that of IL-10. These results indicate that increases in Treg numbers and anti-inflammatory cytokines in polypoid lesions comprise reactive changes in response to the inflammation, which warrants further investigation. [ABSTRACT FROM AUTHOR]