Kichang Lee

Inhibition of VEGF blocks TGF-β1 production through a PI3K/Akt signalling pathway

Vascular endothelial growth factor (VEGF) is a mediator of airway inflammation and remodelling in asthma. Transforming growth factor (TGF)-β1 plays pivotal roles in diverse biological processes, including tissue remodelling and repair in a number of chronic lung diseases. However, there are few studies elucidating the interactions between VEGF and TGF-β1 in allergic airway disease. A murine model of allergic airway disease was used to define the mechanism by which VEGF induces subepithelial fibrosis and to investigate a potential relationship between VEGF and TGF-β1 and the mechanisms by which VEGF signalling regulates TGF-β1 expression in allergic airway disease. The ovalbumin (OVA)-inhaled murine model revealed the following typical pathophysiological features of allergic airway disease in the lungs: increased numbers of inflammatory cells of the airways, airway hyperresponsiveness, increased peribronchial fibrosis, and increased levels of VEGF and TGF-β1. Administration of VEGF inhibitors reduced the pathophysiological signs of allergic airway disease and decreased the increased TGF-β1 levels and peribronchial fibrosis, including phosphoinositide 3-kinase (PI3K) activity after OVA inhalation. In addition, the increased TGF-β1 levels and collagen deposition after OVA inhalation were decreased by administration of PI3K inhibitors. These results suggest that inhibition of vascular endothelial growth factor attenuates peribronchial fibrosis, at least when mediated by regulation of transforming growth factor-β1 expression through phosphoinositide 3-kinase/Akt pathway in a murine model of allergic airway disease.

Phosphoinositide 3-kinase δ inhibitor suppresses interleukin-17 expression in a murine asthma model

Phosphoinositide 3-kinases (PI3Ks) contribute to the pathogenesis of asthma by regulating the activation of inflammatory mediators, inflammatory cell recruitment and immune cell function. Recent findings have indicated that PI3Ks also regulate the expression of interleukin (IL)-17, which has been recognised as an important cytokine involved in airway inflammation. In the present study, we investigated a role of PI3K&dgr; in the regulation of IL-17 expression in allergic airway disease using a murine model of asthma. After ovalbumin inhalation, administration of a selective p110&dgr; inhibitor, IC87114, significantly attenuated airway infiltration of total cells, lymphocytes, neutrophils and eosinophils, as well as airway hyperresponsiveness, and attenuated the increase in IL-17 protein and mRNA expression. Moreover, IC87114 reduced levels of IL-4, -5 and -13, expression of keratinocyte chemoattractant protein and mRNA, and nuclear factor (NF)-&kgr;B activity. In addition, a NF-&kgr;B inhibitor, BAY 11-7085 substantially reduced the increase in IL-17 protein levels. Our results also showed that inhibition of IL-17 activity with an anti-IL-17 antibody remarkably reduced airway inflammation and hyperresponsiveness. These findings suggest that inhibition of the p110&dgr; signalling pathway suppresses IL-17 expression through regulation of NF-&kgr;B activity and, thus, has therapeutic potential in asthma.

FDG-PET for evaluating the antitumor effect of intraarterial 3-bromopyruvate administration in a rabbit VX2 liver tumor model

Objective We wanted to investigate the feasibility of using FDG-PET for evaluating the antitumor effect of intraarterial administration of a hexokinase II inhibitor, 3-bromopyruvate (3-BrPA), in a rabbit VX2 liver tumor model. Materials and Methods VX2 carcinoma was grown in the livers of ten rabbits. Two weeks later, liver CT was performed to confirm appropriate tumor growth for the experiment. After tumor volume-matched grouping of the rabbits, transcatheter intraarterial administration of 3-BrPA was performed (1 mM and 5 mM in five animals each, respectively). FDG-PET scan was performed the day before, immediately after and a week after 3-BrPA administration. FDG uptake was semiquantified by measuring the standardized uptake value (SUV). A week after treatment, the experimental animals were sacrificed and the necrosis rates of the tumors were calculated based on the histopathology. Results The SUV of the VX2 tumors before treatment (3.87 ±1.51 [mean ±SD]) was significantly higher than that of nontumorous liver parenchyma (1.72 ±0.34) (p < 0.0001, Mann-Whitney U test). The SUV was significantly decreased immediately after 3-BrPA administration (2.05 ±1.21) (p = 0.002, Wilcoxon signed rank test). On the one-week follow up PET scan, the FDG uptake remained significantly lower (SUV 1.41 ±0.73) than that before treatment (p = 0.002), although three out of ten animals showed a slightly increasing tendency for the FDG uptake. The tumor necrosis rate ranged from 50.00% to 99.90% (85.48% ±15.87). There was no significant correlation between the SUV or the SUV decrease rate and the tumor necrosis rate in that range. Conclusion Even though FDG-PET cannot exactly reflect the tumor necrosis rate, FDG-PET is a useful modality for the early assessment of the antitumor effect of intraarterial administration of 3-BrPA in VX2 liver tumor.

Effect of topical anesthesia on evaluation of corneal sensitivity and intraocular pressure in rats and dogs

OBJECTIVE To determine the effect of 0.5% proparacaine in tonometry by evaluating corneal touch threshold (CTT) and intraocular pressure (IOP). ANIMAL STUDIED   Nine rats (18 eyes, Sprague-Dawley) and 10 dogs (20 eyes, Beagle) PROCEDURES The IOP and CTT were measured in each eye before and after topical anesthesia with 0.5% proparacaine. The IOP was evaluated using Tonopen for dogs and Tonolab for rats. The corneal sensitivity was evaluated by CTT through a Cochet-Bonnet aesthesiometer. RESULTS The mean IOP was not significantly changed in rats or dogs before and after topical anesthesia. However, after application of proparacaine, CTT was significantly increased in both animal groups compared with that before application of proparacaine. CONCLUSION   From this study, topical anesthesia was found to significantly lower the corneal sensitivity but have little effect on IOP measurements. In ophthalmologic examination, topical anesthesia can be used to reduce corneal sensation without an effect on IOP.

FEASIBILITY OF COMPUTED TOMOGRAPHY IN AWAKE DOGS WITH TRAUMATIC PELVIC FRACTURE

In veterinary medicine, general anesthesia or sedation is generally required to immobilize patients during computed tomography (CT) scanning. This may not be suitable in all patients because of risks of anesthesia. We evaluated the feasibility of pelvic CT examination in 14 awake animals with pelvic trauma. Physical restraint was applied by wrapping the patient in a towel and then taping to the CT table or by directly taping the patient to the CT table. The effect of patient positioning, cooperation on the CT table, preparation time for scanning, scanning time, frequency of repeat scans, image quality, and complications related to physical restraint were evaluated. Fractures were recorded and compared between radiography and CT. Ten of 14 dogs were scanned in lateral recumbency and four in sternal recumbency. All patients were cooperative with the exception of one that moved slightly during the scan. Both physical restraint methods were adequate for CT scanning. Patient preparation took less than 5 min while the scan time was typically less than 1 min. No repeat scans were required in any patient. The transverse CT image quality was good (10/14) or fair (4/14) for interpretation. When comparing the CT images to radiographs, more pelvic fractures were identified with CT than with radiography and a few patients were overdiagnosed based on radiographs. No complications or additional injuries associated with physical restraint were noticed.

Time-dependent low-field MRI characteristics of canine blood: an in vitro study

This study was conducted to assess time-sensitive magnetic resonance (MR) changes in canine blood using low-field MR. Arterial and venous blood samples were collected from eight healthy beagle dogs. Samples were placed in 5-mL tubes and imaged within 3 hours of collection at 1 day intervals from day 1 to day 30. The following sequences were used: T1-weighted (T1W), T2-weighted (T2W), fluid-attenuated inversion recovery (FLAIR), short tau inversion recovery (STIR), and T2-star gradient-echo (T2*-GRE). Visual comparison of the images revealed that four relatively homogenous blood clots and twelve heterogeneous blood clots developed. The margination of the clot and plasma changed significantly on day 2 and day 13. On day 2, heterogeneous blood clots were differentiated into 2 to 3 signal layers in the T2W, T1W, and especially the STIR images. Hypointense signal layers were also detected in the blood clots in STIR images, which have T2 hypo, FLAIR hypo, and T1 hyper intense signals. In all images, these signal layers remained relatively unchanged until day 13. Overall, the results suggest that hematomas are complex on low-field MRI. Accordingly, it may not be feasible to accurately characterize hemorrhages and predict clot age based on low-field MRI.

Comparison of internally cooled wet electrode and hepatic vascular inflow occlusion method for hepatic radiofrequency ablation.

Background/Aims Various strategies to expand the ablation zone have been attempted using hepatic radiofrequency ablation (RFA). The optimal strategy, however, is unknown. We compared hepatic RFA with an internally cooled wet (ICW) electrode and vascular inflow occlusion. Methods Eight dogs were assigned to one of three groups: only RFA using an internally cooled electrode (group A), RFA using an ICW electrode (group B), and RFA using an internally cooled electrode with the Pringle maneuver (group C). The ablation zone diameters were measured on the gross specimens, and the volume of the ablation zone was calculated. Results The ablation zone volume was greatest in group B (1.82±1.23 cm3), followed by group C (1.22±0.47 cm3), and then group A (0.48±0.33 cm3). The volumes for group B were significantly larger than the volumes for group A (p=0.030). There was no significant difference in the volumes between groups A and C (p=0.079) and between groups B and C (p=0.827). Conclusions Both the usage of an ICW electrode and hepatic vascular occlusion effectively expanded the ablation zone. The use of an ICW electrode induced a larger ablation zone with easy handling compared with using hepatic vascular occlusion, although this difference was not statistically significant.

IMAGING DIAGNOSIS—ENDOMETRIAL MINERALIZATION IN A DOG

A 9-year-old intact female mixed breed dog was presented for mammary gland tumor surgery, and preoperative radiographs showed a tubular soft tissue opacity mass with multifocal mineralization in the caudoventral abdominal cavity. Subsequent ultrasonography demonstrated uterine dilation with echogenic fluid and endometrial acoustic shadowing consistent with mineralization. Resection of mammary gland tumors and ovariohysterectomy were performed. Pyometra was diagnosed on cytologic examination of uterine fluid. Histopathology of the uterine tissue confirmed a diagnosis of cystic endometrial hyperplasia with uterine mineralization.

Use of Covered Stents in the Central Vein: A Feasibility Study in a Canine Model

Purpose To evaluate the feasibility of using covered stents vs. bare stents in a model of central vein stenosis with an arteriovenous graft created to mimic the conditions in hemodialysis patients. Methods In 7 mongrel dogs, an expanded polytetrafluoroethylene-covered nitinol stent was placed in one common iliac vein and a bare stent was placed in the contralateral vein. Arteriovenous grafts were created bilaterally between the common femoral artery and vein to induce endothelial damage. Neointima formation in the covered stents was compared to the bare stents at 12 weeks using microscopy and histochemical staining. Results Two dogs were excluded due to thrombosis and infection of the arteriovenous grafts, but all stents in the remaining 5 dogs were patent. Smooth, complete neointimal coverage was observed on the inner surface of all the covered stents without intraluminal thrombus. In contrast, incomplete neointimal coverage was seen in all bare stents, with small focal thrombi adhering to the neointima on 3 bare stents. Focal nodular neointimal hyperplasia with denudation of the endothelium was observed in only 2 bare stents. Mean neointimal thickening was significantly greater in the covered stents. Eccentric neointimal thickening was observed at the inflow and outflow segments of both types of stents. Conclusion Covered stents are technically feasible for the treatment of central vein stenosis, and they demonstrate complete, smooth neointimal coverage in normal central veins, but they also display greater neointimal thickening than bare stents.

Diagnostic imaging features of normal anal sacs in dogs and cats

This study was conducted to provide normal reference features for canine and feline anal sacs using ultrasound, low-field magnetic resonance imaging (MRI) and radiograph contrast as diagnostic imaging tools. A total of ten clinically normal beagle dogs and eight clinically normally cats were included. General radiography with contrast, ultrasonography and low-field MRI scans were performed. The visualization of anal sacs, which are located at distinct sites in dogs and cats, is possible with a contrast study on radiography. Most surfaces of the anal sacs tissue, occasionally appearing as a hyperechoic thin line, were surrounded by the hypoechoic external sphincter muscle on ultrasonography. The normal anal sac contents of dogs and cats had variable echogenicity. Signals of anal sac contents on low-field MRI varied in cats and dogs, and contrast medium using T1-weighted images enhanced the anal sac walls more obviously than that on ultrasonography. In conclusion, this study provides the normal features of anal sacs from dogs and cats on diagnostic imaging. Further studies including anal sac evaluation are expected to investigate disease conditions.