Routine husbandry procedures during animal toxicity studies can result in incidental pathological changes. We report on trauma-induced hepatopathy in newborn Göttingen minipigs. Sixty-four neonatal minipigs were allocated to 13- and 26-week treatment arms. There was a 4-week recovery period for both arms. The animals were divided into 2 treatment groups and a vehicle group and were dosed 3 times daily by direct oral administration using a syringe. During the feeding procedure in the first weeks, the animals had to be handled firmly. After 13 weeks, randomly distributed foci of degeneration/necrosis and focal congestion and/or hemorrhage were found in the livers of several animals from all groups. Reduced incidence and severity were evident in the recovery phase, and the lesions were absent after 26 weeks. These changes were considered as related to the manual handling of the animals. Knowledge of these findings is crucial for interpretation of studies utilizing newborn minipigs.
Background: Prostatic artery embolization (PAE) is an alternative treatment for symptomatic benign prostatic hyperplasia (BPH) in men. A technical modification of conventional PAE has been developed in a canine prostate model consisting of prostatic artery occlusion (PAO) using Onyx ® whose therapeutic effect is prostate shrinkage. However, the underlying mechanisms are not well clarified. The purpose was to evaluate the biological mechanisms responsible for therapeutic effects of PAO in the canine prostate.Methods: Ten adult male beagles (5.0±0.82 years) underwent PAO with Onyx-18 (n=7) and prostatic artery angiography as control (n=3). Blood samples were taken at different time points of follow-up (baseline, 1 week, 2 weeks, 1 month, 3 months and 6 months) to measure the serum canine prostate specific esterase (CPSE). MRI examinations were also performed to document the prostate volume (PV) before and after interventions at different time points of follow-up. Prostates were harvested at 2 weeks (n=2) in the PAOgroup, and the remaining ones (n=8) at 6 months for the determinations of intraprostatic testosterone and dihydrotestosterone (DHT) by ELISA, apoptosis by TUNEL assay and histopathological study. Results:The mean serum CPSE concentration started to decrease significantly from 2 weeks to 6 months after PAO along with PV compared with baseline data. In addition, a moderate but significant correlation was observed between CPSE and PV (r=0.655, P=0.000). Regarding intraprostatic androgens, testosterone was significantly higher after PAO than control (19.70 vs. 4.87 ng/mL, P=0.002), whereas DHT was lower but no significant (112.52 vs. 138.35 pg/mL, P=0.144). In histological study, PAO induced a severe hemorrhagic necrosis in the whole prostates along with inflammatory cell infiltration at early 2 weeks, and then diffuse interstitial fibrosis with atrophy of the glandular epithelium and intraprostatic cavity formation at 6 months.Apoptosis was detected in all specimens with higher apoptotic index after PAO at 2 weeks (7.35%) and at 6 months (4.38%) compared with control (2.64%), without statistically significant difference between groups.
INTRODUCTION New non-invasive technologies for improving early diagnosis of colorectal cancer (CRC) are demanded by clinicians. Optical Coherence Tomography (OCT) provides sub-surface structural information and offers diagnosis capabilities of colon polyps, further improved by machine learning methods. Databases of OCT images are necessary to facilitate algorithms development and testing. MATERIALS AND METHODS A database has been acquired from rat colonic samples with a Thorlabs OCT system with 930nm centre wavelength that provides 1.2KHz A-scan rate, 7μm axial resolution in air, 4μm lateral resolution, 1.7mm imaging depth in air, 6mm x 6mm FOV, and 107dB sensitivity. The colon from anaesthetised animals has been excised and samples have been extracted and preserved for ex-vivo analysis with the OCT equipment. RESULTS This database consists of OCT 3D volumes (C-scans) and 2D images (B-scans) of murine samples from: 1) healthy tissue, for ground-truth comparison (18 samples; 66 C-scans; 17,478 B-scans); 2) hyperplastic polyps, obtained from an induced colorectal hyperplastic murine model (47 samples; 153 C-scans; 42,450 B-scans); 3) neoplastic polyps (adenomatous and adenocarcinomatous), obtained from clinically validated Pirc F344/NTac-Apcam1137 rat model (232 samples; 564 C-scans; 158,557 B-scans); and 4) unknown tissue (polyp adjacent, presumably healthy) (98 samples; 157 C-scans; 42,070 B-scans). CONCLUSIONS A novel extensive ex-vivo OCT database of murine CRC model has been obtained and will be openly published for the research community. It can be used for classification/segmentation machine learning methods, for correlation between OCT features and histopathological structures, and for developing new non-invasive in-situ methods of diagnosis of colorectal cancer.
Introduction The main objective of this study was to characterise an animal model of colon cancer in the F344-ApcPircUwm rat through the analysis of microRNAs expressed in plasma by Next Generation Sequencing. Methods Colonoscopic follow-ups of the colon cancer model were performed for 10 months (n=60). At each follow-up, 2 ml of whole blood was collected in EDTA tubes, centrifuged for plasma extraction and frozen at - 80 °C. After euthanasia of the animals the different regions of the colon and their respective findings were analysed by histopathological analysis to obtain a ground truth. After this, 14 plasma samples were analysed by Next Generation Sequencing to observe the different expressions of microRNAs between the animals corresponding to the Neoplasia group and the healthy animals (n=6/8). Results After the corresponding functional analysis of the microRNAs deregulated in the animals of the colonic adenoma group and the healthy animals, we highlight rno-miR-192–5p, rno-miR-125b-5p and rno-miR-29c-3p, which appear underexpressed in the animals with adenomatous and adenocarcinomatous lesions in the colon. Conclusions The microRNAs deregulated in this animal model compared to their healthy counterpart without lesions obtained by liquid biopsy are miR-125b-5p, miR-192–5p and miR-29c-3p and their study could open the door to novel therapeutic strategies for prognosis and diagnosis by studying their expression in animal models that could be transferred to humans in the fight against colon cancer.
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