Browsing by Subject "Animal model"

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  • Salonius, Eve; Rieppo, Lassi; Nissi, Mikko J.; Pulkkinen, Hertta J.; Brommer, Harold; Bruenott, Anne; Silvast, Tuomo S.; Van Weeren, P. Rene; Muhonen, Virpi; Brama, Pieter A. J.; Kiviranta, Ilkka (2019)
    Aim: The horse joint, due to its similarity with the human joint, is the ultimate model for translational articular cartilage repair studies. This study was designed to determine the critical size of cartilage defects in the equine carpus and serve as a benchmark for the evaluation of new cartilage treatment options. Material and Methods: Circular full-thickness cartilage defects with a diameter of 2, 4, and 8 mm were created in the left middle carpal joint and similar osteochondral (3.5 mm in depth) defects in the right middle carpal joint of 5 horses. Spontaneously formed repair tissue was examined macroscopically, with MR and mu CT imaging, polarized light microscopy, standard histology, and immunohistochemistry at 12 months. Results: Filling of 2 mm chondral defects was good (77.8 +/- 8.5%), but proteoglycan depletion was evident in Safranin-O staining and gadolinium-enhanced MRI (T-1Gd). Larger chondral defects showed poor filling (50.6 +/- 2.7% in 4 mm and 31.9 +/- 7.3% in 8 mm defects). Lesion filling in 2, 4, and 8 mm osteochondral defects was 82.3 +/- 3.0%, 68.0 +/- 4.6% and 70.8 +/- 15.4%, respectively. Type II collagen staining was seen in 9/15 osteochondral defects but only in 1/15 chondral defects. Subchondral bone pathologies were evident in 14/15 osteochondral samples but only in 5/15 chondral samples. Although osteochondral lesions showed better neotissue quality than chondral lesions, the overall repair was deemed unsatisfactory because of the subchondral bone pathologies. Conclusion: We recommend classifying 4 mm as critical osteochondral lesion size and 2 mm as critical chondral lesion size for cartilage repair research in the equine carpal joint model.
  • Watson, Victoria E.; Jacob, Megan E.; Bruno-Bárcena, José M.; Amirsultan, Sophia; Stauffer, Stephen H.; Píqueras, Victoria O.; Frias, Rafael; Gookin, Jody L. (2019)
    Typical enteropathogenic E. coli (tEPEC) carries the highest hazard of death in children with diarrhea and atypical EPEC (aEPEC) was recently identified as significantly associated with diarrheal mortality in kittens. In both children and kittens there is a significant association between aEPEC burden and diarrheal disease, however the infection can be found in individuals with and without diarrhea. It remains unclear to what extent, under what conditions, or by what mechanisms aEPEC serves as a primary pathogen in individuals with diarrhea. It seems likely that a combination of host and bacterial factors enable aEPEC to cause disease in some individuals and not in others. The purpose of this study was to determine the impact of aEPEC on intestinal function and diarrhea in kittens following experimentally-induced carriage and the influence of a disrupted intestinal microbiota on disease susceptibility. Results of this study identify aEPEC as a potential pathogen in kittens. In the absence of disruption to the intestinal microbiota, kittens are resistant to clinical signs of aEPEC carriage but demonstrate significant occult changes in intestinal absorption and permeability. Antibiotic-induced disruption of the intestinal microbiota prior to infection increases subsequent intestinal water loss as determined by % fecal wet weight. Enrichment of the intestinal microbiota with a commensal member of the feline mucosa-associated microbiota, Enterococcus hirae, ameliorated the effects of aEPEC experimental infection on intestinal function and water loss. These observations begin to unravel the mechanisms by which aEPEC infection may be able to exploit susceptible hosts.
  • Ludtka, Christopher; Schwan, Stefan; Friedmann, Andrea; Brehm, Walther; Wiesner, Ingo; Goehre, Felix (2017)
    The primary goal of this study is to clearly define and evaluate new intervertebral disc height parameters in analysing the morphological pathology of disc degeneration for application in damage model and regeneration therapy development, as well as applying traditional variables to 3-D characterization methods. A posterolateral surgical approach was used to induce disc degeneration in an ovine model. At 12-months post-operation, sheep vertebral segments were removed and characterized using micro-CT to evaluate disc height parameters in regard to injury localization. Statistically significant differences between the disc height loss of the left and right side of the disc, consistent with the lateral surgical approach used were seen using the modified average disc height method by Dabbs et al. However, convexity index and the newly proposed Cross Tilt Index did not conclusively demonstrate a difference. Two-dimensional morphological evaluations can be applied in 3-D to provide a more complete picture of disc height loss for injury models. New 3-D parameters that are tailored to the type of surgical approach used should be investigated, with the 9-point system described herein providing a useful basis for derived values. Additionally, the surgical approach chosen when artificially injuring the disc can result in asymmetrical degeneration, as indicated by uneven disc height loss.
  • Schwan, Stefan; Ludtka, Christopher; Wiesner, Ingo; Baerthel, Andre; Friedmann, Andrea; Göhre, Felix (2018)
    This work describes a minimally invasive damage model for ovine lumbar discs via partial nucleotomy using a posterolateral approach. Two cadavers were dissected to analyze the percutaneous corridor. Subsequently, 28 ovine had their annulus fibrosus punctured via awl penetration under fluoroscopic control and nucleus pulposus tissue removed via rongeur. Efficacy was assessed by animal morbidity, ease of access to T12-S1 disc spaces, and production of a mechanical injury as verified by discography, radiography, and histology. T12-S1 were accessible with minimal nerve damage morbidity. Scar tissue sealed the disc puncture site in all animals within 6 weeks, withstanding 1 MP of intradiscal pressure. Partial nucleotomy led to a significant reduction in intervertebral disk height and an increased histological degeneration score. Inducing a reproducible injury pattern of disc degeneration required minimal time, effort, and equipment. The posterolateral approach allows operation on several discs within a single surgery and multiple animal surgeries within a single day.
  • del Amo, Eva M.; Urtti, Arto (2015)
    Intravitreal administration is the method of choice in drug delivery to the retina and/or choroid. Rabbit is the most commonly used animal species in intravitreal pharmacokinetics, but it has been criticized as being a poor model of human eye. The critique is based on some anatomical differences, properties of the vitreous humor, and observed differences in drug concentrations in the anterior chamber after intravitreal injections. We have systematically analyzed all published information on intravitreal pharmacokinetics in the rabbit and human eye. The analysis revealed major problems in the design of the pharmacokinetic studies. In this review we provide advice for study design. Overall, the pharmacokinetic parameters (clearance, volume of distribution, half-life) in the human and rabbit eye have good correlation and comparable absolute values. Therefore, reliable rabbit-to-man translation of intravitreal pharmacokinetics should be feasible. The relevant anatomical and physiological parameters in rabbit and man show only small differences. Furthermore, the claimed discrepancy between drug concentrations in the human and rabbit aqueous humor is not supported by the data analysis. Based on the available and properly conducted pharmacokinetic studies, the differences in the vitreous structure in rabbits and human patients do not lead to significant pharmacokinetic differences. This review is the first step towards inter-species translation of intravitreal pharmacokinetics. More information is still needed to dissect the roles of drug delivery systems, disease states, age and ocular manipulation on the intravitreal pharmacokinetics in rabbit and man. Anyway, the published data and the derived pharmacokinetic parameters indicate that the rabbit is a useful animal model in intravitreal pharmacokinetics. (C) 2015 The Authors. Published by Elsevier Ltd.
  • Tolvanen, Durukan; Tatlisumak, E.; Pedrono, E.; Abo-Ramadan, U.; Tatlisumak, T. (2017)
    Transient ischemic attack (TIA) has received only little attention in the experimental research field. Recently, we introduced a TIA model for mice, and here we set similar principles for simulating this human condition in Wistar rats. In the model: 1) transient nature of the event is ensured, and 2) 24 h after the event animals are free from any sensorimotor deficit and from any detectable lesion by magnetic resonance imaging (MRI). Animals experienced varying durations of ischemia (5, 10, 12.5, 15, 25, and 30 min, n = 6-8 per group) by intraluminal middle cerebral artery occlusion (MCAO). Ischemia severity and reperfusion rates were controlled by cerebral blood flow measurements. Sensorimotor neurological evaluations and MRI at 24 h differentiated between TIA and ischemic stroke. Hematoxylin and eosin staining and apoptotic cell counts revealed pathological correlates of the event. We found that already 12.5 min of ischemia was long enough to induce ischemic stroke in Wistar rats. Ten min or shorter durations induced neither gross neurological deficits nor infarcts visible on MRI, but histologically caused selective neuronal necrosis. A separate group of animals with 10 min of ischemia followed up to 1 week after reperfusion remained free of infarction and any MRI signal change. Thus, 10 min or shorter focal cerebral ischemia induced by intraluminal MCAO in Wistar rats provides a clinically relevant TIA the rat. This model is useful for studying molecular correlates of TIA. (C) 2017 Elsevier B.V. All rights reserved.