Animal experimental models of ischemic wounds - A review of literature.

Critical limb ischemia is a serious form of peripheral arterial disease (PAD). The consequences of lower limb ischemia are pain, claudication and chronic non-healing wounds. Patients with diabetes are especially at a high risk for developing non-healing ulcers. The most serious complication is major amputation. For this reason, there is a significant medical requirement to develop new therapies in order to prevent the progression of PAD. For research purposes, it is crucial to find an appropriate model of chronic ischemia to explore the processes of wound healing. According to recently acquired information, rodents are currently the most commonly used animals in these types of studies. The main advantage of using small animals is the low financial cost due to the relatively small demand for food, water and living space. The disadvantage is their anatomy, which is different from that of humans. Larger animals have a more human-like anatomy and physiology, but they require more expense and space for housing. A bipedicle skin flap and its modifications are popular models for ischemic wounds. In order to secure healing through re-epithelisation, as opposed to contraction in rodents, there is a need to remove the panniculus carnosus muscle. Wounds in other experimental animals heal primarily through re-epithelisation. The application of a silicone mesh underneath the flap prevents vascular regrowth in ischemic tissue. There is an ongoing effort to create in vivo diabetic models for chronic ulcer research. This work presents an overview of existing animal models of ischemic wounds.

Application of animal experimental models in the research of schizophrenia.

Schizophrenia is a relatively common but serious mental illness that results in a heavy burden to patients, their families, and society. The disease can be triggered by multiple factors, while the specific pathogenesis remains unclear. The development of effective therapeutic drugs for schizophrenia relies on a comprehensive understanding of the basic biology and pathophysiology of the disease. Therefore, effective animal experimental models play a vital role in the study of schizophrenia. Based on different molecular mechanisms and modeling methods, the currently used experimental animal experimental models of schizophrenia can be divided into four categories that can better simulate the clinical symptoms and the interplay between susceptible genes and the environment: neurodevelopmental, drug-induced, genetic-engineering, and genetic-environmental interaction of animal experimental models. Each of these categories contains multiple subtypes, which has its own advantages and disadvantages and therefore requires careful selection in a research application. The emergence and utilization of these models are promising in the prediction of the risk of schizophrenia at the molecular level, which will shed light on effective and targeted treatment at the genetic level.

Experimental Animal Model Systems for Understanding Salivary Secretory Disorders.

Salivary secretory disorders are life-disrupting pathologic conditions with a high prevalence, especially in the geriatric population. Both patients and clinicians frequently feel helpless and get frustrated by the currently available therapeutic strategies, which consist mainly of palliative managements. Accordingly, to unravel the underlying mechanisms and to develop effective and curative strategies, several animal models have been developed and introduced. Experimental findings from these models have contributed to answer biological and biomedical questions. This review aims to provide various methodological considerations used for the examination of pathological fundamentals in salivary disorders using animal models and to summarize the obtained findings. The information provided in this review could provide plausible solutions for overcoming salivary disorders and also suggest purpose-specific experimental animal systems.

Hemodynamic Effects of Connection to Continuous Renal Replacement Therapy in a Pediatric Animal Model.

To assess the hemodynamic effects of connection to continuous renal replacement therapy (CRRT) in a pediatric experimental animal model. Prospective experimental study was performed using piglets between 2 and 3 months of age and 9-11 kg. CRRT with a PrismaflexR monitor and HF20 filter (surface of 0.2 m2 ) was started after monitoring and anesthetic induction with an initial blood flow at 20 mL/min with 10 mL/min increases every minute until the goal flow of 5 mL/kg/min was achieved. Heart rate, blood pressure, central venous pressure, cardiac index, and renal blood flow were registered at baseline, 5, 15, 30, 60, 120, 180, 240, and 360 min. IBM SPSS Statistics 20.0 package was used for analysis. A P value of <0.05 was considered statistically significant. Thirty-four piglets were studied. Blood pressure, cardiac output, and systemic vascular resistance significantly decreased 5-min after CRRT connection (mean arterial pressure from 85.5 to 70.8 mm Hg, P < 0.001, cardiac index from 3.6 to 3.3 L/min/m2 P = 0.024, and systemic vascular resistance index from 1759 to 1607 dyn.s/cm5 P = 0.012). No significant changes were found in renal blood flow or central venous pressure. All parameters gradually increased at 15 and 30 min after connection but complete recovery was never achieved. Connection to CRRT produces a significant decrease in arterial pressure, cardiac index, and peripheral vascular resistances in hemodynamically stable piglets.

Recurrent acute thermal lesion induces esophageal hyperproliferative premalignant lesions in mice esophagus.

Hot beverage consumption is a risk factor for esophageal squamous cell carcinoma, but the underlying mechanisms are still unknown. We developed an experimental mouse model to understand the mechanism of thermal lesion to esophageal carcinogenesis. Female BALB/c mice were treated by gavage with water at different temperatures three times a week and nitrosamines in the drinking water. Water at 70°C, but not at lower temperatures, initially induced an esophageal necrosis that healed and became resistant to necrosis after further administrations. However, when 70°C water was associated with N-nitrosodiethylamine at doses above 1 ppm, there was interference in epithelial regeneration, allowing recurrent thermal injury and inflammation. Recurrent thermal injury resulted in hyper proliferative premalignant lesions being induced earlier (at 4 weeks) and at a higher frequency (4-fold increase at 16 weeks) when compared to mice treated with NDEA only. Ki-67 immunostaining revealed that recurrent thermal injury induced basal cell proliferation resulting in the expansion of epithelial basal cells, confirmed by the increase in cytokeratin 14 positive cells with concomitant reduction of differentiated cytokeratin 5 positive cells. We conclude that recurrent thermal lesion may act as a tumor promoter though a strong proliferation stimulus of esophageal epithelial basal cells.

Are Currently Selected Laboratory Animals Useful in the Research of How Female Hormones Influence Orthodontic Biomechanics?

Animal testing was and remains the only method of introducing a certain treatment and medical procedure on humans. On the other hand, animals have their rights resulting from applicable legal acts, including Directive 2010/63/EU and, indirectly, the World Medical Association International Code of Medical Ethics (Helsinki Declaration, 1975, amended 2000). Thus, the question arises whether the credibility of the results of hormonal and orthodontic tests obtained so far and their usefulness for the human population is scientifically justified and worth sacrificing laboratory animals for. Especially that, according to statistical data, about 50% of laboratory animals are euthanized at the conclusion of the experiments. The aim of this article was to determine whether animal experiments are scientifically or morally justified in bringing significant evidence in studies that may validate the influence of changes in the concentration of female hormones secreted by the ovaries in various phases of the menstrual cycle in young patients on the duration of an increased tooth movement rate in orthodontic treatment. Papers reporting the results of the original research into female hormones, either natural or exogeneous ones, likely to alternate the orthodontic tooth movement rate were critically evaluated in terms of animal selection. Thorough analysis supported by veterinary knowledge proved that none of the publications enabled an extrapolation of the results to humans. The evaluation of the relation between the rate of tooth movement upon loading with orthodontic forces and hormones either secreted during the menstrual cycle of women or released from the contraceptives already present in the market, does not require sacrificing laboratory animals.

Prospective analysis of myocardial strain through the evolution of Chagas disease in the hamster animal model.

Speckle tracking echocardiography (STE) enables early diagnosis of myocardial damage by evaluating myocardial strain. We aimed to study sequential changes in structural and ventricular functional parameters during Chagas disease (CD) natural history in an animal model. 37 Syrian hamsters were inoculated intraperitoneally with Trypanosoma cruzi (Chagas) and 20 with saline (Control). Echocardiography was performed before the infection (baseline), at 1 month (acute phase), 4, 6, and 8 months (chronic phase) using Vevo 2100 (Fujifilm Inc.) ultrasound system. Left ventricular end-diastolic diameter, Left ventricular end-systolic diameter (LVESD), Left ventricular ejection fraction (LVEF), Global longitudinal (GLS), circumferential (GCS) and radial (GRS) strain were evaluated. Tricuspid annular plane systolic excursion (TAPSE) was used to assess right ventricular function. At 8 months, animals were euthanized and LV myocardial samples were analyzed for quantitation of inflammation and fibrosis. LVEF decreased over time in Chagas group and a difference from Control was detected at 6 months (p-value of groups#time interaction = 0.005). There was a pronounced decrease in GLS, GCS and TAPSE in Chagas group (p-value of groups#time interaction = 0.003 for GLS, < 0.001 for GCS and < 0.009 for TAPSE vs Control) since the first month. LVESD, LVEF and GLS were significantly correlated to the number of inflammatory cells (r = 0.41, p = 0.046; r = - 0.42, p = 0.042; r = 0.41, p = 0.047) but not to fibrosis. In the Syrian hamster model of CD STE parameters (GLS and GCS) showed an early decrease. Changes in LVEF, LVESD, and GLS were correlated to myocardial inflammation but not to fibrosis.

The Median Nerve Injury Model in Pre-clinical Research - A Critical Review on Benefits and Limitations.

The successful introduction of innovative treatment strategies into clinical practise strongly depends on the availability of effective experimental models and their reliable pre-clinical assessment. Considering pre-clinical research for peripheral nerve repair and reconstruction, the far most used nerve regeneration model in the last decades is the sciatic nerve injury and repair model. More recently, the use of the median nerve injury and repair model has gained increasing attention due to some significant advantages it provides compared to sciatic nerve injury. Outstanding advantages are the availability of reliable behavioural tests for assessing posttraumatic voluntary motor recovery and a much lower impact on the animal wellbeing. In this article, the potential application of the median nerve injury and repair model in pre-clinical research is reviewed. In addition, we provide a synthetic overview of a variety of methods that can be applied in this model for nerve regeneration assessment. This article is aimed at helping researchers in adequately adopting this in vivo model for pre-clinical evaluation of peripheral nerve reconstruction as well as for interpreting the results in a translational perspective.

* The New Zealand White Rabbit as a Model for Preclinical Studies Addressing Tissue Repair at the Level of the Abdominal Wall.

In this report, we review the use of the New Zealand White rabbit as the experimental animal for several models of abdominal wall repair. For the repair of an abdominal wall defect, such as a hernia in clinical practice, multiple types of prosthetic material exist. Before their marketing, each of these biomaterials needs to be tested in a preclinical setting to confirm its biocompatibility and appropriate behavior at the different tissue interfaces. For preclinical trials, we have always used the New Zealand White rabbit as the model owing to its ease of handling and suitable size. This size allows for laparoscopic studies designed to follow the behavior in real time of a biomaterial implanted at the peritoneal interface, a delicate interface that often gives rise to complications in human practice. The size of the rabbit also offers a sufficiently large number of implant samples to be harvested for a complete battery of tests at several time points postimplant. In this review, we first describe the models established and then provide the results obtained so far using these models to test the different types of biomaterial. We end our review with a discussion of the clinical implications of these results.

MicroSPECT and MicroPET Imaging of Small Animals for Drug Development.

The process of drug discovery and development requires substantial resources and time. The drug industry has tried to reduce costs by conducting appropriate animal studies together with molecular biological and genetic analyses. Basic science research has been limited to in vitro studies of cellular processes and ex vivo tissue examination using suitable animal models of disease. However, in the past two decades new technologies have been developed that permit the imaging of live animals using radiotracer emission, Xrays, magnetic resonance signals, fluorescence, and bioluminescence. The main objective of this review is to provide an overview of small animal molecular imaging, with a focus on nuclear imaging (single photon emission computed tomography and positron emission tomography). These technologies permit visualization of toxicodynamics as well as toxicity to specific organs by directly monitoring drug accumulation and assessing physiological and/or molecular alterations. Nuclear imaging technology has great potential for improving the efficiency of the drug development process.

Análisis mediante radiografía convencional de los tejidos dentales y periodontales de cerdo (Sus domesticus) sometidos a altas temperaturas / Conventional X-ray analysis of porcine (Sus domesticus) periodontal and dental tissue subjected to high temperature

Introducción: La implementación de modelos animales para el estudio de los tejidos dentales y periodontales de dientes articulados en sus alvéolos sometidos a altas temperaturas permite el establecimiento de parámetros repetitivos que contribuyen con los procesos de identificación. Objetivo: Describir los cambios radiográficos de los tejidos dentales y periodontales de cerdo (Sus domesticus) sometidos a altas temperaturas. Material y métodos: Se realizó un estudio observacional descriptivo de naturaleza pseudo-experimental in vitro para observar los cambios radiográficos de los tejidos dentales y periodontales en 60 dientes de cerdo doméstico sometidos a altas temperaturas (200, 400, 600, 800 y 1,000 ºC). Resultados: Los tejidos dentales y periodontales estudiados presentan gran resistencia a las altas temperaturas sin variar considerablemente su microestructura, de tal manera que los cambios físicos (estabilidad dimensional, fisuras, grietas y fracturas) que ocurren en la medida que aumenta la temperatura pueden describirse a través de radiografía convencional. Conclusiones: El análisis radiográfico de los dientes articulados en sus respectivos alvéolos se constituye en un mecanismo para determinar la temperatura a la cual estuvo sometido un diente, lo que puede ser empleado durante el proceso de identificación odontológica y documentación de la necropsia médico-legal para el caso de cadáveres o restos humanos quemados, carbonizados e incinerados. El cerdo doméstico (Sus domesticus) se constituye en un modelo animal experimental adecuado para estudiar dichos cambios; sin embargo, se recomienda realizar un estudio en dientes humanos articulados en su respectiva unidad alveolar, para determinar si los hallazgos radiográficos descritos se repiten y son extrapolables.

Introduction: The implementation of animal models for the study of periodontal and dental tissues of teeth articulated into their sockets and subjected to high temperatures allows the establishment of repetitive parameters which might contribute to identification processes. Aim: To describe radiographic changes of pig's (Sus domesticus) periodontal and dental tissues subjected to high temperatures. Material and methods: An in vitro pseudo-experimental, descriptive and observational study was undertaken in order to assess radiological changes of periodontal and dental tissues of 60 domestic pig's teeth which had been subjected to high temperatures (200, 400, 600, 800 and 1,000 ºC). Results: The dental and periodontal tissues subject of this research article presented strong resistance to high temperatures without considerable variation of their micro-structure. Thus, physical changes (dimensional stability, fissures, cracks and fractures) which took place as temperature increased, could be described using a conventional X-ray. Conclusions: Radiographic examination of teeth articulated in their sockets can be established as a mechanism to determine the temperature at which the tooth was subjected. This could be used in processes of dental identification and medical-legal autopsy documentation in cases of burned, carbonized or incinerated human remains. Domestic pigs (Sus domesticus) can be regarded as a suitable experimental animal models to study the aforementioned changes. Nevertheless, a study involving human teeth articulated in their own socket is recommended in order to determine whether the radiographic findings herein described are replicated and can be extrapolated.