The Effects of Heparin Administration in an Animal Model of Chronic Peritoneal Dialysate Exposure

2002 ◽  
Vol 22 (5) ◽  
pp. 566-572 ◽  
Author(s):  
An S. De Vriese ◽  
Siska Mortier ◽  
Maria Cornelissen ◽  
Els Palmans ◽  
Nele J. Vanacker ◽  
...  

Diverse modes of heparin administration have been used in animal models of chronic peritoneal dialysate exposure to maintain catheter patency and prevent fibrinous adhesions. Heparin has biological actions independent of its well-known anticoagulant activity, including the ability to modulate extracellular matrix synthesis, cellular proliferation, angiogenesis, and inflammation. These actions may interfere with peritoneal membrane homeostasis. The present study evaluated the influence of the mode of heparin administration on technique survival and infection rate in a rat model of chronic dialysate exposure. Further, the incorporation of heparin in the peritoneal membrane was examined. A 3.86% glucose dialysate was injected twice daily into Wistar rats with a heparin-coated catheter (group A1), or with a standard catheter with heparin injections during the entire exposure time (group A2) or only during 1 week (group A3). Sham manipulations were performed in a fourth group and a fifth group was left untreated. Technique survival was 80% in group A1, 60% in group A2, and 40% in group A3. The rate of infection was highest in group A1 and lowest in group A2. Intraperitoneally administered heparin accumulated in the peritoneal membrane, whereas dextran, with a molecular weight similar to that of heparin, was not incorporated in the peritoneum. In conclusion, intraperitoneal heparin reduced the incidence of infection in an animal model of chronic dialysate exposure. The best technique survival was, however, obtained using a heparin-coated catheter. Heparin is incorporated in the peritoneal membrane, where it may exert diverse biological actions and thus bias study results. The use of a heparin-coated catheter in combination with antibiotics may be the optimal approach to obtaining peritoneal access in animal models of chronic dialysate exposure.

2001 ◽  
Vol 21 (3_suppl) ◽  
pp. 354-356 ◽  
Author(s):  
An S. De Vriese ◽  
Siska Mortier ◽  
Norbert H. Lameire

Heparin is a glycosaminoglycan with well-known anticoagulant activity. That property is used in animal models of peritoneal dialysis to maintain catheter patency and to prevent the development of peritoneal adhesions. However, heparin has a host of biologic actions beyond its role as an anticoagulant. Heparin modulates the activity of various inflammatory cells, affects the synthesis of extracellular matrix, has antiproliferative effects on several cell types, and influences neoangiogenesis. By virtue of those actions, intraperitoneally administered heparin may interfere with peritoneal membrane homeostasis. The potential side effects of heparin use in animal models of peritoneal dialysis should be recognized to permit correct interpretation of experimental studies conducted in those models.


2015 ◽  
Vol 223 (3) ◽  
pp. 157-164 ◽  
Author(s):  
Georg Juckel

Abstract. Inflammational-immunological processes within the pathophysiology of schizophrenia seem to play an important role. Early signals of neurobiological changes in the embryonal phase of brain in later patients with schizophrenia might lead to activation of the immunological system, for example, of cytokines and microglial cells. Microglia then induces – via the neurotoxic activities of these cells as an overreaction – a rarification of synaptic connections in frontal and temporal brain regions, that is, reduction of the neuropil. Promising inflammational animal models for schizophrenia with high validity can be used today to mimic behavioral as well as neurobiological findings in patients, for example, the well-known neurochemical alterations of dopaminergic, glutamatergic, serotonergic, and other neurotransmitter systems. Also the microglial activation can be modeled well within one of this models, that is, the inflammational PolyI:C animal model of schizophrenia, showing a time peak in late adolescence/early adulthood. The exact mechanism, by which activated microglia cells then triggers further neurodegeneration, must now be investigated in broader detail. Thus, these animal models can be used to understand the pathophysiology of schizophrenia better especially concerning the interaction of immune activation, inflammation, and neurodegeneration. This could also lead to the development of anti-inflammational treatment options and of preventive interventions.


Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4221
Author(s):  
Aage Kristian Olsen Alstrup ◽  
Svend Borup Jensen ◽  
Ole Lerberg Nielsen ◽  
Lars Jødal ◽  
Pia Afzelius

The development of new and better radioactive tracers capable of detecting and characterizing osteomyelitis is an ongoing process, mainly because available tracers lack selectivity towards osteomyelitis. An integrated part of developing new tracers is the performance of in vivo tests using appropriate animal models. The available animal models for osteomyelitis are also far from ideal. Therefore, developing improved animal osteomyelitis models is as important as developing new radioactive tracers. We recently published a review on radioactive tracers. In this review, we only present and discuss osteomyelitis models. Three ethical aspects (3R) are essential when exposing experimental animals to infections. Thus, we should perform experiments in vitro rather than in vivo (Replacement), use as few animals as possible (Reduction), and impose as little pain on the animal as possible (Refinement). The gain for humans should by far exceed the disadvantages for the individual experimental animal. To this end, the translational value of animal experiments is crucial. We therefore need a robust and well-characterized animal model to evaluate new osteomyelitis tracers to be sure that unpredicted variation in the animal model does not lead to a misinterpretation of the tracer behavior. In this review, we focus on how the development of radioactive tracers relies heavily on the selection of a reliable animal model, and we base the discussions on our own experience with a porcine model.


2013 ◽  
Vol 26 (5) ◽  
pp. 264-271 ◽  
Author(s):  
Mousumi Tania ◽  
Md. Asaduzzaman Khan ◽  
Kun Xia

ObjectiveAutism, a lifelong neuro-developmental disorder is a uniquely human condition. Animal models are not the perfect tools for the full understanding of human development and behavior, but they can be an important place to start. This review focused on the recent updates of animal model research in autism.MethodsWe have reviewed the publications over the last three decades, which are related to animal model study in autism.ResultsAnimal models are important because they allow researchers to study the underlying neurobiology in a way that is not possible in humans. Improving the availability of better animal models will help the field to increase the development of medicines that can relieve disabling symptoms. Results from the therapeutic approaches are encouraging remarkably, since some behavioral alterations could be reversed even when treatment was performed on adult mice. Finding an animal model system with similar behavioral tendencies as humans is thus vital for understanding the brain mechanisms, supporting social motivation and attention, and the manner in which these mechanisms break down in autism. The ongoing studies should therefore increase the understanding of the biological alterations associated with autism as well as the development of knowledge-based treatments therapy for those struggling with autism.ConclusionIn this review, we have presented recent advances in research based on animal models of autism, raising hope for understanding the disease biology for potential therapeutic intervention to improve the quality of life of autism individuals.


Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1011
Author(s):  
Thi-Quyen Nguyen ◽  
Rare Rollon ◽  
Young-Ki Choi

Influenza remains one of the most significant public health threats due to its ability to cause high morbidity and mortality worldwide. Although understanding of influenza viruses has greatly increased in recent years, shortcomings remain. Additionally, the continuous mutation of influenza viruses through genetic reassortment and selection of variants that escape host immune responses can render current influenza vaccines ineffective at controlling seasonal epidemics and potential pandemics. Thus, there is a knowledge gap in the understanding of influenza viruses and a corresponding need to develop novel universal vaccines and therapeutic treatments. Investigation of viral pathogenesis, transmission mechanisms, and efficacy of influenza vaccine candidates requires animal models that can recapitulate the disease. Furthermore, the choice of animal model for each research question is crucial in order for researchers to acquire a better knowledge of influenza viruses. Herein, we reviewed the advantages and limitations of each animal model—including mice, ferrets, guinea pigs, swine, felines, canines, and non-human primates—for elucidating influenza viral pathogenesis and transmission and for evaluating therapeutic agents and vaccine efficacy.


Pharmacology ◽  
2021 ◽  
pp. 1-13
Author(s):  
Catarina V. Jota Baptista ◽  
Ana I. Faustino-Rocha ◽  
Paula A. Oliveira

<b><i>Background:</i></b> The Nobel Prize of Physiology or Medicine (NPPM) has recognized the work of 222 scientists from different nationalities, from 1901 until 2020. From the total, 186 award researchers used animal models in their projects, and 21 were attributed to scientists and projects directly related to Pharmacology. In the most recent years, genetics is a dominant scientific area, while at the beginning of the 20th century, most of the studies were more related to anatomy, cytology, and physiology. <b><i>Summary:</i></b> Mammalian models were used in 144 NPPM projects, being rodents the most used group of species. Moreover, 92 researchers included domestic species in their work. The criteria used to choose the species, the number of animals used and the experimental protocol is always debatable and dependent on the scientific area of the study; however, the 3R’s principle can be applied to most scientific fields. Independently of the species, the animal model can be classified in different types and criteria, depending on their ecology, genetics, and mode of action. <b><i>Key-Messages:</i></b> The use of animal models in NPPM awarded projects, namely in Pharmacology, illustrates their importance, need and benefit to improve scientific knowledge and create solutions. In the future, with the contribute of technology, it might be possible to refine the use of animal models in pharmacology studies.


2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Hua-Chuan Zheng ◽  
Yasuo Takano

The incidence of lung adenocarcinoma has been remarkably increasing in recent years due to the introduction of filter cigarettes and secondary-hand smoking because the people are more exposed to higher amounts of nitrogen oxides, especially 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone(NNK), which is widely applied in animal model of lung tumors. In NNK-induced lung tumors, genetic mutation, chromosome instability, gene methylation, and activation of oncogenes have been found so as to disrupt the expression profiles of some proteins or enzymes in various cellular signal pathways. Transgenic animal with specific alteration of lung cancer-related molecules have also been introduced to clarify the molecular mechanisms of NNK in the pathogenesis and development of lung tumors. Based on these animal models, many antioxidant ingredients and antitumor chemotherapeutic agents have been proved to suppress the NNK-induced lung carcinogenesis. In the future, it is necessary to delineate the most potent biomarkers of NNK-induced lung tumorigenesis, and to develop efficient methods to fight against NNK-associated lung cancer using animal models.


2010 ◽  
Vol 30 (8) ◽  
pp. 1412-1431 ◽  
Author(s):  
David W Howells ◽  
Michelle J Porritt ◽  
Sarah SJ Rewell ◽  
Victoria O'Collins ◽  
Emily S Sena ◽  
...  

No single animal model is able to encompass all of the variables known to affect human ischemic stroke. This review highlights the major strengths and weaknesses of the most commonly used animal models of acute ischemic stroke in the context of matching model and experimental aim. Particular emphasis is placed on the relationships between outcome and underlying vascular variability, physiologic control, and use of models of comorbidity. The aim is to provide, for novice and expert alike, an overview of the key controllable determinants of experimental stroke outcome to help ensure the most effective application of animal models to translational research.


2021 ◽  
Vol 12 ◽  
Author(s):  
Mohammad Ali Nilforooshan ◽  
Dorian Garrick

Reduced models are equivalent models to the full model that enable reduction in the computational demand for solving the problem, here, mixed model equations for estimating breeding values of selection candidates. Since phenotyped animals provide data to the model, the aim of this study was to reduce animal models to those equations corresponding to phenotyped animals. Non-phenotyped ancestral animals have normally been included in analyses as they facilitate formation of the inverse numerator relationship matrix. However, a reduced model can exclude those animals and obtain identical solutions for the breeding values of the animals of interest. Solutions corresponding to non-phenotyped animals can be back-solved from the solutions of phenotyped animals and specific blocks of the inverted relationship matrix. This idea was extended to other forms of animal model and the results from each reduced model (and back-solving) were identical to the results from the corresponding full model. Previous studies have been mainly focused on reduced animal models that absorb equations corresponding to non-parents and solve equations only for parents of phenotyped animals. These two types of reduced animal model can be combined to formulate only equations corresponding to phenotyped parents of phenotyped progeny.


2018 ◽  
Vol 29 (7) ◽  
pp. 757-770 ◽  
Author(s):  
Nikita Nirwan ◽  
Preeti Vyas ◽  
Divya Vohora

Abstract Temporal lobe epilepsy (TLE) is the chronic and pharmacoresistant form of epilepsy observed in humans. The current literature is insufficient in explicating the comprehensive mechanisms underlying its pathogenesis and advancement. Consequently, the development of a suitable animal model mimicking the clinical characteristics is required. Further, the relevance of status epilepticus (SE) to animal models is dubious. SE occurs rarely in people; most epilepsy patients never experience it. The present review summarizes the established animal models of SE and TLE, along with a brief discussion of the animal models that have the distinctiveness and carries the possibility to be developed as effective models for TLE. The review not only covers the basic requirements, mechanisms, and methods of induction of each model but also focuses upon their major limitations and possible modifications for their future use. A detailed discussion on chemical, electrical, and hypoxic/ischemic models as well as a brief explanation on the genetic models, most of which are characterized by development of SE followed by neurodegeneration, is presented.


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