scholarly journals Animal Models of Typical Heterotopic Ossification

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Lixin Kan ◽  
John A. Kessler

Heterotopic ossification (HO) is the formation of marrow-containing bone outside of the normal skeleton. Acquired HO following traumatic events is a common and costly clinical complication. In contrast, hereditary HO is rarer, progressive, and life-threatening. Substantial effort has been directed towards understanding the mechanisms underlying HO and finding efficient treatments. However, one crucial limiting factor has been the lack of relevant animal models. This article reviews the major currently available animal models, summarizes some of the insights gained from these studies, and discusses the potential future challenges and directions in HO research.

2021 ◽  
Vol 17 (10) ◽  
pp. e1009966
Author(s):  
Derek R. Stein ◽  
Bryce M. Warner ◽  
Jonathan Audet ◽  
Geoff Soule ◽  
Vinayakumar Siragam ◽  
...  

Nigeria continues to experience ever increasing annual outbreaks of Lassa fever (LF). The World Health Organization has recently declared Lassa virus (LASV) as a priority pathogen for accelerated research leading to a renewed international effort to develop relevant animal models of disease and effective countermeasures to reduce LF morbidity and mortality in endemic West African countries. A limiting factor in evaluating medical countermeasures against LF is a lack of well characterized animal models outside of those based on infection with LASV strain Josiah originating form Sierra Leone, circa 1976. Here we genetically characterize five recent LASV isolates collected from the 2018 outbreak in Nigeria. Three isolates were further evaluated in vivo and despite being closely related and from the same spatial / geographic region of Nigeria, only one of the three isolates proved lethal in strain 13 guinea pigs and non-human primates (NHP). Additionally, this isolate exhibited atypical pathogenesis characteristics in the NHP model, most notably respiratory failure, not commonly described in hemorrhagic cases of LF. These results suggest that there is considerable phenotypic heterogeneity in LASV infections in Nigeria, which leads to a multitude of pathogenesis characteristics that could account for differences between subclinical and lethal LF infections. Most importantly, the development of disease models using currently circulating LASV strains in West Africa are critical for the evaluation of potential vaccines and medical countermeasures.


2005 ◽  
Vol 25 (4_suppl) ◽  
pp. 77-82 ◽  
Author(s):  
Akira Saito

Encapsulating peritoneal sclerosis (EPS) is a life-threatening complication of peritoneal dialysis (PD). The overall prevalence of EPS in Japanese PD patients is 2.3%. Among patients on PD for less than 5 years, the rate is 0.9%; among patients on PD for 5 – 10 years, the rate is 3.8%; and among patients on PD for >10 years, it is 11.5%. Thus, the longer the treatment duration, the higher the prevalence of EPS. Encapsulating peritoneal sclerosis does not result solely from the natural progression of peritoneal sclerosis. A “second hit” event, such as bacterial peritonitis, abdominal bleeding, or abdominal surgery may be needed to trigger the onset of EPS in the face of advanced peritoneal sclerosis. To prevent development of EPS, PD treatment is replaced by other treatments when patients reached high-transport status. Peritoneal lavage and prednisolone administration have been reported to be effective in preventing or stopping the progress of EPS. When bowel obstruction has occurred, total enterolysis to remove the fibrous capsule from the bowel is indicated. To maximize overall quality of life, patients with end-stage renal disease (ESRD) should have the choice to make use of all the treatment modalities available: PD, hemodialysis (HD), and transplantation. Furthermore, the development of truly biocompatible PD equipment—including peritoneal catheters, solutions, and systems—are desirable to extend PD treatment for the long term. The cost of individual products could decrease significantly if PD use were to increase to 30% from 10% among ESRD patients worldwide. As practitioners, we have to further improve the technical survival rate and functional duration of PD treatment so that adequate peritoneal function can be maintained for 10 years in at least 40% of PD patients. The goal is to place PD on par with HD using high-flux dialysis membranes and ultrapure dialysis solution.


2020 ◽  
Vol 4 (2) ◽  
pp. 1-5
Author(s):  
Habib R Khan ◽  
Saima Khan ◽  
Asha Srikanth ◽  
William H T Smith

Abstract Background Capillary leak syndrome (CLS) is a rare connective tissue disease, triggered by the leak of serous fluid into the interstitial spaces, characterized by a hallmark of oedema and effusions in confined spaces. The limiting factor in CLS management appears to be its diagnosis rather than treatment, which is usually to contain the disease progression rather than a cure. Case summary We report a case of a 51-year-old woman with recurrent life-threatening presentations of pericardial effusions, pleural effusions, and generalized swelling of face and extremities. The only notable past medical history was of Type 1 diabetes. Numerous investigations did not lead to specific disease accounting for pericardial effusions and pleural effusions. Eventually, the diagnosis of CLS was made based on hypovolaemic shock, hypoalbuminaemia, and haemoconcentration without the presence of albuminuria. She was managed with steroids to reduce system inflammation and later with immunoglobulins and tumour necrosis factor to contain the disease process. Since her diagnosis and subsequent appropriate management, she has not had further admissions with cardiac tamponade 16 months of follow-up. Discussion The diagnosis of CLS is difficult to make unless there is a high degree of suspicion and until other causes have been ruled out. It remains a challenging condition to manage as the treatment options are limited and patients recurrently present with emergencies until the correct diagnosis is made and the optimal treatment is provided.


2010 ◽  
Vol 23 (06) ◽  
pp. 385-392 ◽  
Author(s):  
S. Barry

SummaryThe ability of non-steroidal anti-inflammatory drugs (NSAID) to inhibit bone healing has been established in experimental animal models using mice, rats, and rabbits. The mechanism of action is largely unknown but stems from prostaglandin inhibition and is likely multifactorial. In human medicine NSAID are known to prevent heterotopic ossification, however the clinical importance of their effects on bone healing remains controversial. Although a small handful of reports suggest that NSAID suppress bone healing in dogs and horses, there is little published information to direct veterinary practice in domestic species.


2021 ◽  
Author(s):  
Rumen Nikolov ◽  
Kalina Koleva

Serotonin syndrome (SS) is a potentially life-threatening adverse drug effect that occurs after an overdose or combined administration of two or more drugs that increase the serotonin levels. In humans, SS is represented by a triad of symptoms including mental status changes, neuromuscular hyperactivity and autonomic dysfunction. The manifestations of the syndrome observed in rodents resemble the symptoms of SS in humans. Theoretically, SS can occur as a result of stimulation of any of the seven families of the serotonin receptors. However, most data support the involvement of 5-HT1A and 5-HT2A receptors. A number of studies indicate the effectiveness of 5-HT2 antagonists and GABA-ergic agents in the treatment of the hyperthermia and other symptoms of SS in rats. Therefore, animal models of SS may help to further elucidate the mechanism of its development and the possibilities for its treatment.


2015 ◽  
Vol 95 (3) ◽  
pp. 1025-1109 ◽  
Author(s):  
O. Friedrich ◽  
M. B. Reid ◽  
G. Van den Berghe ◽  
I. Vanhorebeek ◽  
G. Hermans ◽  
...  

Critical illness polyneuropathies (CIP) and myopathies (CIM) are common complications of critical illness. Several weakness syndromes are summarized under the term intensive care unit-acquired weakness (ICUAW). We propose a classification of different ICUAW forms (CIM, CIP, sepsis-induced, steroid-denervation myopathy) and pathophysiological mechanisms from clinical and animal model data. Triggers include sepsis, mechanical ventilation, muscle unloading, steroid treatment, or denervation. Some ICUAW forms require stringent diagnostic features; CIM is marked by membrane hypoexcitability, severe atrophy, preferential myosin loss, ultrastructural alterations, and inadequate autophagy activation while myopathies in pure sepsis do not reproduce marked myosin loss. Reduced membrane excitability results from depolarization and ion channel dysfunction. Mitochondrial dysfunction contributes to energy-dependent processes. Ubiquitin proteasome and calpain activation trigger muscle proteolysis and atrophy while protein synthesis is impaired. Myosin loss is more pronounced than actin loss in CIM. Protein quality control is altered by inadequate autophagy. Ca2+dysregulation is present through altered Ca2+homeostasis. We highlight clinical hallmarks, trigger factors, and potential mechanisms from human studies and animal models that allow separation of risk factors that may trigger distinct mechanisms contributing to weakness. During critical illness, altered inflammatory (cytokines) and metabolic pathways deteriorate muscle function. ICUAW prevention/treatment is limited, e.g., tight glycemic control, delaying nutrition, and early mobilization. Future challenges include identification of primary/secondary events during the time course of critical illness, the interplay between membrane excitability, bioenergetic failure and differential proteolysis, and finding new therapeutic targets by help of tailored animal models.


2017 ◽  
Vol 10 (1) ◽  
pp. 35-39 ◽  
Author(s):  
Eszter Bogi ◽  
Kristína Belovicova ◽  
Kristína Csatlosova ◽  
Michal Dubovicky

AbstractDepression is one of the most prevalent and life-threatening forms of mental illness affecting about 20% of the population. Depressive disorder as a biochemical phenomenon, was first recognized in the mid-20th century of research, however the etiology of this disease is still not well understood. Although the need to investigate depressive disorders has emerged from the needs of clinical practice, there are many preclinical studies, which brought new insights into this field of research. During experimental work it was crucial to develop appropriate animal models, where the neurohumoral mechanism was similar to humans. In the past decades, several animal models of maternal depression have been developed. We describe the three most popular rodent models of maternal depression which are based on 1. stress prior to gestation, 2. prenatal stress and 3. early life stress. The above-mentioned animal models appear to fulfill many criteria for a relevant animal model of depression; they alter the regulation of the HPA, induce signs of depression-like behavior and several antidepressant treatments can reverse the state induced by maternal stress. Although, they are not able to model all aspects of maternal depression, they are useful models for monitoring neurodevelopmental changes occurring in dams and offspring.


Cureus ◽  
2020 ◽  
Author(s):  
Mohammed Asif ◽  
Kevin M Klifto ◽  
Tomer Lagziel ◽  
Julie Caffrey

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