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Respiratory Pathophysiology
Published in Hyun Jung Kim, Biomimetic Microengineering, 2020
Brian F. Niemeyer, Alexander J. Kaiser, Kambez H. Benam
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease which results from deregulated wound healing and inflammation leading to lung fibrosis and scarring. Fibrosis of the lungs in turn prevents normal, healthy lung function leading to impaired breathing, gas exchange, and ultimately death due to respiratory failure. The prognosis for patients with IPF is quite poor with a median life expectancy of 3 years after diagnosis (Sundarakrishnan et al. 2018). The incidence of IPF has been estimated to be 130,000 in the United States, 300,000 in Europe, and 640,000 in East Asia although the prevalence is on the rise (Sundarakrishnan et al. 2018, Martinez et al. 2017). Although the exact cause IPF has yet to be determined, several factors associated with increased risk of disease have been identified including exposure to cigarette smoke, viral infection, altered bacterial loads and composition, microaspiration of gastric contents, as well as genetic susceptibility (Martinez et al. 2017). Over time, several animal models have been developed for the study of IPF; however, each of these animal systems is derived by artificially triggering fibrosis using various compounds, which may not accurately reflect IPF found in humans as the etiological agent is unknown (Sundarakrishnan et al. 2018, Chua, Gauldie, and Laurent 2005). Further, no current animal model is able to recapitulate all of the aspects of IPF in humans (Chua, Gauldie, and Laurent 2005). The discrepancies between IPF in humans and the current animal models simply highlights the need for complementary in vitro systems capable of replicating the disease in humans.
Inhalation Toxicology
Published in Ronald Scott, of Industrial Hygiene, 2018
The mining of coal has caused a great deal of lung damage over the years. Coal particulate produces characteristic symptoms called coal miner’s pneumoconiosis (black lung disease). Coal dust deposited in the lungs leads to breathlessness. Fibrosis is not a direct symptom. The introduction of wet drilling techniques to minimize dust production was a major advance in reducing the magnitude of this problem.
Environmental factors contribute to skeletal muscle and spinal cord regeneration
Published in David M. Gardiner, Regenerative Engineering and Developmental Biology, 2017
Ophelia Ehrlich, Yona Goldshmit, Peter Currie
Many mouse and zebrafish injury models have been established to study the kinetics of muscle regeneration in vivo, including laceration, freezing, and chemical-induced cardiotoxin injuries (d’Albis et al. 1988; Hawke 2001; Takada et al. 2007; Warren et al. 2007; Seger et al. 2011; Gurevich et al. 2016). Of these injury paradigms, laceration-type injuries, which involve the use of a sharp object to cause direct trauma to the muscle, most accurately model muscle–ECM disruption. These injuries involve the disruption of the connective tissue and myofiber necrosis, followed by inflammation and fiber renewal (Burkin and Kaufman 1999; Almekinders 1999; Boppart et al. 2006; Järvinen et al. 2007; Quintero et al. 2009; de Souza and Gottfried 2013). Within a laceration injury in rats, severed myofibers retract and a hematoma is formed within the first 24 hours after injury (Kaufman et al. 1985; Kääriäinen et al. 1998; Burkin and Kaufman 1999). Inflammatory cells will invade the hematoma and begin to digest the blood clot and necrotic myofibers. Muscle stem cells are attracted to the damaged muscle via cytokines released by macrophages (Mayer et al. 1997; Charge and Rudnicki 2004; Grefte et al. 2007). These cells are also able to secrete ECM proteins that will help anchor fibroblasts within the damaged zone (Lehto et al. 1985; Lehto and Järvinen 1985; Hurme et al. 1991; Vachon et al. 1997). Fibroblasts deposit many ECM proteins, including collagen fibrils that will make up the connective scar tissue (Lehto et al. 1985; Vachon et al. 1997). Within rat laceration injury models, by day 3, the hematoma is replaced by scar tissue. Scar tissue provides a supportive role, keeping the retracted fibers together and providing attachment sites for new myofibers (Kääriäinen et al. 2000; Dumont et al. 2015b). From day 5 post-injury, there is evidence of regenerating fibers that perforate scar tissue; however, if scar tissue is excessive, it will impinge on the ability of muscle fibers to grow through the scar (Hurme et al. 1991; Hurme and Kalimo 1992; Dumont et al. 2015b). Therefore, this scar tissue plays an important supportive role, but it can also become competitive with processes involved in fiber renewal (Kääriäinen et al. 2000; Dumont et al. 2015b). By 21 days after injury, size of the scar tissue is reduced and regenerating fibers have matured; however, skeletal muscle never fully recovers in the rat laceration injury model (Hurme et al. 1991; Kääriäinen et al. 2000; Gnocchi et al. 2009). Fibrosis in scarring is characterized by the accumulation of connective tissue, including collagen (Yao et al. 1996; Sato et al. 2003). Studies of laceration injuries performed on zebrafish also recapitulate many of the observed characteristics of muscle regeneration. Within these models, there was evidence of early muscle regeneration, including muscle fiber necrosis, mononuclear cell invasion, and the initiation of fiber renewal, where muscle stem cells become activated, proliferate, and differentiate into myofibers within the first 7 days after injury (Hughes and Blau 1990; Stoiber and Sanger 1996; Rowlerson et al. 1997).
Magnetic resonance enterography in Crohn’s disease patients: current state of the art and future perspectives
Published in Expert Review of Medical Devices, 2021
Hila Bufman, Rami Eliakim, Noam Tau, Michal Marianne Amitai
Stricturing phenotype of CD is very common, and up to 30% of CD patients will be diagnosed with strictures [45]. While MRE is good at detecting strictures [37], the differentiation of the exact proportion of overlying inflammation in those strictured areas is a major challenge [10]. Table 3 summarizes the last decade major publications regarding this challenge. Inflammation and fibrosis are considered to be on the same spectrum of pathogenesis, and in most fibrotic segments there is also some degree of inflammation. This most likely hinders the ability of MRE to differentiate between the two entities [46]. The importance of this differentiation is due to potential change in treatment in each of those pathologies and their varying prognosis. While inflammatory disease may benefit from medical anti-inflammatory treatment, as of today there is no medical treatment to treat fibrosis once it has occurred, and currently the only treatment options are either surgical of endoscopic dilatation. Figure 3 demonstrates stenotic disease.
Development of MR elastography method to characterize the elastic property of the sterno-cleido-mastoid (SCM) muscle
Published in Computer Methods in Biomechanics and Biomedical Engineering, 2020
P. Pouletaut, F. Charleux, B. Devauchelle, J.M. Constans, R. Ternifi, S. Boussida, A. Hamaoui, C. Krzisch, S.F. Bensamoun
Radiotherapy applied to head and neck cancers causes fibrosis that is a very frequent side effect of this treatment. Fibrosis provides an increase of muscle stiffness, responsible for an impairment in the quality of life of patients (Langendijk et al. 2008), and can obstruct a possible catch-up surgery or a possible re-irradiation (Moloney et al. 2015). The appreciation of radiation-induced cervical fibrosis within the sterno-cleido-mastoid (SCM) muscle is subjective and radiotherapists have attempted to define standardized clinical measurement scales, which bring several objective criteria such as the level of indurations of cutaneous tissues and the quality of life. The correlation between these different classifications is often poor (Davis et al. 2003). Thus, the purpose of this study is to develop MR Elastography (MRE) protocol for healthy neck muscle to latterly used for patient having neck muscle fibrosis.
Low-dose cadmium exposure exacerbates polyhexamethylene guanidine-induced lung fibrosis in mice
Published in Journal of Toxicology and Environmental Health, Part A, 2018
Min-Seok Kim, Sung-Hwan Kim, Doin Jeon, Hyeon-Young Kim, Jin-Young Han, Bumseok Kim, Kyuhong Lee
Extracellular matrix (ECM) is a highly dynamic structural network that is present in all tissues and continuously undergoes balanced remodeling (Bonnans, Chou, and Werb 2015). Remodeling of the ECM by myofibroblasts is important for wound healing; however, dysregulation of ECM remodeling leads to pathological fibrosis (Bonnans, Chou, and Werb 2015; Minton 2014). Multiple mechanisms and mediators contribute to ECM alterations in IPF. MMPs are important regulators of ECM and regulate cytokines, growth factors, ECM deposition, and tissue reorganization (Madala et al. 2010; Wynn 2007). TGF-β1 is a key inducer of epithelial–mesenchymal transition and mediator of pulmonary fibrosis (Border and Noble 1994; Kasai et al. 2005; Li et al. 2016; Luo et al. 2016). Fibronectin is an ECM component. Fibronectin levels increase during tissue repair; however, excessive fibronectin accumulation leading to fibrosis. In the present study, expression of MMP12, TGF-β1, and fibronectin was elevated in pulmonary tissues of mice in the PHMG + CdCl2 compared to PHMG alone (Figure 6). Further, alterations in expression of fibrogenic mediators were consistent with changes in the expression of inflammatory cytokines. Inflammatory cytokines drive the progression of fibrosis in injured tissues by regulating the production of fibrogenic mediators (Borthwick, Wynn, and Fisher 2013). For example, IL-1β is a potent inducer of TGF-β1 and MMP production by various connective tissue cells (Wright, Cawston, and Hazleman 1991; Yue et al. 1994). Therefore, increased expression of these fibrogenic mediators may be attributed to Cd-induced inflammatory responses. In addition, Cd may induce fibrosis through inflammation-independent fibrotic mechanisms. Recently, Hu et al. (2017) noted that exposure to low Cd level stimulates pulmonary fibrotic signaling and myofibroblast differentiation. Li et al. (2017) found that Cd exposure stimulated vimentin phosphorylation and Yes-associated protein 1 (YAP1) activation, leading to peribronchiolar fibrosis and subsequent airway remodeling. However, further studies are needed to completely elucidate the influence of Cd in induction of pulmonary fibrosis.