scholarly journals Use of animal models in elucidating disease pathogenesis in IBD

2014 ◽  
Vol 36 (5) ◽  
pp. 541-551 ◽  
Author(s):  
Puja Vora Khanna ◽  
David Quan Shih ◽  
Talin Haritunians ◽  
Dermot Patrick McGovern ◽  
Stephan Targan
Keyword(s):  
Animal Models ◽  
Disease Pathogenesis

scholarly journals Putative Pathobionts in HLA-B27-Associated Spondyloarthropathy

2021 ◽  
Vol 11 ◽  
Author(s):  
Tejpal Gill ◽  
James T. Rosenbaum
Keyword(s):  
Animal Models ◽  
Microbial Communities ◽  
Underlying Disease ◽  
Disease Development ◽  
Hla B27 ◽  
Disease Pathogenesis ◽  
Fecal Microbiota Transplant ◽  
Germ Free ◽  
Associated Diseases

Spondyloarthritis (SpA) is a group of immune mediated inflammatory diseases with a strong association to the major histocompatibility (MHC) class I molecule, HLA-B27. Although the association between HLA-B27 and AS has been known for almost 50 years, the mechanisms underlying disease pathogenesis are elusive. Over the years, three hypotheses have been proposed to explain HLA-B27 and disease association: 1) HLA B27 presents arthritogenic peptides and thus creates a pathological immune response; 2) HLA-B27 misfolding causes endoplasmic reticulum (ER) stress which activates the unfolded protein response (UPR); 3) HLA-B27 dimerizes on the cell surface and acts as a target for natural killer (NK) cells. None of these hypotheses explains SpA pathogenesis completely. Evidence supports the hypothesis that HLA-B27-related diseases have a microbial pathogenesis. In animal models of various SpAs, a germ-free environment abrogates disease development and colonizing these animals with gut commensal microbes can restore disease manifestations. The depth of microbial influence on SpA development has been realized due to our ability to characterize microbial communities in the gut using next-generation sequencing approaches. In this review, we will discuss various putative pathobionts in the pathogenesis of HLA-B27-associated diseases. We pursue whether a single pathobiont or a disruption of microbial community and function is associated with HLA-B27-related diseases. Furthermore, rather than a specific pathobiont, metabolic functions of various disease-associated microbes might be key. While the use of germ-free models of SpA have facilitated understanding the role of microbes in disease development, future studies with animal models that mimic diverse microbial communities instead of mono-colonization are indispensable. We discuss the causal mechanisms underlying disease pathogenesis including the role of these pathobionts on mucin degradation, mucosal adherence, and gut epithelial barrier disruption and inflammation. Finally, we review the various uses of microbes as therapeutic modalities including pre/probiotics, diet, microbial metabolites and fecal microbiota transplant. Unravelling these complex host-microbe interactions will lead to the development of new targets/therapies for alleviation of SpA and other HLA-B27 associated diseases.

Multiple sclerosis following treatment with a cannabinoid receptor-1 antagonist

2004 ◽  
Vol 10 (3) ◽  
pp. 330-332 ◽  
Author(s):  
B W van Oosten ◽  
J Killestein ◽  
E MH Mathus-Vliegen ◽  
C H Polman
Keyword(s):  
Multiple Sclerosis ◽  
Animal Models ◽  
Receptor Antagonist ◽  
Human Disease ◽  
Cannabinoid Receptor ◽  
Therapeutic Potential ◽  
Laboratory Research ◽  
Cannabinoid Receptor 1 ◽  
Disease Pathogenesis

Laboratory research including animal models of human disease suggests that cannabinoids might have therapeutic potential in multiple sclerosis (MS). We have recently seen a 46-year-old woman who developed MS after starting treatment with a cannabino id recepto r antagonist for obesity. The occurrence of MS several months after starting a cannabinoid receptor antagonist suggests that the cannabino id system might indeed be relevant to disease pathogenesis in MS.

scholarly journals Pulmonary alveolar microlithiasis

2020 ◽  
Vol 29 (158) ◽  
pp. 200024
Author(s):  
Patrick Kosciuk ◽  
Cristopher Meyer ◽  
Kathryn A. Wikenheiser-Brokamp ◽  
Francis X. McCormack
Keyword(s):  
Animal Models ◽  
Disease Management ◽  
Sodium Phosphate ◽  
Clinical Manifestations ◽  
Disease Course ◽  
Disease Pathogenesis ◽  
Pulmonary Alveolar Microlithiasis ◽  
Pathologic Features ◽  
Alveolar Microlithiasis ◽  
Molecular Pathophysiology

Pulmonary alveolar microlithiasis (PAM) is a fascinating rare lung disease that is associated with the accumulation of hydroxyapatite microliths within the lumen of the alveolar spaces. In most patients, PAM is discovered incidentally on radiographs performed for other purposes, and the typical disease course is characterised by slowly progressive respiratory insufficiency over decades. Recent genetic analyses that have revealed that the deficiency of the sodium-phosphate cotransporter NPT2B is the cause of PAM have enabled the development of powerful animal models that inform our approach to disease management and treatment. Here we review the epidemiology and molecular pathophysiology of PAM, as well as the diagnostic approach, clinical manifestations, radiographic and pathologic features, and clinical management of the disease. Although there are no proven treatments for PAM, progress in our understanding of disease pathogenesis is providing insights that suggest strategies for trials.

scholarly journals Animal Models of Alcoholic Liver Disease: Pathogenesis and Clinical Relevance

2017 ◽  
Vol 17 (3) ◽  
pp. 173-186 ◽  
Author(s):  
Bin Gao ◽  
Ming-Jiang Xu ◽  
Adeline Bertola ◽  
Hua Wang ◽  
Zhou Zhou ◽  
...  
Keyword(s):  
Liver Disease ◽  
Animal Models ◽  
Alcoholic Liver Disease ◽  
Clinical Relevance ◽  
Disease Pathogenesis

scholarly journals Understanding Host-Pathogen Interactions in Acute Chorioamnionitis Through the Use of Animal Models

2021 ◽  
Vol 11 ◽  
Author(s):  
Amanda Brosius Lutz ◽  
Salwan Al-Nasiry ◽  
Boris W. Kramer ◽  
Martin Mueller
Keyword(s):  
Animal Models ◽  
Inflammatory Response ◽  
Disease Burden ◽  
Preterm Births ◽  
Therapeutic Approaches ◽  
Host Pathogen Interactions ◽  
Disease Pathogenesis ◽  
Numerous Species ◽  
Host Pathogen ◽  
Key Features

Inflammation of the chorion and/or amnion during pregnancy is called chorioamnionitis. Acute chorioamnionitis is implicated in approximately 40% of preterm births and has wide-ranging implications for the mother, fetus, and newborn. Large disease burden and lack of therapeutic approaches drive the discovery programs to define and test targets to tackle chorioamnionitis. Central to the advancement of these studies is the use of animal models. These models are necessary to deepen our understanding of basic mechanisms of host-pathogen interactions central to chorioamnionitis disease pathogenesis. Models of chorioamnionitis have been developed in numerous species, including mice, rabbits, sheep, and non-human primates. The various models present an array of strategies for initiating an inflammatory response and unique opportunities for studying its downstream consequences for mother, fetus, or newborn. In this review, we present a discussion of the key features of human chorioamnionitis followed by evaluation of currently available animal models in light of these features and consideration of how these models can be best applied to tackle outstanding questions in the field.

Pathogenesis of Wegener's granulomatosis: current concepts

2005 ◽  
Vol 7 (8) ◽  
pp. 1-19 ◽  
Author(s):  
Pasha Sarraf ◽  
Michael C. Sneller
Keyword(s):  
Animal Models ◽  
Wegener’S Granulomatosis ◽  
Granulomatous Inflammation ◽  
Wegener's Granulomatosis ◽  
Small Vessel Vasculitis ◽  
Focused Attention ◽  
Pathogenic Role ◽  
Disease Pathogenesis ◽  
Autoimmune Syndrome

Wegener's granulomatosis (WG) is a complex autoimmune syndrome that is characterised by upper/lower respiratory necrotising granulomatosis, glomerulonephritis and small-vessel vasculitis. Since Wegener's 1936 description, considerable advances in recognition and treatment have changed this disease from a rapidly and uniformly fatal illness to a chronic disease characterised by remissions and relapses. The serendipitous discovery of anti-neutrophil cytoplasmic antibodies (ANCAs) as a marker associated with WG focused attention on the potential pathogenic role of these antibodies and has recently led to the development of novel animal models that might facilitate our understanding of the disease pathogenesis. Future animal models of this disease will have to account for the role of both ANCA-mediated pathology and granulomatous inflammation to enable us to understand the chronic and persistent features of WG in humans.

scholarly journals Microbiome and Graves’ Orbitopathy

2020 ◽  
Vol 9 (Suppl. 1) ◽  
pp. 78-86
Author(s):  
Giulia Masetti ◽  
Marian Ludgate
Keyword(s):  
Mental Health ◽  
Animal Models ◽  
State Of The Art ◽  
Graves Disease ◽  
Potential Importance ◽  
Disease Pathogenesis ◽  
Current State ◽  
Metabolic Products ◽  
Microbiome Research ◽  
Graves Orbitopathy

<b><i>Background:</i></b> Studies from animal models of autoimmunity have highlighted the potential importance of microorganisms and their metabolic products in shaping the immune system. <b><i>Summary:</i></b> This review provides an introduction to the current state-of-the-art in microbiome research both from the perspective of “what is known” and of methodologies for its investigation. It then summarises the evidence for a role for the microbiome in the pathogenesis of Graves’ disease and Graves’ orbitopathy with reference to animal models and studies in human cohorts, from both published and ongoing sources. <b><i>Key Message:</i></b> Microbiome research is in its infancy but has already provided novel insights into disease pathogenesis across the spectrum from cancer to mental health and autoimmunity.

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