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Connective Tissue and Crohn's Disease

Ripalta Colìa, Addolorata Corrado, Francesco Paolo Cantatore
Inflammatory bowel diseases (IBDs) often present as a complex inflammatory process wherein colon lesions (ulcerative colitis, UC) or widespread ulceration and fissure (Crohn's disease, CD) might be accompanied by ancillary extraintestinal manifestations (EIMs) that could involve almost every organ system, but also by autoimmune disorders ranging from psoriasis and rheumatoid arthritis to connective tissue diseases. Certain EIMs are more common related to the activity of the IBD (joint, skin, ocular and oral manifestations), other EIMs typically run a course independent of the IBD activity (hepatobiliary disorders) and some are non-specific disorders (osteoporosis and amyloidosis)...
June 16, 2016: Annals of Medicine
Rachele Ciccocioppo, Giuseppina Cristina Cangemi, Peter Kruzliak, Gino Roberto Corazza
Chronic inflammatory enteropathies, including celiac disease, Crohn's disease, and ulcerative colitis, are lifelong disabling conditions whose cure is still an unmet need, despite the great strides made in understanding their complex pathogenesis. The advent of cellular therapies, mainly based on the use of stem cells, represents a great step forward thanks to their multitarget strategy. Both hematopoietic stem cells (HSC) and mesenchymal stem/stromal cells (MSC) have been employed in the treatment of refractory cases with promising results...
June 2016: Stem Cells
Guan Wee Wong, Michael A Heneghan
For many patients with autoimmune hepatitis (AIH), the presence of extrahepatic features is well recognised both at the time of presentation and during long-term follow-up. Concomitant 'autoimmune disorders' have been described in 20-50% of patients with AIH, both in adults and children. Indeed, the presence of these associated phenomena has been incorporated into both the original and revised International AIH group scoring systems as an aid to codifying the diagnosis. In acute index presentations, non-specific joint pains sometimes flitting in nature have been reported in 10-60% of patients, and while joint swelling is uncommon, rheumatoid arthritis and mixed connective tissue disease have been reported in 2-4% of patients with AIH...
2015: Digestive Diseases
Alfredo J Lucendo
Eosinophilic infiltration into oesophageal tissue, typical of eosinophilic oesophagitis (EoE), has been described in several other conditions, including infections, hypersensitivity, and other autoimmune disorders. Since its description, EoE has been associated with an increasing number of diseases also characterized by tissue infiltration, including eosinophilic gastroenteritis and Crohn's disease. While an association between EoE and coeliac disease was previously reported, it is not supported by recent research...
October 2015: Best Practice & Research. Clinical Gastroenterology
Silvia Speca, Christel Rousseaux, Caroline Dubuquoy, Florian Rieder, Antonella Vetuschi, Roberta Sferra, Ilaria Giusti, Benjamin Bertin, Laurent Dubuquoy, Eugenio Gaudio, Pierre Desreumaux, Giovanni Latella
BACKGROUND: Intestinal fibrosis is mainly associated with Crohn's disease and is defined as a progressive and excessive deposition of extracellular matrix components. No specific antifibrotic therapies are available. In this study, we evaluate the antifibrotic effect of a novel 5-ASA analog able to activate the peroxisome proliferator-activated receptor γ, named GED-0507-34 Levo. METHODS: Colonic fibrosis was induced in 110 C57BL/6 mice by 3 cycles of 2.5% (wt/vol) dextran sulfate sodium administration for 6 weeks...
February 2016: Inflammatory Bowel Diseases
Fanny Coppens, Jegan Iyyathurai, Ségolène Ruer, Antonella Fioravanti, Joemar Taganna, Lars Vereecke, Henri De Greve, Han Remaut
Crohn's disease (CD) is an inflammatory bowel disease characterized by an exaggerated immune response to commensal microbiota in the intestines of patients. Metagenomic studies have identified specific bacterial species and strains with increased prevalence in CD patients, amongst which is the adherent-invasive Escherichia coli (AIEC) strain LF82. AIEC strains express long polar fimbriae (LPF), which are known to target Peyer's patches in a mouse CD model. Here, the recombinant production of a soluble, self-complemented construct of the LpfD protein of E...
August 2015: Acta Crystallographica. Section D, Biological Crystallography
Jeoffrey N L Schouten, Joanne Verheij, Susana Seijo
Idiopathic non-cirrhotic portal hypertension (INCPH) is a rare disease characterized of intrahepatic portal hypertension in the absence of cirrhosis or other causes of liver disease and splanchnic venous thrombosis. The etiology of INCPH can be classified in five categories: 1) immunological disorders (i.e. association with common variable immunodeficiency syndrome, connective tissue diseases, Crohn's disease, etc.), 2) chronic infections, 3) exposure to medications or toxins (e.g. azathioprine, 6- thioguanine, arsenic), 4) genetic predisposition (i...
2015: Orphanet Journal of Rare Diseases
Orazio Palmieri, Teresa M Creanza, Fabrizio Bossa, Orazio Palumbo, Rosalia Maglietta, Nicola Ancona, Giuseppe Corritore, Tiziana Latiano, Giuseppina Martino, Giuseppe Biscaglia, Daniela Scimeca, Michele P De Petris, Massimo Carella, Vito Annese, Angelo Andriulli, Anna Latiano
BACKGROUND: Ulcerative colitis (UC) and Crohn's disease (CD) share some pathogenetic features. To provide new steps on the role of altered gene expression, and the involvement of gene networks, in the pathogenesis of these diseases, we performed a genome-wide analysis in 15 patients with CD and 14 patients with UC by comparing the RNA from inflamed and noninflamed colonic mucosa. METHODS: Two hundred ninety-eight differentially expressed genes in CD and 520 genes in UC were identified...
June 2015: Inflammatory Bowel Diseases
Chao Li, Audra Iness, Jennifer Yoon, John R Grider, Karnam S Murthy, John M Kellum, John F Kuemmerle
Increased TGF-β1 and TGF-β1-dependent Collagen I production in intestinal mesenchymal cells result in fibrosis in patients with Montreal B2 fibrostenotic Crohn's disease. Numerous cytokines, including IL-6, are produced by activated mesenchymal cells themselves and activate STAT3. The aim of the current study was to determine the mechanisms by which STAT-3 activation might result in intestinal fibrosis. Cytokine levels were measured by ELISA. STAT3 and suppressor of cytokine signaling 3 protein levels were measured by immunoblot, STAT3-TGFB1 DNA-binding activity by chromatin immunoprecipitation, and TGFB1 transcriptional activity by luciferase reporter assay...
April 1, 2015: Journal of Immunology: Official Journal of the American Association of Immunologists
Ferruh Artunc, Florian Lang
Effects of mineralocorticoids are not restricted to regulation of epithelial salt transport, extracellular volume and blood pressure; mineralocorticoids also influence a wide variety of seemingly unrelated functions such as inflammation and fibrosis. The present brief review addresses the role of mineralocorticoids in the orchestration of these latter processes. Mineralocorticoids foster inflammation as well as vascular, cardiac, renal and peritoneal fibrosis. Mechanisms involved in mineralocorticoid-sensitive inflammation and fibrosis include the serum- and glucocorticoid-inducible kinase 1 (SGK1), which is genomically upregulated by mineralocorticoids and transforming growth factor β (TGF-β), and stimulated by mineralocorticoid-sensitive phosphatidylinositide 3-kinase...
2014: Nephron. Physiology
Gita Gale, Sofia Ostman, Robert Saalman, Esbjörn Telemo, Mats Jontell, Bengt Hasséus
OBJECTIVES: The aim of this investigation was to characterise and compare the inflammatory infiltrates in patients with orofacial granulomatosis solely (OFG-S) and OFG with coexisting Crohn's disease (OFG+CD). STUDY DESIGN: Biopsy specimens with granulomas were obtained from patients with OFG-S (n=11) and OFG+CD (n=11) and immunostained with antibodies against CD1a, CD3, CD4, CD8, CD11c, CD20, CD68 and mast cell tryptase, followed by quantitative analysis. RESULTS: Analyses of the connective tissue revealed a significantly higher number of CD3-expressing T cells and CD11c-expressing dendritic cells in the connective tissue of patients with OFG-S compared to patients with OFG+CD...
November 2014: Medicina Oral, Patología Oral y Cirugía Bucal
Michael Scharl, Gerhard Rogler
Fistulae represent an important complication in patient suffering from Crohn's disease (CD). Cumulative incidence of fistula formation in CD patients is 17%-50% and about one third of patients suffer from recurring fistulae formation. Medical treatment options often fail and also surgery frequently is not successful. Available data indicate that CD-associated fistulae originate from an epithelial defect that may be caused by ongoing inflammation. Having undergone epithelial to mesenchymal transition (EMT), intestinal epithelial cells (IEC) penetrate into deeper layers of the mucosa and the gut wall causing localized tissue damage formation of a tube like structure and finally a connection to other organs or the body surface...
August 15, 2014: World Journal of Gastrointestinal Pathophysiology
Hugh James Freeman
Spontaneous free perforation of the small intestine is uncommon, especially if there is no prior history of visceral trauma. However, free, even recurrent, perforation may complicate a defined and established clinical disorder, such as Crohn's disease. In addition, free perforation may be the initial clinical presentation of an occult intestinal disorder, such as a lymphoma complicating celiac disease, causing diffuse peritonitis and an acute abdomen. Initial diagnosis of the precise cause may be difficult, but now has been aided by computerized tomographic imaging...
August 7, 2014: World Journal of Gastroenterology: WJG
Jalaj Garg, Parasuram Krishnamoorthy, Chandrasekar Palaniswamy, Ambarish Pandey, Hasan Ahmad
BACKGROUND: The pathophysiology of coronary artery dissection (CD) remains poorly under-stood and little is known about the factors predicting mortality in these patients. We aimed to study the epidemiology of CD and predictors of mortality in these patients. METHODS: All patients diagnosed with CD in the Nationwide Inpatient Sample 2009-2010 database using International Classification of Diseases ninth revision 414.12 were included in the study. Chronic conditions included in the analysis were diabetes mellitus, hypertension, hyperlipidemia, coronary artery disease (CAD), obesity, alcohol use, smoking, heart failure and ventricular arrhythmias...
2015: Cardiology Journal
D Q Shih, L Zheng, X Zhang, H Zhang, Y Kanazawa, R Ichikawa, K L Wallace, J Chen, C Pothoulakis, H W Koon, S R Targan
Intestinal fibrostenosis is among the hallmarks of severe Crohn's disease. Patients with certain TNFSF15 (gene name for TL1A) variants over-express TL1A and have a higher risk of developing strictures in the small intestine. In addition, sustained Tl1a expression in mice leads to small and large intestinal fibrostenosis under colitogenic conditions. The aim of this study was to determine whether established murine colonic fibrosis could be reversed with Tl1a antibody (Ab). Treatment with neutralizing Tl1a Ab reversed colonic fibrosis back to the original pre-inflamed levels, potentially as a result of lowered expression of connective tissue growth factor, Il31Ra, transforming growth factor β1 and insulin-like growth factor-1...
November 2014: Mucosal Immunology
Chao Li, John F Kuemmerle
Crohn's disease is complicated by the development of fibrosis and stricture in approximately 30% to 50% of patients over time. The pathogenesis of fibrostenotic disease is multifactorial involving the activation of mesenchymal cells by cytokines, growth factors, and other mediators released by immune cells, epithelial cells, and mesenchymal cells. Transforming growth factor β, a key activator of mesenchymal cells, is central to the process of fibrosis and regulates numerous genes involved in the disordered wound healing including collagens, and other extracellular matrix proteins, connective tissue growth factor, and insulin-like growth factors...
July 2014: Inflammatory Bowel Diseases
Benjamin E Schreiber, Sarah Twigg, Joe Marais, Andrew C Keat
Saddle-nose deformity can occur as a result of trauma to the nose, but it has also been well described in the setting of infections such as leprosy and syphilis and idiopathic inflammatory conditions such as granulomatosis with polyangiitis (formerly known as Wegener granulomatosis) and relapsing polychondritis. Since these deformities may also arise without an evident precipitating cause, they can pose a diagnostic conundrum. We review 2 cases of saddle-nose deformity that were treated at Northwick Park Hospital in Middlesex, England...
April 2014: Ear, Nose, & Throat Journal
Tara M Connelly, Arthur S Berg, John P Hegarty, Sue Deiling, David Brinton, Lisa S Poritz, Walter A Koltun
OBJECTIVE: To determine if single nuclear polymorphisms (SNPs) in the TFNSF15 gene play a role in patients requiring surgery for diverticulitis. BACKGROUND: A role for a genetic predisposition in diverticulitis is suggested by its association with hereditary connective tissue disorders, youthful onset in some patients, and the observation of families with multiple affected individuals. The TNFSF15 gene has been associated with other inflammatory diseases affecting the colon such as medically refractory ulcerative colitis (UC), aggressive Crohn's disease (CD), and pouchitis after restorative proctocolectomy...
June 2014: Annals of Surgery
S M Sahebally, J P Burke, K H Chang, M G Kiernan, P R O'Connell, J C Coffey
BACKGROUND: Despite advances in medical therapy, there remains no effective preventive or non-surgical therapeutic option for fibrostenotic Crohn's disease (CD). Symptomatic recurrences are common, necessitating reintervention. Intestinal fibroblasts mediate stricture formation, but their exact source is unclear. Recent evidence indicates that circulating fibrocytes drive fibrosis through differentiation into fibroblasts and the production of extracellular matrix proteins. The aim of this review is to describe current understanding of the pathophysiology underlying fibrosis in CD, the cellular and molecular biology of fibrocytes and their role in CD...
November 2013: British Journal of Surgery
John P Burke, Robert M O'Connell, Grainne Lennon, Glen A Doherty, Denise Keegan, Diarmuid O'Donoghue, Hugh Mulcahy, John Hyland, Desmond C Winter, Kieran Sheahan, P Ronan O'Connell
OBJECTIVE: To examine the association between single-nucleotide polymorphisms (SNPs) in CTGF (connective tissue growth factor) and patient outcomes after terminal ileal resection for Crohn's disease. BACKGROUND: The primary indication for intestinal resection in Crohn's disease is fibrostenotic terminal ileal disease. CTGF is a cytokine overexpressed in the intestine of patients with Crohn's disease that influences outcomes in other disease processes. METHODS: DNA was extracted from formalin-fixed, paraffin-embedded tissue from 147 patients with Crohn's disease who had undergone terminal ileal resection between 1981 and 2009...
November 2013: Annals of Surgery
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