Fibromuscular dysplasia: A comprehensive review on evaluation and management and role for multidisciplinary comprehensive care and patient input model.

Fibromuscular dysplasia is a nonatherosclerotic, under-recognized disorder primarily seen in middle-aged women. It can lead to several complications, such as hypertension, headaches, dissections, aneurysms, myocardial infarctions, and cerebrovascular accidents, to name a few. This article provides a comprehensive review of current literature on epidemiology, etiology, diagnosis, treatment, and long-term surveillance and fibromuscular dysplasia management. In addition, it renders the role of education and prevention for patients living with this condition and family screening. Lastly, it emphasizes the importance of a comprehensive multidisciplinary care model and patient input, given the complexity of this disease and its systemic presence and protean manifestations.

Role of chitotriosidase (chitinase 1) under normal and disease conditions.

Mammalian chitinases belong to the glycosyl hydrolase 18 family based on structural homology and the family includes a large number of bacterial and eukaryotic chitinases. Among the mammalian chitinases, chitotriosidase (CHIT1) and acidic mammalian chitinase (AMCase) are capable of hydrolyzing the ß-(1, 4)-linkage between the adjacent N-acetyl glucosamine residues of chitin. CHIT1 is one of the most abundantly secreted proteins, being mainly produced by activated macrophages and epithelial cells. CHIT1 plays a pivotal role in the context of infectious disease including malaria and fungi infections as a host defense towards chitin in pathogen's cell structure and as a diagnostic marker of disease. In contrast, CHI1 released by activated Kupffer cells in liver could induce hepatic fibrosis and cirrhosis. Increased serum levels of CHIT1 were observed in patients with many disorders, including Gaucher's disease, bronchial asthma, and atherosclerosis. Therefore, CHIT1 seems to have dual (regulatory and pathogenic) roles depending on the disease and producing cell types during the inflammatory conditions.

Chitinase 3-like-1 expression in colonic epithelial cells as a potentially novel marker for colitis-associated neoplasia.

Chitinase 3-like-1 (CHI3L1/YKL-40) is a protein secreted from restricted cell types including colonic epithelial cells (CECs) and macrophages. CHI3L1 is an inflammation-associated molecule, and its expression is enhanced in persons with colitis and colon cancer. The biological function of CHI3L1 on CECs is unclear. In this study, we investigated the role of CHI3L1 on CECs during the development of colitis-associated neoplasia. We analyzed colonic samples obtained from healthy persons and from persons with ulcerative colitis with or without premalignant or malignant changes. DNA microarray and RT-PCR analyses significantly increased CHI3L1 expression in non-dysplastic mucosa from patients with inflammatory bowel disease (IBD) who had dysplasia/adenocarcinoma compared with that in healthy persons and in patients with IBD who did not have dysplasia. As determined by IHC, CHI3L1 was expressed in specific cell types in the crypts of colonic biopsies obtained from patients with ulcerative colitis who have remote dysplasia. Purified CHI3L1 efficiently activated the NF-κB signaling pathway and enhanced the secretion of IL-8 and TNF-α in SW480 human colon cancer cells. In addition, colon cancer cell proliferation and migration were significantly promoted in response to CHI3L1 in these cells. In summary, CHI3L1 may contribute to the proliferation, migration, and neoplastic progression of CECs under inflammatory conditions and could be a useful biomarker for neoplastic changes in patients with IBD.

Animal models of colitis-associated carcinogenesis.

Inflammatory bowel disease (IBD) is a group of chronic inflammatory disorders that affect individuals throughout life. Although the etiology and pathogenesis of IBD are largely unknown, studies with animal models of colitis indicate that dysregulation of host/microbial interactions are requisite for the development of IBD. Patients with long-standing IBD have an increased risk for developing colitis-associated cancer (CAC), especially 10 years after the initial diagnosis of colitis, although the absolute number of CAC cases is relatively small. The cancer risk seems to be not directly related to disease activity, but is related to disease duration/extent, complication of primary sclerosing cholangitis, and family history of colon cancer. In particular, high levels and continuous production of inflammatory mediators, including cytokines and chemokines, by colonic epithelial cells (CECs) and immune cells in lamina propria may be strongly associated with the pathogenesis of CAC. In this article, we have summarized animal models of CAC and have reviewed the cellular and molecular mechanisms underlining the development of carcinogenic changes in CECs secondary to the chronic inflammatory conditions in the intestine. It may provide us some clues in developing a new class of therapeutic agents for the treatment of IBD and CAC in the near future.