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Rheumatic manifestations of inflammatory bowel disease

World Journal of Gastroenterology 2009年第44期15卷 5517-5524页

作者： Tatiana sofía Rodríguez-Reyna Cynthia Martínez-Reyes jesús kazúo yamamoto-furusho Department of Immunology and Rheumatology National Institute of Medical Sciences and Nutrition Salvador ZubiránVasco de Quiroga 15Col Sección XVI. DelTlalpanMexico City 14000Mexico Department of Gastro-enterology National Institute of Medical Sciences and Nutrition Salvador ZubiránVasco de Quiroga 15Col Sección XVI. DelTlalpanMexico City 14000Mexico

This article reviews the literature concerning rheu-matic manifestations of inflammatory bowel disease (IBD),including common immune-mediated pathways,frequency,clinical course and therapy. Musculoskel-etal complications are frequent and well-recognized manifestations in IBD,and affect up to 33% of pa-tients with IBD. The strong link between the bowel and the osteo-articular system is suggested by many clinical and experimental observations,notably in HLA-B27 transgenic rats. The autoimmune pathogenic mechanisms shared by IBD and spondyloarthropathies include genetic susceptibility to abnormal antigen pre-sentation,aberrant recognition of self,the presence of autoantibodies against specific antigens shared by the colon and other extra-colonic tissues,and increased intestinal permeability. The response against microor-ganisms may have an important role through molecular mimicry and other mechanisms. Rheumatic mani-festations of IBD have been divided into peripheral arthritis,and axial involvement,including sacroiliitis,with or without spondylitis,similar to idiopathic anky-losing spondylitis. other periarticular features can oc-cur,including enthesopathy,tendonitis,clubbing,peri-ostitis,and granulomatous lesions of joints and *** and osteomalacia secondary to IBD and iatrogenic complications can also occur. The manage-ment of the rheumatic manifestations of IBD consists of physical therapy in combination with local injection of corticosteroids and nonsteroidal anti-inflammatory drugs; caution is in order however,because of their possible harmful effects on intestinal integrity,perme-ability,and even on gut inflammation. sulfasalazine,methotrexate,azathioprine,cyclosporine and lefluno-mide should be used for selected indications. In some cases,tumor necrosis factor-α blocking agents should be considered as first-line therapy.

关键词： Inflammatory bowel disease spondylitis Rheumatic diseases

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Basic and clinical aspects of osteoporosis in inflammatory bowel disease

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World Journal of Gastroenterology 2007年第46期13卷 6156-6165页

作者： Lorena Rodríguez-Bores JosuéBarahona-Garrido jesús K yamamoto-furusho IBD Clinic Department of GastroenterologyInstituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán.Vasco de Quiroga 15 colonia Sección ⅩⅥTlalpanCP 14000México

Low bone mineral density and the increased risk of fracture in gastrointestinal diseases have a multifactorial pathogenesis. Inflammatory bowel disease （IBD） has been associated with an increased risk of osteoporosis and osteopenia and epidemiologic studies have reported an increased prevalence of low bone mass in patients with IBD. Certainly, genetics play an important role, along with other factors such as systemic inflammation, malnutrition, hypogonadism, glucocorticoid therapy in IBD and other lifestyle factors. At a molecular level the proinflammatory cytokines that contribute to the intestinal immune response in IBD are known to enhance bone resorption. There are genes influencing osteoblast function and it is likely that LRP5 may be involved in the skeletal development. Also the identification of vitamin D receptors （VDRs） and some of its polymorphisms have led to consider the possible relationships between them and some autoimmune diseases and may be involved in the pathogenesis through the exertion of its immunomodulatory effects during inflammation. Trying to explain the physiopathology we have found that there is increasing evidence for the integration between systemic inflammation and bone loss likely mediated via receptor for activated nuclear factor kappa-B （RANK）, RANK-ligand, and osteoprotegerin, proteins that can affect both osteoclastogenesis and T-cell activation. Although glucocorticoids can reduce mucosal and systemic inflammation, they have intrinsic qualities that negatively impact on bone mass. It is still controversial if all IBD patients should be screened, especially in patients with preexisting risk factors for bone disease. Available methods to measure BMD include single energy x-ray absorptiometry, DXA, quantitative computed tomography （QCT）, radiographic absorptiometry, and *** is the establish method to determine BMD, and routinely is measured in the hip and the lumbar spine. There are several treatments options that have

关键词： Inflammatory bowel disease osteoporosis

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Novel genetic markers in inflammatory bowel disease

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World Journal of Gastroenterology 2007年第42期13卷 5560-5570页

作者： Lorena Rodríguez-Bores Gabriela C Fonseca Marco A Villeda jesús K yamamoto-furusho IBD Clinic Department of Gastroenterology Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán Vasco de Quiroga 15 colonia Sección XVI Tlalpan CP 14000 México

Genetic factors play a significant role in determining inflammatory bowel disease(IBD)*** data support genetic contribution to the pathogenesis of IBD,which include familial aggregation,twin studies,racial and ethnic differences in disease *** studies have identified several susceptibility genes contained in different genomic regions named IBD1 to *** oligomerization domain(NoD2)and human leukocyte antigen(HLA)genes are the most extensively studied genetic regions(IBD1 and IBD3 respectively)in *** of the NoD2 gene are associated with Crohn's disease(CD)and several HLA genes are associated with ulcerative colitis(UC)and *** like receptors(TLRs)have an important role in the innate immune response against infections by mediating recognition of pathogen-associated microbial *** single-nucleotide polymorphisms(sNPs)in molecules involved in bacterial recognition seems to be essential to define genetic backgrounds at risk of ***,numerous new genes have been identified to be involved in the genetic susceptibility to IBD:NoD1/Caspase-activation recruitment domains 4(CARD4),Chemokine ligand 20(CCL20),IL-11,and IL-18 among *** characterization of these novel genes potentially will lead to the identification of therapeutic agents and clinical assessment of phenotype and prognosis in patients with IBD.

关键词： Genetic Inflammatory bowel disease Human leukocyte antigen Nucleotide oligomerizationdomain Toll like receptors susceptibility

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Factors that influence outcome in non-invasive and invasive treatment in polycystic liver disease patients

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World Journal of Gastroenterology 2008年第20期14卷 3195-3200页

作者： Josué Barahona-Garrido jesús Camacho-Escobedo Eduardo Cerda-Contreras Jorge Hernández-Calleros jesús K yamamoto-furusho Aldo Torre Misael Uribe Department of Gastroenterology National Institute of Health Sciences and Nutrition "Salvador Zubirán" Mexico City 14000 Mexico

AIM: To evaluate the factors that influence outcome of both non-invasive and invasive treatment of polycystic liver disease. METHoDs: Analysis of clinical files of patients with complete follow-up from July 1986 to June 2006. REsULTs: Forty-one patients (male, 7; female, 34), 47.8 ± 11.9 years age, and 5.7 ± 6.7 years follow-up, were studied. Alkaline phosphatase (AP) elevation (15% of patients) was associated with the requirement of invasive treatment (IT, P = 0.005). IT rate was higher in symptomatic than non-symptomatic patients (65.4% vs 14.3%, P = 0.002), and in women taking hormonal replacement therapy (HRT) (P = 0.001). Cysts complications (CC) were more frequent (22%) in the symptomatic patients group (P = 0.023). Patients with body mass index (BMI) > 25 (59%) had a trend to complications after IT (P = 0.075). Abdominal pain was the most common symptom (56%) and indication for IT (78%). Nineteen patients (46%) required a first IT: 12 open fenestration (oF), 4 laparoscopic fenestration (LF) and 3 fenestration with hepatic resection (FHR). Three required a second IT, and one required a third procedure. Complications due to first IT were found in 32% (oF 16.7%, LF 25%, FHR 66.7%), and in thesecond IT in 66.7% (oF 100%). Follow-up mortality rate was 0. CoNCLUsIoN: Presence of symptoms, elevated AP, and CC are associated with IT requirement. HRT is associated with presence of symptoms and IT requirement. Patients with BMI > 25 have a trend be susceptible to IT complications. The proportions of complications are higher in FHR and second IT groups. Rs is more frequent after oF.

关键词： Hepatic cysts open fenestration Laparoscopic fenestration Hepatic resection Recurrenceof symptoms Hormonal replacement therapy

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Genetic factors associated with the development of inflammatory bowel disease

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World Journal of Gastroenterology 2007年第42期13卷 5594-5597页

作者： jesus K yamamoto-furusho Inflammatory Bowel DiseaseClinic Department of Gastroenterology Instituto Nacional deCiencias Médicas y Nutrición Vasco de Quiroga 15 ColoniaSección XVI Tlalpan C.P. 14000 México D.F. México

Crohn's disease(CD)and ulcerative colitis(UC)are complex polygenic disorders,characterized by several genes together with environmental factors contributing to the development of inflammatory bowel disease(IBD).Recent advances in research on genetic susceptibility have allowed the identification of diverse genes at different levels:(1)Innate immunity;(2)Antigen presentation molecules;(3)Epithelial integrity;(4)Drug transporter;(5)Cell *** application of genetic testing into clinical practice is close and all genetic markers may have several clinical implications:prediction of disease phenotype,molecular classification,prevention of complications,and prognosis.

关键词： Genetic susceptibility Inflammatory bowel disease Ulcerative colitis Crohn's disease

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Innovative therapeutics for inflammatory bowel disease

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World Journal of Gastroenterology 2007年第13期13卷 1893-1896页

作者： jesus K yamamoto-furusho Inflammatory Bowel Diseas Clinic Department of Gastroenterology Instituto Nacional d Ciencias Médicas y Nutrición. Vasco de Quiroga 15 Coloni Sección XVI Tlalpan México CP 14000 DF México

Inflammatory bowel diseases (IBD) are chronic inflammatory conditions of the gastrointestinal tract, which clinically present as one of two disorders, Crohn's disease or ulcerative colitis. Mainstays of drug treatments for IBD include aminosalicylates, corticosteroids and immunosuppressants such as azathioprine, methotrexate and cyclosporin. Advances in basic research of the pathophysiological process in IBD have been applied to generate a variety of new therapeutics targeting at different levels of the inflammatory processes. New therapies are classified as: (1) Anti-TNFα antibodies; (2) Recombinant cytokines; (3) selective adhesion blockade; (4) Growth factors; (5) Innate immunostimulation; (6) Nucleic acid based therapies; (7) Gene therapy; (8) Autologous bone-marrow transplantation; (9) Helminths and (10) Extracorporeal immunomodulation. All treatments have the potential to provide more effective and safe treatment for IBD.

关键词： Novel agents Inflammatory bowel diseases Biologic therapy Future agents

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Role of the HLA-DQ locus in the development of chronic gastritis and gastric carcinoma in Mexican patients

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World Journal of Gastroenterology 2006年第48期12卷 7762-7767页

作者： Roberto Herrera-Goepfert jesús K yamamoto-furusho Luis F oate-ocaa Margarita Camorlinga-Ponce Leopoldo Muoz Jorge A Ruiz-Morales Gilberto Vargas-Alarcón Julio Granados Cellular Biology section Department of Pathology Institute Nacional de Cancerologia (INCan) Mexico City Mexico Department of Immunology and Rheumatology Institute Nacional de Ciencias Medicas y Nutricion Salvador Zubiran Mexico City Mexico Department of Gastroenterology Institute Nacional de Ciencias Medicas y Nutricion Salvador Zubiran Mexico City Mexico Department of Gastroenterology (INCan) Mexico City Mexico Medical Research Unit on Infectious and Parasitic Diseases Hospital de Pediatria Centro Medico Nacional Siglo XXI (CMN-SXXI) Institute Mexicano del Seguro Social (IMSS) Mexico City Mexico Department of Immunology and Rheumatology Institute Nacional de Ciencias Medicas y Nutricion Salvador Zubiran Mexico City Mexico Department of Physiology Institute Nacional de Cardiologia Ignacio Chavez Mexico City Mexico

AIM： To determine the HLA-DQ locus in Mexican patients with Chronic gastritis and gastric adenocarcinoma.METHoDs： oligotyping for HLA-DQ locus was performed in 45 Mexican patients with chronic gastritis and 13 Mexican patients with diffuse-type gastric adenocarcinoma, and was then compared with 99 clinically healthy unrelated individuals. H pylori infection and CagA status were assessed in patients by enzyme-linked immunosorbent assay （EUsA） method. REsULTs： We found a significant increased frequency of HLA-DQBI＊0401 allele in Hpylori-positive patients with chronic gastritis when compared with healthy subjects [19 vs 0%, P = 1 × 10^-7, odds ratio （oR） = 4.96; 95% confidence interval （95% CI）, 3.87-6.35]. We also found a significant increased frequency of HLA-DQBI＊0501 in patients with diffuse-type gastric carcinoma in comparison with healthy individuals （P = 1 × 10^4, oR = 13.07; 95% CI, 2.82-85.14）.CoNCLUsIoN： HLA-DQ locus may play a different role in the development of H pylori-related chronic gastritis and difffuse-type gastric adenocarcinoma in the Mexican Mestizo population.

关键词： HLA-DQ HLA-DQ5 HLA-DQBI*0501 Hpy/or/ Chronic gastritis Gastric cancer Diffuse-type adenocarcinoma

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Innate immunity in inflammatory bowel disease

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World Journal of Gastroenterology 2007年第42期13卷 5577-5580页

作者： jesus K yamamoto-furusho Daniel K Podolsky Gastrointestinal Unit and Center for the study of Inflammatory BowelDisease Massachusetts General Hospital and Harvard MedicalSchool Boston MA 02114 United States

The human intestinal tract is home to an enormous bacterial flora. The host defense against microorganisms can be divided into innate and adaptive immunity. The former is the most immediate line of response to immunologic challenges presented by bacteria, viruses, and fungi. The mucosal immune system has evolved to balance the need to respond to pathogens while co-existing with commensal bacteria and food antigens. In inflammatory bowel disease （IBD）, this hyporesponsiveness or tolerance breaks down and inflammation supervenes driven by the intestinal microbial flora. Bacteria contain compounds and are recognized by a variety of receptors, including Toll-like receptors （TLRs） and NoDs （a family of intracellular bacterial sensors） and are potent stimuli of innate immune responses. several mutations in these receptors have been associated with development of IBD.

关键词： Innate Immunity Toll-like receptors Inflammatory bowel disease

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Crohn’s disease:Innate immunodeficiency?

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World Journal of Gastroenterology 2006年第42期12卷 6751-6755页

作者： jesus K yamamoto-furusho Joshua R Korzenik Gastro-intestinal Unit and Center for the study of Inflammatory Bowel Disease Massachusetts General Hospital and Harvard Medical School Boston MA 02114 United States

In the past, Crohn’s disease (CD) has been understood primarily as an immunologic disorder characterized by an abnormal T-cell response. Recent in vitro and in vivo data suggests that CD may instead be precipitated by innate immune dysfunction resulting from a combination of genetic and environmental factors. some reports have demonstrated a defective immune response in a variety of other cellular components, including neutrophils, monocytes and dendritic cells. Recent studies of granulocyte-macrophage colony-stimulating factor (GM- CsF) in CD, aiming to stimulate the innate immune system with the conception that an innate immune defect underlies the development of the disease, have been demonstrated a clinical benefit and reinforce this evolving understanding of the disease.

关键词： Crohn's disease Innate immunity Immunodeficiency NoD2

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Emerging therapeutic options in inflammatory bowel disease

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World Journal of Gastroenterology 2021年第48期27卷 8242-8261页

作者： jesus K yamamoto-furusho Norma N Parra-Holguín Gastroenterology Unit Inflammatory Bowel Disease ClinicInstituto Nacional de Ciencias Medicas y NutricionMexico City 14080Mexico

Inflammatory bowel disease(IBD)is a chronic disease that requires chronic treatment throughout the evolution of the disease,with a complex physiopathology that entails great challenges for the development of new and specific treatments for ulcerative colitis and Crohn's *** anti-tumor necrosis factor alpha therapy has impacted the clinical course of IBD in those patients who do not respond to conventional treatment,so there is a need to develop new therapies and markers of treatment *** pathways involved in the development of the disease are known and the new therapies have focused on blocking the inflammatory process at the gastrointestinal level by oral,intravenous,subcutaneous,and topical *** these new therapies can lead to more personalized treatments with higher success rates and fewer *** treatments have not only focused on clinical remission,but also on achieving macroscopic changes at the endoscopic level and microscopic changes by achieving mucosal *** treatments are mainly based on modifying signaling pathways,by blocking receptors or ligands,reducing cell migration and maintaining the integrity of the epithelial ***,this review presents the efficacy and safety of the new treatments that are currently under study and the advances that have been made in this area in recent years.

关键词： Inflammatory bowel disease Review Emerging Treatment Ulcerative colitis Crohn's disease

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